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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

Highly Sensitive In Vitro Methods for Detection of Residual Undifferentiated Cells in Retinal Pigment Epithelial Cells Derived from Human iPS Cells

Takuya Kuroda, Satoshi Yasuda, Shinji Kusakawa et al. · 2012 · PLoS ONE

Human induced pluripotent stem cells (hiPSCs) possess the capabilities of self-renewal and differentiation into multiple cell types, and they are free of the ethical problems associated with human embryonic stem cells (hESCs). These characteristics make hiPSCs a promising choice for future regenerative medicine research. There are significant obstacles, however, preventing the clinical use of hiPSCs. One of the most obvious safety issues is the presence of residual undifferentiated cells that have tumorigenic potential. To locate residual undifferentiated cells, in vivo teratoma formation assa

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue – a GC-TOFMS based metabolomics study

Jan Budczies, Carsten Denkert, Berit Müller et al. · 2012 · BMC Genomics

BACKGROUND: Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far. RESULTS: A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth

Alex Grier, Xing Qiu, Sanjukta Bandyopadhyay et al. · 2017 · Microbiome

BACKGROUND: Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. RESULTS: With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (ea

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Cholinergic Control over Attention in Rats Prone to Attribute Incentive Salience to Reward Cues

Giovanna Paolone, Christopher C. Angelakos, Paul Meyer et al. · 2013 · Journal of Neuroscience

Some rats [sign-trackers (STs)] are especially prone to attribute incentive salience to reward cues, relative to others [goal-trackers (GTs)]. Thus, reward cues are more likely to promote maladaptive reward-seeking behavior in STs than…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Emergent patterns of collective cell migration under tubular confinement

Wang Xi, Surabhi Sonam, Thuan Beng Saw et al. · 2017 · Nature Communications

Collective epithelial behaviors are essential for the development of lumens in organs. However, conventional assays of planar systems fail to replicate cell cohorts of tubular structures that advance in concerted ways on out-of-plane curved and confined surfaces, such as ductal elongation in vivo. Here, we mimic such coordinated tissue migration by forming lumens of epithelial cell sheets inside microtubes of 1-10 cell lengths in diameter. We show that these cell tubes reproduce the physiological apical-basal polarity, and have actin alignment, cell orientation, tissue organization, and migrat

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Direct Determination of the Mutation Rate in the Bumblebee Reveals Evidence for Weak Recombination-Associated Mutation and an Approximate Rate Constancy in Insects

Haoxuan Liu, Yanxiao Jia, Xiaoguang Sun et al. · 2016 · Molecular Biology and Evolution

Accurate knowledge of the mutation rate provides a base line for inferring expected rates of evolution, for testing evolutionary hypotheses and for estimation of key parameters. Advances in sequencing technology now permit direct estimates…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Assessment of statistical methods from single cell, bulk RNA-seq, and metagenomics applied to microbiome data

Matteo Calgaro, Chiara Romualdi, Levi Waldron et al. · 2020 · Genome biology

BACKGROUND: The correct identification of differentially abundant microbial taxa between experimental conditions is a methodological and computational challenge. Recent work has produced methods to deal with the high sparsity and compositionality characteristic of microbiome data, but independent benchmarks comparing these to alternatives developed for RNA-seq data analysis are lacking. RESULTS: We compare methods developed for single-cell and bulk RNA-seq, and specifically for microbiome data, in terms of suitability of distributional assumptions, ability to control false discoveries, concord

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Phylogenetic assessment of alignments reveals neglected tree signal in gaps

Christophe Dessimoz, Manuel Gil · 2010 · Genome biology

BACKGROUND: The alignment of biological sequences is of chief importance to most evolutionary and comparative genomics studies, yet the two main approaches used to assess alignment accuracy have flaws: reference alignments are derived from the biased sample of proteins with known structure, and simulated data lack realism. RESULTS: Here, we introduce tree-based tests of alignment accuracy, which not only use large and representative samples of real biological data, but also enable the evaluation of the effect of gap placement on phylogenetic inference. We show that (i) the current belief that

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Patient Simple Clinical Colitis Activity Index (P-SCCAI) can detect ulcerative colitis (UC) disease activity in remission: A comparison of the P-SCCAI with clinician-based SCCAI and biological markers

Floor Bennebroek Evertsz, Pythia T. Nieuwkerk, Pieter Stokkers et al. · 2012 · Journal of Crohn s and Colitis

AIM: To develop a patient-based Simple Clinical Colitis Activity Index (P-SCCAI) of ulcerative colitis (UC) activity and to compare it with the clinician-based SCCAI, C-reactive protein (CRP) and Physician's Global Assessment (PGA) of UC…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genes That Escape X-Inactivation in Humans Have High Intraspecific Variability in Expression, Are Associated with Mental Impairment but Are Not Slow Evolving

Yuchao Zhang, Atahualpa Castillo-Morales, Min Jiang et al. · 2013 · Molecular Biology and Evolution

In female mammals most X-linked genes are subject to X-inactivation. However, in humans some X-linked genes escape silencing, these escapees being candidates for the phenotypic aberrations seen in polyX karyotypes. These escape genes have…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Evolutionary Dynamics of Vibrio cholerae O1 following a Single-Source Introduction to Haiti

Lee S. Katz, Aaron Petkau, John Beaulaurier et al. · 2013 · mBio

UNLABELLED: Prior to the epidemic that emerged in Haiti in October of 2010, cholera had not been documented in this country. After its introduction, a strain of Vibrio cholerae O1 spread rapidly throughout Haiti, where it caused over 600,000 cases of disease and >7,500 deaths in the first two years of the epidemic. We applied whole-genome sequencing to a temporal series of V. cholerae isolates from Haiti to gain insight into the mode and tempo of evolution in this isolated population of V. cholerae O1. Phylogenetic and Bayesian analyses supported the hypothesis that all isolates in the sample

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Molecular Genetics and Economics

Jonathan Beauchamp, David Cesarini, Magnus Johannesson et al. · 2011 · The Journal of Economic Perspectives

The costs of comprehensively genotyping human subjects have fallen to the point where major funding bodies, even in the social sciences, are beginning to incorporate genetic and biological markers into major social surveys. How, if at all,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Comparative Genome-Wide Association Studies in Mice and Humans for Trimethylamine N -Oxide, a Proatherogenic Metabolite of Choline and l -Carnitine

Jaana Hartiala, Brian J. Bennett, W.H. Wilson Tang et al. · 2014 · Arteriosclerosis Thrombosis and Vascular Biology

OBJECTIVE: Elevated levels of plasma trimethylamine N-oxide (TMAO), the product of gut microbiome and hepatic-mediated metabolism of dietary choline and L-carnitine, have recently been identified as a novel risk factor for the development…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women

Stephen E. Alway, Jean L. McCrory, Kalen Kearcher et al. · 2017 · The Journals of Gerontology Series A

Older men (n = 12) and women (n = 18) 65-80 years of age completed 12 weeks of exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the hypothesis that RSV treatment combined with exercise would increase mitochondrial…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Histone Demethylase Jarid1b Ensures Faithful Mouse Development by Protecting Developmental Genes from Aberrant H3K4me3

Mareike Albert, Sandra U. Schmitz, Susanne M. Kooistra et al. · 2013 · PLoS Genetics

Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development, and increased incidences of exencephaly. Moreover, in line

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri

Thomas R. Connor, Clare R. Barker, Kate S. Baker et al. · 2015 · eLife

Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the

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Replication FailureOpen accessBiochemistry, Genetics and Molecular Biology

Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies

Cameron D. Palmer, Itsik Pe’er · 2017 · PLoS Genetics

Genome-wide association studies (GWAS) have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate repl

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods

Jill E. Moore, Henry Pratt, Michael Purcaro et al. · 2020 · Genome biology

BACKGROUND: Many genome-wide collections of candidate cis-regulatory elements (cCREs) have been defined using genomic and epigenomic data, but it remains a major challenge to connect these elements to their target genes. RESULTS: To facilitate the development of computational methods for predicting target genes, we develop a Benchmark of candidate Enhancer-Gene Interactions (BENGI) by integrating the recently developed Registry of cCREs with experimentally derived genomic interactions. We use BENGI to test several published computational methods for linking enhancers with genes, including sign

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Uncovering the Genetic History of the Present-Day Greenlandic Population

Ida Moltke, Matteo Fumagalli, Thorfinn Sand Korneliussen et al. · 2014 · The American Journal of Human Genetics

Because of past limitations in samples and genotyping technologies, important questions about the history of the present-day Greenlandic population remain unanswered. In an effort to answer these questions and in general investigate the genetic history of the Greenlandic population, we analyzed ∼200,000 SNPs from more than 10% of the adult Greenlandic population (n = 4,674). We found that recent gene flow from Europe has had a substantial impact on the population: more than 80% of the Greenlanders have some European ancestry (on average ∼25% of their genome). However, we also found that the am

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Failed Experiment ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Two-pore channel (TPC) interactome unmasks isoform-specific roles for TPCs in endolysosomal morphology and cell pigmentation

Yaping Lin-Moshier, Michael V. Keebler, Robert Hooper et al. · 2014 · Proceedings of the National Academy of Sciences

The two-pore channels (TPC1 and TPC2) belong to an ancient family of intracellular ion channels expressed in the endolysosomal system. Little is known about how regulatory inputs converge to modulate TPC activity, and proposed activation…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group

Roisín M. Connolly, Fengmin Zhao, Kathy D. Miller et al. · 2021 · Journal of Clinical Oncology

PURPOSE Endocrine therapy resistance in advanced breast cancer remains a significant clinical problem that may be overcome with the use of histone deacetylase inhibitors such as entinostat. The ENCORE301 phase II study reported improvement…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Scientific Opinion on the re‐evaluation of curcumin (E 100) as a food additive

EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) · 2010 · EFSA Journal

The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion re-evaluating the safety of curcumin (E 100). Curcumin has been previously evaluated by the Joint FAO/WHO Expert Committee on Food Additives…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

How to run far: multiple solutions and sex-specific responses to selective breeding for high voluntary activity levels

Theodore Garland, Scott A. Kelly, Jessica L. Malisch et al. · 2010 · Proceedings of the Royal Society B Biological Sciences

The response to uniform selection may occur in alternate ways that result in similar performance. We tested for multiple adaptive solutions during artificial selection for high voluntary wheel running in laboratory mice. At generation 43,…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Curcumin Treatment Suppresses IKKβ Kinase Activity of Salivary Cells of Patients with Head and Neck Cancer: A Pilot Study

Suejung G. Kim, Mysore S. Veena, Saroj K. Basak et al. · 2011 · Clinical Cancer Research

PURPOSE: To determine whether curcumin would inhibit IκB kinase β (IKKβ) kinase activity and suppress expression of proinflammatory cytokines in head and neck squamous cell carcinoma cancer (HNSCC) patients. EXPERIMENTAL DESIGN: Saliva was…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Cecropin A Alleviates Inflammation Through Modulating the Gut Microbiota of C57BL/6 Mice With DSS-Induced IBD

Zhenya Zhai, Fan Zhang, Ruihua Cao et al. · 2019 · Frontiers in Microbiology

The present study is undertaken to assess the alleviating effects of antimicrobial peptide cecropin A on inflammatory bowel disease (IBD) in C57BL/6 mice and changes in the gut microbiota, compared to an antibiotic gentamicin. Different doses of cecropin A were intraperitoneally injected into C57BL/6 mice for 5 days to determine the safe doses. The injection doses at ≤ 15 mg/kg showed no negative impact on the liver, heart, spleen and kidney. The severe and moderate IBD mice model was successfully established via supplementation of 4% or 2.5% dextran sulfate sodium (DSS) in drinking water for

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Warming Oceans, Phytoplankton, and River Discharge: Implications for Cholera Outbreaks

Antarpreet Jutla, A. S. Akanda, Jeffrey K. Griffiths et al. · 2011 · American Journal of Tropical Medicine and Hygiene

Phytoplankton abundance is inversely related to sea surface temperature (SST). However, a positive relationship is observed between SST and phytoplankton abundance in coastal waters of Bay of Bengal. This has led to an assertion that in a…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials

Linda Spiegelberg, Ruud Houben, Raymon Niemans et al. · 2019 · Clinical and Translational Radiation Oncology

Hypoxia-activated prodrugs (HAPs) are designed to specifically target the hypoxic cells of tumors, which are an important cause of treatment resistance to conventional therapies. Despite promising preclinical and clinical phase I and II…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Comparison of 2 Blood Culture Media Shows Significant Differences in Bacterial Recovery for Patients on Antimicrobial Therapy

Rebecca Zadroga, David N. Williams, Richard L. Gottschall et al. · 2012 · Clinical Infectious Diseases

BACKGROUND: Antimicrobial removal devices in blood culture media are designed to remove antibiotics from the blood culture solution, thereby facilitating bacterial growth. How well these devices function clinically has not been…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Rebecca J. Welly, Tzu‐Wen Liu, Terese M. Zidon et al. · 2016 · Medicine & Science in Sports & Exercise

UNLABELLED: Cardiometabolic impairments that begin early in life are particularly critical, because they often predict metabolic dysfunction in adulthood. Obesity, high-fat diet (HFD), and inactivity are all associated with adipose tissue…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01

Guillem Pascual‐Pasto, Miriam Bazán‐Peregrino, Nagore G. Olaciregui et al. · 2019 · Science Translational Medicine

VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity…

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