bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioma-induced alterations in neuronal activity and neurovascular coupling during disease progression
Authors: Montgomery Mary Katherine , Kim Sharon H. , Dovas Athanassios , Patel Kripa , Mela Angeliki , Humala Nelson , Zhao Hanzhi T. , Thibodeaux David N. , Shaik Mohammed , Ma Ying , Grinband Jack , Chow Daniel S. , Schevon Catherine , Hillman Elizabeth M. C. , Canoll Peter 
Published: September 2019

AbstractDiffusely infiltrating gliomas are known to cause alterations in cortical function, vascular disruption and seizures. These neurological complications present major clinical challenges, yet their underlying mechanisms and causal relationships to disease progression are poorly characterized. Here, we followed glioma progression in awake Thy1-GCaMP6f mice using in-vivo wide-field optical mapping to monitor alterations in both neuronal activity and functional hemodynamics. The bilateral synchrony of spontaneous neuronal activity in glioma-infiltrated cortex gradually decreased, while neurovascular coupling was also progressively disrupted compared to uninvolved cortex. Over time, mice developed diverse patterns of high amplitude discharges and eventually generalized seizures that begin at the infiltrative margin of the tumors. Interictal and seizure events exhibited positive neurovascular coupling in uninfiltrated cortex, however glioma-infiltrated regions exhibited inverted hemodynamic responses driving seizure-evoked hypoxia. These results reveal a landscape of complex physiological interactions occurring during glioma progression and present new opportunities for exploring new biomarkers and therapeutic targets.Highlights-Glioma disrupts neural synchrony between bilateral cortical regions.-WFOM reveals frequent interictal discharges and seizures during glioma progression.-Tumor development is accompanied by local changes in neurovascular coupling.-Altered neurovascular coupling drives hypoperfusion of the tumor during seizures.
High-level cognition during story listening is reflected in high-order dynamic correlations in neural activity patterns
Authors: Owen Lucy L. W. , Chang Thomas H. , Manning Jeremy R. 
Published: September 2019

AbstractOur thoughts arise from coordinated patterns of interactions between brain structures that change with our ongoing experiences. High-order dynamic correlations in neural activity patterns reflect different subgraphs of the brain’s functional connectome that display homologous lower-level dynamic correlations. We tested the hypothesis that high-level cognition is reflected in high-order dynamic correlations in brain activity patterns. We developed an approach to estimating high-order dynamic correlations in timeseries data, and we applied the approach to neuroimaging data collected as human participants either listened to a ten-minute story or listened to a temporally scrambled version of the story. We trained across-participant pattern classifiers to decode (in held-out data) when in the session each neural activity snapshot was collected. We found that classifiers trained to decode from high-order dynamic correlations yielded the best performance on data collected as participants listened to the (unscrambled) story. By contrast, classifiers trained to decode data from scrambled versions of the story yielded the best performance when they were trained using first-order dynamic correlations or non-correlational activity patterns. We suggest that as our thoughts become more complex, they are reflected in higher-order patterns of dynamic network interactions throughout the brain.
Sex-specific transgenerational plasticity I: Maternal and paternal effects on sons and daughters
Authors: Hellmann Jennifer K , Bukhari Syed Abbas , Deno Jack , Bell Alison M 
Published: September 2019

AbstractTransgenerational plasticity (TGP) or parental effects – when parental environments alter the phenotype of future generations – can influence how organisms cope with environmental change. An intriguing, underexplored possibility is that sex –of both the parent and the offspring – plays an important role in driving the evolution of transgenerational plasticity in both adaptive and nonadaptive ways.Here, we evaluate the potential for sex-specific parental effects in a freshwater population of threespined sticklebacks (Gasterosteus aculeatus) by independently and jointly manipulating maternal and paternal experiences and separately evaluating their phenotypic effects in sons versus daughters. We tested the adaptive hypothesis that daughters are more responsive to cues from their mother, while sons are more responsive to cues from their father.We exposed mothers, fathers, or both parents to visual cues of predation risk and measured offspring antipredator traits and brain gene expression.Predator-exposed fathers produced sons that were more risk-prone, while predator-exposed mothers produced more anxious sons and daughters. Further, maternal and paternal effects on offspring survival were nonadditive: offspring with a predator-exposed father, but not two predator-exposed parents, had lower survival against live predators. There were also strong sex-specific effects on brain gene expression: exposing mothers versus fathers to predation risk activated different transcriptional profiles in their offspring, and sons and daughters strongly differed in the ways in which their brain gene expression profiles were influenced by parental experience.We found little evidence to support the hypothesis that offspring prioritize their same-sex parent’s experience. Parental effects varied with both the sex of the parent and the offspring in complicated and nonadditive ways. Failing to account for these sex-specific patterns (e.g., by pooling sons and daughters) would have underestimated the magnitude of parental effects. Altogether, these results draw attention to the potential for sex to influence patterns of TGP and raise new questions about the interface between transgenerational plasticity and sex-specific selective pressures, sexual conflict, and sexual selection.
The evolutionary forces shaping cis and trans regulation of gene expression within a population of outcrossing plants
Authors: Josephs Emily B. , Lee Young Wha , Wood Corlett W. , Schoen Daniel J. , Wright Stephen I. , Stinchcombe John R. 
Published: September 2019

AbstractUnderstanding the persistence of genetic variation within populations has long been a goal of evolutionary biology. One promising route towards achieving this goal is using population genetic approaches to describe how selection acts on the loci associated with trait variation. Gene expression provides a model trait for addressing the challenge of the maintenance of variation because it can be measured genome-wide without information about how gene expression affects traits. Previous work has shown that loci affecting the expression of nearby genes (local or cis-eQTLs) are under negative selection, but we lack a clear understanding of the selective forces acting on variants that affect the expression of genes in trans. Here, we identify loci that affect gene expression in trans using genomic and transcriptomic data from one population of the obligately outcrossing plant, Capsella grandiflora. The allele frequencies of trans-eQTLs are consistent with stronger negative selection acting on trans-eQTLs than cis-eQTLs, and even more strongly on trans-eQTLs associated with the expression of multiple genes. However, despite this general pattern, we still observe the presence of a trans-eQTL at intermediate frequency that affects the expression of a large number of genes in the same coexpression module. Overall, our work highlights the different selective pressures shaping variation in cis- and trans- gene regulation.
MRI ofCapn15knockout mice and analysis of Capn 15 distribution reveal possible roles in brain development and plasticity
Authors: Zha Congyao , Farah Carole A , Fonov Vladimir , Rudko David A , Sossin Wayne S 
Published: September 2019

AbstractThe Small Optic Lobe (SOL) family of calpains are intracellular cysteine proteases that are expressed in the nervous system and play an important role in neuronal development in bothDrosophila, where loss of this calpain leads to the eponymous small optic lobes, and in mouse and human, where loss of this calpain leads to eye anomalies. Some human individuals with biallelic variants in CAPN15 also have developmental delay and autism. However, neither the specific effect of the loss of the Capn15 protein on brain development nor the brain regions where this calpain is expressed in the adult is known. Here we show using small animal MRI that mice with the complete loss of Capn15 have smaller brains overall with larger decreases in the thalamus and subregions of the hippocampus. These losses are not seen inCapn15conditional KO mice where Capn15 is knocked out only in excitatory neurons in the adult. Based on β-galactosidase expression in an insert strain where lacZ is expressed under the control of theCapn15promoter, we show that Capn15 is expressed in adult mice, particularly in neurons involved in plasticity such as the hippocampus, lateral amygdala and Purkinje neurons, and partially in other non-characterized cell types. The regions of the brain in the adult where Capn15 is expressed do not correspond well to the regions of the brain most affected by the complete knockout suggesting distinct roles of Capn15 in brain development and adult brain function.
Distribution and diversity of fish species exposed to artisanal fishery along the Sudanese Red Sea coast
Authors: Olsen Erik , Axelsen Bjørn Erik , Moland Even , Utne-Palm Anne Christine , Elamin Elamin Mohammed , Mukhtar Motassim Ali , Saleh Adel Mohamed , Elamin Sheikheldin Mohamed , Iragi Mohamed Abdelhameed , Gumaa Said Gumaa Fadul 
Published: September 2019

AbstractThe semi-enclosed Red Sea harbours one of the longest coral-reef ecosystems on the planet. The ≈ 850 km section of the western shore, comprising the coastline of the Red Sea State of the Republic of Sudan, has however been sparsely studied. Sudan’s coral reef fishery provides livelihoods to fishers and business opportunities by means of local and regional trade, however, the knowledge level of the state of the natural resources and the impacts of fisheries are poorly known. Here we report the results from the first three comprehensive fisheries research surveys spanning the entire Sudanese coast in 2012-13, representing a new baseline for the western coast fisheries resources. The surveys covered the entire coast from inshore down to about 150 m bottom depth using a combination of baited traps, gillnets and handlines to sample the various reef habitats and fish assemblages. The results demonstrate a uniform latitudinal species distribution with peak catch per unit effort rates in and around the Dungonab Bay area in the north and the outer Suakin archipelago in the south. Functional diversity (Rao’s Q index) was found to be highest in and around the Dungonab Bay area, thus coming through as a regional hot-spot of biodiversity. The results form a baseline for future research and monitoring, thus representing key input for an ecosystem approach to management of Sudan’s coastal artisanal fisheries.
Capacitation-associated alkalization in human sperm is differentially controlled at the subcellular level
Authors: Matamoros-Volante A. , Treviño C.L. 
Published: September 2019

ABSTRACTCapacitation in mammalian sperm involves the accurate balance of intracellular pH (pHi), but the underlying control mechanisms are not fully understood, particularly regarding the spatiotemporal regulation of the proteins involved in such pHimodulation. Here we employed an image-based flow cytometry technique combined with pharmacological approaches to study pHidynamics at the subcellular level during sperm capacitation. We found that, upon capacitation induction, sperm cells undergo intracellular alkalization in the head and principal piece regions, but not in the midpiece. The observed localized pHiincreases require the initial uptake of HCO3-, and it is mediated by several proteins acting in a manner consistent with their subcellular localization. Hv1 proton channel and cAMP-activated Protein Kinase (PKA) antagonists impair alkalization mainly in the principal piece. Na+/HCO3-cotransporter (NBC) and cystic fibrosis transmembrane regulator (CFTR) antagonists impair alkalization only mildly, predominantly in the head. Motility measurements indicate that inhibition of alkalization in the principal piece prevents the development of hyperactivated motility. Altogether, our findings shed light into the complex control mechanisms of pHiand underscore their importance during human sperm capacitation.Summary statementHuman sperm display differential pHiregulation at the subcellular level upon capacitation, involving the participation of PKA kinase signaling pathway and several membrane transport proteins, culminating in hyperactivation.
Model-based species delimitation: are coalescent species reproductively isolated?
Authors: Campillo Luke C. , Barley Anthony J. , Thomson Robert C. 
Published: September 2019

ABSTRACTA large and growing fraction of systematists define species as independently evolving lineages that may be recognized by analyzing the population genetic history of alleles sampled from individuals belonging to those species. This has motivated the development of increasingly sophisticated statistical models rooted in the multispecies coalescent process. Specifically, these models allow for simultaneous estimation of the number of species present in a sample of individuals and the phylogenetic history of those species using only DNA sequence data from independent loci. These methods hold extraordinary promise for increasing the efficiency of species discovery, but require extensive validation to ensure that they are accurate and precise. Whether the species identified by these methods correspond to the species that would be recognized by alternative species recognition criteria (such as measurements of reproductive isolation) is currently an open question, and a subject of vigorous debate. Here we perform an empirical test of these methods by making use of a classic model system in the history of speciation research, flies of the genusDrosophila. Specifically, we use the uniquely comprehensive data on reproductive isolation that is available for this system, along with DNA sequence data, to ask whetherDrosophilaspecies inferred under the multispecies coalescent model correspond to those recognized by many decades of speciation research. We found that coalescent based and reproductive isolation based methods of inferring species boundaries are concordant for 77% of the species pairs. We explore and discuss potential explanations for these discrepancies. We also found that the amount of prezygotic isolation between two species is a strong predictor of the posterior probability of species boundaries based on DNA sequence data, regardless of whether the species pairs are sympatrically or allopatrically distributed.
Skp1 Dimerization Conceals its F-box Protein Binding Site
Authors: Kim Hyun W. , Eletsky Alexander , Gonzalez Karen J. , van der Wel Hanke , Strauch Eva-Maria , Prestegard James H. , West Christopher M. 
Published: September 2019

ABSTRACTSkp1 is an adapter that links F-box proteins to cullin-1 in the Skp1/cullin-1/F-box (SCF) protein family of E3 ubiquitin ligases that targets specific proteins for polyubiquitination and subsequent protein degradation. Skp1 from the amoebozoan Dictyostelium forms a stable homodimer in vitro with a Kd of 2.5 µM as determined by sedimentation velocity studies, yet is monomeric in crystal complexes with F-box proteins. To investigate the molecular basis for the difference, we determined the solution NMR structure of a doubly truncated Skp1 homodimer (Skp1ΔΔ). The solution structure of Skp1ΔΔ dimer reveals a 2-fold symmetry with an interface that buries ∼750 Å2 of predominantly hydrophobic surface. The dimer interface overlaps with subsite-1 of the F-box interaction area, explaining why only the Skp1 monomer binds F-box proteins (FBPs). To confirm the model, Rosetta was used to predict amino acid substitutions that might disrupt the dimer interface, and the F97E substitution was chosen to potentially minimize interference with F-box interactions. A nearly full-length version of Skp1 with this substitution (Skp1ΔF97E) behaved as a stable monomer at concentrations up to 500 µM and actively bound a model FBP, mammalian Fbs1, which suggests that the dimeric state is not required for Skp1 to carry out a basic biochemical function. Finally, Skp1ΔF97E is expected to serve as a monomer model for high-resolution NMR studies previously hindered by dimerization.
Overexpression of mig-6 in cartilage induces an osteoarthritis-like phenotype in mice
Authors: Bellini Melina , Pest Michael A. , Miranda-Rodrigues M. , Jeong JW , Beier Frank 
Published: September 2019

ABSTRACTBackgroundOsteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the Epidermal Growth Factor Receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of articular cartilage and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study.MethodsUtilizing knee joints from cartilage-specific Mig-6 overexpressing (Mig-6over/over) mice (at multiple time points), we evaluated the articular cartilage using histology, immunohistochemical staining and semi-quantitative OARSI scoring at multiple ages. MicroCT analysis was employed to examine skeletal morphometry, body composition, and bone mineral density.ResultsOur data show that cartilage-specific Mig-6 overexpression did not cause any major developmental abnormalities in articular cartilage, although Mig-6over/over mice have slightly shorter long bones compared to the control group. Moreover, there was no significant difference in bone mineral density and body composition in any of the groups. However, our results indicate that Mig-6over/over male mice show accelerated cartilage degeneration at 12 and 18 months of age. Immunohistochemistry for SOX9 demonstrated that the number of positively stained cells in Mig-6over/over mice decreased relative to controls. Immunostaining for MMP13 staining is increased in areas of cartilage degeneration in Mig-6over/over mice. Moreover, staining for phospho-EGFR (Tyr-1173) and lubricin (PRG4) was decreased in the articular cartilage of Mig-6over/over mice.ConclusionOverexpression of Mig-6 in articular cartilage causes no major developmental phenotype; however these mice develop earlier OA during aging. These data demonstrate that Mig-6/EGFR pathways is critical for joint homeostasis and might present a promising therapeutic target for OA.
Mesolimbic microglia display regionally distinct developmental trajectories
Authors: Hope KT , Hawes IA , Bonci A , De Biase LM 
Published: September 2019

ABSTRACTMicroglia play critical roles during CNS development and undergo dramatic changes in tissue distribution, morphology, and gene expression as they transition from embryonic to neonatal to adult microglial phenotypes. Despite the magnitude of these phenotypic shifts, little is known about the time course and dynamics of these transitions and whether they vary across brain regions. Here we define the time course of microglial maturation in key regions of the basal ganglia in mice where significant regional differences in microglial phenotype are present in adults. We found that microglial density peaks in the ventral tegmental area (VTA) and nucleus accumbens (NAc) during the third postnatal week, driven by a burst of microglial proliferation. Microglial abundance is then refined to adult levels through a combination of tissue expansion and microglial programmed cell death. This overproduction and refinement of microglia was significantly more pronounced in the NAc and was accompanied by a sharp peak in NAc microglial lysosome abundance in the third postnatal week. Collectively, these data identify a key developmental window when elevated microglial density in discrete basal ganglia nuclei may support circuit refinement and could increase susceptibility to inflammatory insults.
Aquatic and terrestrial organisms display contrasting life history strategies as a result of environmental adaptations
Authors: Capdevila Pol , Beger Maria , Blomberg Simone P. , Hereu Bernat , Linares Cristina , Salguero-Gómez Roberto 
Published: September 2019

AbstractAimsAquatic and terrestrial realms display stark differences in key environmental factors and phylogenetic composition. Despite such differences, their consequences for the evolution of species’ life history strategies remain poorly understood. Here, we examine whether and how life history strategies vary between terrestrial and aquatic species.LocationGlobal.Time periodVariable, the earliest year being in 1906 and the most recent in 2015.Major taxa studiesMacroscopic animals and plants species.MethodsWe use demographic information for 638 terrestrial and 117 aquatic animal and plant species, to derive key life history traits capturing their population turnover, and investments in survival, development, and reproduction. We use phylogenetically corrected least squares regression to explore the differences in the trade-offs between life history traits in both realms. We then quantify the life history strategies of aquatic and terrestrial species using a phylogenetically corrected principal component analysis.ResultsWe find that the same trade-offs structure terrestrial and aquatic life histories, resulting in two dominant axes of variation describing species’ pace- of-life and reproductive spread through time. Life history strategies differ between aquatic and terrestrial environments, with phylogenetic relationships playing a minor role. We show that adaptations of plants and animals to terrestrial environments have resulted in different life history strategies, particularly with their reproductive mode and longevity. Terrestrial plants display a great diversity of life history strategies, including the species with the longest lifespans. Aquatic animals, on the contrary, exhibit higher reproductive frequency than terrestrial animals, likely due to reproductive adaptations (i.e. internal fecundation) of the later to land.Main conclusionsOur findings show that aquatic and terrestrial species are ruled by the same life history principles, but have evolved different strategies due to distinct selection pressures. Such contrasting life history strategies have important consequences for the conservation and management of aquatic and terrestrial species.