Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Frank Dudbridge · 2013 · PLoS Genetics
Polygenic scores have recently been used to summarise genetic effects among an ensemble of markers that do not individually achieve significance in a large-scale association study. Markers are selected using an initial training sample and used to construct a score in an independent replication sample by forming the weighted sum of associated alleles within each subject. Association between a trait and this composite score implies that a genetic signal is present among the selected markers, and the score can then be used for prediction of individual trait values. This approach has been used to
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Armando E. Giuliano, Linda McCall, Peter D. Beitsch et al. · 2010 · Annals of Surgery
BACKGROUND AND OBJECTIVE: Sentinel lymph node dissection (SLND) has eliminated the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND for patients with tumor-involved SNs…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Philipp Stiefel, Sabrina Schmidt-Emrich, Katharina Maniura‐Weber et al. · 2015 · BMC Microbiology
BACKGROUND: Viability staining with SYTO9 and propidium iodide (PI) is a frequently used tool in microbiological studies. However, data generated by such routinely used method are often not critically evaluated for their accuracy. In this study we aim to investigate the critical aspects of this staining method using Staphylococcus aureus and Pseudomonas aeruginosa as the model microorganisms for high throughput studies in microtiter plates. SYTO9 or PI was added alone or consecutively together to cells and the fluorescence intensities were measured using microplate reader and confocal laser sc
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Fabrice André, Eva Ciruelos, Dejan Juric et al. · 2020 · Annals of Oncology
•In SOLAR-1, the key secondary endpoint of OS was evaluated in patients with HR+, HER2−, PIK3CA-mutated ABC.•Adding alpelisib to fulvestrant numerically improved mOS by 7.9 months, though the result was not statistically significant.•OS…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Thomas Klopstock, Patrick Yu‐Wai‐Man, Konstantinos Dimitriadis et al. · 2011 · Brain
Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Naihui Zhou, Yuxiang Jiang, Timothy Bergquist et al. · 2019 · Genome biology
BACKGROUND: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. RESULTS: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. S
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Kyohei Nishino, Atsushi Nishida, Ryo Inoüe et al. · 2017 · Journal of Gastroenterology
BACKGROUND: The mucosa-associated gut microbiota directly modulates epithelial and mucosal function. In this study, we investigated the mucosa-associated microbial community in patients with inflammatory bowel disease (IBD), using endoscopic brush samples. METHODS: A total of 174 mucus samples from 43 patients with ulcerative colitis (UC), 26 with Crohn's disease (CD) and 14 non-IBD controls were obtained by gentle brushing of mucosal surfaces using endoscopic cytology brushes. The gut microbiome was analyzed using 16S rRNA gene sequencing. RESULTS: There were no significant differences in mic
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Falk Hildebrand, Thi Loan Anh Nguyen, Brigitta M. N. Brinkman et al. · 2013 · Genome biology
BACKGROUND: Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing. RESULTS: We find initial evidence for richness-driven, strain-independent murine enterotypes that show a striking resemblance to those in human, and which associate with calp
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Tiantian Ren, Stan Boutin, Murray M. Humphries et al. · 2017 · Microbiome
BACKGROUND: Our understanding of gut microbiota has been limited primarily to findings from human and laboratory animals, but what shapes the gut microbiota in nature remains largely unknown. To fill this gap, we conducted a comprehensive study of gut microbiota of a well-studied North American red squirrel (Tamiasciurus hudsonicus) population. Red squirrels are territorial, solitary, and live in a highly seasonal environment and therefore represent a very attractive system to study factors that drive the temporal and spatial dynamics of gut microbiota. RESULT: For the first time, this study r
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
David E. Harrison, Randy Strong, David B. Allison et al. · 2013 · Aging Cell
Four agents--acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB)--were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P < 0.0001), but increased female median lifespan by only 5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P < 0.001) in males and 9% (P = 0.001) in females. EST increased male median lifespan by 12% (P = 0.002), but did not le
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
US Preventive Services Task Force, Douglas K Owens, Karina W. Davidson et al. · 2019 · JAMA
Importance: Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased risk for breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast…
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Michelle L. O’Donoghue, Eugene Braunwald, Harvey D. White et al. · 2014 · JAMA
IMPORTANCE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2 enzyme. OBJECTIVE: To…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Anna Müller, Michaela Wenzel, Henrik Strahl et al. · 2016 · Proceedings of the National Academy of Sciences
and different assays, including proteomics, ionomics, and fluorescence light microscopy. We found that daptomycin causes a gradual decrease in membrane potential but does not form discrete membrane pores. Although we found no evidence for…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Corinne F. Maurice, Sarah C. L. Knowles, Joshua Ladau et al. · 2015 · The ISME Journal
Recent studies have provided an unprecedented view of the microbial communities colonizing captive mice; yet the host and environmental factors that shape the rodent gut microbiota in their natural habitat remain largely unexplored. Here, we present results from a 2-year 16 S ribosomal RNA gene sequencing-based survey of wild wood mice (Apodemus sylvaticus) in two nearby woodlands. Similar to other mammals, wild mice were colonized by 10 bacterial phyla and dominated by the Firmicutes, Bacteroidetes and Proteobacteria. Within the Firmicutes, the Lactobacillus genus was most abundant. Putative
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
BI Ageing Clock Team, Thomas M. Stubbs, Marc Jan Bonder et al. · 2017 · Genome biology
BACKGROUND: DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. RESULTS: We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations w
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Alexandra C. Nica, Leopold Parts, Daniel Glass et al. · 2011 · PLoS Genetics
While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Dawn Waterworth, Sally L. Ricketts, Kijoung Song et al. · 2010 · Arteriosclerosis Thrombosis and Vascular Biology
OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Fang Fang Zhang, Roberto Cardarelli, Joan F. Carroll et al. · 2011 · Epigenetics
Reduced levels of global DNA methylation are associated with genomic instability and are independent predictors of cancer risk. Little is known about the environmental determinants of global DNA methylation in peripheral blood. We examined…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Charles E. Vejnar, Evgeny M. Zdobnov · 2012 · Nucleic Acids Research
MicroRNAs, or miRNAs, post-transcriptionally repress the expression of protein-coding genes. The human genome encodes over 1000 miRNA genes that collectively target the majority of messenger RNAs (mRNAs). Base pairing of the so-called miRNA 'seed' region with mRNAs identifies many thousands of putative targets. Evaluating the strength of the resulting mRNA repression remains challenging, but is essential for a biologically informative ranking of potential miRNA targets. To address these challenges, predictors may use thermodynamic, evolutionary, probabilistic or sequence-based features. We dev
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
James J. Goedert, Gieira S. Jones, Xing Hua et al. · 2015 · JNCI Journal of the National Cancer Institute
We investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients, pretreatment, vs 48 control patients. Microbiota profiles in fecal DNA were determined by Illumina sequencing and taxonomy of 16S rRNA genes. Estrogens were quantified in urine. Case-control comparisons employed linear and unconditional logistic regression of microbiota α-diversity (PD_whole tree) and UniFrac analysis of β-diversity, with two-sided statistical tests. Total estrogens correlated with α-diversity in control patients (Spearman Rho = 0.37, P = .009) but not case patients (Spearman
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Georgina Mansell, T.J. Gorrie-Stone, Yanchun Bao et al. · 2019 · BMC Genomics
There has been a steady increase in the number of studies aiming to identify DNA methylation differences associated with complex phenotypes. Many of the challenges of epigenetic epidemiology regarding study design and interpretation have been discussed in detail, however there are analytical concerns that are outstanding and require further exploration. In this study we seek to address three analytical issues. First, we quantify the multiple testing burden and propose a standard statistical significance threshold for identifying DNA methylation sites that are associated with an outcome. Second
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Peiming Zheng, Qin Luo, Weiwei Wang et al. · 2018 · Cell Death and Disease
Abstract Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment and have been shown to contribute to tumor aggressiveness. However, the detailed mechanisms underlying the pro-metastatic effect of TAMs on gastric cancer are not clearly defined. Here, we show that TAMs are enriched in gastric cancer. TAMs are characterized by M2-polarized phenotype and promote migration of gastric cancer cells in vitro and in vivo. Furthermore, we find that M2-derived exosomes determine the TAMs-mediated pro-migratory activity. Using mass spectrometry, we identify that apolipopro
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Jonathan A. Hern, Asma Baig, Gregory I. Mashanov et al. · 2010 · Proceedings of the National Academy of Sciences
G-protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins in the human genome. Events in the GPCR signaling cascade have been well characterized, but the receptor composition and its membrane…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Lasse Folkersen, Eric B. Fauman, Maria Sabater‐Lleal et al. · 2017 · PLoS Genetics
Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We id
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Velma T. E. Aho, Pedro A. B. Pereira, Sari Voutilainen et al. · 2019 · EBioMedicine
BACKGROUND: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
David Habier, Rohan L. Fernando, Dorian J. Garrick · 2013 · Genetics
Genomic best linear unbiased prediction (BLUP) is a statistical method that uses relationships between individuals calculated from single-nucleotide polymorphisms (SNPs) to capture relationships at quantitative trait loci (QTL). We show…
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Julianne L. Holloway, Anthony M. Lowman, Giuseppe R. Palmese · 2012 · Soft Matter
The biocompatibility, processing ease, and mechanical properties of freeze-thawed poly(vinyl alcohol) (PVA)-based hydrogels have encouraged significant research toward developing this material for various biomedical applications.…
View details →Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology
Stephen J. Nicholls, John J.P. Kastelein, Gregory G. Schwartz et al. · 2014 · JAMA
IMPORTANCE: Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Benjamin Haibe‐Kains, Christine Desmedt, Sherene Loi et al. · 2012 · JNCI Journal of the National Cancer Institute
BACKGROUND: Single sample predictors (SSPs) and Subtype classification models (SCMs) are gene expression-based classifiers used to identify the four primary molecular subtypes of breast cancer (basal-like, HER2-enriched, luminal A, and…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Amy R. Romijn, Julia J. Rucklidge, Roeline G. Kuijer et al. · 2017 · Australian & New Zealand Journal of Psychiatry
OBJECTIVES: This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory…
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