bluuebunny/crossref_metadata_2025_split huggingface dataset:
Walking with increased step length variability increases the metabolic cost of walking
Authors: Grimmitt Adam B. , Whelan Maeve E. , Martini Douglas N. , Hoogkamer Wouter 
Published: June 2024

AbstractOlder adults and neurological populations tend to walk with slower speeds, more gait variability, and a higher metabolic cost. This higher metabolic cost could be related to their increased gait variability, but this relationship is still unclear. The purpose of this study was to determine how increased step length variability affects the metabolic cost of waking. Eighteen healthy young adults completed a set of 5-minute trials of treadmill walking at 1.20 m/s while we manipulated their step length variability. Illuminated rectangles were projected onto the surface of a treadmill to cue step length variabilities of 0, 5 and 10% (coefficient of variation). Actual step lengths and their variability were tracked with reflective markers on the feet, while metabolic cost was measured using indirect calorimetry. Changes in metabolic cost across habitual walking (no projections) and the three variability conditions were analyzed using a linear mixed effects model. Metabolic power was largest in the 10% condition (4.30 ± 0.23 W/kg) compared to 0% (4.16 ± 0.18 W/kg) and habitual (3.98 ± 0.25 W/kg). The participant’s actual step length variability did not match projected conditions for 0% (3.10%) and 10% (7.03%). For every 1% increase in step length variability, there is an 0.7% increase in metabolic cost. Our results demonstrate an association between the metabolic cost of walking and gait step length variability. This suggests that increased gait variability contributes to a portion of the increased cost of walking seen in older adults and neurological populations.Summary StatementFor every 1% increase in step length variability, there is an 0.7% increase in the metabolic cost of walking.
Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model
Authors: Bernhardt Sarah M , Ozaki Michelle K , Betts Courtney , Bleyle Lisa A , DeBarber Andrea E , Fornetti Jaime , Liberty Abigail L , De Wilde Elise , Zhang Yi , Xia Zheng , Schedin Pepper 
Published: June 2024

AbstractYoung women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.Statement of SignificanceIn a rodent model of postpartum breast cancer, weaning suppresses hepatic CYP450 activity and renders vitamin D supplementation ineffective, with implications for xenobiotic drug efficacy and safety. A tailored approach to therapy based on reproductive history is crucial for young breast cancer patients, and for healthcare strategies for postpartum women.
Working memory performance predicts, but does not reduce, cocaine- and cannabinoid-seeking in adult male rats
Authors: Stringfield Sierra J. , Kirschmann Erin K. , Torregrossa Mary M. 
Published: June 2024

AbstractBackgroundCognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking.MethodsAdult male rats were trained to perform a ‘simple’ or ‘complex’ version of a delayed- match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug-seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression.ResultsTraining on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence.ConclusionsThese results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance prior to drug exposure may predict vulnerability to future drug use.
Pharmacodynamic modeling of colistin and imipenem againstin vitro Pseudomonas aeruginosabiofilms
Authors: Guo Yuchen , Yin Jinqiu , Aulin Linda B.S. , Ciofu Oana , Moser Claus , Upadhyay Parth J. , Høiby Niels , Wang Hengzhuang , Guo Tingjie , van Hasselt J. G. Coen 
Published: June 2024

ABSTRACTIntroductionAntibiotic treatment of chronic biofilm-associated infections can be challenging. Characterization of pharmacokinetic-pharmacodynamic (PK-PD) relationships for biofilm-associated infections may be relevant to inform the design of antibiotic treatment regimens for biofilm-associated infections. To this end, we aim to develop a mathematical PK-PD model for planktonic and biofilm bacterial infections and demonstrate how PK-PD simulations can be used to design optimized dosing schedules, using imipenem and colistin as proof-of-concept examples.MethodsPharmacodynamic models were developed using time-kill assay data from planktonic and alginate-bead biofilm cultures ofPseudomonas aeruginosaexposed to imipenem or colistin. The PD models were coupled to population PK models for plasma and epithelial lining fluid (ELF) to translate PD relationships for clinical dosing schedules and PK-PD indices.ResultsThe developed models incorporated sensitive and resistant bacterial subpopulations and were able to adequately capture the observed time-kill data. Simulation studies identified differences in suppression of bacterial growth dynamics for multiple clinical intravenous and inhalation-based treatment regimens and were used to infer biofilm-specific PK-PD indices associated with ELF target site concentrations.ConclusionIn conclusion, we demonstrate the utility of mathematical modeling for the characterization of PK-PD relationships underlying time-kill kinetic profiles in biofilm-associated infections and their utility in translating experimental findings to inform the optimization of clinical dosing schedules.
Caldas meets Janzen: Thermal regimes of montane plants and implications for global patterns of speciation
Authors: Sanchez Adriana , Quintero Ignacio , Pedraza Sara , Bonilla Diana , Lohmann Lúcia G. , Cadena Carlos Daniel , Zapata Felipe 
Published: June 2024

AbstractThe seasonality hypothesis posits that limited seasonal temperature variability in tropical mountains leads to greater climatic zonation along elevation gradients compared to temperate regions. This is predicted to result in narrow thermal tolerances and restricted dispersal for organisms, which may reduce gene flow and increase opportunities for climate-associated parapatric or allopatric speciation in tropical mountains relative to temperate-zone mountains. This hypothesis has been tested in various animal groups but not in plants. We examine the elevational and thermal ranges of pairs of sister species of angiosperms from mountains worldwide. Our findings indicate no significant difference in the breadth and overlap of elevational ranges between tropical and temperate species. However, tropical species have narrower thermal ranges and show greater similarity in these ranges between sister species compared to temperate ones. Such narrow thermal specialization in tropical plants facilitates population divergence and allopatric speciation within thermal zones more than in temperate species.
The curses of performing differential expression analysis using single-cell data
Authors: Wu Chih-Hsuan , Zhou Xiang , Chen Mengjie 
Published: June 2024

AbstractDifferential expression analysis is pivotal in single-cell transcriptomics for unraveling cell-type– specific responses to stimuli. While numerous methods are available to identify differentially expressed genes in single-cell data, recent evaluations of both single-cell–specific methods and methods adapted from bulk studies have revealed significant shortcomings in performance. In this paper, we dissect the four major challenges in single-cell DE analysis: normalization, excessive zeros, donor effects, and cumulative biases. These “curses” underscore the limitations and conceptual pitfalls in existing workflows. In response, we introduce a novel paradigm addressing several of these issues.
vClassifier: a toolkit for species-level classification of prokaryotic viruses
Authors: Zhou Kun , Kosmopoulos James C. , Anantharaman Karthik 
Published: June 2024

AbstractAs the most abundant and diverse biological entities, prokaryotic viruses play pivotal roles in ecological systems. Their taxonomic classification has been instrumental in elucidating their diversity and ecological functions. However, determination of viral taxonomy remains a considerable challenge. Recently developed approaches succeed in assignment of viral taxonomy at higher ranks, such as at the family level and above, but struggle at the subfamily level and below to the genus and species resolutions. Here, we describe the vClassifier toolkit, a phylogeny-informed methodology to provide species-level taxonomic assignments of viruses. We used single-copy marker genes relevant to specific taxa and reference phylogenetic trees for these groups which facilitates direct comparisons with the taxonomic framework of the International Committee on Taxonomy of Viruses (ICTV). Our method demonstrated significant congruence with the ICTV taxonomy, showing 84−91% alignment at the subfamily and genus levels. For species-level classification, our strategy was integrated with average nucleotide identity, yielding a high congruence rate of over 92% with the taxonomic data from the NCBI Virus database. Benchmarking comparisons revealed that vClassifier matches or surpasses other available tools regarding precision and classification success rates. By achieving objectivity and high levels of consistency, vClassifier streamlines the taxonomic categorization of prokaryotic viral genomes. Accurate assignments at the subfamily, genus, and species levels will significantly refine the taxonomic resolution of viruses, fostering a deeper understanding of viral diversity in microbiomes and ecosystems.
A Patient-Specific Morphoelastic Growth Model of Aortic Dissection Evolution
Authors: Khabaz Kameel , Kim Junsung , Milner Ross , Nguyen Nhung , Pocivavsek Luka 
Published: June 2024

AbstractThe human aorta undergoes complex morphologic changes that indicate the evolution of disease. Finite element analysis enables the prediction of aortic pathologic states, but the absence of a biomechanical understanding hinders the applicability of this computational tool. We incorporate geometric information from computed tomography angiography (CTA) imaging scans into finite element analysis (FEA) to predict a trajectory of future geometries for four aortic disease patients. Through defining a geometric correspondence between two patient scans separated in time, a patient-specific FEA model can recreate the deformation of the aorta between the two time points, showing pathologic growth drives morphologic heterogeneity. A shape-size geometric feature space plotting the variance of the shape index versus the inverse square root of aortic surface area (δ𝒮 vs.) quantitatively demonstrates the simulated breakdown in aortic shape. An increase in δ𝒮 closely parallels the true geometric progression of aortic disease patients.
Computational identification of surface markers for isolating distinct subpopulations from heterogeneous cancer cell populations
Authors: Gardner Andrea L. , Jost Tyler A. , Brock Amy 
Published: June 2024

AbstractIntratumor heterogeneity reduces treatment efficacy and complicates our understanding of tumor progression. There is a pressing need to understand the functions of heterogeneous tumor cell subpopulations within a tumor, yet biological systems to study these processesin vitroare limited. With the advent of single-cell RNA sequencing (scRNA-seq), it has become clear that some cancer cell line models include distinct subpopulations. Heterogeneous cell lines offer a unique opportunity to study the dynamics and evolution of genetically similar cancer cell subpopulations in controlled experimental settings. Here, we present clusterCleaver, a computational package that uses metrics of statistical distance to identify candidate surface markers maximally unique to transcriptomic subpopulations in scRNA-seq which may be used for FACS isolation. clusterCleaver was experimentally validated using the MDA-MB-231 and MDA-MB-436 breast cancer cell lines. ESAM and BST2/tetherin were experimentally confirmed as surface markers which identify and separate major transcriptomic subpopulations within MDA-MB-231 and MDA-MB-436 cells, respectively. clusterCleaver is a computationally efficient and experimentally validated workflow for identification and enrichment of distinct subpopulations within cell lines which paves the way for studies on the coexistence of cancer cell subpopulations in well-definedin vitrosystems.
RESPIRATION DEFECTS LIMIT SERINE SYNTHESIS REQUIRED FOR LUNG CANCER GROWTH AND SURVIVAL
Authors: Lopes Eduardo Cararo , Shi Fuqian , Sawant Akshada , Ibrahim Maria , Gomez-Jenkins Maria , Hu Zhixian , Manchiraju Pranav , Bhatt Vrushank , Wang Wenping , Hinrichs Christian S. , Wallace Douglas C. , Su Xiaoyang , Rabinowitz Joshua D. , Chan Chang S. , Guo Jessie Yanxiang , Ganesan Shridar , Lattime Edmund C. , White Eileen 
Published: June 2024

SUMMARYMitochondrial function is important for both energetic and anabolic metabolism. Pathogenic mitochondrial DNA (mtDNA) mutations directly impact these functions, resulting in the detrimental consequences seen in human mitochondrial diseases. The role of pathogenic mtDNA mutations in human cancers is less clear; while pathogenic mtDNA mutations are observed in some cancer types, they are almost absent in others. We report here that the proofreading mutant DNA polymerase gamma (PolGD256A) induced a high mtDNA mutation burden in non-small-cell lung cancer (NSCLC), and promoted the accumulation of defective mitochondria, which is responsible for decreased tumor cell proliferation and viability and increased cancer survival. In NSCLC cells, pathogenic mtDNA mutations increased glycolysis and caused dependence on glucose. The glucose dependency sustained mitochondrial energetics but at the cost of a decreased NAD+/NADH ratio that inhibitedde novoserine synthesis. Insufficient serine synthesis, in turn, impaired the downstream synthesis of GSH and nucleotides, leading to impaired tumor growth that increased cancer survival. Unlike tumors with intact mitochondrial function, NSCLC with pathogenic mtDNA mutations were sensitive to dietary serine and glycine deprivation. Thus, mitochondrial function in NSCLC is required specifically to sustain sufficient serine synthesis for nucleotide production and redox homeostasis to support tumor growth, explaining why these cancers preserve functional mtDNA.In briefHigh mtDNA mutation burden in non-small-cell lung cancer (NSCLC) leads to the accumulation of respiration-defective mitochondria and dependency on glucose and glycolytic metabolism. Defective respiratory metabolism causes a massive accumulation of cytosolic nicotinamide adenine dinucleotide + hydrogen (NADH), which impedes serine synthesis and, thereby, glutathione (GSH) and nucleotide synthesis, leading to impaired tumor growth and increased survival.HighlightsProofreading mutations in Polymerase gamma led to a high burden of mitochondrial DNA mutations, promoting the accumulation of mitochondria with respiratory defects in NSCLC.Defective respiration led to reduced proliferation and viability of NSCLC cells increasing survival to cancer.Defective respiration caused glucose dependency to fuel elevated glycolysis.Altered glucose metabolism is associated with high NADH that limits serine synthesis, leading to impaired GSH and nucleotide production.Mitochondrial respiration defects sensitize NSCLC to dietary serine/glycine starvation, further increasing survival.Abstract Figure
Efficient small fragment sequencing of human, cow, and bison miRNA, small RNA or csRNA-seq libraries using AVITI
Authors: McDonald Anna L. , Boddicker Andrew M. , Savenkova Marina I. , Brabb Ian M. , Qi Xiaodong , Moré Daniela D. , Cunha Cristina W. , Zhao Junhua , Duttke Sascha H. 
Published: June 2024

ABSTRACTNext-Generation Sequencing (NGS) catalyzed breakthroughs across various scientific domains. Illumina’s sequencing by synthesis method has long been essential for NGS but emerging technologies like Element Biosciences’ sequencing by avidity (AVITI) represent a novel approach. It has been reported that AVITI offers improved signal-to-noise ratios and cost reductions. However, the method relies on rolling circle amplification which can be impacted by polymer size, raising questions about its efficacy sequencing small RNAs (sRNA) molecules including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and others that are crucial regulators of gene expression and involved in various biological processes. In addition, capturing capped small RNAs (csRNA-seq) has emerged as a powerful method to map active or “nascent” RNA polymerase II transcription initiation in tissues and clinical samples. Here, we report a new protocol for seamlessly sequencing short DNA fragments on the AVITI and demonstrate that AVITI and Illumina sequencing technologies equivalently capture human, cattle (Bos taurus) and the bison (Bison bison) sRNA or csRNA sequencing libraries, augmenting the confidence in both approaches. Additionally, analysis of generated nascent transcription start sites (TSSs) data for cattle and bison revealed inaccuracies in their current genome annotations and highlighted the possibility and need to translate small RNA sequencing methodologies to livestock. Our accelerated and optimized protocol therefore bridges the advantages of AVITI sequencing and critical methods that rely on sequencing short DNA fragments.
Avian Atlas: Unveiling the Diversity Divide in Desert Realms between Tropics
Authors: Mukherjee Manasi , Mukerji Mitali 
Published: June 2024

AbstractUnderstanding diversity gradients across global deserts remains a significant challenge. The unique characteristics of deserts complicate conservation efforts for these biomes, which are highly affected by climate change. Here, we conduct a comprehensive study of ecological traits to determine the behavior and uniqueness of avian communities in ten major tropical deserts, using crowd-sourced avian diversity data fromGBIF.orgas a key analytical tool. Our results reveal significant variations in bird diversity among tropical deserts, with heightened diversity in deserts near the Tropic of Cancer (TCan) compared to those near the Tropic of Capricorn (TCap).The analysis of ecological traits indicates that, unlike TCap deserts, TCan deserts have a higher prevalence of migratory species. This is facilitated by a broader niche breadth among sedentary bird species, which reduces niche competition and allows the influx of migratory invertivores. This study is the first to identify a differential avian diversity gradient within tropical deserts, demonstrating that avian species richness in deserts is more closely linked to tropical locations than to realm classifications.Recognizing the vulnerability of TCap deserts and the diverse trophic roles played by avian species, our analysis underscores the need for targeted conservation strategies. Protecting the unique avian diversity in TCan deserts and mitigating extinction risks in TCap deserts are essential steps to ensure the resilience and sustainability of these critical ecosystems.
Brachiopod genome unveils the evolution of the BMP–Chordin network in bilaterian body patterning
Authors: Lewin Thomas D. , Shimizu Keisuke , Liao Isabel Jiah-Yih , Chen Mu-En , Endo Kazuyoshi , Satoh Noriyuki , Holland Peter W. H. , Wong Yue Him , Luo Yi-Jyun 
Published: June 2024

AbstractBone morphogenetic protein (BMP) signalling is crucial in regulating dorsal–ventral patterning and cell fate determination during early development in bilaterians. Interactions between BMP ligands and their main antagonist, Chordin, establish BMP gradients, subdivide embryos into distinct territories and organise body plans. However, the molecular control and evolutionary origins of dorsal–ventral patterning within spiralians, one of the three major bilaterian groups, have been obscured by their unique embryonic development. Here we present the chromosome-level genome of a spiralian with deuterostome-like development, the brachiopodLingula anatina, and apply functional transcriptomics to study dorsal–ventral patterning under the control of BMP signalling. We uncover the presence of a dorsal–ventral BMP signalling gradient in theL. anatinagastrula withbmp2/4andchordinexpressed at its dorsal and ventral sides, respectively. Using small-molecule drugs, exogenous recombinant BMP proteins and RNA sequencing, we show that a high level of BMP pathway activation inhibits the expression of neural genes during gastrula and larval stages. We also show that BMP signalling splits the developing larval shell field into two valves. The discovery of a BMP-mediated dorsal–ventral patterning system in a spiralian, similar to those observed in deuterostomes and non-spiralian protostomes, suggests deep conservation of this mechanism across all three major bilaterian clades. This is further supported by striking similarities in the gene sets regulated by BMP signalling in brachiopods and the vertebrate modelXenopus. We argue that the spiralian ancestor retained the basal bilaterian mechanism of dorsal–ventral patterning, although downstream components of the BMP–Chordin network have undergone dynamic evolutionary changes.