bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological and Behavioral Factors Associated With Positive Chlamydia Retests
Authors: Smith Kirsty S. , Guy Rebecca , Danielewski Jennifer , Tabrizi Sepehr N. , Fairley Christopher K. , McNulty Anna M. , Rawlinson William , Saville Marion , Garland Suzanne M. , Donovan Basil , Kaldor John M. , Hocking Jane S.
Published: April 2017

Background

Repeat chlamydia detection after treatment is common, and there is concern that treatment failure may be a cause.

Methods

Within a randomized trial, we established a prospective cohort of 600 participants with anogenital chlamydia diagnoses (200 each of women, heterosexual men, and men who have sex with men [MSM]). Participants were invited for repeat testing at 3 months and to complete a behavioral survey at 4 months. Positive samples were analyzed for organism DNA load and genovar. We estimated repeat chlamydia positivity, reinfection and treatment failure rates, and investigated the biological and behavioral factors associated with a repeat positive test.

Results

A total of 290 participants (100 women, 89 heterosexual men, 101 MSM) were retested at 1 to 4 months, with 43 repeat positives, including 26 classed as reinfection and 9 as treatment failures. Comparing MSM with heterosexual men and women combined, repeat positivity was higher (20.8% vs 11.6%, P = 0.04), and treatment failure was higher (6.9% vs 1.1%, P = 0.01), but there was no difference in reinfection rates (11.9% vs 7.4%, P = 0.21). Among MSM, the odds of repeat positivity increased by 90% with each additional log organism load in the original specimen (baseline) (adjusted odds ratio, 1.9; 95% confidence interval, 1.1–3.2). Among heterosexuals, the odds of repeat positivity decreased by 10% with each additional week delay in being retested for chlamydia (adjusted odds ratio, 0.9; 95% confidence interval, 0.8–0.9).

Conclusions

Positive retests were more common among MSM than heterosexuals. Treatment failure was more common in MSM with rectal chlamydia, reinforcing concerns about azithromycin treatment failure.
Urinary Meatal Swabbing Detects More Men Infected With Mycoplasma genitalium and Four Other Sexually Transmitted Infections Than First Catch Urine
Authors: Chernesky Max , Jang Dan , Smieja Marek , Arias Manuel , Martin Irene , Weinbaum Barbara , Getman Damon
Published: April 2017

Urinary meatal swabs compared with urine showed higher infection rates for Mycoplasma genitalium (15.3% vs 12.6%, P = 0.035), Chlamydia trachomatis (11.3% vs 9.3%, P = 0.039), Neisseria gonorrhoeae (1.4% vs 1.1%, P = 1.00), Trichomonas vaginalis (8.0% vs 1.7%, P < 0.001), and high-risk human papillomavirus (5.9% vs 3.4%, P = 0.078) respectively.
Characteristics of Submacular Hemorrhages in Age-Related Macular Degeneration
Authors: Kim Jae Hui , Chang Young Suk , Kim Jong Woo , Kim Chul Gu
Published: April 2017

Purpose

The aims of this research are to report the incidence and characteristics of submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD) and to compare the detailed morphologic features of hemorrhages between typical neovascular AMD and polypoidal choroidal vasculopathy (PCV).

Methods

This retrospective observational study included 791 eyes of 791 patients who had newly diagnosed neovascular AMD at a single institution. The incidence and extent of submacular hemorrhage of one disc area or greater were estimated and compared between typical neovascular AMD and PCV. In addition, submacular hemorrhages were classified into groups according to location (location of fovea at the center of the hemorrhage versus at the periphery of the hemorrhage) and morphology (circular versus irregular margin). The proportion of each subtype of neovascular AMD was evaluated according to the aforementioned classification.

Results

Among those included, 129 (16.3%) eyes exhibited submacular hemorrhage at initial presentation. Among the 627 eyes with available indocyanine green angiography findings, the incidence of submacular hemorrhage was greater in PCV (23.6%, 78 of 330 eyes) than in typical neovascular AMD (9.4%, 28 of 297 eyes; χ2 test, P < .001). When divided into four groups according to hemorrhage shape and location (central and circular, central and irregular, peripheral and circular, and peripheral irregular), the proportion of eyes in these groups was significantly different between the two disease groups (χ2 test, P = .018).

Conclusions

The incidence of submacular hemorrhage was greater in PCV than in typical neovascular AMD. The morphology and location of submacular hemorrhage may provide useful clues to differentiate PCV from typical neovascular AMD.
Deimatism: a neglected component of antipredator defence
Authors: Umbers Kate D. L. , De Bona Sebastiano , White Thomas E. , Lehtonen Jussi , Mappes Johanna , Endler John A.
Published: April 2017

Deimatic or ‘startle’ displays cause a receiver to recoil reflexively in response to a sudden change in sensory input. Deimatism is sometimes implicitly treated as a form of aposematism (unprofitability associated with a signal). However, the fundamental difference is, in order to provide protection, deimatism does not require a predator to have any learned or innate aversion. Instead, deimatism can confer a survival advantage by exploiting existing neural mechanisms in a way that releases a reflexive response in the predator. We discuss the differences among deimatism, aposematism, and forms of mimicry, and their ecological and evolutionary implications. We highlight outstanding questions critical to progress in understanding deimatism.
Collective benefits in traffic during mega events via the use of information technologies
Authors: Xu Yanyan , González Marta C.
Published: April 2017

Information technologies today can inform each of us about the route with the shortest time, but they do not contain incentives to manage travellers such that we all get collective benefits in travel times. To that end we need travel demand estimates and target strategies to reduce the traffic volume from the congested roads during peak hours in a feasible way. During large events, the traffic inconveniences in large cities are unusually high, yet temporary, and the entire population may be more willing to adopt collective recommendations for collective benefits in traffic. In this paper, we integrate, for the first time, big data resources to estimate the impact of events on traffic and propose target strategies for collective good at the urban scale. In the context of the Olympic Games in Rio de Janeiro, we first predict the expected increase in traffic. To that end, we integrate data from mobile phones, Airbnb, Waze and transit information, with game schedules and expected attendance in each venue. Next, we evaluate different route choice scenarios for drivers during the peak hours. Finally, we gather information on the trips that contribute the most to the global congestion which could be redirected from vehicles to transit. Interestingly, we show that (i) following new route alternatives during the event with individual shortest times can save more collective travel time than keeping the routine routes used before the event, uncovering the positive value of information technologies during events; (ii) with only a small proportion of people selected from specific areas switching from driving to public transport, the collective travel time can be reduced to a great extent. Results are presented online for evaluation by the public and policymakers (
www.flows-rio2016.com
(last accessed 3 September 2017)).
Enhancing regenerative approaches with nanoparticles
Authors: van Rijt Sabine , Habibovic Pamela
Published: April 2017

In this review, we discuss recent developments in the field of nanoparticles and their use in tissue regeneration approaches. Owing to their unique chemical properties and flexibility in design, nanoparticles can be used as drug delivery systems, to create novel features within materials or as bioimaging agents, or indeed these properties can be combined to create smart multifunctional structures. This review aims to provide an overview of this research field where the focus will be on nanoparticle-based strategies to stimulate bone regeneration; however, the same principles can be applied for other tissue and organ regeneration strategies. In the first section, nanoparticle-based methods for the delivery of drugs, growth factors and genetic material to promote tissue regeneration are discussed. The second section deals with the addition of nanoparticles to materials to create nanocomposites. Such materials can improve several material properties, including mechanical stability, biocompatibility and biological activity. The third section will deal with the emergence of a relatively new field of research using nanoparticles in advanced cell imaging and stem cell tracking approaches. As the development of nanoparticles continues, incorporation of this technology in the field of regenerative medicine will ultimately lead to new tools that can diagnose, track and stimulate the growth of new tissues and organs.
Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against
Trichuris muris
infection
Authors: Gomez-Samblas M. , García-Rodríguez J. J. , Trelis M. , Bernal D. , Lopez-Jaramillo F. J. , Santoyo-Gonzalez F. , Vilchez S. , Espino A. M. , Bolás-Fernández F. , Osuna A.
Published: April 2017

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode
Angiostrongylus costaricensis
(rPP2A) was used for intranasal immunization in mice previously infected with
Trichuris muris
. The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other experimental groups. Also, these animals presented significantly different chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft cells did not vary between groups, the intensity of fluorescence per cell was significant in the group immunized with the rPP2A-OVS. The results of the present study suggest that mice immunized with the lipopeptide are capable of activating a combined Th17/Th9 response. This strategy of immunization may be of great applicability not only in immunotherapy and immunoprophylaxis to control diseases caused by nematodes but also in pathologies necessitating action at the level of the Th9 response in the intestinal mucosa.
An agent-based model of anoikis in the colon crypt displays novel emergent behaviour consistent with biological observations
Authors: Ingham-Dempster Tim , Walker Dawn C. , Corfe Bernard M.
Published: April 2017

Colorectal cancer (CRC) is a major cause of cancer mortality. Colon crypts are multi-cellular flask-shaped invaginations of the colonic epithelium, with stem cells at their base which support the continual turnover of the epithelium with loss of cells by anoikis from the flat mucosa. Mutations in these stem cells can become embedded in the crypts, a process that is strongly implicated in CRC initiation. We describe a computational model which includes novel features, including an accurate representation of the geometry of the crypt mouth. Model simulations yield previously unseen emergent phenomena, such as localization of cell death to a small region of the crypt mouth which corresponds with that observed
in vivo
. A mechanism emerges in the model for regulation of crypt cellularity in response to changes in either cell proliferation rates or membrane adhesion strengths. We show that cell shape assumptions influence this behaviour, with cylinders recapitulating biology better than spheres. Potential applications of the model include determination of roles of mutations in neoplasia and exploring factors for altered crypt morphodynamics.
Failure mechanism of hollow tree trunks due to cross-sectional flattening
Authors: Huang Yan-San , Hsu Fu-Lan , Lee Chin-Mei , Juang Jia-Yang
Published: April 2017

Failure of hollow trees in urban areas is a worldwide concern, and it can be caused by different mechanisms, i.e. bending stresses or flattening-related failures. Here we derive a new analytical expression for predicting the bending moment for tangential cracking, and compare the breaking moment of various failure modes, including Brazier buckling, tangential cracking, shear failure and conventional bending failure, as a function of
t
/
R
ratio, where
t
and
R
are the trunk wall thickness and trunk radius, respectively, of a hollow tree. We use Taiwan red cypress as an example and show that its failure modes and the corresponding
t
/
R
ratios are: Brazier buckling (Mode I), tangential cracking followed by longitudinal splitting (Mode II) and conventional bending failure (Mode III) for 0 < 
t
/
R
 < 0.06, 0.06 < 
t
/
R
 < 0.27 and 0.27 < 
t
/
R
 < 1, respectively. The exact values of those ratios may vary within and among species, but the variation is much smaller than individual mechanical properties. Also, shear failure, another type of cracking due to maximum shear stress near the neutral axis of the tree trunk, is unlikely to occur since it requires much larger bending moments. Hence, we conclude that tangential cracking due to cross-sectional flattening, followed by longitudinal splitting, is dominant for hollow trunks. Our equations are applicable to analyse straight hollow tree trunks and plant stems, but are not applicable to those with side openings or those with only heart decay. Our findings provide insights for those managing trees in urban situations and those managing for conservation of hollow-dependent fauna in both urban and rural settings.
What a difference a day makes—female behaviour is less predictable near ovulation
Authors: Kästner Niklas , Richter S. Helene , Gamer Matthias , Kaiser Sylvia , Sachser Norbert
Published: April 2017

‘Animal personalities’ have been shown to exist in many species. Yet, fluctuations in the stability of these inter-individual behavioural differences are not well understood. Against this background, we wondered whether behavioural consistency over time is affected by the reproductive cycle. Female mice were tested twice at an interval of eight weeks in four paradigms assessing social interest as well as anxiety-like behaviour and exploratory locomotion. Twenty-two individuals were tested repeatedly near ovulation, whereas another twenty-two were tested repeatedly in the non-receptive phase. While we found no major behavioural effects at the group level, the reproductive state indeed had profound effects on behavioural stability over time: social interest as well as anxiety-like behaviour proved to be significantly less predictable near ovulation. It is generally believed that phenotypic plasticity is limited due to the costs it brings about. In this context, our data indicate that females accept higher costs in phases directly related to fitness maximization.
Optimal localization of diffusion sources in complex networks
Authors: Hu Zhao-Long , Han Xiao , Lai Ying-Cheng , Wang Wen-Xu
Published: April 2017

Locating sources of diffusion and spreading from minimum data is a significant problem in network science with great applied values to the society. However, a general theoretical framework dealing with optimal source localization is lacking. Combining the controllability theory for complex networks and compressive sensing, we develop a framework with high efficiency and robustness for optimal source localization in arbitrary weighted networks with arbitrary distribution of sources. We offer a minimum output analysis to quantify the source locatability through a minimal number of messenger nodes that produce sufficient measurement for fully locating the sources. When the minimum messenger nodes are discerned, the problem of optimal source localization becomes one of sparse signal reconstruction, which can be solved using compressive sensing. Application of our framework to model and empirical networks demonstrates that sources in homogeneous and denser networks are more readily to be located. A surprising finding is that, for a connected undirected network with random link weights and weak noise, a single messenger node is sufficient for locating any number of sources. The framework deepens our understanding of the network source localization problem and offers efficient tools with broad applications.
Chance long-distance or human-mediated dispersal? HowAcacia s.l. farnesianaattained its pan-tropical distribution
Authors: Bell Karen L. , Rangan Haripriya , Fernandes Manuel M. , Kull Christian A. , Murphy Daniel J.
Published: April 2017

Acacia s.l. farnesiana, which originates from Mesoamerica, is the most widely distributedAcacia s.l.species across the tropics. It is assumed that the plant was transferred across the Atlantic to southern Europe by Spanish explorers, and then spread across the Old World tropics through a combination of chance long-distance and human-mediated dispersal. Our study uses genetic analysis and information from historical sources to test the relative roles of chance and human-mediated dispersal in its distribution. The results confirm the Mesoamerican origins of the plant and show three patterns of human-mediated dispersal. Samples from Spain showed greater genetic diversity than those from other Old World tropics, suggesting more instances of transatlantic introductions from the Americas to that country than to other parts of Africa and Asia. Individuals from the Philippines matched a population from South Central Mexico and were likely to have been direct, trans-Pacific introductions. Australian samples were genetically unique, indicating that the arrival of the species in the continent was independent of these European colonial activities. This suggests the possibility of pre-European human-mediated dispersal across the Pacific Ocean. These significant findings raise new questions for biogeographic studies that assume chance or transoceanic dispersal for disjunct plant distributions.
A physical description of the adhesion and aggregation of platelets
Authors: Chopard Bastien , de Sousa Daniel Ribeiro , Lätt Jonas , Mountrakis Lampros , Dubois Frank , Yourassowsky Catherine , Van Antwerpen Pierre , Eker Omer , Vanhamme Luc , Perez-Morga David , Courbebaisse Guy , Lorenz Eric , Hoekstra Alfons G. , Boudjeltia Karim Zouaoui
Published: April 2017

The early stages of clot formation in blood vessels involve platelet adhesion–aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailedin vitroexperiments, using the well-known Impact-R device, and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account the differential role of pre-activated and non-activated platelets, as well as the three-dimensional nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet aggregate formation in our experiment. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally. They also provide a value of the effective diffusion of platelets in blood subject to the shear rate produced by the Impact-R.
Uncertainty transformation via Hopf bifurcation in fast–slow systems
Authors: Kuehn Christian
Published: April 2017

Propagation of uncertainty in dynamical systems is a significant challenge. Here we focus on random multiscale ordinary differential equation models. In particular, we study Hopf bifurcation in the fast subsystem for random initial conditions. We show that a random initial condition distribution can be transformed during the passage near a delayed/dynamic Hopf bifurcation: (i) to certain classes of symmetric copies, (ii) to an almost deterministic output, (iii) to a mixture distribution with differing moments and (iv) to a very restricted class of general distributions. We prove under which conditions the cases (i)–(iv) occur in certain classes vector fields.
The roles of impact and inertia in the failure of a shoelace knot
Authors: Daily-Diamond Christopher A. , Gregg Christine E. , O'Reilly Oliver M.
Published: April 2017

The accidental untying of a shoelace while walking often occurs without warning. In this paper, we discuss the series of events that lead to a shoelace knot becoming untied. First, the repeated impact of the shoe on the floor during walking serves to loosen the knot. Then, the whipping motions of the free ends of the laces caused by the leg swing produce slipping of the laces. This leads to eventual runaway untangling of the knot. As demonstrated using slow-motion video footage and a series of experiments, the failure of the knot happens in a matter of seconds, often without warning, and is catastrophic. The controlled experiments showed that increasing inertial effects of the swinging laces leads to increased rate of knot untying, that the directions of the impact and swing influence the rate of failure, and that the knot structure has a profound influence on a knot's tendency to untie under cyclic impact loading.
Not equal in the face of habitat change: closely related fishes differ in their ability to use predation-related information in degraded coral
Authors: Ferrari Maud C. O. , McCormick Mark I. , Allan Bridie J. M. , Chivers Douglas P.
Published: April 2017

Coral reefs are biodiversity hotpots that are under significant threat due to the degradation and death of hard corals. When obligate coral-dwelling species die, the remaining species must either move or adjust to the altered conditions. Our goal was to investigate the effect of coral degradation on the ability of coral reef fishes to assess their risk of predation using alarm cues from injured conspecifics. Here, we tested the ability of six closely related species of juvenile damselfish (Pomacentridae) to respond to risk cues in both live coral or dead-degraded coral environments. Of those six species, two are exclusively associated with live coral habitats, two are found mostly on dead-degraded coral rubble, while the last two are found in both habitat types. We found that the two live coral associates failed to respond appropriately to the cues in water from degraded habitats. In contrast, the cue response of the two rubble associates was unaffected in the same degraded habitat. Interestingly, we observed a mixed response from the species found in both habitat types, with one species displaying an appropriate cue response while the other did not. Our second experiment suggested that the lack of responses stemmed from deactivation of the alarm cues, rather than the inability of the species to smell. Habitat preference (live coral versus dead coral associates) and phylogeny are good candidates for future work aimed at predicting which species are affected by coral degradation. Our results point towards a surprising level of variation in the ability of congeneric species to fare in altered habitats and hence underscores the difficulty of predicting community change in degraded habitats.
Changes in the location of biodiversity–ecosystem function hot spots across the seafloor landscape with increasing sediment nutrient loading
Authors: Thrush Simon F. , Hewitt Judi E. , Kraan Casper , Lohrer A. M. , Pilditch Conrad A. , Douglas Emily
Published: April 2017

Declining biodiversity and loss of ecosystem function threatens the ability of habitats to contribute ecosystem services. However, the form of the relationship between biodiversity and ecosystem function (BEF) and how relationships change with environmental change is poorly understood. This limits our ability to predict the consequences of biodiversity loss on ecosystem function, particularly in real-world marine ecosystems that are species rich, and where multiple ecosystem functions are represented by multiple indicators. We investigated spatial variation in BEF relationships across a 300 000 m
2
intertidal sandflat by nesting experimental manipulations of sediment pore water nitrogen concentration into sites with contrasting macrobenthic community composition. Our results highlight the significance of many different elements of biodiversity associated with environmental characteristics, community structure, functional diversity, ecological traits or particular species (ecosystem engineers) to important functions of coastal marine sediments (benthic oxygen consumption, ammonium pore water concentrations and flux across the sediment–water interface). Using the BEF relationships developed from our experiment, we demonstrate patchiness across a landscape in functional performance and the potential for changes in the location of functional hot and cold spots with increasing nutrient loading that have important implications for mapping and predicating change in functionality and the concomitant delivery of ecosystem services.
Transcriptomics of an extended phenotype: parasite manipulation of wasp social behaviour shifts expression of caste-related genes
Authors: Geffre Amy C. , Liu Ruolin , Manfredini Fabio , Beani Laura , Kathirithamby Jeyaraney , Grozinger Christina M. , Toth Amy L.
Published: April 2017

Parasites can manipulate host behaviour to increase their own transmission and fitness, but the genomic mechanisms by which parasites manipulate hosts are not well understood. We investigated the relationship between the social paper wasp,
Polistes dominula
, and its parasite,
Xenos vesparum
(Insecta: Strepsiptera), to understand the effects of an obligate endoparasitoid on its host's brain transcriptome. Previous research suggests that
X. vesparum
shifts aspects of host social caste-related behaviour and physiology in ways that benefit the parasitoid. We hypothesized that
X. vesparum
-infested (stylopized) females would show a shift in caste-related brain gene expression. Specifically, we predicted that stylopized females, who would normally be workers, would show gene expression patterns resembling pre-overwintering queens (gynes), reflecting gyne-like changes in behaviour. We used RNA-sequencing data to characterize patterns of brain gene expression in stylopized females and compared these with those of unstylopized workers and gynes. In support of our hypothesis, we found that stylopized females, despite sharing numerous physiological and life-history characteristics with members of the worker caste, show gyne-shifted brain expression patterns. These data suggest that the parasitoid affects its host by exploiting phenotypic plasticity related to social caste, thus shifting naturally occurring social behaviour in a way that is beneficial to the parasitoid.
Environmental modification via a quorum sensing molecule influences the social landscape of siderophore production
Authors: Popat Roman , Harrison Freya , da Silva Ana C. , Easton Scott A. S. , McNally Luke , Williams Paul , Diggle Stephen P.
Published: April 2017

Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed ‘public goods’ because they are costly for individuals to produce and can be exploited by non-producers (cheats). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS, therefore, determines the cooperative phenotype of individuals, and influences conflict over public goods. In addition to their regulatory functions, many QS molecules have additional properties that directly modify the prevailing environment. This leads to the possibility that QS molecules could influence conflict over public goods indirectly through non-signalling effects, and the impact of this on social competition has not previously been explored. ThePseudomonas aeruginosaQS signal molecule PQS is a powerful chelator of iron which can cause an iron starvation response. Here, we show that PQS stimulates a concentration-dependent increase in the cooperative production of iron scavenging siderophores, resulting in an increase in the relative fitness of non-producing siderophore cheats. This is likely due to an increased cost of siderophore output by producing cells and a concurrent increase in the shared benefits, which accrue to both producers and cheats. Although PQS can be a beneficial signalling molecule forP. aeruginosa, our data suggest that it can also render a siderophore-producing population vulnerable to competition from cheating strains. More generally, our results indicate that the production of one social trait can indirectly affect the costs and benefits of another social trait.
Survival Beyond the Perinatal Period Expands the Phenotypes Caused by Mutations inGLE1
Authors: Said Edith , Chong Jessica X. , Hempel Maja , Denecke Jonas , Soler Paul , Strom Tim , Nickerson Deborah A. , Kubisch Christian , Bamshad Michael ,   University of Washington Center for Mendelian Genomics, Lessel Davor
Published: April 2017

Mutations inGLE1underlie Lethal Congenital Contracture syndrome (LCCS1) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD). Both LCCS1 and LAAHD are characterized by reduced fetal movements, congenital contractures, and a severe form of motor neuron disease that results in fetal death or death in the perinatal period, respectively. Via trio-exome sequencing, we identified bi-allelic mutations inGLE1in two unrelated individuals with motor delays, feeding difficulties and respiratory insufficiency who survived beyond the perinatal period. Each affected child had missense variants predicted to result in amino acid substitutions near the C-terminus of GLE1 that are predicted to disrupt protein-protein interaction or GLE1 protein targeting. We hypothesize that mutations that preserve function of the coiled-coil domain of GLE1 cause LAAHD whereas mutations that abolish the function of the coiled-coil domain cause LCCS1. The phenotype of LAAHD is now expanded to include multiple individuals surviving into childhood suggesting that LAAHD is a misnomer and should be re-named Arthrogryposis with Anterior Horn Cell Disease (AAHD). Too few cases have been reported to identify significant genotype-phenotype relationships, but given that perinatal lethality in AAHD typically resulted from respiratory failure, it is possible that early or aggressive airway management such as early tracheostomy and ventilation may enable survival beyond the perinatal period.
Dynamical Features of Human EEG Scale Systematically with Life Context
Authors: Parameshwaran Dhanya , Thiagarajan Tara C.
Published: April 2017

We have previously shown that the complexity of human brain activity and the emergence and strength of alpha oscillation as measured by EEG scale dramatically with access to the features of modernization. Here we show that these features of the EEG, while correlated to one another are distinct in their origin and that while complexity is most strongly related to travel or geofootprint, energy of the alpha oscillation scales more systematically with fuel consumption. Finally, composite EEG scores representing the dominant principal component scale in remarkable lockstep with the dominant component of the features of modernization. This demonstrates that human brain dynamics, and therefore cognitive outcome, are profoundly and systematically tied to the context of life experience. Indeed the implication is that ‘normal’ brain function is not absolute and can only be considered in relation to or conditional on the context in which it is embedded.
Deep experimental profiling of microRNA diversity, deployment, and evolution across theDrosophilagenus
Authors: Mohammed Jaaved , Flynt Alex S. , Panzarino Alexandra M. , Mondal Md Mosharrof Hussein , Siepel Adam , Lai Eric C.
Published: April 2017

Comparative genomic analyses of microRNAs (miRNAs) have yielded myriad insights into their biogenesis and regulatory activity. While miRNAs have been deeply annotated in a small cohort of model organisms, evolutionary assessments of miRNA flux are clouded by the functional uncertainty of orthologs in related species, and insufficient data regarding the extent of species-specific miRNAs. We address this by generating a comparative small RNA (sRNA) catalog of unprecedented breadth and depth across theDrosophilagenus, extending our extant deep analyses ofD. melanogasterwith sRNA data from multiple tissues of 11 other fly species. Aggregate analysis of several billion sRNA reads permits curation of accurate and holistic compendia of miRNAs across this genus, providing abundant opportunities to identify species- and clade-specific variation in miRNA identity, abundance, and processing. Amongst well-conserved miRNAs, we observe unexpected cases of clade-specific variation in 5′ end precision, occasional antisense loci, and some putatively non-canonical loci. We also employ strict criteria to identify a massive set (649) of novel, evolutionarily-restricted miRNAs. Amongst the bulk collection of species-restricted miRNAs, two notable subpopulations of rapidly-evolving miRNAs are splicing-derived mirtrons and testis-restricted, clustered (TRC) canonical miRNAs. We quantify rates of miRNA birth and death using our annotation and a phylogenetic model for estimating rates of miRNA turnover in the presence of annotation uncertainty. We show striking differences in birth and death rates across miRNA classes defined by biogenesis pathway, genomic clustering, and tissue restriction, and even identify variation heterogeneity amongstDrosophilaclades. In particular, distinct molecular rationales underlie the distinct evolutionary behavior of different miRNA classes. We broaden observations made fromD. melanogasteras Drosophilid-wide principles for opposing evolutionary viewpoints for miRNA maintenance. Mirtrons are associated with a high rate of 3′ untemplated addition, a mechanism that impedes their biogenesis, whereas TRC miRNAs appear to evolve under positive selection. Altogether, these data reveal miRNA diversity amongstDrosophilaspecies and permit future discoveries in understanding their emergence and evolution.
Compressed timeline of recent experience in monkey lPFC
Authors: Tiganj Zoran , Cromer Jason A. , Roy Jefferson E. , Miller Earl K. , Howard Marc W.
Published: April 2017

Cognitive theories suggest that working memory maintains not only the identity of recently-presented stimuli but also a sense of the elapsed time since the stimuli were presented. Previous studies of the neural underpinnings of working memory have focused on sustained firing, which can account for maintenance of the stimulus identity, but not for representation of the elapsed time. We analyzed single-unit recordings from the lateral prefrontal cortex (lPFC) of two macaque monkeys during performance of a delayed-match-to-category task. Each sample stimulus triggered a consistent sequence of neurons, with each neuron in the sequence firing during a circumscribed period of time. These sequences of neurons encoded both stimulus identity and the elapsed time. The encoding of the elapsed time became less precise as the sample stimulus receded into the past. These findings suggest that working memory includes a compressed timeline of what happened when, consistent with longstanding cognitive theories of human memory.

Significance Statement

Place cells in the hippocampus and other brain regions provide basis functions to support the dimension of physical space. Time cells, which activate sequentially provide analogous support for the dimension of time. We observed time cells in the macaque lPFC during a working memory task. The time cells we observed were stimulus specific meaning that they provide not only information about timing, but also conjunctively code what and when information. This representation thus constitutes a manifold with both temporal dimension and a stimulus-coding dimension that could support working memory. These temporal basis functions maintain a logarithmically-compressed timeline of the recent past, providing strong empirical support to long-standing cognitive theories of human memory.
Anillin proteins stabilize the cytoplasmic bridge between the two primordial germ cells during C. elegans embryogenesis
Authors: Goupil Eugénie , Amini Rana , Labbé Jean-Claude
Published: April 2017

Stable cytoplasmic bridges arise from failed cytokinesis, the last step of cell division, and are a key feature of syncytial architectures in the germ line of most metazoans. Whereas the C. elegans germ line is syncytial, its formation remains poorly understood. We studied the role of ANI-2, a noncanonical and shorter form of the actomyosin scaffold protein anillin that is expressed specifically during embryogenesis in the germ line precursor blastomere, P4. We found that the P4 blastomere does not complete abscission following cytokinesis, leaving a stable cytoplasmic bridge between the two daughter cells. Interestingly, depletion of ANI-2 results in a regression of the membrane partition between the two cells, indicating that ANI-2 is required to stabilize the cytoplasmic bridge. We identified several contractility regulators that, like ANI-2, localize to the cytoplasmic bridge and are required to stabilize it. Epistatic analysis of these regulators’ mutual dependencies revealed a pathway in which Rho regulators promote ANI-2 accumulation at the stable cytoplasmic bridge, which in turns promotes the accumulation of the non-muscle myosin II NMY-2 and the midbody component CYK-7 at the bridge, in part by limiting the accumulation of canonical anillin ANI-1. Our results uncover key steps in C. elegans germ line formation and define a set of conserved regulators that ensure the proper stability of the primordial germ cell cytoplasmic bridge during embryonic development.
Anterior cingulate cortex represents action-state predictions and causally mediates model-based reinforcement learning in a two-step decision task
Authors: Akam Thomas , Rodrigues-Vaz Ines , Marcelo Ivo , Zhang Xiangyu , Pereira Michael , Oliveira Rodrigo Freire , Dayan Peter , Costa Rui M.
Published: April 2017

The anterior cingulate cortex (ACC) is implicated in learning the value of actions, but it remains poorly understood whether and how it contributes to model-based mechanisms that use action-state predictions and afford behavioural flexibility. To isolate these mechanisms, we developed a multi-step decision task for mice in which both action-state transition probabilities and reward probabilities changed over time. Calcium imaging revealed ramps of choice-selective neuronal activity, followed by an evolving representation of the state reached and trial outcome, with different neuronal populations representing reward in different states. ACC neurons represented the current action-state transition structure, whether state transitions were expected or surprising, and the predicted state given chosen action. Optogenetic inhibition of ACC blocked the influence of action-state transitions on subsequent choice, without affecting the influence of rewards. These data support a role for ACC in model-based reinforcement learning, specifically in using action-state transitions to guide subsequent choice.

Highlights

A novel two-step task disambiguates model-based and model-free RL in mice.

ACC represents all trial events, reward representation is contextualised by state.

ACC represents action-state transition structure, predicted states, and surprise.

Inhibiting ACC impedes action-state transitions from influencing subsequent choice.
Transcriptome sequencing and delimitation of cryptic Oscarella species (O. carmela and O. pearsei sp. nov) from California, USA
Authors: Ereskovsky Alexander , Richter Daniel J. , Lavrov Dennis V. , Schippers Klaske J. , Nichols Scott A.
Published: April 2017

The homoscleromorph sponge Oscarella carmela, first described from central California, USA is shown to represent two morphologically similar but phylogenetically distant species that are co-distributed. We here describe a new species as Oscarella pearsei, sp. nov. and redescribe Oscarella carmela; the original description was based upon material from both species. Further, we correct the identification of published genomic/transcriptomic resources that were originally attributed to O. carmela, and present new Illumina-sequenced transcriptome assemblies for each of these species, and the mitochondrial genome sequence for O. pearsei sp. nov. Using SSU and LSU ribosomal DNA and the mitochondrial genome, we report the phylogenetic relationships of these species relative to other Oscarella species, and find strong support for placement of O. pearsei sp. nov. in a clade defined by the presence of spherulous cells that contain paracrystalline inclusions; O. carmela lacks this cell type and is most closely related to the Western Pacific species, O. malakhovi. Oscarella pearsei sp. nov and O. carmela can be tentatively distinguished based upon gross morphological differences such as color, surface texture and extent of mucus production, but can be more reliably identified using mitochondrial and nuclear barcode sequencing, ultrastructural characteristics of cells in the mesohyl, and the morphology of the follicle epithelium which surrounds the developing embryo in reproductively active individuals. Usually, cryptic species are very closely related to each other, but in this case and in sponges generally, cryptic species may be very distantly related because sponges can be difficult to identify based upon gross morphological characteristics.
Household triclosan and triclocarban exposure impacts the adult intestinal microbiome but not the infant intestinal microbiome
Authors: Ribado Jessica V. , Ley Catherine , Haggerty Thomas D. , Tkachenko Ekaterina , Bhatt Ami S. , Parsonnet Julie
Published: April 2017

In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products. This decision was due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the intestinal microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction of either infant or maternal intestinal microbiotas following 10 months of exposure after birth. However, broadly antibiotic-resistant species from the phylum Proteobacteria were enriched in stool samples from mothers in TC households only after the introduction of triclosan-containing toothpaste. Despite the minimal effects of TC exposure from wash products on the gut microbial community of infants and adults, these results suggest detected taxonomic differences are associated with potential harmful effects on host physiology, highlighting the need for consumer safety testing of self-care products not subject to the ban on the human microbiome and health outcomes.
Stags, Hawks, and Doves: Social Evolution Theory and Individual Variation in Cooperation
Authors: Van Cleve Jeremy
Published: April 2017

One of the triumphs of evolutionary biology is the discovery of robust mechanisms that promote the evolution of cooperative behaviors even when those behaviors reduce the fertility or survival of cooperators. Though these mechanisms, kin selection, reciprocity, and nonlinear payoffs to cooperation, have been extensively studied separately, investigating their joint effect on the evolution of cooperation has been more difficult. Moreover, how these mechanisms shape variation in cooperation is not well known. Such variation is crucial for understanding the evolution of behavioral syndromes and animal personality. Here, I use the tools of kin selection theory and evolutionary game theory to build a framework that integrates these mechanisms for pairwise social interactions. Using relatedness as a measure of the strength of kin selection, responsiveness as a measure of reciprocity, and synergy as a measure of payoff nonlinearity, I show how different combinations of these three parameters produce directional selection for or against cooperation or variation in levels of cooperation via balancing or diversifying selection. Moreover, each of these outcomes maps uniquely to one of four classic games from evolutionary game theory, which means that modulating relatedness, responsiveness, and synergy effectively transforms the payoff matrix from one the evolutionary game to another. Assuming that cooperation exacts a fertility cost on cooperators and provides a fertility benefit to social partners, a prisoner’s dilemma game and directional selection against cooperation occur when relatedness and responsiveness are low and synergy is not too positive. Enough positive synergy in these conditions generates a stag-hunt game and diversifying selection. High levels of relatedness or responsiveness turn cooperation from a fitness cost into a fitness benefit, which produces a mutualism game and directional selection for cooperation when synergy is not too negative. Sufficiently negative synergy in this case creates a hawk-dove game and balancing selection for cooperation. I extend the results with relatedness and synergy to larger social groups and show that how group size changes the effect of relatedness and synergy on selection for cooperation depends on how the per capita benefit of cooperation changes with group size. Together, these results provide a general framework with which to generate comparative predictions that can be tested using quantitative genetic techniques and experimental techniques that manipulate investment in cooperation. These predictions will help us understand both interspecific variation in cooperation as well as within-population and within-group variation in cooperation related to behavioral syndromes.