1,349 results match your criteria: "Center for Molecular Medicine and Genetics[Affiliation]"

Preeclampsia is a pregnancy disorder with substantial perinatal and maternal morbidity and mortality. Pregnant women at risk of preeclampsia would benefit from early detection for follow-up, timely interventions and delivery. Several attempts have been made to identify protein biomarkers of preeclampsia, but findings vary with demographics, clinical characteristics, and time of sampling.

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[This corrects the article DOI: 10.3389/fonc.2024.

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Using educational frameworks for learner assessment in genetic counseling (GC) training may help students and supervisors articulate developmentally appropriate clinical skills-based objectives and tasks that align with various stages of training as students work toward achieving entry-level competency. This professional issues case study describes how two GC programs adapted and implemented the RIME (Reporter-Interpreter-Manager-Educator) learner assessment framework, originally designed for medical education, to support and assess students' acquisition of practice-based competencies (PBCs) during clinical fieldwork placements. Each RIME level describes a different set of expectations regarding the skills students should be able to demonstrate based on the level of training they have achieved up to that point in time.

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Background: Genetic colocalization analysis is a statistical method that evaluates whether two traits (e.g., osteoarthritis [OA] risk and microRNA [miRNA] expression levels) share the same or distinct genetic association signals in a locus typically identified in genome-wide association studies (GWAS).

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MicroRNA signature for early prediction of knee osteoarthritis structural progression using integrated machine and deep learning approaches.

Osteoarthritis Cartilage

November 2024

Henry Ford Health + Michigan State University Health Sciences, Detroit, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, USA. Electronic address:

Objective: Conventional methodologies are ineffective in predicting the rapid progression of knee osteoarthritis (OA). MicroRNAs (miRNAs) show promise as biomarkers for patient stratification. We aimed to develop a miRNA prognosis model for identifying knee OA structural progressors/non-progressors using integrated machine/deep learning tools.

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Circular RNAs (circRNAs) has recently been considered a class of endogenous RNAs that form a continuous closed loop with an ability to cancer development. Due to its properties, circRNAs has promising potential to be considered as non-invasive cancer biomarkers. The present review comprehensively and systematically assessed the role of circRNAs as diagnostic markers in blood or tissue samples of colorectal cancer (CRC) patients.

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The rising incidences of myocardial infarction (MI), often affecting individuals without traditional risk factors, highlight the urgent need for improved early detection using personal health data. However, health surveys and electronic health records (EHRs) frequently suffer from class imbalances, leading to prediction biases and differences between specificity and sensitivity, which hinder reliable model development despite the valuable insights contained in these datasets. To address this, we have introduced a novel approach to enhance MI risk prediction using self-reported attributes from the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS) dataset.

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Endocrine pathology in young rabbits with cystic fibrosis.

eGastroenterology

November 2024

Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Background: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the transmembrane conductance regulator gene. CF-related pancreatic lesions are known to cause exocrine dysfunctions such as pancreatic insufficiency, and endocrine dysfunctions, including CF related diabetes. In a previous study, we generated CF rabbits using CRISPR/Cas9-mediated gene editing.

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Lipid droplet targeting of ABHD5 and PNPLA3 I148M is required to promote liver steatosis.

bioRxiv

November 2024

Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, 48202.

The storage and release of triacylglycerol (TAG) in lipid droplets (LDs) is regulated by dynamic protein interactions. α/β hydrolase domain-containing protein 5 (ABHD5; also known as CGI-58) is a membrane/LD bound protein that functions as a co-activator of Patatin Like Phospholipase Domain Containing 2 (PNPLA2; also known as Adipose triglyceride lipase, ATGL) the rate-limiting enzyme for TAG hydrolysis. The dysregulation of TAG hydrolysis is involved in various metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD).

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The Mitochondrial Unfolded Protein Response (UPR), a mitochondria-originated stress response to altered mitochondrial proteostasis, plays important roles in various pathophysiological processes. In this study, we revealed that the endoplasmic reticulum (ER)-tethered stress sensor CREBH regulates UPR to maintain mitochondrial homeostasis and function in the liver. CREBH is enriched in and required for hepatic Mitochondria-Associated Membrane (MAM) expansion induced by energy demands.

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Mitochondria are essential to cellular function as they generate the majority of cellular ATP, mediated through oxidative phosphorylation, which couples proton pumping of the electron transport chain (ETC) to ATP production. The ETC generates an electrochemical gradient, known as the proton motive force, consisting of the mitochondrial membrane potential (ΔΨ, the major component in mammals) and ΔpH across the inner mitochondrial membrane. Both ATP production and reactive oxygen species (ROS) are linked to ΔΨ, and it has been shown that an imbalance in ΔΨ beyond the physiological optimal intermediate range results in excessive ROS production.

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Reduced expressions of TCA cycle genes during aging in humans and mice.

Biochem Biophys Res Commun

December 2024

Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA. Electronic address:

Aging is associated with a decline in physiological functions and an increased risk of metabolic disorders. The liver, a key organ in metabolism, undergoes significant changes during aging that can contribute to systemic metabolic dysfunction. This study investigates the expression of genes involved in the tricarboxylic acid (TCA) cycle, a critical pathway for energy production, in the aging liver.

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Background: Miscarriages cause a greater loss-of-life than cardiovascular diseases, but knowledge about environmentally induced miscarriages is limited. Cultured naïve pluripotent embryonic stem cells (ESC) differentiate into extra-embryonic endoderm/extraembryonic endoderm (XEN) or formative pluripotent ESC, during the period emulating maximal miscarriage of peri-implantation development. In previous reports using small marker sets, hyperosmotic sorbitol, or retinoic acid (RA) decreased naïve pluripotency and increased XEN by FACS quantitation.

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Redefining the accumulated temperature index for accurate prediction of rice flowering time in diverse environments.

Plant Biotechnol J

January 2025

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, China.

Accurate prediction of flowering time across diverse environments is crucial for effective crop management and breeding. While the accumulated temperature index (ATI) is widely used as an indicator for estimating flowering time, its traditional definition lacks systematic evaluation and genetic basis understanding. Here, using data from 422 rice hybrids across 47 locations, we identified the optimal ATI calculation window as 1 day after sowing to 26 days before flowering.

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Impaired secretion of an essential blood coagulation factor fibrinogen leads to hepatic fibrinogen storage disease (HFSD), characterized by the presence of fibrinogen-positive inclusion bodies and hypofibrinogenemia. However, the molecular mechanisms underlying the biogenesis of fibrinogen in the endoplasmic reticulum (ER) remain unexplored. Here we uncover a key role of SEL1L-HRD1 complex of ER-associated degradation (ERAD) in the formation of aberrant inclusion bodies, and the biogenesis of nascent fibrinogen protein complex in hepatocytes.

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Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice.

J Immunol

December 2024

Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Detroit, MI and Bethesda, MD.

Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation.

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In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female health, potentially increasing risks for future pregnancies upon return to Earth, particularly related to small-for-gestational-age (SGA) fetuses.

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Problem: Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.

Method Of Study: This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls.

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Radiotherapy and breast cancer: finally, an lncRNA perspective on radiosensitivity and radioresistance.

Front Oncol

September 2024

Department of Biology, College of Science, Mathematics, and Technology, Wenzhou-Kean University, Wenzhou, China.

Radiotherapy (RT) serves as one of the key adjuvant treatments in management of breast cancer. Nevertheless, RT has two major problems: side effects and radioresistance. Given that patients respond differently to RT, it is imperative to understand the molecular mechanisms underlying these differences.

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VMAP: Vaginal Microbiome Atlas during Pregnancy.

JAMIA Open

October 2024

Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA 94143, United States.

Objectives: To enable interactive visualization of the vaginal microbiome across the pregnancy and facilitate discovery of novel insights and generation of new hypotheses.

Material And Methods: Vaginal Microbiome Atlas during Pregnancy (VMAP) was created with R shiny to generate visualizations of structured vaginal microbiome data from multiple studies.

Results: VMAP (http://vmapapp.

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Pathologies in adipose (fat) tissue function are linked with human diseases such as diabetes, obesity, metabolic syndrome, and cancer. Dynamic, rapid release of metabolites has been observed in adipocyte cells and tissue, yet higher temporal resolution is needed to adequately study this process. In this work, a microfluidic device with precise and regular valve-automated droplet sampling, termed a microfluidic analog-to-digital converter (μADC), was used to sample secretions from ∼0.

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Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

Wellcome Open Res

October 2023

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

Article Synopsis
  • Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
  • Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
  • The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
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The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.

Int J Mol Sci

August 2024

Center for Molecular Medicine and Genetics, Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, stochastic gene mutations play a role in aiding the growth of the cancer population, with their importance depending on the initial emergence of the new system.

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Germline variant profiling of CHEK2 sequencing variants in breast cancer patients.

Cancer Genet

November 2024

Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, United States; Department of Oncology, Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, United States. Electronic address:

The cell cycle checkpoint kinase 2 (CHEK2) is a tumor suppressor gene coding for a protein kinase with a role in the cell cycle and DNA repair pathways. Variants within CHEK2 are associated with an increased risk of developing breast, colorectal, prostate and several other types of cancer. Comprehensive genetic risk assessment leads to early detection of hereditary cancer and provides an opportunity for better survival.

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