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Browse the failure-mode index

414 real negative results, null findings, and replication failures in Biochemistry, Genetics and Molecular Biology. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Targeted Reactivation of FMR1 Transcription in Fragile X Syndrome Embryonic Stem Cells

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Significant association between genes encoding virulence factors with antibiotic resistance and phylogenetic groups in community acquired uropathogenic Escherichia coli isolates

Zahra Yazdanpour, Omid Tadjrobehkar, Motahareh Shahkhah · 2020 · BMC Microbiology

BACKGROUND: Antibiotic resistance is an increasing phenomenon in many bacterial pathogens including uropathogenic Escherichia coli. Hypothetical anti-virulent agents could be a solution, but first clear virulence associated gene-pool of antibiotic resistant isolates have to be determined. The aim of this study is to investigate the significant associations between genes encoding VFs with antibiotic resistance and phylogenetic groups in UPEC isolates. RESULTS: The majority of 248 UPEC isolates belonged to phylogenetic group B2 (67.3%). The maximum and minimum resistance was attributed to amoxic

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction

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)

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Analysis of two language-related genes in autism

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Documentation of an Imperative To Improve Methods for Predicting Membrane Protein Stability

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Autologous Haematopoietic Stem Cell Transplantation for Crohn’s Disease: A Retrospective Survey of Long-term Outcomes From the European Society for Blood and Marrow Transplantation

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Potential distributions of Bacillus anthracis and Bacillus cereus biovar anthracis causing anthrax in Africa

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Comparison of the Conformations of KRAS Isoforms, K-Ras4A and K-Ras4B, Points to Similarities and Significant Differences

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,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma

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,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Umbrella and basket trials in oncology: ethical challenges

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Herpes Simplex Virus Requires Poly(ADP-Ribose) Polymerase Activity for Efficient Replication and Induces Extracellular Signal-Related Kinase-Dependent Phosphorylation and ICP0-Dependent Nuclear Localization of Tankyrase 1

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

No Significant Differences in Muscle Growth and Strength Development When Consuming Soy and Whey Protein Supplements Matched for Leucine Following a 12 Week Resistance Training Program in Men and Women: A Randomized Trial

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Gut-Brain Axis in Healthy Females: Lack of Significant Association between Microbial Composition and Diversity with Psychiatric Measures

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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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours

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)

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer’s disease GWAS and self-report proxy phenotype GWAX

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Prospective associations of plasma phospholipids and mild cognitive impairment/dementia among African Americans in the ARIC Neurocognitive Study

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…

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Replication FailureBiochemistry, Genetics and Molecular Biology

Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate‐Gene Studies

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos

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,

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Multibreed genomic prediction using multitrait genomic residual maximum likelihood and multitask Bayesian variable selection

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Leveraging Multiple Layers of Data To Predict Drosophila Complex Traits

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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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome-Wide Association Study of Gene by Smoking Interactions in Coronary Artery Calcification

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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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Partial Deficiency of Sphingosine-1-Phosphate Lyase Confers Protection in Experimental Autoimmune Encephalomyelitis

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Significant difference between sirolimus and paclitaxel nanoparticles in anti-proliferation effect in normoxia and hypoxia: The basis of better selection of atherosclerosis treatment

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Low Glycaemic Index Diet in Pregnancy Induces DNA Methylation Variation in Blood of Newborns: Results from the ROLO Randomised Controlled Trial

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

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Phase 1b open-label randomized study of the oncolytic adenovirus DNX-2401 administered with or without interferon gamma for recurrent glioblastoma.

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,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Outcomes of Using Colistin for Treating Multidrug Resistant Acinetobacter Species Bloodstream Infections

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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Performance of virtual screening against GPCR homology models: Impact of template selection and treatment of binding site plasticity

Mariama Jaiteh, Ismael Rodríguez‐Espigares, Jana Selent et al. · 2020 · PLoS Computational Biology

Rational drug design for G protein-coupled receptors (GPCRs) is limited by the small number of available atomic resolution structures. We assessed the use of homology modeling to predict the structures of two therapeutically relevant GPCRs and strategies to improve the performance of virtual screening against modeled binding sites. Homology models of the D2 dopamine (D2R) and serotonin 5-HT2A receptors (5-HT2AR) were generated based on crystal structures of 16 different GPCRs. Comparison of the homology models to D2R and 5-HT2AR crystal structures showed that accurate predictions could be obta

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with cancer recurrence and patient survival in patients with uterine cervical cancer

Shun‐Long Weng, Wenjun Wu, Yi‐Hsuan Hsiao et al. · 2018 · International Journal of Medical Sciences

Up to date, no study explores the relationship of single nucleotide polymorphisms (SNPs) of long non-coding RNAs HOTAIR (lncRNAs HOTAIR) with cancer recurrence and patient survival in uterine cervical cancer for Taiwanese women. We…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Systemic release of high mobility group box 1 (HMGB1) protein is associated with severe and fatal Plasmodium falciparum malaria

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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