Similar Datasets
Project description:Scientific evidence suggests that not only murine scent communication is regulated by major urinary proteins, but that their expression may also vary in response to metabolism via a yet unknown mechanism. Major urinary proteins are expressed mainly in the liver, showing a sexually dimorphic pattern with substantially higher expression in males. Here, we investigate the metabolic implications of a major urinary protein knockout in twelve-week-old male and female C57BL/6N mice during ad libitum feeding. Despite both sexes of major urinary protein knockout mice displayed numerically increased body weight and visceral adipose tissue proportions compared to sex-matched wildtype mice, the main genotype-specific metabolic differences were observed exclusively in males. Male major urinary protein knockout mice exhibited plasma and hepatic lipid accumulation accompanied by a hepatic transcriptome indicating an activation of lipogenesis. These findings match the higher major urinary protein expression in male compared to female wildtype mice, suggesting a more distinct reduction in energy requirements in male compared to female major urinary protein knockout mice. The observed sex-specific anabolic phenotype confirms a role of major urinary protein in metabolism and, since major urinary proteins are not expressed in humans, suggests the major urinary protein knockout mouse as a potential alternative model for translational metabolism research which needs to be further elucidated.
2022-08-01 | GSE188156 | GEO
Project description:Scientific evidence suggests that not only murine scent communication is regulated by major urinary proteins, but that their expression may also vary in response to metabolism via a yet unknown mechanism. Major urinary proteins are expressed mainly in the liver, showing a sexually dimorphic pattern with substantially higher expression in males. Here, we investigate the metabolic implications of a major urinary protein knockout in twelve-week-old male and female C57BL/6N mice during ad libitum feeding. Despite both sexes of major urinary protein knockout mice displayed numerically increased body weight and visceral adipose tissue proportions compared to sex-matched wildtype mice, the main genotype-specific metabolic differences were observed exclusively in males. Male major urinary protein knockout mice exhibited plasma and hepatic lipid accumulation accompanied by a hepatic transcriptome indicating an activation of lipogenesis. These findings match the higher major urinary protein expression in male compared to female wildtype mice, suggesting a more distinct reduction in energy requirements in male compared to female major urinary protein knockout mice. The observed sex-specific anabolic phenotype confirms a role of major urinary protein in metabolism and, since major urinary proteins are not expressed in humans, suggests the major urinary protein knockout mouse as a potential alternative model for translational metabolism research which needs to be further elucidated.
2022-08-01 | GSE188157 | GEO
Project description:Apart from acute and chronic blood pressure lowering, we have no specific medications to prevent intracerebral haemorrhage (ICH) or improve outcomes once bleeding has occurred. One reason for this may be related to particular limitations associated with the current pre-clinical models of ICH, leading to a failure to translate into the clinic. It would seem that a breakdown in the 'drug development pipeline' currently exists for translational ICH research which needs to be urgently addressed. Here, we review the most commonly used pre-clinical models of ICH and discuss their advantages and disadvantages in the context of translational studies. We propose that to increase our chances of successfully identifying new therapeutics for ICH, a bi-directional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key pre-clinical observations. Furthermore, we highlight that post-mortem/ex-vivo ICH patient material is a precious and underused resource which could play an essential role in the verification of experimental results prior to consideration for further clinical investigation. Embracing multidisciplinary collaboration between pre-clinical and clinical ICH research groups will be essential to ensure the success of this type of approach in the future.
| S-EPMC7575484 | biostudies-literature
Project description:Infection with Mycobacterium tuberculosis predominantly establishes subclinical latent infection over the lifetime of an individual, with a fraction of infected individuals rapidly progressing to active disease. The immune control in latent infection can be perturbed by comorbidities such as diabetes mellitus, obesity, smoking, and coinfection with helminthes or HIV. Modeling the varying aspects of natural infection remains incomplete when using zebrafish and mice. However, the nonhuman primate model of tuberculosis offers a unique and accurate model to investigate host responses to infection, test novel therapeutics, and thoroughly assess preclinical vaccine candidates. Rhesus macaques and cynomolgus macaques manifest the full gamut of clinical and pathological findings in human Mycobacterium tuberculosis infection, including the ability to co-infect macaques with Simian Immunodeficiency Virus to model HIV co-infection. Here we discuss advanced techniques to assay various clinical outcomes of the natural progression of infection as well as therapeutics in development and novel preclinical vaccines. Finally, we survey the translational aspects of nonhuman primate research and argue the urgent need to thoroughly examine preclinical therapeutics and vaccines using this model prior to clinical implementation.
| S-EPMC6279141 | biostudies-literature
Project description:PURPOSE:There is significant need for well-characterized antibodies to the spectrum of human proteins encoded by the genome. Advances in tissue-based proteomic profiling have led to the discovery of many candidate molecular biomarkers and therapeutic targets for which development of clinical assays is depending on high quality antibodies. We developed an antibody validation approach for screening of new mAbs. EXPERIMENTAL DESIGN:We utilized a multi-stage approach of protein array and immunohistochemistry. In the first phase, we screened the NCI60 panel of cell lines by means of protein array and select antibodies based on concordance of mRNA expression to protein array signal. Results of this assay are used to predict antibody titer for immunohistochemistry on the NCI60 cell lines, presented as a tissue microarray. In the final stage, we created a tissue-based protein expression map by performing immunohistochemistry on a multi-tumor tissue microarray. RESULTS:The success rate of this systematic antibody-screening tool was approximately 93% as measured by the results from the protein array. Data from the NCI60 protein array could be used to predict antibody titer for immunohistochemistry, improving the success rate of immunohistochemical assay development. CONCLUSIONS AND CLINICAL RELEVANCE:The presented strategy of antibody validation and characterization can be provided a new tool for exploration of human proteome.
| S-EPMC3839105 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-01-21 | GSE165191 | GEO
Project description:The baseline immune landscape of spontaneous canine HNSCC tumors was asssessed using immunohistochemistry and nanostring gene expression profiling of 34 canine oral carcinoma tumors and two normal oral mucosal tissue samples.
2022-09-24 | GSE213726 | GEO
Project description:To investigate the extent of similarity in epigenetic programming among human, baboon and mouse PSCs, we examined genome-wide patterns of four chromatin modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac) and DNA methylation in baboon iPSC and ESCs. We show that baboon pluripotent cells (PSCs) recapitulate key molecular features of human PSCs with much greater accuracy than that found in PSCs from non-primate species. Specifically, baboon and human PSCs exhibit significantly greater conservation of gene expression patterns, higher sequence and structural homology among pluripotency factors, more equivalent genome-wide patterns of histone and DNA methylation modifications, and similar maintenance of bivalent programming of developmental genes than that found between human and non-primate PSCs.
2021-01-21 | GSE165189 | GEO
Project description:BackgroundThere is a lack of predictive preclinical animal models combining atherosclerosis and type 2 diabetes. APOE∗3-Leiden (E3L) mice are a well-established model for diet-induced hyperlipidemia and atherosclerosis, and glucokinase+/- (GK+/-) mice are a translatable disease model for glucose control in type 2 diabetes. The respective mice respond similarly to lipid-lowering and antidiabetic drugs as humans. The objective of this study was to evaluate/characterize the APOE∗3-Leiden.glucokinase+/- (E3L.GK+/-) mouse as a novel disease model to study the metabolic syndrome and diabetic complications.MethodsFemale E3L.GK+/-, E3L, and GK+/- mice were fed fat- and cholesterol-containing diets for 37 weeks, and plasma parameters were measured throughout. Development of diabetic macro- and microvascular complications was evaluated.ResultsCholesterol and triglyceride levels were significantly elevated in E3L and E3L.GK+/- mice compared to GK+/- mice, whereas fasting glucose was significantly increased in E3L.GK+/- and GK+/- mice compared to E3L. Atherosclerotic lesion size was increased 2.2-fold in E3L.GK+/- mice as compared to E3L (p = 0.037), which was predicted by glucose exposure (R 2 = 0.636, p = 0.001). E3L and E3L.GK+/- mice developed NASH with severe inflammation and fibrosis which, however, was not altered by introduction of the defective GK phenotype, whereas mild kidney pathology with tubular vacuolization was present in all three phenotypes.ConclusionsWe conclude that the E3L.GK+/- mouse is a promising novel diet-inducible disease model for investigation of the etiology and evaluation of drug treatment on diabetic atherosclerosis.
| S-EPMC6425338 | biostudies-literature
Project description:The introduction of injury models for neonatal mouse hearts has accelerated research on the mechanisms of cardiac regeneration in mammals. However, some existing models, such as apical resection and ligation of the left anterior descending artery, produce variable results, which may be due to technical difficulties associated with these methods. Here we present an alternative model for the study of cardiac regeneration in neonatal mice in which cryoinjury is used to induce heart injury. This model yields a reproducible injury size, does not induce known mechanisms of cardiac regeneration and leads to a sustained reduction of cardiac function. This protocol uses reusable cryoprobes that can be assembled in 5 min, with the entire procedure taking 15 min per pup. The subsequent heart collection and fixation takes 2 d to complete. Cryoinjury results in a myocardial scar, and the size of injury can be scaled by the use of different cryoprobes (0.5 and 1.5 mm). Cryoinjury models are medically relevant to diseases in human infants with heart disease. In summary, the myocardial cryoinjury model in neonatal mice described here is a useful tool for cardiac translational and regeneration research.
| S-EPMC5464389 | biostudies-literature