bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin signalling's role in mediating tissue-specific nutritional plasticity and robustness in the horn-polyphenic beetleOnthophagus taurus
Authors: Casasa Sofia , Moczek Armin P.
Published: December 2018

Organisms cope with nutritional variation via developmental plasticity, adjusting trait size to nutrient availability for some traits while enabling others to develop in a nutritionally robust manner. Yet, the developmental mechanisms that regulate organ-specific growth across nutritional gradients remain poorly understood. We assessed the functions of members of the insulin/insulin-like signalling pathway (IIS) in the regulation of nutrition sensitivity and robustness in males of the horn-polyphenic beetleOnthophagus taurus, as well as potential regulatory interactions between IIS and two other growth-regulating pathways: Doublesex and Hedgehog signalling. Using RNAinterference(RNAi), we experimentally knocked down both insulin receptors (InR1andInR2) and Foxo, a growth inhibitor. We then performed morphometric measurements on horns, a highly nutrition-sensitive trait, and genitalia, a largely nutrition-insensitive trait. Finally, we used quantitative real-time polymerase chain reaction to assess expression levels ofdoublesexand the Hedgehog signalling genesmoothenedfollowing IIS-RNAi. Our results suggest that nutrition responsiveness of both traits is regulated by different IIS components, which transduce nutritional conditions to both Doublesex and Hedgehog pathways, albeit via different IIS pathway members. Combined with previous studies, our findings suggest that separate origins of trait exaggeration among insect lineages were enabled through the independent co-option of IIS, yet via reliance on different components therein.
Factors influencing within-group conflict over defence against conspecific outsiders seeking breeding positions
Authors: Schindler Susanne , Radford Andrew N.
Published: December 2018

In social species, groups face a variety of threats from conspecific outsiders. Defensive actions are therefore common, but there is considerable variation in which individuals contribute and to what extent. There has been some theoretical exploration of this variation when the defence is of shared resources, but the relative contributions when a single intruder threatens a particular breeding position have received less attention. Defensive actions are costly, both for the individual and dependent young, and contributions are likely to differ depending on individual sex, rank and size, current breeding stage, infanticide risk and relatedness levels. Here, we model analytically the relative fitness benefits of different group members to engaging in defence against individual intruders and determine when within-group conflicts of interest might arise over these defensive contributions. Conflicts of interest between the challenged breeder and other group members depend on relatedness to the brood and the potential relatedness reduction if an intruder acquires breeding status. Conflicts are more likely to occur when there is a low chance of winning the contest, low infanticide rates, inefficient defence from helpers, a long remaining brood-dependency period and high external (non-contest-related) mortality. Our work can help explain variation in defensive actions against out-group threats.
Consequences of sex change for effective population size
Authors: Waples Robin S. , Mariani Stefano , Benvenuto Chiara
Published: December 2018

Sequential hermaphroditism, where males change to females (protandry) or the reverse (protogyny), is widespread in animals and plants, and can be an evolutionarily stable strategy (ESS) if fecundity rises faster with age in the second sex. Sequential hermaphrodites also generally have sex ratios skewed towards the initial sex, and standard theory based on fixed sexes indicates that this should reduce effective population size (Ne) and increase the deleterious effects of genetic drift. We show that despite having skewed sex ratios, populations that change sex at the ESS age do not have reducedNecompared with fixed-sex populations with an even sex ratio. This implies that the ability of individuals to operate as both male and female allows the population to avoid some evolutionary constraints imposed by fixed sexes. Furthermore,Newould be maximized if sex change occurred at a different (generally earlier) age than is selected for at the individual level, which suggests a potential conflict between individual and group selection. We also develop a novel method to quantify the strength of selection for sex reversal.
Observing grooming promotes affiliation in Barbary macaques
Authors: Berthier Juliette M. , Semple Stuart
Published: December 2018

Observing friendly social interactions makes people feel good and, as a result, then act in an affiliative way towards others. Positive visual contagion of this kind is common in humans, but whether it occurs in non-human animals is unknown. We explored the impact on female Barbary macaques of observing grooming, a behaviour that physiological and behavioural studies indicate has a relaxing effect on the animals involved. We compared females' behaviour between two conditions: after observing conspecifics groom, and in a matched control period. We found that observing grooming was associated with reduced behavioural indicators of anxiety, suggesting that seeing others groom is, in itself, relaxing. Observing grooming was also associated with a shorter latency to becoming involved in a grooming bout (and higher likelihood both of initiating that bout and being the groomer rather than groomee), and with elevated rates of other affiliative behaviours. These results provide evidence for positive visual contagion; this phenomenon may contribute fundamentally to group cohesion not just in this species, but also in the many mammal and bird species where grooming occurs. Our study highlights the importance of exploring social behaviour beyond the level of the interacting individuals, within the broader social context where it occurs.
Metabolic physiology explains macroevolutionary trends in the melanic colour system across amniotes
Authors: Eliason Chad M. , Clarke Julia A.
Published: December 2018

Metabolism links organisms to their environment through its effects on thermoregulation, feeding behaviour and energetics. Genes involved in metabolic processes have known pleiotropic effects on some melanic colour traits. Understanding links between physiology and melanic colour is critical for understanding the role of, and potential constraints on, colour production. Despite considerable variation in metabolic rates and presumed ancestral melanic coloration in vertebrates, few studies have looked at a potential relationship between these two systems in a comparative framework. Here, we test the hypothesis that changes in melanosome shape in integumentary structures track metabolic rate variation across amniotes. Using multivariate comparative analyses and incorporating both extant and fossil taxa, we find significantly faster rates of melanosome shape evolution in taxa with high metabolic rates, as well as both colour- and clade-specific differences in the relationship between metabolic rate and melanosome shape. Phylogenetic tests recover an expansion in melanosome morphospace in maniraptoran dinosaurs, as well as rate shifts within birds (in songbirds) and mammals. These findings indicate another core phenotype influenced by metabolic changes in vertebrates. They also provide a framework for testing clade-specific gene expression patterns in the melanocortin system and may improve colour reconstructions in extinct taxa.
Variability and repeatability of noctule bat migration in Central Europe: evidence for partial and differential migration
Authors: Lehnert Linn S. , Kramer-Schadt Stephanie , Teige Tobias , Hoffmeister Uwe , Popa-Lisseanu Ana , Bontadina Fabio , Ciechanowski Mateusz , Dechmann Dina K. N. , Kravchenko Kseniia , Presetnik Priemoz , Starrach Martin , Straube Michael , Zoephel Ulrich , Voigt Christian C.
Published: December 2018

Each year, large numbers of bats move across Europe between their summer and winter areas, yet even though many of them are endangered and legally protected, we are unaware about many aspects of their migratory behaviour. Here, takingNyctalus noctulaas a model species, we used stable hydrogen isotopic values in fur (δ2Hf) as an endogenous marker to shed light on the migratory behaviour of more than 1000 bats from hibernacula across Central Europe. Specifically, we asked the following questions: how flexible is migration in temperate zone bats? Which general migration pattern do noctule bats follow? How repeatable and thus predictable is the migratory behaviour of individuals? Do morphological correlates of migration occur in bats? Our study confirmed that noctule bats engage in partial and female-biased migration across Europe, suggesting the strongest migration pressures for northern populations. Further, we revealed a combination of partial and differential migration patterns with highly variable migration distances which lead to a pronounced mixing of different source populations in hibernacula where mating occurs. Most individuals were consistent in their migration strategy over time, i.e. 86% could be repeatedly assigned to either long-distance or regional origin across years. This is consistent with our finding that the between-individual component explained 84% of the variation inδ2Hfvalues, suggesting specialized individual migratory behaviours and a strong natal philopatry. We discovered a positive correlation between forearm length and migration distance and support for sex-specific effects of migration on body condition. Our study elucidated migration patterns over large geographical scales, demonstrating that considerable numbers of migratory bats originating from distant populations depend on hibernacula across Central Europe, calling for international conservation management.
Household members do not contact each other at random: implications for infectious disease modelling
Authors: Goeyvaerts Nele , Santermans Eva , Potter Gail , Torneri Andrea , Van Kerckhove Kim , Willem Lander , Aerts Marc , Beutels Philippe , Hens Niel
Published: December 2018

Airborne infectious diseases such as influenza are primarily transmitted from human to human by means of social contacts, and thus easily spread within households. Epidemic models, used to gain insight into infectious disease spread and control, typically rely on the assumption of random mixing within households. Until now, there has been no direct empirical evidence to support this assumption. Here, we present the first social contact survey specifically designed to study contact networks within households. The survey was conducted in Belgium (Flanders and Brussels) from 2010 to 2011. We analysed data from 318 households totalling 1266 individuals with household sizes ranging from two to seven members. Exponential-family random graph models (ERGMs) were fitted to the within-household contact networks to reveal the processes driving contact between household members, both on weekdays and weekends. The ERGMs showed a high degree of clustering and, specifically on weekdays, decreasing connectedness with increasing household size. Furthermore, we found that the odds of a contact between older siblings and between father and child are smaller than for any other pair. The epidemic simulation results suggest that within-household contact density is the main driver of differences in epidemic spread between complete and empirical-based household contact networks. The homogeneous mixing assumption may therefore be an adequate characterization of the within-household contact structure for the purpose of epidemic simulations. However, ignoring the contact density when inferring based on an epidemic model will result in biased estimates of within-household transmission rates. Further research regarding the implementation of within-household contact networks in epidemic models is necessary.
Torpor reduces predation risk by compensating for the energetic cost of antipredator foraging behaviours
Authors: Turbill Christopher , Stojanovski Lisa
Published: December 2018

Foraging activity is needed for energy intake but increases the risk of predation, and antipredator behavioural responses, such as reduced activity, generally reduce energy intake. Hence, the mortality and indirect effects of predation risk are dependent on the energy requirements of prey. Torpor, a controlled reduction in resting metabolism and body temperature, is a common energy-saving mechanism of small mammals that enhances their resistance to starvation. Here we test the hypothesis that torpor could also reduce predation risk by compensating for the energetic cost of antipredator behaviours. We measured the foraging behaviour and body temperature of house mice in response to manipulation of perceived predation risk by adjusting levels of ground cover and starvation risk by 24 h food withdrawal every third day. We found that a voluntary reduction in daily food intake in response to lower cover (high predation risk) was matched by the extent of a daily reduction in body temperature. Our study provides the first experimental evidence of a close link between energy-saving torpor responses to starvation risk and behavioural responses to perceived predation risk. By reducing the risk of starvation, torpor can facilitate stronger antipredator behaviours. These results highlight the interplay between the capacity for reducing metabolic energy expenditure, optimal decisions about foraging behaviour and the life-history ecology of prey.
Disturbance reverses classic biodiversity predictions in river-like landscapes
Authors: Harvey Eric , Gounand Isabelle , Fronhofer Emanuel A. , Altermatt Florian
Published: December 2018

Global analyses of biodiversity consistently reveal recurrent patterns of species distributions worldwide. However, unveiling the specific mechanisms behind those patterns remains logistically challenging, yet necessary for reliable biodiversity forecasts. Here, we combine theory and experiments to investigate the processes underlying spatial biodiversity patterns in dendritic, river-like landscapes, iconic examples of highly threatened ecosystems. We used geometric scaling properties, common to all rivers, to show that the distribution of biodiversity in these landscapes fundamentally depends on how ecological selection is modulated across space: while uniform ecological selection across the network leads to higher diversity in downstream confluences, this pattern can be inverted by disturbances when population turnover (i.e. local mortality) is higher upstream than downstream. Higher turnover in small headwater patches can slow down ecological selection, increasing local diversity in comparison to large downstream confluences. Our results show that disturbance-mediated slowing down of competitive exclusion can generate a specific transient signature in terms of biodiversity distribution when applied over a spatial gradient of disturbance, which is a common feature of many river landscapes.
Better than expected: the influence of option expectations during decision-making
Authors: Rigoli Francesco , Dolan Raymond
Published: December 2018

Our choices often arise from a consideration of options presented in a sequence (e.g. the products in a supermarket row). However, whether the precise sequential order of option presentation affects decision-making remains poorly understood. A recent model of choice proposes that, in a set of options presented sequentially, those that are better than expected will be perceived as more valuable, even when options are objectively equivalent within the set. Inspired by this proposal, we devised a novel decision-making task where we manipulated the order of option presentation together with expectations about option value. Even when we compared trials that were exactly equivalent except for option order, we observed a striking preference for options that were better than expected. Our findings show that expectations about options affect which option will be favoured within a sequence, an influence which is manifested as a preference for better-than-expected options. The findings have potential practical implications, as for example they may help policymakers in devising nudge strategies that rely on ad hoc option orders.
Macropinosomes as units of signal transduction
Authors: Swanson Joel A. , Yoshida Sei
Published: December 2018

Macropinosome formation occurs as a localized sequence of biochemical activities and associated morphological changes, which may be considered a form of signal transduction leading to the construction of an organelle. Macropinocytosis may also convey information about the availability of extracellular nutrients to intracellular regulators of metabolism. Consistent with this idea, activation of the metabolic regulator mechanistic target of rapamycin complex-1 (mTORC1) in response to acute stimulation by growth factors and extracellular amino acids requires internalization of amino acids by macropinocytosis. This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway. Because the biochemical signals required for the construction of macropinosomes are also required for cell growth, and inhibition of macropinocytosis inhibits growth factor signalling to mTORC1, we propose that signalling by growth factor receptors is organized into stochastic, structure-dependent cascades of chemical reactions that both build a macropinosome and stimulate mTORC1. More generally, as discrete units of signal transduction, macropinosomes may be subject to feedback regulation by metabolism and cell dimensions.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Vibrio cholerae O6 gastroenteritis in a patient with lupus nephritis – a report from coastal Karnataka, South India
Authors: Ballal Mamatha , Shetty Vignesh , Bangera Sohan Rodney , Mukhopadhyay Asish , Chowdhury Goutam , Samanta Prosenjit , Prabhu Akshata , Anusha H. C.
Published: December 2018

Introduction.
Vibrio cholerae O1 strains are responsible for pandemics of cholera and major epidemics in the world. All the remaining V. cholerae non-O1/non-O139 strains are less virulent and are responsible for sporadic cases of gastroenteritis. These non-O1/non-O139 serogroups have more than 200 somatic antigens, and mostly lack cholera toxin and toxin co-regulated pilus encoding genes. Toxigenic and non-toxigenic non-O1/non-O139 V. cholerae have caused several diarrhoeal outbreaks in India and other countries. Acute gastroenteritis is the typical clinical sign and symptom of non-O1/non-O139 V. cholerae infection for both periodical and outbreak cases; in contrast, these V. cholerae are rarely associated with extraintestinal infections.

Case presentation. Here, we present a case of a 27-year-old female with underlying kidney disease (lupus nephritis) presenting with loose stools, vomiting and fever. V. cholerae O6 was isolated from a faecal sample, which was positive for hlyA and the type III secretion system. The present case is, to the best of our knowledge, the first such case to be reported from South India.

Conclusion. The V. cholerae O6 associated with autoimmune disease in the present study demonstrates the role of this pathogen in acute gastroenteritis, and if it is left undiagnosed it can lead to septicaemia and other complications. The pathogenic mechanisms of non-O1/non-O139 V. cholerae are multivariate, virulence factors being naturally present in these strains. Therefore, further epidemiological studies are necessary to determine the virulence factors and their pathogenic mechanisms. Non-O1/non-O139 V. cholerae can undoubtedly be the cause of diarrhoea and it would be important to extend bacteriological identification in this line as well as in all cases of gastroenteritis of unknown aetiology.
Successful exome capture and sequencing in lemurs using human baits
Authors: Webster Timothy H. , Guevara Elaine E. , Lawler Richard R. , Bradley Brenda J.
Published: December 2018

Objectives

We assessed the efficacy of exome capture in lemurs using commercially available human baits.

Materials and Methods

We used two human kits (Nimblegen SeqCap EZ Exome Probes v2.0; IDT xGen Exome Research Panel v1.0) to capture and sequence the exomes of wild Verreaux’s sifakas (Propithecus verreauxi,n = 8), a lemur species distantly related to humans. For comparison, we also captured exomes of a primate species more closely related to humans (Macaca mulatta,n= 4). We mapped reads to both the human reference assembly and the most closely related reference for each species before calling variants. We used measures of mapping quality and read coverage to compare capture success.

Results

We observed high and comparable mapping qualities for both species when mapped to their respective nearest-relative reference genomes. When investigating breadth of coverage, we found greater capture success in macaques than sifakas using both nearest-relative and human assemblies. Exome capture in sifakas was still highly successful with more than 90% of annotated coding sequence in the sifaka reference genome captured, and 80% sequenced to a depth greater than 7x using Nimblegen baits. However, this success depended on probe design: the use of IDT probes resulted in substantially less callable sequence at low-to-moderate depths.

Discussion

Overall, we demonstrate successful exome capture in lemurs using human baits, though success differed between kits tested. These results indicate that exome capture is an effective and economical genomic method of broad utility to evolutionary primatologists working across the entire primate order.
Model Annotation and Discovery with the Physiome Model Repository
Authors: Sarwar Dewan M , Kalbasi Reza , Gennari John H , Carlson Brian E , Neal Maxwell L , Bono Bernard de , Atalag Koray , Hunter Peter J , Nickerson David P
Published: December 2018

Motivation: Mathematics and physics based computational models have the potential to help interpret and encapsulate biological phenomena in a computable and reproducible form. Similarly, comprehensive descriptions of such models encoded in computable form help to ensure that such models are accessible, discoverable, and reusable. To this end, researchers have developed tools and standards to encode mathematical models of biological systems enabling reproducibility and reuse; tools and guidelines to facilitate semantic description of mathematical models; and repositories in which to archive, share, and discover models. Biologists and clinicians can leverage these resources to investigate specific questions and hypotheses. Results: We have comprehensively annotated a cohort of models with biological semantics. These annotated models are freely available in the Physiome Model Repository (PMR). To demonstrate the benefits of this approach, we have developed a web-based tool which enables users to discover models relevant to their work, with a particular focus on epithelial transport. In helping a user to discover relevant models this tool will provide users with suggestions for similar or alternative models they may wish to explore or utilize in their model based on the models they would like to use. The semantic annotation and the web tool we have developed is a new contribution enabling scientists to discover relevant models in the PMR as candidates for reuse in their own scientific endeavours. We believe that this approach demonstrates how semantic web technologies and methodologies can contribute to biomedical and clinical research. Availability and implementation: https://github.com/dewancse/model-discovery-tool
iScore: A novel graph kernel-based function for scoring protein-protein docking models
Authors: Geng Cunliang , Jung Yong , Renaud Nicolas , Honavar Vasant , Bonvin Alexandre M.J.J. , Xue Li C.
Published: December 2018

Protein complexes play a central role in many aspects of biological function. Knowledge of the three-dimensional (3D) structures of protein complexes is critical for gaining insights into the structural basis of interactions and their roles in the biomolecular pathways that orchestrate key cellular processes. Because of the expense and effort associated with experimental determination of 3D structures of protein complexes, computational docking has evolved as a valuable tool to predict the 3D structures of biomolecular complexes. Despite recent progress, reliably distinguishing near-native docking conformations from a large number of candidate conformations, the so-called scoring problem, remains a major challenge. Here we present iScore, a novel approach to scoring docked conformations that combines HADDOCK energy terms with a score obtained using a graph representation of the protein-protein interfaces and a measure of evolutionary conservation. It achieves a scoring performance competitive with, or superior to that of the state-of-the-art scoring functions on independent data sets consisting docking software-specific data sets and the CAPRI score set built from a wide variety of docking approaches. iScore ranks among the top scoring approaches on the CAPRI score set (13 targets) when compared with the 37 scoring groups in CAPRI. The results demonstrate the utility of combining evolutionary and topological, and physicochemical information for scoring docked conformations. This work represents the first successful demonstration of graph kernel to protein interfaces for effective discrimination of near-native and non-native conformations of protein complexes. It paves the way for the further development of computational methods for predicting the structure of protein complexes.
Iso-propyl stilbene: A life-cycle signal?
Authors: Hapeshi Alexia , Benarroch Jonatan Mimon , Clarke David James , Waterfield Nicholas Robin
Published: December 2018

Members of the Gram-negative bacterial genusPhotorhabdusare all highly insect pathogenic and exist in an obligate symbiosis with the entomopathogenic nematode wormHeterorhabditis. All members of the genus produce the small molecule 3,5-dihydroxy-4-isopropyl-trans-stilbene (IPS) as part of their secondary metabolism. IPS is a multi-potent compound that has antimicrobial, antifungal and anticancer activities and also plays an important role in symbiosis with the nematode. In this study we have examined the response ofPhotorhabdusitself to exogenous ectopic addition of IPS at physiologically relevant concentrations. We observed that the bacteria had a measureable phenotypic response, which included a decrease in bioluminescence and pigment production. This was reflected in changes in its transcriptomic response, in which we reveal a reduction in transcript levels of genes relating to many fundamental cellular processes, such as translation and oxidative phosphorylation. Our observations suggest that IPS plays an important role in the biology ofPhotorhabdusbacteria, fulfilling roles in quorum sensing, antibiotic-competition advantage and maintenance of the symbiotic developmental cycle.
Implementation of an antibody characterization process: Application to the major ALS/FTD disease gene C9ORF72
Authors: Laflamme Carl , McKeever Paul , Kumar Rahul , Schwartz Julie , Chen Carol X.-Q. , You Zhipeng , Xiao Shangxi , Benaliouad Faiza , Gileadi Opher , McBride Heidi M. , Durcan Thomas M. , Edwards Aled , Robertson Janice , McPherson Peter S.
Published: December 2018

Rigorously characterized antibodies are a key resource in biomedical research, yet there are no community-accepted processes to characterize the quality of research grade antibodies. This has led to a proliferation of poorly characterized antibodies of suspect quality, which in turn has led to flaws in the literature that hamper research progress, including the study of human disease. We selected the human protein C9ORF72 as a test case to implement a more standardized antibody characterization process. Mutations in the gene C9ORF72 are the major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia but much remains unknown regarding the function of the encoded protein. We used CRISPR/Cas9-based knockout cells and knockout mice as controls to characterize 14 C9ORF72 antibodies including 12 commercially available antibodies advertised as selective for C9ORF72. We found one monoclonal antibody that is specific for the protein in immunoblot and that also recognizes C9ORF72 specifically in immunohistochemical applications on brain sections. A second C9ORF72 monoclonal antibody is effective for immunoprecipitation and immunofluorescence. Some of the antibodies that do not recognize C9ORF72 have been used in highly cited papers, raising concern over conclusions regarding previously reported C9ORF72 properties.
G-OnRamp: A Galaxy-based platform for creating genome browsers for collaborative genome annotation
Authors: Liu Yating , Sargent Luke , Leung Wilson , Elgin Sarah C.R. , Goecks Jeremy
Published: December 2018

Summary: G-OnRamp provides a user-friendly, web-based platform for collaborative, end-to-end annotation of eukaryotic genomes using UCSC Assembly Hubs and JBrowse/Apollo genome browsers with evidence tracks derived from sequence alignments, ab initio gene predictors, RNA-Seq data, and repeat finders. Researchers can use the G-OnRamp output to visualize large genomics datasets, and can utilize the output to drive collaborative genome annotation projects in both research and educational settings. Availability and Implementation: The G-OnRamp virtual machine images and tutorials are freely available on the G-OnRamp web site (http://g-onramp.org/deployments). The G-OnRamp source code is freely available under an Academic Free License version 3.0 through the goeckslab GitHub repository (https://github.com/goeckslab). Contact: goecksj@ohsu.edu
SGK phosphorylates Cdc25 and Myt1 to trigger cyclin B-Cdk1 activation at the meiotic G2/M transition
Authors: Hiraoka Daisaku , Hosoda Enako , Chiba Kazuyoshi , Kishimoto Takeo
Published: December 2018

The kinase cyclin B-Cdk1 complex is a master regulator of M-phase in both mitosis and meiosis. At the G2/M transition, cyclin B-Cdk1 activation is initiated by a trigger that reverses the balance of activities between Cdc25 and Wee1/Myt1, and is further accelerated by autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to be the cyclin A-Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce cyclin B-Cdk1 activation, cyclin A-Cdk1 is non-essential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger cyclin B-Cdk1 activation in starfish oocytes. After hormonal stimulation of the meiotic G2/M transition, SGK is activated by cooperation between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.
Introducing THOR, a model microbiome for genetic dissection of community behavior
Authors: Lozano Gabriel L , Bravo Juan I , Garavito Diago Manuel F , Park Hyun Bong , Hurley Amanda , Peterson S Brook , Stabb Eric V , Crawford Jason M , Broderick Nichole A , Handelsman Jo
Published: December 2018

The quest to manipulate microbiomes has intensified, but many microbial communities have proven recalcitrant to sustained change. Developing model communities amenable to genetic dissection will underpin successful strategies for shaping microbiomes by advancing understanding of community interactions. We developed a model community with representatives from three dominant rhizosphere taxa: the Firmicutes, Proteobacteria, and Bacteroidetes. We chose Bacillus cereus as a model rhizosphere Firmicute and characterized twenty other candidates, including hitchhikers that co-isolated with B. cereus from the rhizosphere. Pairwise analysis produced a hierarchical interstrain-competition network. We chose two hitchhikers - Pseudomonas koreensis from the top tier of the competition network and Flavobacterium johnsoniae from the bottom of the network to represent the Proteobacteria and Bacteroidetes, respectively. The model community has several emergent properties - induction of dendritic expansion of B. cereus colonies by either of the other members and production of more robust biofilms by the three members together than individually. Moreover, P. koreensis produces a novel family of alkaloid antibiotics that inhibit growth of F. johnsoniae, and production is inhibited by B. cereus. We designate this community THOR, because the members are the hitchhikers of the rhizosphere. The genetic, genomic, and biochemical tools available for dissection of THOR provide the means to achieve a new level of understanding of microbial community behavior.
In vitro activity of the new β-lactamase inhibitors relebactam and vaborbactam in combination with β-lactams against Mycobacterium abscessus complex clinical isolates
Authors: Kaushik Amit , Ammerman Nicole C. , Lee Jin , Martins Olumide , Kreiswirth Barry N , Lamichhane Gyanu , Parrish Nicole M , Nuermberger Eric
Published: December 2018

Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to MABC’s intrinsic resistance to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC to some β-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-β-lactam-based β-lactamase inhibitors, relebactam and vaborbactam, would also increase susceptibility of MABC to β-lactams. The objective of the present study was to evaluate the in vitro activity of various marketed β-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both β-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem/vaborbactam combination is now marketed and an imipenem/relebactam combination is currently in phase III trials, these fixed combinations may become the β-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual β-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a β-lactamase inhibitor, deserving of further evaluation in combination with these carbapenem/β-lactamase inhibitor products.
Effect of KNL1 on the proliferation and apoptosis of colorectal cancer cells
Authors: Bai Tianliang , Liu Yabin , Li Binghui
Published: December 2018

Background: To identify the expression of KNL1 in colorectal tumor tissues and to clarify the function of this gene on the proliferation capability of colorectal cancer cells.
Methods: Thirty-six pairs of colorectal tumor and normal tissue were collected and subjected to quantitative PCR analysis. KNL1 was under-expressed using lentiviral transfection, and the function of KNL1 was evaluated by proliferation assay, colony formation and apoptosis assay.
Results: KNL1 was highly expressed in colorectal tumor tissues. KNL1 downregulation inhibited colorectal cancer cell proliferation and promoted apoptosis.
Conclusions: KNL1 plays an effective role in decreasing the apoptosis and promoting the proliferation of colorectal cancer cells.
FERARI: a novel tether involved in endocytic recycling
Authors: Solinger Jachen A , Raschid Harun-Or , Spang Anne
Published: December 2018

Endosomal transport is essential for cellular organization and compartmentalization and cell-cell communication. Sorting endosomes provide a crossroad for various trafficking pathways and determine recycling, secretion or degradation of proteins. The organisation of these processes requires membrane tethering factors to coordinate Rab GTPase function with membrane fusion. Here, we report a conserved tethering complex that acts in the Rab11 recycling pathways at sorting endosomes, which we name FERARI (Factor for Endosome Recycling And Retromer Interactions). The Rab binding module of FERARI consists of Rab11FIP5/RFIP-2 and rabenosyn-5/RABS-5, while the SNARE interacting module comprises VPS45 and VIPAS39/SPE-39. Unexpectedly, the membrane fission protein EHD1/RME-1 is also a FERARI component. Thus, FERARI appears to combine fusion activity through the SM protein VPS45 with pinching activity through EHD1/RME-1 on SNX-1-positive endosomal membranes. We propose that coordination of fusion and pinching through a kiss-and-stay mechanism drives sorting at endosomes into recycling pathways.
Pandoravirus celtis illustrates the microevolution processes at work in the giant Pandoraviridae genomes
Authors: Legendre Matthieu , Alempic Jean-Marie , Philippe Nadège , Lartigue Audrey , Jeudy Sandra , Poirot Olivier , Ta Ngan Thi , Nin Sébastien , Couté Yohann , Abergel Chantal , Claverie Jean-Michel
Published: December 2018

With genomes of up to 2.7 Mb propagated in µm-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including 3 others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, P. celtis, closely related (96% identical genome) to the previously described P. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs (ORFans), with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in P. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase.
Nanobody Detection of Standard Fluorescent Proteins Enables Multi-Target DNA-PAINT with High Resolution and Minimal Displacement Errors
Authors: Sograte-Idrissi Shama , Oleksiievets Nazar , Isbaner Sebastian , Eggert-Martinez Mariana , Enderlein Jörg , Tsukanov Roman , Opazo Felipe
Published: December 2018

DNA-PAINT is a rapidly developing fluorescence super-resolution technique which allows for reaching spatial resolutions below 10 nm. It also enables the imaging of multiple targets in the same sample. However, using DNA-PAINT to observe cellular structures at such resolution remains challenging. Antibodies, which are commonly used for this purpose, lead to a displacement between the target protein and the reporting fluorophore of 20-25 nm, thus limiting the resolving power. Here, we used nanobodies to minimize this linkage error to ~4 nm. We demonstrate multiplexed imaging by using 3 nanobodies, each able to bind to a different family of fluorescent proteins. We couple the nanobodies with single DNA strands via a straight forward and stoichiometric chemical conjugation. Additionally, we built a versatile computer-controlled microfluidic setup to enable multiplexed DNA-PAINT in an efficient manner. As a proof of principle, we labeled and imaged proteins on mitochondria, the Golgi apparatus, and chromatin. We obtained super-resolved images of the 3 targets with 20 nm resolution, and within only 35 minutes acquisition time.
SimNIBS 2.1: A Comprehensive Pipeline for Individualized Electric Field Modelling for Transcranial Brain Stimulation
Authors: Saturnino Guilherme B. , Puonti Oula , Nielsen Jesper D , Antonenko Daria , Madsen Kristoffer Hougaard H , Thielscher Axel
Published: December 2018

Numerical simulation of the electric fields induced by Non-Invasive Brain Stimulation (NIBS), using realistic anatomical head models has gained interest in recent years for understanding the NIBS effects in individual subjects. Although automated tools for generating the head models and performing the electric field simulations have become available, individualized modelling is still not standard practice in NIBS studies. This is likely partly explained by the lack of robustness and usability of the previously available software tools, and partly by the still developing understanding of the link between physiological effects and electric field distributions in the brain. To facilitate individualized modelling in NIBS, we have introduced the SimNIBS (Simulation of NIBS) software package, providing easy-to-use automated tools for electric field modelling. In this article, we give an overview of the modelling pipeline in SimNIBS 2.1, with step-by-step examples of how to run a simulation. Furthermore, we demonstrate a set of scripts for extracting average electric fields for a group of subjects, and finally demonstrate the accuracy of automated placement of standard electrode montages on the head model. SimNIBS 2.1 is freely available at www.simnibs.org.
Antibody-mediated immobilization of virions in mucus
Authors: Jensen Melanie A. , Wang Ying-Ying , Lai Samuel K. , Forest M. Gregory , McKinley Scott A.
Published: December 2018

Antibodies have been shown to hinder the movement of Herpes Simplex Virus (HSV) virions in cervicovaginal mucus (CVM), as well as other viruses in other mucus secretions. However, it has not been possible to directly observe the mechanisms underlying this phenomenon, so the nature of virion-antibody-mucin interactions remain poorly understood. In this work, we analyzed thousands of virion traces from single particle tracking experiments to explicate how antibodies must cooperate to immobilize virions for relatively long time periods. First, using a clustering analysis, we observed a clear separation between two classes of virion behavior: Freely Diffusing and Immobilized. While the proportion of Freely Diffusing virions decreased with antibody concentration, the magnitude of their diffusivity did not, implying an all-or-nothing dichotomy in the pathwise effect of the antibodies. Proceeding under the assumption that all binding events are reversible, we used a novel switch-point detection method to conclude that there are very few, if any, state-switches on the experimental time scale of twenty seconds. To understand this slow state-switching, we analyzed a recently proposed continuous-time Markov chain model for binding kinetics and virion movement. Model analysis implied that virion immobilization requires cooperation by multiple antibodies that are simultaneously bound to the virion and mucin matrix, and that there is an entanglement phenomenon that accelerates antibody-mucin binding when a virion is immobilized. In addition to developing a widely-applicable framework for analyzing multi-state particle behavior, this work substantially enhances our mechanistic understanding of how antibodies can reinforce a mucus barrier against passive invasive species.
Functional characterization of Arabidopsis ARGONAUTE 3 in reproductive tissue
Authors: Jullien Pauline E. , Grob Stefan , Marchais Antonin , Pumplin Nathan , Chevalier Clement , Otto Caroline , Schott Gregory , Voinnet Olivier
Published: December 2018

Arabidopsis encodes ten ARGONAUTE (AGO) effectors of RNA silencing, canonically loaded with either 21-22nt small RNAs (sRNA) to mediate post-transcriptional-gene-silencing (PTGS) or 24nt sRNAs to promote RNA-directed-DNA-methylation. Using full-locus constructs, we characterized the expression, biochemical properties, and possible modes of action of AGO3. Although AGO3 arose from a recent duplication at the AGO2 locus, their expression differs drastically, with AGO2 being expressed in both male and female gametes whereas AGO3 accumulates in aerial vascular terminations and specifically in chalazal seed integuments. Accordingly, AGO3 down-regulation alters gene expression in siliques. Similar to AGO2, AGO3 binds sRNAs with a strong 5’-adenosine bias, but unlike most Arabidopsis AGOs - AGO2 included - it binds efficiently both 24nt and 21nt sRNAs. AGO3 immunoprecipitation experiments in siliques revealed that these sRNAs mostly correspond to genes and intergenic regions. in a manner reflecting their respective accumulation from their loci-of-origin. AGO3 localizes to the cytoplasm and co-fractionates with polysomes to possibly mediate PTGS via translation inhibition.

Significance statement

The regulation of gene expression by small RNAs is key for proper plant development and defense. Here, we characterize Arabidopsis AGO3 expression pattern, microRNA regulation and biochemical properties during sexual reproduction.
Human Gene Expression Variability and its Dependence on Methylation and Aging
Authors: Bashkeel Nasser , Perkins Theodore J. , Kærn Mads , Lee Jonathan M.
Published: December 2018

Background

Phenotypic variability of human populations is partly the result of gene polymorphism and differential gene expression. As such, understanding the molecular basis for diversity requires identifying genes with both high and low population expression variance and identifying the mechanisms underlying their expression control. Key issues remain unanswered with respect to expression variability in human populations. The role of gene methylation as well as the contribution that age, sex and tissue-specific factors have on expression variability are not well understood.

Results

Here we used a novel method that accounts for sampling error to classify human genes based on their expression variability in normal human breast and brain tissues. We find that high expression variability is almost exclusively unimodal, indicating that variance is not the result of segregation into distinct expression states. Genes with high expression variability differ markedly between tissues and we find that genes with high population expression variability are likely to have age-, but not sex-dependent expression. Lastly, we find that methylation likely has a key role in controlling expression variability insofar as genes with low expression variability are likely to be non-methylated.

Conclusions

We conclude that gene expression variability in the human population is likely to be important in tissue development and identity, methylation, and in natural biological aging. The expression variability of a gene is an important functional characteristic of the gene itself and the classification of a gene as one with Hyper-Variability or Hypo-Variability in a human population or in a specific tissue should be useful in the identification of important genes that functionally regulate development or disease.