bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sweet solutions: nectar chemistry and quality
Authors: Nicolson Susan W. 
Published: May 2022

Nectar, the main floral reward for pollinators, varies greatly in composition and concentration. The assumption that nectar quality is equivalent to its sugar (energy) concentration is too simple. Diverse non-sugar components, especially amino acids and secondary metabolites, play various roles in nutrition and health of pollinators. Many nectar compounds have indirect effects by altering the foraging behaviour of pollinators or protecting them from disease. This review also emphasizes the water component of nectar, often ignored because of evaporative losses and difficulties in sampling small nectar volumes. Nectar properties vary with environmental factors, pollinator visits and microbial contamination. Pollination mutualisms depend on the ability of insect and vertebrate pollinators to cope with and benefit from the variation and diversity in nectar chemistry.This article is part of the theme issue ‘Natural processes influencing pollinator health: from chemistry to landscapes’.
Behavioural regulation of mineral salt intake in honeybees: a self-selection approach
Authors: de Sousa Raquel T. , Darnell Robyn , Wright Geraldine A. 
Published: May 2022

Minerals are required in small amounts to sustain metabolic activity in animals, but mineral deficiencies can also lead to metabolic bottlenecks and mineral excesses can induce toxicity. For these reasons, we could reasonably expect that micronutrients are actively regulated around nutritional optima. Honeybees have co-evolved with flowering plants such that their main sources of nutrients are floral pollen and nectar. Like other insects, honeybees balance their intake of multiple macronutrients during food consumption using a combination of pre- and post-ingestive mechanisms. How they regulate their intake of micronutrients using these mechanisms has rarely been studied. Using two-choice feeding assays, we tested whether caged and broodless young workers preferred solutions containing individual salts (NaCl, KCl, CaCl2, MgCl2) or metals (FeCl3, CuCl2, ZnCl2, MnCl2) in a concentration-dependent manner. We found that young adult workers could only self-select and optimize their dietary intake around specific concentrations of sodium, iron and copper. Bees largely avoided high concentration mineral solutions to minimize toxicity. These experiments demonstrate the limits of the regulation of intake of micronutrients in honeybees. This is the first study to compare this form of behaviour in one organism for eight different micronutrients.This article is part of the theme issue ‘Natural processes influencing pollinator health: from chemistry to landscapes’.
Resource competition drives an invasion-replacement event among shrew species on an island
Authors: Browett Samuel S. , Synnott Rebecca , O’Meara Denise B. , Antwis Rachael E. , Browett Stephen S. , Bown Kevin J. , Wangensteen Owen S. , Dawson Deborah A. , Searle Jeremy B. , Yearsley Jon M. , McDevitt Allan D. 
Published: May 2022

AbstractInvasive mammals are responsible for the majority of native species extinctions on islands. While most of these extinction events will be due to novel interactions between species (e.g. exotic predators and naive prey), it is more unusual to find incidences where a newly invasive species causes the decline/extinction of a native species on an island when they normally coexist elsewhere in their overlapping mainland ranges.We investigated if resource competition between two insectivorous small mammals was playing a significant role in the rapid replacement of the native pygmy shrew (Sorex minutus) in the presence of the recently invading greater white-toothed shrew (Crocidura russula) on the island of Ireland.We used DNA metabarcoding of gut contents from >300 individuals of both species to determine each species’ diet and measured the size of individuals (weight and length) during different stages of the invasion in Ireland (before, during and after the species come into contact with one another) and on a French island where both species have long coexisted (acting as a natural ‘control’ site). Dietary composition, niche width and overlap and size were compared in these different stages.The size of the invasive C. russula and composition of its diet changes between when it first invades an area and after it becomes established. Individuals are larger and they consume larger invertebrates at the invasion front, before switching towards the smaller prey taxa that are more essential for the survival of the native species after establishment. As a result, the level of interspecific dietary overlap increases from between 11–14% when they first come into contact with each other to between 39–46% after the invasion.Here we show that an invasive species can quickly alter its dietary niche in a new environment, leading to negative impacts that were not previously predicted based on the coexistence of these species in other parts of their mainland ranges. As well as causing the replacement of a native small mammal, the invasive shrew may be rapidly exhausting local resources of larger invertebrate species. These subsequent changes in terrestrial invertebrate communities could have severe impacts further downstream on ecosystem functioning and services.
Normative Decision Rules in Changing Environments
Authors: Barendregt Nicholas W , Gold Joshua I , Josić Krešimir , Kilpatrick Zachary P 
Published: May 2022

AbstractModels based on normative principles have played a major role in our understanding of how the brain forms decisions. However, these models have typically been derived for simple, stable environments, and their relevance to decisions under more naturalistic, dynamic conditions is unclear. We previously derived a normative decision model in which evidence accumulation is adapted to environmental dynamics (Glaze et al., 2015), but the evolution of commitment rules (e.g., thresholds on the accumulated evidence) under such dynamic conditions is not fully understood. Here we derive a normative model for decisions based on changing evidence or reward. In these cases, performance (reward rate) is maximized using adaptive decision thresholds that best account for diverse environmental changes, in contrast to predictions of many previous decision models. These adaptive thresholds exhibit several distinct temporal motifs that depend on the specific, predicted and experienced changes in task conditions. These adaptive decision strategies perform robustly even when implemented imperfectly (noisily) and can account for observed response times on a task with time-varying evidence better than commonly used constant-threshold or urgency-gating models. These results further link normative and neural decision-making while expanding our view of both as dynamic, adaptive processes that update and use expectations to govern both deliberation and commitment.
Leverage drug perturbation to reveal genetic regulators of hepatic gene expression in African Americans
Authors: Zhong Yizhen , De Tanima , Avitia Juan , Alarcon Cristina , Perera Minoli A. 
Published: May 2022

AbstractBackgroundExpression quantitative loci (eQTL) studies have paved the way in identifying genetic variation impacting gene expression levels. African Americans (AAs) are disproportionately underrepresented in eQTL studies, resulting in a lack of power to identify population-specific regulatory variations especially related to drug response. Specific drugs are known to affect the biosynthesis of drug metabolism enzymes as well as other genes. We used drug perturbation in cultured primary hepatocytes derived from AAs to determine the effect of drug treatment on eQTL mapping and to identify the drug response eQTLs (reQTLs) that show altered effect size following drug treatment.MethodsWhole-genome genotyping (Illumina MEGA array) and RNA-sequencing were performed on 60 primary hepatocyte cultures after treatment with 6 drugs (Rifampin, Phenytoin, Carbamazepine, Dexamethasone, Phenobarbital, and Omeprazole) and at baseline (no treatment). eQTLs were mapped by treatment and jointly using Meta Tissue.ResultsWe found varying transcriptional changes across different drug treatments and identified Nrf2 as a potential general transcriptional regulator. We jointly mapped eQTL with gene expression data for across all drug treatments and baseline which increased our power to detect eQTLs by 2.7-fold. We also identified 2,988 reQTLs (eQTLs with altered effect size after drug treatment), which were more likely to overlap transcription factor binding sites and uncovered a novel reQTL, rs61017966 that increasesCYP3A5gene expression, a major drug metabolizing enzyme responsible for both drug response and adverse events across several drug classes.ConclusionsOur results provide novel insights into the genetic regulation of gene expression in hepatocytes through drug perturbation and provide insight into SNPs that effect the liver’s ability to respond to transcription upregulation.
Predicting mechanisms of action at genetic loci associated with discordant effects on type 2 diabetes and abdominal fat accumulation
Authors: Aberra Yonathan Tamrat , Ma Lijiang , Björkegren Johan L.M. , Civelek Mete 
Published: May 2022

ABSTRACTMetabolic syndrome (MetSyn) is a cluster of dysregulated metabolic conditions that occur together to increase the risk for cardiometabolic disorders such as type 2 diabetes (T2D). One key condition associated with MetSyn, abdominal obesity, is measured by computing the ratio of waist-to-hip circumference adjusted for the body-mass index (WHRadjBMI). WHRadjBMI and T2D are complex traits with genetic and environmental components, which has enabled genome-wide association studies (GWAS) to identify hundreds of loci associated with both. Statistical genetics analyses of these GWAS have predicted that WHRadjBMI is a strong causal risk factor of T2D and that these traits share genetic architecture at many loci. To date, no variants have been described that are simultaneously associated with protection from T2D but with increased abdominal obesity. Here, we used colocalization analysis to identify genetic variants with a shared association for T2D and abdominal obesity. This analysis revealed the presence of five loci associated with discordant effects on T2D and abdominal obesity. The alleles of the lead genetic variants in these loci that were protective against T2D were also associated with increased abdominal obesity. We further used publicly available expression, epigenomic, and genetic regulatory data to predict the effector genes (eGenes) and functional tissues at the 2p21, 5q21.1, and 19q13.11 loci. We also computed the correlation between the subcutaneous adipose tissue (SAT) expression of predicted effector genes (eGenes) with metabolic phenotypes and adipogenesis. We proposed a model to resolve the discordant effects at the 5q21.1 locus. We find that eGenes gypsy retrotransposon integrase 1 (GIN1), diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2), and peptidylglycine alpha-amidating monooxygenase (PAM) represent the likely causal eGenes at the 5q21.1 locus. Taken together, these results are the first to describe a potential mechanism through which a genetic variant can confer increased abdominal obesity but protection from T2D risk. Understanding precisely how and which genetic variants confer increased risk for MetSyn will develop the basic science needed to design novel therapeutics for metabolic syndrome.
Temperature-dependent gene regulatory divergence underlies local adaptation with gene flow in the Atlantic silverside
Authors: Jacobs Arne , Velotta Jonathan P. , Tigano Anna , Wilder Aryn P. , Baumann Hannes , Therkildsen Nina O. 
Published: May 2022

AbstractGene regulatory divergence is thought to play an important role in adaptation, yet its extent and underlying mechanisms remain largely elusive under scenarios of local adaptation with gene flow. Local adaptation is widespread in marine species despite generally high connectivity and often associated with tightly-linked genomic architectures, such as chromosomal inversions. To investigate gene regulatory evolution under gene flow and the role of discrete genomic regions associated with local adaptation to a steep thermal gradient, we generated RNA-seq data from Atlantic silversides (Menidia menidia) from two locally adapted populations and their F1 hybrids, reared under two different temperatures. We found substantial divergence in gene expression and thermal plasticity, with up to 31% of genes being differentially expressed, and primarily trans-rather than cis-regulatory divergence between populations, despite ongoing gene flow. Substantially reduced thermal plasticity, temperature-dependent gene misexpression and the disruption of co-expression networks in hybrids point toward a role of regulatory incompatibilities in maintaining local adaptation, particularly under colder temperatures, which appear more challenging for this species. Adaptive chromosomal inversions seem to play an important role in gene regulatory divergence through the accumulation of regulatory incompatibilities but are not consistently enriched for divergently regulated genes. Together, these results highlight that gene regulation can diverge substantially among populations connected by strong gene flow in marine environments, partly due to the accumulation of temperature-dependent regulatory incompatibilities within inversions.
Sleep spindles in primates: modelling the effects of distinct laminar thalamocortical connectivity in core, matrix, and reticular thalamic circuits
Authors: Yazdanbakhsh Arash , Barbas Helen , Zikopoulos Basilis 
Published: May 2022

AbstractSleep spindles are associated with the beginning of deep sleep and memory consolidation and are disrupted in schizophrenia and autism. In primates, distinct core and matrix thalamocortical (TC) circuits regulate sleep-spindle activity, through communications that are filtered by the inhibitory thalamic reticular nucleus (TRN) however, little is known about typical TC network interactions and the mechanisms that are disrupted in brain disorders. We developed a primate-specific, circuit-based TC computational model with distinct core and matrix loops that can simulate sleep spindles. We implemented novel multilevel cortical and thalamic mixing, and included local thalamic inhibitory interneurons, and direct layer 5 projections of variable density to TRN and thalamus to investigate the functional consequences of different ratios of core and matrix node connectivity contribution to spindle dynamics. Our simulations showed that spindle power in primates can be modulated based on the level of cortical feedback, thalamic inhibition, and engagement of model core vs. matrix, with the latter having a greater role in spindle dynamics. The study of the distinct spatial and temporal dynamics of core-, matrix-, and mix-generated sleep spindles establishes a framework to study disruption of TC circuit balance underlying deficits in sleep and attentional gating seen in autism and schizophrenia.
Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-March 31, 2022
Authors: Wang Xiangshi , Chang Hailing , Tian He , Li Jingjing , Wei Zhongqiu , Wang Yixue , Xia Aimei , Ge Yanling , Wang Jiali , Liu Gongbao , Cai Jiehao , Wang Jianshe , Zhu Qirong , Zhu Yanfeng , Zhai Xiaowen , Zeng Mei 
Published: May 2022

AbstractObjectivesTo understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai.MethodsThis study included local COVID-19 cases <18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease.ResultsA total of 376 pediatric cases of COVID-19 (median age:6.0±4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children;3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35% (RR 0.65, 95% CI:0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration: 1.7±1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%), school (21.8%) and residential area (8.8%).ConclusionThe surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer protection against symptomatic infection and febrile disease.
All-trans retinoic acid enhances the anti-tumour effects of fimaporfin-based photodynamic therapy
Authors: Wong Judith Jing Wen , Lorenz Susanne , Selbo Pål Kristian 
Published: May 2022

AbstractThe vitamin A metabolite all-trans retinoic acid (ATRA; tretinoin) has anticancer potential. However, lack of clinical success has prevented its approval for solid tumours. Herein, we propose combining short-term low-dose ATRA preconditioning with fimaporfin-based photodynamic therapy (ATRA+PDT) for the improved treatment of solid cancers. Compared to monotherapies, ATRA+PDT induced synergistic cytotoxic responses including promotion of apoptosis in colon and breast carcinoma cell lines. Neither enhanced activity of alkaline phosphatase (ALP) nor increased expression of CD133 was detected after ATRA treatment indicating that ATRA+PDT cause cell death independent of differentiation. In the human colorectal adenocarcinoma cell line HT-29, the effect of ATRA+PDT on gene expression was evaluated by RNA sequencing (RNA-seq). We identified 1129 differentially expressed genes (DEGs) after ATRA+PDT compared to PDT. Ingenuity Pathway Analysis (IPA) predicted the unfolded protein response (UPR), interferon (IFN) signaling and retinoic acid-mediated apoptosis signaling as strongly activated canonical pathways after ATRA+PDT compared to PDT. A validation of the RNA-sec data by RT-qPCR revealed that ATRA+PDT elevated mRNA expression of early growth response 1 (EGR1) and strongly the stress-induced activating transcription factor 3 (ATF3), of which was confirmed on the protein level. In addition, ATRA+PDT abolished mRNA expression of regenerating islet-derived protein 4 (REG4). During the first 20 days post-ATRA+PDT, we obtained significant anti-tumour responses in HT-29 xenografts, including complete responses in 2/5 mice. In conclusion, ATRA+PDT represent a novel combination therapy for solid tumours that should be further tested in immunocompetent preclinical models.
Classification of electrically-evoked compound action potentials in the parkinsonian subthalamic nucleus region
Authors: Rosing Joshua , Doyle Alex , Brinda AnneMarie , Blumenfeld Madeline , Lecy Emily , Spencer Chelsea , Dao Joan , Krieg Jordan , Wilmerding Kelton , Sullivan Disa , Best Sendréa , Mohanty Biswaranjan , Wang Jing , Johnson Luke A. , Vitek Jerrold L. , Johnson Matthew D. 
Published: May 2022

AbstractElectrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson’s disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n=3) or non-directional (n=1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6-7.4 ms after a stimulus pulse). Using these ECAP features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson’s disease with DBS therapy.
Cells function as a ternary logic gate to decide migration direction under integrated chemical and fluidic cues
Authors: Moon Hye-ran , Saha Soutick , Mugler Andrew , Han Bumsoo 
Published: May 2022

AbstractCells sense various environmental cues and process intracellular signals to decide their migration direction in many physiological and pathological processes. Although several signaling molecules have been identified in these directed migrations, it still remains elusive how cells decipher multiple cues, specifically chemical and fluidic cues. Here, we investigated the cellular signal processing machinery by reverse-engineering directed cell migration under integrated chemical and fluidic cues. We exposed controlled chemical and fluidic cues to cells using a microfluidic platform and analyzed the extracellular coupling of the cues with respect to the cellular detection limit. Then, the cell’s migratory behavior was reverse-engineered to build the cell’s intrinsic signal processing system as a logic gate. Our primary finding is that the cellular signal processing machinery functions as a ternary logic gate to decipher integrated chemical and fluidic cues. The proposed framework of the ternary logic gate suggests a systematic approach to understand how cells decode multiple cues to make decisions in migration.
Sugar transporter Slc37a2 regulates bone metabolism via a dynamic tubular lysosomal network in osteoclasts
Authors: Ng Pei Ying , Ribet Amy B.P. , Guo Qiang , Mullin Benjamin H. , Tan Jamie W.Y. , Landao-Bassonga Euphemie , Stephens Sébastien , Chen Kai , Abudulai Laila , Bollen Maike , Nguyen Edward T.T.T. , Kular Jasreen , Papadimitriou John M. , Søe Kent , Teasdale Rohan D. , Xu Jiake , Parton Robert G. , Takanayagi Hiroshi , Pavlos Nathan J. 
Published: May 2022

ABSTRACTOsteoclasts are giant bone-digesting cells that harbour specialized lysosome-related organelles termed secretory lysosomes (SLs). SLs store cathepsin K and serve as a membrane precursor to the ruffled border, the osteoclast’s ‘resorptive apparatus’. Yet, the molecular composition and spatiotemporal organization of SLs remains incompletely understood. Here, using organelle-resolution proteomics, we identify member a2 of the solute carrier 37 family (Slc37a2) as a SL sugar transporter. We demonstrate that Slc37a2 localizes to the SL limiting membrane and that these organelles adopt a hitherto unnoticed but dynamic tubular network in living osteoclasts that is required for bone digestion. Accordingly, mice lacking Slc37a2 accrue high bone mass owing to uncoupled bone metabolism and disturbances in SL export of monosaccharide sugars, a prerequisite for SL delivery to the ruffled border. Thus, Slc37a2 is a physiological component of the osteoclast’s unique secretory organelle and a potential therapeutic target for metabolic bone diseases.