bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive functions and genetic architecture of the seminal fluid and sperm proteomes of the mosquitoAedes aegypti
Authors: Degner Ethan C. , Ahmed-Braimah Yasir H. , Borziak Kiril , Wolfner Mariana F. , Harrington Laura C. , Dorus Steve 
Published: August 2018

AbstractThe yellow fever mosquito,Aedes aegypti,transmits several viruses, including dengue, Zika, and chikungunya. Some proposed efforts to control this vector involve manipulating reproduction to suppress wild populations or replacing them with disease-resistant mosquitoes. The design of such strategies requires an intimate knowledge of reproductive processes, yet our basic understanding of reproductive genetics in this vector remains largely incomplete. To accelerate future investigations, we have comprehensively catalogued sperm and seminal fluid proteins (SFPs) transferred to females in the ejaculate using tandem mass spectrometry. By excluding female-derived proteins using an isotopic labelling approach, we identified 870 sperm proteins and 280 seminal fluid proteins. Functional composition analysis revealed parallels with known aspects of sperm biology and SFP function in other insects. To corroborate our proteome characterization, we also generated transcriptomes for testes and the male accessory glands—the primary contributors toAe. aegyptisperm and seminal fluid, respectively. Differential gene expression of accessory glands from virgin and mated males suggests that protein translation is upregulated post-mating. Several SFP transcripts were also modulated after mating, but >90% remained unchanged. Finally, a significant enrichment of SFPs was observed on chromosome 1, which harbors the male sex determining locus in this species. Our study provides a comprehensive proteomic and transcriptomic characterization of ejaculate production and composition and thus provides a foundation for future investigations ofAe. aegyptireproductive biology, from functional analysis of individual proteins to broader examination of reproductive processes.
β-actin mRNA interactome mapping by proximity biotinylation
Authors: Mukherjee Joyita , Hermesh Orit , Eliscovich Carolina , Nalpas Nicolas , Franz-Wachtel Mirita , Maček Boris , Jansen Ralf-Peter 
Published: August 2018

AbstractThe molecular function and fate of mRNAs are controlled by RNA-binding proteins (RBPs). However, identification of the interacting proteome of a specific mRNA in vivo is still very challenging. Based on the widely-used RNA tagging with MS2 aptamers for RNA visualization, we developed a novel RNA proximity biotinylation (RNA-BioID) method by tethering biotin ligase (BirA*) via MS2 coat protein (MCP) at the 3’-UTR of endogenous MS2 tagged β-actin mRNA (MBS) in mouse embryonic fibroblasts (MEFs). We demonstrate the dynamics of the β-actin mRNA interactome by characterizing its changes upon serum-induced localization of the mRNA. Apart from the previously known interactors, we identified over 60 additional β-actin associated RBPs by RNA-BioID. Among them the KH-domain containing protein FUBP3/MARTA2 has shown to be required for β-actin mRNA localization. We found that FUBP3 binds to the 3’-UTR of β-actin mRNA, is essential for β-actin mRNA localization but does not interact with the characterized β-actin zipcode element. RNA-BioID provides a tool to identify new mRNA interactors and to study the dynamic view of the interacting proteome of endogenous mRNAs in space and time.Significance statementTransport of specific mRNAs to defined sites in the cytoplasm allows local protein production and contributes to cell polarity, embryogenesis, and neuronal function. These localized mRNAs contain signals (zipcodes) that help directing them to their destination site. Zipcodes are recognized by RNA-binding proteins that, with the help of molecular motor proteins and supplementary factors, mediate mRNA trafficking. To identify all proteins assembling with a localized mRNA we advanced a proximity labeling method (BioID) by tethering a biotin ligase to the 3’ untranslated region of mRNA encoding the conserved beta-actin protein. We demonstrate that this method allows the identification of novel, functionally important proteins that are required for mRNA localization.
Alternative oxidase induction protects Candida albicans from respiratory stress and promotes hyphal growth
Authors: Duvenage Lucian , Walker Louise A. , Bojarczuk Aleksandra , Johnston Simon A. , McCallum Donna M. , Munro Carol A. , Gourlay Campbell W. 
Published: August 2018

AbstractThe human fungal pathogenCandida albicanspossesses two genes expressing a cyanide-insensitive Alternative Oxidase (Aox) enzymes in addition to classical and parallel electron transfer chains (ETC). In this study, we examine the role of Aox inC.albicansunder conditions of respiratory stress, which may be inflicted during its interaction with the human host or co-colonising bacteria. We find that the level of Aox expression is sufficient to modulate resistance to classical ETC inhibition under respiratory stress and are linked to gene expression changes that can promote both survival and pathogenicity. For example we demonstrate that Aox function is important for the regulation of filamentation inC.albicansand observe that cells lacking Aox function lose virulence in a zebrafish infection model. Our investigations also identify that pyocyanin, a phenazine produced by the co-colonising bacteriumPseudomonas aeruginosa, inhibits Aox-based respiration inC.albicans. These results suggest that Aox plays important roles within respiratory stress response pathways whichC.albicansmay utilise both as a commensal organism and as a pathogen.
The evolution of infanticide by females in mammals
Authors: Lukas Dieter , Huchard Elise 
Published: August 2018

AbstractIn most mammalian species, females regularly interact with kin, and it may thus be difficult to understand the evolution of some aggressive and harmful competitive behaviour among females, such as infanticide. Here, we investigate the evolutionary determinants of infanticide by females by combining a quantitative analysis of the taxonomic distribution of infanticide with a qualitative synthesis of the circumstances of infanticidal attacks in published reports. Our results show that female infanticide is widespread across mammals and varies in relation to social organization and life-history, being more frequent where females breed in groups and have intense bouts of high reproductive output. Specifically, female infanticide occurs where the proximity of conspecific offspring directly threatens the killer’s reproductive success by limiting access to critical resources for her dependent progeny, including food, shelters, care or a social position. In contrast, infanticide is not immediately modulated by the degree of kinship among females, and females occasionally sacrifice closely related juveniles. Our findings suggest that the potential direct fitness rewards of gaining access to reproductive resources have a stronger influence on the expression of female aggression than the indirect fitness costs of competing against kin.
Applying optimal control theory to complex epidemiological models to inform real-world disease management
Authors: Bussell E.H. , Dangerfield C.E. , Gilligan C.A. , Cunniffe N.J. 
Published: August 2018

SummaryMathematical models provide a rational basis to inform how, where and when to control disease. Assuming an accurate spatially-explicit simulation model can be fitted to spread data, it is straightforward to use it to test the performance of a range of management strategies. However, the typical complexity of simulation models and the vast set of possible controls mean that only a small subset of all possible strategies can ever be tested. An alternative approach – optimal control theory – allows the very best control to be identified unambiguously. However, the complexity of the underpinning mathematics means that disease models used to identify this optimum must be very simple. We highlight two frameworks for bridging the gap between detailed epidemic simulations and optimal control theory: open-loop and model predictive control. Both these frameworks approximate a simulation model with a simpler model more amenable to mathematical analysis. Using an illustrative example model we show the benefits of using feedback control, in which the approximation and control are updated as the epidemic progresses. Our work illustrates a new methodology to allow the insights of optimal control theory to inform practical disease management strategies, with the potential for application to diseases of plants, animals and humans.
Neural basis of Transcranial Magnetic Stimulation at the single-cell Level
Authors: Romero Maria C. , Davare Marco , Armendariz Marcelo , Janssen Peter 
Published: August 2018

AbstractTranscranial Magnetic Stimulation (TMS) can non-invasively modulate neural activity in humans. Despite three decades of research, the spatial extent of the cortical area activated by TMS is still controversial. Moreover, how TMS interacts with task-related activity during motor behavior is unknown. We applied single-pulse TMS over the macaque parietal cortex while recording single-unit activity at various distances from the center of stimulation during grasping. The spatial extent of the TMS-induced activation was remarkably restricted, affecting single neurons in a volume of cortex measuring less than 2 mm. In task-related neurons, TMS evoked a transient excitation followed by reduced activity, which was paralleled by a significantly longer grasping time. Furthermore, TMS- induced activity and task-related activity did not summate in single neurons. These results furnish crucial experimental evidence for the neural basis of the TMS effect at the single-cell level and uncover, the neural underpinnings of behavioral effects of TMS.
Compressive strengths of PEG gels with glycerol and bioglass particles
Authors: Golshan Ariel , Curtis Jenesis A. , Lianos Vasilios , Rabbany Sina Y. , de Guzman Roche C. 
Published: August 2018

ABSTRACTPoly(ethylene glycol) (PEG)-based materials can potentially be used as biomechanical matrices for regenerative medicine implants including the replacement of intervertebral (IV) discs. Glycerol and other plasticizers (low-MW PEG, propylene glycol, and sorbitol) were added to the bulk PEG matrix, gelled using chemical and photochemical methods at different temperature and pressure settings, and compression properties acquired and analyzed. Incorporation of surface bioactive glass particles shortened the blood clotting time, while alginate and laponite additives improved the gel’s mechanical properties to 645 kPa compressive modulus, 12% yield strain, and 79 kPa yield strength. This IV disc-modeled system endured the cyclic loading and unloading test indicative of an elastic response; but required improvement of its biomechanical tolerance.
Genotype-Phenotype Relations of the von Hippel-Lindau Tumor Suppressor Inferred from a Large-Scale Analysis of Disease Mutations and Interactors
Authors: Minervini Giovanni , Quaglia Federica , Tabaro Francesco , Tosatto Silvio C.E. 
Published: August 2018

AbstractFamiliar cancers represent a privileged point of view for studying the complex cellular events inducing tumor transformation. Von Hippel-Lindau syndrome, a familiar predisposition to develop cancer is a clear example. Here, we present our efforts to decipher the role of von Hippel-Lindau tumor suppressor protein (pVHL) in cancer insurgence. We collected high quality information about both pVHL mutations and interactors to investigate the association between patient phenotypes, mutated protein surface and impaired interactions. Our data suggest that different phenotypes correlate with localized perturbations of the pVHL structure, with specific cell functions associated to different protein surfaces. We propose five different pVHL interfaces to be selectively involved in modulating proteins regulating gene expression, protein homeostasis as well as to address extracellular matrix (ECM) and ciliogenesis associated functions. These data were used to drive molecular docking of pVHL with its interactors and guide Petri net simulations of the most promising alterations. We predict that disruption of pVHL association with certain interactors can trigger tumor transformation, inducing metabolism imbalance and ECM remodeling. Collectively taken, our findings provide novel insights into VHL-associated tumorigenesis. This highly integrated in silico approach may help elucidate novel treatment paradigms for VHL disease.Author summaryCancer is generally caused by a series of mutations accumulating over time in a healthy tissue, which becomes re-programmed to proliferate at the expense of the hosting organism. This process is difficult to follow and understand as events in a multitude of different genes can lead to similar outcomes without apparent cause. The von Hippel-Lindau (VHL) tumor suppressor is one of the few genes harboring a familiar cancer syndrome, i.e. VHL mutations are known to cause a predictable series of events leading cancer in the kidneys and a few selected other tissues. This article describes a large-scale analysis to relate known VHL mutations to specific cancer pathways by looking at the molecular interactions. Different cancer types appear to be caused by mutations changing the surface of specific parts of the VHL protein. By looking at the VHL interactors involved, it is therefore possible to identify other candidate genes for mutations leading to very similar cancer types.
The impact of global transcriptional regulation on bacterial gene order
Authors: Yubero Pablo , Poyatos Juan F. 
Published: August 2018

AbstractBacterial gene expression depends on the allocation of limited transcriptional resources provided a particular growth rate and growth condition. Early studies in a few genes suggested this global regulation to generate a unifying hyperbolic expression pattern. Here, we developed a large-scale method that generalizes these experiments to quantify the response to growth of over 700 genes thata priorido not exhibit any specific control. We distinguish a core subset following a promoter-specific hyperbolic response. Within this group, we sort genes with regard to their responsiveness to the global regulatory program to show that those with a particularly sensitive linear response are located near the origin of replication. We then find evidence that this genomic architecture is biologically significant by examining position conservation ofE. coligenes in 100 bacteria. The response to the transcriptional resources of the cell results consequently in an additional feature contributing to bacterial genome organization.
Analysis of a structured intronic region of the LMP2 pre-mRNA from EBV reveals associations with human regulatory proteins
Authors: Kumarasinghe Nuwanthika , Moss Walter N. 
Published: August 2018

ABSTRACTObjective: The pre-mRNA of the Epstein–Barr virus LMP2 (latent membrane protein 2) has a region of unusual RNA structure that partially spans two consecutive exons and the entire intervening intron; suggesting RNA folding might affect splicing—particularly via interactions with human regulatory proteins. To better understand the roles of protein associations with this structured intronic region, we undertook a combined bioinformatics (motif searching) and experimental analysis (biotin pulldowns and RNA immunoprecipitations) of protein binding. Result: Characterization of the ribonucleoprotein composition of this region revealed several human proteins as interactors: regulatory proteins hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1), hnRNP U, HuR (human antigen R), and PSF (polypyrimidine tract-binding protein-associated splicing factor), as well as, unexpectedly, the cytoskeletal protein actin. Treatment of EBV-infected cells with drugs that alter actin polymerization specifically showed marked effects on splicing in this region. This suggests a potentially novel role for nuclear actin in regulation of viral RNA splicing.
Familial acanthosis nigricans with the FGFR3 mutation: Differences of pigmentation between male and female patients
Authors: Yasuda Masahito , Morimoto Naoko , Shimizu Akira , Toyoshima Takae , Yokoyama Yoko , Ishikawa Osamu 
Published: August 2018

AbstractFamilial acanthosis nigricans caused by the mutation of the fibroblast growth factor receptor 3 (FGFR3) gene is characterized by short stature, hypochondroplasia and acanthosis nigricans. We herein report a Japanese family that showed a missense mutation of c.1948A>C (p.K650Q) in FGFR3. The pigmentation of acanthosis nigricans was more prominent in male patients than in female patients in this family. We immunohistochemically analyzed the distribution of melanocytes. Although pigmentation in the basal layer was denser in the proband, there was no difference in the distribution and number of melanocytes.
How Monetary Policy Affects Your Gross Domestic Product
Authors: Haldane Andrew G 
Published: August 2018

AbstractDuring the financial crisis, monetary policy was loosened significantly. Debate continues about the extent to which low interest rates and quantitative easing (QE) may have had adverse distributional impacts, whether by income, wealth, age or region. Using quantified simulations on micro data, I show that looser monetary policy had a significantly positive financial impact on the majority of cohorts of UK society. The impact of monetary policy loosening on income and wealth inequality was small and the overall impact on household welfare significantly positive. These results differ from public perceptions of monetary policy. Personalised information on the impact of monetary policy on household balance sheets could help to correct these misperceptions.
Meadow Restoration Increases Baseflow and Groundwater Storage in the Sierra Nevada Mountains of California
Authors: Hunt Luke J.H. , Fair Julie , Odland Maxwell 
Published: August 2018

AbstractIn mountains of the western United States, channel incision has drawn down the water table across thousands of square kilometers of meadow floodplain. Here climate change is resulting in earlier melt and reduced snowpack and water resource managers are responding by investing in meadow restoration to increase springtime storage and summer flows. The record‐setting California drought (2012–2015) provided an opportunity to evaluate this strategy under the warmer and drier conditions expected to impact mountain water supplies. In 2012, 0.1 km2 of meadow floodplain was reconnected by filling an incised channel through Indian Valley in the central Sierra Nevada Mountains of California. Despite sustained drought conditions after restoration, summer baseflow from the meadow increased 5–12 times. Before restoration, the total summer outflow from the meadow was 5% more than the total summer inflow. After restoration, total summer outflow from the meadow was between 35% and 95% more than total summer inflow. In the worst year of the drought (2015), when inflow to the meadow ceased for at least one month, summer baseflow was at least five times greater than before restoration. Groundwater levels also rose at four out of five sites near the stream channel. Filling the incised channel and reconnecting the meadow floodplain increased water availability and streamflow, despite unprecedented drought conditions.
Early onset neutropenia and thrombocytopenia following rituximab in lupus nephritis
Authors: Shah Sanket , Kavadichanda Chengappa G. , Belani Pooja , Ganesh Rajesh N. , Negi Vir Singh 
Published: August 2018

AbstractBiologics have emerged as an important modality of treatment in rheumatic diseases and have allowed the rheumatologist to explore varied therapeutic uses of these drugs. Rituximab, a monoclonal antibody against CD20 receptor is an important member of the biologic armamentarium for the treatment of various refractory autoimmune inflammatory rheumatic diseases. The drug is now widely used in systemic lupus erythematosus for several complications which are refractory to conventional therapy. Although relatively safe, the post‐marketing surveillance of rituximab has revealed a few rare but important adverse reactions. Cytopenia including neutropenia following rituximab, has been vastly reported as a late event (>4 weeks), but a few cases of early onset neutropenia (EON) and thrombocytopenia are also found in the literature. We describe a case of a 35‐year‐old woman with refractory lupus nephritis who developed asymptomatic EON and thrombocytopenia following rituximab infusion. The neutropenia responded well to granulocyte colony‐stimulating factor treatment and the platelets spontaneously recovered. This case report is aimed at highlighting the importance of identifying early onset cytopenia following rituximab which may have an important bearing on the final outcome for the patient.
Exploring population responses to environmental change when there is never enough data: a factor analytic approach
Authors: Hindle Bethan J. , Rees Mark , Sheppard Andy W. , Quintana‐Ascencio Pedro F. , Menges Eric S. , Childs Dylan Z. 
Published: August 2018

Abstract

Temporal variability in the environment drives variation in vital rates, with consequences for population dynamics and life‐history evolution. Integral projection models (IPMs) are data‐driven structured population models widely used to study population dynamics and life‐history evolution in temporally variable environments. However, many datasets have insufficient temporal replication for the environmental drivers of vital rates to be identified with confidence, limiting their use for evaluating population level responses to environmental change.

Parameter selection, where the kernel is constructed at each time step by randomly selecting the time‐varying parameters from their joint probability distribution, is one approach to including stochasticity in IPMs. We consider a factor analytic (FA) approach for modelling the covariance matrix of time‐varying parameters, whereby latent variable(s) describe the covariance among vital rate parameters. This decreases the number of parameters to estimate and, where the covariance is positive, the latent variable can be interpreted as a measure of environmental quality. We demonstrate this using simulation studies and two case studies.

The simulation studies suggest the FA approach provides similarly accurate estimates of stochastic population growth rate to estimating an unstructured covariance matrix. We demonstrate how the latent parameter can be perturbed to show how selection on reproductive delays in the monocarp Carduus nutans changes under different environmental conditions. We develop a demographic model of the fire dependent herb Eryngium cuneifolium to show how a putative driver of the variation in environmental quality can be incorporated with the addition of a single parameter. Using perturbation analyses we determine optimal management strategies for this species.

This approach estimates fewer parameters than previous approaches and allows novel eco‐evolutionary insights. Predictions on population dynamics and life‐history evolution under different environmental conditions can be made without necessarily identifying causal factors. Putative environmental drivers can be incorporated with relatively few parameters, allowing for predictions on how populations will respond to changes in the environment.