scholarly journals Studies overestimate the extent of circadian rhythm reprogramming in response to dietary and genetic changes

2020 ◽  
Author(s):  
Anne Pelikan ◽  
Hanspeter Herzel ◽  
Achim Kramer ◽  
Bharath Ananthasubramaniam
Keyword(s):  
R Package ◽  
Biological Data ◽  
Venn Diagram ◽  
Multiple Time ◽  
Genetic Changes ◽  
Physiological Processes ◽  
Multiple Time Points ◽  
Gain Loss ◽  
Diagram Analysis

AbstractThe circadian clock modulates key physiological processes in many organisms. This widespread role of circadian rhythms is typically characterized at the molecular level by profiling the transcriptome at multiple time points. Subsequent analysis identifies transcripts with altered rhythms between control and perturbed conditions, i.e., are differentially rhythmic (DiffR). Commonly, Venn Diagram analysis (VDA) compares lists of rhythmic transcripts to catalog transcripts with rhythms in both conditions or have gained or lost rhythms. However, unavoidable errors in the rhythmicity detection propagate to the final DiffR classification resulting in overestimated DiffR. We show using artificial experiments constructed from biological data that VDA indeed produces excessive false DiffR hits both in the presence and absence of true DiffR transcripts. We present a hypothesis testing and a model selection approaches in an R-package compareRhythms that instead compare circadian amplitude and phase of transcripts between the two conditions. These methods identify transcripts with ‘gain’, ‘loss’, ‘change’ or have the ‘same’ rhythms; the third category is missed by VDA. We reanalyzed three studies on the interplay between metabolism and the clock in the mouse liver that used VDA. We found not only fewer DiffR transcripts than originally reported, but VDA overlooked many relevant DiffR transcripts. Our analyses confirmed some and contradicted other conclusions in the original studies and also generated novel hypotheses. Our insights also generalize easily to studies using other -omics technologies. We trust that avoiding Venn Diagrams and using our R-package will contribute to improved reproducibility in chronobiology.

THE ROLE OF MEMORY PERSPECTIVE IN SOCIAL PHOBIA: IMMEDIATE AND DELAYED MEMORIES FOR ROLE-PLAYED SITUATIONS

2002 ◽  
Vol 30 (4) ◽  
pp. 415-425 ◽  
Author(s):  
Meredith E. Coles ◽  
Cynthia L. Turk ◽  
Richard G. Heimberg
Keyword(s):  
Social Phobia ◽  
Multiple Time ◽  
Behavioral Models ◽  
Social Situations ◽  
Time Points ◽  
Cognitive Behavioral Models ◽  
Multiple Time Points ◽  
Memory Perspective ◽  
Field Perspective

Cognitive-behavioral models (Clark & Wells, 1995; Rapee & Heimberg, 1997) and recent research suggest that individuals with social phobia (SP) experience both images (Hackmann, Surawy, & Clark, 1998) and memories (Coles, Turk, Heimberg, & Fresco, 2001; Wells, Clark, & Ahmad, 1998) of anxiety-producing social situations from an observer perspective. The current study examines memory perspective for two role-played situations (speech and social interaction) at multiple time points (immediate and 3 weeks post) in 22 individuals with generalized SP and 30 non-anxious controls (NACs). At both time points, SPs recalled the role-plays from a more observer/less field perspective than did NACs. Further, over time, the memory perspective of SPs became even more observer/less field while the memory perspective of NAC remained relatively stable.

scholarly journals Lung and Abdominal Biopsies in the Age of Precision Medicine

2019 ◽  
Vol 36 (03) ◽  
pp. 255-263 ◽  
Author(s):  
Leonard Dalag ◽  
Jonathan K. Fergus ◽  
Steven M. Zangan
Keyword(s):  
Precision Medicine ◽  
Recurrent Disease ◽  
State Of The Art ◽  
Diagnostic Yield ◽  
Multiple Time ◽  
New Paradigm ◽  
Tissue Acquisition ◽  
Multiple Time Points ◽  
Pathologic Analysis

AbstractImage-guided percutaneous needle biopsies (PNBs) are one of the most common procedures performed in radiology departments today. Rapid developments in precision medicine, which identifies molecular and genomic biomarkers in cancers, have ushered a new paradigm of oncologic workup and treatment. PNB has conventionally been used to establish a benign or malignant nature of a lesion during initial diagnosis or in suspected metastatic or recurrent disease. However, increasing amounts of tissue are being required to meet the demands of molecular pathologic analysis, which are now being sought at multiple time points during the course of the disease to guide targeted therapy. As primary providers of biopsy, radiologists must be proactive in these developments to improve diagnostic yield and tissue acquisition in PNB. Herein, we discuss the important and expanding role of PNB in the age of precision medicine and review the technical considerations of percutaneous lung and intra-abdominal biopsy. Finally, we examine promising state-of-the-art techniques in PNB that may safely increase tissue acquisition for optimal molecular pathologic analysis.

scholarly journals Simphony: simulating large-scale, rhythmic data

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6985 ◽  
Author(s):  
Jordan M. Singer ◽  
Darwin Y. Fu ◽  
Jacob J. Hughey
Keyword(s):  
Experimental Design ◽  
Large Scale ◽  
Method Development ◽  
Negative Binomial ◽  
Simulated Data ◽  
R Package ◽  
General Purpose ◽  
Computational Method ◽  
Multiple Time ◽  
Multiple Time Points

Simulated data are invaluable for assessing a computational method’s ability to distinguish signal from noise. Although many biological systems show rhythmicity, there is no general-purpose tool to simulate large-scale, rhythmic data. Here we present Simphony, an R package for simulating data from experiments in which the abundances of rhythmic and non-rhythmic features (e.g., genes) are measured at multiple time points in multiple conditions. Simphony has parameters for specifying experimental design and each feature’s rhythmic properties (e.g., amplitude and phase). In addition, Simphony can sample measurements from Gaussian and negative binomial distributions, the latter of which approximates read counts from RNA-seq data. We show an example of using Simphony to evaluate the accuracy of rhythm detection. Our results suggest that Simphony will aid experimental design and computational method development. Simphony is thoroughly documented and freely available at https://github.com/hugheylab/simphony.

scholarly journals MIR31 May Mediate Multiple Biology Processes To Promote Vocal Fold Wound Healing

2021 ◽  
Author(s):  
Haizhou Wang ◽  
Wen Xu
Keyword(s):  
Wound Healing ◽  
Network Analysis ◽  
Vocal Fold ◽  
Strong Association ◽  
Multiple Time ◽  
Collagen Production ◽  
Keratinocyte Proliferation ◽  
Multiple Time Points ◽  
The Relationship

Abstract The aim of this study was to explore the role of MIR31 in vocal fold wound healing (VFWH) and its possible mechanism. MIR31 expression was studied in rat vocal fold tissue at multiple time points (1, 4, and 8 weeks) after vocal fold injury. Co-expression analysis, pathway analysis, and literature-based network analysis were conducted to explore the possible mechanism underlying the relationship between MIR31 and VFWH. MIR31 expression was significantly elevated after vocal fold injury (p<5.65e-5), which also presented decreased expression in the late stage of VFWH process compared to the early and middle stages (p<5.40e-3). MIR31 also presented strong co-expression with 17 VFWH-significant genes (absolute value of ROH∈(0.63, 0.83)), which were mainly involved in collagen production. Literature-based network analysis showed that MIR31 could suppress two inhibitors (gene SMAD1 and HDAC2) of wound healing and activate one promoter (adenosine triphosphate). MIR31 could also mediate multiple biology processes that were associated with wound healing, including keratinocyte proliferation, collagen production, and inflammation. This study supports a strong association between MIR31 and the process of vocal fold wound healing, which may be related to collagen synthesis and other biological processes that need further study.

scholarly journals Overview on the Different Patterns of Tumor Vascularization

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 639
Author(s):  
Domenico Ribatti ◽  
Francesco Pezzella
Keyword(s):  
Vasculogenic Mimicry ◽  
Endothelial Cell Proliferation ◽  
Published Data ◽  
Alternative Mechanism ◽  
Tumor Vascularization ◽  
Angiogenic Therapy ◽  
Physiological Processes ◽  
Inhibition Of Angiogenesis ◽  
Therapeutic Development

Angiogenesis is a crucial event in the physiological processes of embryogenesis and wound healing. During malignant transformation, dysregulation of angiogenesis leads to the formation of a vascular network of tumor-associated capillaries promoting survival and proliferation of the tumor cells. Starting with the hypothesis formulated by Judah Folkman that tumor growth is angiogenesis-dependent, this area of research has a solid scientific foundation and inhibition of angiogenesis is a major area of therapeutic development for the treatment of cancer. Over this period numerous authors published data of vascularization of tumors, which attributed the cause of neo-vascularization to various factors including inflammation, release of angiogenic cytokines, vasodilatation, and increased tumor metabolism. More recently, it has been demonstrated that tumor vasculature is not necessarily derived by endothelial cell proliferation and sprouting of new capillaries, but alternative vascularization mechanisms have been described, namely vascular co-option and vasculogenic mimicry. In this article, we have analyzed the mechanisms involved in tumor vascularization in association with classical angiogenesis, including post-natal vasculogenesis, intussusceptive microvascular growth, vascular co-option, and vasculogenic mimicry. We have also discussed the role of these alternative mechanism in resistance to anti-angiogenic therapy and potential therapeutic approaches to overcome resistance.

scholarly journals Physical activity levels among ovarian cancer survivors: a prospective longitudinal cohort study

2021 ◽  
pp. ijgc-2020-002107
Author(s):  
Tamara Jones ◽  
Carolina Sandler ◽  
Dimitrios Vagenas ◽  
Monika Janda ◽  
Andreas Obermair ◽  
...  
Keyword(s):  
Physical Activity ◽  
Ovarian Cancer ◽  
Stage Iv ◽  
Multiple Time ◽  
Activity Levels ◽  
Prospective Longitudinal Study ◽  
Physical Activity Advice ◽  
Physical Activity Levels ◽  
Multiple Time Points ◽  
Prospective Longitudinal

ObjectivePhysical activity following cancer diagnosis is associated with improved outcomes, including potential survival benefits, yet physical activity levels among common cancer types tend to decrease following diagnosis and remain low. Physical activity levels following diagnosis of less common cancers, such as ovarian cancer, are less known. The objectives of this study were to describe physical activity levels and to explore characteristics associated with physical activity levels in women with ovarian cancer from pre-diagnosis to 2 years post-diagnosis.MethodsAs part of a prospective longitudinal study, physical activity levels of women with ovarian cancer were assessed at multiple time points between pre-diagnosis and 2 years post-diagnosis. Physical activity levels and change in physical activity were described using metabolic equivalent task hours and minutes per week, and categorically (sedentary, insufficiently, or sufficiently active). Generalized Estimating Equations were used to explore whether participant characteristics were related to physical activity levels.ResultsA total of 110 women with ovarian cancer with a median age of 62 years (range 33–88) at diagnosis were included. 53–57% of the women were sufficiently active post-diagnosis, although average physical activity levels for the cohort were below recommended levels throughout the 2-year follow-up period (120–142.5min/week). A decrease or no change in post-diagnosis physical activity was reported by 44–60% of women compared with pre-diagnosis physical activity levels. Women diagnosed with stage IV disease, those earning a lower income, those receiving chemotherapy, and those currently smoking or working were more likely to report lower physical activity levels and had increased odds of being insufficiently active or sedentary.ConclusionsInterventions providing patients with appropriate physical activity advice and support for behavior change could potentially improve physical activity levels and health outcomes.

scholarly journals Pannexins and Connexins: Their Relevance for Oocyte Developmental Competence

2021 ◽  
Vol 22 (11) ◽  
pp. 5918
Author(s):  
Paweł Kordowitzki ◽  
Gabriela Sokołowska ◽  
Marta Wasielak-Politowska ◽  
Agnieszka Skowronska ◽  
Mariusz T. Skowronski
Keyword(s):  
Assisted Reproductive Technologies ◽  
Mammalian Species ◽  
Atp Release ◽  
Reproductive Technologies ◽  
High Energy ◽  
Developmental Competence ◽  
Physiological Processes ◽  
Protein Group ◽  
Multicellular Organisms

The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways, which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possibly due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed and, at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.

scholarly journals The role of habitat configuration in shaping animal population processes: a framework to generate quantitative predictions

Oecologia ◽  
2021 ◽  
Author(s):  
Peng He ◽  
Pierre-Olivier Montiglio ◽  
Marius Somveille ◽  
Mauricio Cantor ◽  
Damien R. Farine
Keyword(s):  
Population Level ◽  
R Package ◽  
Habitat Configuration ◽  
Modelling Framework ◽  
Alternative Habitat ◽  
Animal Populations ◽  
Research Questions ◽  
Habitat Networks ◽  
Animal Habitat

AbstractBy shaping where individuals move, habitat configuration can fundamentally structure animal populations. Yet, we currently lack a framework for generating quantitative predictions about the role of habitat configuration in modulating population outcomes. To address this gap, we propose a modelling framework inspired by studies using networks to characterize habitat connectivity. We first define animal habitat networks, explain how they can integrate information about the different configurational features of animal habitats, and highlight the need for a bottom–up generative model that can depict realistic variations in habitat potential connectivity. Second, we describe a model for simulating animal habitat networks (available in the R package AnimalHabitatNetwork), and demonstrate its ability to generate alternative habitat configurations based on empirical data, which forms the basis for exploring the consequences of alternative habitat structures. Finally, we lay out three key research questions and demonstrate how our framework can address them. By simulating the spread of a pathogen within a population, we show how transmission properties can be impacted by both local potential connectivity and landscape-level characteristics of habitats. Our study highlights the importance of considering the underlying habitat configuration in studies linking social structure with population-level outcomes.

scholarly journals The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eileen M. Boyle ◽  
Shayu Deshpande ◽  
Ruslana Tytarenko ◽  
Cody Ashby ◽  
Yan Wang ◽  
...  
Keyword(s):  
Tumour Suppressor Genes ◽  
Multiple Time ◽  
Clonal Structure ◽  
Time To Progression ◽  
Novel Mutations ◽  
Evolutionary Patterns ◽  
Risk Of Progression ◽  
Multiple Time Points ◽  
Smoldering Myeloma ◽  
Copy Number Changes

AbstractSmoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5–8.1), p = 0.001). In an analysis of change in clonal structure over time we studied 53 samples from nine patients at multiple time points. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are key mechanisms underlying the transition to MM, which can precede progression and be used to guide early intervention strategies.

A zero-inflated non-negative matrix factorization for the deconvolution of mixed signals of biological data

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yixin Kong ◽  
Ariangela Kozik ◽  
Cindy H. Nakatsu ◽  
Yava L. Jones-Hall ◽  
Hyonho Chun
Keyword(s):  
Matrix Factorization ◽  
Factor Model ◽  
R Package ◽  
Biological Data ◽  
Superior Performance ◽  
Sequencing Data ◽  
Fecal Microbiome ◽  
Brain Gene Expression ◽  
Cell Transcriptome ◽  
Non Negative Matrix Factorization

Abstract A latent factor model for count data is popularly applied in deconvoluting mixed signals in biological data as exemplified by sequencing data for transcriptome or microbiome studies. Due to the availability of pure samples such as single-cell transcriptome data, the accuracy of the estimates could be much improved. However, the advantage quickly disappears in the presence of excessive zeros. To correctly account for this phenomenon in both mixed and pure samples, we propose a zero-inflated non-negative matrix factorization and derive an effective multiplicative parameter updating rule. In simulation studies, our method yielded the smallest bias. We applied our approach to brain gene expression as well as fecal microbiome datasets, illustrating the superior performance of the approach. Our method is implemented as a publicly available R-package, iNMF.

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