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1

Ambrus, J. L., C. H. Jurgensen, E. J. Brown, and A. S. Fauci. "Purification to homogeneity of a high molecular weight human B cell growth factor; demonstration of specific binding to activated B cells; and development of a monoclonal antibody to the factor." Journal of Experimental Medicine 162, no. 4 (October 1, 1985): 1319–35. http://dx.doi.org/10.1084/jem.162.4.1319.

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High molecular weight B cell growth factor (HMW-BCGF) produced by a T cell line was purified to homogeneity and demonstrated to bind specifically to activated human B cells. A monoclonal antibody to HMW-BCGF was developed that (a) specifically inhibited the activity of HMW-BCGF in enhancing B cell proliferation, (b) specifically bound to HMW-BCGF in Western blots, (c) specifically absorbed HMW-BCGF activity from culture supernatants, and (d) specifically absorbed an internally labeled protein from T-ALL supernatant which comigrates with HMW-BCGF on sodium dodecyl sulfate-polyacrylamide gels. This antibody should help in cloning the gene for HMW-BCGF and further exploring the physiologic roles of HMW-BCGF.
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2

Soulavie, Fabien, David Piepenbrock, Joëlle Thomas, Jennifer Vieillard, Jean-Luc Duteyrat, Elisabeth Cortier, Anne Laurençon, Martin C. Göpfert, and Bénédicte Durand. "hemingway is required for sperm flagella assembly and ciliary motility in Drosophila." Molecular Biology of the Cell 25, no. 8 (April 15, 2014): 1276–86. http://dx.doi.org/10.1091/mbc.e13-10-0616.

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Cilia play major functions in physiology and development, and ciliary dysfunctions are responsible for several diseases in humans called ciliopathies. Cilia motility is required for cell and fluid propulsion in organisms. In humans, cilia motility deficiencies lead to primary ciliary dyskinesia, with upper-airways recurrent infections, left–right asymmetry perturbations, and fertility defects. In Drosophila, we identified hemingway (hmw) as a novel component required for motile cilia function. hmw encodes a 604–amino acid protein characterized by a highly conserved coiled-coil domain also found in the human orthologue, KIAA1430. We show that HMW is conserved in species with motile cilia and that, in Drosophila, hmw is expressed in ciliated sensory neurons and spermatozoa. We created hmw-knockout flies and found that they are hearing impaired and male sterile. hmw is implicated in the motility of ciliated auditory sensory neurons and, in the testis, is required for elongation and maintenance of sperm flagella. Because HMW is absent from mature flagella, we propose that HMW is not a structural component of the motile axoneme but is required for proper acquisition of motile properties. This identifies HMW as a novel, evolutionarily conserved component necessary for motile cilium function and flagella assembly.
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3

Deng, Zhiying, Jichun Tian, and Ruibo Hu. "The accumulation of high molecular weight glutenin subunits (HMW-GS) and their relation to dough rheological quality in Chinese winter wheat." Australian Journal of Agricultural Research 57, no. 1 (2006): 41. http://dx.doi.org/10.1071/ar05080.

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Six winter wheat cultivars were categorised into high gluten, medium gluten, and low gluten according to their protein content and gluten index. The object of this study was to determine the accumulation of high molecular weight glutenin subunits (HMW-GS) and their relationship to dough rheological quality. They were grown in 3 replicates on experimental plots at the Shandong Agricultural University research farm in 2001. HMW-GS compositions during grain development were investigated by SDS-PAGE procedures, followed by imaging densitometry to determine quantitative variations. Initial formation time of HMW-GS was different among cultivars. HMW-GS in cultivars with high gluten had formed completely by 10 days after anthesis, but were still only partially formed at this time in cultivars having weak gluten. Accumulation quantities of HMW-GS followed with grain development. Individual HMW-GS accumulated rapidly between 25 days after anthesis and maturity. The kinetic accumulation trend for the individual HMW-GS was similar in the same type of cultivars, but quantities were different. Strong cultivars had more kinetic accumulation quantities of HMW-GS than weak cultivars. HMW-GS kinetic accumulation quantities during grain development were significantly positively correlated with dough rheological characteristics and SDS-sedimentation volume.
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4

Kellermair, Joerg, Sahrai Saeed, Helmut W. Ott, Juergen Kammler, Hermann Blessberger, Markus Suppan, Michael Grund, et al. "High-molecular-weight von Willebrand Factor multimer ratio differentiates true-severe from pseudo-severe classical low-flow, low-gradient aortic stenosis." European Heart Journal - Cardiovascular Imaging 21, no. 10 (May 17, 2020): 1123–30. http://dx.doi.org/10.1093/ehjci/jeaa056.

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Abstract Aims Upon high wall shear stress, high-molecular-weight (HMW) von Willebrand Factor (VWF) multimers are degraded, thus, HMW VWF multimer deficiency mirrors haemodynamics at the site of aortic stenosis (AS). The aim of the present study was to analyse the role of HMW VWF multimer ratio for subcategorization of classical low-flow, low-gradient (LF/LG) AS. Methods and results Eighty-three patients with classical LF/LG AS were prospectively recruited and HMW VWF multimer pattern was analysed using a densitometric quantification of western blot bands. Patients were subclassified into true-severe (TS) and pseudo-severe (PS) classical LF/LG AS based on dobutamine stress echocardiography (DSE). Positive and negative predictive values (PPV/NPV) of HMW VWF multimer ratio for diagnosis of the TS subtype were calculated. HMW VWF multimer ratio in TS classical LF/LG AS was significantly decreased compared to PS classical LF/LG AS (0.86 ± 0.27 vs. 1.06 ± 0.09, P < 0.001). HMW VWF multimer deficiency occurred exclusively in the TS subtype with an optimal PPV of 1.000 and NPV of 0.379. HMW VWF multimer ratio showed a strong correlation with mean transvalvular pressure gradients during DSE (r = −0.616; P < 0.001). HMW VWF multimer ratio measured at baseline was higher compared to levels measured after DSE (0.87 ± 0.27 vs. 0.84 ± 0.31; P = 0.031) indicating DSE-induced increased proteolysis. Conclusion HMW VWF multimer ratio represents a valuable biomarker for classical LF/LG AS subclassification and mirrors haemodynamics during DSE. HMW VWF multimer ratio identifies the TS subtype without the use of other imaging techniques.
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5

Li, Yi, Jiahui Fu, Qun Shen, and Dong Yang. "High-Molecular-Weight Glutenin Subunits: Genetics, Structures, and Relation to End Use Qualities." International Journal of Molecular Sciences 22, no. 1 (December 26, 2020): 184. http://dx.doi.org/10.3390/ijms22010184.

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High-molecular-weight glutenin subunits (HMW-GSs) are storage proteins present in the starchy endosperm cells of wheat grain. Encoding the synthesis of HMW-GS, the Glu-1 loci located on the long arms of group 1 chromosomes of the hexaploid wheat (1A, 1B, and 1D) present multiple allelism. In hexaploid wheat cultivars, almost all of them express 3 to 5 HMW-GSs and the 1Ay gene is always silent. Though HMW-GSs are the minor components in gluten, they are crucial for dough properties, and certain HMW-GSs make more positive contributions than others. The HMW-GS acts as a “chain extender” and provides a disulfide-bonded backbone in gluten network. Hydrogen bonds mediated by glutamine side chains are also crucial for stabilizing the gluten structure. In most cases, HMW-GSs with additional or less cysteines are related to the formation of relatively more or less interchain disulfide bonds and HMW-GSs also affect the gluten secondary structures, which in turn impact the end use qualities of dough.
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6

Ueshima, S., K. Silence, D. Collen, and H. R. Lijnen. "Molecular Conversions of Recombinant Staphylokinase During Plasminogen Activation in Purified Systems and in Human Plasma." Thrombosis and Haemostasis 70, no. 03 (1993): 495–99. http://dx.doi.org/10.1055/s-0038-1649612.

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SummaryRecombinant staphylokinase (STAR) is produced as a 136 amino acid protein with NH2-terminal sequence Ser-Ser-Ser (mature STAR, HMW-STAR), which may be converted to lower molecular weight forms (LMW-STAR) by removal of the first six residues (yielding STAR-Δ6 with NH2-terminal Gly-Lys-Tyr-) or the first ten residues (yielding STAR-Δ10 with NH2-terminal Lys-Gly-Asp-). In the present study the occurrence and effects of these conversions during plasminogen activation by HMW-STAR were studied in purified systems and in human plasma.In stoichiometric mixtures of HMW-STAR and native human plasminogen (Glu-plasminogen), rapid and quantitative conversion of HMW-STAR to LMW-STAR occurred, concomitant with exposure of the active site in the plasmin-STAR complex. NH2-terminal amino acid sequence analysis revealed the sequence Lys-Gly-Asp- in addition to the known sequences of the Lys-plasmin chains, identifying STAR-Δ10 as the derivative generated from HMW-STAR. In mixtures of catalytic amount of HMW-STAR and human plasminogen, plasmin generation occurred progressively, following an initial lag phase, during which HMW-STAR was converted to LMW-STAR. Plasmin-mediated conversion of HMW-STAR to LMW-STAR obeyed Michaelis-Menten kinetics with K m = 3.6 μM and k 2 = 0.38 s−1. The specific clot lysis activities of HMW-STAR (122,000 ± 8,000 units/mg) and LMW-STAR (129,000 ± 8,000 units/mg) were indistinguishable.In an in vitro system consisting of a 60 μl plasma clot submerged in 250 μl plasma, 80% clot lysis within 1 h was obtained with 70 nM HMW-STAR. This was associated with fibrinogen depletion and conversion of 20% of the HMW-STAR to LMW-STAR. Addition of 100 nM HMW-STAR to human plasma in the absence of a clot did not induce significant fibrinogen breakdown (≥ 90% residual fibrinogen after 2 h), and was not associated with significant coversion to LMW-STAR (≤10% within 2 h). With 400 nM HMW-STAR, fibrinogen depletion in plasma occurred within 1 h, and 80% conversion to LMW-STAR was observed. Thus, at fibrinolytically active concentrations which do not cause fibrinogen breakdown, no significant conversion of HMW-STAR to LMW-STAR occurs in human plasma in the absence of a clot.These findings indicate that the conversion of HMW-STAR to LMW-STAR may occur in association with clot lysis, but is not required to induce it.
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7

Eglit, Triin, Margus Lember, Inge Ringmets, and Tarvo Rajasalu. "Gender differences in serum high-molecular-weight adiponectin levels in metabolic syndrome." European Journal of Endocrinology 168, no. 3 (March 2013): 385–91. http://dx.doi.org/10.1530/eje-12-0688.

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ObjectiveThe objective of this study was to estimate gender-specific associations between metabolic syndrome (MS) and high-molecular-weight (HMW) adiponectin in an Estonian adult population.MethodsPlasma HMW adiponectin was measured in 458 subjects (191 men) who participated in a population-based cross-sectional multicenter study (n=495) on the prevalence of metabolic disorders in Estonia. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria.ResultsMedian HMW adiponectin levels (μg/ml) were significantly lower among all subjects with MS compared with subjects without MS: 2.1 vs 2.8 in men (P=0.002) and 3.1 vs 5.1 in women (P<0.001). In a fully adjusted, logistic regression model containing HMW adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR), BMI, and age, HMW adiponectin was significantly associated with MS only in women. Comparison of HMW adiponectin and HOMA-IR as markers for MS indicated that HOMA-IR predicted MS better than did HMW adiponectin in both genders. However, after adjusting for age and BMI, HOMA-IR was a significantly better predictor only in men. HMW adiponectin and HOMA-IR predicted the presence of MS at the same level in women. Areas under the receiver operating characteristic curves for HMW adiponectin and HOMA-IR were 0.833 vs 0.88 in men (P=0.02) and 0.897 vs 0.907 in women (P=0.5).ConclusionsThese data suggest that the association between low HMW adiponectin levels and presence of MS might be stronger in women compared with men.
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8

Sinha, Madhur K., Traci Songer, Qiang Xiao, John H. Sloan, Jin Wang, Shaoquen Ji, William E. Alborn, et al. "Analytical Validation and Biological Evaluation of a High–Molecular-Weight Adiponectin ELISA." Clinical Chemistry 53, no. 12 (December 1, 2007): 2144–51. http://dx.doi.org/10.1373/clinchem.2007.090670.

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Abstract Background: Of the 3 circulating multimeric forms of adiponectin, the high–molecular-weight (HMW) form, as measured by size-exclusion and/or immunoblotting techniques, is a better index of insulin sensitivity for monitoring health and disease than is total adiponectin. We aimed to develop a simple ELISA to measure HMW adiponectin. Methods: We pretreated serum or plasma samples with digestion solution containing proteinase K (Millipore, ESDS). HMW (Millipore, EZHMWA-64K) and total adiponectin (Millipore, EZHADP-61K) concentrations were measured in treated and untreated samples, respectively, from 108 individuals and from 20 morbidly obese patients before and at 1, 3, 6, and 12 months after gastric-bypass surgery. Results: The ELISA has a dynamic range of 3–200 μg/L and a detection limit of 0.8 μg/L. Intraassay and interassay CVs were &lt;4% and &lt;10%, respectively. Sample-dilution curves paralleled the calibration curves. Fast protein liquid chromatography profiles of the proteinase K-treated samples revealed predominantly HMW adiponectin. Values for HMW adiponectin produced with this method are comparable with those obtained with Western blot analysis (y = 0.77x − 0.15; r = 0.96; n = 56). Body mass index (BMI)- and sex-related changes were more pronounced for HMW adiponectin and percentage of HMW adiponectin than for total adiponectin. HMW and total adiponectin increased after bypass surgery, but changes in HMW adiponectin were more pronounced and preceded changes in total adiponectin. Conclusion: This simple, rapid ELISA for HMW adiponectin recognizes the HMW isoform, produces results closely correlated with those obtained with Western blotting, and appears to better distinguish BMI-, sex-, and weight loss–associated differences than assays for total adiponectin.
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9

Lämmle, Bernhard, Bruce L. Zuraw, Mary Jo Heeb, Hans Peter Schwarz, Mauro Berrettini, John G. Curd, and John H. Griffin. "Detection and Quantitation of Cleaved and Uncleaved High Molecular Weight Kininogen in Plasma by Ligand Blotting with Radiolabeled Plasma Prekallikrein or Factor XI." Thrombosis and Haemostasis 59, no. 02 (1988): 151–61. http://dx.doi.org/10.1055/s-0038-1642745.

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SummaryA method for the quantitative assay of native single chain and kallikrein cleaved two-chain high molecular weight (HMW)-kininogen in plasma is described. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma is followed by electrotransfer of the electropherogram to nitrocellulose membranes and detection of the blotted HMW-kininogen with its physiologic ligands, radiolabeled plasma prekallikrein or radiolabeled factor XI. Using unreduced SDS-PAGE cleaved two-chain HMW-kininogen (Mr ∼107,000 and 95,000), is elec-trophoretically separated from uncleaved single chain HMW-kininogen (Mr ∼150,000). Counting the radioactivity of the nitrocellulose pieces corresponding to cleaved HMW-kininogen permits its quantitative measurement by comparison with standards consisting of decreasing amounts of fully dextran sulfate activated normal human plasma. Single chain HMW-kininogen is similarly assayed using reduced SDS-PAGE and unactivated normal human plasma standards.This technique is highly specific and sensitive to about 50 ng of either cleaved or uncleaved HMW-kininogen. Varying amounts of cleaved HMW-kininogen were found in a small series of plasmas from patients suffering from various inflammatory conditions. Higher levels of in vivo cleaved HMW-kininogen were observed during acute attacks of hereditary angioedema due to Cl-inhibitor deficiency. This technique may be useful for the assessment of the degree of in vitro or in vivo activation of the contact system.
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10

van Schilfgaarde, Muriel, Peter van Ulsen, Paul Eijk, Michiel Brand, Martin Stam, Jamal Kouame, Loek van Alphen, and Jacob Dankert. "Characterization of Adherence of NontypeableHaemophilus influenzae to Human Epithelial Cells." Infection and Immunity 68, no. 8 (August 1, 2000): 4658–65. http://dx.doi.org/10.1128/iai.68.8.4658-4665.2000.

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ABSTRACT The adherence of 58 nontypeable Haemophilus influenzaeisolates obtained from patients with otitis media or chronic obstructive pulmonary disease (COPD) and obtained from the throats of healthy individuals to Chang and NCI-H292 epithelial cells was compared. Otitis media isolates, but not COPD isolates, adhered significantly more to both cell lines than did throat isolates. Since high-molecular-weight (HMW) proteins are major adhesins of nontypeableH. influenzae, the isolates were screened for HMW protein expression by Western blotting with two polyclonal sera and PCR withhmw-specific primers. Twenty-three of the 32 adhering isolates (72%) and only 1 of the 26 nonadherent strains were HMW protein or hmw gene positive. Among the 32 isolates adhering to either cell line, 5 different adherence patterns were distinguished based on the inhibiting effect of dextran sulfate. UsingH. influenzae strain 12 expressing two well-defined HMW proteins (HMW1 and HMW2) and its isogenic mutants as a reference, we observed HMW1-like adherence to both cell lines for 16 of the 32 adherent isolates. Four others showed HMW2-like adherence to NCI-H292. Of the three other patterns of adherence, one probably also involved HMW protein. Screening of the isolates with six HMW-specific monoclonal antibodies in a whole-cell enzyme-linked immunosorbent assay showed that the HMW proteins of COPD isolates and carrier isolates were more distinct from the HMW proteins from H. influenzae strain 12 than those from otitis media isolates. Characterization of the HMW protein of a COPD isolate by adherence and DNA sequence analysis showed that despite large sequence diversity in the hmwA gene, probably resulting in the antigenic differences, the HMW protein mediated the HMW2-like adherence of this strain.
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11

Kleniewski, J., and V. Donaldson. "Granulocyte elastase cleaves human high molecular weight kininogen and destroys its clot-promoting activity." Journal of Experimental Medicine 167, no. 6 (June 1, 1988): 1895–907. http://dx.doi.org/10.1084/jem.167.6.1895.

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Purified human granulocyte elastase cleaved purified human high molecular weight (HMW) kininogen into multiple low molecular weight fragments, and destroyed the clot-promoting activity of the HMW kininogen. Elastase digestion did not release kinin or destroy the bradykinin portion of the HMW kininogen molecule; kallikrein could release kinin from the elastase-induced low molecular weight digestion products of HMW kininogen. Purified alpha 1-antitrypsin prevented the destruction of the clot-promoting activity of HMW kininogen by elastase; it also delayed the clotting of normal plasma. Elastase may play a significant role in altered hemostasis as well as fibrinolysis, in areas of inflammation to which polymorphonuclear leukocytes have been attracted.
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12

Wang, H. Q., and X. Y. Zhang. "An approach for isolating high-molecular-weight glutenin subunit genes using monoclonal antibodies." Genome 49, no. 2 (February 1, 2006): 181–89. http://dx.doi.org/10.1139/g05-094.

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High-molecular-weight glutenin subunits (HMW-GSs) play an important role in the breadmaking quality of wheat flour. In China, cultivars such as Triticum aestivum 'Xiaoyan No. 6' carrying the 1Bx14 and 1By15 glutenin subunits usually have attributes that result in high-quality bread and noodles. HMW-GS 1Bx14 and 1By15 were isolated by preparative sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and used as an antigen to immunize BALB/c mice. A resulting monoclonal antibody belonging to the IgG1 subclass was shown to bind to all HMW-GSs of Triticum aestivum cultivars, but did not bind to other storage proteins of wheat seeds in a Western blot analysis. After screening a complementary DNA expression library from immature seeds of 'Xiaoyan No. 6' using the monoclonal antibody, the HMW-GS 1By15 gene was isolated and fully sequenced. The deduced amino acid sequence showed an extra stretch of 15 amino acid repeats consisting of a hexapeptide and a nonapeptide in the repetitive domain of this y-type HMW subunit. Bacterial expression of a modified 1By15 gene, in which the coding sequence for the signal peptide was removed and a BamHI site eliminated, gave rise to a protein with mobility identical to that of HMW-GSs extracted from seeds of 'Xiaoyan No. 6' via SDS-PAGE. This approach for isolating genes using specific monoclonal antibody against HMW-GS genes is a good alternative to the extensively used polymerase chain reaction (PCR) technology based on sequence homology of HMW-GSs in wheat and its relatives.Key words: wheat, HMW-GS, monoclonal antibody, immunoscreen.
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13

Lang, Susanne M. "Akute COPD-Exazerbationen: Positive Wirkung von inhalierter hochmolekularer Hyaluronsäure bei schwerer Ateminsuffizienz." Kompass Pneumologie 9, no. 3 (2021): 134–35. http://dx.doi.org/10.1159/000516521.

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<b>Background:</b> Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. AECOPD treatment remains limited. High molecular weight hyaluronan (HMW-HA) is a glycosaminoglycan sugar, which is a physiological constituent of the lung extracellular matrix and has notable anti-inflammatory and hydrating properties. <b>Research question:</b> We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD. <b>Methods:</b> We conducted a single center, randomized, placebo-controlled, double-blind study to investigate the effect of inhaled HMW-HA in patients with severe AECOPD necessitating non-invasive positive-pressure ventilation (NIPPV). Primary endpoint was time until liberation from NIPPV. <b>Results:</b> Out of 44 screened patients, 41 were included in the study (21 for placebo and 20 for HMW-HA). Patients treated with HMW-HA had significantly shorter duration of NIPPV. HMW-HA treated patients also had lower measured peak airway pressures on the ventilator and lower systemic inflammation markers after liberation from NIPPV. In vitro testing showed that HMW-HA significantly improved mucociliary transport in air-liquid interface cultures of primary bronchial cells from COPD patients and healthy primary cells exposed to cigarette smoke extract. <b>Interpretation:</b> Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD. Beneficial effects of HMW-HA on mucociliary clearance and inflammation may account for some of the effects (NCT02674880, www.clinicaltrials.gov).
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de Munk, Gerard A. W., Eleonore Groeneveld, and Dingeman C. Rijken. "Comparison of the In Vitro Fibrinolytic Activities of Low and High Molecular Weight Single-Chain Urokinase-Type Plasminogen Activator." Thrombosis and Haemostasis 70, no. 03 (1993): 481–85. http://dx.doi.org/10.1055/s-0038-1649609.

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SummaryThe fibrinolytic activity of low molecular weight (LMW) single-chain urokinase-type plasminogen activator (scu-PA) lacking the epidermal growth factor domain and the kringle domain was compared with the activity of high molecular weight (HMW) scu-PA. LMW scu-PA was 1-5 times less active than HMW scu-PA in a fibrin plate method, in a purified fibrin clot lysis assay and in a plasma clot lysis assay. Time course experiments in a chromogenic plasminogen activator assay suggested that LMW scu-PA was less sensitive to activation by plasmin than HMW scu-PA. This was confirmed in a scu-PA activation test, which showed that at a concentration of 40 IU/ml LMW scu-PA required a three-fold higher plasmin concentration for 50% activation in 20 min than did HMW scu-PA. Kinetic experiments in the presence of 0.1 M NaCl showed non-standard Michaelis-Menten kinetics for the activation by plasmin of both HMW and LMW scu-PA. In contrast, standard kinetics was observed at 0.15 M NaCl, showing a 2.6-fold lower catalytic efficiency for LMW scu-PA than for HMW scu-PA. It is concluded that the plasmin activation of LMW scu-PA is about three times slower than the activation of HMW scu-PA. This explains, at least partially, the lower fibrinolytic activity of LMW scu-PA in comparison with HMW scu-PA.
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Chang, JJ, CF Scott, and RW Colman. "Role of arginine residues in the coagulant activity of high molecular weight kininogen." Blood 67, no. 3 (March 1, 1986): 805–10. http://dx.doi.org/10.1182/blood.v67.3.805.805.

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Abstract High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a procofactor that, after cleavage by kallikrein or factor XIIa, gains ability to bind to the surface. The mechanism responsible for this increased affinity for the surface is unknown. We hypothesized that modification of arginine residues may prevent cleavage of HMW kininogen, since the initial kallikrein-induced cleavage sites on the HMW kininogen molecule are at the NH2 terminal and the COOH terminal of the bradykinin-containing portion of the molecule, each of which contains arginine. We found that modification with butanedione of four arginine residues in the HMW kininogen molecule prevented bradykinin release, which results from cleavage of HMW kininogen. Furthermore, HMW kininogen coagulant activity was lost, in proportion to the degree of arginine modification, until 6.6 residues had been modified. Complex formation with prekallikrein, however, was found to be uneffected by the modification of modified HMW kininogen. To account for the loss of coagulant activity, we also examined the ability of modified HMWKa (active cofactor) to bind to an activating surface. The affinity of modified HMWKa for kaolin was tenfold less than the affinity of unmodified HMWKa. These data suggest that arginine residues play a critical role in the ability of HMW kininogen to function as an activation cofactor, both by preventing the cleavages that produce HMWKa as well as by decreasing the affinity of HMWKa for the surface.
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Chang, JJ, CF Scott, and RW Colman. "Role of arginine residues in the coagulant activity of high molecular weight kininogen." Blood 67, no. 3 (March 1, 1986): 805–10. http://dx.doi.org/10.1182/blood.v67.3.805.bloodjournal673805.

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High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a procofactor that, after cleavage by kallikrein or factor XIIa, gains ability to bind to the surface. The mechanism responsible for this increased affinity for the surface is unknown. We hypothesized that modification of arginine residues may prevent cleavage of HMW kininogen, since the initial kallikrein-induced cleavage sites on the HMW kininogen molecule are at the NH2 terminal and the COOH terminal of the bradykinin-containing portion of the molecule, each of which contains arginine. We found that modification with butanedione of four arginine residues in the HMW kininogen molecule prevented bradykinin release, which results from cleavage of HMW kininogen. Furthermore, HMW kininogen coagulant activity was lost, in proportion to the degree of arginine modification, until 6.6 residues had been modified. Complex formation with prekallikrein, however, was found to be uneffected by the modification of modified HMW kininogen. To account for the loss of coagulant activity, we also examined the ability of modified HMWKa (active cofactor) to bind to an activating surface. The affinity of modified HMWKa for kaolin was tenfold less than the affinity of unmodified HMWKa. These data suggest that arginine residues play a critical role in the ability of HMW kininogen to function as an activation cofactor, both by preventing the cleavages that produce HMWKa as well as by decreasing the affinity of HMWKa for the surface.
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17

Zheng, Jia, Xinhua Xiao, Qian Zhang, Lili Mao, Ming Li, Miao Yu, Jianping Xu, and Ying Wang. "Correlation of High-Molecular-Weight Adiponectin and Leptin Concentrations with Anthropometric Parameters and Insulin Sensitivity in Newborns." International Journal of Endocrinology 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/435376.

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Objective. High-molecular-weight adiponectin (HMW-adiponectin) and leptin are two important adipokines. The aim of this study was to examine the association between the two adipokines and anthropometric measurements of neonates at birth. Furthermore, we would like to explore whether HMW-adiponectin and leptin correlate with insulin sensitivity in neonates.Methods. Venous cord blood samples were obtained from 266 full-term healthy neonates consecutively born at Peking Union Medical College Hospital. HMW-adiponectin, leptin, blood glucose, and insulin concentrations were measured.Results. HMW-adiponectin and leptin were significantly higher in females compared with males (P=0.031andP=0.000, resp.). Univariate correlation analysis showed that leptin concentrations in cord blood were positively associated with gestational age, birth weight, body length, ponderal index, placenta weight, insulin, and insulin sensitivity (allP<0.001). However, there was no correlation between cord blood HMW-adiponectin levels and foetal anthropometric measurements or foetal insulin sensitivity indicators (allP>0.05). Multivariate linear regression analysis indicated that leptin (B=-0.126,P=0.045) in cord blood was independently associated with insulin sensitivity.Conclusions. Leptin concentrations, but not HMW-adiponectin, were positively associated with foetal anthropometric measurements. Leptin concentrations are significantly associated with foetal insulin sensitivity, and there were no significant correlations between HMW-adiponectin levels and foetal insulin sensitivity.
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Song, Lijun, Liqun Li, Liye Zhao, Zhenzhen Liu, Tingting Xie, and Xuejun Li. "Absence of Dx2 at Glu-D1 Locus Weakens Gluten Quality Potentially Regulated by Expression of Nitrogen Metabolism Enzymes and Glutenin-Related Genes in Wheat." International Journal of Molecular Sciences 21, no. 4 (February 18, 2020): 1383. http://dx.doi.org/10.3390/ijms21041383.

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Absence of high-molecular-weight glutenin subunit (HMW-GS) Dx2 weakens the gluten quality, but it is unclear how the absence of Dx2 has these effects. Thus, we investigated the gluten quality in terms of cytological, physicochemical, and transcriptional characteristics using two near-isogenic lines with Dx2 absent or present at Glu-D1 locus. Cytological observations showed that absence of Dx2 delayed and decreased the accumulation of protein bodies (PBs), where fewer and smaller PBs formed in the endosperm. The activity and gene expression levels of nitrogen assimilation and proteolysis enzymes were lower in HMW-D1a without Dx2 than HMW-D1p with Dx2, and thus less amino acid was transported for protein synthesis in the grains. The expression pattern of genes encoding Glu-1Dx2+1Dy12 was similar to those of three transcription factors, where these genes were significantly down-regulated in HMW-D1a than HMW-D1p. Three genes involving with glutenin polymerization were also down-regulated in HMW-D1a. These results may explain the changes in the glutenin and glutenin macropolymer (GMP) levels during grain development. Therefore, we suggest that the lower nitrogen metabolism capacity and expression levels of glutenin synthesis-related genes in HMW-D1a accounted for the lower accumulation of glutenin, GMP, and PBs, thereby weakening the structural‒thermal properties of gluten.
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Ma, Xin, Xuye Du, Cunyao Bo, Hongwei Wang, Anfei Li, and Lingrang Kong. "Modification of a novel x-type high-molecular-weight glutenin subunit gene from Aegilops markgrafii to improve dough strength of wheat flour." Crop and Pasture Science 69, no. 9 (2018): 873. http://dx.doi.org/10.1071/cp18036.

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High-molecular-weight glutenin subunits (HMW-GS) in bread wheat are major determinants of dough viscoelastic properties and the end-use quality of wheat flour. Cysteine residues, which form intermolecular disulphide bonds in HMW-GS, could improve the strength of gluten. To our knowledge, the number and position of cysteine residues in HMW-GS are conserved between wheat (Triticum aestivum) and Aegilops markgrafii. In the present study, we modified a gene (1Cx1.1) from Ae. markgrafii for an HMW-GS that possessed the typical structure and conserved number of cysteines. Site-directed mutagenesis was carried out in 1Cx1.1 to investigate how the position of cysteine residues in HMW-GS affects the mixing properties of dough. Six HMW-GS containing an extra cysteine residue were expressed in Escherichia coli, and the proteins were purified at sufficient scale for incorporation into flour to test dough quality. There were large differences in dough property among samples containing different modified subunits. Cysteine substituting in the N-terminal or repetitive-domain of HMW-GS could significantly improve dough quality. The results showed that the strategy was useful for providing genetic resources for gene engineering, and hence could be valuable for improving the processing quality of wheat.
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Sato, Yoshiaki, Hironori Yoshino, Eichi Tsuruga, and Ikuo Kashiwakura. "Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-like Receptor Agonist and Radiation." Current Cancer Drug Targets 20, no. 5 (June 5, 2020): 372–81. http://dx.doi.org/10.2174/1568009620666200115161717.

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Background: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play key roles in the antiviral response, but recent works show that RLR activation elicits anticancer activity as well, including apoptosis. Previously, we demonstrated that the anticancer activity of the RLR agonist Poly(I:C)-HMW/LyoVec™ [Poly(I:C)-HMW] against human lung cancer cells was enhanced by cotreatment with ionizing radiation (IR). In addition, cotreatment with Poly(I:C)-HMW and IR induced apoptosis in a Fas-independent manner, and increased Fas expression on the cell surface. Objective: The current study investigated the resultant hypothesis that Fas ligand (FasL) may enhance apoptosis in lung cancer cells cotreated with Poly(I:C)-HMW+IR. Methods: FasL was added into culture medium at 24 h following cotreatment with Poly(I:C)- HMW+IR, after upregulation of cell surface Fas expression on human lung cancer cells A549 and H1299 have already been discussed. Results: FasL enhanced the apoptosis of A549 and H1299 cells treated with Poly(I:C)-HMW+IR. Similarly, IR alone - and not Poly(I:C)-HMW - resulted in the upregulation of cell surface Fas expression followed by a high response to FasL-induced apoptosis, thus suggesting that the high sensitivity of cells treated with Poly(I:C)-HMW+IR to FasL-induced apoptosis resulted from the cellular response to IR. Finally, knockdown of Fas by siRNA confirmed that the high response of treated cells to FasL-induced apoptosis is dependent on Fas expression. Conclusion: In summary, the present study indicates that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR is responsive to FasL-induced apoptosis, and a combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy.
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Alvarez, M. L., S. Guelman, N. G. Halford, S. Lustig, M. I. Reggiardo, N. Ryabushkina, P. Schewry, J. Stein, and R. H. Vallejos. "Silencing of HMW glutenins in transgenic wheat expressing extra HMW subunits." Theoretical and Applied Genetics 100, no. 2 (January 2000): 319–27. http://dx.doi.org/10.1007/s001220050042.

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22

Indulekha, K., J. Surendar, R. M. Anjana, K. Gokulakrishnan, M. Balasubramanyam, V. Aravindhan, and V. Mohan. "Circulating Levels of High Molecular Weight (HMW) Adiponectin and Total Adiponectin in Relation to Fat Distribution, Oxidative Stress and Inflammation in Asian Indians." Disease Markers 33, no. 4 (2012): 185–92. http://dx.doi.org/10.1155/2012/672939.

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Aim: To look at the association of total and high molecular weight (HMW) adiponectin with markers of fat distribution, oxidative stress and inflammation in Asian Indians.Methods: A total of 120 subjects were chosen randomly from Chennai Urban Rural Epidemiological Study. Fasting HMW adiponectin levels, TNF-alpha and oxidized LDL were measured using ELISA. High sensitivity C reactive protein (hsCRP) was measured by a high sensitive nephelometric assay. Lipid peroxidation was measured by Tbars assay and protein carbonyl content was assessed by DNPH assay. Visceral and subcutaneous fat areas were assessed by computed tomography (CT) scan.When stratified based on the tertiles of visceral fat, the levels of total (p= 0.03) and HMW adiponectin (p= 0.007) were highest in the first tertile followed by tertiles 2 and 3 whereas in tertiles of subcutaneous fat, there was no such trend. With increasing tertiles of Tbars, the levels of total (p= 0.03) and HMW adiponectin decreased (p= 0.002). The levels of HMW (p< 0.001) but not total adiponectin was also found to decrease with increasing tertiles of Protein carbonyl content. The levels of Total (p= 0.02) and HMW adiponectin (p= 0.004) were highest in the first tertile of oxidized LDL followed by tertile 2 and tertile 3. With increasing tertiles of TNF-alpha total (p= 0.01) and HMW adiponectin (p= 0.004) was found to decrease. With increasing tertiles of hs-CRP, Total (p= 0.005) and HMWadiponectin (p= 0.007)was found to decrease.Conclusion: Oxidative stress markers, visceral but not subcutaneous fat and inflammation are associated with total and HMW adiponectin levles in Asian Indians.
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Gueugnon, Carine, Fabienne Mougin, Marie-Laure Simon-Rigaud, Jacques Regnard, Véronique Nègre, and Gilles Dumoulin. "Effects of an in-patient treatment program based on regular exercise and a balanced diet on high molecular weight adiponectin, resistin levels, and insulin resistance in adolescents with severe obesity." Applied Physiology, Nutrition, and Metabolism 37, no. 4 (August 2012): 672–79. http://dx.doi.org/10.1139/h2012-045.

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Adiponectin, the most abundant hormone produced by adipose tissue, circulates in 3 isoforms, including high molecular weight (HMW) adiponectin. The latter has been suggested to be a better predictor of metabolic disturbances and insulin resistance associated with obesity. This study investigated changes in total and HMW adiponectin, resistin, and homeostasis model assessment (HOMA) during a 9-month in-patient treatment program based on physical exercise and a balanced diet in 32 severely obese adolescents. Total and HMW adiponectin, resistin, and HOMA were measured at baseline (month 0) and during the program (months 3, 6, 9). In addition, a control group of 15 teenagers served as a reference for the baseline assessments. At baseline, HMW adiponectin was more markedly decreased in obese adolescents than total adiponectin, and both were lower than in controls. Conversely, resistin and HOMA were higher in obese adolescents. During the program, there was a significant change in body composition and improved insulin sensitivity among obese teenagers. In addition, HMW adiponectin and the ratio of HMW-to-total adiponectin increased throughout the study, whereas total adiponectin only increased up until the sixth month. On the contrary, resistin did not show any significant change. In obese adolescents, a long-term combination of aerobic exercise and a balanced diet, inducing change in body composition and improved insulin sensitivity, markedly increased HMW adiponectin compared with total adiponectin, without any change in resistin concentrations. Our results thus suggest that the determination of HMW adiponectin could be more useful than measurement of total adiponectin in clinical settings.
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Du, Xuye, Biya Xia, Fang He, and Mingjian Ren. "1Mx2.1, a novel high-molecular-weight glutenin subunit from Aegilops comosa and its relationship to high-quality dough." Plant Genetic Resources: Characterization and Utilization 17, no. 04 (April 1, 2019): 379–81. http://dx.doi.org/10.1017/s1479262119000091.

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AbstractHigh-molecular-weight glutenin subunit (HMW-GS) of endosperm is mainly correlated with dough quality of bread wheat. In wheat cultivars, the HMW-GS genes with good processing quality are limited. However, there are an amount of excellent HMW-GS genes presenting in wheat-related species. In this work, two novel HMW-GS genes located on 1 M chromosome from Aegilops comosa have been cloned, designated as 1Mx2.1 and 1My12.1, respectively. The molecular structure of 1Mx2.1 and 1My12.1 showed high similarity with the published HMW-GS, but containing unique structures. 1Mx2.1 contained an extra cysteine residue in the repetitive domain, and 1My12.1 lost the conservative cysteine residue in the C-terminal domain. In vitro mixing test has indicated that 1Mx2.1 contributes excellent dough quality. The Ae. comosa can be used as an important genetic resource for wheat quality improvement.
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25

Hayashi, H., F. Ishimaru, T. Fujita, N. Tsurumi, T. Tsuda, and I. Kimura. "Molecular genetic survey of five Japanese families with high-molecular- weight kininogen deficiency." Blood 75, no. 6 (March 15, 1990): 1296–304. http://dx.doi.org/10.1182/blood.v75.6.1296.1296.

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Abstract Analyses of the kininogen (KGN) molecule and KGN gene status in five Japanese families with high-molecular-weight (HMW) KGN deficiency were performed by the immunoblotting method with monoclonal antibodies to HMW-KGN, and by the Southern blotting method with the cDNA for human low-molecular-weight prekininogen. No molecular abnormality of KGN was detected in the DNA from four patients with total KGN deficiency or one patient with isolated HMW-KGN deficiency. In the former, the KGN gene appeared to be grossly normal at the level of the whole genome on Southern blotting. In isolated HMW-KGN deficiency, a partial deletion in intron 7 was found by restriction analyses of EcoRI, BamHI, HindIII, Sca I, and Bgl II fragments. This partial deletion is assumed to be related to an abnormality of the alternative RNA splicing events for HMW-prekininogen mRNA.
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Hayashi, H., F. Ishimaru, T. Fujita, N. Tsurumi, T. Tsuda, and I. Kimura. "Molecular genetic survey of five Japanese families with high-molecular- weight kininogen deficiency." Blood 75, no. 6 (March 15, 1990): 1296–304. http://dx.doi.org/10.1182/blood.v75.6.1296.bloodjournal7561296.

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Analyses of the kininogen (KGN) molecule and KGN gene status in five Japanese families with high-molecular-weight (HMW) KGN deficiency were performed by the immunoblotting method with monoclonal antibodies to HMW-KGN, and by the Southern blotting method with the cDNA for human low-molecular-weight prekininogen. No molecular abnormality of KGN was detected in the DNA from four patients with total KGN deficiency or one patient with isolated HMW-KGN deficiency. In the former, the KGN gene appeared to be grossly normal at the level of the whole genome on Southern blotting. In isolated HMW-KGN deficiency, a partial deletion in intron 7 was found by restriction analyses of EcoRI, BamHI, HindIII, Sca I, and Bgl II fragments. This partial deletion is assumed to be related to an abnormality of the alternative RNA splicing events for HMW-prekininogen mRNA.
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27

Jang, You-Ran, Kyoungwon Cho, Se Won Kim, Susan B. Altenbach, Sun-Hyung Lim, Jae-Ryeong Sim, and Jong-Yeol Lee. "Development of an Optimized MALDI-TOF-MS Method for High-Throughput Identification of High-Molecular-Weight Glutenin Subunits in Wheat." Molecules 25, no. 18 (September 22, 2020): 4347. http://dx.doi.org/10.3390/molecules25184347.

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Because high-molecular-weight glutenin subunits (HMW-GS) are important contributors to wheat end-use quality, there is a need for high-throughput identification of HMW-GS in wheat genetic resources and breeding lines. We developed an optimized method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to distinguish individual HMW-GS by considering the effects of the alkylating reagent in protein extraction, solvent components, dissolving volume, and matrix II components. Using the optimized method, 18 of 22 HMW-GS were successfully identified in standard wheat cultivars by differences in molecular weights or by their associations with other tightly linked subunits. Interestingly, 1Bx7 subunits were divided into 1Bx7 group 1 and 1Bx7 group 2 proteins with molecular weights of about 82,400 and 83,000 Da, respectively. Cultivars containing the 1Bx7 group 2 proteins were distinguished from those containing 1Bx7OE using well-known DNA markers. HMW-GS 1Ax2* and 1Bx6 and 1By8 and 1By8*, which are difficult to distinguish due to very similar molecular weights, were easily identified using RP-HPLC. To validate the method, HMW-GS from 38 Korean wheat varieties previously evaluated by SDS-PAGE combined with RP-HPLC were analyzed by MALDI-TOF-MS. The optimized MALDI-TOF-MS method will be a rapid, high-throughput tool for selecting lines containing desirable HMW-GS for breeding efforts.
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Lennon, Jay T. "Diversity and Metabolism of Marine Bacteria Cultivated on Dissolved DNA." Applied and Environmental Microbiology 73, no. 9 (March 2, 2007): 2799–805. http://dx.doi.org/10.1128/aem.02674-06.

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ABSTRACT Dissolved DNA (dDNA) is a potentially important source of energy and nutrients in aquatic ecosystems. However, little is known about the identity, metabolism, and interactions of the microorganisms capable of consuming dDNA. Bacteria from Eel Pond (Woods Hole, MA) were cultivated on low-molecular-weight (LMW) or high-molecular-weight (HMW) dDNA, which served as the primary source of carbon, nitrogen, and phosphorus. Cloning and sequencing of 16S rRNA genes revealed that distinct bacterial assemblages with comparable levels of taxon richness developed on LMW and HMW dDNA. Since the LMW and HMW dDNA used in this study were stoichiometrically identical, the results confirm that the size alone of dissolved organic matter can influence bacterial community composition. Variation in the growth and metabolism of isolates provided insight into mechanisms that may have generated differences in bacterial community composition. For example, bacteria from LMW dDNA enrichments generally grew better on LMW dDNA than on HMW dDNA. In contrast, bacteria isolated from HMW dDNA enrichments were more effective at degrading HMW dDNA than bacteria isolated from LMW dDNA enrichments. Thus, marine bacteria may experience a trade-off between their ability to compete for LMW dDNA and their ability to access HMW dDNA via extracellular nuclease production. Together, the results of this study suggest that dDNA turnover in marine ecosystems may involve a succession of microbial assemblages with specialized ecological strategies.
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Magkos, Faidon, B. Selma Mohammed, and Bettina Mittendorfer. "Enhanced insulin sensitivity after acute exercise is not associated with changes in high-molecular weight adiponectin concentration in plasma." European Journal of Endocrinology 162, no. 1 (January 2010): 61–66. http://dx.doi.org/10.1530/eje-09-0756.

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Background and objectiveThe effect of exercise on the plasma concentration of high-molecular weight (HMW) adiponectin (i.e. the biologically active form of circulating adiponectin) and the possible role of HMW adiponectin in mediating the exercise-induced enhancement of insulin action are not known. The aim of this study was to evaluate the relationship between the post-exercise increase in insulin sensitivity and plasma HMW adiponectin concentration.Design and methodsWe measured total and HMW adiponectin concentrations in plasma using an ELISA kit, and insulin sensitivity using the updated homeostasis model assessment of insulin sensitivity (HOMA2-IS) score in the basal, overnight fasted state, once ∼12 h after a single bout of moderate-intensity endurance exercise and once after an equivalent period of rest, in 27 healthy men and women (age: 29±1 years and body mass index: 24.7±0.8 kg/m2).ResultsThe HOMA2-IS score was 18±7% greater after exercise than after rest (229±20 and 196±17 respectively;P=0.006), whereas the concentrations of total adiponectin (7.8±0.5 and 7.7±0.5 mg/l respectively;P=0.597) and HMW adiponectin (3.0±0.3 and 3.0±0.3 mg/l respectively;P=0.625) were not different. The exercise-induced change in HOMA2-IS score was not related to changes in total and HMW adiponectin concentrations (P>0.3).ConclusionsChanges in HMW adiponectin concentration are not involved in the acute exercise-induced enhancement of insulin action.
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Wright, Olivia R. L., Ingrid J. Hickman, William G. Petchey, Clair M. Sullivan, Cynthia Ong, Felicity J. Rose, Choaping Ng, Johannes B. Prins, Jonathan P. Whitehead, and Trisha M. O'Moore-Sullivan. "The effect of 25-hydroxyvitamin D on insulin sensitivity in obesity: is it mediated via adiponectin?" Canadian Journal of Physiology and Pharmacology 91, no. 6 (June 2013): 496–501. http://dx.doi.org/10.1139/cjpp-2012-0436.

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There has been substantial recent interest in using vitamin D to improve insulin sensitivity and preventing/delaying diabetes in those at risk. There is little consensus on the physiological mechanisms and whether the association is direct or indirect through enhanced production of insulin-sensitising chemicals, including adiponectin. We examined cross-sectional associations between serum 25-hydroxyvitamin D (25(OH)D) and insulin sensitivity (Matsuda index), parathyroid hormone (PTH), waist circumference, body mass index (BMI), triglycerides (TG), total and high molecular weight (HMW) adiponectin, HMW : total adiponectin ratio (HMW : total adiponectin), and total cholesterol : HDL cholesterol ratio (TC:HDL cholesterol) in 137 Caucasian adults of mean age 43.3 ± 8.3 years and BMI 38.8 ± 6.9 kg/m2. Total adiponectin (standardised β = 0.446; p < 0.001), waist circumference (standardised β = –0.216; p < 0.05), BMI (standardised β = –0.212; p < 0.05), and age (standardised β = –0.298; p < 0.001) were independently associated with insulin sensitivity. Serum 25(OH)D (standardised β = 0.114; p = 0.164) was not associated with insulin sensitivity, total or HMW adiponectin, HMW : total adiponectin, or lipids. Our results provide the novel finding that 25(OH)D is not associated with HMW adiponectin or HMW : total adiponectin in nondiabetic, obese adults and support the lack of association between 25(OH)D and lipids noted by others in similar groups of patients.
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31

Han, Xinjun, Yan Feng, Xinbing Han, Haiqing Guo, Jianbo Zhu, Chao Ning, Fen Liu, Shidong Li, Xiaomei Li, and Yi-ning Yang. "8-Week Basic Military Training Improves Adiponectin Multimer Ratio in Healthy Young Males." International Journal of Sports Medicine 40, no. 01 (November 27, 2018): 43–51. http://dx.doi.org/10.1055/a-0770-6093.

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AbstractTo investigate the effect of exercise on adiponectin in young healthy human males, we examined serum total adiponectin and high-molecular-weight (HMW) adiponectin in newly recruited male soldiers who participated in an 8-week basic military training (BMT). A total of 95 males (mean age, 18.79±1.50 years) were sampled from among 1,100 new male army recruits in China. Participants were separated into 3 groups according to their body mass index (BMI): overweight group (BMI: 24.9 kg/m2 to<30 kg/m2; n=26); normal-weight group (BMI: 18.5 kg/m2 to<24.9 kg/m2; n=40); and underweight group (BMI:<18.5 kg/m2; n=29). Anthropometric measurements, fasting serum total adiponectin, HMW adiponectin, and lipid profiles were recorded at baseline and at the end of the 8-week BMT. After the 8-week BMT, the HMW/total adiponectin ratio (HMW/total ratio) and HDL cholesterol improved significantly (p<0.001 and p<0.001, respectively). HMW/total ratio showed significant correlations with HDL cholesterol. Our study suggests that an 8-week BMT can improve the HMW/total ratio in healthy young males regardless of their BMI and anthropometry. Both HMW/total ratio and HDL cholesterol can serve as potential biomarkers for assessing the efficacy of exercise and may have metabolic benefits for preventing obesity and obesity-related disease.
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32

Haberichter, Sandra L., Paula M. Jacobi, Veronica H. Flood, Pamela A. Christopherson, Joan Cox Gill, Daniel B. Bellissimo, and Kenneth D. Friedman. "Quantitative Analysis of VWF Multimer Structure: Discrimination Between VWD Subtypes." Blood 118, no. 21 (November 18, 2011): 1215. http://dx.doi.org/10.1182/blood.v118.21.1215.1215.

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Abstract Abstract 1215 The diagnosis of von Willebrand disease (VWD) and discrimination between its subtypes includes analysis of VWF:Ag, VWF:RCo, and VWF multimer structure. VWF multimer analysis is qualitative, and therefore a subjective assessment open to interpretation. It is often difficult to assess subtle differences in multimer structure. To address these shortcomings we have developed a quantitative method for analysis of VWF multimers. We have analyzed multimer structure for VWD patients and healthy controls recruited through the Zimmerman Program for the Molecular and Clinical Biology of von Willebrand Disease (ZPMCB-VWD). The patient population includes type 1 and type 2 VWD with well-defined genotypes and phenotypes. Multimer analysis was performed using a 0.65% LiDS-agarose gel electrophoresis system and western blotting with chemilumiscent detection using the Fujifilm LAS-3000 luminescent image analyzer. Densitometry was performed and area-under-the-curve calculated using MultiGauge analysis software. We calculated the percentage of low molecular weight (LMW) multimers defined as bands 1 – 5, mid-molecular weight (MMW) multimers (bands 6 – 10) and high molecular weight (HMW) multimers (bands >10). For healthy controls, the distribution of multimer density (mean ± standard deviation) was 25.3 ± 2.7% HMW, 56.1 ± 4.9% MMW, and 18.6 ± 3.4% LMW. Type 1 VWD (including type 1C) patients had a similar distribution of multimers (22.5 ± 7.6% HMW, 48.5 ± 6.7% MMW, 29.0 ± 7.2 % LMW), although there was a slight shift in distribution to increased LMW. For some type 1C patients with mutations including C1130Y and W1144G, we observed a small loss of HMW multimers (14.2 ± 0.8% HMW, 51.1 ± 1.4% MMW, 34.7 ± 2.3% LMW), as has been previously reported in patients with a C1130F variation. In contrast, some patients with the type 1C “Vicenza” mutation, R1205H, demonstrated increased HMW multimers (32.6 ± 1.0% HMW, 42.2 ± 4.0% MMW, 25.2 ± 3.0% LMW) as previously reported. Although the multimers in the type 1 patients are essentially normal, quantitative analysis reveals subtle abnormalities in structure. In type 2B VWD patients with mutations including V1316M, R1306W, and R1341W, a loss of HMW and MMW multimers was observed (7.1 ± 3.2% HMW, 40.4 ± 8.3% MMW, and 52.5 ± 11.4% LMW). A greater loss of HMW and MMW multimers was observed in patients with type 2A VWD with mutations including Y1349C, R1597W, G1609R, I1628T, G1631D, and G1670S (3.5 ± 6.2% HMW, 19.7 ± 20.4% MMW, and 76.9 ± 26.3% LMW). The type 2A subjects consisted of two groups: those with a virtually complete loss of HMW and MMW (0.0 ± 0% HMW, 4.0 ± 1.0% MMW, and 96.0 ± 1.0% LMW), and those with loss of HMW and decreased MMW (8.7 ± 7.5% HMW, 41.0 ± 14.7% MMW, and 50.3 ± 20.9% LMW). The latter group had a similar multimer distribution to that of type 2B VWD subjects. While most type 2A patients with mutations associated with increased susceptibility to ADAMTS13 proteolysis had severe multimer abnormalities (>95% LMW), some had only moderate abnormalities. Our study demonstrates that quantitative analysis of VWF multimer patterns more clearly distinguishes patients with various subtypes of VWD than subjective analysis. Although one of the two groups of type 2A patients is similar to the type 2B group, the other group is clearly different and is associated with specific genotypes, perhaps eliminating the need for DNA sequence analysis to make a definitive diagnosis for this group. This technique provides an objective measure of VWF structure to better characterize subtle changes observed in the subtypes of VWD and may help to determine the nature of any additional clinical laboratory testing to reach a clear-cut diagnosis. Disclosures: No relevant conflicts of interest to declare.
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Vawser, M.-J., and G. B. Cornish. "Over-expression of HMW glutenin subunit Glu-B1 7x in hexaploid wheat varieties (Triticum aestivum)." Australian Journal of Agricultural Research 55, no. 5 (2004): 577. http://dx.doi.org/10.1071/ar03227.

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In Canada in 1993, a special market class of wheat, Canada Western Extra Strong (CWES), was established to segregate wheat varieties known to produce very strong and extensible doughs. These exceptional dough properties enable CWES cultivars to be blended with wheats of lesser quality as well as being suited to the manufacture of frozen dough products. The high molecular weight (HMW) glutenin allele (Glu-B1al) that confers these properties, particularly dough strength, has now been identified. Typically, the presence of the Glu-B1al (7+8*) allele is associated with the overexpression of HMW-GS 1Bx 7. RP-HPLC was used to quantify the proportion (% area) of individual HMW-GS relative to total HMW-GS in wheat varieties of different origin. The B genome contributed the highest percentage of HMW-GS, with the exception of Glu-B1d (6+8*) where the D genome contributed the most. Cultivars that possessed the Glu-B1al allele contained a significantly higher (P < 0.001) proportion of HMW-GS (56.80 ± 3.25%) encoded by the B genome. This suggests that the proportion of Glu-B1 subunits, relative to the total amount of HMW-GS expressed, has a major effect on dough strength. We also identified germplasm, of different origin, that contains the Glu-B1al allele and overexpresses subunit 7, including the most likely source of this allele in bread wheat cultivars. The Glu-B1al allele in the varieties identified in this paper could be traced, at least through one parent, to the Argentinean bread wheat cultivar Klein Universal II. RP-HPLC elution and expression profiles of various common HMW-GS are also discussed.
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Kothapalli, Devashish, Liang Zhao, Elizabeth A. Hawthorne, Yan Cheng, Eric Lee, Ellen Puré, and Richard K. Assoian. "Hyaluronan and CD44 antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells." Journal of Cell Biology 176, no. 4 (February 12, 2007): 535–44. http://dx.doi.org/10.1083/jcb.200611058.

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High molecular weight (HMW) hyaluronan (HA) is widely distributed in the extracellular matrix, but its biological activities remain incompletely understood. We previously reported that HMW-HA binding to CD44 antagonizes mitogen-induced S-phase entry in vascular smooth muscle cells (SMCs; Cuff, C.A., D. Kothapalli, I. Azonobi, S. Chun, Y. Zhang, R. Belkin, C. Yeh, A. Secreto, R.K. Assoian, D.J. Rader, and E. Puré. 2001. J. Clin. Invest. 108:1031–1040); we now characterize the underlying molecular mechanism and document its relevance in vivo. HMW-HA inhibits the mitogen-dependent induction of cyclin D1 and down-regulation of p27kip1 in vascular SMCs. p27kip1 messenger RNA levels were unaffected by HMW-HA, but the expression of Skp2, the rate-limiting component of the SCF complex that degrades p27kip1, was reduced. Rescue experiments identified cyclin D1 as the primary target of HMW-HA. Similar results were observed in fibroblasts, and these antimitogenic effects were not detected in CD44-null cells. Analysis of arteries from wild-type and CD44-null mice showed that the effects of HMW-HA/CD44 on cyclin D1 and Skp2 gene expression are detected in vivo and are associated with altered SMC proliferation after vascular injury.
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Drake, Allison S., Brady T. Michael, Xin Hui Wang, Sheila J. N. Sait, Justin C. Earp, William J. Jusko, Soldano Ferrone, Eunice S. Wang, and Meir Wetzler. "The Effects of Anti-High Molecular Weight-Melanoma Associated Antigen (HMW-MAA) Monoclonal Antibodies (mAb) Against 11q23 Positive Acute Leukemia Cells." Blood 108, no. 11 (November 16, 2006): 4550. http://dx.doi.org/10.1182/blood.v108.11.4550.4550.

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Abstract Acute leukemia with 11q23 aberrations is associated with especially poor outcome to standard treatment. HMW-MAA is a membrane bound proteoglycan that has been targeted in the treatment of malignant melanoma. It is widely distributed on 11q23-positive leukemic cells and is not expressed on normal hematopoietic cells. Finally, HMW-MAA is believed to function by signaling through the focal adhesion kinase (Fak)/proline-rich tyrosine kinase 2 (Pyk2) pathways and by supporting angiogenesis via its expression on pericytes. We hypothesized that inhibition of HMW-MAA with mAb directed against specific HMW-MAA determinants would effectively limit the growth of 11q23-positive acute leukemia cells in vitro and in vivo, by affecting Fak/Pyk2 pathways. We examined an 11q23-positive acute myeloid leukemia (AML) cell line (ML-2) and leukemia cells from two patients (one AML, one acute lymphoblastic leukemia) with 11q23 aberrations. Our results demonstrate that ML-2 cells expressed only the VT68.2 and 225.28 determinants, while primary acute leukemia cells expressed VT68.2, 225.28, and 763.74 determinants. Treatment of ML-2 cells with mAb against VT68.2 and 225.28 in vitro did not affect overall proliferation but downregulated phosphorylated (p) Pyk2 expression as determined by Western blotting. Further, anti-HMW-MAA mAb treatment enhanced the anti-proliferative effect of cytarabine (y=0.7875) in vitro. Based on these results, we then evaluated the dose-response relationships and toxicities of anti-HMW-MAA mAb alone and in combination with cytarabine in subcutaneous ML-2 xenografts grown in SCID mice. A trend towards tumor inhibition was noted following high dose (1 mg/kg 2x/week) anti-225 mAb therapy but was not seen at lower (0.25 and 0.5 mg/kg) anti-225 mAb doses. Mice demonstrated no side effects or weight loss as a result of anti-225 therapy. No downregulation of pPyk2 in tumor cells was observed following anti-225 therapy at any dose. Furthermore, combination anti-225.28 HMW-MAA mAb and cytarabine treatment (at increasing cytarabine doses) did not result in improved tumor inhibition as compared to cytarabine alone (p&gt;0.05). We then evaluated the effects of HMW-MAA anti-225.28 and anti-763.74 mAb alone or together for treatment of NOD/SCID mice engrafted with primary 11q23-positive leukemia patient cells. Combination anti-HMW-MAA mAb therapy resulted in no prolongation in survival of engrafted mice as compared to control treated animals. We were able to confirm the presence of high levels of circulating HMW-MAA mAb in the serum of animals 4 days following mAb injection. In addition, explanted ML-2 cells harvested following xenograft growth still maintained expression of the HMW-MAA determinants. We conclude that naïve anti-HMW-MAA mAb neither caused a statistically significant inhibitory effect nor enhanced the effect of cytarabine on 11q23-positive acute leukemia cells in vivo. Future studies using radiolabelled or toxin-conjugated antibodies may enhance the anti-tumor effects of targeted HMW-MAA immunotherapy for 11q23-positive acute leukemia.
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36

Konduru, Ramakrishna R., Steven N. Liss, and D. Grant Allen. "Recalcitrant Organics Emerging from Biological Treatment of Kraft Mill Effluents." Water Quality Research Journal 36, no. 4 (November 1, 2001): 737–57. http://dx.doi.org/10.2166/wqrj.2001.039.

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Abstract Recalcitrant organic matter (ROM) in combined kraft mill effluents is that organic matter remaining in the effluents after primary and secondary treatment. Recalcitrant organic matter comprises of both high molecular weight (HMW) and low molecular weight (LMW) components and is of interest, since environmental regulators are considering placing limits on final effluent COD and colour. Biologically treated pulp mill effluent was fractionated by ultrafiltration to study the contributions of the high and low molecular weight recalcitrant organics towards final effluent COD and AOX. Batch biodegradation tests were carried out on lab-generated biotreated effluent from lab scale sequencing batch reactors operating at 35, 45, 55 and 60°C, to investigate if the residual recalcitrant fraction could be further degraded. Biodegradation tests involved the optimization of the microbiological medium by the addition of either an alternate carbon source (glucose) or a carbon-nitrogen substrate (yeast extract). Treatment temperatures and nutrient levels were varied and the effect of each of these four factors on the biodegradability of the recalcitrant fractions was studied. The recalcitrant portion was found to be resistant to further biodegradation, even under optimized microbiological conditions. The HMW fraction of the ROM obtained from final biotreated effluent from a bleached kraft pulp mill (HMW ROMMill) was studied for its ability to bind other organic model pollutants in an aqueous environment. Pentachlorophenol (PCP) was tested for its binding onto the HMW ROMMill, using toxicity as a surrogate parameter for binding, in the Microtox™ test. Equilibrium dialysis studies were carried out to investigate the ability of HMW ROMMill to bind 14C-Benzopyrene (BaP) and 3H-dehydroabietic acid (DHA). Microtox™ studies failed to indicate the binding of PCP onto HMW ROMMill. BaP and DHA however did bind onto HMW ROMMill. BaP binding onto HMW ROMMill was higher than DHA binding, possibly due to its hydrophobicity. Also, increasing the dissolved organic carbon concentration of HMW ROMMill led to a decrease in the partition coefficient values for both BaP and DHA.
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Ainaa Almardhiyah, Abd Rashid, Zahali Zunura’in, Venkata Murali Krishna Bhavaraju, Siew Hua Gan, Abdullah Sarimah, Syed Abdullah Sharifah Zahhura, and Jan Mohamed Hamid Jan. "Nutritional Status Influences High-Molecular Weight (HMW) Adiponectin levels in Breast Cancer Patients: Comparison with Healthy Controls." World Nutrition Journal 2, no. 2 (January 4, 2019): 15. http://dx.doi.org/10.25220/wnj.v02.i2.0004.

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Introduction: Breast cancer is the leading killer of women in Malaysia. Nutritional status and adiponectin are modifiable risk factors for breast cancer occurrence which can be efficiently targeted. The purpose of this study was to determine the relationship between nutritional status and high molecular weight (HMW) adiponectin levels among breast cancer patients as compared to controls. Methods: This was a case- control study, conducted in Hospital Universiti Sains Malaysia and Universiti Sains Malaysia campus. Newly diagnosed breast cancer cases (n=55) were assigned as cases while healthy controls (n=58) were staff members of HUSM and USM campus. Sociodemographic and reproductive data were obtained with a standard questionnaire while the dietary data was obtained from a validated diet history questionnaire. Anthropometric assessments [weight, height, hip, waist circumference (WC) and body fat composition] were measured while overnight fasting venous blood samples were analysed for lipid profiles, glucose, insulin, high sensitivity C-reactive protein and HMW adiponectin. Results: A significant linear negative relationship exists between WC and HMW adiponectin (β=-0.05; p=0.005) among breast cancer cases. Additionally, HDL cholesterol was positively associated with HMW adiponectin (β=1.83; p=0.010) among the cases. BMI was negatively associated with HMW adiponectin (β=-0.02; p=0.001) among healthy controls. Conclusion: Our findings suggest that WC, BMI and HDL cholesterol had significant relationship with HMW adiponectin. Low levels of HMW adiponectin, low WC and high HDL levels may be protective against breast cancer
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Oslovičová, V., Z. Gálová, M. Chňapek, and Ž. Balážová. "Identification of Triticum aestivum L., Triticum spelta L. and Triticum durum DESF. genotypes on the HMW-GS base." Plant, Soil and Environment 56, No. 2 (February 26, 2010): 82–86. http://dx.doi.org/10.17221/2435-pse.

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The main goal of this work was to identify genotypes of three wheat species Triticum aestivum</i> L., <i>Triticum spelta</i> L., <i>Triticum durum</i> DESF.) on the basis of individual high-molecular-weight glutenin subunits (HMW-GS) and to predict their technological quality. Detection of HMW-GS was carried out by the standard reference method ISTA SDS-PAGE and the Glu-score was calculated according to the catalogue of alleles for HMW-GS. Among the common wheat varieties the highest Glu-score (10) was determined for the cultivars Axis, Istra and Solara. The most frequently occurring HMW-GS in genotypes of <i>Triticum aestivum</i> L. were 0; 7 + 9; 5 + 10. On the other hand, in the spelt wheat the highest frequency of HMW-GS was detected for 2*; 6 + 8; 2 + 12. The Glu-score for <i>Triticum spelta</i> L. genotypes ranged from 6 to 8. Among the <i>Triticum durum</i> DESF. cultivars, up to 71% were characterized by Glu-score 4, which predetermines them for special baking purposes. The most frequent combination of HMW-GS in durum wheat was 0 and 7 + 8. Thus, SDS PAGE of HMW-GS can be used for identification, differentiation and characterization of different species of wheat and for prediction of bread-making quality of wheat.
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39

Singleton, Patrick A., Tamara Mirzapoiazova, Yurong Guo, Saad Sammani, Nurbek Mambetsariev, Frances E. Lennon, Liliana Moreno-Vinasco, and Joe G. N. Garcia. "High-molecular-weight hyaluronan is a novel inhibitor of pulmonary vascular leakiness." American Journal of Physiology-Lung Cellular and Molecular Physiology 299, no. 5 (November 2010): L639—L651. http://dx.doi.org/10.1152/ajplung.00405.2009.

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Endothelial cell (EC) barrier dysfunction results in increased vascular permeability, a perturbation observed in inflammatory states, tumor angiogenesis, atherosclerosis, and both sepsis and acute lung injury. Therefore, agents that enhance EC barrier integrity have important therapeutic implications. We observed that binding of high-molecular-weight hyaluronan (HMW-HA) to its cognate receptor CD44 within caveolin-enriched microdomains (CEM) enhances human pulmonary EC barrier function. Immunocytochemical analysis indicated that HMW-HA promotes redistribution of a significant population of CEM to areas of cell-cell contact. Quantitative proteomic analysis of CEM isolated from human EC demonstrated HMW-HA-mediated recruitment of cytoskeletal regulatory proteins (annexin A2, protein S100-A10, and filamin A/B). Inhibition of CEM formation [caveolin-1 small interfering RNA (siRNA) and cholesterol depletion] or silencing (siRNA) of CD44, annexin A2, protein S100-A10, or filamin A/B expression abolished HMW-HA-induced actin cytoskeletal reorganization and EC barrier enhancement. To confirm our in vitro results in an in vivo model of inflammatory lung injury with vascular hyperpermeability, we observed that the protective effects of HMW-HA on LPS-induced pulmonary vascular leakiness were blocked in caveolin-1 knockout mice. Furthermore, targeted inhibition of CD44 expression in the mouse pulmonary vasculature significantly reduced HMW-HA-mediated protection from LPS-induced hyperpermeability. These data suggest that HMW-HA, via CD44-mediated CEM signaling events, represents a potentially useful therapeutic agent for syndromes of increased vascular permeability.
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40

Yannakoulia, Mary, Nikos Yiannakouris, Labros Melistas, Evaggelia Fappa, Nikoletta Vidra, Meropi D. Kontogianni, and Christos S. Mantzoros. "Dietary factors associated with plasma high molecular weight and total adiponectin levels in apparently healthy women." European Journal of Endocrinology 159, no. 4 (October 2008): R5—R10. http://dx.doi.org/10.1530/eje-08-0331.

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ObjectiveOur aim was to investigate associations between dietary factors and high molecular weight (HMW) as well as total adiponectin in a sample of apparently healthy adult Mediterranean women.Design and methodsTwo hundred and twenty women were enrolled in this study. Anthropometric and body composition measurements were performed in all subjects. Fasting blood samples were taken; HMW and total adiponectin concentrations were measured. Food intake was evaluated using 3-day food records. The frequency of consumption of several food groups was approximately quantified in terms of number of servings per day. Furthermore, dietary intakes of betaine, choline, and free choline were estimated.ResultsWomen in the highest HMW adiponectin tertile had higher fruit intake compared with those with lower levels, after adjusting for potential confounders (P=0.04). On the contrary, dietary betaine and choline intakes were not different among HMW adiponectin tertiles. In linear models, fruit consumption, controlling for biological and lifestyle variables, was significantly related to HMW adiponectin (partial r=0.15, P=0.04), but the association with total adiponectin did not reach statistical significance (partial r=0.11, P=0.12). A significant negative correlation between total adiponectin and refined cereals was also observed (partial r=−0.16, P=0.03).DiscussionThis is the first study that evaluates associations between dietary factors and HMW adiponectin levels. The associations found are moderate and indicate that, after multivariate adjustment, fruit consumption is related to HMW adiponectin in both linear and nonlinear models.
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Tao, Tao, Edmond P. Wickham, WuQiang Fan, Jiejin Yang, and Wei Liu. "Distribution of adiponectin multimeric forms in Chinese women with polycystic ovary syndrome and their relation to insulin resistance." European Journal of Endocrinology 163, no. 3 (September 2010): 399–406. http://dx.doi.org/10.1530/eje-10-0021.

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ObjectiveAdiponectin, an abundant adipokine with insulin-sensitizing properties, exists in different multimeric forms, including low-molecular weight, medium-molecular weight, and high-molecular weight (HMW) species. Alterations in the distribution of adiponectin multimers and the relationship between adiponectin multimers and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) remain unclear. The objective of this study was to compare adiponectin multimerization status and estimate insulin sensitivity in Chinese women with PCOS compared with age- and body mass index (BMI)-matched controls.MethodsCross-sectional study involving 64 Chinese women with PCOS and 59 normal women. Circulating total adiponectin and its multimeric forms were determined by ELISA, and IR was estimated using the homeostasis model assessment IR index (HOMA-IR).ResultsAfter controlling for BMI status, levels of both total and HMW adiponectin were significantly lower in women with PCOS compared with normal women (P<0.05). Furthermore, HMW adiponectin provided a stronger contribution to models predicting IR than total adiponectin. Lastly, decreased HMW adiponectin was associated with increased HOMA-IR in both normal and PCOS women, and this association was independent of both overall adiposity and visceral adiposity.ConclusionLevels of both total and HMW adiponectin were decreased in Chinese women with PCOS compared with normal control women, and the differences in HMW adiponectin persisted after controlling for BMI. Furthermore, HMW adiponectin is a stronger predictor of IR than total adiponectin in both women with PCOS and normal women.
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42

Kajendran, Kirushanthy, Naduviladath Vishvanath Chandrasekharan, Chamari Madhu Hettiarachchi, and Wijerupage Sandhya Sulochana Wijesundera. "Cloning and characterization of high molecular weight glutenin gene from Triticum aestivum cultivar Dacke." International Journal of Scientific Reports 4, no. 10 (September 29, 2018): 254. http://dx.doi.org/10.18203/issn.2454-2156.intjscirep20184193.

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<p class="abstract"><strong>Background:</strong> High molecular weight (HMW) glutenin protein plays a crucial role in determining dough viscoelastic properties that determines the quality of wheat flour. The aim of the present study was to isolate, clone and analyze (<em>in silico</em>) the HMW glutenin gene of <em>Triticum aestivum</em> cultivar Dacke.</p><p class="abstract"><strong>Methods:</strong> Primers were designed to amplify a 2445 bp fragment of HMW glutenin gene. Ax type HMW glutenin gene from <em>Triticum aestivum</em> cultivar Dacke was isolated using PCR and it was sequenced by primer walking. </p><p class="abstract"><strong>Results:</strong> Amplified HMW glutenin gene was designated as HMWGAx. Sequence analysis revealed a complete open reading frame encoding 815 amino acid residues with N- and C terminal non-repetitive domain and a central repetitive domain. The calculated molecular weight of the deduced HMW glutenin protein was ~88 kDa and the number of cysteine residues in the HMWGAx was four, in accordance with other x type HMW glutenin proteins. Phylogenetic analysis revealed 100% homology to the previously studied Ax2* type HMW glutenin gene from cultivar Cheyenne. Predicted secondary structure results showed that it was similar to1Ax1 type of common wheat (<em>Triticum aestivum</em>), having superior flour milling quality.</p><p><strong>Conclusions:</strong> Sequence analysis suggests that HMWGAx protein significantly and positively correlates with the properties of elasticity and extensibility of gluten. </p>
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43

Peters, M. G., J. L. Ambrus, A. S. Fauci, and E. J. Brown. "The Bb fragment of complement factor B acts as a B cell growth factor." Journal of Experimental Medicine 168, no. 4 (October 1, 1988): 1225–35. http://dx.doi.org/10.1084/jem.168.4.1225.

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The process of B cell growth and differentiation into plasma cells is highly regulated and may be influenced by a large number of inflammatory mediators, including complement components. We have studied the regulatory influence of Bb, a 60-kD peptide created during the cleavage of complement Factor B by Factor D and C3b. Purified Bb alone had no effect on proliferation and differentiation of human splenic or tonsillar B cells. However, when B cells were activated by Staphylococcus aureus Cowan I (SAC), Bb enhanced proliferation in a dose-dependent manner. Bb also enhanced proliferation when cocultured with SAC and suboptimal concentrations of purified 60-kD B cell growth factor (HMW-BCGF), a previously described lymphokine that is known to possess growth-promoting activity. However, Bb had no effect on cells treated with optimal concentrations of HMW-BCGF. Like HMW-BCGF, Bb's major effect was on the larger in vivo activated B cells. Half-maximal enhancement of proliferation was reached at a Bb concentration of 1-10 nM. Of note is the fact that antibody to Factor B recognized HMW-BCGF, and an mAb to HMW-BCGF also recognized Factor B and Bb, but not Ba. Moreover, radiolabeled Bb bound saturably to activated B cells and to an EBV-transformed human B cell line. The binding of Bb was inhibited by HMW-BCGF but not by Ba or IgG. Thus, Bb is antigenically and functionally related to HMW-BCGF, and can act as a B cell growth and differentiation factor at potentially physiologic concentrations. These data suggest that Bb may be important in amplifying the immune response in areas of inflammation. Since complement activation occurs at inflammatory sites long before induction of HMW-BCGF synthesis, Bb may be an early signal for the clonal expansion of antigen-activated B cells.
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Gálová, Z., MichalíkI, H. Knoblochová, and E. Gregová. "Variation in HMW glutenin subunits of different species of wheat." Plant, Soil and Environment 48, No. 1 (December 11, 2011): 15–19. http://dx.doi.org/10.17221/4199-pse.

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Method ISTA SDS-PAGE was used for separation, detection and evaluation of high molecular weight glutenin subunits (HMW) in the different wheat species. The relation has been studied between the HMW glutenin subunit alleles and the bread-making quality of 25 world wheat cultivars and 21 regional varieties common wheat varieties (Triticum aestivum L.), 17 winter spelt wheat (Triticum spelta L.), 3 durum wheat cultivars (Triticum durum DESF.), 9 cultivars of Triticum turgidum L. and 5 cultivars of Triticum polonicum L. The highest frequency of occurrence of HMW glutenin subunits 2*, 13 + 16 and 5 + 10 were found in world wheat cultivars. In Slovak wheat varieties were analysed subunits 0, 7 + 9 and 5 + 10, 2 + 12. The HMW subunits 0, 7 + 8 with Glu-score 4 were determined in Triticum durum DESF. Three electrophoretical profile groups of different HMW glutenin subunits were found in Triticum turgidum L. and Triticum polonicum L. and six electrophoretical profile groups were determined in Triticum spelta L. The verified correlations between bread-making quality and specific HMW subunits of glutenin can be utilised by wheat breeders using SDS-PAGE of proteins as a screening test for the prediction of bread-making quality of wheat.
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Tang, Kang, Chunmei Zhang, Yusi Zhang, Yun Zhang, Ran Zhuang, Boquan Jin, and Ying Ma. "Sustained High Levels of Both Total and High Molecular Weight Adiponectin in Plasma during the Convalescent Phase of Haemorrhagic Fever with Renal Syndrome Are Associated with Disease Severity." Journal of Immunology Research 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/6468097.

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Haemorrhagic fever with renal syndrome (HFRS) is characterised by an uncontrolled immune response that causes vascular leakage. Adiponectin (APN) is an adipocytokine involved in prorevascularisation and immunomodulation. To investigate the possible effects of APN in the pathogenesis of HFRS, total and high molecular weight (HMW) APN levels in the plasma of patients with HFRS were quantified using enzyme-linked immunosorbent assay (ELISA). Compared with those in healthy controls, the plasma total and HMW APN levels in patients were elevated to different degrees from the fever onset and remained high at the convalescent phase. Consistent with these results, western blot analysis additionally showed that low molecular weight (LMW), middle molecular weight (MMW), and HMW APN levels were all elevated and contributed to the elevation of the total APN level. Importantly, sustained high levels of total and HMW APN at the convalescent phase were significantly higher in patients with critical disease than those in patients with mild or moderate disease. Moreover, total and HMW APN levels negatively correlated with white blood cell count and positively correlated with platelet count and serum albumin level. These results may provide insights into understanding the roles of total and HMW APN in the pathogenesis of HFRS.
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46

Horáková, Dagmar, Kateřina Azeem, Radka Benešová, Dalibor Pastucha, Vladimír Horák, Lenka Dumbrovská, Arnošt Martínek, et al. "Total and High Molecular Weight Adiponectin Levels and Prediction of Cardiovascular Risk in Diabetic Patients." International Journal of Endocrinology 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/545068.

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The study aimed at assessing the potential use of lower total and HMW adiponectin levels for predicting cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Concentrations of total adiponectin or high molecular weight (HMW) adiponectin decrease in association with the development of metabolic dysfunction such as obesity, insulin resistance, or T2DM. Increased adiponectin levels are associated with a lower risk for coronary heart disease. A total of 551 individuals were assessed. The first group comprised metabolically healthy participants (143 females, and 126 males) and the second group were T2DM patients (164 females, and 118 males). Both total adiponectin and HMW adiponectin in diabetic patients were significantly lower when compared with the group of metabolically healthy individuals. There was a weak monotonic correlation between HMW adiponectin levels and triglycerides levels. Binary logistic regression analysis, gender adjusted, showed a higher cardiovascular risk in diabetic persons when both total adiponectin (OR = 1.700) and HMW adiponectin (OR = 2.785) levels were decreased. A decrease in total adiponectin levels as well as a decrease in its HMW adiponectin is associated with a higher cardiovascular risk in individuals with T2DM. This association suggests that adiponectin levels may be potentially used as an epidemiological marker for cardiovascular risk in diabetic patients.
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47

Buscher, Amy Z., Katie Burmeister, Stephen J. Barenkamp, and Joseph W. St. Geme. "Evolutionary and Functional Relationships among the Nontypeable Haemophilus influenzae HMW Family of Adhesins." Journal of Bacteriology 186, no. 13 (July 1, 2004): 4209–17. http://dx.doi.org/10.1128/jb.186.13.4209-4217.2004.

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ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a common cause of localized respiratory tract disease and initiates infection by colonizing the nasopharynx. Approximately 75 to 80% of NTHi clinical isolates produce proteins that belong to the HMW family of adhesins, which are believed to facilitate colonization. The prototype HMW adhesins are designated HMW1 and HMW2 and were identified in NTHi strain 12. HMW1 and HMW2 are 71% identical and 80% similar overall, yet display differing cellular binding specificities. In the present study we set out to define more clearly the relationships between HMW1 and HMW2 and other members of the HMW family of adhesins. PCR analysis of 49 epidemiologically distinct isolates revealed that all strains possessing hmw genes as determined by Southern analysis contain two hmw loci in conserved, unlinked physical locations on the chromosome. Functional analysis of the HMW adhesins produced by three unrelated strains demonstrated that each isolate possesses one protein with HMW1-like adherence properties and another with HMW2-like adherence properties. These findings suggest that the hmw1 and hmw2 loci may have arisen via a gene duplication event in an ancestral strain. In addition, they support the hypothesis that the distinct binding specificities of HMW1 and HMW2 emerged early and have persisted over time, suggesting an ongoing selective advantage.
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48

Arese, Marco, Yan Chen, Robert Z. Florkiewicz, Anna Gualandris, Bin Shen, and Daniel B. Rifkin. "Nuclear Activities of Basic Fibroblast Growth Factor: Potentiation of Low-Serum Growth Mediated by Natural or Chimeric Nuclear Localization Signals." Molecular Biology of the Cell 10, no. 5 (May 1999): 1429–44. http://dx.doi.org/10.1091/mbc.10.5.1429.

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Human basic fibroblast growth factor (FGF-2) occurs in four isoforms: a low molecular weight (LMW FGF-2, 18 kDa) and three high molecular weight (HMW FGF-2, 22, 22.5, and 24 kDa) forms. LMW FGF-2 is primarily cytoplasmic and functions in an autocrine manner, whereas HMW FGF-2s are nuclear and exert activities through an intracrine, perhaps nuclear, pathway. Selective overexpression of HMW FGF-2 forms in fibroblasts promotes growth in low serum, whereas overexpression of LMW FGF-2 does not. The HMW FGF-2 forms have two functional domains: an amino-terminal extension and a common 18-kDa amino acid sequence. To investigate the role of these regions in the intracrine signaling of HMW FGF-2, we produced stable transfectants of NIH 3T3 fibroblasts overexpressing either individual HMW FGF-2 forms or artificially nuclear-targeted LMW FGF-2. All of these forms of FGF-2 localize to the nucleus/nucleolus and induce growth in low serum. The nuclear forms of FGF-2 trigger a mitogenic stimulus under serum starvation conditions and do not specifically protect the cells from apoptosis. These data indicate the existence of a specific role for nuclear FGF-2 and suggest that LMW FGF-2 represents the biological messenger in both the autocrine/paracrine and intracrine FGF-2 pathways.
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49

Folwell, Benjamin D., Terry J. McGenity, and Corinne Whitby. "Biofilm and Planktonic Bacterial and Fungal Communities Transforming High-Molecular-Weight Polycyclic Aromatic Hydrocarbons." Applied and Environmental Microbiology 82, no. 8 (February 5, 2016): 2288–99. http://dx.doi.org/10.1128/aem.03713-15.

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ABSTRACTHigh-molecular-weight polycyclic aromatic hydrocarbons (HMW-PAHs) are natural components of fossil fuels that are carcinogenic and persistent in the environment, particularly in oil sands process-affected water (OSPW). Their hydrophobicity and tendency to adsorb to organic matter result in low bioavailability and high recalcitrance to degradation. Despite the importance of microbes for environmental remediation, little is known about those involved in HMW-PAH transformations. Here, we investigated the transformation of HMW-PAHs using samples of OSPW and compared the bacterial and fungal community compositions attached to hydrophobic filters and in suspension. It was anticipated that the hydrophobic filters with sorbed HMW-PAHs would select for microbes that specialize in adhesion. Over 33 days, more pyrene was removed (75% ± 11.7%) than the five-ring PAHs benzo[a]pyrene (44% ± 13.6%) and benzo[b]fluoranthene (41% ± 12.6%). For both bacteria and fungi, the addition of PAHs led to a shift in community composition, but thereafter the major factor determining the fungal community composition was whether it was in the planktonic phase or attached to filters. In contrast, the major determinant of the bacterial community composition was the nature of the PAH serving as the carbon source. The main bacteria enriched by HMW-PAHs werePseudomonas,Bacillus, andMicrobacteriumspecies. This report demonstrates that OSPW harbors microbial communities with the capacity to transform HMW-PAHs. Furthermore, the provision of suitable surfaces that encourage PAH sorption and microbial adhesion select for different fungal and bacterial species with the potential for HMW-PAH degradation.
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50

Regano, Edelmiro, Virtudes Vila, Justo Aznar, Victoria Lacueva, Vicenta Martinez, and Miguel Ruano. "Studies on the Functionality of Newly Synthesized Fibrinogen after Treatment of Acute Myocardial Infarction with Streptokinase, Increase in the Rate of Fibrinopeptide Release." Thrombosis and Haemostasis 70, no. 06 (1993): 0978–83. http://dx.doi.org/10.1055/s-0038-1649710.

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SummaryIn 15 patients with acute myocardial infarction who received 1,500,000 U of streptokinase, the gradual appearance of newly synthesized fibrinogen and the fibrinopeptide release during the first 35 h after SK treatment were evaluated. At 5 h the fibrinogen circulating in plasma was observed as the high molecular weight fraction (HMW-Fg). The concentration of HMW-Fg increased continuously, and at 20 h reached values higher than those obtained from normal plasma. HMW-Fg represented about 95% of the total fibrinogen during the first 35 h. The degree of phosphorylation of patient fibrinogen increased from 30% before treatment to 65% during the first 5 h, and then slowly declined to 50% at 35 h.The early rates of fibrinopeptide A (FPA) and phosphorylated fibrinopeptide A (FPAp) release are higher in patient fibrinogen than in isolated normal HMW-Fg and normal fibrinogen after thrombin addition. The early rate of fibrinopeptide B (FPB) release is the same for the three fibrinogen groups. However, the late rate of FPB release is higher in patient fibrinogen than in normal HMW-Fg and normal fibrinogen. Therefore, the newly synthesized fibrinogen clots faster than fibrinogen in the normal steady state.In two of the 15 patients who had occluded coronary arteries after SK treatment the HMW-Fg and FPAp levels increased as compared with the 13 patients who had patent coronary arteries.These results provide some support for the idea that an increased synthesis of fibrinogen in circulation may result in a procoagulant tendency. If this is so, the HMW-Fg and FPAp content may serve as a risk index for thrombosis.
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