bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexually antagonistic coevolution between the sex chromosomes of Drosophila melanogaster
Authors: Lund-Hansen Katrine K. , Olito Colin , Morrow Edward H. , Abbott Jessica K. 
Published: October 2019

AbstractAntagonistic interactions between the sexes are important drivers of evolutionary divergence. Interlocus sexual conflict is generally described as a conflict between alleles at two interacting loci whose identity and genomic location are arbitrary. Here we build on previous theory and suggest that when these two loci are located on the sex chromosomes it can lead to cycles of antagonistic coevolution between them, and therefore between the sexes. We tested this hypothesis by performing experimental crosses using Drosophila melanogaster in which we reciprocally exchanged the sex chromosomes between five wild-type populations in a round-robin design. Disrupting putatively coevolved sex chromosome pairs resulted in increased male reproductive success in 16 out of 20 experimental populations (10 of which were significant), but also resulted in lower offspring egg-to-adult viability that affected both male and female fitness. After 25 generations of experimental evolution these sexually antagonistic fitness effects appeared to have been resolved. To help formalise our hypothesis, we developed population genetic models of antagonistic coevolution using fitness expressions based on our empirical results. Our models support the conclusion that antagonistic coevolution between the sex chromosomes is plausible under the fitness effects observed in our experiments. Together, our results lend both empirical and theoretical support to the idea that a cycle of antagonistic coevolution can occur between sex chromosomes and illustrates how this process may drive genetic and phenotypic divergence between populations.SignificanceSex chromosomes are not only involved in genetic sex determination – they are also important factors in sexual conflict and speciation. Here, using a combination of experiments and population genetic models, we show that the sex chromosomes in Drosophila melanogaster can coevolve antagonistically. We found that swapping sex chromosomes between five Drosophila melanogaster populations increased male fitness at the cost of reduced offspring survival. After 25 generations, the increase had disappeared, consistent with the completion of a cycle of antagonistic coevolution. Using parameter values based on these empirical data, our models show that antagonistic coevolution between the sex chromosomes is a biologically plausible explanation for the results. Thus, our results point to a potentially important path to speciation through sexual conflict.
PLETHORA-WOX5 interaction and subnuclear localisation controlArabidopsisroot stem cell maintenance
Authors: Burkart Rebecca C. , Strotmann Vivien I. , Kirschner Gwendolyn K. , Akinci Abdullah , Czempik Laura , Dolata Anika , Maizel Alexis , Weidtkamp-Peters Stefanie , Stahl Yvonne 
Published: October 2019

AbstractMaintenance and homeostasis of the stem cell niche (SCN) in theArabidopsisroot is essential for growth and development of all root cell types. The SCN is organized around a quiescent center (QC) maintaining the stemness of cells in direct contact. The key transcription factors (TFs) WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and PLETHORAs (PLTs) are expressed in the SCN where they maintain the QC and regulate distal columella stem cell (CSC) fate. Here, we describe the concerted mutual regulation of the key TFs WOX5 and PLTs on a transcriptional and protein interaction level. Additionally, by applying a novel SCN staining method, we demonstrate that both WOX5 and PLTs regulate root SCN homeostasis as they control QC quiescence and CSC fate interdependently. Moreover, we uncover that some PLTs, especially PLT3, contain intrinsically disordered prion-like domains (PrDs) that are necessary for complex formation with WOX5 and its recruitment to subnuclear microdomains/nuclear bodies (NBs) in the CSCs. We propose that this partitioning of PLT-WOX5 complexes to NBs, possibly by phase separation, is important for CSC fate determination.
MicroCT optimisation for imaging fascicular anatomy in peripheral nerves
Authors: Thompson Nicole , Ravagli Enrico , Mastitskaya Svetlana , Iacoviello Francesco , Aristovich Kirill , Perkins Justin , Shearing Paul R , Holder David 
Published: October 2019

AbstractVagus nerve stimulation (VNS) is a promising therapy for treatment of various conditions resistant to standard therapeutics. However, due to the lack of understanding of the fascicular organisation of the vagus nerve, VNS leads to unwanted off-target effects. Micro-computed tomography (microCT) can be used to trace fascicles from periphery and image fascicular anatomy. In this work we optimised the microCT protocol of the rat sciatic and subsequent pig vagus nerves.After differential staining, the optimal staining time was selected and scanning parameters were altered in subsequent scans. Scans were reconstructed, visualised in ImageJ and fascicles segmented with a custom algorithm in Matlab to determine ultimate parameters for tracking of the nerve. Successful segmentation for tracking of individual fascicles was achieved after 24 hours and 120 hours of staining with Lugol’s solution (1% total iodine) for rat sciatic and pig vagus nerves, respectively, and the following scanning parameters: 4 µm voxel size, 35 kVp energy, 114 µA current, 4 W power, 0.25 fps in 4 s exposure time, 3176 projections and a molybdenum target.The optimised microCT protocol allows for segmentation and tracking of the fascicles within the nerve. This will be used to scan the full length of the pig, and possibly, the human vagus nerves. The resulting segmentation map of the functional anatomical organisation of the vagus nerve will enable selective VNS ultimately allowing for the avoidance of the off-target effects and improving its therapeutic efficacy.
Exploration of the role of CHRNA5-A3-B4 genotype in smoking behaviours
Authors: Lassi Glenda , Tan Vanessa , Mahedy Liam , Oliveira Ana Sofia F. , Dyer Maddy L. , Drax Katie , Dawkins Lynne , Rennard Stephen , Matcham James , Timpson Nicholas J. , Eisen Tim , Munafò Marcus R. 
Published: October 2019

AbstractGenome-wide association studies have identified associations between variation at rs16969968/rs1051730 in the CHRNA5–A3–B4 gene cluster and smoking related outcomes. Experiments in rodents have described the nicotinic acetylcholine receptors (nAChRs) subunits encoded by this gene cluster and showed a lack of nicotine aversion in nAChRs deficient animal models. We conducted a nicotine challenge and a smoking topography study in humans, hypothesising that: 1. responses to a nicotine challenge would differ according to the rs16969968/rs1051730 genotype and 2. genotype may influence nicotine intake via smoking topography.We used linear regressions to examine associations between rs16969968/rs1051730 genotype and subjective (questionnaires) and objective (physiological parameters) responses following acute nicotine exposure in never smokers (hypothesis 1) or cigarette smoking in current smokers (hypothesis 2). There was evidence to suggest nicotine exposure increases blood pressure and heart rate, and negatively affects mood, but insufficient evidence that these effects differ by genotype. Carriers of the minor allele following smoking one cigarette, exhibited reduced cravings (b=-2.46, 95% CI -4.87 to - 0.06, p=0.04) and inhaled less smoke per cigarette (b=-0.24, 95% CI - 0.43 to - 0.06, p=0.01) and per puff (b=-0.18, 95% CI -0.32 to -0.01, p=0.02). These results suggest that we need to carefully consider the translational value of the findings of aversion behaviour in nAChRs rodent models, and that deeper inhalation does not explain the strong association between rs16969968/rs1051730 genotype and objective biomarkers of tobacco exposure.
Extensive In Silico Analysis of ATL1 Gene: Discovered Five Mutations that may Cause Hereditary Spastic Paraplegia Type 3A
Authors: Mustafa Mujahed I. , Murshed Naseem S. , Abdelmoneim Abdelrahman H. , Abdelmageed Miysaa I. , Elfadol Nafisa M. , Makhawi Abdelrafie M. 
Published: October 2019

ABSTRACTBACKGROUNDHereditary spastic paraplegia type 3A (SPG3A) is a neurodegenerative disease inherited type of Hereditary spastic paraplegia (HSP). It is the second most frequent type of HSP; which Characterized by muscle stiffness with paraplegia and early-onset of symptoms. This is the first translational bioinformatics analysis in a coding region of ATL1 gene which aims to categorize nsSNPs to be used as genomic biomarkers; also it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.METHODSThe raw data of ATL1 gene were retrieved from dbSNP database, and then run into numerous computational analysis tools. Additionally; we submitted the common six deleterious outcomes from the previous functional analysis tools to I-mutant 3.0, and MUPro respectively, to investigate their effect on structural level. The 3D structure of ATL1 was predicted by RaptorX and modeled using UCSF Chimera to compare the differences between the native and the mutant amino acids.RESULTSFive nsSNPs out of 249 were classified as the most deleterious (rs746927118, rs979765709, rs119476049, rs864622269, rs1242753115).CONCLUSIONSIn this study the impact of nsSNPs in the ATL1 gene was investigated by various bioinformatics tools, that revealed five nsSNPs (V67F, T120I, R217Q, R495W and G504E) are deleterious SNPs, which have a functional impact on ATL1 protein; and therefore, can be used as genomic biomarkers specifically before 4 years old; also it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.
Liver X Receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms
Authors: Parigi Sara M. , Das Srustidhar , Frede Annika , Cardoso Rebeca F. , Tripathi Kumar Parijat , Doñas Cristian , Hu Yue O. O. , Antonson Per , Engstrand Lars , Gustafsson Jan-Åke , Villablanca Eduardo J. 
Published: October 2019

AbstractThe gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4+ T helper (Th) cell differentiation. Dietary compounds can be sensed by nuclear receptors (NRs) that consequently exerts pleiotropic effects including immune modulation. However, how NRs regulate distinct intestinal Th subsets remain poorly understood. Here, we found that under homeostatic condition Liver X receptor (LXR), a sensor of cholesterol metabolites, controls RORγt+ Treg and Th17 cells in the intestine draining mesenteric lymph node (MLN). Mechanistically, while lack of LXR signaling in CD11c+ myeloid cells led to an increase in RORγt+ Treg, modulation of MLN Th17 was independent of LXR signaling in either immune or epithelial cells. Of note, LXRα modulated only the Th17 cells, but not RORγt+ Treg in the MLN and horizontal transfer of microbiota between LXRα−/− and WT mice was sufficient to partially increase the MLN Th17 in WT mice. While LXRα deficiency increased the abundance of Ruminococcaceae and Lachnospiraceae bacterial families compared to the WT littermates, microbiota ablation including ablation of SFB was not sufficient to dampen LXRα-mediated expansion of MLN Th17. Altogether, our results suggest that LXR modulates RORγt+ Treg and Th17 cells in the MLN through distinct mechanisms.
A meta-analysis reveals temperature, dose, life stage, and taxonomy influence host susceptibility to a fungal parasite
Authors: Sauer Erin L. , Cohen Jeremy M. , Lajeunesse Marc J. , McMahon Taegan A. , Civitello David J. , Knutie Sarah A. , Nguyen Karena , Roznik Elizabeth A. , Sears Brittany F. , Bessler Scott , Delius Bryan K. , Halstead Neal , Ortega Nicole , Venesky Matthew D. , Young Suzanne , Rohr Jason R. 
Published: October 2019

AbstractComplex ecological relationships, such as host-parasite interactions, are often modeled with laboratory experiments. However, some experimental laboratory conditions, such as temperature or infection dose, are regularly chosen based on convenience or convention and it is unclear how these decisions systematically affect experimental outcomes. Here, we conducted a meta-analysis of 58 laboratory studies that exposed amphibians to the pathogenic fungusBatrachochytrium dendrobatidis(Bd) to better understand how laboratory temperature, host life stage, infection dose, and host species affect host mortality. We found that host mortality was driven by thermal mismatches: hosts native to cooler environments experienced greater Bd-induced mortality at relatively warm experimental temperatures and vice versa. We also found that Bd dose positively predicted Bd-induced host mortality and that the superfamilies Bufonoidea and Hyloidea were especially susceptible to Bd. Finally, the effect of Bd on host mortality varied across host life stages, with larval amphibians experiencing lower risk of Bd-induced mortality than adults or metamorphs. Metamorphs were especially susceptible and experienced mortality when inoculated with much smaller Bd doses than the average dose used by researchers. Our results suggest that when designing experiments on species interactions, researchers should carefully consider the experimental temperature, and inoculum dose, and life stage and taxonomy of the host species.
Behavioral and physiological evidence that increasing group size ameliorates the impacts of social disturbance
Authors: Anderson Hannah M. , Little Alexander G. , Fisher David N. , McEwen Brendan L. , Culbert Brett M. , Balshine Sigal , Pruitt Jonathan N. 
Published: October 2019

ABSTRACTIntra-group social stability is important for the long-term productivity and health of social organisms. We evaluated the effect of group size on group stability in the face of repeated social perturbations using a cooperatively breeding fish, Neolamprologus pulcher. In a laboratory study, we compared both the social and physiological responses of individuals from small versus large groups to the repeated removal and replacement of the most dominant group member (the breeder male). Individuals living in large groups were overall more resistant to instability but were seemingly slower to recover from perturbation. Members of small group were more vulnerable to instability but recovered faster. Breeder females in smaller groups also showed greater physiological preparedness for instability following social perturbations. In sum, we recover both behavioral and physiological evidence that living in larger groups helps to dampen the impacts of social instability in this system.Summary StatementSocial stability is vital for group productivity and long-term persistence. Here, both behavioral and physiological evidence conveys that larger groups are less susceptible to social disturbance.
Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction
Authors: Alabi Opeyemi , Robinson Mara , Fortunato Michael , Kable Joe W. , Fuccillo Marc V. 
Published: October 2019

SUMMARYGoal-directed behaviors, complex action sequences that maximize reward, are essential for normal function and are significantly impaired across neuropsychiatric disorders. Despite extensive associations between genetic mutations and these brain disorders, the mechanisms by which candidate genes contribute to goal-directed dysfunction remains unclear, owing to challenges in (1) describing aspects of reward processing that drive goal-directed dysfunction, (2) localizing these deficits to specific brain circuits and (3) relating changes in physiology to behavioral alterations. Here we examined mice with mutations in Neurexin1α, a presynaptically-localized adhesion molecule with widespread neuropsychiatric dis ease association, in value-based decision-making paradigms. We found that Neurexin1α knockout animals exhibited blunted choice bias towards outcomes associated with greater benefits. Mutant mice were similarly impaired in avoiding costlier, benefit-neutral actions. Analysis of trial-by-trial choice data via reinforcement learning models suggested these behavioral patterns were driven largely by deficits in the updating and representation of choice values. Employing conditional gene ablation and region-specific Cre-recombinase strains, we revealed that Neurexin1α disruption within forebrain excitatory projection neurons, but not thalamic population s, recapitulated most aspects of the whole-brain knockout phenotype. Finally, utilizing in vivo recordings of direct pathway spiny neuron population calcium activity, we demonstrated that selective knockout of Neurexin1α within forebrain excitatory neurons disrupts reward-associated neural signals within striatum, a major site of feedback-based learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in reward-associated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.
A portable and cost-effective microfluidic system for massively parallel single-cell transcriptome profiling
Authors: Liu Chuanyu , Wu Tao , Fan Fei , Liu Ya , Wu Liang , Junkin Michael , Wang Zhifeng , Yu Yeya , Wang Weimao , Wei Wenbo , Yuan Yue , Wang Mingyue , Cheng Mengnan , Wei Xiaoyu , Xu Jiangshan , Shi Quan , Liu Shiping , Chen Ao , Wang Ou , Ni Ming , Zhang Wenwei , Shang Zhouchun , Lai Yiwei , Guo Pengcheng , Ward Carl , Volpe Giacomo , Wang Lei , Zheng Huan , Liu Yang , Peters Brock A. , Beecher Jody , Zhang Yongwei , Esteban Miguel A. , Hou Yong , Xu Xun , Chen I-Jane , Liu Longqi 
Published: October 2019

AbstractSingle-cell technologies are becoming increasingly widespread and have been revolutionizing our understanding of cell identity, state, diversity and function. However, current platforms can be slow to apply to large-scale studies and resource-limited clinical arenas due to a variety of reasons including cost, infrastructure, sample quality and requirements. Here we report DNBelab C4 (C4), a negative pressure orchestrated, portable and cost-effective device that enables high-throughput single-cell transcriptional profiling. C4 system can efficiently allow discrimination of species-specific cells at high resolution and dissect tissue heterogeneity in different organs, such as murine lung and cerebral cortex. Finally, we show that the C4 system is comparable to existing platforms but has huge benefits in cost and portability and, as such, it will be of great interest for the wider scientific community.
Glutamate-ammonia ligase promotes lung cancer cell growth through an enzyme-independent upregulation of CaMK2G under a glutamine-sufficient condition
Authors: Zhao Jiangsha , Zeng Xiankun , Hou Steven X. 
Published: October 2019

SUMMARYGlutamate-ammonia ligase (GLUL) is highly expressed in many cancer cells. Synthesizing glutamine by its enzyme function has been found to be important for supporting cancer cell survival and growth under glutamine restriction. However, GLUL’s functions under a glutamine-sufficient condition still have not been uncovered. Here we find that GLUL is highly expressed in lung cancer cells and provides survival and growth advantages under both glutamine restriction and adequacy conditions. Knocking down GLUL can block lung cancer cell growth in an enzyme-independent way when glutamine is sufficient. Mechanistically, GLUL regulates Calcium/Calmodulin Dependent Protein Kinase II Gamma (CaMK2G) expression at the transcription level, and CaMK2G is a major mediator in controlling cell growth under GLUL. The transcriptional regulation of CaMK2G is partially mediated by SMAD4. Our data unveil a new enzyme-independent function of GLUL in lung cancer cells under a glutamine-sufficient condition.
Developmental Changes in EEG Phase Amplitude Coupling and Phase Preference over the First Three Years After Birth
Authors: Mariscal Michael G. , Levin April R. , Gabard-Durnam Laurel J. , Tager-Flusberg Helen , Nelson Charles A. 
Published: October 2019

AbstractThe coupling of the phase of slower electrophysiological oscillations with the amplitude of faster oscillations, termed phase-amplitude coupling (PAC), is thought to facilitate dynamic connectivity in the brain. Though the brain undergoes dramatic changes in connectivity during the first few years of life, how PAC changes through this developmental period has not been studied. Here, we examined PAC through electroencephalography (EEG) data collected longitudinally during an awake, eyes-open EEG collection paradigm in 98 children between the ages of 3 months and 3 years. We implement a novel technique developed for capturing both PAC strength and phase preference (i.e., where in the slower oscillation waveform the faster oscillation shows increased amplitude) simultaneously, and employed non-parametric clustering methods to evaluate our metrics across a range of frequency pairs and electrode locations. We found that frontal and occipital PAC, primarily between the alpha-beta and gamma frequencies, increased from early infancy to early childhood (p = 1.35 x 10-5). Additionally, we found frontal gamma coupled with the trough of the alpha-beta waveform, while occipital gamma coupled with the peak of the alpha-beta waveform. This opposing trend may reflect each region’s specialization towards feedback or feedforward processing, respectively.Significance StatementThe brain undergoes significant changes in functional connectivity during infancy and early childhood, enabling the emergence of higher-level cognition. Phase-amplitude coupling (PAC) is thought to support the functional connectivity of the brain. Here, we find PAC increases from 3 months to 3 years of age. We additionally report the frontal and occipital brain areas show opposing forms of PAC; this difference could facilitate each region’s tendency towards bottom-up or top-down processing.