bluuebunny/crossref_metadata_2025 huggingface dataset:
Septic Shock Nonsurvivors Have Persistently Elevated Acylcarnitines Following Carnitine Supplementation
Authors: Puskarich Michael A. , Evans Charles R. , Karnovsky Alla , Das Arun K. , Jones Alan E. , Stringer Kathleen A.
Published: September 2017

Introduction:

Sepsis-induced metabolic disturbances include hyperlactatemia, disruption of glycolysis, protein catabolism, and altered fatty acid metabolism. It may also lower serum l-carnitine that supports the use of l-carnitine supplementation as a treatment to ameliorate several of these metabolic consequences.

Methods:

To further understand the association between l-carnitine-induced changes in serum acylcarnitines, fatty acid metabolism and survival, serum samples from (T0), 12 hfollowing completion (T24) of l-carnitine (n = 16) or placebo (n = 15) administration, and 48 h (T48) after enrollment from patients with septic shock enrolled in a randomized control trial were assayed for acylcarnitines, free fatty acids, and insulin. Data were analyzed comparing 1-year survivors and nonsurvivors within treatment groups.

Results:

Mortality was 8 of 16 (50%) and 12 of 15 (80%) at 1 year for l-carnitine and placebo-treated patients, respectively. Free carnitine, C2, C3, and C8 acylcarnitines were higher among nonsurvivors at enrollment. l-Carnitine treatment increased levels of all measured acylcarnitines; an effect that was sustained for at least 36 h following completion of the infusion and was more prominent among nonsurvivors. Several fatty acids followed a similar, though less consistent pattern. Glucose, lactate, and insulin levels did not differ based on survival or treatment arm.

Conclusions:

In human patients with septic shock, l-Carnitine supplementation increases a broad range of acylcarnitine concentrations that persist after cessation of infusion, demonstrating both immediate and sustained effects on the serum metabolome. Nonsurvivors demonstrate a distinct metabolic response to l-carnitine compared with survivors, which may indicate preexisting or more profound metabolic derangement that constrains any beneficial response to treatment.
Pretreatment With Argon Protects Human Cardiac Myocyte-Like Progenitor Cells from Oxygen Glucose Deprivation-Induced Cell Death by Activation of AKT and Differential Regulation of Mapkinases
Authors: Qi Hong , Soto-Gonzalez Lourdes , Krychtiuk Konstantin A. , Ruhittel Sarah , Kaun Christoph , Speidl Walter S. , Kiss Attila , Podesser Bruno K. , Yao Shanglong , Markstaller Klaus , Klein Klaus U. , Tretter Verena
Published: September 2017

Background:

The noble gas argon induces cardioprotection in a rabbit model of myocardial ischemia and reperfusion. However, no studies in human primary cells or subjects have been performed so far. We used human cardiac myocyte-like progenitor cells (HCMs) to investigate the protective effect on the cellular level.

Methods:

HCMs were pretreated with 30% or 50% argon before oxygen–glucose deprivation (OGD) and reperfusion. We evaluated apoptotic states by flow cytometry and the activation of mitogen-activated protein kinase (MAPKs) members extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38 MAPkinase, and protein kinase B (Akt) by Westernblot analysis and by activity assays of downstream transcription factors. Specific inhibitors were used to proof a significant participation of these pathways in the protection by argon. Beneficial effects were further assessed by TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay, lactate dehydrogenase (LDH), mitochondrial deoxyribonucleic acid (mtDNA), and cytokine release.

Results:

Pretreatment with 30% or 50% argon for 90 min before OGD resulted in a significant protection of HCMs against apoptosis. This effect was reversed by the application of MAPK and Akt inhibitors during argon exposure. Argon 30% reduced the release of LDH by 33% and mtDNA by 45%. The release of interleukin 1β was reduced by 44% after OGD and more than 90% during reperfusion.

Conclusions:

Pretreatment with argon protects HCMs from apoptosis under ischemic conditions via activation of Akt, Erk, and biphasic regulation of JNK. Argon gas is cheap and easily administrable, and might be a novel therapy to reduce myocardial ischemia–reperfusion injury.
Neurological toxicities associated with immune-checkpoint inhibitors
Authors: Touat Mehdi , Talmasov Daniel , Ricard Damien , Psimaras Dimitri
Published: September 2017

Purpose of review

Immune-checkpoint inhibitors (ICIs) constitute a novel class of agents recently approved to treat a number of human malignancies. Due to their immunomodulatory mechanism of action, ICIs can generate a wide range of immune-related adverse events (irAEs) of which neurological toxicities are of special interest because of their potential severity. The objective of this review is to examine the recent literature describing neurological irAEs and discuss their optimal management.

Recent findings

As opposed to irAEs involving other organs, neurological complications of ICIs are uncommon. These complications encompass various toxicities of the central and peripheral nervous systems, including myositis, myasthenia gravis, demyelinating polyradiculoneuropathy, meningitis and encephalitis. Neurologic irAEs are often responsive to corticosteroids and other immune-modulating treatments (e.g. plasmapheresis, intravenous immunoglobulin), which have been used in patients presenting with severe neurologic irAEs or irAEs unresponsive to corticosteroids. Data from literature indicate that early treatment is critical for reducing the morbidity associated with neurologic irAEs.

ICI-associated irAEs constitute a new group of neurologic complications of systemic anticancer therapies. Although potentially severe, these rare neurologic toxicities are often responsive to immune-modulating therapies. Early recognition and treatment is crucial for timely improvement of functional outcome and requires a multidisciplinary approach.
LRP1 Regulates Peroxisome Biogenesis and Cholesterol Homeostasis in Oligodendrocytes and is Required in CNS Myelin Development and Repair
Authors: Lin林靚蘋 Jing-Ping , Mironova Yevgeniya A. , Shrager Peter , Giger Roman J.
Published: September 2017

The low-density lipoprotein related-receptor-1 (LRP1) is a large endocytic and signaling receptor. We show thatLrp1is required for proper CNS myelinogensisin vivo. Either global inducible or oligodendrocyte (OL)-lineage specific ablation ofLrp1impairs myelin development and adult white matter repair. In primary oligodendrocyte progenitor cells (OPCs),Lrp1deficiency reduces cholesterol levels and attenuates differentiation into mature OLs. Despite a strong increase in the sterol-regulatory element-binding protein-2,Lrp1-/-OPCs are not able to maintain normal cholesterol levels, suggesting more global metabolic deficits. Mechanistic studies identified a decrease in peroxisomal biogenesis factor-2 and a reduction in peroxisomes localized to OL processes. Treatment ofLrp1-/-OPCs with cholesterol or pharmacological activation of peroxisome proliferator-activated receptor-γ with pioglitazone is not sufficient to promote differentiation; however when combined, cholesterol and pioglitazone treatment enhance OL production. Collectively, our studies identify a novel link between LRP1, peroxisomes, and OPC differentiation during white matter development and repair.
Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs
Authors: Carlevaro-Fita Joana , Polidori Taisia , Das Monalisa , Navarro Carmen , Zoller Tatjana I. , Johnson Rory
Published: September 2017

The sequence domains underlying long noncoding RNA (lncRNA) activities, including their characteristic nuclear enrichment, remain largely unknown. It has been proposed that these domains can originate from neofunctionalised fragments of transposable elements (TEs), otherwise known as RIDLs (Repeat Insertion Domains of Long Noncoding RNA), although just a handful have been identified. It is challenging to distinguish functional RIDL instances against a numerous genomic background of neutrally-evolving TEs. We here show evidence that a subset of TE types experience evolutionary selection in the context of lncRNA exons. Together these comprise an enrichment group of 5374 TE fragments in 3566 loci. Their host lncRNAs tend to be functionally validated and associated with disease. This RIDL group was used to explore the relationship between TEs and lncRNA subcellular localisation. Using global localisation data from ten human cell lines, we uncover a dose-dependent relationship between nuclear/cytoplasmic distribution, and evolutionarily-conserved L2b, MIRb and MIRc elements. This is observed in multiple cell types, and is unaffected by confounders of transcript length or expression. Experimental validation with engineered transgenes shows that these TEs drive nuclear enrichment in a natural sequence context. Together these data reveal a role for TEs in regulating the subcellular localisation of lncRNAs.
The Role Of Circle Of Willis Anatomy Variations In Cardio-embolic Stroke - A Patient-specific Simulation Based Study
Authors: Mukherjee Debanjan , Jani Neel D. , Narvid Jared , Shadden Shawn C.
Published: September 2017

We describe a patient-specific simulation based investigation on the role of Circle of Willis anatomy in cardioembolic stroke. Our simulation framework consists of medical image-driven modeling of patient anatomy including the Circle, 3D blood flow simulation through patient vasculature, embolus transport modeling using a discrete particle dynamics technique, and a sampling based approach to incorporate parametric variations. A total of 24 (four patients and six Circle anatomies including the complete Circle) models were considered, with cardiogenic emboli of varying sizes and compositions released virtually and tracked to compute distribution to the brain. The results establish that Circle anatomical variations significantly influence embolus distribution to the six major cerebral arteries. Embolus distribution to MCA territory is found to be least sensitive to the influence of anatomical variations. For varying Circle topologies, differences in flow through cervical vasculature are observed. This incoming flow is recruited differently across the communicating arteries of the Circle for varying anastomoses. Emboli interact with the routed flow, and can undergo significant traversal across the Circle arterial segments, depending upon their inertia and density ratio with respect to blood. This interaction drives the underlying biomechanics of embolus transport across the Circle, explaining how Circle anatomy influences embolism risk.
Catecholaminergic modulation of the avoidance of cognitive control
Authors: Froböse Monja I. , Swart Jennifer C. , Cook Jennifer L. , Geurts Dirk E.M. , den Ouden Hanneke E.M. , Cools Roshan
Published: September 2017

The catecholamines have long been associated with cognitive control and value-based decision-making. More recently, we proposed that the catecholamines might modulate value-based decision-making about whether or not to engage in cognitive control. We test this hypothesis by assessing effects of a catecholamine challenge in a large sample of young, healthy adults (n = 100) on the avoidance of a cognitively demanding control process: task switching. Prolonging catecholamine transmission by blocking reuptake with methylphenidate altered the avoidance, but not the execution of cognitive control. Crucially, these effects could be isolated by taking into account individual differences in trait impulsivity, so that participants with higher trait impulsivity became more avoidant of cognitive control, despite faster task performance. One implication of these findings is that performance-enhancing effects of methylphenidate may be accompanied by an undermining effect on the willingness to exert cognitive control. Taken together, these findings integrate hitherto segregated literatures on catecholamines’ roles in value-based learning/choice and cognitive control.
High-Throughput Identification of Genetic Variation Impact on pre-mRNA Splicing Efficiency
Authors: Adamson Scott I. , Zhan Lijun , Graveley Brenton R.
Published: September 2017

Abstract

Understanding the functional impact of genomic variants is a major goal of modern genetics and personalized medicine. Although many synonymous and non-coding variants act through altering the efficiency of pre-mRNA splicing, it is difficult to predict how these variants impact pre-mRNA splicing. Here, we describe a massively parallel approach we used to test the impact of 2,059 human genetic variants spanning 110 alternative exons on pre-mRNA splicing. This method yields data that reinforces known mechanisms of pre-mRNA splicing, can rapidly identify genomic variants that impact pre-mRNA splicing, and will be useful for increasing our understanding of genome function.
Binge-like Acquisition of α-pyrrolidinopentiophenone (α-PVP) Self-Administration in Female Rats
Authors: Javadi-Paydar Mehrak , Harvey Eric L. , Grant Yanabel , Vandewater Sophia A. , Creehan Kevin M. , Nguyen Jacques D. , Dickerson Tobin J. , Taffe Michael A.
Published: September 2017

The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with violent and/or bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a closely related drug, 3,4-methylenedioxypyrovalerone. The binge-like acquisition pattern appeared to be novel for rat IVSA, thus the present study was designed to determine if this effect generalizes to IVSA of α-PVP in female rats. Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers that contained an activity wheel. Groups of animals were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel-access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel-access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution. This confirms the high reinforcer efficacy of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.
Lipid-Uptake Pathways and Lipid-Protein interactions in P-glycoprotein Revealed by Coarse-Grained Molecular Dynamics Simulations
Authors: Barreto-Ojeda E. , Corradi V. , Gu R.-X. , Tieleman D.P.
Published: September 2017

P-glycoprotein (P-gp) exports a broad range of dissimilar compounds, including drugs, lipids and lipid-like molecules. Due to its substrate promiscuity, P-gp is a key player in the development of cancer multidrug resistance (MDR). Although P-gp is one of the most studied members of ABC-transporters, the mechanism of how its substrates access the cavity remains unclear. In this work, we performed coarse-grained (CG) molecular dynamics (MD) simulations to explore possible pathways of lipid-uptake in the inward-facing conformation of P-gp embedded in bilayers with different PC:PE lipid ratios. Our results show that in the inward facing orientation only lipids from the lower leaflet are taken up by the transporter. We identify positively charged residues at the portals of P-gp that favor lipid entrance to the cavity, as well as lipid binding sites, in good agreement with previous experimental studies. Our results show no selectivity for PC vs. PE lipids. We offer several examples of lipid uptake-pathways for PC and PE lipids that help to elucidate the molecular mechanism of substrate-uptake in P-gp.
MEBS, a software platform to evaluate large (meta)genomic collections according to their metabolic machinery: unraveling the sulfur cycle
Authors: Anda Valerie De , Zapata-Peñasco Icoquih , Poot-Hernandez Augusto Cesar , Eguiarte Luis E. , Contreras-Moreira Bruno , Souza Valeria
Published: September 2017

BACKGROUND

The increasing number of metagenomic and genomic sequences has dramatically improved our understanding of microbial diversity, yet our ability to infer metabolic capabilities in such datasets remains challenging.

FINDINGS

We describe the Multigenomic Entropy Based Score pipeline (MEBS), a software platform designed to evaluate, compare and infer complex metabolic pathways in large ‘omic’ datasets, including entire biogeochemical cycles. MEBS is open source and available throughhttps://github.com/eead-csic-compbio/metagenome_Pfam_score. To demonstrate its use we modeled the sulfur cycle by exhaustively curating the molecular and ecological elements involved (compounds, genes, metabolic pathways and microbial taxa). This information was reduced to a collection of 112 characteristic Pfam protein domains and a list of complete-sequenced sulfur genomes. Using the mathematical framework of relative entropy(H’),we quantitatively measured the enrichment of these domains among sulfur genomes. The entropy of each domain was used to both: build up a final score that indicates whether a (meta)genomic sample contains the metabolic machinery of interest and to propose marker domains in metagenomic sequences such as DsrC (PF04358). MEBS was benchmarked with a dataset of 2,107 non-redundant microbial genomes from RefSeq and 935 metagenomes from MG-RAST. Its performance, reproducibility, and robustness were evaluated using several approaches, including random sampling, linear regression models, Receiver Operator Characteristic plots and the Area Under the Curve metric (AUC). Our results support the broad applicability of this algorithm to accurately classify (AUC=0.985) hard to culture genomes (e.g.,Candidatus Desulforudis audaxviator),previously characterized ones and metagenomic environments such as hydrothermal vents, or deep-sea sediment.

CONCLUSIONS

Our benchmark indicates that an entropy-based score can capture the metabolic machinery of interest and be used to efficiently classify large genomic and metagenomic datasets, including uncultivated/unexplored taxa
Genetic diversity and mother-child overlap of the gut associated microbiota determined by reduced genome sequencing
Authors: Ravi Anuradha , Avershina Ekaterina , Angell Inga Leena , Ludvigsen Jane , Manohar Prashanth , Padmanaban Sumathi , Nachimuthu Ramesh , Rudi Knut
Published: September 2017

The genetic diversity and sharing of the mother-child associated microbiota remain largely unexplored. This severely limits our functional understanding of gut microbiota transmission patterns. The aim of our work was therefore to use a novel reduced metagenome sequencing in combination with shotgun and 16S rRNA gene sequencing to determine both the metagenome genetic diversity and the mother-to-child sharing of the microbiota. For a cohort of 17 mother-child pairs we found an increase of the collective metagenome size from about 100 Mbp for 4-day-old children to about 500 Mbp for mothers. The 4-day-old children shared 7% of the metagenome sequences with the mothers, while the metagenome sequence sharing was more than 30% among the mothers. We found 15 genomes shared across more than 50% of the mothers, of which 10 belonged toClostridia. OnlyBacteroidesshowed a direct mother-child association, withB. vulgatusbeing abundant in both 4-day-old children and mothers. In conclusion, our results support a common pool of gut bacteria that are transmitted from adults to infants, with most of the bacteria being transmitted at a stage after delivery.
Lipid-protein interactions are unique fingerprints for membrane proteins
Authors: Corradi Valentina , Mendez-Villuendas Eduardo , Ingólfsson Helgi I. , Gu Ruo-Xu , Siuda Iwona , Melo Manuel N. , Moussatova Anastassiia , Degagné Christine , Sejdiu Besian I. , Singh Gurpreet , Wassenaar Tsjerk A. , Magnero Karelia Delgado , Marrink Siewert J. , Tieleman D. Peter
Published: September 2017

Cell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Understanding the lateral organization principles of these complex mixtures is essential for life and health. However, our current understanding of the detailed organization of cell membranes remains rather elusive, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of ten membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between leaflets. The simulations detail how each protein modulates its local lipid environment through local lipid composition, thickness, curvature and lipid dynamics. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far reaching implications for the overall organization of the cell membrane.
Comprehensive analysis of central carbon metabolism reveals multiple connections between nutrients, biosynthetic capacity, and cell morphology inEscherichia coli
Authors: Westfall Corey S. , Levin Petra Anne
Published: September 2017

Bacterial morphology is a complex trait that is highly sensitive to changes in the environment. For heterotrophic organisms, such asEscherichia coli, increases in nutrient levels are frequently accompanied by several-fold increases in both size and growth rate. Despite the dramatic nature of these changes, how alterations in nutrient availability translate into changes in growth and morphology remains a largely open question. To understand the signaling networks coupling nutrient availability with size and shape, we examined the impact of deletions in the entirety of non-essential central carbon metabolic genes onE. coligrowth rate and cell size. Our data reveal the presence of multiple metabolic nodes that play important yet distinctive roles in shaping the cell. Consistent with recent work from our lab and others, although both are sensitive to nutrient availability, size and growth rate vary independently. Cell width and length also appear to be independent phenomena, influenced by different aspects of central carbon metabolism. These findings highlight the diversity of factors that can impact cell morphology and provide a foundation for further studies.

Author summary

Often taken for granted, the shape of bacterial cells is a complex trait that is highly sensitive to environmental perturbations. Nutrients in particular, strongly impact bacterial morphology together with growth rate. The ubiquitous, rod-shaped bacteriaEscherichia coliincreases both length and width several fold upon a shift from nutrient poor to nutrient rich medium, a change accompanied by an equally dramatic increase in growth rate. Central carbon metabolism is an obvious site for the integration of nutrient dependent signals that dictate cell size and shape. To develop a clearer picture of the molecular mechanisms coupling nutrient assimilation with cell growth and morphology, we screened the entirety of nonessential carbon metabolic genes for their contribution to growth rate and cell shape. Our data reveal the presence of multiple regulatory circuits coordinating different metabolic pathways with specific aspects of cell growth and morphology. Together, these data firmly establish a role for central carbon metabolism as an environmentally sensitive sculptor of bacterial cells.
A Sequel to Sanger: Amplicon Sequencing That Scales
Authors: Hebert Paul DN , Braukmann Thomas WA , Prosser Sean WJ , Ratnasingham Sujeevan , deWaard Jeremy R , Ivanova Natalia V , Janzen Daniel H , Hallwachs Winnie , Naik Suresh , Sones Jayme E , Zakharov Evgeny V
Published: September 2017

Although high-throughput sequencers (HTS) have largely displaced their Sanger counterparts, the short read lengths and high error rates of most platforms constrain their utility for amplicon sequencing. The present study tests the capacity of single molecule, real-time (SMRT) sequencing implemented on the SEQUEL platform to overcome these limitations, employing 658 bp amplicons of the mitochondrial cytochromecoxidase I gene as a model system. By examining templates from more than 5,000 species and 20,000 specimens, the performance of SMRT sequencing was tested with amplicons showing wide variation in GC composition and varied sequence attributes. SMRT and Sanger sequences were very similar, but SMRT sequencing provided more complete coverage, especially for amplicons with homopolymer tracts. Because it can characterize amplicon pools from 10,000 DNA extracts in a single run, the SEQUEL reduces costs 40-fold from Sanger analysis. Reflecting the capacity of each instrument to recover sequences from more than five million DNA extracts a year, this platform facilitates massive amplicon characterization.
BioSankey: Visualizing microbial communities and gene expression data over time
Authors: Platzer Alexander , Polzin Julia , Han Ping Penny , Rembart Klaus , Nussbaumer Thomas
Published: September 2017

Metagenomics, RNA-seq, WGS (Whole Genome Sequencing) and other types of next-generation sequencing techniques provide quantitative measurements for single strains and genes over time. To obtain a global overview of the experiment and to explore the full potential of a given dataset, intuitive and interactive visualization tools are needed. Therefore, we establishedBioSankey, which allows to visualize microbial species in microbiome studies and gene expression over time as a Sankey diagram. These diagrams are embedded into a project-specific HTML page, that contains all information as provided during the installation process.BioSankeycan be easily applied to analyse bacterial communities in time-series datasets. Furthermore, it can be used to analyse the fluctuations of differentially expressed genes (DEG). The output ofBioSankeyis a project-specific HTML page, which depends only on JavaScript to enable searches of interesting species or genes of interest without requiring a web server or connection to a database to exchange results among collaboration partners.BioSankeyis a tool to visualize different data elements from single and dual RNA-seq datasets as well as from metagenomes studies.
Impaired hippocampal representation of place in theFmr1-knockout mouse model of Fragile X syndrome
Authors: Arbab Tara , Pennartz Cyriel MA , Battaglia Francesco P
Published: September 2017

Fragile X syndrome (FXS) is an X-chromosome linked intellectual disability and the most common genetic cause of autism spectrum disorder (ASD). Building upon demonstrated deficits in neuronal plasticity and spatial memory in FXS, we investigated how spatial information processing is affectedin vivoin an FXS mouse model (Fmr1-KO). Healthy hippocampal neurons (so-called place cells) exhibit place-related activity during spatial exploration, and the stability of these spatial representations can be taken as an index of memory function. We find impaired stability and reduced specificity ofFmr1-KO spatial representations. This is a potential biomarker for the cognitive dysfunction observed in FXS, informative on the ability to integrate sensory information into an abstract representation and successfully retain this conceptual memory. Our results provide key insight into the biological mechanisms underlying cognitive disabilities in FXS and ASD, paving the way for a targeted approach to remedy these.
Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches
Authors: Ciernia Annie Vogel , Laufer Benjamin I. , Dunaway Keith W. , Mordaunt Charles E. , Coulson Rochelle L. , Totah Theresa S. , Stolzenberg Danielle S. , Frahm Jaime , Singh-Taylor Akanksha , Baram Tallie Z. , LaSalle Janine M. , Yasui Dag H.
Published: September 2017

Background

Maternal care during early-life plays a crucial role in the sculpting of the mammalian brain. Augmented maternal care during the first postnatal week promotes life-long stress resilience and improved memory compared with the outcome of routine rearing conditions. Recent evidence suggests that this potent phenotypic change commences with altered synaptic connectivity of stress sensitive hypothalamic neurons. However, the epigenomic basis of the long-lived consequences is not well understood.

Methods

Here, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to examine the effects of augmented maternal care on DNA cytosine methylation, gene expression, and miRNA expression.

Results

A significant decrease in global DNA methylation was observed in offspring hypothalamus following a week of augmented maternal care, corresponding to differential methylation and expression of thousands of genes. Differentially methylated and expressed genes were enriched for functions in neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation, as well as known stress response genes. Twenty prioritized genes with three lines of evidence (methylation, expression, and altered miRNA target) were identified as highly relevant to the stress resiliency phenotype.

Conclusions

This combined unbiased approach enabled the discovery of novel genes and gene pathways that advance our understanding of the central epigenomic mechanisms underlying the profound effects of maternal care on the developing brain.
A Dynamic Bayesian Observer Model Reveals Origins of Bias in Visual Path Integration
Authors: Lakshminarasimhan Kaushik J , Petsalis Marina , Park Hyeshin , DeAngelis Gregory C , Pitkow Xaq , Angelaki Dora E
Published: September 2017

Path integration is a navigation strategy by which animals track their position by integrating their self-motion velocity over time. To identify the computational origins of bias in visual path integration, we asked human subjects to navigate in a virtual environment using optic flow, and found that they generally travelled beyond the goal location. Such a behaviour could stem from leaky integration of unbiased self-motion velocity estimates, or from a prior expectation favouring slower speeds that causes underestimation of velocity. We tested both alternatives using a probabilistic framework that maximizes expected reward, and found that subjects’ biases were better explained by a slow-speed prior than imperfect integration. When subjects integrate paths over long periods, this framework intriguingly predicts a distance-dependent bias reversal due to build-up of uncertainty, which we also confirmed experimentally. These results suggest that visual path integration performance is limited largely by biases in processing optic flow rather than by suboptimal signal integration.
Factors associated with reporting of sexual assault among college and non-college women
Authors: Spohn Ryan , Bjornsen Abby , Wright Emily M.
Published: September 2017

Purpose

The purpose of this paper is to examine factors impacting college and non-college women reporting sexual assault to police. The goal is to increase knowledge regarding differences in the rates of reporting and reasons for reporting across these two groups.

Design/methodology/approach

Participants were drawn from a national telephone survey of US women and a sample of US college women. Bivariate and multivariate analyses were conducted to determine factors influencing the reporting of sexual assault to police.

Findings

Non-college women were more likely than college women to report to police. Women who perceived their victimization as rape were much more likely to report to the police and women who had contact with a helping agency were also much more likely to report their assault. Contacting a helping agency is more relevant to non-college women’s reporting to police, while considering the assault a rape is more important for college women.

Practical implications

The results suggest that significant work is needed to encourage women in college to view sexual assaults as worthy of reporting. Boosting victim awareness and access to services is paramount. Providing education and empowerment to student victims to inform their perceptions about the definition of rape is vital, as women perceiving sexual assault as rape are more likely to report the incident.

Originality/value

The research significantly adds to the literature indicating differences in rates of reporting and the factors that impact reporting uniquely for college vs non-college women.
Leukocyte profiles are associated with longevity and survival, but not migratory effort: A comparative analysis of shorebirds
Authors: Minias Piotr , Włodarczyk Radosław , Meissner Włodzimierz
Published: September 2017

Assessment of leukocyte profiles has become an increasingly popular tool in the fields of ecology and ecophysiology. The ratio of heterophils to lymphocytes (H/L ratio) is of special utility, as it reflects physiological adaptation of an organism to cope either with an infection through injury (via heterophils) or a communicable disease (via lymphocytes). Thus, elevated H/L ratios may constitute an adaptation to risky environments (i.e. associated with high risk of injury). While intra‐population variation in avian H/L ratio has been extensively studied, we are aware of no studies that linked this trait to life‐history components at the interspecific level.

We measured H/L ratio in over 400 shorebirds from 19 species during their autumn migration through Central Europe. Phylogenetically informed comparative methods were used to test whether H/L ratio was related to: (1) annual survival and life span; (2) migratory effort, as measured with total migration distance and migratory energy reserves and (3) confounding variables such as body size or breeding latitude.

A relatively strong phylogenetic signal and spatial phylogenetic autocorrelation indicated that most diversification in shorebird H/L ratios occurred relatively early in radiation of this group.

Comparative analysis gave strong support for the negative associations of H/L ratio with residual life span and annual survival. In contrast, we found no support for the effect of migratory behaviour on H/L ratios, suggesting that leukocyte profiles in shorebirds may not constitute an important physiological adaptation for long‐distance migration.

Our study provided the first comparative evidence for a link between H/L ratios and important life‐history traits in birds. Strong negative associations with annual survival and residual life span indicate that leukocyte profiles may form an adaptive basis for life‐history strategies in birds.

A plain language summary is available for this article.
The costs of parasite infection: Effects of removing lungworms on performance, growth and survival of free‐ranging cane toads
Authors: Finnerty Patrick B. , Shine Richard , Brown Gregory P.
Published: September 2017

Most research on the effects of parasites on their hosts has focused on the parasites of mammals or birds (especially, domesticated taxa) rather than systems in which the hosts are ectothermic wildlife species.

We used experimental methods (antihelminthic drugs) to quantify the effects of lungworms (Rhabdias pseudosphaerocephala) on their anuran hosts, the invasive cane toad (Rhinella marina).

In captivity, eradicating lungworms enhanced toad activity (measures of boldness and level of spontaneous activity), performance (locomotor speed, climbing ability) and foraging success (feeding rate).

In free‐ranging toads (n = 123) at a site in tropical Australia, eradicating lungworm infection increased rates of host survival by 8%, movement by 20%, growth by 28% and elaboration of male secondary sexual characteristics by 30%. The presence of the lungworm thus has a substantial negative effect on fitness‐related traits of the host.

Given their long shared evolutionary history and the mild inflammatory and immune response elicited by the parasite in the host, the magnitude of the effects of parasite removal were surprising. Parasites may impose hidden costs, related to modification of host behaviour or metabolism. Experimental removal of parasites can be a useful means of quantifying costs of infection.

A plain language summary is available for this article.
Balanced‐budget rules and aggregate instability: The role of consumption taxes in a monetary economy
Authors: Xue Jianpo , Yip Chong K.
Published: September 2017

In a real macroeconomic model, it is well established that a balanced‐budget rule based on consumption tax can rule out indeterminacy. The present paper shows, both analytically and numerically, that such a balanced‐budget rule induces indeterminacy and, hence, aggregate instability in a standard one‐sector cash‐in‐advance economy. From a policy perspective, our results raise possible concerns that balanced‐budget rules with endogenous consumption tax could have destabilizing effects under the current over‐easy monetary environment.
Unwilling Subjects of Financialization
Authors: Fields Desiree
Published: September 2017

This article seeks to advance debates about the financialization of housing by focusing on the emergence of rental housing as a frontier for financialization, a dynamic that is increasingly relevant since the global financial crisis. Situated in New York City, the research focuses on an aggressive wave of investment in affordable rent‐stabilized properties by private equity firms, their efforts to release value from these properties, and the implications of the 2008 financial crisis for their investment strategies and thus for tenants’ experience of home. Through detailed empirical analysis tracing the connections between how rental housing has been constituted as a new site for private equity investment globally, the local conditions facilitating this process in New York and how it reshaped everyday life for tenants, the article theorizes tenants as unwilling subjects of financialization. Yet unwillingness does not necessarily translate into being overtaken; it also connotes reluctance and indeed struggle. This novel conceptualization highlights the ways in which financialization meets with dissent, and its necessarily contingent and incomplete nature. The article therefore develops the wider intellectual project of understanding financialization not as a monolithic and inevitable process, but as one characterized by resistance from without and contradiction from within.
The Financialization of A Social Housing Provider
Authors: Aalbers Manuel B. , Loon Jannes Van , Fernandez Rodrigo
Published: September 2017

Why does a social housing provider bet on interest rate fluctuations? This article presents a case study of the financialization of both housing and the state. Social housing in the Netherlands is provided by non‐profit housing associations that have since 1989 been set apart from the state. Many associations started developing housing for profit, borrowing on global capital markets or buying derivatives. Whereas other semi‐public institutions moved into the world of finance due to financial constraints, housing associations did so to capitalize on the possibilities offered by their asset‐rich portfolios. Vestia, the largest of them all, is an extreme––but not exceptional––case of what can happen when public goals are left to be realized by inadequately supervised and poorly managed private organizations. As a result of gambling on derivatives, Vestia had to be bailed out to the tune of over 2 billion euros. To recoup the losses, housing was sold off and rents were raised. Almost half of Dutch housing associations used derivatives, although most refrained from using them purely speculatively. The changes in the housing sector that led to its financialization cannot be separated from the wider financialization of the state.
Privatization, Financialization and State Restructuring in Eastern Germany: The case of Am südpark
Authors: Bernt Matthias , Colini Laura , Förste Daniel
Published: September 2017

Using a mix of survey data, results from a study on local planning politics and fieldwork, this article discusses the interplay of planning and welfare policies with global financial markets in the ‘making’ of social segregation in Halle‐Neustadt, a borough in the German city of Halle (Saale). Here, different developments come together. First, Halle‐Neustadt has experienced two waves of privatization, leading to a complete change of ownership structures, marked by the rise of financial investors. Second, welfare cuts have put increasing pressure on welfare recipients to live in the cheapest housing available. This has led to the emergence of a ‘Hartz IV business model’ based on low, but state‐subsidized, rents. Third, new planning policies have led to a massive drop in house prices, thus facilitating the use of ‘leverage’ strategies for financial investors. We expand on an already developed debate, providing new insights about relations between planning, state restructuring and financialization in a German context. We demonstrate that a broad array of changes in national regulatory settings, policy change in different sectors and local particularities can all be crucial in enabling financialization. We conclude that research should place greater emphasis on the state in providing explanations and take differences in context more seriously.
Assessment of cerebral perfusion with contrast‐enhanced ultrasound during constriction of the neck mimicking malposition of the BD Odon Device™: a study in newborn piglets
Authors: de Lange C , D Saugstad O , Solberg R
Published: September 2017

Objective

The BD Odon Device™ is a new instrument for operative vaginal birth with potential for preventing maternal, fetal and newborn morbidity/mortality during a complicated second stage of labour. The device is a plastic sleeve with an air chamber inflated around the baby's head which is gently pulled through the birth canal. The aim was to monitor changes in cerebral circulation during constriction of the neck to evaluate a risk of potential malposition of the device.

Design

Randomised prospective study.

Population or sample

Twelve newborn piglets.

Methods

The anaesthetised piglets were exposed to hypoxia until base excess was –20 mmol/l and/or mean arterial blood pressure had decreased to 20 mmHg. At reoxygenation, an air chamber was inflated around the neck to 300 mmHg and the piglets randomised into three groups: 10 (n = 5), 5 (n = 5) or 2 (n = 2) minutes’ occlusion. Cerebral perfusion was evaluated with transcranial contrast‐enhanced ultrasound at four time‐points, and analysed in the carotid arteries, basal ganglia, cortex and whole brain. Statistical analysis used ANOVA, linear mixed model, Kruskal–Wallis H‐test.

Main outcome measures

Perfusion parameters; peak intensity, time to peak intensity, upslope, mean transit time, area under the curve.

Results

The haemodynamic response was comparable between groups. Perfusion parameters showed a slight increase at end hypoxia followed by a decrease during occlusion, especially in the cortex (P = 0.00–0.2). After deflation, perfusion returned towards baseline values.

Conclusions

Simulation of malposition of the Odon Device was performed using a newborn hypoxic piglet model. Considerable compression of the neck vessels was applied, with only a moderate decrease in perfusion and with restoration of haemodynamics/cerebral perfusion after decompression.

Tweetable abstract

Malposition of Odon Device™ in a piglet model revealed a reversible decrease in cerebral perfusion during neck constriction.
Design and development of the BD Odon DeviceTM: a human factors evaluation process
Authors: O'Brien SM , Mouser A , Odon JE , Winter C , Draycott TJ , Sumitro T , Alisantoso D , Lim WL , Merialdi M , Stankovic AK , Crofts JF
Published: September 2017

Objective

To (1) determine how intended users interact with and use the BD Odon Device in simulation, (2) use these findings to alter progressively the design of the BD Odon Device and (3) validate that these changes have improved the ability of practitioners to use the BD Odon Device.

Design

Human factors evaluation study.

Setting

Simulation suite designed to mimic delivery room.

Population or sample

Three hundred and ninety simulated operative births, performed by 100 practising clinicians.

Methods

Simulated operative vaginal births performed using the BD Odon Device and the device Instructions for use were subjected to three formative human factors evaluations and one human factors validation test. Following each evaluation, findings were reviewed and the design of the BD Odon Device and Instructions for use were modified.

Main outcome measures

Successful performance of an operative vaginal birth using the BD Odon Device in accordance with provided training and Instructions for use.

Results

Using version two of the BD Odon Device, and following exposure to face‐to‐face training and written instructions, 25% of accouchers were able successfully to perform a simulated operative vaginal birth. In the final evaluation, following device design and training material alterations, all accouchers were able successfully to perform a simulated operative vaginal birth using version four of the BD Odon Device.

Conclusions

Human factors evaluations have enabled a multi‐professional device and training materials design team to alter the design of the BD Odon Device and the Instructions for use in an evidence‐based fashion. This process has resulted in a device which has a predictable and likely safe pattern of use.

Tweetable abstract

Human Factors evaluations help make the BD Odon Device safe and usable for clinical practice.
The role of operative vaginal birth in the 21st century and a way forward
Authors: Draycott TJ , Di Renzo GC
Published: September 2017

Effective devices and effective, validated training can improve operative vaginal birth outcomes for women and their babies.

Tweetable abstract

Effective devices and effective, validated training can improve operative vaginal birth outcomes for women and their babies.
Social Security Disability Insurance Enrollment and Health Care Employment
Authors: Pellegrini Lawrence C. , Geissler Kimberley H.
Published: September 2017

Objective

To examine the relationship between Social Security Disability Insurance (SSDI) enrollment and health care employment.

Data Sources

State‐year level data from government and other publicly available sources for all states (2000–2014).

Study Design

Population‐weighted linear regression analyses model associations between each health care employment measure and each SSDI enrollment measure (i.e., SSDI overall, physical, or mental health enrollment rates), controlling for factors associated with health care employment, state fixed effects, and secular time trends.

Data Collection

Data are gathered from publicly available sources.

Principal Findings

A one standard deviation increase in SSDI enrollment per 100,000 population is associated with a statistically significant 2.6 and 4.5 percent increase in the mean employment rate per 100,000 population for health care practitioner and technical occupations and health care support occupations, respectively. The size of this relationship varies by the type of disabling condition for SSDI enrollment (physical versus mental health).

Conclusions

Social Security Disability Insurance enrollment is significantly associated with health care employment at the state level. Quantifying the magnitude of this relationship is important given high SSDI enrollment rates as well as evolving policy and demographic shifts related to the SSDI program.