bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgenic Zebrafish Models Reveal Distinct Molecular Mechanisms for Cataract-linked αA-Crystallin Mutants
Authors: Wu Shu-Yu , Zou Ping , Mishra Sanjay , Mchaourab Hassane S 
Published: July 2018

AbstractMutations in the small heat shock proteins α-crystallins have been linked to autosomal dominant cataracts in humans. Extensive studies in vitro have revealed a spectrum of alterations to the structure and function of these proteins including shifts in the size of the oligomer, modulation of subunit exchange and modification of their affinity to client proteins. Although mouse models of these mutants were instrumental in identifying changes in cellular proliferation and lens development, a direct comparative analysis of their effects on lens proteostasis has not been performed. Here, we have transgenically expressed cataract-linked mutants of αA- and αB-crystallin in the zebrafish lens to dissect the underlying molecular changes that contribute to the loss of lens optical properties. Zebrafish lines expressing these mutants displayed a range of morphological lens defects. Phenotype penetrance and severity were dependent on the mutation even in fish lines lacking endogenous α-crystallin. The mechanistic origins of these differences were investigated by the transgenic co-expression of a destabilized human γD-crystallin mutant. We found that the R49C but not the R116C mutant of αA-crystallin promoted aggregation of γD-crystallin, although both mutants have similar affinity to client proteins in vitro. Our working model attributes these differences to the propensity of R49C, located in the buried N-terminal domain of αA-crystallin, to disulfide crosslinking as previously demonstrated in vitro. Our findings complement and extend previous work in mouse models and emphasize the need of investigating chaperone/client protein interactions in appropriate cellular context.
Life history of the Rio Grande leopard frog (Lithobates berlandieri) in Texas
Authors: Hughes Daniel F. , Meshaka Walter E. 
Published: July 2018

ABSTRACTWe ascertained various life-history traits from an examination of 310 museum specimens of the Rio Grande leopard frog (Lithobates berlandieriBaird, 1859) collected during 1907–2016 from Texas, USA.Lithobates berlandieriwas captured during every month of the year except November, and adults were most frequently encountered during January–September with a distinct peak in May. Mean body size of adult males (69.5 mm) was smaller than that of adult females (77.5 mm), and both sexes were larger in mean body sizes than those of New Mexico populations (M = 64.4 mm; F = 73.5 mm). Females were gravid during January–September, and most gravid females were captured from late-winter to early-summer. Gonadal enlargement in males was generally high throughout January–September with no detectable seasonal increase. Feeding became widespread in both sexes during May–June shortly after a spring breeding bout. Spent females were common in July and lipid deposition increased in June/July, signaling oogenesis for breeding in the fall. From 15 gravid females, we estimated a mean clutch size of 3,107 eggs which was correlated with female body size, yet egg diameter was not related to clutch or body size. Age to metamorphosis was likely 2 to 4 months depending upon whether eggs were laid in the winter/spring or late fall. If metamorphosis occurred in May/June, the minimum size at sexual maturity in adult males (50.1 mm) could have been reached in 3–4 months and in 6–7 months for adult females (57.2 mm). Mean adult body sizes, however, may have taken 12 to 17 months to reach. A synthesis across Texas populations suggests that the breeding season extends almost continuously from the fall through the winter and spring until mid-summer and is interrupted by winter and summer peaks in seasonal temperatures.
Dynamics of genomic change during evolutionary rescue in the seed beetleCallosobruchus maculatus
Authors: Rêgo Alexandre , Messina Frank J. , Gompert Zachariah 
Published: July 2018

AbstractRapid adaptation can prevent extinction when populations are exposed to extremely marginal or stressful environments. Factors that affect the likelihood of evolutionary rescue from extinction have been identified, but much less is known about the evolutionary dynamics (e.g., rates and patterns of allele frequency change) and genomic basis of successful rescue, particularly in multicellular organisms. We conducted an evolve-and-resequence experiment to investigate the dynamics of evolutionary rescue at the genetic level in the cowpea seed beetle,Callosobruchus maculatus, when it is experimentally shifted to a stressful host plant, lentil. Low survival (∼1%) at the onset of the experiment caused population decline. But adaptive evolution quickly rescued the population, with survival rates climbing to 69% by the F5 generation and 90% by the F10 generation. Population genomic data showed that rescue likely was caused by rapid evolutionary change at multiple loci, with many alleles fixing or nearly fixing within five generations of selection on lentil. Selection on these loci was only moderately consistent in time, but parallel evolutionary changes were evident in sublines formed after the lentil line had passed through a bottleneck. By comparing estimates of selection and genomic change on lentil across five independentC. maculatuslines (the new lentil-adapted line, three long-established lines, and one case of failed evolutionary rescue), we found that adaptation on lentil occurred via somewhat idiosyncratic evolutionary changes. Overall, our results suggest that evolutionary rescue in this system can be caused by very strong selection on multiple loci driving rapid and pronounced genomic change.
Predation risk and resource abundance mediate foraging behaviour and intraspecific resource partitioning among consumers in dominance hierarchies
Authors: Naman Sean M. , Ueda Rui , Sato Takuya 
Published: July 2018

AbstractDominance hierarchies and unequal resource partitioning among individuals are key mechanisms of population regulation. The strength of dominance hierarchies can be influenced by size dependent trade-offs between foraging and predator avoidance whereby competitively inferior subdominants can access a larger proportion of limiting resources by accepting higher predation risk. Foraging-predation risk trade-offs also depend on resource abundance. Yet, few studies have manipulated predation risk and resource abundance simultaneously; consequently, their joint effect on resource partitioning within dominance hierarchies are not well understood. We addressed this gap by measuring behavioural responses of masu salmon to experimental manipulations of predation risk and resource abundance in a natural temperate forest stream. Responses to predation risk depended on body size such that larger dominants exhibited more risk-averse behaviour (e.g., lower foraging and appearance rates) relative to smaller subdominants after exposure to a simulated predator. The magnitude of this effect was lower when resources were elevated, indicating that dominant fish accepted a higher predation risk to forage on abundant resources. However, the influence of resource abundance did not extend to the population level, where predation risk altered the distribution of foraging attempts (a proxy for energy intake) from being skewed towards large individuals to being skewed towards small individuals after predator exposure. Our results imply that size dependent foraging-predation risk trade-offs can mediate the strength of dominance hierarchies by allowing competitively inferior subdominants to access resources that would otherwise be monopolized.Author Contributions:SN, TS, and RU designed the study and performed the fieldwork; SN analyzed the data and wrote the manuscript with input from all authors.
Intragenomic Conflict over Bet-Hedging
Authors: Wilkins Jon F , Bhattacharya Tanmoy 
Published: July 2018

AbstractGenomic imprinting, where an allele’s expression pattern depends on its parental origin, is thought to result primarily from an intragenomic evolutionary conflict. Imprinted genes are widely expressed in the brain and have been linked to various phenotypes, including behaviors related to risk tolerance. In this paper, we analyze a model of evolutionary bet-hedging in a system with imprinted gene expression. Previous analyses of bet-hedging have shown that natural selection may favor alleles and traits that reduce reproductive variance, even at the expense of reducing mean reproductive success, with the trade-off between mean and variance depending on the population size. In species where the sexes have different reproductive variances, this bet-hedging trade-off differs between maternally and paternally inherited alleles. Where males have the higher reproductive variance, alleles are more strongly selected to reduce variance when paternally inherited than when maternally inherited. We connect this result to phenotypes connected with specific imprinted genes, including delay discounting and social dominance. The empirical patterns are consistent with paternally expressed imprinted genes promoting risk-averse behaviors that reduce reproductive variance. Conversely, maternally expressed imprinted genes promote risk-tolerant, variance-increasing behaviors. We indicate how future research might further test the hypotheses suggested by our analysis.
Curvature Dependent constraints drive remodeling of epithelia
Authors: Maechler Florian A. , Allier Cédric , Roux Aurélien , Tomba Caterina 
Published: July 2018

AbstractEpithelial tissues are essential to keep a proper barrier for the organism. They usually have highly curved shapes, such as tubules or cysts. However, interplays between the environment and cell mechanical properties to set the shape are not known. In this study, we encapsulated two epithelial cell lineages, MDCK and J3B1A, into hollow alginate tubes and grew them under cylindrical confinement. Once formed, the epithelial MDCK layer detached from the alginate shell, while J3B1A layer remained adherent. Detachment resulted from contractile forces within cell layers that pulled cells away from the shell. We concluded that J3B1A cells have lower contractility than MDCK cells. As the pulling forces depend on the radius of the tube, we induced detachment of J3B1A cells by reducing the size of the hollow tube by two. Moreover, in bent tubes, detachment was more pronounced on the outer side of the turn, while extrusion occurred in the inner side, further highlighting the coupling between curvature and cell contractility.
Testing Causal Bidirectional Influences between Physical Activity and Depression using Mendelian Randomization
Authors: Choi Karmel W. , Chen Chia-Yen , Stein Murray B. , Klimentidis Yann C. , Wang Min-Jung ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Koenen Karestan C. , Smoller Jordan W. 
Published: July 2018

AbstractBackground:Burgeoning evidence from randomized controlled trials and prospective cohort studies suggests that physical activity protects against depression, pointing to a potential modifiable target for prevention. However, the direction of this inverse association is not clear: physical activity may reduce risk for depression, and/or depression may result in decreased physical activity. Here, we used bidirectional two-sample Mendelian randomization (MR) to test causal influences between physical activity and depression.Methods:For genetic instruments, we selected independent top SNPs associated with major depressive disorder (MDD, N = 143,265) and two physical activity phenotypes—self-reported (N = 377,234) and objective accelerometer-based (N = 91,084)—from the largest available, non-overlapping genome-wide association results. We used two sets of genetic instruments: (1) only SNPs previously reported as genome-wide significant, and (2) top SNPs meeting a more relaxed threshold (p < 1×10-7). For each direction of influence, we combined the MR effect estimates from each instrument SNP using inverse variance weighted (IVW) meta-analysis, along with other standard MR methods such as weighted median, MR-Egger, and MR-PRESSO.Results:We found evidence for protective influences of accelerometer-based activity on MDD (IVW odds ratio (OR) = 0.74 for MDD per 1 SD unit increase in average acceleration, 95% confidence interval (CI) = 0.59-0.92, p =.006) when using SNPs meeting the relaxed threshold (i.e., 10 versus only 2 genome-wide significant SNPs, which provided insufficient data for sensitivity analyses). In contrast, we found no evidence for negative influences of MDD on accelerometer-based activity (IVW b = 0.04 change in average acceleration for MDD versus control status, 95% CI = −0.43-0.51, p =.87). Furthermore, we did not see evidence for causal influences between self-reported activity and MDD, in either direction and regardless of instrument SNP criteria.Discussion:We apply MR for the first time to examine causal influences between physical activity and MDD. We discover that objectively measured—but not self-reported—physical activity is inversely associated with MDD. Of note, prior work has shown that accelerometer-based physical activity is more heritable than self-reported activity, in addition to being more representative of actual movement. Our findings validate physical activity as a protective factor for MDD and point to the importance of objective measurement of physical activity in epidemiological studies in relation to mental health. Overall, this study supports the hypothesis that enhancing physical activity is an effective prevention strategy for depression.
Parkinson-associatedSNCAenhancer variants revealed by open chromatin in mouse dopamine neurons
Authors: McClymont Sarah A. , Hook Paul W. , Soto Alexandra I. , Reed Xylena , Law William D. , Kerans Samuel J. , Waite Eric L. , Briceno Nicole J. , Thole Joey F. , Heckman Michael G. , Diehl Nancy N. , Wszolek Zbigniew K. , Moore Cedric D. , Zhu Heng , Akiyama Jennifer A. , Dickel Diane E. , Visel Axel , Pennacchio Len A. , Ross Owen A. , Beer Michael A. , McCallion Andrew S. 
Published: July 2018

ABSTRACTThe progressive loss of midbrain (MB) dopaminergic (DA) neurons defines the motor features of Parkinson disease (PD) and modulation of risk by common variation in PD has been well established through GWAS. Anticipating that a fraction of PD-associated genetic variation mediates their effects within this neuronal population, we acquired open chromatin signatures of purified embryonic mouse MB DA neurons. Correlation with >2,300 putative enhancers assayed in mice reveals enrichment for MB cis-regulatory elements (CRE), data reinforced by transgenic analyses of six additional sequences in zebrafish and mice. One CRE, within intron 4 of the familial PD geneSNCA, directs reporter expression in catecholaminergic neurons of transgenic mice and zebrafish. Sequencing of this CRE in 986 PD patients and 992 controls reveals two common variants associated with elevated PD risk. To assess potential mechanisms of action, we screened >20,000 DNA interacting proteins and identify a subset whose binding is impacted by these enhancer variants. Additional genotyping across theSNCAlocus identifies a single PD-associated haplotype, containing the minor alleles of both of the aforementioned PD-risk variants. Our work posits a model for how common variation atSNCAmay modulate PD risk and highlights the value of cell context-dependent guided searches for functional non-coding variation.
Synchronised brood transport by ants occurs without communication
Authors: Mersch Danielle P. , Eckmann Jean-Pierre , Crespi Alessandro , Keller Laurent 
Published: July 2018

AbstractCollective behaviours in societies such as those formed by ants are thought to be the result of distributed mechanisms of information processing and direct decision-making by well-informed individuals, but their relative importance remains unclear. Here we tracked all ants and brood movements to investigate the decision strategy underlying brood transport in nests of the antCamponotus fellah. Changes in environmental conditions induced workers to quickly transport the brood to a preferred location. Only a minority of the workers, mainly nurses, participated in this task. Using a large number of statistical tests we could further show that these transporters omitted to recruit help, and relied only on private information rather than information obtained from other workers. This reveals that synchronised group behaviour, often suggestive of coordinated actions among workers, can also occur in the complete absence of communication.
Fast and interpretable alternative splicing and differential gene-level expression analysis using transcriptome segmentation with Yanagi
Authors: Gunady Mohamed K , Mount Stephen M , Bravo Héctor Corrada 
Published: July 2018

AbstractIntroduction:Analysis of differential alternative splicing from RNA-seq data is complicated by the fact that many RNA-seq reads map to multiple transcripts, besides, the annotated transcripts are often a small subset of the possible transcripts of a gene. Here we describe Yanagi, a tool for segmenting transcriptome to create a library of maximal L-disjoint segments from a complete transcriptome annotation. That segment library preserves all transcriptome substrings of length L and transcripts structural relationships while eliminating unnecessary sequence duplications.Contributions:In this paper, we formalize the concept of transcriptome segmentation and propose an efficient algorithm for generating segment libraries based on a length parameter dependent on specific RNA-Seq library construction. The resulting segment sequences can be used with pseudo-alignment tools to quantify expression at the segment level. We characterize the segment libraries for the reference transcriptomes of Drosophila melanogaster and Homo sapiens and provide gene-level visualization of the segments for better interpretability. Then we demonstrate the use of segments-level quantification into gene expression and alternative splicing analysis. The notion of transcript segmentation as introduced here and implemented in Yanagi opens the door for the application of lightweight, ultra-fast pseudo-alignment algorithms in a wide variety of RNA-seq analyses.Conclusion:Using segment library rather than the standard transcriptome succeeds in significantly reducing ambigious alignments where reads are multimapped to several sequences in the reference. That allowed avoiding the quantification step required by standard kmer-based pipelines for gene expression analysis. Moreover, using segment counts as statistics for alternative splicing analysis enables achieving comparable performance to counting-based approaches (e.g. rMATS) while rather using fast and lighthweight pseudo alignment.
SosA inhibits cell division inStaphylococcus aureusin response to DNA damage
Authors: Bojer Martin S. , Wacnik Katarzyna , Kjelgaard Peter , Gallay Clement , Bottomley Amy L. , Cohn Marianne T. , Lindahl Gunnar , Frees Dorte , Veening Jan-Willem , Foster Simon J. , Ingmer Hanne 
Published: July 2018

AbstractInhibition of cell division is critical for cell viability under DNA damaging conditions. In bacterial cells, DNA damage induces the SOS response, a process that inhibits cell division while repairs are being made. In coccoid bacteria, such as the human pathogenStaphylococcus aureus, the process remains poorly understood. Here we have characterized an SOS-induced cell-division inhibitor, SosA, inS. aureus. We find that in contrast to the wildtype,sosAmutant cells continue division under DNA damaging conditions with decreased viability as a consequence. Conversely, overproduction of SosA leads to cell division inhibition and reduced growth. The SosA protein is localized in the bacterial membrane and mutation of an extracellular amino acid, conserved between homologs of other staphylococcal species, abolished the inhibitory activity as did truncation of the C-terminal 30 amino acids. In contrast, C-terminal truncation of 10 amino acids lead to SosA accumulation and a strong cell division inhibitory activity. A similar phenotype was observed upon expression of wildtype SosA in a mutant lacking the membrane protease, CtpA. Thus, the extracellular C-terminus of SosA is required both for cell-division inhibition and for turnover of the protein. Functional studies showed that SosA is likely to interact with one or more divisome components and, without interfering with early cell-division events, halts cell division at a point where septum formation is initiated yet being unable to progress to septum closure. Our findings provide important insights into cell-division regulation in staphylococci that may foster development of new classes of antibiotics targeting this essential process.ImportanceStaphylococcus aureusis a serious human pathogen and a model organism for cell-division studies in spherical bacteria. We show that SosA is the DNA-damage-inducible cell-division inhibitor inS. aureusthat upon expression causes cell swelling and cessation of the cell cycle at a characteristic stage post septum initiation but prior to division plate completion. SosA appears to function via an extracellular activity and is likely to do so by interfering with the essential membrane-associated division proteins, while at the same time being negatively regulated by the membrane protease CtpA. This report represents the first description of the process behind cell-division inhibition in coccoid bacteria. As several pathogens are included in this category, uncovering the molecular details of SosA activity and control can lead to identification of new targets for development of valuable anti-bacterial drugs.
Resource limitation modulates the fate of dissimilated nitrogen in a dual-pathway Actinobacterium
Authors: Vuono David C. , Read Robert W. , Hemp James , Sullivan Benjamin W. , Arnone John A. , Neveux Iva , Blank Bob , Staub Carl , Loney Evan , Miceli David , Winkler Mari , Chakraborty Romy , Stahl David A. , Grzymski Joseph J. 
Published: July 2018

AbstractRespiratory ammonification and denitrification are two evolutionarily unrelated dissimilatory nitrogen (N) processes central to the global N cycle, the activity of which is thought to be controlled by carbon (C) to nitrate (NO3-) ratio. Here we find thatIntrasporangium calvumC5, a novel menaquinone-based dual-pathway denitrifier/respiratory ammonifier, disproportionately utilizes ammonification rather than denitrification when grown under carbon or nitrate limitation, not C:NO3-ratio. Instead, C:NO3-ratio is a confounding variable for resource limitation. We find that the protein atomic composition for denitrification modules (NirK) are significantly cost minimized for C and N compared to ammonification modules (NrfA), indicating that resource limitation is a major selective pressure imprinted in the architecture of these proteins. The evolutionary precedent for these findings suggests ecological and biogeochemical importance as evidenced by higher growth rates whenI. calvumgrows predominantly using its ammonification pathway and by assimilating its end-product (ammonium) for growth under ammonium-deplete conditions. Genomic analysis ofI. calvumfurther reveals a versatile ecophysiology to cope with nutrient stress and redox conditions. Metabolite and transcriptional profiles during growth indicate that transcript abundances encoding for its nitrite reducing enzyme modules, NrfAH and NirK, significantly increase in response to nitrite production. Mechanistically, our results suggest that pathway selection is driven by intracellular redox potential (redox poise), which may be lowered during resource limitation, thereby decreasing catalytic activity of upstream electron transport steps needed for denitrification enzymes. Our work advances our understanding of the biogeochemical flexibility of N-cycling organisms, pathway evolution, and ecological food-webs.