bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological and Physiological Characteristics of Ebf2-EGFP-Expressing Cajal-Retzius Cells in Developing Mouse Neocortex
Authors: Sun Le , Chen Ruiguo , Bai Ye , Li Jia , Wu Qian , Shen Qin , Wang Xiaoqun
Published: September 2018

Cajal-Retzius (CR) cells are one of the earliest populations of neurons in the cerebral cortex of rodents and primates, and they play a critical role in corticogenesis and cortical lamination during neocortical development. However, a comprehensive morphological and physiological profile of CR cells in the mouse neocortex has not yet been established. Here, we systematically investigated the dynamic development of CR cells in Tg(Ebf2-EGFP)58Gsat/Mmcd mice. The morphological complexity, membrane activities and presynaptic inputs of CR cells coordinately increase and reach a plateau at P5–P9 before regressing. Using 3D reconstruction, we delineated a parallel-stratification pattern of the axonal extension of CR cells. Furthermore, we found that the morphological structure and presynaptic inputs of CR cells were disturbed in Reelin-deficient mice. These findings confirm that CR cells undergo a transient maturation process in layer 1 before disappearing. Importantly, Reelin deficiency impairs the formation of synaptic connections onto CR cells. In conclusion, our results provide insights into the rapid maturation and axonal stratification of CR cells in layer 1. These findings suggest that both the electrophysiological activities and the morphology of CR cells provide vital guidance for the modulation of early circuits, in a Reelin-dependent manner.
Congestion management in protected areas: accounting for respondents’ inattention and preference heterogeneity in stated choice data
Authors: Thiene Mara , Franceschinis Cristiano , Scarpa Riccardo
Published: October 2018

Congestion levels in protected areas can be predicted by destination choice models estimated from choice data. There is growing evidence of subjects’ inattention to attributes in choice experiments. We estimate an attribute non-attendance latent class–random parameters model (LC–RPL) that jointly handles inattention and preference heterogeneity. We use data from a choice experiment designed to elicit visitors’ preferences towards sustainable management of a protected area in the Italian Alps. Results show that the LC–RPL model produces improvements in model fit and reductions in the implied rate of inattention, as compared to traditional approaches. Implications of results for park management authorities are discussed.
Patterns and factors affecting antenatal care utilization in Damietta Governorate, Egypt: a retrospective cross-sectional study
Authors: Farrag Nesrine S , Abdelwahab Farida , Ismail Ghada R
Published: October 2018

Background

Timely antenatal care (ANC) has been proven to save lives and maximizes health and potential. The study aimed to assess ANC utilization rates in Damietta district, Egypt and to identify the components of ANC provided and factors affecting utilization rates.

Methods

A cross-sectional study was conducted in four Family Health Centers (FHC) in Damietta district. The study included any mother, who gave birth within the last 6 months, after giving written consent to participate. Women were interviewed about their experience with ANC during the last pregnancy using a pre-designed questionnaire.

Results

The study found that ~85% of the mothers have ever attended ANC during the last pregnancy, two-thirds were regular attendants. Urban residence, being not working, having high education and high family income were positively associated with utilization of ANC (P < 0.001). Only 30% of the mothers received ANC in FHCs, while the majority received ANC at private clinics. Rates of receiving ANC components were variable with significantly higher rates in private clinics than governmental FHCs (P < 0.001 for most components). Health education was the least ANC component to be received by mothers at governmental and private sites.

Conclusion

More work is needed to improve the utilization of ANC in FHCs. Providers of ANC should be trained and supervised to provide full package of ANC especially health education message, being the most neglected component of ANC.
Race and Objective Social Isolation: Older African Americans, Black Caribbeans, and Non-Hispanic Whites
Authors: Taylor Robert Joseph , Chatters Linda M , Taylor Harry O
Published: September 2018

Objectives

Social isolation is a major risk factor for poor physical and mental health among older adults. This study investigates the correlates of objective social isolation among older African Americans, Black Caribbean immigrants, and non-Hispanic Whites.

Methods

The analysis is based on the older subsample (n = 1,439) of the National Survey of American Life. There are eight indicators of objective social isolation: no contact with neighbors, neighborhood groups, friends, family members, religious congregation members, not being married and no romantic involvement, living alone, and not being a parent.

Results

Very few older Americans are socially isolated from family and friends. Non-Hispanic Whites are more likely than both African Americans and Black Caribbeans to live alone, to be childless, and have limited contact with religious congregation members. For both African Americans and Black Caribbeans, being female is protective against social isolation, but for both populations, men are more likely to be married or have a romantic partner. For African Americans, residing in the South is also protective against social isolation.

Discussion

This analysis provides greater clarity on racial and ethnic differences in social isolation among older adults, as well as within-group differences in objective social isolation among African Americans and Black Caribbeans.
Impact of Self-Acupressure on Co-Occurring Symptoms in Cancer Survivors
Authors: Zick Suzanna Maria , Sen Ananda , Hassett Afton Luevano , Schrepf Andrew , Wyatt Gwen Karilyn , Murphy Susan Lynn , Arnedt John Todd , Harris Richard Edmund
Published: October 2018

Background

Cancer survivors with fatigue often experience depressive symptoms, anxiety, and pain. Previously, we reported that self-acupressure improved fatigue; however, its impact on other co-occurring symptoms and their involvement in treatment action has not been explored.

Methods

Changes in depressive symptoms, anxiety, and pain were examined prior to and following two formulas of self-acupressure and usual care using linear mixed models in 288 women from a previously reported clinical trial. Participants were categorized by random assignment into one of three groups: 1) relaxing acupressure, 2) stimulating acupressure, or 3) usual care. Moderators investigated were body mass index, age, depressive symptoms, anxiety, sleep and pain, and mediators were change in these symptoms.

Results

Following treatment, depressive symptoms improved statistically significantly for the relaxing acupressure group (41.5%) compared with stimulating acupressure (25%) and usual care (7.7%). Both acupressure groups were associated with greater improvements in anxiety than usual care, but only relaxing acupressure was associated with greater reductions in pain severity, and only stimulating acupressure was associated with greater reductions in pain interference. There were no statistically significant moderators of sleep quality, anxiety, or depressive symptoms. Fatigue statistically significantly moderated pain, and age statistically significantly modified fatigue. Changes in depressive symptoms and sleep quality statistically significantly mediated the relationship between relaxing acupressure and usual care on fatigue; however, the effect was small.

Conclusions

Acupressure was associated with greater improvements than usual care in anxiety, pain, and symptoms of depression in breast cancer survivors with troublesome fatigue. These findings warrant further evaluation in suitably controlled randomized trials.
Providing Advice to Jobseekers at Low Cost: An Experimental Study on Online Advice
Authors: Belot Michèle , Kircher Philipp , Muller Paul
Published: October 2018

We develop and evaluate experimentally a novel tool that redesigns the job search process by providing tailored advice at low cost. We invited jobseekers to our computer facilities for twelve consecutive weekly sessions to search for real jobs on our web interface. For one-half, instead of relying on their own search criteria, we use readily available labour market data to display relevant alternative occupations and associated jobs. The data indicate that this broadens the set of jobs they consider and increases their job interviews especially for participants who otherwise search narrowly and have been unemployed for a few months.
Zika Virus Infection
Authors: Grazel Regina , Harris-Haman Pamela
Published: October 2018

Background:

Zika virus (ZIKV) is an emergent flavivirus, transmitted predominately by Aedes genus mosquitos that recently reached the Americas and was soon implicated in an increase in microcephaly and other serious birth defects.

Purpose:

This report provides updated information and recommendations on testing, screening, and care for pregnant women and infants affected by ZIKV.

Methods:

Current published recommendations from the Centers for Disease Control and Prevention, the World Health Organization, and the American Academy of Pediatrics were reviewed and included in this report.

Results:

Although largely a self-limiting disease usually without symptoms, pregnant women and their fetuses are at greatest risk. Maternal transmission of ZIKV to the fetus can lead to congenital Zika infection with potentially devastating sequelae to the infant. The available evidence suggests that infection during the first trimester of pregnancy, in which the fetus' central nervous system is being formed, is associated with higher risk of brain abnormalities and perinatal loss.

Implications for Practice:

Uncertainties remain about the course of the disease, and the full spectrum of effects of the virus on the developing infant is not yet understood. Infants with congenital Zika syndrome need coordinated follow-up and long-term specialty care, as well as support for the family.

Implications for Research:

There is no known cure for ZIKV infection and no vaccine is currently available. The full spectrum of developmental disabilities and other adverse early childhood outcomes associated with congenital ZIKV infection needs to be studied.
Clinical Care of Lesbian and Bisexual Women for the Obstetrician Gynecologist
Authors: McCUNE KAITLYN C. , IMBOREK KATHERINE L.
Published: October 2018

Sexual minority women are more likely to delay care, less likely to have a usual place of care, and more likely to exhibit higher risk behaviors such as smoking, obesity, heavy drinking resulting in a disproportionate number of chronic conditions. It is imperative for obstetrician-gynecologists to be at the forefront of providing comprehensive health care to all women, no matter their sexual orientation. This article seeks to discuss health care disparities as well as health behaviors and outcomes in this population. In addition, it will review the appropriate recommendations for clinical care of sexual minority women for the obstetrician/gynecologist.
More Than Just a Game
Authors: Blauwet Cheri A.
Published: October 2018

Although people with disabilities make up a large proportion of our global population and are known to be disproportionately impacted by sedentary lifestyles leading to chronic disease, programs promoting physical activity often fail to address their unique needs. Both environmental and attitudinal factors also act as barriers to full participation. In this context, increasing evidence shows the positive impact of physical activity and sport on outcomes related to physical health, mental health, community participation, and, in some cases, neurorecovery for people with disabilities. Thus, participation should be seen not only as a medical intervention but also as a rights-based issue. We, as physiatrists, can be agents of change by promoting concepts of universal design and inclusion in physical activity and sport programs.
Notch2 signaling regulates Id4 and cell cycle genes to maintain neural stem cell quiescence in the adult hippocampus
Authors: Zhang Runrui , Boareto Marcelo , Engler Anna , Louvi Angeliki , Giachino Claudio , Iber Dagmar , Taylor Verdon
Published: September 2018

Neural stem cells (NSCs) in the adult hippocampal dentate gyrus (DG) can be quiescent or proliferative, but how they are maintained is largely unknown. With age DG NSCs become increasingly dormant, which impinges on neuron generation. We addressed how NSC activity is controlled and found that Notch2 promotes quiescence by regulating their transition to the activated state. Notch2-ablation induces cell cycle genes and markers of active NSCs. Conversely, quiescent NSC-associated genes, including Id4, are down regulated after Notch2 deletion. We found that Notch2 binds the Id4 promoter and positively regulates transcription. Similar to Notch2, Id4 overexpression promotes DG NSC quiescence and Id4 knockdown rescues proliferation, even when Notch2 signaling is activated. We show that Notch2 regulates age-dependent DG NSC dormancy and Notch2 inhibition rejuvenates neurogenesis in the DG of aged mice. Our data indicate that a Notch2-Id4 axis promotes adult DG NSC quiescence and dormancy.
MetaMap, an interactive webtool for the exploration of metatranscriptomic reads in human disease-related RNA-seq data
Authors: Simon LM , Tsitsiridis G , Angerer P , Theis FJ
Published: September 2018

Motivation

The MetaMap resource contains metatranscriptomic expression data from screening >17,000 RNA-seq samples from >400 archived human disease-related studies for viral and microbial reads, so-called “metafeatures”. However, navigating this set of large and heterogeneous data is challenging, especially for researchers without bioinformatic expertise. Therefore, a user-friendly interface is needed that allows users to visualize and statistically analyse the data.

Results

We developed an interactive frontend to facilitate the exploration of the MetaMap resource. The webtool allows users to query the resource by searching study abstracts for keywords or browsing expression patterns for specific metafeatures. Moreover, users can manually define sample groupings or use the existing annotation for downstream analysis. The web tool provides a large variety of analyses and visualizations including dimension reduction, differential abundance analysis and Krona visualizations. The MetaMap webtool represents a valuable resource for hypothesis generation regarding the impact of the microbiome in human disease.

Availability

The presented web tool can be accessed at https://github.com/theislab/MetaMap
DISNET: A framework for extracting phenotypic disease information from public sources
Authors: Lagunes-García Gerardo , Rodríguez-González Alejandro , Prieto-Santamaría Lucía , García del Valle Eduardo P. , Zanin Massimiliano , Menasalvas-Ruiz Ernestina
Published: September 2018

Within the global endeavour of improving population health, one major challenge is the increasingly high cost associated with drug development. Drug repositioning, i.e. finding new uses for existing drugs, is a promising alternative; yet, its effectiveness has hitherto been hindered by our limited knowledge about diseases and their relationships. In this paper, we present DISNET (disnet.ctb.upm.es), a web-based system designed to extract knowledge from signs and symptoms retrieved from medical databases, and to enable the creation of customisable disease networks. We here present the main features of the DISNET system. We describe how information on diseases and their phenotypic manifestations is extracted from Wikipedia, PubMed and Mayo Clinic; specifically, texts from these sources are processed through a combination of text mining and natural language processing techniques. We further present a validation of the processing performed by the system; and describe, with some simple use cases, how a user can interact with it and extract information that could be used for subsequent analyses.
Divergent neuronal DNA methylation patterns across human cortical development: Critical periods and a unique role of CpH methylation
Authors: Price AJ , Collado-Torres L , Ivanov NA , Xia W , Burke EE , Shin JH , Tao R , Ma L , Jia Y , Hyde TM , Kleinman JE , Weinberger DR , Jaffe AE
Published: September 2018

We have characterized the landscape of DNA methylation (DNAm) across the first two decades of human neocortical development in NeuN+ neurons using whole-genome bisulfite sequencing and compared them to non-neurons (primarily glia) and prenatal homogenate cortex. We show that DNAm changes more dramatically during the first five years of postnatal life than during the entire remaining period. We further refined global patterns of increasingly divergent neuronal CpG and CpH methylation (mCpG and mCpH) into six developmental trajectories and found that in contrast to genome-wide patterns, neighboring mCpG and mCpH levels within these regions were highly correlated. We then integrated paired RNA-seq data and identified direct regulation of hundreds of transcripts and their splicing events exclusively by mCpH levels, independently from mCpG levels, across this period. We finally explored the relationship between DNAm patterns and development of brain-related phenotypes and found enriched heritability for many phenotypes within DNAm features we identify.
Copy parents or follow friends? Juvenile foraging behaviour changes with social environment
Authors: Franks Victoria R. , Ewen John G. , McCready Mhairi , Thorogood Rose
Published: September 2018

The first few months of juvenile independence is a critical period for survival as young must learn new behaviours to forage efficiently. Social learning by observing parents (vertical transmission) or others (horizontal/oblique transmission) may be important to overcome naivety, but these tutors are likely to differ in their reliability due to variation in their own experience. How young animals use different social information sources, however, has received little attention. Here we tested if wild juvenile hihi (Notiomystis cincta, a New Zealand passerine) retained foraging behaviours learned from parents, or if behaviour changed after independence in response to peers. We first trained parents with feeders during chick rearing: one-third could access food from any direction, one-third could access food from one side only, and the remaining third had no feeder. During post-fledge parental care, juveniles chose the same side as their parents. Once independent, juveniles formed mixed-treatment groups naturally so we then presented feeders with two equally profitable sides. Juveniles with natal feeder experience were quicker to use these feeders initially, but side choice was now random. Over time, however, juveniles converged on using one side of the feeder (which differed between groups). This apparent conformity was because juvenile hihi paid attention to the behaviour of their group and were more likely to choose the locally-favoured side as the number of visits to that side increased. They did not copy the choice of specific individuals, even when they were more social or more familiar with the preceding bird. Our study shows that early social experiences with parents affect foraging decisions, but later social environments lead juveniles to modify their behaviour.
A ghost of dioecy past and the legacy of sexual dimorphism: low siring success of hermaphrodites after the breakdown of dioecy
Authors: Blanco Luis Santos del , Tudor Eleri , Pannell John R.
Published: September 2018

Evolutionary transitions from dioecy to hermaphroditism must overcome the inertia of sexual dimorphism because modified males or females will express the opposite sexual function for which their phenotypes have been optimized. We tested this prediction by comparing the siring success of female-derived hermaphrodites of the plant Mercurialis annua with males and hermaphrodites that present a male-like inflorescence. We found that pollen dispersed by female-derived hermaphrodites was about a third poorer at siring outcross offspring than that from hermaphrodites with male-like inflorescences, illustrating the notion that a ‘ghost of dioecy past’ compromises the fitness of derived hermaphrodites in outcrossing populations. We conclude that whereas dioecy might evolve from hermaphroditism by conferring upon individuals certain benefits of sexual specialization, reversals from dioecy to hermaphroditism must often be limited to situations in which outcrossing cannot be maintained and inbreeding is favored. Our study provides novel empirical support for evolutionary models for the breakdown of dioecy.
Size-based ecological interactions drive food web responses to climate warming
Authors: Lindmark Max , Ohlberger Jan , Huss Magnus , Gårdmark Anna
Published: September 2018

Predicting the impacts of climate change on animal populations and communities requires understanding of feedbacks between direct physiological responses and indirect effects via ecological interactions. Food-dependent body growth and within-species size variation have major effects on dynamics of populations and communities through feedbacks between individual performance and population size structure. Moreover, evidence suggests a link between temperature and population size structure, but we lack an understanding of how this is mediated by species interactions when life history processes are food-dependent. Here, we use a dynamic stage-structured biomass model with food-, size- and temperature-dependent life history processes to assess how temperature affects coexistence, stability and size structure in a tri-trophic food chain. We show that predator biomass densities decline with warming either gradually or in the form of collapses, depending on which consumer life stage they predominantly feed on. Collapses occur when warming destabilizes the community and induces alternative stable states via Allee effects, which emerge when predators promote their own food source through predation. By contrast, warming at low temperatures stabilizes the community as limit cycles turn to fixed point dynamics, unless predators feed only on juveniles. Elevated costs of being large in warmer environments accelerate the decline in predator persistence and mean body size of the community. These results suggest that predator persistence in warmer climates may be lower than previously acknowledged when accounting for size- and food-dependence of life history processes, and that interactions within and between species can mediate the effects of warming on food web stability.

Significance

Climate warming is altering the dynamics and structure of aquatic ecosystems worldwide. Predicting food web reorganization under rising temperatures requires an understanding of physiological responses and ecological interactions of organisms, both of which depend on body size. We show that size variation within species, food-dependent growth and ecological interactions critically affect how food chains respond to warming. Specifically, warming can stabilize or destabilize food chains and expose predators to increased risk of sudden collapses, resulting in alternative stable food web states. Increasing temperatures can cause abrupt reductions in mean community body size, primarily due to loss of top predators. The potential loss of biodiversity and shifts in ecosystem stability are among the major challenges caused by a warming climate.
Gsmodutils: A python based framework for test-driven genome scale metabolic model development
Authors: Gilbert James P , Pearcy Nicole , Norman Rupert , Millat Thomas , Winzer Klaus , King John , Hodgman Charlie , Minton Nigel , Twycross Jamie
Published: September 2018

Motivation

Genome scale metabolic models (GSMMs) are increasingly important for systems biology and metabolic engineering research as they are capable of simulating complex steady-state behaviour. Constraints based models of this form can include thousands of reactions and metabolites, with many crucial pathways that only become activated in specific simulation settings. However, despite their widespread use, power and the availability of tools to aid with the construction and analysis of large scale models, little methodology is suggested for the continued management of curated large scale models. For example, when genome annotations are updated or new understanding regarding behaviour of is discovered, models often need to be altered to reflect this. This is quickly becoming an issue for industrial systems and synthetic biotechnology applications, which require good quality reusable models integral to the design, build and test cycle.

Results

As part of an ongoing effort to improve genome scale metabolic analysis, we have developed a test-driven development methodology for the continuous integration of validation data from different sources. Contributing to the open source technology based around COBRApy, we have developed thegsmodutilsmodelling framework placing an emphasis on test-driven design of models through defined test cases. Crucially, different conditions are configurable allowing users to examine how different designs or curation impact a wide range of system behaviours, minimising error between model versions.

Availability

The software framework described within this paper is open source and freely available fromhttp://github.com/SBRCNottingham/gsmodutils
Changes in social groups across reintroductions and effects on post-release survival
Authors: Franks Victoria R. , Andrews Caitlin E. , Ewen John G. , McCready Mhairi , Parker Kevin A. , Thorogood Rose
Published: September 2018

Reintroductions are essential to many conservation programmes, and thus much research has focussed on understanding what determines the success of these translocation interventions. However, while reintroductions disrupt both the abiotic and social environments, there has been less focus on the consequences of social disruption. Therefore, here we investigate if moving familiar social groups may help animals (particularly naïve juveniles) adjust to their new environment and increase the chances of population establishment. We used social network analysis to study changes in group composition and individual sociality across a reintroduction of 40 juvenile hihi (Notiomystis cincta), a threatened New Zealand passerine. We collected observations of groups before a translocation to explore whether social behaviour before the reintroduction predicted associations after, and whether reintroduction influenced individual sociality (degree). We also assessed whether grouping familiar birds during temporary captivity in aviaries maintained group structure and individual sociality, compared to our normal translocation method (aviaries of random familiarity). Following release, we measured if survival depended on how individual sociality had changed. By comparing these analyses with birds that remained at the source site, we found that translocation lead to re-assortment of groups: non-translocated birds maintained their groups, but translocated juveniles formed groups with both familiar and unfamiliar birds. Aviary holding did not improve group cohesion; instead, juveniles were less likely to associate with aviary-mates. Finally, we found that translocated juveniles that lost the most associates experienced a small but significant tendency for higher mortality. This suggests sociality loss may have represented a disruption that affected their ability to adapt to a new site.
Is there a BMAA transfer in the pelagic and benthic food webs in the Baltic Sea?
Authors: Zguna Nadezda , Karlson Agnes , Ilag Leopold L. , Garbaras Andrius , Gorokhova Elena
Published: September 2018

The evidence regarding BMAA occurrence in the Baltic Sea is contradictory, with benthic sources appearing to be more important than pelagic ones. The latter is counterintuitive considering that pelagic primary producers, such as diatoms, dinoflagellates, and cyanobacteria, are the only plausible source of this compound in the food webs. To elucidate BMAA distribution in trophic pathways, we analyzed BMAA in the pelagic and benthic food webs sampled in summer 2010 in the Northern Baltic Proper. As potential BMAA sources, phytoplankton communities in early and late summer were used. As pelagic consumers, zooplankton, mysids and zooplanktivorous fish (herring) were used, whereas benthic invertebrates (amphipods, priapulids, polychaetes, and clams) and benthivorous fish (perch and flounder) represented the benthic food chain. To establish the trophic structure of the system, the stable isotope (δ13C and δ15N) composition of its components was determined. Contrary to the reported ubiquitous occurrence of BMAA in the Baltic food webs, only phytoplankton and lower consumers (zooplankton and mysids) of the pelagic food chain tested positive. Given that our analytical approaches were adequate, we conclude that no measurable levels of this compound occurred in the benthic invertebrates and any of the tested fish species in the study area. These findings indicate that widely assumed presence and transfer of BMAA to the top consumers in the food webs of the Baltic Sea and, possibly, other systems remain an open question. More controlled experiments and field observations are needed to understand the transfer and possible transformation of BMAA in the food web under various environmental settings.
Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders
Authors: Kiat Pua Emmanuel Peng , Ball Gareth , Adamson Chris , Bowden Stephen , Seal Marc L
Published: September 2018

The neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n=100; n=84 males; mean age: 11.43 years; mean IQ: 110.58) was strictly matched to a control participant (n=100; n=84 males; mean age: 11.43 years; mean IQ: 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and bootstrapped permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features, p=0.01, n=5000 permutations; 10 surface area features, p=0.006, n=5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.
Cholinergic switch between two types of slow waves in cerebral cortex
Authors: Nghiem Trang-Anh E , Tort-Colet Núria , Górski Tomasz , Ferrari Ulisse , Moghimyfiroozabad Shayan , Goldman Jennifer S. , Teleńczuk Bartosz , Capone Cristiano , Bal Thierry , di Volo Matteo , Destexhe Alain
Published: September 2018

Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordingsin vivo,in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory vs excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was testedin vitroby varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.
Reduced frontal gamma power at 24 months is associated with better expressive language in toddlers at risk for autism
Authors: Wilkinson Carol L. , Levin April R. , Gabard-Durnam Laurel J. , Tager-Flusberg Helen , Nelson Charles A.
Published: September 2018

Gamma oscillations have been associated with early language development in typically developing toddlers, and gamma band abnormalities have been observed in individuals with ASD, as well high-risk infant siblings (those having an older sibling with autism), as early as 6-months of age. The current study investigated differences in baseline frontal gamma power and its association with language development in toddlers at high versus low familial risk for autism. EEG recordings as well as cognitive and behavioral assessments were acquired at 24-months as part of prospective, longitudinal study of infant siblings of children with and without autism. Diagnosis of autism was determined at 24–36 months, and data was analyzed across three outcome groups - low risk without ASD (n=43), high-risk without ASD (n=42), and high-risk with ASD (n=16). High-risk toddlerswithoutASD had reduced baseline frontal gamma power (30–50Hz) compared to low-risk toddlers. Among high-risk toddlers increased frontal gamma was only marginally associated with ASD diagnosis (p=0.06), but significantly associated with reduced expressive language ability (p=0.007). No association between gamma power and language was present in the low-risk group. These findings suggest that differences in gamma oscillations in high-risk toddlers may represent compensatory mechanisms associated with improved developmental outcomes.
Switching toxic protein function in life cells
Authors: Faden Frederik , Mielke Stefan , Dissmeyer Nico
Published: September 2018

Toxic proteins are prime targets for molecular farming and efficient tools for targeted cell ablation in genetics, developmental biology, and biotechnology. Achieving conditional activity of cytotoxins and their maintenance in form of stably transformed transgenes is challenging. We demonstrate here a switchable version of the highly cytotoxic bacterial ribonuclease barnase by using efficient temperature-dependent control of protein accumulation in living multicellular organisms. By tuning the levels of the protein, we were able to control the fate of a plant organin vivo. The on-demand-formation of specialized epidermal cells (trichomes) through manipulating stabilization versus destabilization of barnase is a proof-of-concept for a robust and powerful tool for conditional switchable cell arrest. We present this tool both as a potential novel strategy for the manufacture and accumulation of cytotoxic proteins and toxic high-value products in plants or for conditional genetic cell ablation.
Dynamic interaction network inference from longitudinal microbiome data
Authors: Lugo-Martinez Jose , Ruiz-Perez Daniel , Narasimhan Giri , Bar-Joseph Ziv
Published: September 2018

Background

Several studies have focused on the microbiota living in environmental niches including human body sites. In many of these studies researchers collect longitudinal data with the goal of understanding not just the composition of the microbiome but also the interactions between the different taxa. However, analysis of such data is challenging and very few methods have been developed to reconstruct dynamic models from time series microbiome data.

Results

Here we present a computational pipeline that enables the integration of data across individuals for the reconstruction of such models. Our pipeline starts by aligning the data collected for all individuals. The aligned profiles are then used to learn a dynamic Bayesian network which represents causal relationships between taxa and clinical variables. Testing our methods on three longitudinal microbiome data sets we show that our pipeline improve upon prior methods developed for this task. We also discuss the biological insights provided by the models which include several known and novel interactions.

Conclusions

We propose a computational pipeline for analyzing longitudinal microbiome data. Our results provide evidence that microbiome alignments coupled with dynamic Bayesian networks improve predictive performance over previous methods and enhance our ability to infer biological relationships within the microbiome and between taxa and clinical factors.
Transcriptional initiation and mechanically driven propagation of a tissue morphogenetic wave during axis elongation
Authors: Bailles Anais , Collinet Claudio , Philippe Jean-Marc , Lenne Pierre-François , Munro Edwin , Lecuit Thomas
Published: September 2018

Tissue morphogenesis emerges from coordinated cell shape changes driven by actomyosin contraction1, 2. Spatial patterns of gene expression regionalize and polarize cell behaviours, such as apical constriction in the ventral mesoderm and cell intercalation in the lateral ectoderm ofDrosophila3. Thus, tissue dynamics is largely governed genetically. Actomyosin contractile networks drive cell and tissue-level shape changes and can respond to mechanical stimuli4–9. However how genetic information and mechanical control drive tissue-level morphogenesis is not well understood.

Here we report two phases and modalities of Rho1 and non-muscle MyosinII (MyoII) activation in theDrosophilaposterior endoderm. First, Rho1/MyoII are induced apically in a spatially restricted primordium region via localized transcription of the GPCR ligand Fog. Second, a tissue-scale travelling wave of Rho1/MyoII activation and cell invagination progresses anteriorly across the dorsal epithelium at a constant speed of 1 cell every 3 minutes. Remarkably, the MyoII wave does not require sustained gene transcription, and is also insensitive to perturbations in the level and pattern of Fog expression. Thus, whilefogtranscription initiates Rho1/MyoII activation in the primordium, Fog delivery does not govern wave dynamics. Instead, perturbing the mechanical environment of the endoderm impaired MyoII wave dynamics. MyoII inhibition blocked acute Rho1 activation and propagation, suggesting that MyoII contractility provides both local feedback amplification and spatial coupling necessary for wave progression. Finally, we identify a cycle of 3D cell deformations that link MyoII activation and invagination in one row of cells to vitelline membrane attachment, apical spreading, MyoII activation and invagination in the next row, to drive anterior progression of the invagination wave. Thus endoderm morphogenesis emerges from local transcriptional initiation and a mechanically driven travelling cycle of cell contraction and deformation.
A Genetically Engineered Primary Human Natural Killer Cell Platform for Cancer Immunotherapy
Authors: Pomeroy Emily J. , Hunzeker John T. , Kluesner Mitchell T. , Crosby Margaret R. , Lahr Walker S. , Bendzick Laura , Miller Jeffrey S. , Webber Beau R. , Geller Melissa A. , Walcheck Bruce , Felices Martin , Starr Timothy K. , Moriarity Branden S.
Published: September 2018

Tumors can evade natural killer (NK) cells by activating inhibitory pathways. We therefore have developed a highly efficient CRISPR/Cas9-based method for editing the genome of peripheral blood human NK cells (PB-NKs) to knock out ADAM17 and PD1 or knock-in genes using recombinant AAV6. Our method allows editing of PB-NKs at efficiencies reaching 90%, equivalent to methods reported for primary human T cells. Moreover, we demonstrate that ADAM17 and PD1 KO PB-NKs have significantly improved activity, cytokine production, and cancer cell cytotoxicity. Our platform represents a feasible method for generating engineered NK cells as a universal therapeutic for cancer immunotherapy.
A phylogenomic resolution of the sea urchin tree of life
Authors: Mongiardino Koch Nicolás , Coppard Simon E. , Lessios Harilaos A. , Briggs Derek E. G. , Mooi Rich , Rouse Greg W.
Published: September 2018

Background

Echinoidea is a clade of marine animals including sea urchins, heart urchins, sand dollars and sea biscuits. Found in benthic habitats across all latitudes, echinoids are key components of marine communities such as coral reefs and kelp forests. A little over 1,000 species inhabit the oceans today, a diversity that traces its roots back at least to the Permian. Although much effort has been devoted to elucidating the echinoid tree of life using a variety of morphological data, molecular attempts have relied on only a handful of genes. Both of these approaches have had limited success at resolving the deepest nodes of the tree, and their disagreement over the positions of a number of clades remains unresolved.

Results

We performed de novo sequencing and assembly of 17 transcriptomes to complement available genomic resources of sea urchins and produce the first phylogenomic analysis of the clade. Multiple methods of probabilistic inference recovered identical topologies, with virtually all nodes showing maximum support. In contrast, the coalescent-based method ASTRAL-II resolved one node differently, a result apparently driven by gene tree error induced by evolutionary rate heterogeneity. Regardless of the method employed, our phylogenetic structure deviates from the currently accepted classification of echinoids, with neither Acroechinoidea (all euechinoids except echinothurioids), nor Clypeasteroida (sand dollars and sea biscuits) being monophyletic as currently defined. We demonstrate the strength and distribution of phylogenetic signal throughout the genome for novel resolutions of these lineages and rule out systematic biases as possible explanations.

Conclusions

Our investigation substantially augments the molecular resources available for sea urchins, providing the first transcriptomes for many of its main lineages. Using this expanded genomic dataset, we resolve the position of several clades in agreement with early molecular analyses but in disagreement with morphological data. Our efforts settle multiple phylogenetic uncertainties, including the position of the enigmatic deep-sea echinothurioids and the identity of the sister clade to sand dollars. We offer a detailed assessment of evolutionary scenarios that could reconcile our findings with morphological evidence, opening up new lines of research into the development and evolutionary history of this ancient clade.
Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks
Authors: Murrow Lyndsay M. , Weber Robert J. , Caruso Joseph A. , McGinnis Christopher S. , Phong Kiet , Gascard Philippe , Borowsky Alexander D. , Desai Tejal A. , Thomson Matthew , Tlsty Thea , Gartner Zev J.
Published: September 2018

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks.
Brittleness in model selection analysis of single neuron firing rates
Authors: Chandrasekaran Chandramouli , Soldado-Magraner Joana , Peixoto Diogo , Newsome William T. , Shenoy Krishna V. , Sahani Maneesh
Published: September 2018

Models of complex heterogeneous systems like the brain are inescapably incomplete, and thus always falsified with enough data. As neural data grow in volume and complexity, absolute measures of adequacy are being replaced by model selection methods that rank the relative accuracy of competing theories. Selection still depends on incomplete mathematical instantiations, but the implicit expectation is that ranking is robust to their details. Here we highlight a contrary finding of “brittleness,” where data matching one theory conceptually are ranked closer to an instance of another. In particular, selection between recent models of decision making is conceptually misleading when data are simulated with minor distributional mismatch, with mixed secondary signals, or with non-stationary parameters; and decision-related responses in macaque cortex show features suggesting that these effects may impact empirical results. We conclude with recommendations to mitigate such brittleness when using model selection to study neural signals.
System-level analysis of metabolic trade-offs during anaerobic photoheterotrophic growth inRhodopseudomonas palustris
Authors: Navid Ali , Jiao Yongqin , Wong Sergio Ernesto , Pett-Ridge Jennifer
Published: September 2018

Background

Living organisms need to allocate their limited resources in a manner that optimizes their overall fitness by simultaneously achieving several different biological objectives. Examination of these biological trade-offs can provide invaluable information regarding the biophysical and biochemical bases behind observed cellular phenotypes. A quantitative knowledge of a cell system’s critical objectives is also needed for engineering of cellular metabolism, where there is interest in mitigating the fitness costs that may result from human manipulation.

Results

To study metabolism in photoheterotrophs, we developed and validated a genome-scale model of metabolism inRhodopseudomonas palustris, a metabolically versatile gram-negative purple non-sulfur bacterium capable of growing phototrophically on various carbons sources, including inorganic carbon and aromatic compounds. To quantitatively assess trade-offs among a set of important biological objectives during different metabolic growth modes, we used our new model to conduct an 8-dimensional multi-objective flux analysis of metabolism inR. palustris. Our results revealed that phototrophic metabolism inR. palustrisis a light-limited growth mode under anaerobic conditions, regardless of the available carbon source. Under photoheterotrophic conditions,R. Palustrisprioritizes the optimization of carbon efficiency, followed by ATP production and biomass production rate, in a Pareto-optimal manner. To achieve maximum carbon fixation, cells appear to divert limited energy resources away from growth and toward CO2fixation, even in presence of excess reduced carbon. We also found that to achieve the theoretical maximum rate of biomass production, anaerobic metabolism requires import of additional compounds (such as protons) to serve as electron acceptors. Finally, we found that production of hydrogen gas, of potential interest as a candidate biofuel, lowers the cellular growth rates under all circumstances.

Conclusions

Photoheterotrophic metabolism ofR. palustrisis primarily regulated by the amount of light it can absorb and not the availability of carbon. However, despite carbon’s secondary role as a regulating factor,R. palustris’metabolism strives for maximum carbon efficiency, even when this increased efficiency leads to slightly lower growth rates.