bluuebunny/crossref_metadata_2025 huggingface dataset:
New developments in Charcot–Marie–Tooth neuropathy and related diseases
Authors: Pareyson Davide , Saveri Paola , Pisciotta Chiara
Published: July 2017

Purpose of review

Charcot–Marie–Tooth disease (CMT) and related neuropathies represent a heterogeneous group of hereditary disorders. The present review will discuss the most recent advances in the field.

Recent findings

Knowledge of CMT epidemiology and frequency of the main associated genes is increasing, with an overall prevalence estimated at 10–28/100 000. In the last years, the huge number of newly uncovered genes, thanks to next-generation sequencing techniques, is challenging the current classification of CMT. During the last 18 months other genes have been associated with CMT, such as PMP2, MORC2, NEFH, MME, and DGAT2. For the most common forms of CMT, numerous promising compounds are under study in cellular and animal models, mainly targeting either the protein degradation pathway or the protein overexpression. Consequently, efforts are devoted to develop responsive outcome measures and biomarkers for this overall slowly progressive disorder, with quantitative muscle MRI resulting the most sensitive-to-change measure.

This is a rapidly evolving field where better understanding of pathophysiology is paving the way to develop potentially effective treatments, part of which will soon be tested in patients. Intense research is currently devoted to prepare clinical trials and develop responsive outcome measures.
Familial amyloid polyneuropathy
Authors: Adams David , Cauquil Cécile , Labeyrie Céline
Published: July 2017

Purpose of review

Transthyretin familial amyloid polyneuropathy is the most disabling hereditary polyneuropathy of adult onset because of a point mutation of transthyretin gene. This review updates our knowledge about natural history of the disease, phenotypes, diagnosis tools for small and large fibers involvement, expert's consensus for both symptomatic and asymptomatic follow-up, and treatment's research.

Recent findings

Access to TTR gene sequencing permit diagnosis and first reports of the disease in nonendemic countries (EU countries, United States, China, India). Most studies showed a more severe natural history of the neuropathy in nonendemic countries. First European consensus for management has been established. New long-term results allow selection of best candidates for liver transplantation based on phenotype and cardiac involvement. Multimodal evaluation of small fiber neuropathy and resonance magnetic neurography are under development. New results are available for long-term effect of tafamidis in late-onset patients. TTR gene silencing drugs are subject to phase 3 clinical trials.

New methods for the evaluation of the disease are being developed. The TTR gene silencing strategy will be available by the end of 2017.
Physiological mechanisms underlying animal social behaviour
Authors: Seebacher Frank , Krause Jens
Published: July 2017

Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission–fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’.
Injury-mediated decrease in locomotor performance increases predation risk in schooling fish
Authors: Krause J. , Herbert-Read J. E. , Seebacher F. , Domenici P. , Wilson A. D. M. , Marras S. , Svendsen M. B. S. , Strömbom D. , Steffensen J. F. , Krause S. , Viblanc P. E. , Couillaud P. , Bach P. , Sabarros P. S. , Zaslansky P. , Kurvers R. H. J. M.
Published: July 2017

The costs and benefits of group living often depend on the spatial position of individuals within groups and the ability of individuals to occupy preferred positions. For example, models of predation events for moving prey groups predict higher mortality risk for individuals at the periphery and front of groups. We investigated these predictions in sardine (Sardinella aurita) schools under attack from group hunting sailfish (Istiophorus platypterus) in the open ocean. Sailfish approached sardine schools about equally often from the front and rear, but prior to attack there was a chasing period in which sardines attempted to swim away from the predator. Consequently, all sailfish attacks were directed at the rear and peripheral positions of the school, resulting in higher predation risk for individuals at these positions. During attacks, sailfish slash at sardines with their bill causing prey injury including scale removal and tissue damage. Sardines injured in previous attacks were more often found in the rear half of the school than in the front half. Moreover, injured fish had lower tail-beat frequencies and lagged behind uninjured fish. Injuries inflicted by sailfish bills may, therefore, hinder prey swimming speed and drive spatial sorting in prey schools through passive self-assortment. We found only partial support for the theoretical predictions from current predator–prey models, highlighting the importance of incorporating more realistic predator–prey dynamics into these models.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’.
The role of physiological traits in assortment among and within fish shoals
Authors: Killen Shaun S. , Marras Stefano , Nadler Lauren , Domenici Paolo
Published: July 2017

Individuals of gregarious species often group with conspecifics to which they are phenotypically similar. This among-group assortment has been studied for body size, sex and relatedness. However, the role of physiological traits has been largely overlooked. Here, we discuss mechanisms by which physiological traits—particularly those related to metabolism and locomotor performance—may result in phenotypic assortment not only among but also within animal groups. At the among-group level, varying combinations of passive assortment, active assortment, phenotypic plasticity and selective mortality may generate phenotypic differences among groups. Even within groups, however, individual variation in energy requirements, aerobic and anaerobic capacity, neurological lateralization and tolerance to environmental stressors are likely to produce differences in the spatial location of individuals or associations between group-mates with specific physiological phenotypes. Owing to the greater availability of empirical research, we focus on groups of fishes (i.e. shoals and schools). Increased knowledge of physiological mechanisms influencing among- and within-group assortment will enhance our understanding of fundamental concepts regarding optimal group size, predator avoidance, group cohesion, information transfer, life-history strategies and the evolutionary effects of group membership. In a broader perspective, predicting animal responses to environmental change will be impossible without a comprehensive understanding of the physiological basis of the formation and functioning of animal social groups.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’.
Boldness traits, not dominance, predict exploratory flight range and homing behaviour in homing pigeons
Authors: Portugal Steven J. , Ricketts Rhianna L. , Chappell Jackie , White Craig R. , Shepard Emily L. , Biro Dora
Published: July 2017

Group living has been proposed to yield benefits that enhance fitness above the level that would be achieved through living as solitary individuals. Dominance hierarchies occur commonly in these social assemblages, and result, by definition, in resources not being evenly distributed between group members. Determinants of rank within a dominance hierarchy can be associated with morphological characteristics, previous experience of the individual, or personality traits such as exploration tendencies. The purpose of this study was to investigate whether greater exploration and positive responses to novel objects in homing pigeons (Columba livia) measured under laboratory conditions were associated with (i) greater initial exploration of the local area around the home loft during spontaneous exploration flights (SEF), (ii) faster and more efficient homing flights when released from further afield, and (iii) whether the traits of greater exploration and more positive responses to novel objects were more likely to be exhibited by the more dominant individuals within the group. There was no relationship between laboratory-based novel object exploration and position within the dominance hierarchy. Pigeons that were neophobic under laboratory conditions did not explore the local area during SEF opportunities. When released from sites further from home, neophobic pigeons took longer routes to home compared to those birds that had not exhibited neophobic traits under laboratory conditions, and had spontaneously explored to a greater extent. The lack of exploration in the neophobic birds is likely to have resulted in the increased costs of homing following release: unfamiliarity with the landscape likely led to the greater distances travelled and less efficient routes taken. Birds that demonstrated a lack of neophobia were not the dominant individuals inside the loft, and thus would have less access to resources such as food and potentially mates. However, a lack of neophobia makes the subordinate position possible, because subordinate birds that incur high travel costs would become calorie restricted and lose condition. Our results address emerging questions linking individual variation in behaviour with energetics and fitness consequences.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’.
Collective foraging in spatially complex nutritional environments
Authors: Lihoreau Mathieu , Charleston Michael A. , Senior Alistair M. , Clissold Fiona J. , Raubenheimer David , Simpson Stephen J. , Buhl Camille
Published: July 2017

Nutrition impinges on virtually all aspects of an animal's life, including social interactions. Recent advances in nutritional ecology show how social animals often trade-off individual nutrition and group cohesion when foraging in simplified experimental environments. Here, we explore how the spatial structure of the nutritional landscape influences these complex collective foraging dynamics in ecologically realistic environments. We introduce an individual-based model integrating key concepts of nutritional geometry, collective animal behaviour and spatial ecology to study the nutritional behaviour of animal groups in large heterogeneous environments containing foods with different abundance, patchiness and nutritional composition. Simulations show that the spatial distribution of foods constrains the ability of individuals to balance their nutrient intake, the lowest performance being attained in environments with small isolated patches of nutritionally complementary foods. Social interactions improve individual regulatory performances when food is scarce and clumpy, but not when it is abundant and scattered, suggesting that collective foraging is favoured in some environments only. These social effects are further amplified if foragers adopt flexible search strategies based on their individual nutritional state. Our model provides a conceptual and predictive framework for developing new empirically testable hypotheses in the emerging field of social nutrition.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’.
Costs and benefits of group living in primates: an energetic perspective
Authors: Markham A. Catherine , Gesquiere Laurence R.
Published: July 2017

Group size is a fundamental component of sociality, and has important consequences for an individual's fitness as well as the collective and cooperative behaviours of the group as a whole. This review focuses on how the costs and benefits of group living vary in female primates as a function of group size, with a particular emphasis on how competition within and between groups affects an individual's energetic balance. Because the repercussions of chronic energetic stress can lower an animal's fitness, identifying the predictors of energetic stress has important implications for understanding variation in survivorship and reproductive success within and between populations. Notably, we extend previous literature on this topic by discussing three physiological measures of energetic balance—glucocorticoids, c-peptides and thyroid hormones. Because these hormones can provide clear signals of metabolic states and processes, they present an important complement to field studies of spatial and temporal changes in food availability. We anticipate that their further application will play a crucial role in elucidating the adaptive significance of group size in different social and ecological contexts.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals'.
Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives
Authors: Spencer Karen A.
Published: July 2017

The social world is filled with different types of interactions, and social experience interacts with stress on several different levels. Activation of the neuroendocrine axis that regulates the response to stress can have consequences for innumerable behavioural responses, including social decision-making and aspects of sociality, such as gregariousness and aggression. This is especially true for stress experienced during early life, when physiological systems are developing and highly sensitive to perturbation. Stress at this time can have persistent effects on social behaviours into adulthood. One important question remaining is to what extent these effects are adaptive. This paper initially reviews the current literature investigating the complex relationships between the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems and several aspects of social behaviour in vertebrates. In addition, the review explores the evidence surrounding the potential for ‘social programming’ via differential development and activation of the HPA axis, providing an insight into the potential for positive effects on fitness following early life stress. Finally, the paper provides a framework from which novel investigations could work to fully understand the adaptive significance of early life effects on social behaviours.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals'.
Two social brains: neural mechanisms of intersubjectivity
Authors: Vogeley Kai
Published: July 2017

It is the aim of this article to present an empirically justified hypothesis about the functional roles of the two social neural systems, namely the so-called ‘mirror neuron system’ (MNS) and the ‘mentalizing system’ (MENT, also ‘theory of mind network’ or ‘social neural network’). Both systems are recruited during cognitive processes that are either related to interaction or communication with other conspecifics, thereby constituting intersubjectivity. The hypothesis is developed in the following steps: first, the fundamental distinction that we make between persons and things is introduced; second, communication is presented as the key process that allows us to interact with others; third, the capacity to ‘mentalize’ or to understand the inner experience of others is emphasized as the fundamental cognitive capacity required to establish successful communication. On this background, it is proposed that MNS serves comparably early stages of social information processing related to the ‘detection’ of spatial or bodily signals, whereas MENT is recruited during comparably late stages of social information processing related to the ‘evaluation’ of emotional and psychological states of others. This hypothesis of MNS as a social detection system and MENT as a social evaluation system is illustrated by findings in the field of psychopathology. Finally, new research questions that can be derived from this hypothesis are discussed.

This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’.
Sharing of carbapenemase-encoding plasmids between Enterobacteriaceae in UK sewage uncovered by MinION sequencing
Authors: Ludden Catherine , Reuter Sandra , Judge Kim , Gouliouris Theodore , Blane Beth , Coll Francesc , Naydenova Plamena , Hunt Martin , Tracey Alan , Hopkins Katie L. , Brown Nicholas M. , Woodford Neil , Parkhill Julian , Peacock Sharon J.
Published: July 2017

Dissemination of carbapenem resistance among pathogenic Gram-negative bacteria is a looming medical emergency. Efficient spread of resistance within and between bacterial species is facilitated by mobile genetic elements. We hypothesized that wastewater contributes to the dissemination of carbapenemase-producing Enterobacteriaceae (CPE), and studied this through a cross-sectional observational study of wastewater in the East of England. We isolated clinically relevant species of CPE in untreated and treated wastewater, confirming that waste treatment does not prevent release of CPE into the environment. We observed that CPE-positive plants were restricted to those in direct receipt of hospital waste, suggesting that hospital effluent may play a role in disseminating carbapenem resistance. We postulated that plasmids carrying carbapenemase genes were exchanged between bacterial hosts in sewage, and used short-read (Illumina) and long-read (MinION) technologies to characterize plasmids encoding resistance to antimicrobials and heavy metals. We demonstrated that different CPE species (Enterobacter kobei and Raoultella ornithinolytica) isolated from wastewater from the same treatment plant shared two plasmids of 63 and 280 kb. The former plasmid conferred resistance to carbapenems (bla
OXA-48), and the latter to numerous drug classes and heavy metals. We also report the complete genome sequence for Enterobacter kobei. Small, portable sequencing instruments such as the MinION have the potential to improve the quality of information gathered on antimicrobial resistance in the environment.
Comparison of classical multi-locus sequence typing software for next-generation sequencing data
Authors: Page Andrew J. , Alikhan Nabil-Fareed , Carleton Heather A. , Seemann Torsten , Keane Jacqueline A. , Katz Lee S.
Published: July 2017

Multi-locus sequence typing (MLST) is a widely used method for categorizing bacteria. Increasingly, MLST is being performed using next-generation sequencing (NGS) data by reference laboratories and for clinical diagnostics. Many software applications have been developed to calculate sequence types from NGS data; however, there has been no comprehensive review to date on these methods. We have compared eight of these applications against real and simulated data, and present results on: (1) the accuracy of each method against traditional typing methods, (2) the performance on real outbreak datasets, (3) the impact of contamination and varying depth of coverage, and (4) the computational resource requirements.
MassBlast: A workflow to accelerate RNA-seq and DNA database analysis
Authors: Veríssimo André , Bassard Jean-Etienne , Julien-Laferrière Alice , Sagot Marie-France , Vinga Susana
Published: July 2017

Current workflows for sequence analysis heavily depend on user input and manual curation. New specialized tools and methods are appearing all the time, but the actions required for a full analysis are disconnected and very time-consuming. The software we propose, MassBlast, combines BLAST+ and an automated workflow analysis to filter the results and significantly improve the annotation of multiple sequencing databases for exploring new biosynthetic pathways and new protein families, among other applications. MassBlast is fully configurable and reproducible.

Availability and Implementation

The MassBlast package is written in Ruby. Source code and releases are freely available from Github (https://github.com/averissimo/mass-blast) for all major platforms (Linux, MS Windows and OS X) under the GPLv3 license.

Contact

andre.verissimo@tecnico.ulisboa.pt
Changes in extracellular matrix cause RPE cells to make basal deposits and activate the alternative complement pathway
Authors: Fernandez-Godino Rosario , Bujakowska Kinga M. , Pierce Eric A.
Published: July 2017

The design of efficient therapies for age-related macular degeneration (AMD) is limited by our understanding of the pathogenesis of basal deposits, which form between retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) early in disease, and involve activation of the complement system. To investigate the roles of BrM, RPE and complement in AMD, we generated ARPE-19 cells with the p.R345W mutation inEFEMP1, which causes early-onset macular degeneration. The ARPE-19-EFEMP1R345W/R345Wcells make abnormal extracellular matrix (ECM) that binds active complement C3 and causes the formation of basal deposits by normal human fetal (hf)RPE cells. hfRPE cells grown on abnormal ECM or BrM explants from AMD donors show chronic activation of the alternative complement pathway by excessive deposition of C3b. This process is exacerbated by impaired ECM turnover via increased matrix metalloproteinase-2 (MMP-2) activity. Therapies that target ECM synthesis and turnover and activation of C3 could be effective for early AMD.
Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0
Authors: Koch Mathilde , Duigou Thomas , Carbonell Pablo , Faulon Jean-Loup
Published: July 2017

Background

Network generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for.

Results

Here, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure biosynthetic accessibility. We finally use our workflow on anE. colimodel to completeE. colimetabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of anE. colicell lysate interfacing our workflow with OpenMS through the KNIME analytics platform.

Conclusion

We provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including, molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper.
Motor expertise facilitates the precision of state extrapolation in perception
Authors: Ludolph Nicolas , Plöger Jannis , Giese Martin A. , Ilg Winfried
Published: July 2017

Predicting the behavior of objects in the environment is an important requirement to overcome latencies in the sensorimotor system and realize precise actions in rapid situations. Internal forward models that were acquired during motor training might not only be used for efficiently controlling fast motor behavior but also to facilitate extrapolation performance in purely perceptual tasks. In this study, we investigated whether preceding virtual cart-pole balancing training facilitates the ability to extrapolate the pole motion. We compared a group of 10 subjects, proficient in performing the cart-pole balancing task, to 10 naïve subjects. Our results demonstrate that preceding motor training increases the precision of pole movement extrapolation, although extrapolation is not trained explicitly. Additionally, we modelled subjects’ behaviors and show that the difference in extrapolation performance can be explained by individual differences in the accuracy of internal forward models. When subjects are provided with feedback about the true pole movement in a second phase, both groups improve rapidly. The results indicate that the perceptual capability to extrapolate the state of the cart-pole system accurately is implicitly trained during motor learning. We discuss these results in the context of shared representations and action-perception transfer.
Facultative adjustment of paternal care in the face of female infidelity in dunnocks
Authors: Santos Eduardo S. A. , Nakagawa Shinichi
Published: July 2017

A much-debated issue is whether or not males should reduce parental care when they lose paternity (i.e. the certainty of paternity hypothesis). While there is general support for this relationship across species, within-population evidence is still contentious. Among the main reasons behind such problem is the confusion discerning between-from within-individual patterns. Here, we tested this hypothesis empirically by investigating the parental care of male dunnocks(Prunella modularis)in relation to paternity. We used a thorough dataset of observations in a wild population, genetic parentage, and a within-subject centring statistical approach to disentangle paternal care adjustment within-male and between males. We found support for the certainty of paternity hypothesis, as there was evidence for within-male adjustment in paternal care when socially monogamous males lost paternity to extra-pair sires. There was little evidence of a between-male effect overall. Our findings show that monogamous males adjust paternal care when paired to the same female partner. We also show that – in monogamous broods – the proportion of provisioning visits made by males yields fitness benefits in terms of fledging success. Our results suggest that socially monogamous females that engage in extra-pair behaviour may suffer fitness costs, as their partners’ reduction in paternal care can negatively affect fledging success.
Cortical circuit-based lossless neural integrator for perceptual decision-making
Authors: Lee Jung H. , Tsunada Joji , Vijayan Sujith , Cohen Yale E.
Published: July 2017

The intrinsic uncertainty of sensory information (i.e., evidence) does not necessarily deter an observer from making a reliable decision. Indeed, uncertainty can be reduced by integrating (accumulating) incoming sensory evidence. It is widely thought that this accumulation is instantiated via recurrent rate-code neural networks. Yet, these networks do not fully explain important aspects of perceptual decision-making, such as a subject’s ability to retain accumulated evidence during temporal gaps in the sensory evidence. Here, we utilized computational models to show that cortical circuits can switch flexibly between ‘retention’ and ‘integration’ modes during perceptual decision-making. Further, we found that, depending on how the sensory evidence was readout, we could simulate ‘stepping’ and ‘ramping’ activity patterns, which may be analogous to those seen in different studies of decision-making in the primate parietal cortex. This finding may reconcile these previous empirical studies because it suggests these two activity patterns emerge from the same mechanism.
Mechanisms of surface antigenic variation in the human pathogenic fungusPneumocystis jirovecii
Authors: Schmid-Siegert Emanuel , Richard Sophie , Luraschi Amanda , Mühlethaler Konrad , Pagni Marco , Hauser Philippe M.
Published: July 2017

Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose byPneumocystis jirovecii.This uncultivable fungus is an obligate pulmonary pathogen which causes pneumonia in immuno-compromised individuals, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a singleP. jiroveciistrain from a bronchoalveolar lavage fluid specimen of a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily which included five families encoding adhesive GPI-anchored glycoproteins, and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination, and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favoured by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i)P. jiroveciicell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists in the continuous production of new subpopulations composed of cells which are antigenically different.
Optical inhibition of zebrafish behavior with anion channelrhodopsins
Authors: Mohamed Gadisti Aisha , Cheng Ruey-Kuang , Ho Joses , Krishnan Seetha , Mohammad Farhan , Claridge-Chang Adam , Jesuthasan Suresh
Published: July 2017

In behavioral analysis, optical electrical silencing provides a way to test neuronal necessity. Two light-gated anion channels, GtACR1 and GtACR2, have recently been shown—in neuronal culture and inDrosophila—to inhibit neurons potently. Here, we test the usefulness of these channels in zebrafish. When the GtACRs were expressed in motor neurons and actuated with blue or green light, fish spontaneous movement was inhibited. In GtACR1-expressing fish, only 3 µW/mm2of light was sufficient to have an effect; GtACR2, which is poorly trafficked, required stronger illumination. After light offset, GtACR-expressing fish movement increased; this suggested that termination of light-induced neural inhibition may lead to depolarization. Consistent with this, two-photon imaging of spinal neurons showed that intracellular calcium also increased following light offset. The activity elicited at light offset needs to be taken into consideration in experimental design, although this property may help provide insight into the effects of stimulating a circuit transiently. These results show that GtACR1 and GtACR2 can be used to optically inhibit neurons in zebrafish, and thus to test neural circuit necessity.
Comparison of fine-scale recombination maps in fungal plant pathogens reveals dynamic recombination landscapes and intragenic hotspots
Authors: Stukenbrock Eva H. , Dutheil Julien Y.
Published: July 2017

Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation and rates of adaptation. In many organisms recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate and positions of recombination hotspot can be studied using population genomics data and statistical methods. In this study, we conducted population genomics analyses to address the evolution of recombination in two closely related fungal plant pathogens: the prominent wheat pathogenZymoseptoria triticiand a sister species infecting wild grassesZymoseptoria ardabiliae. We specifically addressed whether recombination landscapes, including hotspot positions, are conserved in the two recently diverged species and if recombination contributes to rapid evolution of pathogenicity traits. We conducted a detailed simulation analysis to assess the performance of methods of recombination rate estimation based on patterns of linkage disequilibrium, in particular in the context of high nucleotide diversity. Our analyses reveal overall high recombination rates, a lack of suppressed recombination in centromeres and significantly lower recombination rates on chromosomes that are known to be accessory. The comparison of the recombination landscapes of the two species reveals a strong correlation of recombination rate at the megabase scale, but little correlation at smaller scales. The recombination landscapes in both pathogen species are dominated by frequent recombination hotspots across the genome including coding regions, suggesting a strong impact of recombination on gene evolution. A significant but small fraction of these hotspots co-localize between the two species, suggesting that hotspots dynamics contribute to the overall pattern of fast evolving recombination in these species.
A mouse model of necrotic biliary pancreatitis induced by combining gallstone formation and ligation of the biliary-pancreatic duct
Authors: Yuan Zuobiao , Zheng Junyuan , Mei Zhu , Hu Guoyong , Zeng Yue
Published: July 2017

Objective

The aim of the present investigation is to develop a mouse model of biliary pancreatitis with characteristics of both gallstone formation and pancreatitis, mimicking the human etiology and pathphysiological character.

Design

Male C57BL/6 mice were fed with chow, high fat/cholesterol and lithogenic diet for 12 weeks respectively. Laparotomy was done followed by ligation of pancreatic duct (PD), bile duct and pancreatic duct (BPD), or sham operation.

Results

Little or no evidence of pancreatitis was observed in PD group of mice fed with chow or high fat/cholesterol diet, or in the tail of pancreata removed from animals fed with lithogenic diet. In the head of pancreas, pancreas damage was dramatically more severe in the lithogenic group. When bile reflux was blocked by BPD, pancreas damage markedly reduced to level of chow diet group. The lithogenic diet group also developed significantly more severe multi organ dysfunction syndrome (MODS) in the lung, kidney and liver. The severity of pancreatitis is associated with persistent high bile level of cholesterol and bile acid after obstruction of the biliary-pancreatic duct. Cholesterol crystal aggravated injury of pancreatic acinar cells caused by taurocholate. After obstruction of the biliary-pancreatic duct, in the lithogenic diet group, liver Abcg8 and Cyp7a1 was up-regulated, compared to the control group.

Conclusion

We developed a mouse model of severe biliary pancreatitis in both local pancreas damage and MODS. This model provides a sound explanation for the Opie theory dilemma and a potential therapeutical direction in clinical practice as well.

Summary statement

A biliary pancreatitis has characters of both gallstone and pancreatitis, mimicking human etiology and pathophysiology, which gave a clear answer to the long time Opie theory dilemma.
Biochemical characterization and essentiality ofPlasmodiumfumarate hydratase
Authors: Jayaraman Vijay , Suryavanshi Arpitha , Kalale Pavithra , Kunala Jyothirmai , Balaram Hemalatha
Published: July 2017

Plasmodium falciparum(Pf), the causative agent of malaria has an iron-sulfur cluster-containing class I fumarate hydratase (FH) that catalyzes the interconversion of fumarate to malate, a well-known reaction in the tricarboxylic acid cycle. In humans, the same reaction is catalyzed by class II FH that has no sequence or structural homology with the class I enzyme. Fumarate, generated in large quantities in the parasite as a byproduct of AMP synthesis is converted to malate by the action of FH, and subsequently used in the generation of the key metabolites oxaloacetate, aspartate and pyruvate. Here we report on the kinetic characterization of purified recombinant PfFH, functional complementation offhdeficiency inEscherichia coliand mitochondrial localization in the parasite. The substrate analog, mercaptosuccinic acid was found to be a potent inhibitor of PfFH with a Kivalue in the nanomolar range. Knockout of thefhgene was not possible inP. bergheiwhen drug-selection of the transfectants was performed in BALB/c mice while the gene was amenable to knockout when C57BL/6 mice were used as host, thereby indicating mouse-strain dependent essentiality of thefhgene to the parasite.
A Fluorogenic Array Tag for Temporally Unlimited Single Molecule Tracking
Authors: Ghosh Rajarshi P , Franklin J Matthew , Draper Will E. , Shi Quanming , Liphardt Jan T.
Published: July 2017

Cellular processes take place over many timescales, prompting the development of precision measurement technologies that cover milliseconds to hours. Here we describe ArrayG, a bipartite fluorogenic system composed of a GFP-nanobody array and monomeric wtGFP binders. The free binders are initially dim but brighten 15 fold upon binding the array, suppressing background fluorescence. By balancing rates of intracellular binder production, photo-bleaching, and stochastic binder exchange on the array, we achieved temporally unlimited tracking of single molecules. Fast (20-180Hz) tracking of ArrayG tagged kinesins and integrins, for thousands of frames, revealed repeated state-switching and molecular heterogeneity. Slow (0.5 Hz) tracking of single histones for as long as 1 hour showed fractal dynamics of chromatin. We also report ArrayD, a DHFR-nanobody-array tag for dual color imaging. The arrays are aggregation resistant and combine high brightness, background suppression, fluorescence replenishment, and extended choice of fluorophores, opening new avenues for seeing and tracking single molecules in living cells.
Do Sigmoidal Acquisition Curves Indicate Conformity?
Authors: Smaldino Paul E. , Aplin Lucy M. , Farine Damien R.
Published: July 2017

The potential for behaviours to spread via cultural transmission has profound implications for our understanding of social dynamics and evolution. Several studies have provided empirical evidence that local traditions can be maintained in animal populations via conformist learning (i.e. copying the majority). A conformist bias can be characterized by a sigmoidal relationship between a behavior’s prevalence in the population and an individual’s propensity to adopt that behavior. For this reason, the presence of conformist learning in a population is often inferred from a sigmoidal acquisition curve in which the overall rate of adoption for the behavior is taken as the dependent variable. However, the validity of sigmoidal acquisition curves as evidence for conformist learning has recently been challenged by models suggesting that such curves can arise via alternative learning rules that do not involve conformity. We review these models, and find that the proposed alternative learning mechanisms either rely on faulty or unrealistic assumptions, or apply only in very specific cases. We therefore recommend that sigmoidal acquisition curves continue to be taken as evidence for conformist learning. Our paper also highlights the importance of understanding the generative processes of a model, rather than only focusing solely on the patterns produced. By studying these processes, our analysis suggests that current practices by empiricists have provided robust evidence for conformist transmission in both humans and non-human animals.
KinFin: Software for taxon-aware analysis of clustered protein sequences
Authors: Laetsch Dominik R. , Blaxter Mark L.
Published: July 2017

The field of comparative genomics is concerned with the study of similarities and differences between the information encoded in the genomes of organisms. A common approach is to define gene families by clustering protein sequences based on sequence similarity, and analyse protein cluster presence and absence in different species groups as a guide to biology. Due to the high dimensionality of these data, downstream analysis of protein clusters inferred from large numbers of species, or species with many genes, is non-trivial, and few solutions exist for transparent, reproducible and customisable analyses. We present KinFin, a streamlined software solution capable of integrating data from common file formats and delivering aggregative annotation of protein clusters. KinFin delivers analyses based on systematic taxonomy of the species analysed, or on user-defined groupings of taxa, for example sets based on attributes such as life history traits, organismal phenotypes, or competing phylogenetic hypotheses. Results are reported through graphical and detailed text output files. We illustrate the utility of the KinFin pipeline by addressing questions regarding the biology of filarial nematodes, which include parasites of veterinary and medical importance. We resolve the phylogenetic relationships between the species and explore functional annotation of proteins in clusters in key lineages and between custom taxon sets, identifying gene families of interest. KinFin can easily be integrated into existing comparative genomic workflows and promotes transparent and reproducible analysis of clustered protein data.
Signatures of the evolution of parthenogenesis and cryptobiosis in panagrolaimid nematodes
Authors: Schiffer Philipp H. , Danchin Etienne G.J. , Burnell Ann M. , Schiffer Anne-Marike , Creevey Christopher J. , Wong Simon , Dix Ilona , O’Mahony Georgina , Culleton Bridget A. , Rancurel Corinne , Stier Gary , Martínez-Salazar Elizabeth A. , Marconi Aleksandra , Trivedi Urmi , Kroiher Michael , Thorne Michael A.S. , Schierenberg Einhard , Wiehe Thomas , Blaxter Mark
Published: July 2017

Most animal species reproduce sexually, but parthenogenesis, asexual reproduction of various forms, has arisen repeatedly. Parthenogenetic lineages are usually short lived in evolution; though in some environments parthenogenesis may be advantageous, avoiding the cost of sex.Panagrolaimusnematodes have colonised environments ranging from arid deserts to arctic and antarctic biomes. Many are parthenogenetic, and most have cryptobiotic abilities, being able to survive repeated complete desiccation and freezing. It is not clear which genomic and molecular mechanisms led to the successful establishment of parthenogenesis and the evolution of cryptobiosis in animals in general. At the same time, model systems to study these traits in the laboratory are missing.

We compared the genomes and transcriptomes of parthenogenetic and sexualPanagrolaimusable to survive crybtobiosis, as well as a non-cryptobioticPropanogrolaimusspecies, to identify systems that contribute to these striking abilities. The parthenogens are most probably tripoids originating from hybridisation (allopolyploids). We identified genomic singularities like expansion of gene families, and selection on genes that could be linked to the adaptation to cryptobiosis. AllPanagrolaimushave acquired genes through horizontal transfer, some of which are likely to contribute to cryptobiosis. Many genes acting inC. elegansreproduction and development were absent in distant nematode species (including the Panagrolaimids), suggesting molecular pathways cannot directly be transferred from the model system.

The easily culturedPanagrolaimusnematodes offer a system to study developmental diversity in Nematoda, the molecular evolution of parthenogens, the effects of triploidy on genomes stability, and the origin and biology of cryptobiosis.
Innovation and organizational development: the role of organizational leadership
Authors: Anning-Dorson Thomas , Odoom Raphael Kofi , Acheampong George , Tweneboah-Koduah Ernest
Published: July 2017

Purpose

The purpose of this paper is to assess the moderation effect of organizational leadership on the relationship between service firm’s innovation strategy and organizational development. The study argues that in Ghana where power distance is high, organizational leadership provides the needed impetus for strategies such as innovation to achieve enhanced firm performance.

Design/methodology/approach

Data were collected from different service firms across Ghana for this study. A confirmatory factor analysis was used for construct reliability and validity checks. Robust regression estimations were then performed to test the hypothesized relationships.

Findings

The results show that both product innovation as strategy and organizational leadership are positively related to organizational development (i.e. financial and non-financial performance). It was also found that organizational leadership does not only serve as a predictor of strategy formulation but provides the necessary strategic fit between a firm’s strategy and business environment to achieve organizational development.

Originality/value

This study has shown that in high-power distance cultures, firms that are able to align their leadership orientation with their institutional environment are able to create a better fit between their strategic orientation and business environment in order to enhance organizational development.