Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Matthew R. Masters, Amr H. Mahmoud, Markus A. Lill · 2025 · Nature Communications
Co-folding models represent a major innovation in deep-learning-based protein-ligand structure prediction. The recent publications of RoseTTAFold All-Atom, AlphaFold3, and others have shown high-quality results on predicting the structures of proteins interacting with small-molecules, nucleic-acids, and other proteins. Despite these advanced capabilities and broad potential, the current study presents critical findings that question the adherence of these models to fundamental physical principles. Through adversarial examples based on established physical, chemical, and biological principles,
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Jill M. Haenfler, Geena Skariah, Caitlin M. Rodriguez et al. · 2018 · Frontiers in Molecular Neuroscience
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism. It results from expansion of a CGG nucleotide repeat in the 5’ untranslated region of FMR1. Large expansions elicit repeat and promoter hyper-methylation, heterochromatin formation, FMR1 transcriptional silencing, and loss of the Fragile X protein, FMRP. Efforts aimed at correcting the sequelae resultant from FMRP loss have thus far proven insufficient, perhaps because of FMRP’s pleiotropic functions. As the repeats do not disrupt the FMRP coding sequence, reactivation of endogenous FMR1 gene exp
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Juan Pablo Nani, Fernanda Marcondes de Rezende, Francisco Peñagaricano · 2019 · BMC Genomics
BACKGROUND: Fertility is among the most important economic traits in dairy cattle. Genomic prediction for cow fertility has received much attention in the last decade, while bull fertility has been largely overlooked. The goal of this study was to assess genomic prediction of dairy bull fertility using markers with large effect and functional annotation data. Sire conception rate (SCR) was used as a measure of service sire fertility. Dataset consisted of 11.5 k U.S. Holstein bulls with SCR records and about 300 k single nucleotide polymorphism (SNP) markers. The analyses included the use of bo
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Katarzyna A. Cieslik, George E. Taffet, Jeffrey R. Crawford et al. · 2013 · Journal of Molecular and Cellular Cardiology
We have demonstrated that scar formation after myocardial infarction (MI) is associated with an endogenous pool of CD44(pos)CD45(neg) multipotential mesenchymal stem cells (MSC). MSC differentiate into fibroblasts secreting collagen that forms a scar and mature into myofibroblasts that express alpha smooth muscle actin (α-SMA) that stabilizes the scar. In the aging mouse, cardiac repair after MI is associated with impaired differentiation of MSC; MSC derived from the aged hearts form dysfunctional fibroblasts that deposit less collagen in response to transforming growth factor beta-1 (TGF-β1)
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Claudio Toma, Amaia Hervás, Bàrbara Torrico et al. · 2012 · Psychiatric Genetics
Impairment of language abilities is a common feature in autistic individuals. Heterozygous mutations in the Forkhead Box P2 (FOXP2) gene lead to a severe spoken language disorder. Recently, several studies have pinpointed the involvement…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Brett M. Kroncke, Amanda M. Duran, Jeffrey Mendenhall et al. · 2016 · Biochemistry
There is a compelling and growing need to accurately predict the impact of amino acid mutations on protein stability for problems in personalized medicine and other applications. Here the ability of 10 computational tools to accurately…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Stéphanie Gaillard, Marianna Zahurak, Anup Sharma et al. · 2019 · Cancer
BACKGROUND: Epigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC-486…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Charlotte Brierley, Cristina Castilla‐Llorente, Myriam Labopin et al. · 2018 · Journal of Crohn s and Colitis
BACKGROUND AND AIMS: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with severe, treatment-refractory Crohn's disease [CD]. The evidence base for AHSCT for CD is limited, with one…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Daniel Romero-Álvarez, A. Townsend Peterson, Johanna S. Salzer et al. · 2020 · PLoS neglected tropical diseases
BACKGROUND: Bacillus cereus biovar anthracis (Bcbva) is an emergent bacterium closely related to Bacillus anthracis, the etiological agent of anthrax. The latter has a worldwide distribution and usually causes infectious disease in mammals associated with savanna ecosystems. Bcbva was identified in humid tropical forests of Côte d'Ivoire in 2001. Here, we characterize the potential geographic distributions of Bcbva in West Africa and B. anthracis in sub-Saharan Africa using an ecological niche modeling approach. METHODOLOGY/PRINCIPAL FINDINGS: Georeferenced occurrence data for B. anthracis and
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Dipongkor Saha, Samuel D. Rabkin, Robert L. Martuza · 2020 · Journal for ImmunoTherapy of Cancer
Background Temozolomide (TMZ) chemotherapy is a current standard of care for glioblastoma (GBM), however it has only extended overall survival by a few months. Because it also modulates the immune system, both beneficially and negatively,…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Karolina Strzebońska, Marcin Waligóra · 2019 · BMC Medical Ethics
BACKGROUND: Novel precision oncology trial designs, such as basket and umbrella trials, are designed to test new anticancer agents in more effective and affordable ways. However, they present some ethical concerns referred to scientific validity, risk-benefit balance and informed consent. Our aim is to discuss these issues in basket and umbrella trials, giving examples of two ongoing cancer trials: NCI-MATCH (National Cancer Institute - Molecular Analysis for Therapy Choice) and Lung-MAP (Lung Cancer Master Protocol) study. MAIN BODY: We discuss three ethical requirements for clinical trials w
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Zhuan Li, Yohei Yamauchi, Maki Kamakura et al. · 2011 · Journal of Virology
Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Mayukh Chakrabarti, Hyunbum Jang, Ruth Nussinov · 2016 · The Journal of Physical Chemistry B
Human HRAS, KRAS, and NRAS genes encode four isoforms of Ras, a p21 GTPase. Mutations in KRAS account for the majority of RAS-driven cancers. The KRAS has two splice variants, K-Ras4A and K-Ras4B. Due to their reversible palmitoylation,…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Heidi Lynch, Matthew P. Buman, Jared M. Dickinson et al. · 2020 · International Journal of Environmental Research and Public Health
There are conflicting reports regarding the efficacy of plant versus animal-derived protein to support muscle and strength development with resistance training. The purpose of this study was to determine whether soy and whey protein supplements matched for leucine would comparably support strength increases and muscle growth following 12 weeks of resistance training. Sixty-one untrained young men (n = 19) and women (n = 42) (18–35 year) enrolled in this study, and 48 completed the trial (17 men, 31 women). All participants engaged in supervised resistance training 3×/week and consumed 19 grams
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Susan C. Kleiman, Emily Bulik-Sullivan, Elaine M. Glenny et al. · 2017 · PLoS ONE
OBJECTIVE: This study examined associations between the composition and diversity of the intestinal microbiota and measures of depression, anxiety, eating disorder psychopathology, stress, and personality in a group of healthy adult females. METHODS: Female participants (n = 91) ages 19-50 years with BMI 18.5-25 kg/m2 were recruited from central North Carolina between July 2014 and March 2015. Participants provided a single fecal sample and completed an online psychiatric questionnaire that included five measures: (i) Beck Anxiety Inventory; (ii) Beck Depression Inventory-II; (iii) Eating Diso
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Haijie Liu, Yang Hu, Yan Zhang et al. · 2022 · Alzheimer s Research & Therapy
BACKGROUND: Until now, Mendelian randomization (MR) studies have investigated the causal association of risk factors with Alzheimer's disease (AD) using large-scale AD genome-wide association studies (GWAS), GWAS by proxy (GWAX), and meta-analyses of GWAS and GWAX (GWAS+GWAX) datasets. However, it currently remains unclear about the consistency of MR estimates across these GWAS, GWAX, and GWAS+GWAX datasets. METHODS: Here, we first selected 162 independent educational attainment genetic variants as the potential instrumental variables (N = 405,072). We then selected one AD GWAS dataset (N = 63
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Małgorzata Bulkowska, Agata Rybicka, Kerem Mert Senses et al. · 2017 · BMC Cancer
BACKGROUND: MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans. METHODS: Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases)
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Danni Li, Jeffrey R. Misialek, Eric Boerwinkle et al. · 2016 · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring
INTRODUCTION: The objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
M.P.L. Calus, Michael E. Goddard, Yvonne C. J. Wientjes et al. · 2018 · Journal of Dairy Science
Genomic prediction is applicable to individuals of different breeds. Empirical results to date, however, show limited benefits in using information on multiple breeds in the context of genomic prediction. We investigated a multitask…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Kristin M. Burkart, Tamar Sofer, Stephanie J. London et al. · 2018 · American Journal of Respiratory and Critical Care Medicine
Abstract Rationale Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry. Objectives Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations. Methods GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies. Measurements and Main Results Among 11,
View details →Replication FailureBiochemistry, Genetics and Molecular Biology
Kyle M. Walsh, Erik L. Anderson, Helen M. Hansen et al. · 2012 · Genetic Epidemiology
Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Fabio Morgante, Wen Huang, Peter Sørensen et al. · 2020 · G3 Genes Genomes Genetics
Abstract The ability to accurately predict complex trait phenotypes from genetic and genomic data are critical for the implementation of personalized medicine and precision agriculture; however, prediction accuracy for most complex traits is currently low. Here, we used data on whole genome sequences, deep RNA sequencing, and high quality phenotypes for three quantitative traits in the ∼200 inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to compare the prediction accuracies of gene expression and genotypes for three complex traits. We found that expression levels (r
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Klaudia Jomová, Suliman Yousef Alomar, Richard Valko et al. · 2025 · Archives of Toxicology
Abstract Cellular systems responsible for the formation and removal of reactive oxygen species (ROS), functioning within physiological limits, are essential for maintaining intracellular redox balance. This state is known as oxidative eustress. Key redox signaling molecules, such as superoxide anion radical (O 2 •— ) and hydrogen peroxide (H 2 O 2 ), operate at nanomolar concentrations and are produced by NADPH oxidases (regulated by various factors), the mitochondrial electron transport chain (ETC), and numerous enzymes. In addition, cell signaling is influenced by nitric oxide (NO • ) and re
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Andreas Billich, Thomas Baumruker, Christian Beerli et al. · 2013 · PLoS ONE
BACKGROUND: Sphingosine-1-phosphate (S1P) regulates the egress of T cells from lymphoid organs; levels of S1P in the tissues are controlled by S1P lyase (Sgpl1). Hence, Sgpl1 offers a target to block T cell-dependent inflammatory processes. However, the involvement of Sgpl1 in models of disease has not been fully elucidated yet, since Sgpl1 KO mice have a short life-span. METHODOLOGY: We generated inducible Sgpl1 KO mice featuring partial reduction of Sgpl1 activity and analyzed them with respect to sphingolipid levels, T-cell distribution, and response in models of inflammation. PRINCIPAL FIN
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Linda M. Polfus, Jennifer A. Smith, Lawrence C. Shimmin et al. · 2013 · PLoS ONE
Many GWAS have identified novel loci associated with common diseases, but have focused only on main effects of individual genetic variants rather than interactions with environmental factors (GxE). Identification of GxE interactions is particularly important for coronary heart disease (CHD), a major preventable source of morbidity and mortality with strong non-genetic risk factors. Atherosclerosis is the major cause of CHD, and coronary artery calcification (CAC) is directly correlated with quantity of coronary atherosclerotic plaque. In the current study, we tested for genetic variants influe
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Aisling A. Geraghty, Alexandra Sexton‐Oates, Eileen C. O’Brien et al. · 2018 · Nutrients
The epigenetic profile of the developing fetus is sensitive to environmental influence. Maternal diet has been shown to influence DNA methylation patterns in offspring, but research in humans is limited. We investigated the impact of a low glycaemic index dietary intervention during pregnancy on offspring DNA methylation patterns using a genome-wide methylation approach. Sixty neonates were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet to prevent macrosomia) study: 30 neonates from the low glycaemic index intervention arm and 30 from the control, whose mothers re
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Youlu Chen, Yong Zeng, Xiaowei Zhu et al. · 2020 · Bioactive Materials
Compared with paclitaxel, sirolimus has been more used in the treatment of vascular restenosis gradually as an anti-proliferative drug, but few basic studies have elucidated its mechanism. The anti-proliferative effects of sirolimus or…
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Frederick F. Lang, Nam Tran, Vinay K. Puduvalli et al. · 2017 · Journal of Clinical Oncology
2002 Background: DNX-2401 is a replication-competent, tumor-selective, oncolytic adenovirus with enhanced infectivity that causes durable tumor control by killing tumor cells and eliciting antitumor immunity. To increase immune activation,…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Seung-Kwan Lim, Sang‐Oh Lee, Seong-Ho Choi et al. · 2011 · Journal of Korean Medical Science
Despite the identification of Acinetobacter baumannii isolates that demonstrate susceptibility to only colistin, this antimicrobial agent was not available in Korea until 2006. The present study examined the outcomes of patients with…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Sarah J. Higgins, Katharine He Xing, Hani Kim et al. · 2013 · Malaria Journal
BACKGROUND: Severe falciparum malaria (SM) pathogenesis has been attributed, in part, to deleterious systemic host inflammatory responses to infection. High mobility group box 1 (HMGB1) protein is an important mediator of inflammation implicated in sepsis pathophysiology. METHODS: Plasma levels of HMGB1 were quantified in a cohort of febrile Ugandan children with Plasmodium falciparum infection, enrolled in a prospective observational case-controlled study, using a commercial enzyme-linked immunosorbent assay. The utility of HMGB1 to distinguish severe malaria (SM; n = 70) from uncomplicated m
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