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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

Cell density and mobility protect swarming bacteria against antibiotics

Mitchell T. Butler, Qingfeng Wang, Rasika M. Harshey · 2010 · Proceedings of the National Academy of Sciences

Swarming bacteria move in multicellular groups and exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

DNA methylation profiles of human active and inactive X chromosomes

Andrew J. Sharp, Elisavet Stathaki, Eugenia Migliavacca et al. · 2011 · Genome Research

X-chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell. To characterize epigenetic changes that accompany this process, we measured DNA methylation…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome-Wide Association Study of Coronary Heart Disease and Its Risk Factors in 8,090 African Americans: The NHLBI CARe Project

Guillaume Lettre, Cameron D. Palmer, Taylor Young et al. · 2011 · PLoS Genetics

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage t

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Positively Charged Residues Are the Major Determinants of Ribosomal Velocity

Catherine A. Charneski, Laurence D. Hurst · 2013 · PLoS Biology

Both for understanding mechanisms of disease and for the design of transgenes, it is important to understand the determinants of ribosome velocity, as changes in the rate of translation are important for protein folding, error attenuation, and localization. While there is great variation in ribosomal occupancy along even a single transcript, what determines a ribosome's occupancy is unclear. We examine this issue using data from a ribosomal footprinting assay in yeast. While codon usage is classically considered a major determinant, we find no evidence for this. By contrast, we find that posit

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Purging of highly deleterious mutations through severe bottlenecks in Alpine ibex

Christine Grossen, Frédéric Guillaume, Lukas F. Keller et al. · 2020 · Nature Communications

Human activity has caused dramatic population declines in many wild species. The resulting bottlenecks have a profound impact on the genetic makeup of a species with unknown consequences for health. A key genetic factor for species survival is the evolution of deleterious mutation load, but how bottleneck strength and mutation load interact lacks empirical evidence. We analyze 60 complete genomes of six ibex species and the domestic goat. We show that historic bottlenecks rather than the current conservation status predict levels of genome-wide variation. By analyzing the exceptionally well-ch

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Exaggerated false positives by popular differential expression methods when analyzing human population samples

Yumei Li, Xinzhou Ge, Fanglue Peng et al. · 2022 · Genome biology

When identifying differentially expressed genes between two conditions using human population RNA-seq samples, we found a phenomenon by permutation analysis: two popular bioinformatics methods, DESeq2 and edgeR, have unexpectedly high false discovery rates. Expanding the analysis to limma-voom, NOISeq, dearseq, and Wilcoxon rank-sum test, we found that FDR control is often failed except for the Wilcoxon rank-sum test. Particularly, the actual FDRs of DESeq2 and edgeR sometimes exceed 20% when the target FDR is 5%. Based on these results, for population-level RNA-seq studies with large sample s

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Magnetic Resonance Imaging Response Monitoring of Breast Cancer During Neoadjuvant Chemotherapy: Relevance of Breast Cancer Subtype

Claudette E. Loo, Marieke E. Straver, Sjoerd Rodenhuis et al. · 2011 · Journal of Clinical Oncology

PURPOSE: To evaluate the relevance of breast cancer subtypes for magnetic resonance imaging (MRI) markers for monitoring of therapy response during neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: MRI examinations were performed in…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children

Gemma C. Sharp, Debbie A. Lawlor, Rebecca C. Richmond et al. · 2015 · International Journal of Epidemiology

BACKGROUND: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. METHODS: We used multivariable linear…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study

Christopher S. Carlson, Tara C. Matise, Kari E. North et al. · 2013 · PLoS Biology

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, ty

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Populations of a cyprinid fish are self-sustaining despite widespread feminization of males

Patrick B. Hamilton, Elizabeth Nicol, Eliane S. R. De-Bastos et al. · 2014 · BMC Biology

BACKGROUND: Treated effluents from wastewater treatment works can comprise a large proportion of the flow of rivers in the developed world. Exposure to these effluents, or the steroidal estrogens they contain, feminizes wild male fish and…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration

Manjit Mehat, Venki Sundaram, Caterina Ripamonti et al. · 2018 · Ophthalmology

PURPOSE: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. DESIGN: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). PARTICIPANTS: Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. M

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Social disadvantage, genetic sensitivity, and children’s telomere length

Colter Mitchell, John Hobcraft, Sara McLanahan et al. · 2014 · Proceedings of the National Academy of Sciences

Disadvantaged social environments are associated with adverse health outcomes. This has been attributed, in part, to chronic stress. Telomere length (TL) has been used as a biomarker of chronic stress: TL is shorter in adults in a variety…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

Feargal J. Ryan, Anna M. Ahern, Rachel S. Fitzgerald et al. · 2020 · Nature Communications

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epi

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Comparison of two cone beam computed tomographic systems versus panoramic imaging for localization of impacted maxillary canines and detection of root resorption

Ali Alqerban, Reinhilde Jacobs, Steffen Fieuws et al. · 2011 · European Journal of Orthodontics

The diagnostic accuracy for the localization of impacted canines and the detection of canine-induced root resorption of maxillary incisors were compared between conventional radiographic procedures using one two-dimensional (2D) panoramic…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma

Alba A. Brandes, Alain Carpentier, Santosh Kesari et al. · 2016 · Neuro-Oncology

BACKGROUND: The combination of galunisertib, a transforming growth factor (TGF)-β receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models of glioblastoma. METHODS: Galunisertib (300 mg/day) was…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome Wide Analyses Reveal Little Evidence for Adaptive Evolution in Many Plant Species

Toni I. Gossmann, Bao‐Hua Song, Aaron J. Windsor et al. · 2010 · Molecular Biology and Evolution

The relative contribution of advantageous and neutral mutations to the evolutionary process is a central problem in evolutionary biology. Current estimates suggest that whereas Drosophila, mice, and bacteria have undergone extensive…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Darwinian Dynamics of Intratumoral Heterogeneity: Not Solely Random Mutations but Also Variable Environmental Selection Forces

Mark C. Lloyd, Jessica J. Cunningham, Marilyn M. Bui et al. · 2016 · Cancer Research

Spatial heterogeneity in tumors is generally thought to result from branching clonal evolution driven by random mutations that accumulate during tumor development. However, this concept rests on the implicit assumption that cancer cells…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice

Jacob M. Allen, Margret E. Berg Miller, Brandt D. Pence et al. · 2015 · Journal of Applied Physiology

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Social Transfer of Pathogenic Fungus Promotes Active Immunisation in Ant Colonies

Matthias Konrad, Meghan L. Vyleta, Fabian J. Theis et al. · 2012 · PLoS Biology

Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors amon

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Identifying significant edges in graphical models of molecular networks

Marco Scutari, Radhakrishnan Nagarajan · 2013 · Artificial Intelligence in Medicine

OBJECTIVE: Modelling the associations from high-throughput experimental molecular data has provided unprecedented insights into biological pathways and signalling mechanisms. Graphical models and networks have especially proven to be useful abstractions in this regard. Ad hoc thresholds are often used in conjunction with structure learning algorithms to determine significant associations. The present study overcomes this limitation by proposing a statistically motivated approach for identifying significant associations in a network. METHODS AND MATERIALS: A new method that identifies significa

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Multiplex genome editing by natural transformation

Ankur B. Dalia, EmilyKate McDonough, Andrew Camilli · 2014 · Proceedings of the National Academy of Sciences

Editing bacterial genomes is an essential tool in research and synthetic biology applications. Here, we describe multiplex genome editing by natural transformation (MuGENT), a method for accelerated evolution based on the cotransformation…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Association between Cigarette Smoking Status and Composition of Gut Microbiota: Population-Based Cross-Sectional Study

Su Hwan Lee, Yeojun Yun, Soo Jung Kim et al. · 2018 · Journal of Clinical Medicine

There have been few large-scale studies on the relationship between smoking and gut microbiota. We investigated the relationship between smoking status and the composition of gut microbiota. This was a population-based cross-sectional study using Healthcare Screening Center cohort data. A total of 758 men were selected and divided into three groups: never (n = 288), former (n = 267), and current smokers (n = 203). Among the three groups, there was no difference in alpha diversity, however, Jaccard-based beta diversity showed significant difference (p = 0.015). Pairwise permutational multivaria

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF).

Peter N. Alexandrov, Prerna Dua, James M. Hill et al. · 2012 · PubMed

Human cerebrospinal fluid (CSF), produced by the choroid plexus and secreted into the brain ventricles and subarachnoid space, plays critical roles in intra-cerebral transport and the biophysical and immune protection of the brain. CSF…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

High Trans-ethnic Replicability of GWAS Results Implies Common Causal Variants

Urko M. Marigorta, Arcadi Navarro · 2013 · PLoS Genetics

Genome-wide association studies (GWAS) have detected many disease associations. However, the reported variants tend to explain small fractions of risk, and there are doubts about issues such as the portability of findings over different ethnic groups or the relative roles of rare versus common variants in the genetic architecture of complex disease. Studying the degree of sharing of disease-associated variants across populations can help in solving these issues. We present a comprehensive survey of GWAS replicability across 28 diseases. Most loci and SNPs discovered in Europeans for these cond

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Reconstructing the origin and spread of horse domestication in the Eurasian steppe

Vera Warmuth, Anders Eriksson, Mim A. Bower et al. · 2012 · Proceedings of the National Academy of Sciences

Despite decades of research across multiple disciplines, the early history of horse domestication remains poorly understood. On the basis of current evidence from archaeology, mitochondrial DNA, and Y-chromosomal sequencing, a number of…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus

A. Michael Lincoff, Jean‐Claude Tardif, Gregory G. Schwartz et al. · 2014 · JAMA

IMPORTANCE: No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator-activated receptors with insulin-sensitizing…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Limits of long-term selection against Neandertal introgression

Martin Petr, Svante Pääbo, Janet Kelso et al. · 2019 · Proceedings of the National Academy of Sciences

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-cover

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Molecular evolution of genes in avian genomes

Kiwoong Nam, Carina F. Mugal, Benoît Nabholz et al. · 2010 · Genome biology

BACKGROUND: Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologs of chicken, zebra finch, a lizard and three mammalian species. RESULTS: We found clear differences in the substitution rate at fourfold degenerate

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Prediction of Ubiquitination Sites by Using the Composition of k-Spaced Amino Acid Pairs

Zhen Chen, Yongzi Chen, Xiao Feng Wang et al. · 2011 · PLoS ONE

As one of the most important reversible protein post-translation modifications, ubiquitination has been reported to be involved in lots of biological processes and closely implicated with various diseases. To fully decipher the molecular mechanisms of ubiquitination-related biological processes, an initial but crucial step is the recognition of ubiquitylated substrates and the corresponding ubiquitination sites. Here, a new bioinformatics tool named CKSAAP_UbSite was developed to predict ubiquitination sites from protein sequences. With the assistance of Support Vector Machine (SVM), the highl

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