bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heuristics for the De Bruijn Graph Sequence Mapping Problem
Authors: Rocha Lucas B. , Adi Said Sadique , Araujo Eloi 
Published: February 2023

AbstractIn computational biology, mapping a sequencesonto a sequence graphGis a significant challenge. One possible approach to addressing this problem is to identify a walkpinGthat spells a sequence which is most similar tos. This problem is known as the Graph Sequence Mapping Problem (GSMP). In this paper, we study an alternative problem formulation, namely the De Bruijn Graph Sequence Mapping Problem (BSMP), which can be stated as follows: given a sequencesand a De Bruijn graphGk(wherek≥ 2), find a walkpinGkthat spells a sequence which is most similar tosaccording to a distance metric. We present both exact algorithms and approximate distance heuristics for solving this problem, using edit distance as a criterion for measuring similarity.
A high-resolution aerial camera survey of Uganda’s Queen Elizabeth Protected Area improves detection of wildlife and delivers a surprisingly high estimate of the elephant population
Authors: Lamprey Richard H , Keigwin Michael , Tumwesigye Charles 
Published: February 2023

ABSTRACTThe Queen Elizabeth Protected Area (QEPA) hosts some 60% of Uganda’s elephants and large populations of buffalo, hippopotamus and Uganda kob. However, the area is subjected to continued poaching, livestock incursions, animal disease and invasive plant species. Population estimates derived from aerial observers have shown great variability, and therefore trends are hard to discern. The Uganda Wildlife Authority (UWA) reguires precise wildlife population estimates to guide conservation actions. The aim of this study is to provide accurate and precise baseline estimates for wildlife populations of QEPA using aerial imagery and high sampling intensity, and to improve survey methods for determining future trends. High-resolution cameras, orientated at 45°, captured images along sample strips to left and right of the aircraft. Transects at 1 km separation gave a high sampling intensity of 28% to improve precision. We captured 43000 images for visual enumeration of 13 wildlife species. Population estimates (Ŷ), standard errors (SE) and relative margins of error (RME =95% c.l/Ŷ) were determined using ‘Jolly II’, Marriott and bootstrapping methods. With improved detection using imagery the QEPA elephant population is estimated at 4 711 ± 1106 (95% c. I), which is 62% higher than the previous observer-based estimate of 2900 in 2014, and the highest since counts began in the 1960s. The survey achieved an RME for elephants of 23%, making this one of the most precise counts for any similar-sized elephant area in Africa. The buffalo, Uganda kob and hippopotamus populations have stabilized at ‘safe’ levels but remain well below the high point of the mid-1990s; the high density of bone patches indicate high mortality, attributable to disease and to the continued invasion of the unpalatable grass speciesImperata cylindrica, which now covers 50% of the grassland area. Our methods indicate that methods and sample parameters prescribed by international elephant counting standards can be revised and improved using aerial cameras, especially for smaller survey areas.Short Summary TextUganda’s Queen Elizabeth Protected Area (QEPA) continues its recovery since the decimation of wildlife by militias in the 1970s, but it is challenging to track wildlife trends due to the variability in population estimates. To improve accuracy and precision, we conducted the first aerial count of QEPA using high-resolution imaging. This approach has indicated that the elephant population is at its highest levels since surveys began in the 1960s. Meanwhile, buffalo, topi and Uganda kob are stagnating below previous 1990s levels. We suggest the use of camera systems in future surveys to improve the accuracy and precision of counts, in order to guide effective management.
UPF3A is a ubiquitously expressed NMD factor among mouse tissues
Authors: Ma Xin , Li Yan , Chen Chengyan , Li Tangliang 
Published: February 2023

AbstractNonsense-mediated mRNA decay (NMD), an important post-transcriptional regulatory mechanism in gene expression, is actively involved in a series of cellular and physiological processes, thus controlling cell fate and tissue homeostasis. Defects in NMD cause human diseases such as neurodevelopmental disorders, tumorigenesis and autoimmunity. UPF3 (Up- frameshift protein 3), first identified in the baker’s yeast, is a core NMD factor. UPF3A and UPF3B, the two UPF3 paralogs emerging in vertebrates, have either activating or suppressing roles in NMD. Previous studies found that UPF3B protein is ubiquitously expressed in almost all mammalian organs, while UPF3A protein is hardly detectable in most of mammalian tissues, except in the testis. One hypothesis explaining this phenomena is the functional antognism between UPF3A and UPF3B in NMD. Thus, UPF3B competitively binds to UPF2 with higher affinity than UPF3A, which finally destabilizes UPF3A protein. In the present study, we quantitatively evaluated the expression of UPF3A and UPF3B in nine major tissues and reproductive organs of wild type male and female mice. Our study confirmed that UPF3A has the highest expression in male germlines. To our surprise, we found in most tissues, including brain and thymus, the protein level of UPF3A is comparable with that of UPF3B. In spleen and lung, UPF3A is higher than UPF3B. These findings are further supported by publicly available gene expression data. Thus, our study demonstrated that UPF3A protein is ubiquitously expressed in mouse tissues, and may play important roles in the homeostasis of multiple mammalian tissues.
Microxanox: an R package for simulating an aquaticMICRobial ecosystem that can occupyOXic orANOXic states
Authors: Krug Rainer M , Petchey Owen L. 
Published: February 2023

AbstractMicroxanoxis an R package to simulate a three functional group ecosystem (cyanobacteria, phototrophic sulfur bacteria, and sulfate-reducing bacteria) with four chemical substrates (phosphorus, oxygen, reduced sulfur, and oxidized sulfur) using a set of ordinary differential equations. Simulations can be run individually or over a parameter range, to find stable states. The model can be implemented with different numbers of species per functional group. The package is constructed in such a way that the results contain the input parameter used, so that a saved results can be loaded again and the simulation be repeated. Furthermore, the package framework and code should serve as a useful starting point for making simulation models of other types of ecosystem.
Coupling of Nuclear Translocation to Cell Size Promotes Robustness to Fluctuations in YAP/TAZ Concentration
Authors: Jones Ian , Arias-Garcia Mar , Pascual-Vargas Patricia , Beykou Melina , Dent Lucas , Chaudhuri Tara Pal , Roumeliotis Theodoros , Choudhary Jyoti , Sero Julia , Bakal Chris 
Published: February 2023

The concentration of many transcription factors exhibit high cell-to-cell variability due to differences in synthesis, degradation, and cell size. How these factors are robust to fluctuations in concentration is poorly understood. Here we quantified the single cell levels of the YAP/TAZ transcriptional co-activators in parallel with cell morphology for over 400,000 single cells across 17 cell lines. We show the whole cell concentration of YAP/TAZ sub-scales with respect to size as cells grow during proliferation. However, the mean nuclear concentration of YAP/TAZ remains constant during the cell cycle. Theoretical modelling demonstrates that the extent to which whole cell YAP/TAZ dilutes in single cells during proliferative growth dictates the variability of YAP/TAZ levels across the population. Integrative analysis of imaging and proteomic data show the average nuclear YAP/TAZ concentration is predicted by differences in RAS/MAPK signalling, focal adhesion maturation, and nuclear transport processes. We developed a statistical framework capable of discriminating between perturbations that affect YAP/TAZ directly, or via changes in morphology. Deployment of these models on genetic screening data or small-molecule treatments reveal that inhibition of MEK, CDK4/6, LATS and RhoGTPases decouple nuclear YAP/TAZ from cell morphology by regulating nuclear translocation. Thus signalling activity couples size changes to YAP/TAZ translocation; leading to a stable pool of nuclear YAP/TAZ during proliferation.Significance StatementMany proteins dilute/concentrate with changes in cell size. It is unclear how robustness in cell signalling emerges across differently sized cells, with varying intracellular protein concentrations, over generations. Here, we have shown that despite whole cell dilution of the transcriptional co activators YAP/TAZ with increasing size, a steady-state nuclear concentration distribution is maintained across the population. Thus nuclear transport promotes robustness of signal response in the face of a dwindling cytoplasmic YAP/TAZ levels. An integrative approach revealed that focal adhesions, RAS/MAPK and nuclear import contributes to the the maintenance of YAP/TAZ nuclear levels. Cells appear to have evolved systems to ensure robustness against alterations to cell size during the cell cycle.
Skeletal morphology of bird wings is determined by thermoregulatory demand for heat dissipation in warmer climates
Authors: Weeks Brian C. , Harvey Christina , Tobias Joseph A. , Sheard Catherine , Zhou Zhizhuo , Fouhey David F. 
Published: February 2023

AbstractThe tendency for animals in warmer climates to be longer-limbed (Allen’s Rule) is widely attributed to the demands of thermoregulation. However, the underlying mechanism remains unclear, because variation in limb-length can typically be driven by selection for both efficient heat retention and increased heat dissipation capacity. Using comparative phylogenetic models, we find that occurrence in warmer climates is associated with longer wing bones for 1,520 species of passerine birds. The highly vascularized musculature along these bones is only uncovered during flight, when the wings function as the primary site of heat exchange, cooling the organism by dissipating excess heat generated by muscular activity. Conversely, the musculature along the wing bones is insulated by feathering when at rest, playing a negligible role in heat retention, even in colder climates. Given this asymmetry in thermoregulatory roles, we can identify the positive relationship between temperature and wing bone length as a phenotypic gradient shaped by increased demand for heat dissipation in warmer climates. Our findings provide a clear illustration of the mechanism by which global warming can drive spatial and temporal trends in appendage length, and also highlight the role of heat dissipation in reshaping even the most critical features of vertebrate anatomy.Significance StatementAnimals tend to be longer-limbed in warmer climates, but it remains unclear whether this pattern is driven by selection for cold tolerance at low temperatures or efficient heat dissipation at high temperatures. We show that for 1,520 species of passerines, bird wing bones are relatively longer in warmer climates. The vascularized musculature along these bones primarily functions in heat exchange during flight, when the overwhelming thermoregulatory challenge is dissipating heat, suggesting longer wing-bone length is driven by heat dissipation demands. Our findings reveal the pervasive impacts of thermoregulatory demands on even the most important functional traits.
Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging
Authors: Yeh Chung-Yang , Chini Lucas C.S. , Davidson Jessica W. , Garcia Gonzalo G. , Gallagher Meredith S. , Freichels Isaac T. , Calubag Mariah F. , Rodgers Allison C. , Green Cara L. , Babygirija Reji , Sonsalla Michelle M. , Pak Heidi H. , Trautman Michaela , Hacker Timothy A. , Miller Richard A , Simcox Judith , Lamming Dudley W. 
Published: February 2023

AbstractIn defiance of the paradigm that calories from all sources are equivalent, we and others have shown that dietary protein is a dominant regulator of healthy aging. The restriction of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan when initiated in young or adult mice. However, many interventions are less efficacious or even deleterious when initiated in aged animals. Here, we investigate the physiological, metabolic, and molecular consequences of consuming a diet with a 67% reduction of all amino acids (Low AA), or of isoleucine alone (Low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. We find that both diet regimens effectively reduce adiposity and improve glucose tolerance, which were benefits that were not mediated by reduced calorie intake. Both diets improve specific aspects of frailty, slow multiple molecular indicators of aging rate, and rejuvenate the aging heart and liver at the molecular level. These results demonstrate that Low AA and Low Ile diets can drive youthful physiological and molecular signatures, and support the possibility that these dietary interventions could help to promote healthy aging in older adults.
Clustering-independent estimation of cell abundances in bulk tissues using single-cell RNA-seq data
Authors: Aubin Rachael G. , Montelongo Javier , Hu Robert , Gunther Elijah , Nicodemus Patrick , Camara Pablo G. 
Published: February 2023

SummarySingle-cell RNA-sequencing has transformed the study of biological tissues by enabling transcriptomic characterizations of their constituent cell states. Computational methods for gene expression deconvolution use this information to infer the cell composition of related tissues profiled at the bulk level. However, current deconvolution methods are restricted to discrete cell types and have limited power to make inferences about continuous cellular processes like cell differentiation or immune cell activation. We present ConDecon, a clustering-independent method for inferring the likelihood for each cell in a single-cell dataset to be present in a bulk tissue. ConDecon represents an improvement in phenotypic resolution and functionality with respect to regression-based methods. Using ConDecon, we discover the implication of neurodegenerative microglia inflammatory pathways in the mesenchymal transformation of pediatric ependymoma and characterize their spatial trajectories of activation. The generality of this approach enables the deconvolution of other data modalities such as bulk ATAC-seq data.
Nucleus Accumbens Local Circuit for Cue-Dependent Aversive Learning
Authors: Belilos Andrew , Gray Cortez , Sanders Christie , Black Destiny , Mays Elizabeth , Richie Christopher , Sengupta Ayesha , Hake Holly , Francis T. Chase 
Published: February 2023

SummaryResponse to threatening environmental stimuli requires detection and encoding of important environmental features that dictate threat. Aversive events are highly salient which promotes associative learning about stimuli that signal this threat. The nucleus accumbens is uniquely positioned to process this salient, aversive information and promote motivated output, through plasticity on the major projection neurons in the brain area. We uncovered a nucleus accumbens core local circuit whereby excitatory plasticity facilitates learning and recall of discrete aversive cues. We demonstrate that putative nucleus accumbens substance P release and long-term excitatory plasticity on dopamine 2 receptor expressing projection neurons is required for cue-dependent fear learning. Additionally, we found fear learning and recall were dependent on distinct projection-neuron subtypes. Our work demonstrates a critical role for Nucleus Accumbens substance P in cue-dependent aversive learning.
Spontaneous onset of cellular markers of inflammation and genome instability during aging in the immune niche of the naturally short-lived turquoise killifish (Nothobranchius furzeri)
Authors: Morabito Gabriele , Dönertas Handan Melike , Sperti Luca , Seidel Jens , Poursadegh Aysan , Poeschla Michael , Valenzano Dario Riccardo 
Published: February 2023

AbstractTurquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates, recapitulating several aspects of human aging, including protein aggregation, telomere shortening, cellular senescence, and declined antibody diversity. The mechanistic causes of systemic aging in killifish are still poorly understood. Here we ask whether killifish undergo significant age-dependent changes in the main hematopoietic organ, which together could contribute to systemic aging. To characterize immune aging in killifish, we employed single-cell RNA sequencing, proteomics, cytometry and a functional in vitro assay. Our data indicate how old killifish display increased inflammatory markers, and while immune cells from adult killifish display increased markers of proliferation and replication-independent DNA repair in progenitor-like cell clusters, progenitors from old killifish display extensive markers of DNA double-strand breaks. In less than 10 weeks, killifish undergo several dramatic spontaneous aging-related changes in the immune niche, which could be functionally linked with its extensive systemic aging and serve as targets for anti-aging interventions.
Watching ion-driven kinetics of ribozyme folding and misfolding caused by energetic and topological frustration one molecule at a time
Authors: Hori Naoto , Thirumalai D. 
Published: February 2023

AbstractFolding of ribozymes into well-defined tertiary structures usually requires divalent cations. How Mg2+ions direct the folding kinetics has been a long-standing unsolved problem because experiments cannot detect the positions and dynamics of ions. To address this problem, we used molecular simulations to dissect the folding kinetics of theAzoarcusribozyme by monitoring the path each molecule takes to reach the folded state. We quantitatively establish that Mg2+binding to specific sites, coupled with counter-ion release of monovalent cations, stimulate the formation of secondary and tertiary structures, leading to diverse pathways that include direct rapid folding and trapping in misfolded structures. In some molecules, key tertiary structural elements form when Mg2+ions bind to specific RNA sites at the earliest stages of the folding, leading to specific collapse and rapid folding. In others, the formation of non-native base pairs, whose rearrangement is needed to reach the folded state, is the rate-limiting step. Escape from energetic traps, driven by thermal fluctuations, occurs readily. In contrast, the transition to the native state from long-lived topologically trapped native-like metastable states is extremely slow. Specific collapse and formation of energetically or topologically frustrated states occur early in the assembly process.Graphical abstract
The synergetic effect from the combination of different adsorption resins in batch and semi-continuous cultivations ofS. cerevisiaecell factories to produce acetylated Taxanes precursors of the anticancer drug Taxol
Authors: Santoyo-Garcia Jorge H. , Walls Laura E. , Valdivia-Cabrera Marissa , Malci Koray , Jonguitud-Borrego Nestor , Halliday Karen J. , Rios-Solis Leonardo 
Published: February 2023

AbstractIn situproduct recovery is an efficient way to intensify bioprocesses as it can perform adsorption of the desired natural products in the cultivation. However, it is common to use only one adsorbent (liquid or solid) to perform the product recovery. For this study, the use of anin situproduct recovery method with three combined commercial resins (HP-20, XAD7HP and HP-2MG) with different chemical properties was performed. A new yeast strain ofSaccharomyces cerevisiaewas engineered using CRISPR Cas9 (strainEJ2) to deliver heterologous expression of oxygenated acetylated taxanes that are precursors of the anticancer drug Taxol ® (paclitaxel). Microscale cultivations using a definitive screening design (DSD) were set to get the best resin combinations and concentrations to retrieve high taxane titers. Once the best resin treatment was selected by the DSD, semi-continuous cultivation in high throughput microscale was performed to increase the total taxanes yield up to 783 ± 33 mg/L. The best T5α-yl Acetate yield obtained was up to 95 ± 4 mg/L, the highest titer of this compound ever reported by a heterologous expression. It was also observed that by using a combination of the resins in the cultivation, 8 additional uncharacterized taxanes were found in the gas chromatograms compared to the dodecane overlay method. Lastly, the cell-waste reactive oxygen species concentrations from the yeast were 1.5-fold lower in the resin’s treatment compared to the control with no adsorbent aid. The possible future implications of this method could be critical for bioprocess intensification, allowing the transition to a semi-continuous flow bioprocess. Further, this new methodology broadens the use of different organisms for natural product synthesis/discovery benefiting from clear bioprocess intensification advantages.
Liver-specific LXR inhibition represses reverse cholesterol transport in cholesterol-fed mice
Authors: Nishida Takafumi , Ayaori Makoto , Arakawa Junko , Suenaga Yumiko , Shiotani Kazusa , Uto-Kondo Harumi , Komatsu Tomohiro , Nakaya Kazuhiro , Endo Yasuhiro , Sasaki Makoto , Ikewaki Katsunori 
Published: February 2023

AbstractObjectiveHigh density lipoprotein (HDL) exerts an anti-atherosclerotic effect via reverse cholesterol transport (RCT). Several phases of RCT are transcriptionally controlled by Liver X receptors (LXRs). Although macrophage LXRs reportedly promote RCT, it is still uncertain whether hepatic LXRs affect RCTin vivo.Approach and ResultsTo address this question, we induced hepatic overexpression of sulfotransferase family cytosolic 2B member 1 (Sult2b1) in mice. Sult2b1 facilitates generation of sulfated cholesterol, resulting in reduced production of LXR ligands (oxysterols), which impairs LXR signaling. Adenoviral vectors expressing Sult2b1 (Ad-Sult2b1) or luciferase were intravenously injected into mice under a normal or high-cholesterol diet. Hepatic Sult2b1 overexpression resulted in reduced expression of LXR-target genes - ATP-binding cassette transporter G5/G8, cholesterol 7α hydroxylase and LXRα itself - respectively reducing or increasing cholesterol levels in HDL and apolipoprotein B–containing lipoproteins (apoB-L). A macrophage RCT assay revealed that Sult2b1 overexpression inhibited fecal excretion of macrophage-derived3H-cholesterol only under a high-cholesterol diet. In a HDL kinetic study, Ad-Sult2b1 promoted catabolism/hepatic uptake of HDL-derived cholesterol, thereby reducing fecal excretion. We next performed anin vitrolipoprotein production assay which revealed a Sult2b1-mediated reduction/increase in HDL or apoB-L secretion from hepatocytes, respectively. Finally, in LXRα/β double knockout mice, hepatic Sult2b1 overexpression increased apoB-L levels, but there were no differences in HDL levels or RCT compared to the control, indicating that Sult2b1-mediated effects on HDL/RCT and apoB-L were distinct: the former was LXR-dependent, but not the latter.ConclusionsHepatic LXR inhibition negatively regulates circulating HDL levels and RCT by reducing LXR-target gene expression.Graphic Abstract