bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Renal Anionic Secretion Following Living-donor and Deceased-donor Renal Transplantation: A Clinical Pharmacokinetic Study of Cefoxitin Microdosing
Authors: Kalluri Hari V. , Sood Puneet , Zhao Wenchen , Randhawa Parmjeet S. , Tevar Amit D. , Hariharan Sundaram , Humar Abhinav , Venkataramanan Raman 
Published: May 2020

Background.
Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs).

Methods.
The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation.

Results.
No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls.

Conclusions.
These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.
MatchMaker: A Deep Learning Framework for Drug Synergy Prediction
Authors: Kuru Halil Ibrahim , Tastan Oznur , Cicek A. Ercument 
Published: May 2020

AbstractDrug combination therapies have been a viable strategy for the treatment of complex diseases such as cancer due to increased efficacy and reduced side effects. However, experimentally validating all possible combinations for synergistic interaction even with high-throughout screens is intractable due to vast combinatorial search space. Computational techniques can reduce the number of combinations to be evaluated experimentally by prioritizing promising candidates. We present MatchMaker that predicts drug synergy scores using drug chemical structure information and gene expression profiles of cell lines in a deep learning framework. For the first time, our model utilizes the largest known drug combination dataset to date, DrugComb. We compare the performance of MatchMaker with the state-of-the-art models and observe up to ~ 20% correlation and ~ 40% mean squared error (MSE) improvements over the next best method. We investigate the cell types and drug pairs that are relatively harder to predict and present novel candidate pairs. MatchMaker is built and available athttps://github.com/tastanlab/matchmaker
Dynamic Loading of Human Engineered Heart Tissue Enhances Contractile Function and Drives Desmosome-linked Disease Phenotype
Authors: Bliley Jacqueline M. , Vermeer Mathilde C.S.C , Duffy Rebecca M. , Batalov Ivan , Kramer Duco , Tashman Joshua W. , Shiwarski Daniel J. , Lee Andrew , Teplenin Alexander S. , Volkers Linda , Coffin Brian , Hoes Martijn F. , Kalmykov Anna , Palchesko Rachelle N. , Sun Yan , Jongbloed Jan D.H. , Bomer Nils , de Boer Rudolf. A. , Suurmeijer Albert J.H. , Pijnappels Daniel A. , Bolling Maria C. , van der Meer Peter , Feinberg Adam W. 
Published: May 2020

ABSTRACTThe role mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes in the heart. However, most EHT systems are unable to model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained fractional shortening of >10%. To do this, 3D EHTs are integrated with an elastic polydimethylsiloxane (PDMS) strip that provides mechanical pre- and afterload to the tissue in addition to enabling contractile force measurements based on strip bending. Our results demonstrate in wild-type EHTs that dynamic loading is beneficial based on the magnitude of the forces, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we use hiPSC–derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy (ACM) due to mutations in desmoplakin. We demonstrate that manifestation of this desmosome-linked disease state requires the dyn-EHT conditioning and that it cannot be induced using 2D or standard 3D EHT approaches. Thus, dynamic loading strategy is necessary to provoke a disease phenotype (diastolic lengthening, reduction of desmosome counts, and reduced contractility), which are akin to primary endpoints of clinical disease, such as chamber thinning and reduced cardiac output.Single Sentence SummaryDevelopment of a dynamic mechanical loading platform to improve contractile function of engineered heart tissues and study cardiac disease progression.
Chromosome-scale assembly and annotation of the macadamia genome (Macadamia integrifoliaHAES 741)
Authors: Nock Catherine J. , Baten Abdul , Mauleon Ramil , Langdon Kirsty S. , Topp Bruce , Hardner Craig , Furtado Agnelo , Henry Robert J. , King Graham J. 
Published: May 2020

AbstractMacadamia integrifoliais a representative of the large basal eudicot family Proteaceae and the main progenitor species of the Australian native nut crop macadamia. Since its commercialisation in Hawaii fewer than 100 years ago, global production has expanded rapidly. However, genomic resources are limited in comparison to other horticultural crops. The first draft assembly ofM. integrifoliahad good coverage of the functional gene space but its high fragmentation has restricted its use in comparative genomics and association studies. Here we have generated an improved assembly of cultivar HAES 741 (4,094 scaffolds, 745 Mb, N50 413 kb) using a combination of Illumina paired and PacBio long read sequences. Scaffolds were anchored to 14 pseudo-chromosomes using seven genetic linkage maps. This assembly has improved contiguity and coverage, with >120 Gb of additional sequence. Following annotation, 34,274 protein-coding genes were predicted, representing 92% of the expected gene content. Our results indicate that the macadamia genome is repetitive and heterozygous. The total repeat content was 55% and genome-wide heterozygosity, estimated by read mapping, was 0.98% or one SNP per 102 bp. This is the first chromosome-scale genome assembly for macadamia and the Proteaceae. It is expected to be a valuable resource for breeding, gene discovery, conservation and evolutionary genomics.
Marriage in the Melting Pot: An evolutionary approach to European ancestry, homogamy and fertility in the United States
Authors: Schahbasi Alexander , Huber Susanne , Fieder Martin 
Published: May 2020

AbstractObjectiveTo understand marriage patterns, homogamy and fertility of women of European ancestry in the United States from an evolutionary perspective we aim to investigate if a prevalence for ancestral homogamy exists, the factors influencing a female preference for an ancestral homogamous vs. an heterogamous marriage, if an ancestral homogamous vs. heterogamous marriages influences fertility and if there is an inherted component of the tendency to marry homogamously vs. heterogamously. Furthermore we aim to determine the heritability of homogamous vs. heterogamous marriage behaviour.MethodsWe used the census data of 369,121 US women married only once and aged between 46 and 60 years, provided by IPUMS USA (https://usa.ipums.org/usa/). We used linear mixed models to determine associations of the probability of a homogamous vs. heterogamous marriage and the individual fertility of a women. We aimed to estimate the heritability (in our case genetic & parental environment) of marriage behaviour using a linear mixed model.ResultsWe found, that ancestral heterogamous marriages are more frequent (56.5%), compared to homogamous marriages (43.5%). Most of the variance in inter- ancestry marriage and fertility is explained by ancestry per se, followed by the ratio of individuals of a certain ancestral background in a county: the more individuals of a certain ancestry live in a county the lower is the tendency to marry someone of a different ancestral background. Furthermore we found that about 11.8% of the marriage behaviour is heritable. Being in a homogamous marriage as well as the income of the spouse are both significantly positively associated with the number of children a women has and the probability that a women has at least one child.DiscussionThe most important explaining factor (in terms of variance explained) for being in an ancestral homogamous vs. heterogamous marriage, for number of children, as well as childlessness is the ancestry of the women. Albeit we are not able to distinguish the genetic and social heritability on basis of our data, with a total value of 11.8% variance explained, only a small heritability for in-group vs, out-group marriage behaviour is indicated.
DeepGraphMol, a multi-objective, computational strategy for generating molecules with desirable properties: a graph convolution and reinforcement learning approach
Authors: Khemchandani Yash , O’Hagan Stephen , Samanta Soumitra , Swainston Neil , Roberts Timothy J. , Bollegala Danushka , Kell Douglas B. 
Published: May 2020

AbstractWe address the problem of generating novel molecules with desired interaction properties as a multi-objective optimization problem. Interaction binding models are learned from binding data using graph convolution networks (GCNs). Since the experimentally obtained property scores are recognised as having potentially gross errors, we adopted a robust loss for the model. Combinations of these terms, including drug likeness and synthetic accessibility, are then optimized using reinforcement learning based on a graph convolution policy approach. Some of the molecules generated, while legitimate chemically, can have excellent drug-likeness scores but appear unusual. We provide an example based on the binding potency of small molecules to dopamine transporters. We extend our method successfully to use a multi-objective reward function, in this case for generating novel molecules that bind with dopamine transporters but not with those for norepinephrine. Our method should be generally applicable to the generationin silicoof molecules with desirable properties.
Tuberculosis causes highly conserved metabolic changes in human patients, mycobacteria-infected mice and zebrafish larvae
Authors: Ding Yi , Raterink Robert Jan , Marín-Juez Rubén , Veneman Wouter J. , Egbers Koen , van den Eeden Susan , Haks Mariëlle C. , Joosten Simone A. , Ottenhoff Tom H.M. , Harms Amy C. , Alia A. , Hankemeier Thomas , Spaink Herman P. 
Published: May 2020

AbstractTuberculosis is a highly infectious and potentially fatal disease accompanied by wasting symptoms, which cause severe metabolic changes in infected people. In this study we have compared the effect of mycobacteria infection on the level of metabolites in blood of humans and mice and whole zebrafish larvae using one highly standardized mass spectrometry pipeline, ensuring technical comparability of the results. Quantification of a range of circulating small amines showed that the levels of the majority of these compounds were significantly decreased in all three groups of infected organisms. Ten of these metabolites were common between the three different organisms comprising: methionine, asparagine, cysteine, threonine, serine, tryptophan, leucine, citrulline, ethanolamine and phenylalanine. The metabolomic changes of zebrafish larvae after infection were confirmed by nuclear magnetic resonance spectroscopy. Our study identified common biomarkers for tuberculosis disease in humans, mice and zebrafish, showing across species conservation of metabolic reprogramming processes as a result of disease. Apparently, the mechanisms underlying these processes are independent of environmental, developmental and vertebrate evolutionary factors. The zebrafish larval model is highly suited to further investigate the mechanism of metabolic reprogramming and the connection with wasting syndrome due to infection by mycobacteria.
Inversion Genotyping in theAnopheles gambiaeComplex Using High-Throughput Array and Sequencing Platforms
Authors: Love R. Rebecca , Pombi Marco , Guelbeogo Moussa W. , Campbell Nathan R. , Stephens Melissa T. , Dabire Roch K. , Costantini Carlo , della Torre Alessandra , Besansky Nora J. 
Published: May 2020

ABSTRACTChromosomal inversion polymorphisms have special importance in theAnopheles gambiaecomplex of malaria vector mosquitoes, due to their role in local adaptation and range expansion. The study of inversions in natural populations is reliant on polytene chromosome analysis by expert cytogeneticists, a process that is limited by the rarity of trained specialists, low throughput, and restrictive sampling requirements. To overcome this barrier, we ascertained tag single nucleotide polymorphisms (SNPs) that are highly correlated with inversion status (inverted or standard orientation). We compared the performance of the tag SNPs using two alternative high throughput molecular genotyping approaches versus traditional cytogenetic karyotyping of the same 960 individualAn. gambiaeandAn. coluzziimosquitoes sampled from Burkina Faso, West Africa. We show that both molecular approaches yield comparable results, and that either one performs as well or better than cytogenetics in terms of genotyping accuracy. Given the ability of molecular genotyping approaches to be conducted at scale and at relatively low cost without restriction on mosquito sex or developmental stage, molecular genotyping via tag SNPs has the potential to revitalize research into the role of chromosomal inversions in the behavior and ongoing adaptation ofAn. gambiaeandAn. coluzziito environmental heterogeneities.
Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice
Authors: Rynes Mathew L , Surinach Daniel , Linn Samantha , Laroque Michael , Rajendran Vijay , Dominguez Judith , Hadjistamolou Orestes , Navabi Zahra S , Ghanbari Leila , Johnson Gregory W , Nazari Mojtaba , Mohajerani Majid , Kodandaramaiah Suhasa B 
Published: May 2020

ABSTRACTThe advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the “Mesoscope,” a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 µm. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.
Male-mediated maturation in a wild primate
Authors: Lu Amy , Feder Jacob A. , Snyder-Mackler Noah , Bergman Thore J. , Beehner Jacinta C. 
Published: May 2020

AbstractIn humans, a controversial hypothesis suggests that father absence promotes early puberty in daughters. Data from rodents confirm females accelerate maturation with exposure to novel males (“Vandenbergh effect”) and delay it with exposure to male relatives. Here, we report the first case of male-mediated maturation in a wild primate, geladas (Theropithecus gelada). Females were more likely to mature after a change in the reproductive male: some matured earlier than expected (Vandenbergh effect) and some later (due to father presence). Novel males stimulated a surge in estrogens for all immature females - even females too young to mature. Although male-mediated puberty accelerated first births, the effect was modest, suggesting that alternative scenarios, such as co-evolution with the Bruce effect (male-mediated fetal loss) may explain this phenomenon.One Sentence SummaryNovel males induce an estrogen surge, male-mediated puberty, and a head-start on reproduction for immature female geladas.
Worker-behavior and behavior-behavior interaction networks in the trap-jaw antOdontomachus chelifer(Latreille, 1802) (Hymenoptera: Formicidae)
Authors: Neves Felipe Marcel , Borges Marcelo Eduardo , Pie Marcio R. 
Published: May 2020

AbstractDivision of labor is among the main factors to explain the evolutionary success of social systems, from the origins of multicellularity to complex animal societies. The remarkable ecological success of social insects seems to have been largely driven by ergonomic advantages stemming from the behavioral specialization of workers. However, little is known about how individuals and their corresponding behavioral repertoires are related to each other within a division of labor context, particularly by viewing such relationships as complex networks. Applications of network theory to the study of social insects are almost exclusively used to analyze behavioral interactions between individuals, rather than to the study of relations among individuals and behaviors. Here, we use an approach to the study of the organization of the behavioral repertoire of ant colonies that considers both individual-behavior interactions and behavior-behavior interactions, besides colony time budgets. Our study investigates the organization of division of labor in colonies of the trap-jaw antOdontomachus chelifer(Latreille, 1802). All the behavioral acts (including inactivity) performed within three queenright colonies of different sizes (n = 7, 30, and 60 workers) were studied under controlled laboratory conditions. Each ant was individually marked and observed by scan sampling in 10 min intervals for 10 h each (n = 5,919 behavioral acts). We describe the network topologies in terms of centrality, specialization, modularity, and nestedness. This study shows that workers ofO. cheliferare organized according to structured networks, composed of individuals exhibiting varying degrees of specialization. The observed centrality scores indicate that some behaviors could have a disproportionately larger impact on the network organization (especially self-grooming). The results underscore the potential of the use of complex networks (particularly measures of modularity and nestedness) in order to discover and study novel organizational patterns of social groups in animal behavior.
A validation of Illumina EPIC array system with bisulfite-based amplicon sequencing
Authors: Noble Alexandra , Pearson John , Boden Joseph , Horwood John , Gemmell Neil , Kennedy Martin , Osborne Amy 
Published: May 2020

AbstractThe Illumina Infinium® MethylationEPIC BeadChip system (hereafter EPIC array) is considered to be the current gold standard detection method for assessing DNA methylation at the genome-wide level. EPIC arrays are used for hypothesis generation or pilot studies, the natural conclusion is to validate methylation candidates and expand these in a larger cohort, in a targeted manner. As such, an accurate smaller-scale, targeted technique, that generates data at the individual CpG level that is equivalent to the EPIC array, is needed. Here, we tested an alternative DNA methylation detection technique, known as bisulfite-based amplicon sequencing (BSAS), to determine its ability to validate CpG sites detected in EPIC array studies. BSAS was able to detect differential DNA methylation at CpG sites to a degree which correlates highly with the EPIC array system. However, BSAS correlated less well with EPIC array data when the magnitude of change via EPIC array was greater than 5%, suggesting that this lower specificity at larger differential methylation values is a consequence of PCR amplification that BSAS requires. However, our data suggests that BSAS does offer advantages that the EPIC array: BSAS amplifies a region of the genome (~500bp) around a CpG of interest, allowing analyses of other CpGs in the region that may not be present on the EPIC array, aiding discovery of novel CpG sites and differentially methylated regions of interest. We conclude that BSAS offers a valid investigative tool for specific regions of the genome that are currently not contained on the array system.
Proteomic responses to ocean acidification in the brain of juvenile coral reef fish
Authors: Tsang Hin Hung , Welch Megan , Munday Philip L. , Ravasi Timothy , Schunter Celia 
Published: May 2020

AbstractElevated CO2levels predicted to occur by the end of the century can affect the physiology and behaviour of marine fishes. For one important survival mechanism, the response to chemical alarm cues from conspecifics, substantial among-individual variation in the extent of behavioural impairment when exposed to elevated CO2has been observed in previous studies. Whole brain transcriptomic data has further emphasized the importance of parental phenotypic variation in the response of juvenile fish to elevated CO2. In this study, we investigate the genome-wide proteomic responses of this variation in the brain of 5-week old spiny damselfish,Acanthochromis polyacanthus. We compared the expression of proteins in the brains of juvenileA. polyacanthusfrom two different parental behavioural phenotypes (sensitive and tolerant) that had been experimentally exposed to short-term, long-term and inter-generational elevated CO2. Our results show differential expression of key proteins related to stress response and epigenetic markers with elevated CO2exposure. Proteins related to neurological development were also differentially expressed particularly in the long-term developmental treatment, which might be critical for juvenile development. By contrast, exposure to elevated CO2in the parental generation resulted in only three differentially expressed proteins in the offspring, revealing potential for inter-generational acclimation. Lastly, we found a distinct proteomic pattern in juveniles due to the behavioural sensitivity of parents to elevated CO2, even though the behaviour of the juvenile fish was impaired regardless of parental phenotype. Our data shows that developing juveniles are affected in their brain protein expression by elevated CO2, but the effect varies with the length of exposure as well as due to variation of parental phenotypes in the population.