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Journal articles on the topic 'DS rodent models'

Author: Grafiati
Published: 14 December 2024

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1

Zhang, Tan, Xin Wang, Hannah M. Jester, Xueyan Zhou, and Tao Ma. "Characterization of Apathy-Like Behaviors in Mouse Models of Down Syndrome." Journal of Alzheimer's Disease 101, no. 4 (2024): 1217–26. http://dx.doi.org/10.3233/jad-240675.

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Background: Apathy is a state of decreased interest, lack of initiative, reduced goal-directed activity and blunted emotional responses. Apathy is one of the most common neuropsychiatric symptoms (NPS) in patients with Alzheimer’s disease (AD) and is also relatively omnipresent in individuals with Down syndrome (DS). Little is known about the apathy-like behaviors in rodent models of AD and DS. Objective: This study aimed to characterize apathy-like behaviors with aging in two established DS mouse models: Ts65Dn and Dp16. Methods: A battery of behavioral tests including nestlet shredding, marb
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2

Bartesaghi, Renata, Stefano Vicari, and William C. Mobley. "Prenatal and Postnatal Pharmacotherapy in Down Syndrome: The Search to Prevent or Ameliorate Neurodevelopmental and Neurodegenerative Disorders." Annual Review of Pharmacology and Toxicology 62, no. 1 (2022): 211–33. http://dx.doi.org/10.1146/annurev-pharmtox-041521-103641.

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Those with Down syndrome (DS)—trisomy for chromosome 21—are routinely impacted by cognitive dysfunction and behavioral challenges in children and adults and Alzheimer's disease in older adults. No proven treatments specifically address these cognitive or behavioral changes. However, advances in the establishment of rodent models and human cell models promise to support development of such treatments. A research agenda that emphasizes the identification of overexpressed genes that contribute demonstrably to abnormalities in cognition and behavior in model systems constitutes a rational next ste
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3

Deckert, Jutta, Jenny Thirlway, Yun-Hee Park, et al. "Abstract 1753: IKS014, a HER2-targeting antibody drug conjugate incorporating novel bioconjugation and tumor-selective linker technology with improved in vivo efficacy and tolerability." Cancer Research 82, no. 12_Supplement (2022): 1753. http://dx.doi.org/10.1158/1538-7445.am2022-1753.

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Abstract HER2 has long been a target of high interest for antibody and antibody drug conjugate (ADC) therapeutics due to its well-documented overexpression in breast, gastric and lung cancer. While trastuzumab and ado-trastuzumab emtansine (T-DM1) have become an integral part of treatment paradigms for HER2-positive cancer, the more recent approvals of the fam-trastuzumab deruxtecan (DS-8201) ADC and the Fc-engineered margetuximab antibody have highlighted the potential for continued improvement over existing HER2-targeting therapies. IKS014 is a HER2-directed ADC that incorporates site-direct
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4

Zhang, Xichen, Michael W. Epperly, Mark A. Kay, et al. "Minicircle Plasmid Containing the Human Manganese Superoxide Dismutase (MnSOD) Transgene Confers Radioprotection to Hematopoietic Progenitor Cell Line 32Dcl3." Blood 110, no. 11 (2007): 5138. http://dx.doi.org/10.1182/blood.v110.11.5138.5138.

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Abstract Manganese superoxide dismutase plasmid/liposomes (MnSOD-PL) delivered by intratracheal, intraesophageal, or intraoral routes in rodent models has been demonstrated to confer organ specific ionizing irradiation protection. In addition intravenous injections of MnSOD-PL protect mice from whole body irradiation. Currently a seven week phase I/II clinical trial is in progress in lung cancer patients consisting of twice weekly swallowed MnSOD-PL for protection of the esophagus from chemoradiotherapy damage. To prepare for a potential clinical trial of systemic MnSOD-PL for radioprotection
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5

Jin, Shanshan, Xiaochen Zhang, Yunlu Jia, et al. "The design, preclinical study and phase I dose escalation plan of a HER2 targeted immunoliposome (HF-K1) for HER2 low solid tumor treatment." Journal of Clinical Oncology 42, no. 16_suppl (2024): 3035. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.3035.

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3035 Background: Doxorubicin liposome formulations are being used extensively in the clinic in anthracycline chemotherapy with reduced cardiotoxicity. However, they did not improve clinical outcome because the cancer cell uptake of PEG-coated liposomes is poor. So, the concept of coating antibodies on the liposome surface was initiated and they were named immunoliposomes. There have been numerous studies conducted world-wide for the development of immunoliposomes but none have progressed to late-stage development. Our work draws on the experiences of these prior studies with a new perspective.
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6

Nonoguchi, Hannah A., Timothy Wee Shang Kouo, Sandhya Kortagere, Joshua Hillman, David L. Boyle, and Chitra D. Mandyam. "Lipopolysaccharide Exposure Differentially Alters Plasma and Brain Inflammatory Markers in Adult Male and Female Rats." Brain Sciences 12, no. 8 (2022): 972. http://dx.doi.org/10.3390/brainsci12080972.

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Humans and rodents have sexually dimorphic immune responses, which could influence the brain’s response to a systemic inflammatory insult. Lipopolysaccharide (LPS) is a stimulator of the innate immune system and is routinely used in animal models to study blood–brain barrier (BBB) dysfunction under inflammatory conditions. Therefore, we examined whether inflammatory response to LPS and the associated BBB disruption differed in male and female adult rats. Rats were treated with saline or two injections of 1 mg/kg LPS and studied 24 h after the second LPS injection. Plasma isolated from trunk bl
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7

Venkateshappa, Chandregowda, Kishore Narayanan, Rashmi Nair, et al. "Abstract 4432: A highly differentiated A2AR inhibitor for potential use in cancer therapy." Cancer Research 83, no. 7_Supplement (2023): 4432. http://dx.doi.org/10.1158/1538-7445.am2023-4432.

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Abstract As a potent immunosuppressor adenosine is essential for maintaining tissue homeostasis and preventing an overzealous immune response during inflammation and infection. However, adenosine generated within the tumor microenvironment by the action of ectonucleotides hinders the immune reaction towards cancer cells by signaling through adenosine receptors such as high affinity A2AR expressed on immune cells. Tumors evade the immune response by usurping pathways that negatively regulate normal immune responses. Resistance to inhibition of immune checkpoint targets arises because of an upre
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8

Khare, Leena, Ramulu Poddutoori, Subhendu Mukherjee, et al. "Abstract B172: Potent anti-tumor activity of a selective and orally bioavailable reversible covalent CDK12 inhibitor." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): B172. http://dx.doi.org/10.1158/1535-7163.targ-23-b172.

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Abstract Cyclin-dependent kinase 12 (CDK12), in association with Cyclin K (CycK), regulates the elongation of transcription by modifying RNA polymerase II (RNAP II) through phosphorylation at Serine 2 (pS2) in the C-terminal domain, CDK12 plays an important role in maintaining genomic stability by modulating crucial cellular processes such as DNA damage response, splicing, and pre-mRNA processing. Overexpression of CDK12 has been observed in various tumor types, suggesting its potential oncogenic properties like other kinases involved in transcription. Given its significance in transcription a
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9

Farrell, Clíona, Paige Mumford, Millie Beament та ін. "Modelling of the development and response to amyloid‐β accumulation in the context of trisomy21 in the rodent brain". Alzheimer's & Dementia 19, S12 (2023). http://dx.doi.org/10.1002/alz.075677.

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AbstractBackgroundIndividuals who have Down syndrome (DS), a genetic condition caused by having three copies of chromosome 21, frequently develop early‐onset Alzheimer’s disease (AD). This is caused by the additional copy of the APP gene, located on chromosome 21, which leads to a raised abundance of amyloid‐β. However, significant evidence demonstrates that the additional copy of other genes on the chromosome modifies the accumulation and response to amyloid‐β. Here we present a series of rodent preclinical models of AD‐DS, which we use to investigate this biology and can be used to test pote
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10

Farrell, Clíona, Paige Mumford, and Frances K. Wiseman. "Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches." Frontiers in Neuroscience 16 (June 7, 2022). http://dx.doi.org/10.3389/fnins.2022.909669.

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There are an estimated 6 million people with Down syndrome (DS) worldwide. In developed countries, the vast majority of these individuals will develop Alzheimer's disease neuropathology characterized by the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles within the brain, which leads to the early onset of dementia (AD-DS) and reduced life-expectancy. The mean age of onset of clinical dementia is ~55 years and by the age of 80, approaching 100% of individuals with DS will have a dementia diagnosis. DS is caused by trisomy of chromosome 21 (Hsa21) thus an additional copy o
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11

Chang, Pishan, Marta Pérez-González, Jessica Constable, et al. "Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation." Neuroscientist, September 24, 2024. http://dx.doi.org/10.1177/10738584241271414.

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Down syndrome (DS), a prevalent cognitive disorder resulting from trisomy of human chromosome 21 (Hsa21), poses a significant global health concern. Affecting approximately 1 in 800 live births worldwide, DS is the leading genetic cause of intellectual disability and a major predisposing factor for early-onset Alzheimer’s dementia. The estimated global population of individuals with DS is 6 million, with increasing prevalence due to advances in DS health care. Global efforts are dedicated to unraveling the mechanisms behind the varied clinical outcomes in DS. Recent studies on DS mouse models
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12

Sasaki, Masato, Mina Delawary, Hidetaka Sakurai, et al. "Novel LCAT (Lecithin:Cholesterol Acyltransferase) Activator DS-8190a Prevents the Progression of Plaque Accumulation in Atherosclerosis Models." Arteriosclerosis, Thrombosis, and Vascular Biology, October 22, 2020. http://dx.doi.org/10.1161/atvbaha.120.314516.

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Objective: Enhancement of LCAT (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. To evaluate this concept, we characterized our novel, orally administered, small-molecule LCAT activator DS-8190a, which was created from high-throughput screening and subsequent derivatization. We also focused on its mechanism of LCAT activation and the therapeutic activity with improvement of HDL (high-density lipoprotein) functionality. Approach and Results: DS-8190a activated human and cynomolgus monkey but not mouse LCAT enzymes in vitro. DS-8190a was orally
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13

Wong, Helen, Jordan M. Buck, Curtis Borski, et al. "RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer’s disease, and normative aging." Journal of Neurodevelopmental Disorders 14, no. 1 (2022). http://dx.doi.org/10.1186/s11689-022-09444-y.

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Abstract Background Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer’s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been imp
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14

Hill, Lisa J., Hannah F. Botfield, Ghazala Begum, et al. "ILB® resolves inflammatory scarring and promotes functional tissue repair." npj Regenerative Medicine 6, no. 1 (2021). http://dx.doi.org/10.1038/s41536-020-00110-2.

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AbstractFibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring. There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without d
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15

Ramos-Mondragon, Roberto, Chunling Chen, Julie Ziobro, et al. "Abstract 12541: Development of a Transgenic Rabbit Model of Dravet Syndrome." Circulation 146, Suppl_1 (2022). http://dx.doi.org/10.1161/circ.146.suppl_1.12541.

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Introduction: Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in patients with epilepsy. While SUDEP mechanisms are not understood, there is evidence to implicate autonomic dysfunction and cardiac arrhythmias. Loss-of-function variants in SCN1A are linked to Dravet syndrome (DS). Importantly, SCN1A is expressed in both heart and brain in humans and rodents. Studies on Scn1a+/- DS mice and induced pluripotent stem cell (iPSC)-derived cardiac myocytes from DS patients show altered cardiac electrophysiology that serves as substrates for arrhythmias. However, no mouse or iP
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