bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions
Authors: Reemst Kitty , Kracht Laura , Kotah Janssen M. , Rahimian Reza , van Irsen Astrid A.S. , Sotomayor Gonzalo Congains , Verboon Laura , Brouwer Nieske , Simard Sophie , Turecki Gustavo , Mechawar Naguib , Kooistra Susanne M. , Eggen Bart J. L. , Korosi Aniko 
Published: July 2022

AbstractEarly-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2 – 9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to CTRL microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.
Tra1 controls the transcriptional landscape of the aging cell
Authors: Bari Khaleda Afrin , Berg Matthew D. , Genereaux Julie , Brandl Christopher J. , Lajoie Patrick 
Published: July 2022

ABSTRACTGene expression undergoes considerable changes during the aging process. The mechanisms regulating the transcriptional response to cellular aging remain poorly understood. Here, we employ the budding yeast Saccharomyces cerevisiae to better understand how organisms adapt their transcriptome to promote longevity. Chronological lifespan (CLS) assays in yeast measure the survival of non-dividing cells at stationary phase over time, providing insights into the aging process of post-mitotic cells. Tra1 is an essential component of both the yeast SAGA/SLIK and NuA4 complexes, where it recruits these complexes to acetylate histones at targeted promoters. Importantly, Tra1 regulates the transcriptional response to multiple stresses. To evaluate the role of Tra1 in chronological aging, we took advantage of a previously characterized mutant allele that carries mutations in the TRA1 PI3K domain (tra1Q3). We found that loss of functions associated with tra1Q3 sensitized cells to growth media acidification and shortens lifespan. Transcriptional profiling reveals that genes differentially regulated by Tra1 during the aging process are enriched for components of the response to stress. Notably, expression of catalases (CTA1, CTT1) involved in hydrogen peroxide detoxification decreases in chronologically aged tra1Q3 cells. Consequently, they display increased sensitivity to oxidative stress. tra1Q3 cells are unable to grow on glycerol indicating a defect in mitochondria function. Aged tra1Q3 cells also display reduced expression of peroxisomal genes, exhibit decreased numbers of peroxisomes and cannot grow on media containing oleate. Thus, Tra1 emerges as an important regulator of longevity in yeast via multiple mechanisms.
A maximum-type microbial differential abundance test with application to high-dimensional microbiome data analyses
Authors: Li Zhengbang , Yu Xiaochen , Guo Hongping , Lee TingFang , Hu Jiyuan 
Published: July 2022

AbstractBackgroundHigh-throughput metagenomic sequencing technologies have shown prominent advantages over traditional pathogen detection methods, bringing great potential in clinical pathogen diagnosis and treatment of infection diseases. Yet, how to accurately detect the difference of microbiome profiles between treatment or disease conditions remains computationally challenging.ResultsIn this study, we propose a novel test for identifying the difference between two high-dimensional microbiome abundance data matrices based on the centred log-ratio transformation of the microbiome compositions. The test p-value can be calculated directly with a closed-form solution from the derived asymptotic null distribution. We also investigate the asymptotic statistical power against sparse alternatives which are typically encountered in microbiome studies. The proposedMaximum-type test isEqual-Covariance-Assumption-Free (MECAF), making it widely applicable to studies that compare microbiome compositions between conditions. Our simulation studies demonstrated that the proposed MECAF test achieves desirable power than competing methods while having the type I error rate well controlled under various scenarios. The usefulness of the proposed test is further illustrated with two real microbiome data analyses. The source code of the proposed method is freely available athttps://github.com/JiyuanHu.ConclusionsMECAF is a flexible differential abundance test and achieves statistical efficiency in analyzing high-throughput microbiome data. The proposed new method will allow us to efficiently discover shifts of microbiome abundances between disease and treatment conditions, broadening our understanding of the disease and ultimately improving clinical diagnosis and treatment.
R methylCIPHER: A Methylation Clock Investigational Package for Hypothesis-Driven Evaluation & Research
Authors: Thrush Kyra L. , Higgins-Chen Albert T. , Liu Zuyun , Levine Morgan E. 
Published: July 2022

AbstractBackgroundEpigenetic clocks are promising tools for the study of aging in humans. The clocks quantify biological aging above and beyond chronological age, demonstrate systematic associations with risk factors that accelerate aging, and predict age-related morbidity and mortality. There is interest in using them as surrogate endpoints in intervention studies. However, the large number of clocks, decentralized publication and explosive popularity in the last decade has made for poor accessibility and standardization. This has hampered the abilities of new researchers to conduct truly hypothesis driven research—whether by not knowing about the best available clocks for a given question, or by systematically testing many or all as they become available.ResultsWe report a centralized R package which can be installed and run locally on the user’s machine, and provides a standardized syntax for epigenetic clock calculation. The package includes a set of helper functions to assist with navigating clock literature and selecting clocks for analysis, as well as affording the user with the details of clock calculation. We describe each clock’s resilience to missing CpG information, combined with functionality to assess the need for imputation in the user’s own data. Furthermore, we demonstrate that while CpGs may not be shared among clocks with similar outputs, many clocks have highly correlated outputs.ConclusionsDue to the previous decentralization of epigenetic clocks, gathering code and performing systematic analysis, particularly in protected datasets, has required significant information gathering effort. Here, we offer an R package with standardized implementation and potential for future growth and clock incorporation to assist with hypothesis driven investigation of aging as measured by epigenetic clocks. We show the potential of this package to drive the user to think globally about signals captured by epigenetic clocks, as well as to properly identify the potential and limitations of each clock in their current research.
Teeth outside the mouth: the evolution and development of shark denticles
Authors: Cooper Rory L. , Nicklin Ella F. , Rasch Liam J. , Fraser Gareth J. 
Published: July 2022

AbstractVertebrate skin appendages are incredibly diverse. This diversity, which includes structures such as scales, feathers, and hair, likely evolved from a shared anatomical placode, suggesting broad conservation of the early development of these organs. Some of the earliest known skin appendages are dentine and enamel-rich tooth-like structures, collectively known as odontodes. These appendages evolved over 450 million years ago. Elasmobranchs (sharks, skates, and rays) have retained these ancient skin appendages in the form of both dermal denticles (scales) and oral teeth. Despite our knowledge of denticle function in adult sharks, our understanding of their development and morphogenesis is less advanced. Even though denticles in sharks appear structurally similar to oral teeth, there has been limited data directly comparing the molecular development of these distinct elements. Here, we chart the development of denticles in the embryonic small-spotted catshark (Scyliorhinus canicula) and characterise the expression of conserved genes known to mediate dental development. We find that shark denticle emergence shares a vast gene expression signature with developing teeth. However, denticles have restricted regenerative potential, as they lack asox2+stem cell niche associated with the maintenance of a dental lamina, an essential requirement for continuous tooth replacement. We compare developing denticles to other skin appendages, including both sensory skin appendages and avian feathers. This reveals that denticles are not only tooth-like in structure, but that they also share an ancient developmental gene set that is likely common to all epidermal appendages.
Discrete GPCR-triggered endocytic modes enable β-arrestins to flexibly regulate cell signaling
Authors: Barsi-Rhyne Benjamin , Manglik Aashish , von Zastrow Mark 
Published: July 2022

Abstractβ-arrestins are master regulators of cellular signaling that operate by desensitizing ligand-activated G protein-coupled receptors (GPCRs) at the plasma membrane and promoting their subsequent endocytosis. The endocytic activity of β-arrestins is ligand-dependent, triggered by GPCR binding, and increasingly recognized to have a multitude of downstream signaling and trafficking consequences that are specifically programmed by the bound GPCR. However, only one biochemical ‘mode’ for GPCR-mediated triggering of the endocytic activity is presently known– displacement of the β-arrestin C-terminus (CT) to expose CCP-binding determinants that are masked in the inactive state. Here we revise this view by uncovering a second mode of GPCR-triggered endocytic activity that is independent of the β-arrestin CT and, instead, requires the cytosolic base of the β-arrestin C-lobe (CLB). We further show each of the discrete endocytic modes is triggered in a receptor-specific manner, with GPCRs that bind β-arrestin transiently (‘class A’) primarily triggering the CLB-dependent mode and GPCRs that bind more stably (‘class B’) triggering both the CT and CLB-dependent modes in combination. Moreover, we show that each mode has opposing effects on the net signaling output of receptors– with the CLB-dependent mode promoting rapid signal desensitization and the CT-dependent mode enabling prolonged signaling. Together, these results fundamentally revise understanding of how β-arrestins operate as efficient endocytic adaptors while facilitating diversity and flexibility in the control of cell signaling.
Attitude of reproductive age women towards male involvement in family planning; a community-based cross-sectional study in Nakawa Division, Kampala, Uganda
Authors: Wambete Sarah Namee , Baru Ararso , Serwaa Dorcas , Dzantor Edem Kojo , Poku-Agyemang Evelyn , Kukeba Margaret Wekem , Olayemi Oladapo O. 
Published: July 2022

AbstractBackgroundIn African countries, men are often the primary decision-makers and that have a significant influence on their spouse’s health and access to health care including family planning (FP) decisions. This study aimed to assess the attitude of women in Nakawa Division, Kampala, Uganda towards male involvement in FP and the associated factors.MethodsThis was a community-based cross-sectional study carried out in Nakawa Division, Kampala, Uganda. A total of 480 women aged 18-49 years were selected as participants for the study using multi-stage sampling. A semi-structured interviewer-administered questionnaire was used to collect information from the participants. The data collected was analyzed using SPSS version 22. Data were described using frequency and percentage while associations were assessed using logistic regression analysis at P<0.05.ResultsA total of 485 participants with mean age of 28.29±6.57 years were involved in this study; 197(41.0%) were aged 26-33 years, 399 (83.1%) were Christians, 240(50.0%) had attained secondary school education and 239(49.8%) of their partners had attained tertiary education. The most utilized contraceptives among the women were injectables 151(32.5%), pills 122(26.2%), condoms 76(16.3%), implants 37(8%) and calendar method 30(6.5%). More, 302/465(62.9%) of the women had adequate partner involvement in their FP and a total of 438/480 (91.3%) of the participants had favorable attitude of women toward male involvement in FP. After adjusting for confounders, participants with an average monthly income of 600,000/= and above were more likely to have favorable attitude towards male involvement in FP (AOR=10.51, 95% CI {1.19−93.25}, p=0.035) compared with those earning 0-100,000/= average monthly income per month. Also, participants with adequate male partner involvement in FP/contraceptive use were more likely to have favorable attitude towards male involvement in FP (AOR=2.78, 95% CI {1.23−6.30, p<0.014)ConclusionThe study found high favourable attitude of women towards male partner involvement at FP. The average monthly income of participants and male involvement were predictors of favourable attitude towards male involvement in FP. This finding indicates the need for increased sensitization of the men as a means of attaining the broader objective of increasing male partner involvement in FP for better contraceptive use and better birth spacing.
Phosphotungstic acid (PTA) preferentially binds to collagen-rich regions of porcine carotid arteries and human atherosclerotic plaques using 3D micro-computed tomography (CE-μCT)
Authors: Hanly A. , Johnston R. D , Lemass C. , Jose A. , Tornifoglio B. , Lally C. 
Published: July 2022

AbstractBackground and aimsAtherosclerotic plaque rupture in the carotid artery can cause small emboli to travel to cerebral arteries, causing blockages and preventing blood flow leading to stroke. Contrast enhanced micro computed tomography (CEμCT) using a novel stain, phosphotungstic acid (PTA) can provide insights into the microstructure of the vessel wall and atherosclerotic plaque, and hence their likelihood to rupture. Furthermore, it has been suggested that collagen content and orientation can be related to mechanical integrity. This study aims to build on existing literature and establish a robust and reproducible staining and imaging technique to non-destructively quantify the collagen content within arteries and plaques as an alternative to routine histology.MethodsPorcine carotid arteries and human atherosclerotic plaques were stained with a concentration of 1% PTA staining solution and imaged using MicroCT to establish the in-situ architecture of the tissue and measure collagen content. A histological assessment of the collagen content was also performed from picrosirius red (PSR) staining.ResultsPTA stained arterial samples highlight the reproducibility of the PTA staining and MicroCT imaging technique used with a quantitative analysis showing a positive correlation between the collagen content measured from CEμCT and histology. Furthermore, collagen-rich areas can be clearly visualised in both the vessel wall and atherosclerotic plaque. 3D reconstruction was also performed showing that different layers of the vessel wall and various atherosclerotic plaque components can be differentiated using Hounsfield Unit (HU) values.ConclusionsThe work presented here is unique as it offers a quantitative method of segmenting the vessel wall into its individual components and non-destructively quantifying the collagen content withing these tissues, whilst also delivering a visual representation of the fibrous structure using a single contrast agent.Graphical Abstract
Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications
Authors: Yadav Shital , Tawade Pratik , Bachal Ketaki , Rakshe Makrand A. , Pundlik Yash , Gandhi Prasanna S. , Majumder Abhijit 
Published: July 2022

AbstractMicrofluidic concentration gradient generators are useful in drug testing. drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (μCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a Multiport Lifted Hele-Shaw Cell (MLHSC). Using the shaped ceramic structure as template, the microfluidic concentration gradient generator (μCGG) was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates were studied usingCOMSOL simulations. The simulation result was further validated by creating fluorescein dye (Fluorescein isothiocanate, FITC) gradient in the fabricated μCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug - curcumin - using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa to be 28.6 ± 6.1 μM which matched well with the conventional muti-well drug testing method (34.9 ± 1.7 μM). This method of μCGG fabrication has multiple advantages over conventional photolithography such as: i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilised to achieve broad range of concentration gradient to be used for various biological and non-biological applications.Table of Content
Universality of spatial livestock disease transmission patterns
Authors: Boender Gert Jan , Hagenaars Thomas J. 
Published: July 2022

AbstractThe risk of epidemic spread of diseases in livestock poses a threat to animal and often also human health. Important for the assessment of the effect of control measures is a statistical model quantification of between-farm transmission during epidemics. In particular, quantification of the between-farm transmission kernel has proven its importance for a range of different diseases in livestock. In this paper we explore if a comparison of the different transmission kernels yields further insight. Our comparison identifies universal features that connect across the different pathogen-host combinations and thereby provide generic insights.Comparison of the shape of the spatial transmission kernel suggests that, in absence of animal movement bans, the distance dependence of transmission has a universal shape analogous to Lévy-walk model descriptions of human movement patterns. Also, our analysis suggests that interventions such as movement bans and zoning, through their impact on these movement patterns, change the shape of the kernel in a universal fashion. We discuss how the generic insights obtained can be of practical use for assessing risks of spread and optimizing control measures, in particular when outbreak data is scarce.
Does forest heterogeneity affect mean throughfall for regenerating secondary forests on Borneo?
Authors: Keller Nadine , van Meerveld Ilja , Philipson Christopher David , Asner Gregory P. , Godoong Elia , Tangki Hamzah , Ghazoul Jaboury 
Published: July 2022

AbstractTropical landscape regeneration affects hydrological ecosystem functioning by regulating the amount of water that reaches the soil surface and changing soil infiltration rates. This affects the recharge and storage of water in the soil and streamflow responses. Therefore, it is important to assess how the fraction of rainfall that reaches the forest floor changes as secondary forests mature, and how forest structure affects throughfall via changes in storage capacity and evapotranspiration. Therefore, we monitored throughfall for twelve regenerating, logged-over forest plots in Sabah, Malaysian Borneo over a 7-month period and tested if inclusion of measures of forest heterogeneity improved the prediction of throughfall as a fraction of precipitation. On average across all plots, throughfall was 84% of precipitation, but was lower (as low as 74%) in plots with a longer recovery time since logging. There was a significant relationship between throughfall and tree density and basal area, as well as the Shannon Diversity Index and the coefficient of variation of the diameter at breast height, although species and structural diversity measures (Shannon Index and the coefficient of variation) did not improve model performance substantially. The overall best performing model was a linear regression with tree density. There was no relation between LiDAR-derived Top of Canopy (TCH) and mean throughfall, suggesting that this remotely sensed proxy of canopy height is not needed to estimate throughfall and more in-depth analysis of other LiDAR-products such as point clouds may be required. Our results imply that estimating throughfall in this forest type can be reliably achieved using tree density, and that this is not substantially affected by species diversity or structural heterogeneity variables, at least in the context of logged and regenerating forests in Sabah.Graphical abstractForest of a similar size or height can have a different structure. In this study we investigate if diversity also affects the amount of throughfall for plots across a disturbance gradient.