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1
Quax, R. A. M., J. A. M. van Laar, R. van Heerebeek, K. Greiner, E. Ben-Chetrit, M. Stanford, G. R. Wallace, et al. "Glucocorticoid sensitivity in Behçet's disease." Endocrine Connections 1, no. 2 (November 2012): 103–11. http://dx.doi.org/10.1530/ec-12-0056.
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ObjectiveGlucocorticoid (GC) sensitivity is highly variable among individuals and has been associated with susceptibility to develop (auto-)inflammatory disorders. The purpose of the study was to assess GC sensitivity in Behçet's disease (BD) by studying the distribution of four GC receptor (GR) gene polymorphisms and by measuring in vitro cellular GC sensitivity.MethodsHealthy controls and patients with BD in three independent cohorts were genotyped for four functional GR gene polymorphisms. To gain insight into functional differences in in vitro GC sensitivity, 19 patients with BD were studied using two bioassays and a whole-cell dexamethasone-binding assay. Finally, mRNA expression levels of GR splice variants (GR-α and GR-β) were measured.ResultsHealthy controls and BD patients in the three separate cohorts had similar distributions of the four GR polymorphisms. The Bcll and 9β minor alleles frequency differed significantly between Caucasians and Mideast and Turkish individuals.At the functional level, a decreased in vitro cellular GC sensitivity was observed. GR number in peripheral blood mononuclear cells was higher in BD compared with controls. The ratio of GR-α/GR-β mRNA expression levels was significantly lower in BD.ConclusionsPolymorphisms in the GR gene are not associated with susceptibility to BD. However, in vitro cellular GC sensitivity is decreased in BD, possibly mediated by a relative higher expression of the dominant negative GR-β splice variant. This decreased in vitro GC sensitivity might play an as yet unidentified role in the pathophysiology of BD.
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Vardy, Janette L., Haryana M. Dhillon, Gregory Russell Pond, Sean Rourke, Wei Xu, Corrinne Renton, Anna Dodd, Philip James Beale, Stephen John Clarke, and Ian Tannock. "Cognitive function and fatigue in colorectal cancer (CRC) patients: A prospective longitudinal controlled study." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 9021. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.9021.
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9021 Background: A subset of cancer patients has cognitive impairment and fatigue after chemotherapy (CTh). We evaluated these symptoms and potential mechanisms in CRC patients and healthy controls (HC). Methods: Cognitive function was evaluated in CRC patients and HC at baseline (pre-CTh), 6 and 12 months. Group 1A (Stage II/III) received CTh and Gr 1B (Stage I/II) no CTh. Gr 2 had limited metastatic CRC. All subjects completed cognitive assessment and questionnaires for fatigue, QOL, anxiety/depression, and perceived cognitive function. Blood tests evaluated: 10 cytokines, clotting factors, sex hormones, CEA, CBC and apolipoprotein genotyping as potential causal factors. Primary endpoints: cognitive function and fatigue (Gr. 1A & 1B) at 12 months. Associations between results and demographic and disease-related factors were sought. Results: 359 CRC patients (173 Gr 1A, 116 Gr 1B, 70 Gr. 2) and 72 HC were assessed. Median age 58 (23-75 years); 58% male. Cognitive impairment: baseline Gr 1A 34% vs 1B 32.5% (p=.9), Gr 1 33% vs HC 10% (p<0.001); 12 months Gr 1A 21% vs 1B 16% (p=0.43), Gr 1 19% vs HC 2% (p=0.001). Cognitive domains most affected: verbal & visual memory, processing speed. Men had greater impairment than women (p<0.009). Cognitive decline from 0-12 months: Gr 1A 30%, Gr 1B 19%, Gr 2 24%, and HC 16%. Perceived cognitive impairment at 12 months: Gr 1A 19% vs 1B 7% (p=.04), Gr 1 14% vs HC 0% (p=.009). Fatigue was greatest in Gr 1A (70%) at 6 months; at 12 months Gr. 1A 46% vs 1B 31% (p=0.056), Gr 2 60%, HC 36%. Cytokines were elevated in CRC patients compared to HC. No association was found with cognitive function and: fatigue, QOL, anxiety/depression, cytokines, sex hormones, clotting factors, CEA or apoE genotype. Objective cognitive function was associated with perceived cognitive function at baseline only. Fatigue at baseline was associated with hemoglobin and at 12 months with neutrophil count. Conclusions: Compared to HC, CRC patients had more cognitive impairment at baseline, 6 and 12 months; but impairment was not significantly different between those who did and did not receive CTh. The mechanisms of cognitive impairment remain unknown. Fatigue improved with time.
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Hooker, P. "12 The conferences." Greece and Rome 50, Supplement 1 (October 1, 2003): 169–82. http://dx.doi.org/10.1093/gr/50.suppl_1.169.
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Ramamoorthy, Sivapriya, and John A. Cidlowski. "Ligand-Induced Repression of the Glucocorticoid Receptor Gene Is Mediated by an NCoR1 Repression Complex Formed by Long-Range Chromatin Interactions with Intragenic Glucocorticoid Response Elements." Molecular and Cellular Biology 33, no. 9 (February 19, 2013): 1711–22. http://dx.doi.org/10.1128/mcb.01151-12.
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Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing this clinical problem affecting patients with chronic inflammatory disorders. Since the cellular level of the glucocorticoid receptor (GR) is a critical determinant of glucocorticoid sensitivity and resistance, we investigated the molecular mechanisms mediating repression of glucocorticoid receptor gene expression. We show here that glucocorticoid-induced repression of GR gene expression is mediated by inhibition of transcription initiation. This process is orchestrated by the recruitment of agonist-bound GR to exon 6, followed by the assembly of a GR-NCoR1-histone deacetylase 3-containing repression complex at the transcriptional start site of the GR gene. A functional negative glucocorticoid response element (nGRE) in exon 6 of the GR gene and a long-range interaction occurring between this intragenic response element and the transcription start site appear to be instrumental in this repression. This autoregulatory mechanism of repression implies that the GR concentration can coordinate repression with excess ligand, regardless of the combinatorial associations of tissue-specific transcription factors. Consequently, the chronic nature of inflammatory conditions involving long-term glucocorticoid administration may lead to constitutive repression of GR gene transcription and thus to glucocorticoid resistance.
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Young, Bryan G., David J. Gibson, Karla L. Gage, Joseph L. Matthews, David L. Jordan, Micheal D. K. Owen, David R. Shaw, Stephen C. Weller, and Robert G. Wilson. "Agricultural Weeds in Glyphosate-Resistant Cropping Systems in the United States." Weed Science 61, no. 1 (March 2013): 85–97. http://dx.doi.org/10.1614/ws-d-12-00001.1.
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A segment of the debate surrounding the commercialization of genetically engineered (GE) crops, such as glyphosate-resistant (GR) crops, focuses on the theory that implementation of these traits is an extension of the intensification of agriculture that will further erode the biodiversity of agricultural landscapes. A large field-scale study was conducted in 2006 in the United States on 156 different field sites with a minimum 3-yr history of GR corn, cotton, or soybean in the cropping system. The impact of cropping system, crop rotation, frequency of using the GR crop trait, and several categorical variables on emerged weed density and diversity was analyzed. Species richness, evenness, Shannon's H′, proportion of forbs, erect growth habit, and C3species diversity were all greater in agricultural sites that lacked crop rotation or were in a continuous GR crop system. Rotating between two GR crops (e.g., corn and soybean) or rotating to a non-GR crop resulted in less weed diversity than a continuous GR crop. The composition of the weed flora was more strongly related to location (geography) than any other parameter. The diversity of weed flora in agricultural sites with a history of GR crop production can be influenced by several factors relating to the specific method in which the GR trait is integrated (cropping system, crop rotation, GR trait rotation), the specific weed species, and the geographical location. The finding that fields with continuous GR crops demonstrated greater weed diversity is contrary to arguments opposing the use of GE crops. These results justify further research to clarify the complexities of crops grown with herbicide-resistance traits, or more broadly, GE crops, to provide a more complete characterization of their culture and local adaptation.
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Garini, Ardiya. "KADAR HEMOGLOBIN PADA PASIEN GAGAL GINJAL KRONIK YANG MENJALANI HEMODIALISIS." JPP (Jurnal Kesehatan Poltekkes Palembang) 13, no. 2 (December 23, 2019): 111–16. http://dx.doi.org/10.36086/jpp.v13i2.234.
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Latar belakang : Gagal ginjal merupakan kondisi yang mengakibatkan ginjal kehilangan kemampuannya untuk mempertahankan volume dan komposisi cairan tubuh dalam keadaan asupan makan normal. Faktor utama penyebab anemia pada gagal ginjal kronik disebabkan berkurangnya sel darah merah akibat turunnya kadar hormon eritropoetin (EPO). Salah satu terapi pada pasien gagal ginjal kronik adalah dengan hemodialisis, tetapi cara ini dapat menimbulkan komplikasi diantaranya anemia yang semakin parah.
Tujuan : untuk mengetahui gambaran kadar hemoglobin pada pasien gagal ginjal kronik yang menjalani hemodialisis berdasarkan umur, jenis kelamin, lama sakit dan lama hemodialisis. Jenis penelitian yang digunakan adalah survey deskriftif dengan pendekatan cross sectional. Tempat penelitian di RSI Siti Khodijah Palembang dengan jumlah 48 sampel.
Hasil : Rata-rata kadar hemoglobin = 8,065 gr/dl. Rata-rata kadar hemoglobin perempuan = 7,794 gr/dl, laki-laki = 8,213 gr/dl Rata-rata kadar hemoglobin remaja = 6,150 gr/dl, dewasa = 7,831 gr/dl, lansia 8,273 gr/dl. Rata-rata kadar hemoglobin dengan lama sakit ≤ 3 bulan = 6,750 gr/dl dan > 3 bulan = 8,122 gr/dl. Rata-rata kadar hemoglobin dengan lama hemodialisis ≤ 12 bulan = 7,600 gr/dl, > 12 bulan = 8,186 gr/dl.
Kesimpulan : Kadar hemoglobin yang rendah didapat pada pasien jenis kelamin perempuan, berumur remaja, lama sakit ≤ 3 bulan dan lama hemodialisis ≤ 12 bulan.
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Li, Mao, John F. Leatherland, Matt M. Vijayan, W. Allan King, and Pavneesh Madan. "Glucocorticoid receptor activation following elevated oocyte cortisol content is associated with zygote activation, early embryo cell division, and IGF system gene responses in rainbow trout." Journal of Endocrinology 215, no. 1 (July 10, 2012): 137–49. http://dx.doi.org/10.1530/joe-12-0030.
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Increasedin ovocortisol content of rainbow trout oocytes from ∼3.5 to ∼5.0 ng.oocyte−1before fertilization enhances the growth of embryos and juveniles and changes the long-term expression pattern of IGF-related genes. This study used embryos reared from oocytes enriched with cortisol and the glucocorticoid receptor (GR) antagonist, RU486, to determine whether the growth-promoting actions of cortisol involve GR protein activation and modulation ofgrexpression. Whole-mountin situimmunohistofluorescence studies of zygotes showed that enhanced oocyte cortisol increased the immunofluorescent GR signal and activated the relocation of GR from a general distribution throughout the cytoplasm to an accumulation in the peri-nuclear cytoplasm.In ovocortisol treatment increased the number of embryonic cells within 48-h post-fertilization, and RU486 partially suppressed this cortisol stimulation of cell duplication. In addition, there was complex interplay between the expression ofgrandigfsystem-related genes spatiotemporally in the different treatment groups, suggesting a role for GR in the regulation of the expression of development. Taken together, these findings indicate an essential role for GR in the regulation of epigenomic events in very early embryos that promoted the long-term growth effects of the embryos and juvenile fish. Moreover, the pretreatment of the oocyte with RU486 had a significant suppressive effect on the maternal mRNA transcript number ofgrandigfsystem-related genes in oocytes and very early stage embryos, suggesting an action of antagonist on the stability of the maternal transcriptome.
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Nandula, Vijay K., Jeffery D. Ray, Daniela N. Ribeiro, Z. Pan, and Krishna N. Reddy. "Glyphosate Resistance in Tall Waterhemp (Amaranthus tuberculatus) from Mississippi is due to both Altered Target-Site and Nontarget-Site Mechanisms." Weed Science 61, no. 3 (September 2013): 374–83. http://dx.doi.org/10.1614/ws-d-12-00155.1.
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A tall waterhemp population from Missisippi was suspected to be resistant to glyphosate. Glyphosate dose response experiments resulted in GR50(dose required to reduce plant growth by 50%) values of 1.28 and 0.28 kg ae ha−1glyphosate for the glyphosate-resistant (GR) and -susceptible (GS) populations, respectively, indicating a five-fold resistance. The absorption pattern of14C-glyphosate between the GR and GS populations was similar up to 24 h after treatment (HAT). Thereafter, the susceptible population absorbed more glyphosate (55 and 49% of applied) compared to the resistant population (41 and 40% of applied) by 48 and 72 HAT, respectively. Treatment of a single leaf in individual plants with glyphosate at 0.84 kg ha−1, in the form of 10 1-µl droplets, provided greater control (85 vs. 29%) and shoot fresh weight reduction (73 vs. 34% of nontreated control) of the GS plants compared to the GR plants, possibly indicating a reduced movement of glyphosate in the GR plants. The amount of14C-glyphosate that translocated out of the treated leaves of GR plants (20% of absorbed at 24 HAT and 23% of absorbed at 48 HAT) was significantly lower than the GS plants (31% of absorbed at 24 HAT and 32% of absorbed at 48 HAT). A potential difference in shikimate accumulation between GR and GS populations at different concentrations of glyphosate was also studied in vitro. The IC50(glyphosate concentration required to cause shikimate accumulation at 50% of peak levels measured) values for the GR and GS populations were 480 and 140 µM of glyphosate, respectively, resulting in more shikimate accumulation in the GS than the GR population. Sequence analysis of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), the target site of glyphosate, from GR and GS plants identified a consistent single nucleotide polymorphism (T/C, thymine/cytosine) between GR/GS plants, resulting in a proline to serine amino acid substitution at position 106 in the GR population. The GR and GS plants contained equal genomic copy number ofEPSPS, which was positively correlated withEPSPSgene expression. Thus, glyphosate resistance in the tall waterhemp population from Mississippi is due to both altered target site and nontarget site mechanisms. This is the first report of an alteredEPSPS-based resistance in a dicot weed species that has evolved resistance to glyphosate.
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Kheradpour, P., A. Stark, S. Roy, and M. Kellis. "Reliable prediction of regulator targets using 12 Drosophila genomes." Genome Research 17, no. 12 (December 1, 2007): 1919–31. http://dx.doi.org/10.1101/gr.7090407.
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Chandi, Aman, David L. Jordan, Alan C. York, Susana R. Milla-Lewis, James D. Burton, A. Stanley Culpepper, and Jared R. Whitaker. "Interference and Control of Glyphosate-Resistant and -Susceptible Palmer Amaranth (Amaranthus palmeri) Populations under Greenhouse Conditions." Weed Science 61, no. 2 (June 2013): 259–66. http://dx.doi.org/10.1614/ws-d-12-00063.1.
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Interference for 40 d after emergence (DAE) of corn, cotton, peanut, and snap bean by four glyphosate-resistant (GR) and four glyphosate-susceptible (GS) Palmer amaranth populations from Georgia and North Carolina was compared in the greenhouse. Greater interference from Palmer amaranth, measured as crop height and fresh weight reduction, was noted in cotton and peanut compared with corn or snap bean. Crop height 15 to 40 DAE was reduced similarly by GR and GS populations. Crop fresh weight, however, was reduced 25 and 19% in the presence of GS and GR populations, respectively. Measured as percent reduction in fresh weight, GR and GS populations of Palmer amaranth were controlled similarly by glufosinate, lactofen, paraquat, and trifloxysulfuron applied POST. Atrazine and dicamba controlled GR populations more effectively than GS populations.
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Yang, Yang, Xini Zhang, Zhen Luo, Xi Wang, Dongqiang Ye, and Weijie Fu. "Alterations in Running Biomechanics after 12 Week Gait Retraining with Minimalist Shoes." International Journal of Environmental Research and Public Health 17, no. 3 (January 28, 2020): 818. http://dx.doi.org/10.3390/ijerph17030818.
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Purpose: The intervention of 12 week gait retraining with minimalist shoes was established to examine its effect on impact forces, joint mechanics, and vertical stiffness during running. Methods: Thirty male recreational runners were randomly assigned to the gait retraining + minimalist shoe (n = 15, GR) and minimalist shoe (n = 15, MIN) groups. The ground reaction force and marker trajectories were collected before and after intervention at a speed of 3.33 ± 5% m/s. Results: A total of 17 participants (9 in the GR group and 8 in the MIN group) completed the training. After training, (1) the loading rate of both groups decreased significantly, and the loading rate of the GR group was lower than that of the MIN group. (2) The foot strike angle of the GR group decreased significantly after training, and the plantarflexion angle and hip joint angular extension velocity increased in both groups. (3) The moment of ankle joint increased in the GR group, and the stiffness of lower limbs was significantly improved in both groups. Conclusion: The 12 week gait retraining with minimalist shoes converted rearfoot strikers into forefoot strikers with a rate of 78% (7/9). More importantly, such a combined program, compared to the training with only minimalist shoes, can avoid the peak impact force and decrease the loading rate more effectively, thus providing a potential means of reducing risk of running injury caused by impact forces. Moreover, the increased vertical stiffness of lower extremity after gait retraining may improve running economy and corresponding energy utilization. However, these observations also suggest that the sole use of minimalist footwear may have limited effects on reducing running-related impacts.
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Nuryanto, Nuryanto. "Pengaruh Umur Pemangkasan Batang Tanaman Jagung Diatas Tongkol (Topping) Untuk Pakan Ternak Terhadap Bobot Panen Tanpa Klobot." Jurnal Pengembangan Penyuluhan Pertanian 16, no. 29 (September 26, 2019): 56. http://dx.doi.org/10.36626/jppp.v16i29.68.
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Penelitian ini dilaksanakan selama 4 bulan (Mei sampai dengan Agustus 2018) dilahan sawah seluas 1.000 m2 di Desa Pagersari, Mungkid, Magelang. Lahan dibagi 64 petak (2,25 x 6 m) untuk ditanami jagung hibrida jarak baris 70 cm dan jarak dalam baris 20 cm. Secara acak, 64 petak dibagi 8 macam perlakuan umur pemangkasan tanaman jagung diatas tongkol untuk pakan ternak (topping) dan diulang 8 kali. Penelitian ini bertujuan untuk mengetahui bobot hijauan pakan tenak hasil hasil topping (gr/btg) dan bobot panen jagung tanpa klobot (gr/tkl). Data dianalisis dengan Rancangan Acak Lengkap (8 X 8) danuntuk uji kepastiannya digunakan Duncan’s Multiple Range Test. Hasil penelitianmenunjukkan bahwa, umur topping berpengaruh sangat nyata (P < 0,01) terhadap bobot hijauan pakan ternak maupun bobot panen jagung tanpa klobot. Pada umur topping 8 sampai dengan 11 minggu, bobot hijauan hasil topping semakin menurun, yakni berturut-turut 148 gr/btg, 120 gr /btg, 114 gr/btg dan 113 gr/btg tetapi bobot panen jagung tanpa klobot semakin meningkat, yakni berturut-turut 127 gr/tkl, 139 gr/tkl, 149 gr/tkl dan 159 gr/tkl. Mulai umur topping 12 sampai dengan 15 minggu, kedua variabel cenderung konstan, yakni bobot hijaun hasil topping berturut-turut 107 gr/btg, 101 gr/btg, 100gr/btgdan 100 gr/btg sedangkan bobot panen jagung tanpa klobot berturut-turut adalah 180 gr/tkl, 181 gr/tkl, 186 gr/tkl dan 187 gr/tkl. Disimpulkan bahwa, agar bobot panen tanpa klobot tidak terpengaruh, maka pemangkasan tanaman jagung diatas tongkol (topping) untuk pakan ternak seyogyanya dilakukan mulai umur 12 minggu.
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Rasmussen, John W., Jason W. Tam, Nihal A. Okan, Patricio Mena, Martha B. Furie, David G. Thanassi, Jorge L. Benach, and Adrianus W. M. van der Velden. "Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia." Infection and Immunity 80, no. 7 (April 23, 2012): 2371–81. http://dx.doi.org/10.1128/iai.00365-12.
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ABSTRACTRecent studies have linked accumulation of the Gr-1+CD11b+cell phenotype with functional immunosuppression in diverse pathological conditions, including bacterial and parasitic infections and cancer. Gr-1+CD11b+cells were the largest population of cells present in the spleens of mice infected with sublethal doses of theFrancisella tularensislive vaccine strain (LVS). In contrast, the number of T cells present in the spleens of these mice did not increase during early infection. There was a significant delay in the kinetics of accumulation of Gr-1+CD11b+cells in the spleens of B-cell-deficient mice, indicating that B cells play a role in recruitment and maintenance of this population in the spleens of mice infected withF. tularensis. The splenic Gr-1+CD11b+cells in tularemia were a heterogeneous population that could be further subdivided into monocytic (mononuclear) and granulocytic (polymorphonuclear) cells using the Ly6C and Ly6G markers and differentiated into antigen-presenting cells followingex vivoculture. Monocytic, CD11b+Ly6ChiLy6G−cells but not granulocytic, CD11b+Ly6CintLy6G+cells purified from the spleens of mice infected withF. tularensissuppressed polyclonal T-cell proliferation via a nitric oxide-dependent pathway. Although the monocytic, CD11b+Ly6ChiLy6G−cells were able to suppress the proliferation of T cells, the large presence of Gr-1+CD11b+cells in mice that survivedF. tularensisinfection also suggests a potential role for these cells in the protective host response to tularemia.
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Alquéres, Sylvia, Carlos Meneses, Luc Rouws, Michael Rothballer, Ivo Baldani, Michael Schmid, and Anton Hartmann. "The Bacterial Superoxide Dismutase and Glutathione Reductase Are Crucial for Endophytic Colonization of Rice Roots by Gluconacetobacter diazotrophicus PAL5." Molecular Plant-Microbe Interactions® 26, no. 8 (August 2013): 937–45. http://dx.doi.org/10.1094/mpmi-12-12-0286-r.
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Gluconacetobacter diazotrophicus is an aerobic diazotrophic plant-growth-promoting bacterium isolated from different gramineous plants. We showed that reactive oxygen species (ROS) were produced at early stages of rice root colonization, a typical plant defense response against pathogens. The transcription of the pathogen-related-10 gene of the jasmonic acid (JA) pathway but not of the PR-1 gene of the salicylic acid pathway was activated by the endophytic colonization of rice roots by G. diazotrophicus strain PAL5. Quantitative polymerase chain reaction analyses showed that, at early stages of colonization, the bacteria upregulated the transcript levels of ROS-detoxifying genes such as superoxide dismutase (SOD) and glutathione reductase (GR). To proof the role of ROS-scavenging enzymes in the colonization and interaction process, transposon insertion mutants of the SOD and GR genes of strain PAL5 were constructed. The SOD and GR mutants were unable to efficiently colonize the roots, indicated by the decrease of tightly root-associated bacterial cell counts and endophytic colonization and by fluorescence in situ hybridization analysis. Interestingly, the mutants did not induce the PR-10 of the JA-pathway, probably due to the inability of endophytic colonization. Thus, ROS-scavenging enzymes of G. diazotrophicus strain PAL5 play an important role in the endophytic colonization of rice plants.
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Ivanov, Dmitry O., and Vitaly V. Derevtsov. "Assessment of body length in infants born with different types of mild prenatal development delay." Pediatrician (St. Petersburg) 10, no. 6 (March 4, 2020): 13–18. http://dx.doi.org/10.17816/ped10613-18.
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Objective. To assess the length of the body in infants from mothers with a burdened somatic and obstetric-gynecological history, including with a delay in the growth of the fetus of various types of mild severity, in comparison with each other, with healthy children from practically healthy mothers and with children from mothers with an aggravated somatic and obstetric-gynecological history, but without delayed fetal growth.
Material and methods. 166 new-borns were monitored since birth, including 72 infants born after abnormal pregnancies with mild foetus growth and development retardation (gr. 1), and 69 infants born after abnormal pregnancies, but without any retardation (gr. 2), born by mothers with previous somatic and gynaecological disorders. The symmetrical intrauterine growth and development retardation was diagnosed in 15 infants (20.83%) (subgr. 1b), whereas the dissymmetric retardation was diagnosed in 57 children (79.17%) (subgr. 1a) from gr. 1. Practically healthy infants born by practically healthy mothers after normal pregnancies made up gr. 3 (25 subjects). Children are full-term, looked round in 1 (154), 3 (138), 6 (131), 12 (119 children) months. Comprehensive analysis of history, inspection, body height. Distribution-free statistical analysis methods.
Results. The differences (p 0.01) in body length (Me, cm) in children at birth between the subgr. 1b (48) and gr. 2 (52); in 1 month between subgr. 1a (53) and 1b (52.5); in 3 months between subgr. 1a (60) and gr. 2 (62); in 6 months between subgr. 1a (66.5) and 1b (65.5); in 12 months between subgr. 1a (74.25) and 1b (73), subgr. 1a and gr. 2 (76), subgr. 1b and gr. 2. Increase of body length to 1 month in children subgr. 1a (4) and 1b (4.5) in comparison with children gr. 2 and 3 by 1 and 1.5 cm respectively more; to 3 months in children subgr. 1a (7) and gr. 2 (7) are comparable and more than children subgr. 1b. by 0.5 cm, gr. 3 by 1 and 0.5 cm respectively; to 6 months in children subgr. 1a (6.5) and 1b (6.5) more than the gr. 2 by 0.5 cm, less than the children gr. 3 by 0.5 cm; to 12 months in children subgr. 1a and 1b; gr. 1, 2 and 3 are comparable. To 12 months in children subgr. 1b in relation to children gr. 2 and 3 less by 0.5 cm.
Conclusion. The established difference in body-length should be taken into account during the dispensary observation in order to decide whether to carry out corrective measures.
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Johnson, D. W., J. N. Berg, C. J. Gallione, K. A. McAllister, J. P. Warner, E. A. Helmbold, D. S. Markel, C. E. Jackson, M. E. Porteous, and D. A. Marchuk. "A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12." Genome Research 5, no. 1 (August 1, 1995): 21–28. http://dx.doi.org/10.1101/gr.5.1.21.
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Heger, A., and C. P. Ponting. "Evolutionary rate analyses of orthologs and paralogs from 12 Drosophila genomes." Genome Research 17, no. 12 (December 1, 2007): 1837–49. http://dx.doi.org/10.1101/gr.6249707.
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Stage, D. E., and T. H. Eickbush. "Sequence variation within the rRNA gene loci of 12 Drosophila species." Genome Research 17, no. 12 (December 1, 2007): 1888–97. http://dx.doi.org/10.1101/gr.6376807.
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Stark, A., P. Kheradpour, L. Parts, J. Brennecke, E. Hodges, G. J. Hannon, and M. Kellis. "Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes." Genome Research 17, no. 12 (December 1, 2007): 1865–79. http://dx.doi.org/10.1101/gr.6593807.
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Dassonvalle, Jonatan, Francisco Díaz-Castro, Camila Donoso-Barraza, Carlos Sepúlveda, Francisco Pino-de la Fuente, Pamela Pino, Alejandra Espinosa, Mario Chiong, Miguel Llanos, and Rodrigo Troncoso. "Moderate Aerobic Exercise Training Prevents the Augmented Hepatic Glucocorticoid Response Induced by High-Fat Diet in Mice." International Journal of Molecular Sciences 21, no. 20 (October 14, 2020): 7582. http://dx.doi.org/10.3390/ijms21207582.
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Glucocorticoids (GCs) are critical regulators of energy balance. Their deregulation is associated with the development of obesity and metabolic syndrome. However, it is not understood if obesity alters the tissue glucocorticoid receptor (GR) response, and moreover whether a moderate aerobic exercise prevents the alteration in GR response induced by obesity. Methods: To evaluate the GR response in obese mice, we fed C57BL6J mice with a high-fat diet (HFD) for 12 weeks. Before mice were sacrificed, we injected them with dexamethasone. To assess the exercise role in GR response, we fed mice an HFD and subjected them to moderate aerobic exercise three times a week. Results: We found that mice fed a high-fat diet for 12 weeks developed hepatic GC hypersensitivity without changes in the gastrocnemius or epididymal fat GR response. Therefore, moderate aerobic exercise improved glucose tolerance, increased the corticosterone plasma levels, and prevented hepatic GR hypersensitivity with an increase in epididymal fat GR response. Conclusion: Collectively, our results suggest that mice with HFD-induced obesity develop hepatic GR sensitivity, which could enhance the metabolic effects of HFD in the liver. Moreover, exercise was found to be a feasible non-pharmacological strategy to prevent the deregulation of GR response in obesity.
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Kwong, Raymond W. M., and Steve F. Perry. "Cortisol regulates epithelial permeability and sodium losses in zebrafish exposed to acidic water." Journal of Endocrinology 217, no. 3 (March 15, 2013): 253–64. http://dx.doi.org/10.1530/joe-12-0574.
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The effects of cortisol on epithelial permeability and sodium (Na+) handling during acid exposure were investigated in larval zebrafish (Danio rerio). The results demonstrated that the whole-body absorption of the paracellular permeability marker polyethylene glycol-4000 (PEG-4000) decreased with increasing levels of exogenous cortisol. Western blot analysis revealed that the abundance of the epithelial tight junction proteins occludin-a and claudin-b was increased after cortisol treatment. Furthermore, translational gene knockdown of claudin-b using an antisense morpholino oligonucleotide caused an increase in the permeability to PEG-4000, which was mitigated by cortisol treatment, further suggesting a role for cortisol in reducing paracellular permeability. Exposure to acidic water (pH 4.0 vs 7.6) caused an expected increase in the diffusive loss of Na+and a decrease in whole-body Na+levels. These disruptive effects of acute acid exposure on Na+balance were reduced by treatment of larvae with exogenous cortisol. Translational knockdown of the glucocorticoid receptor (GR) abolished the effects of cortisol on epithelial PEG permeability, suggesting that activation of GR was probably the major signaling pathway for reducing epithelial permeability. During acid exposure, the epithelial PEG permeability in the GR morphants was significantly higher than in the control fish. Additionally, GR morphants exhibited a more pronounced diffusive loss of Na+than the control fish during acid exposure. These findings suggest that cortisol may help to minimize the negative consequences of acid exposure on Na+homoeostasis via GR-mediated reductions in epithelial permeability and paracellular Na+loss.
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DeLozier, Olivia Mallory, Sophie Y. Dream, James W. Findling, Ty Brian Carroll, Douglas B. Evans, and Tracy S. Wang. "Confirmation of Feasibility of Selective Glucocorticoid Replacement Following Unilateral Adrenalectomy for Hypercortisolism and Primary Aldosteronism." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A80—A81. http://dx.doi.org/10.1210/jendso/bvab048.162.
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Abstract Background: Secondary adrenal insufficiency (AI) can develop following unilateral adrenalectomy (UA) foradrenal-dependent hypercortisolism (HC) and has been reported after UA for primaryaldosteronism (PA). An institutional study previously demonstrated that cosyntropin stimulationtesting on postoperative day 1 (POD1-CST) successfully identified patients who requiredglucocorticoid replacement (GR) following UA; 50% of HC patients required GR and no PApatients required GR. The aim of this study was to reevaluate the need for GR following UA forpatients with HC and PA in a larger cohort of patients. Methods We reviewed 108 patients from a prospectively maintained adrenal database who underwent UAfor HC (n=74), PA (n=22), and concurrent HC/PA (n=12) from 9/2014-10/2020. PA patientswithout preoperative evaluation for HC were excluded. Patients with 1mg dexamethasonesuppression test (DST) cortisol >1.8 (µg/dL) were defined as having mild HC, with ³5 defined asovert Cushing’s Syndrome (CS). All patients underwent our institutional POD1-CST protocoland GR was initiated for patients with basal cortisol £5 or stimulated cortisol £14 (<18 prior to4/2017). Results: Overall, 51 (47%) patients had an abnormal POD1-CST and were discharged on GR (44 HC, 1PA, and 6 HC/PA). Two (2%) patients with CS had a normal POD1-CST but developed AIrequiring GR at 8 and 12 weeks post UA. Of the 74 patients with HC, 44 (59%) had an abnormalPOD1-CST and were discharged on GR, including 19/28 (68%) with CS and 25/46 (54%) withmild HC. Preoperative DST cortisol was higher in HC patients who required GR compared topatients with a normal POD1-CST (4.1 vs 3.6; p=0.007). Median cortisol levels for HC patientswith an abnormal POD1-CST vs those with a normal test were: basal: 3.8 vs 15.6 (p=0.027); 30-minute: 10.1 vs 20.1 (p=0.403); and 60-minute 11.4 vs 22.2 (p=0.260). Of the 22 PA patients, 19(86%) had a normal POD1-CST. Median cortisol levels for PA patients with an abnormal POD1-CST vs those with a normal test were: basal: 0.4 vs 12.1; 30-minute: 8.8 vs 24.6; and 60-minute:12.2 vs 28.9. Of the 3 (14%) PA patients with an abnormal POD1-CST, 1 was dischargedwith GR and began tapering after 2 weeks; the other 2 did not require GR and did not developAI. Of the 12 patients with combined PA/HC, 6 (50%) were discharged on GR based on POD1-CST. GR was required by 30 (59%) patients for <3 months and 82% for <12 months; 7/9 whorequired GR >12 months had CS. Conclusions: Using a standard protocol for POD1-CST in patients who underwent unilateral adrenalectomyfor HC, PA, or combined PA/HC, this study demonstrated that routine GR is not required in 32%of patients with CS and 46% of patients with mild HC. POD1-CST safely identifies patients whowill require GR with no immediate concern for adrenal insufficiency. These data also suggestthat routine evaluation for AI in postoperative PA patients is not needed if cortisol excess hasbeen excluded preoperatively.
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Deng, Liqin, Xini Zhang, Songlin Xiao, Yang Yang, Lu Li, and Weijie Fu. "Changes in the Plantar Flexion Torque of the Ankle and in the Morphological Characteristics and Mechanical Properties of the Achilles Tendon after 12-Week Gait Retraining." Life 10, no. 9 (August 22, 2020): 159. http://dx.doi.org/10.3390/life10090159.
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Purpose: Although the Achilles tendon (AT) is the largest and strongest tendon, it remains one of the most vulnerable tendons among elite and recreational runners. The present study aims to explore the effects of 12-week gait retraining (GR) on the plantar flexion torque of the ankle and the morphological and mechanical properties of the AT. Methods: Thirty-four healthy male recreational runners (habitual rearfoot strikers) who never tried to run in minimal shoes were recruited, and the intervention was completed (20 in the GR group vs. 14 in the control (CON) group). The participants in the GR group were asked to run in minimal shoes (INOV-8 BARE-XF 210) provided by the investigators with forefoot strike patterns during the progressive 12-week GR. Meanwhile, the participants in the CON group were instructed to run in their own running shoes, which they were familiar with, with original foot strike patterns and intensities. The morphological properties of the AT, namely, length and cross-sectional area (CSA), were obtained by using an ultrasound device. A dynamometer was utilized simultaneously to measure and calculate the plantar flexion torque of the ankle, the rate of torque development, the peak force of the AT, and the stress and strain of the AT. Results: After 12-week GR, the following results were obtained: (1) A significant time effect in the peak ankle plantarflexion torque was observed (p = 0.005), showing a 27.5% increase in the GR group; (2) A significant group effect in the CSA was observed (p = 0.027), specifically, the increase in CSA was significantly larger in the GR group than the CON group; (3) A significant time effect in the peak AT force was observed (p = 0.005), showing a 27.5% increase in the GR group. Conclusion: The effect of 12 weeks of GR is an increase in AT CSA, plantar flexor muscle strength of the ankle, and peak AT force during a maximal voluntary isometric contraction test. These changes in AT morphology and function could be positive for tendon health and could prevent future AT injury.
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Gomez-Roca, C. A., S. Koscielny, C. Dromain, I. Marzouk, F. Bidault, R. Bahleda, C. Ferte, C. Massard, and J. Soria. "Comparison between RECIST evaluations and variations in tumor growth dynamics in patients included in phase I trials." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 2515. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2515.
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2515 Background: Monitoring of treatment efficacy is mainly based on RECIST post-treatment evaluations. We investigated the impact of pre-treatment tumor growth dynamics on the evaluation of response to treatment in phase I trials. Methods: Response at 12 weeks was evaluated using RECIST criteria in 76 patients treated in phase I trials. All patients had a scannographic evaluation at the start of the experimental treatment (D0), at least 2 evaluations before D0 and one evaluation after D0. The mean time between evaluations was 6 weeks. Tumor growth rate (GR=% change in tumor volume per month) was calculated for the pre-treatment period (from the 1st available evaluation to D0), and the experimental period (after D0). GR was compared to RECIST and to time to progression. Disease control (DC) was defined as stable disease, partial response or complete response. We also classified patients according to the variation in GR. Results: A total of 550 evaluations were performed: 256 before D0, 76 at D0 and 218 after. Tumor GR differed according to the time period: 26.6% per month during pre-treatment period vs. 6.6% in experimental period (P<0.01). The GR was significantly higher in patients without DC during pre-treatment (30% vs. 19%; P=0.003) and experimental time periods (+13% vs. -9%; P=0.0005). There was a significant association between a time to progression > 12 weeks and a decrease in GR during the experimental period (P=0.01). Several discordances however were noted. Eight patients with a time to progression >12 weeks (8/46=17%) had an increased GR with the experimental treatment. Thirteen patients who progressed <12 weeks (13/22=59%) had a decreased GR with the experimental treatment. Conclusions: Pre-treatment growth dynamic may directly impact RECIST evaluation of tumor response and thus should be carefully documented. Patients with slow growing tumors tend to experience DC, even if treatment has little effect. The evaluation of response to treatment should take into account pre-treatment tumor GR. No significant financial relationships to disclose.
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Stephenson, J., R. J. Amato, S. Hotte, J. Nemunaitis, B. Berman, K. Bélanger, T. A. Patterson, A. R. Macleod, G. K. Reid, and R. E. Martell. "A dose and schedule optimizing evaluation of MG98 given as either a 2 hour IV infusion twice weekly or as a 7 day continuous infusion in combination with interferon alpha (INF) in nephrectomized patients (pts) with advanced renal cell carcinoma (RCC)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14557. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14557.
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14557 Background: RCC is often associated with hypermethylated and silenced tumour suppressor genes. The enzyme DNMT1 is responsible for the majority of cellular DNA methylating capacity. MG98 is a second generation antisense inhibitor of DNMT1 which has been shown to reduce DNMT1 mRNA and protein. Methods: A trial of MG98 given as a 2 hour IV infusion twice weekly (Intermittent Schedule, IS) or as a 7 day continuous infusion (CI) in combination with INF has been conducted with nephrectomized pts with advanced RCC. Main endpoints: identification of the optimum regimen, safety, tolerability, pharmacokinetics (PK) and the degree of PBL DNMT1 mRNA suppression. Results: CI schedule: dose levels of 125mg of MG98 combined with 12 MIU of INF (125/12) and 125/9 have been evaluated (9 pts). The MTD has been reached; thrombocytopenia is dose limiting at 125/12. Pt demographics: M:F= 6:3, mean age of 63.2y (52–71). Most common Adverse Events (AEs): fever and chills (gr.1), fatigue (gr.1–2; 100% of pts), nausea and anorexia (gr.1–2), vomiting (gr.2; 66%). Best response: Stable Disease (SD) =3; Partial Response (PR) =1. Currently within the IS schedule, 3 dose levels (9 pts) have been evaluated: 160/12, 200/12 and 200/9, totaling 26 cycles. The MTD has been reached, with GI/constitutional symptoms being dose limiting at 200/12. Demographics: M:F= 7:2 median age 59.8y (40–76). Most common AEs in the first 3 pts are nausea and chills (100% of patients); fatigue (gr.1–2) and fever (66%; gr. 1–3). Best responses: 3 SD, 1 PR. PK evaluation on both schedules revealed no interaction between INF and MG98. DNMT1 inhibition data will be presented. Conclusions: Combination of INF and MG98 exhibits clinical activity and acceptable safety. [Table: see text]
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Arifuzzaman, M. "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Research 16, no. 5 (May 1, 2006): 686–91. http://dx.doi.org/10.1101/gr.4527806.
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Beckie, Hugh J., Robert E. Blackshaw, Ryan Low, Linda M. Hall, Connie A. Sauder, Sara Martin, Randall N. Brandt, and Scott W. Shirriff. "Glyphosate- and Acetolactate Synthase Inhibitor–Resistant Kochia (Kochia scoparia) in Western Canada." Weed Science 61, no. 2 (June 2013): 310–18. http://dx.doi.org/10.1614/ws-d-12-00140.1.
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In summer, 2011, we investigated suspected glyphosate-resistant (GR) kochia in three chem-fallow fields (designated F1, F2, F3, each farmed by a different grower) in southern Alberta. This study characterizes glyphosate resistance in those populations, based on data from dose–response experiments. In a greenhouse experiment, the three populations exhibited a resistance factor ranging from 4 to 6 based on shoot biomass response (GR50ratios), or 5 to 7 based on survival response (LD50ratios). Similar results were found in a field dose–response experiment at Lethbridge, AB, in spring 2012 using the F2 kochia population. In fall 2011, we surveyed 46 fields within a 20-km radius of the three chem-fallow fields for GR kochia. In the greenhouse, populations were screened with glyphosate at 900 g ae ha−1. Seven populations were confirmed as GR, the farthest site located about 13 km from the three originally confirmed populations. An additional GR population more than 100 km away was later confirmed. Populations were screened for acetolactate synthase (ALS)–inhibitor (thifensulfuron : tribenuron) and dicamba resistance in the greenhouse, with molecular characterization of ALS-inhibitor resistance in the F1, F2, and F3 populations. All GR populations were resistant to the ALS-inhibiting herbicide, but susceptible to dicamba. ALS-inhibitor resistance in kochia was conferred by Pro197, Asp376, or Trp574amino acid substitutions. Based upon a simple empirical model with a parameter for selection pressure, calculated from weed relative abundance and glyphosate efficacy, and a parameter for seedbank longevity, kochia, wild oat, and green foxtail were the top three weeds, respectively, predicted at risk of selection for glyphosate resistance in the semiarid Grassland region of the Canadian prairies; wild oat, green foxtail, and cleavers species were predicted at greatest risk in the subhumid Parkland region. This study confirms the first occurrence of a GR weed in western Canada. Future research on GR kochia will include monitoring, biology and ecology, fitness, mechanism of resistance, and best management practices.
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Tournigand, C., B. Samson, W. Scheithauer, C. Louvet, T. Andre, G. Lledo, J. Latreille, F. Viret, B. Chibaudel, and A. de Gramont. "mFOLFOX-bevacizumab or XELOX-bevacizumab then bevacizumab (B) alone or with erlotinib (E) in first-line treatment of patients with metastatic colorectal cancer (mCRC): Interim safety analysis of DREAM study." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 4077. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.4077.
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4077 Background: Anti-VEGF or EGFR inhibitors demonstrated clinical activity in combination with chemotherapy (CT) in mCRC. The DREAM trial compares, after an induction CT of 6 cy of FOLFOX-B or XELOX-B, a maintenance with B ± E. We report here a pre-planned safety analysis of induction (I) and maintenance (M) phase for the first 200 patients. Methods: Patients (pts) with untreated mCRC were randomly assigned to 2 arms (I): mFOLFOX+B (n=100), or mXELOX+B (n=100). mFOLFOX-B: LV 400 mg/m2, Oxaliplatin (ox) 100 mg/m2, B 5 mg/kg d1, 5FU ci 2.4g/m2 46h, q2w, mXELOX-B: Ox 100 mg/m2 d1, capecitabine 2.5 g/m2 d1–7, B 5mg/kg, q2w. To date, 117 pts with a disease control after 6 cy have had a 2nd randomisation (M): B alone (7.5 mg/kg q3w, n=56) or B+E 150 mg/d (n=61) until PD. Results: Pts characteristics were: sex: 124M/76F, median age: 62.4 years (26–80), primary tumors: colon 152, rectum 53, synchronous metastases: 150 pts, > 1 metastase site: 115, PS 0/1: 134/66, Alk. Ph.>UNL: 87 pts, and LDH>UNL: 88pts. For I, 92 pts in mFOLFOX-B and 93 in XELOX-B were evaluable for toxicity (tox). Tox (%) for mFOLFOX-B/XELOX-B were: any toxicity grade (gr) 3 or 4: 21/30; neutropenia gr 3 6/1, gr 4 0/2; febrile neutropenia gr 3 1/1, gr 4 0/1; thrombopenia gr 3 0/1, gr 4 0/2; anemia gr 2 8/15, gr 3 2/1; nausea gr 2 17/15, gr 3 4/6; vomiting gr 2 10/12, gr 3 2/5; mucositis gr 2 6/6, gr 3 0/4; diarrhea gr 2 8/12, gr 3 5/20, gr 4 0/1; neuropathy gr 2 23/17 gr 3 3/1; HFS gr 2 0/7, gr 3 0/2; hypertension gr 2 2/3, gr 3 1/0; proteinuria gr 2 1/5; SAEs 14/25. For M, 56 pts in B and 61 pts in B+E were evaluable. Tox (% B/B+E) were: neutropenia gr 2 0/3; thrombopenia gr 2 2/0; nausea gr 2 2/2, gr 3 2/0; vomiting gr 3 2/0; mucositis gr 2 2/3; diarrhea gr 2 0/6, gr 3 2/6; skin tox gr 1 9/31, gr 2 0/38, gr 3 0/16, gr 4 0/2; proteinuria gr 2 5/5; hypertension gr 1 9/15, gr 2 3/8, gr 3 3/0. Conclusions: This interim safety analysis demonstrated that induction with mFOLFOX-B or XELOX-B as well as maintenance with B or B + E appears to be well-tolerated, without unexpected side effects. The DREAM study is ongoing, with a prolonged induction phase of 6 months (3 mo with ox then 3 mo with fluoropyrimidines-B) before randomisation for maintenance therapy. [Table: see text]
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Marhadi, Marhadi, Henri Wibowo, and Vivie Amelia Kurniawan. "Analisis Penurunan Eceng Gondok (Eichornia Crassipes) dalam Perbaikan Kualitas Air Ditinjau Dari Parameter Timbal (Pb) dan Besi (Fe)." Jurnal Civronlit Unbari 3, no. 2 (October 27, 2018): 82. http://dx.doi.org/10.33087/civronlit.v3i2.37.
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Danau Sipin memiliki potensi perairan umum yang cukup besar dengan luas 40 Ha mengalami degradasi fungsi lingkungan ditandai dengan fluktuasi debit air antara musim kemarau dan musim hujan pendangkalan alur sungai dan semakin berkurangnya kapasitas penampungan air danau, Tujuan Penelitianmengetahui berapa perbandingan penurunan parameter Pb dan Fe oleh eceng gondok dari setiap bak, perubahan Ph dan Suhu dari setiap bak dan perubahan fisik eceng gondok sebelum dan sesudah penellitian. Metode penelitian mengetahui penurunan kadar timbal (Pb) dan besi (Fe) terhadap eceng gondok. Pada penelitian ini dibagi 4 perlakuan dengan berat eceng gondok yang berbeda namun kapasitas air sama yaitu sebesar 12 liter di setiap bak, dengan perlakuan sebagai berikut, pemberian eceng gondok atau disebut dengan bak kontrol (K) perlakuan pertama pemberikan eceng gondok sebesar 200, perlakuan kedua pemberian eceng gondok sebesar 400 gr dan perlakuan ketiga pemberian eceng gondok sebesar 600 gr,.masing-masing dari perlakuan tersebut mengalami pengontrolan yang sama, yaitu mengecek perubahan kadar pH dan suhu serta waktu detensi awal eceng gondok kontak dengan air sampel selama 9 hari. Setelah 9 hari dilakukan pengambilan sampel ke 2, pada hari ke 11 dilakukan pengambilan sampel ke 3, dan pada hari ke 13 dilakukan pengambilan sampel terakhir. Hasil penelitian untuk parameter besi (Fe) pengujian pada bak 200 gr sebesar rata-rata - 0.01 mg/L - 0.023 mg/L, bak 400 gr rata-rata sebesar 0.01 mg/L, bak 600 gr sebesar rata-rata 0.01 mg/L - 0.032 mg/L untuk pengujianparameter timbal (Pb) pada bak 200 gr sebesar 0.02 mg/L, bak 400 gr sebesar 0.02 mg/L, bak 600 gr sebesar 0.02 mg/L, untuk pengukuran pH dan suhu mencapai 29? dengan pH bak 200 gr 5, pH bak 400 gr 6, pH bak 600 gr 6,5 dan pH bak K 6. Perubahan fisik eceng gondok sebelum dan sesudah eksperimen sangat terlihat jelas pada daun dan batangnya, sebelum penelitian eceng gondok pada setiap bak berwarna hijau dan batang yang segar dan setelah penelitian ada beberapa eceng gondok yang berubah warna kekuningan dan layu dan perubahan pada airnya. Eceng gondok 600gr dengan kapasitas air 12 liter, selain daun eceng gondoknya yang menguning dan batangnya yang layu, dan air berubah semakin keruh dikarenakan kapasitas air 12 liter tidak cukup menampung eceng gondok dengan berat 600 gr.
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Dewi, Asti Rosmala, Agus Susanto, and Yanti Rusyanti. "The treatment of gingival recession with coronally advanced flap with platelet-rich fibrin." Dental Journal (Majalah Kedokteran Gigi) 52, no. 1 (March 31, 2019): 8. http://dx.doi.org/10.20473/j.djmkg.v52.i1.p8-12.
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Background: Of the various techniques developed for the treatment of gum recession, the current innovation in the use of platelet rich plasma (PRF) has been applied to the treatment of root-end closure procedures. Purpose: This study analyzed the effect of the coronally advanced flap (CAF) in combination with platelet-rich fibrin (PRF) during treatment of gingival recession. Methods: This research constituted an experimental study incorporating a split-mouth design which was conducted on eight participants (with 16 recession defects) who were divided into two groups consisting of the CAF group with PRF and another CAF group without PRF. Clinical parameters consisting of gingival recession (GR), keratinized gingival width (KGW), recession width (RW) and clinical attachment level (CAL) were measured both before and 21 days after surgery). Results: The average differences between clinical parameters in the test group were as follows: GR (2.25 ± 0.27), KGW (1.81 ± 0.75), RW (3.44 ± 1.35), and CAL (2.56 ± 0.50); while in the control group they were as follows: GR (2.00 ± 0.71), KGW (1.94 ± 0.78), RW (3.50 ± 1.91) and CAL (2.00 ± 0.76). There were significant differences in the GR and CAL between the test and control groups (p ≤ 0.05). Conclusion: A combination of the CAF procedure and PRF was proven to be more effective in covering the GR and increasing the CAL.
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Donet, Eva, Pilar Bosch, Ana Sanchis, Pilar Bayo, Angel Ramírez, José L. Cascallana, Ana Bravo, and Paloma Paloma. "Transrepression Function of the Glucocorticoid Receptor Regulates Eyelid Development and Keratinocyte Proliferation but Is Not Sufficient to Prevent Skin Chronic Inflammation." Molecular Endocrinology 22, no. 4 (April 1, 2008): 799–812. http://dx.doi.org/10.1210/me.2007-0284.
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Glucocorticoids (GCs) play a key role in skin homeostasis and stress responses acting through the GC receptor (GR), which modulates gene expression by DNA binding-dependent (transactivation) and -independent (transrepression) mechanisms. To delineate which mechanisms underlie the beneficial and adverse effects mediated by GR in epidermis and other epithelia, we have generated transgenic mice that express a mutant GR (P493R, A494S), which is defective for transactivation but retains transrepression activity, under control of the keratin 5 promoter (K5-GR-TR mice). K5-GR-TR embryos exhibited eyelid opening at birth and corneal defects that resulted in corneal opacity in the adulthood. Transgenic embryos developed normal skin, although epidermal atrophy and focal alopecia was detected in adult mice. GR-mediated transrepression was sufficient to inhibit keratinocyte proliferation induced by acute and chronic phorbol 12-myristate 13-acetate exposure, as demonstrated by morphometric analyses, bromodeoxyuridine incorporation, and repression of keratin 6, a marker of hyperproliferative epidermis. These antiproliferative effects were mediated through negative interference of GR with MAPK/activator protein-1 and nuclear factor-κB activities, although these interactions occurred with different kinetics. However, phorbol 12-myristate 13-acetate-induced inflammation was only partially inhibited by GR-TR, which efficiently repressed IL-1β and MMP-3 genes while weakly repressing IL-6 and TNF-α. Our data highlight the relevance of deciphering the mechanisms underlying GR actions on epithelial morphogenesis as well as for its therapeutic use to identify more restricted targets of GC administration.
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Hewavitharana, Shashika S., and Mark Mazzola. "Carbon Source-Dependent Effects of Anaerobic Soil Disinfestation on Soil Microbiome and Suppression of Rhizoctonia solani AG-5 and Pratylenchus penetrans." Phytopathology® 106, no. 9 (September 2016): 1015–28. http://dx.doi.org/10.1094/phyto-12-15-0329-r.
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The effect of carbon source on efficacy of anaerobic soil disinfestation (ASD) toward suppression of apple root infection by Rhizoctonia solani AG-5 and Pratylenchus penetrans was examined. Orchard grass (GR), rice bran (RB), ethanol (ET), composted steer manure (CM), and Brassica juncea seed meal (SM) were used as ASD carbon inputs, with plant assays conducted in natural and pasteurized orchard soils. Subsequent studies investigated the effect of GR application rate used in ASD on control of these pathogens. In general, apple root infection by R. solani AG-5 was significantly lower in ET, GR, RB, and SM ASD treatments compared with the control. Among different ASD treatments, apple seedling growth was significantly greater when GR or SM was used as the carbon input relative to all other ASD treatments. R. solani AG-5 DNA abundance was significantly reduced in all ASD treatments, regardless of amendment type, compared with the control. In independent experiments, ASD-GR was consistently superior to ASD-CM for limiting pathogen activity in soils. ASD treatment with a grass input rate of 20 t ha−1 provided superior suppression of P. penetrans but grass application rate did not affect ASD efficacy in control of R. solani AG-5. The soil microbiome from ASD-GR-treated soils was clearly distinct from the control and ASD-CM-treated soils. In contrast, composition of the microbiome from control and ASD-CM-treated soils could not be differentiated. Comparative results from pasteurized and nonpasteurized soils suggest that there is potential for GR based ASD treatment to recruit microbial elements that persist over the anaerobic phase of soil incubation, which may functionally contribute to disease suppression. When ASD was conducted with GR, microbial diversity was markedly reduced relative to the control or ASD-CM soil suggesting that this parameter, typically associated with system resilience, was not instrumental to the function of ASD-induced soil suppressiveness.
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Lin, M. F., J. W. Carlson, M. A. Crosby, B. B. Matthews, C. Yu, S. Park, K. H. Wan, et al. "Revisiting the protein-coding gene catalog of Drosophila melanogaster using 12 fly genomes." Genome Research 17, no. 12 (December 1, 2007): 1823–36. http://dx.doi.org/10.1101/gr.6679507.
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Termemil, Farida, Marwa Ahmed-Malek, Assia Bourouba, and Mohamed-rida Benloucif. "Study of the Fe(II-III) hydroxysalts transformation according to the pH and the concentration of the ions present." Mediterranean Journal of Chemistry 7, no. 5 (December 9, 2018): 359–69. http://dx.doi.org/10.13171/mjc751912081134ft.
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Sulphated green rust, GR (SO4 2- ), is one of the main corrosion products of carbon steel in marine environments. It is Fe (II)-Fe(III) hydroxylsalt in sheets, consisting of alternating layers of iron-hydroxide type Fe(OH)2 , loaded positively due to the presence of the cations Fe(III) and negative interlayers consisting of anions and water molecules. This compound is strongly associated with the metabolism of sulphate-reducing bacteria, and can also evolve under cathodic protection. Thus, recently, GR (CO3 2- ) has been detected in place of GR (SO4 2- ) on already corroded ordinary steel, newly subjected to cathodic protection. This presence is due to the pH and[SO4 2−] [HCO3 − ⁄ ] conditions imposed by the cathodic protection. In this paper, we chemically synthesize sulfated and carbonate green rust in a chlorinated medium; we then study their respective transformation according to the concentration [SO4 2- ] / [HCO3 - ] ratio and pH. Our results show that from a GR (SO4 2- ), GR (CO3 2- ) is formed from a pH ≥8.2 for [SO4 2- ] / [HCO3 - ] = 12 and without any change in pH for [SO4 2- ] / [HCO3 - ] <12. Whereas from GR (CO3 2- ), GR (SO4 2- ) is formed for [SO4 2- ] / [HCO3 - ] > 1 without any change in pH.
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Matthews, S. G., K. Yang, and J. R. G. Challis. "Changes in glucocorticoid receptor mRNA in the developing ovine pituitary and the effects of exogenous cortisol." Journal of Endocrinology 144, no. 3 (March 1995): 483–90. http://dx.doi.org/10.1677/joe.0.1440483.
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Abstract Developmental changes in pituitary glucocorticoid receptor (GR) mRNA were examined during gestation and early neonatal life using in situ hybridization. Pituitaries were harvested from sheep fetuses at days 60–80, 100–120, 130–135, 140–142 and term, and from lambs of days 0–7 and 30–60, and adults. GR mRNA was present in the pars distalis by day 60, levels increased through gestation, and there was a redistribution of GR mRNA, resulting in a relatively greater abundance at the base of the pars distalis. At term, there was a significant (P<0·05 compared with the day 140–142 fetuses) elevation of GR mRNA, which was maintained in the newborn lamb, reaching highest levels at days 30–60 of neonatal life. GR mRNA was undetectable in the pars intermedia until day 120, but subsequently increased to high levels at term. Interestingly, the expression of GR mRNA in the pars intermedia dropped precipitously in the newborn (P<0·05 compared with term), though levels recovered in the older lambs and adults. The regional and cellular distribution of GR mRNA correlated closely with the presence of immuno-reactive GR (irGR) in the pituitary; the majority of irGR was present in the nuclei. Intrafetal infusion of cortisol (12 h; 5 μg/min) in late gestation (day 135) had no effect on GR mRNA expression in either the pars distalis or pars intermedia. These results indicated that, in the fetal pituitary, (1) the GR gene is expressed in both the pars distalis and pars intermedia, (2) levels of GR mRNA in the fetal pituitary correlated with the distribution of nuclear irGR, (3) GR mRNA is present at higher levels in the inferior aspect of the pars distalis, its abundance increases immediately prior to parturition and is maintained in the newborn, and (4) cortisol infusion for 12 h does not affect GR mRNA in either region of the pituitary, suggesting that, in the short term, glucocorticoids do not directly regulate GR synthesis. Journal of Endocrinology (1995) 144, 483–490
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Jha, Prashant, and Jason K. Norsworthy. "Influence of Late-Season Herbicide Applications on Control, Fecundity, and Progeny Fitness of Glyphosate-Resistant Palmer Amaranth (Amaranthus palmeri) Biotypes from Arkansas." Weed Technology 26, no. 4 (December 2012): 807–12. http://dx.doi.org/10.1614/wt-d-12-00060.1.
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Experiments were conducted in 2008 and 2009 in Fayetteville, AR, to determine the influence of late-season herbicide applications on control, seed reduction, seed viability, and seedling fitness of two glyphosate-resistant (GR) Palmer amaranth biotypes, one from Mississippi County (MC) and the other from Lincoln County (LC) in Arkansas. Glyphosate (870 g ae ha−1), glufosinate (820 g ai ha−1), 2,4-D amine (1,060 g ae ha−1), dicamba (280 g ae ha−1), and pyrithiobac (70 g ai ha−1) were each applied at the first visible sign of inflorescence of GR Palmer amaranth plants. Glufosinate, 2,4-D, and dicamba provided 52 to 74% control of MC GR Palmer amaranth plants 28 d after treatment (DAT). The LC biotype was larger (94 cm tall) than the MC biotype was (64 cm tall) at application and was more difficult to control. Although control of GR Palmer amaranth was inadequate, late-season applications of glufosinate, 2,4-D, and dicamba reduced seed production of the LC biotype by 75 to 87% and production of the MC biotype by 94 to 95% compared with nontreated plants. Irrespective of biotypes, glufosinate, 2,4-D, and glyphosate reduced 100-seed weight by 22% compared with the nontreated control, and viability of seeds produced by treated plants was only 45 to 61% compared with 97% seed viability in nontreated plants. Glyphosate, glufosinate, 2,4-D, or dicamba reduced cumulative seedling emergence by an average of 84% compared with the nontreated check. Seedling biomass was four times greater for the LC than for the MC biotype, suggesting greater vigor and fitness for the LC progeny. This research demonstrates that a single, late-season (early inflorescence stage) application of glufosinate, 2,4-D, or dicamba could potentially reduce seedbank replenishment of GR Palmer amaranth. Additionally, reduction in seed weight, viability, and seedling recruitment would impair the success of GR Palmer amaranth progeny in the following season.
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Tarigan, M. Rafii Ma'arif, and Masnadi Munir. "Pengaruh Pemberian Jentik Nyamuk (Culex sp) Dan Cacing Sutera (Tubifex sp) Terhadap Pertumbuhan Ikan Cupang (Betta splendens)." Best Journal (Biology Education, Sains and Technology) 1, no. 1 (August 3, 2018): 01–07. http://dx.doi.org/10.30743/best.v1i1.617.
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Penelitian ini bertujuan untuk mengetahui pengaruh pemberian jentik nyamuk (Culex sp) dan cacing sutera (Tubifex sp) terhadap pertumbuhan ikan cupang (Betta splendens) dan melihat pertumbuhan ikan cupang dari parameter berat tubuh ikan dan panjang tubuh ikan. Metode yang digunakan adalah metode eksperimental dengan Rancangan Acak Kelompok Non Faktorial dengan taraf perlakuan pemberian cacing sutera 10 ekor, pemberian cacing sutera 12 ekor, pemberian jentik nyamuk 10 ekor dan pemberian jentik nyamuk 12 ekor. Jumlah ulangan 6, jumlah perlakuan 4, jumlah akuarium 24 buah, jumlah ikan keseluruhan 24 ekor. Paramater yang diamati adalah berat tubuh ikan dan panjang tubuh ikan cupang (Betta splendens). Data yang diperoleh dianalisis dengan analisis sidik ragam. Hasil Penelitian dari parameter pertumbuhan yang dihitung berupa pertambahan berat, dan pertambahan panjang yaitu pertambahan berat ikan cupang (Betta splendens) dari pemberian cacing sutera 10 ekor sebesar1,75 gr, dan panjang tubuh sebesar 3,05 cm, pemberian cacing sutera 12 ekor sebesar 2,55 gr dan panjang tubuh 3,25 cm, pemberian jentik nyamuk 10 ekor sebesar 3,44 gr dan panjang tubuh 4,31 cm, pemberian jentik nyamuk 12 ekor sebesar 4,85 gr dan panjang tubuh 6,12 cm. Perlakuan yang menggunakan pakan jentik nyamuk menghasilkan pertumbuhan paling tinggi dibandingkan perlakuan pemberian cacing sutera. Ini dikarenakan kandungan nutrisi yang terdapat pada jentik nyamuk lebih tinggi dibandingkan nutrisi pada cacing sutera.
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Lu, Kim D., Shlomit Radom-Aizik, Fadia Haddad, Frank Zaldivar, Monica Kraft, and Dan M. Cooper. "Glucocorticoid receptor expression on circulating leukocytes differs between healthy male and female adults." Journal of Clinical and Translational Science 1, no. 2 (February 15, 2017): 108–14. http://dx.doi.org/10.1017/cts.2016.20.
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IntroductionThe glucocorticoid receptor (GR) is a key receptor involved in inflammatory responses and is influenced by sex steroids. This study measured GR expression on circulating leukocyte subtypes in males and females.MethodsA total of 23 healthy adults (12 female) participated in this study. GR expression was measured in leukocyte subtypes using flow cytometry. Peripheral blood mononuclear cell (PBMC) gene expression of GR (NR3C1), GR β, TGF-β1 and 2, and glucocorticoid-induced leucine zipper (GILZ) were determined by real-time polymerase chain reaction.ResultsLeukocyte GR was lower in females, particularly in granulocytes, natural killer cells, and peripheral blood mononuclear cells (p≤0.01). GR protein expression was different across leukocyte subtypes, with higher expression in eosinophils compared with granulocytes, T lymphocytes, and natural killer cells (p<0.05). There was higher gene expression of GR β in males (p=0.03).ConclusionsThis is the first study to identify sexual dimorphism in GR expression in healthy adults using flow cytometry. These results may begin to explain the sexual dimorphism seen in many diseases and sex differences in glucocorticoid responsiveness.
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Mahdipour, Elahe, Jayne C. Charnock, and Kimberly A. Mace. "Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells." Blood 117, no. 3 (January 20, 2011): 815–26. http://dx.doi.org/10.1182/blood-2009-12-259549.
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Abstract Injury induces the recruitment of bone marrow-derived cells (BMDCs) that contribute to the repair and regeneration process. The behavior of BMDCs in injured tissue has a profound effect on repair, but the regulation of BMDC behavior is poorly understood. Aberrant recruitment/retention of these cells in wounds of diabetic patients and animal models is associated with chronic inflammation and impaired healing. BMD Gr-1+CD11b+ cells function as immune suppressor cells and contribute significantly to tumor-induced neovascularization. Here we report that Gr-1+CD11b+ cells also contribute to injury-induced neovascularization, but show altered recruitment/retention kinetics in the diabetic environment. Moreover, diabetic-derived Gr-1+CD11b+ cells fail to stimulate neovascularization in vivo and have aberrant proliferative, chemotaxis, adhesion, and differentiation potential. Previously we demonstrated that gene transfer of HOXA3 to wounds of diabetic mice is taken up by and expressed by recruited BMDCs. This is associated with a suppressed inflammatory response, enhanced neovascularization, and accelerated wound healing. Here we show that sustained expression of Hoxa3 in diabetic-derived BMD Gr-1+CD11b+ cells reverses their diabetic phenotype. These findings demonstrate that manipulation of adult stem/progenitor cells ex vivo could be used as a potential therapy in patients with impaired wound healing.
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LINARDOU, Kalirroe. "Mary and her Books in the Kokkinobaphos Manuscripts: Female Literacy or Visual Strategies of Narration?" Δελτίον Χριστιανικής Αρχαιολογικής Εταιρείας 47 (November 23, 2011): 35. http://dx.doi.org/10.12681/dchae.604.
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<p><span lang="el-GR">Η μελέτη </span><span lang="el-GR">αυτή εξετάζει τη λειτουργία του βιβλίου ως πολυσήμαντου εικαστικού συμβόλου στις μικρογραφίες δύο εικονογραφημένων βυζαντινών χειρογράφων των μέσων του 12</span><sup><span lang="el-GR">ου</span></sup><span lang="el-GR"> αι., στις Ομιλίες του μοναχού Ιακώβου της Μονής Κοκκινοβάφου, και προσπαθεί να καταδείξει ότι </span><span lang="el-GR">τα βιβλία/σύμβολα στα χέρια της Μαρίας επιστρατεύτηκαν για να εξυπηρετήσουν, πρωταρχικά και μεταξύ άλλων, τη διαδικασία της εικαστικής αφήγησης.</span></p>
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Wang, Jianxin, and David B. Wolff. "Evaluation of TRMM Rain Estimates Using Ground Measurements over Central Florida." Journal of Applied Meteorology and Climatology 51, no. 5 (May 2012): 926–40. http://dx.doi.org/10.1175/jamc-d-11-080.1.
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AbstractThis study evaluates space-based rain estimates from the Tropical Rainfall Measuring Mission (TRMM) satellite using ground-based measurements from the radar (GR) and tipping-bucket rain gauges (TG) over the TRMM Ground Validation (GV) site at Melbourne, Florida. The satellite rain products are derived from the TRMM Microwave Imager (TMI), precipitation radar (PR), and combined (COM) rain algorithms using observations from both instruments. The TRMM satellite and GV rain products are spatiotemporally matched and are intercompared at multiple time scales over the 12-yr period from 1998 to 2009. On monthly and yearly scales, the TG agree excellently with the GR because the GR rain rates are generated using the TG data as a constraint on a monthly basis. However, large disagreements exist between the GR and TG at shorter time scales because of their significantly different spatial and temporal sampling modes. The yearly biases relative to the GR for the PR and TMI are generally negative, with a few exceptions. The COM bias fluctuates from year to year over the 12-yr period. The PR, TMI, and COM are in good overall agreement with the GR in the lower range of rain rates, but the agreement is notably worse at higher rain rates. The diurnal cycle of rainfall is captured well by all products, but the peak satellite-derived rainfall (PR, TMI, and COM) lags the peak from the ground measurements (GR and TG) by ~1 h.
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Situmorang, Median Ramot, Nur Ariyani Agustina, and Bayu Pratomo. "PENGARUH PEMBERIAN PUPUK HAYATI MIKORIZA DAN PUPUK KASCING TERHADAP PERTUMBUHAN BIBIT KELAPA SAWIT (Elaeis guineensis Jacq.) DI PRE NURSERY." Jurnal Agro Estate 4, no. 2 (December 24, 2020): 59–70. http://dx.doi.org/10.47199/jae.v4i2.143.
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Penelitian ini bertujuan untuk mengetahui pertumbuhan bibit kelapa sawit setelah diberi pupuk hayati mikoriza dan pupuk kascing dengan dosis yang berbeda. Penelitian ini menggunakan metode eksperimen dengan Rancangan Acak Kelompok (RAK) 2 Faktorial. Faktor pertama adalah pupuk mikoriza yang terdiri dari 4 taraf yaitu: Kontrol (M0), 4 gr (M1), 8 gr (M2), 12 gr (M3) dan faktor kedua adalah pupuk kascing yang terdiri dari 4 taraf yaitu: Kontrol (K1), 40 gr (K1), 80 gr (K2), 120 gr (K3). Data dianalisis dengan menggunakan sidik ragam (Analysis of Variance), dilanjutkan dengan uji DMRT (Duncan’s Multiple Range Test) dengan signifikan 5 %. Berdasarkan hasil analisis data yang diperoleh bahwa perlakuan pupuk hayati mikoriza tidak berpengaruh nyata terhadap pertumbuhan kelapa sawit, sedangkan pemberian pupuk kascing berpengaruh nyata terhadap pertumbuhan tanaman kelapa sawit, serta interaksi berpengaruh nyata terhadap jumlah daun (3.00 helai) pada minggu ke 8 setelah tanam.
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Traynor, A. M., S. Dubey, J. Eickhoff, J. M. Kolesar, S. M. Marcotte, L. C. Hammes, C. M. Hallahan, C. E. Moore, J. Zwiebel, and J. H. Schiller. "A phase II study of vorinostat (NSC 701852 ) in patients (pts) with relapsed non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18044. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18044.
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18044 Background: Vorinostat is a small molecule inhibitor of histone deacetylase (HDAC). HDAC inhibitors have shown preclinical activity in lung cancer and are postulated to have an antitumor effect by alteration in acetylation status of histone and non-histone proteins. Methods: Pts with relapsed NSCLC who failed no more than 1 prior cytotoxic therapy were eligible. Treatment: vorinostat, 400 mg po daily in a 21 day cycle. Primary objective: response rate (RR), with goal of at least one responder in first 14 evaluable pts. Secondary objectives: time to progression (TTP), overall survival (OS), safety, and correlative assays. Results: 14 pts enrolled from 12/05- 12/06. Median age 59.5 yrs (range 47–79). 11 females. PS 0:1, 10 pts:4 pts. Thirteen of 14 pts had only 1 prior cytotoxic regimen; 1 pt had only prior erlotinib. Best response to prior treatment: stable disease (SD; 11 pts), progressive disease (PD; 3 pts). Median time since last prior therapy: 2.1 mo (range 0.2–78.5). Vorinostat treatment compliance: 95.8 %. Two pts were not evaluable for response due to not completing Cycle 1 of treatment due to PD. No objective antitumor responses have been seen in the first 12 evaluable pts. Seven pts experienced SD (median 4.2 mo, range 2–10.7). Median TTP: 2.8 mo (range 1–10.7+); median OS 6.5 mo (range 1.4–10.7+); estimated 6 mo OS rate 50% (SE 16%). Grade (Gr) 5 toxicity: CVA (1 pt). Gr 3/4 toxicities: neutropenia (Gr 4–1 pt), lymphopenia (Gr 3–2 pts), fatigue (Gr 3–1 pt), elevated alk phos (Gr 3–1 pt), memory impairment (Gr 3–1 pt), PE/DVT (Gr 3–1 pt; Gr 4–2 pts), dehydration (Gr 3–1 pt). Data from the following correlative studies will be updated: p53 status, gene expression, H3 acetylation, transcription of p21, Nur77, Hsp70, erbB1 and 2, and Akt, cell cycle arrest, and assay of isoprostanes generated by treatment with vorinostat. Conclusions: Vorinostat 400 mg daily is tolerable with more than 80% of patients completing Cycle 1. Vorinostat yields TTP in relapsed NSCLC similar to that of other targeted agents. Although 4 of 14 pts experienced vascular events on treatment, these occurrences are common in this disease setting. At least two additional pts are still to be accrued. Further studies in NSCLC should focus on combining vorinostat with other antitumor agents. No significant financial relationships to disclose.
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Hu, Xiao, Sarah Du, Cansu Tunca, Timothy Braden, Kelly R. Long, Jamie Lee, Elizabeth G. Webb, et al. "The Antagonists But Not Partial Agonists of Glucocorticoid Receptor Ligands Show Substantial Side Effect Dissociation." Endocrinology 152, no. 8 (May 10, 2011): 3123–34. http://dx.doi.org/10.1210/en.2010-1447.
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A synthetic glucocorticoid receptor (GR) ligand with the efficacy of a glucocorticoid, but without the accompanying side effects, would meet an unmet medical need for the treatment of inflammatory diseases. It was hypothesized that a GR ligand that shifted helix 12 in a manner distinct from an agonist and an antagonist would confer a distinct GR conformation, resulting in differential gene expression and, ultimately, dissociation of antiinflammatory activity from side effects. A structural feature expected to interfere with helix 12 was incorporated into a nonsteroidal, tricyclic scaffold to create novel, high-affinity, and selective GR ligands that manifested a dual function in cellular assays, partial but robust agonist activity for inflammatory cytokine inhibition, and full antagonist activity for reporter gene activation. In contrast, analogs not likely to hinder helix 12 exhibited partial agonist activity for reporter gene activation. The requirement of full antagonist activity for substantial side effect dissociation was demonstrated in primary human preadipocytes, hepatocytes, and osteoblasts in which effects on adipogenesis, key genes involved in gluconeogenesis, and genes important for bone formation were examined, respectively. The dissociated GR ligands, despite lacking significant reporter gene activation, weakly recruit a limited number of coactivators such as peroxisomal proliferator-activated receptor-γ coactivator 1α. Transcriptional activation was sensitive to both peroxisomal proliferator-activated receptor-γ coactivator 1α and GR levels, providing a basis for cell-selective modulation of gene expression. The antiinflammatory activity of the dissociated ligands was further demonstrated in mouse models of inflammation. Together these results suggest that these ligands are promising candidates with robust antiinflammatory activity and likely dissociation against glucocorticoid-induced side effects.
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Robben, Paul M., Marie LaRegina, William A. Kuziel, and L. David Sibley. "Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis." Journal of Experimental Medicine 201, no. 11 (May 31, 2005): 1761–69. http://dx.doi.org/10.1084/jem.20050054.
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Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1−/CCR2−/CX3CR1high) or responding to sites of inflammation (Gr-1+/CCR2+/CX3CR1lo). Gr-1+ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1+ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1+ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2−/− and MCP-1−/− mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1+ monocytes. The failure to recruit Gr-1+ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-α, and IFN-γ. The profound susceptibility of CCR2−/− mice establishes Gr-1+ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1+ monocytes may be an important general mechanism for resistance to intracellular pathogens.
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Tahvanainen, E., A. S. Villanueva, H. Forsius, P. Salo, and A. de la Chapelle. "Dominantly and recessively inherited cornea plana congenita map to the same small region of chromosome 12." Genome Research 6, no. 4 (April 1, 1996): 249–54. http://dx.doi.org/10.1101/gr.6.4.249.
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Alvarez-Ponce, D., M. Aguade, and J. Rozas. "Network-level molecular evolutionary analysis of the insulin/TOR signal transduction pathway across 12 Drosophila genomes." Genome Research 19, no. 2 (December 3, 2008): 234–42. http://dx.doi.org/10.1101/gr.084038.108.
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Alimi, J. P. "Reverse Transcriptase-Polymerase Chain Reaction Validation of 25 "Orphan" Genes from Escherichia coli K-12 MG1655." Genome Research 10, no. 7 (July 1, 2000): 959–66. http://dx.doi.org/10.1101/gr.10.7.959.
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Parkinson, Nicholas J., Matthew Roddis, Ben Ferneyhough, Gang Zhang, Adam J. Marsden, Siarhei Maslau, Yasmin Sanchez-Pearson, et al. "Violation of the 12/23 rule of genomic V(D)J recombination is common in lymphocytes." Genome Research 25, no. 2 (November 3, 2014): 226–34. http://dx.doi.org/10.1101/gr.179770.114.
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Underwood, Matthew G., Nader Soltani, David C. Hooker, Darren E. Robinson, Joseph P. Vink, Clarence J. Swanton, and Peter H. Sikkema. "The Addition of Dicamba to POST Applications of Quizalofop-p-ethyl or Clethodim Antagonizes Volunteer Glyphosate-Resistant Corn Control in Dicamba-Resistant Soybean." Weed Technology 30, no. 3 (September 2016): 639–47. http://dx.doi.org/10.1614/wt-d-16-00016.1.
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Two studies consisting of six field experiments each were conducted at three locations in southwestern Ontario, Canada, in 2014 and 2015 to evaluate the possible antagonism when dicamba was added to quizalofop-p-ethyl or clethodim for the control of volunteer glyphosate-resistant (GR) corn. At 4 wk after application (WAA), quizalofop-p-ethyl at 24, 30, or 36 g ai ha−1provided 88, 94, and 95% control of volunteer GR corn, respectively. The addition of dicamba at 300 or 600 g ae ha−1to quizalofop-p-ethyl (24 g ha−1) reduced the activity of quizalofop-p-ethyl on volunteer GR corn by 12 and 20%. At 4 WAA, clethodim at 30, 37.5, and 45 g ai ha−1provided 85, 91, and 95% control of volunteer GR corn, respectively. The addition of dicamba at 300 or 600 g ha−1to clethodim (30 g ha−1) resulted in antagonism, causing a reduction in volunteer GR corn by 12 and 11%, respectively. In general, there was greater antagonism when the high rate of dicamba was tank-mixed with the lower rate of the graminicide. There was no antagonistic effect on soybean yield by tank-mixing dicamba with either graminicide at all rates evaluated. Based on these results, volunteer GR corn can be controlled effectively by increasing the rate of the graminicide when tankmixed with dicamba.