bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence of Hepatitis E Virus Infection Among People Living With HIV in the Central African Republic
Authors: Demi Sibiro Ornella Anne , Manirakiza Alexandre , Komas Narcisse Patrice
Published: November 2018

Background

Hepatitis E virus (HEV) is a waterborne virus that causes acute hepatitis in immunocompromised patients and those who are immunocompetent. Few cases of chronic HEV have been described in industrialized countries. The Central African Republic is 1 of the few countries in the world that is endemic for both HIV and HEV. The prevalence of HIV infection is estimated to be 4.9% among adults aged 15–49 years, and hepatitis E is epidemo-endemic. The aim of this study was to characterize the epidemiology of HEV infection in people living with HIV (PLHIV) in Bangui.

Methods

A cross-sectional study was conducted between April and September 2015 based on answers to a questionnaire, and blood samples were collected for determination of immunological markers by enzyme-linked immunosorbent assay and molecular tests.

Results

Of the 200 PLHIV included, 15 (7.5%) had the IgM that characterizes acute HEV infection; 8.9% were women, and 2.2% were men. The overall seroprevalence of IgG was 68% (48% women and 70.4% men), indicating that men are statistically significantly more exposed to HEV than women. HEV infection had no effect on transaminase or T-CD4+ lymphocyte cell levels. The origin of infection could not be identified.

Conclusions

The seroprevalence of HEV is very high among PLHIV and in the general population of Bangui. This must be taken into account in studies of the risk factors of PLHIV infected with HEV.
Identification of Somatotopic Organization and Optimal Stimulation Site Within the Subthalamic Nucleus for Parkinson's Disease
Authors: Sasaki Tatsuya , Kuwahara Ken , Kin Ittetsu , Okazaki Mihoko , Sasada Susumu , Shinko Aiko , Kameda Masahiro , Yasuhara Takao , Agari Takashi , Date Isao
Published: November 2018

BACKGROUND

Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease.

OBJECTIVE

To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording.

METHODS

STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed.

RESULTS

The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and −0.45 ± 1.5, and −2.5 ± 1.1 and −3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position.

CONCLUSION

Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.
Opioid-Induced Reductions in Gait Variability in Healthy Volunteers and Individuals with Knee Osteoarthritis
Authors: Henriksen Marius , Alkjær Tine , Raffalt Peter C , Jørgensen Louse , Bartholdy Cecilie , Hansen Steen Honoré , Bliddal Henning
Published: November 2018

Objective. To investigate differences in gait variability induced by two different single-dose opioid formulations and an inert placebo in healthy volunteers and knee osteoarthritis patients. Design. Experimental, randomized, double-blinded, crossover study of inert placebo (calcium tablets), 50 mg of tapentadol, and 100 mg of tramadol. Setting. Laboratory setting. Subjects. Healthy volunteers and knee osteoarthritis patients. Methods. At three visits, separated by seven days, one tablet was administered per visit according to the randomization code. At each visit, a baseline measurement was done before tablet administration, after which hourly measurements were performed for six hours, yielding a total of seven measurements per visit. Gait variability was measured by three-dimensional gait analysis, recorded during six minutes of continuous treadmill walking at self-selected speed. One hundred seventy gait cycles were identified from detection of clear events of the knee joint angle trajectories. Gait variability was assessed as average standard deviations over a gait cycle of the sacrum displacements and accelerations; sagittal plane ankle, knee, and hip joint angles; step widths; and stride times. Results. Twenty-four opioid-naïve and neurologically intact participants (12 healthy volunteers and 12 knee osteoarthritis patients) were included and completed the experiment. Tapentadol reduced the variability of sacrum displacements and accelerations compared with placebo and tramadol. There were no differences between experimental conditions regarding the variability in lower-extremity joint angle variability, step widths, or stride times. Conclusions. In opioid-naïve and neurologically intact individuals, tapentadol seems to reduce movement variability during treadmill walking, compared with placebo and tramadol. This can be interpreted as a loss of adaptability that might increase the risk of falling if the system is perturbed.
Practice Variations in Exercise Training Programs in Dutch Cardiac Rehabilitation Centers: Prospective, Observational Study
Authors: Vromen Tom , Peek Niels , Abu-Hanna Ameen , Kemps Hareld M
Published: November 2018

Background

A recent survey among Dutch cardiac rehabilitation centers demonstrated considerable between-center variations in the contents of exercise training programs. For patients entering cardiac rehabilitation, current guidelines recommend tailored exercise training programs based on patient characteristics and rehabilitation goals.

Objective

This study was to analyze to what extent these patient characteristics are determinants of variations in training programs.

Design

This was a prospective, observational study with cross-sectional measurements among 10 cardiac rehabilitation centers.

Methods

The following data were obtained about patients entering cardiac rehabilitation: referral diagnosis, rehabilitation goals, and exercise training variables. Primary outcomes were variations in total aerobic training time, intensity, and volume before and after case-mix correction for population differences between centers. Secondary outcomes were variations in other training characteristics and the role of exercise testing in the determination of training intensity. Also, the roles of diagnosis and training goals in determining aerobic training time and intensity were studied.

Results

Data from 700 participants were analyzed. There were significant variations between centers in all aerobic and most resistance training characteristics. For aerobic training intensity, time, and volume, great variations remained after case-mix correction. An exercise test was performed for 656 participants (93.7%) but was used to determine training intensity in only 344 (52.4%) of these participants. In most centers, referral diagnosis and rehabilitation goals were unrelated to aerobic training time or intensity.

Limitations

Some form of selection bias cannot be excluded because the competing centers represented a minority of Dutch exercise-based cardiac rehabilitation centers.

Conclusions

This study showed that the contents of training programs varied considerably between cardiac rehabilitation centers, independent of population differences. Furthermore, aerobic training time and intensity were mostly unrelated to rehabilitation goals and referral diagnosis.
Distant Reading the Body, 1640–1699
Authors: Mann Rachel , Gavin Michael
Published: November 2018

This paper analyses seventeenth-century discourse of the human body over the Early English Books Online full-text corpus. Anatomy and medicine depict the body as a physiological object, knowable mainly through its parts and processes. Fiction and poetry tend to represent the body as a social entity, knowable primarily through intersubjective action and ethical ideals. In both contexts, bodies are perceived and described through close attention to their parts, but when bodies are conceived as such, they are described as abstract entities that organize the whole. This distinction is difficult to see at the level of close reading but unmistakable at larger scale. Deep conceptual structures at work underneath both anatomy and fiction, we argue, underlie a conception of the body that informs more particularized notions of mobility, sociality, and physicality.
The Effect of Foot Massage on Pain Intensity and Anxiety in Patients Having Undergone a Tibial Shaft Fracture Surgery: A Randomized Clinical Trial
Authors: Pasyar Nilofar , Rambod Masoume , Kahkhaee Fateme Rezaee
Published: November 2018

Objective:

To determine the effect of massage therapy on pain intensity and anxiety in patients who have undergone tibial shaft fracture surgery.

Design:

This study was a randomized clinical trial with a pre–post design. As the study included 2 treatment groups, it was a parallel study.

Setting:

Khatam-Al-Anbia Hospital in Zahedan, Iran, between July and August 2017.

Patients:

In all, 66 patients who underwent a tibial shaft fracture surgery were enrolled and randomly assigned to intervention and control groups (33 patients each).

Intervention:

The intervention included a 10-minute foot massage (5 minutes per leg) using sweet almond oil, the most common lubricant used in massage therapy.

Main Outcome Measurements:

Data were collected using pain numeric rating scale and Spielberger State-Trait Anxiety Inventory before and after intervention.

Results:

After intervention, the mean scores for pain intensity, and anxiety in the intervention and control groups were 4.72 (0.97) and 5.72 (0.91), and 42.84 (6.50) and 58.36 (10.37), respectively. A significant difference was noted between the intervention and control groups concerning pain intensity and anxiety.

Conclusions:

The results indicated that massage therapy reduced pain intensity and anxiety in patients who underwent tibial shaft fracture surgery. Therefore, using massage as a noninvasive and acceptable intervention is suggested in orthopaedic surgery, especially after tibial shaft fracture surgeries.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Prevalence of Asymptomatic Intraductal Papillary Mucinous Neoplasms in Healthy and Ill Populations Detected by Ultrasonography
Authors: Ricci Claudio , Migliori Marina , Imbrogno Andrea , Mazzotta Elena , Felicani Cristina , Serra Carla , Bergonzoni Barbara , Calculli Lucia , Casadei Riccardo
Published: November 2018

Objectives

The aim of this study was to establish the prevalence of intraductal papillary mucinous neoplasms (IPMNs) without and with high-risk stigmata (HRS)/worrisome features (WF) and the epidemiologic association between IPMNs and other diseases.

Methods

Ultrasound examinations of outpatients were evaluated. The IPMN was confirmed by magnetic resonance imaging. The prevalence of IPMNs and HRS/WF IPMNs was calculated. The association between IPMNs and other diseases was studied.

Results

The prevalence rate of IPMNs was 3.4%. A total of 1,531,264 IPMNs were expected in Italian population (2.5%), whereas 2257 per 100,000 citizens (2.3%) were expected in the European standard population (ESP2013). The prevalence rates of HRS/WF IPMNs were 0.5%, 0.7%, and 0.6%, in our, the Italian, and the ESP2013 populations, respectively. A total of 432,881 and 620 HRS/WF IPMNs per 100,000 residents were expected in the Italian and the ESP2013 populations, respectively. The IPMN prevalence increased over 50 years of age (odds ratio [OR], 3.2; P < 0.001) and over 70 years of age (OR, 1.9; P < 0.001). Female sex was related to the presence of IPMNs (OR, 1.9; P < 0.001).

Conclusions

Intraductal papillary mucinous neoplasms had a high prevalence in asymptomatic nonhospitalized populations. Age older than 50 years identified a possible risk category.
The use and misuse of herbarium specimens in evaluating plant extinction risks
Authors: Nic Lughadha Eimear , Walker Barnaby E. , Canteiro Cátia , Chadburn Helen , Davis Aaron P. , Hargreaves Serene , Lucas Eve J. , Schuiteman André , Williams Emma , Bachman Steven P. , Baines David , Barker Amy , Budden Andrew P. , Carretero Julia , Clarkson James J. , Roberts Alexandra , Rivers Malin C.
Published: November 2018

Herbarium specimens provide verifiable and citable evidence of the occurrence of particular plants at particular points in space and time, and are vital resources for assessing extinction risk in the tropics, where plant diversity and threats to plants are greatest. We reviewed approaches to assessing extinction risk in response to the Convention on Biological Diversity's Global Strategy for Plant Conservation Target 2: an assessment of the conservation status of all known plant species by 2020. We tested five alternative approaches, using herbarium-derived data for trees, shrubs and herbs in five different plant groups from temperate and tropical regions. All species were previously fully assessed for the IUCN Red List. We found significant variation in the accuracy with which different approaches classified species as threatened or not threatened. Accuracy was highest for the machine learning model (90%) but the least data-intensive approach also performed well (82%). Despite concerns about spatial, temporal and taxonomic biases and uncertainties in herbarium data, when specimens represent the best available evidence for particular species, their use as a basis for extinction risk assessment is appropriate, necessary and urgent. Resourcing herbaria to maintain, increase and disseminate their specimen data is essential to guide and focus conservation action.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Results dissemination from clinical trials conducted at German university medical centres was delayed and incomplete
Authors: Wieschowski Susanne , Riedel Nico , Wollmann Katharina , Kahrass Hannes , Müller-Ohlraun Stephanie , Schürmann Christopher , Kelley Sean , Kszuk Ute , Siegerink Bob , Dirnagl Ulrich , Meerpohl Jörg , Strech Daniel
Published: November 2018

Objective

Timely and comprehensive reporting of clinical trial results build the backbone of evidence-based medicine and responsible research. The proportion of timely disseminated trial results can inform alternative national and international benchmarking of university medical centers (UMCs).

Study Design and Setting

For all German UMCs we tracked all registered trials completed between 2009 and 2013. The results and an interactive website benchmark German UMCs regarding their performance in results dissemination.

Results

We identified and tracked 2,132 clinical trials. For 1,509 trials, one of the German UMCs took the academic lead. Of these 1,509 “lead trials”, 39% published their results (mostly via journal publications) in a timely manner (<24 months after completion). More than six years after study completion, 26% of all eligible lead trials still had not disseminated results.

Conclusion

Despite substantial attention from many stakeholders to the topic, there is still a strong delay or even absence of results dissemination for many trials. German UMCs have several opportunities to improve this situation. Further research should evaluate whether and how a transparent benchmarking of UMC performance in results dissemination helps to increase value and reduce waste in medical research.
Bone marrow-on-a-chip: Emulating the human bone marrow
Authors: Sieber Stefan , Winter Annika , Wachsmuth Johanna , David Rhiannon , Stecklum Maria , Hellmeyer Lars , Ewart Lorna , Marx Uwe , Lauster Roland , Rosowski Mark
Published: November 2018

Multipotent hematopoietic stem and progenitor cells HSPC reside in specialized stem cell niches within the bone marrow, that provide a suitable microenvironment for lifelong maintenance of the stem cells. Meaningful in vitro models recapitulating the in vivo stem cell niche biology can be employed for both basic research as well as for applied sciences and represent a powerful tool to reduce animal tests in preclinical studies. Recently we published the generation of an in vitro bone marrow niche model, capable of long-term cultivation of HSC based on an organ-on-a-chip platform. This study provides a detailed analysis of the 3D culture system including matrix environment analysis by SEM, transcriptome analysis and system intrinsic differentiation induction. Furthermore, the bone marrow on a chip model can serve to multiply and harvest HSPC, since repeated cell removal not compromised the functionality of the culture system. The prolongation of the culture time to 8 weeks demonstrate the capacity to apply the model in repeated drug testing experiments. The quality of the presented system is emphasized by the differentiation capacity of long-term cultivated HSPC in vitro and in vivo. Transplanted human HSPC migrated actively into the bone marrow of irradiated mice and contributed to the long-term reconstitution of the hematopoietic system after four and eight weeks of in vitro cultivation.

The introduced system offers a multitude of possible applications to address a broad spectrum of questions regarding HSPC, the corresponding bone marrow niche biology, and pathological aberrations.
Proteostasis environment shapes higher-order epistasis operating on antibiotic resistance
Authors: Guerrero Rafael F. , Scarpino Samuel V. , Rodrigues João V. , Hartl Daniel L. , Ogbunugafor C. Brandon
Published: November 2018

Recent studies have shown that higher-order epistasis is ubiquitous and can have large effects on complex traits. Yet, we lack frameworks for understanding how epistatic interactions are influenced by basic aspects of cell physiology. In this study, we assess how protein quality control machinery—a critical component of cell physiology—affects epistasis for different traits related to bacterial resistance to antibiotics. Specifically, we attempt to disentangle the interactions between different protein quality control genetic backgrounds and two sets of mutations: (i) SNPs associated with resistance to antibiotics in an essential bacterial enzyme (dihydrofolate reductase, or DHFR) and (ii) differing DHFR bacterial species-specific amino acid background sequences (Escherichia coli, Listeria grayi, andChlamydia muridarum). In doing so, we add nuance to the generic observation that non-linear genetic interactions are widespread and capricious in nature, by proposing a mechanistically-grounded analysis of how proteostasis shapes epistasis. These findings simultaneously fortify and demystify the role of environmental context in modulating higher-order epistasis, with direct implications for evolutionary theory, genetic modification technology, and efforts to manage antimicrobial resistance.
DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction
Authors: Weinstein Joshua A. , Regev Aviv , Zhang Feng
Published: November 2018

Analyzing the spatial organization of molecules in cells and tissues is a cornerstone of biological research and clinical practice. However, despite enormous progress in profiling the molecular constituents of cells, spatially mapping these constituents remains a disjointed and machinery-intensive process, relying on either light microscopy or direct physical registration and capture. Here, we demonstrate DNA microscopy, a new imaging modality for scalable, optics-free mapping of relative biomolecule positions. In DNA microscopy of transcripts, transcript molecules are tagged in situ with randomized nucleotides, labeling each molecule uniquely. A second in situ reaction then amplifies the tagged molecules, concatenates the resulting copies, and adds new randomized nucleotides to uniquely label each concatenation event. An algorithm decodes molecular proximities from these concatenated sequences, and infers physical images of the original transcripts at cellular resolution. Because its imaging power derives entirely from diffusive molecular dynamics, DNA microscopy constitutes a chemically encoded microscopy system.
3D brain angiogenesis model to reconstitute maturation of functional human blood-brain barrier in vitro
Authors: Lee Somin , Chung Minhwan , Li Jeon Noo
Published: November 2018

0.

Human central nervous system (CNS) vasculature in brain expresses a distinctive barrier phenotype, the blood–brain barrier (BBB), which protects the brain against harmful pathogens. Since the BBB contributes to low success rate in CNS pharmacotherapy by restricting drug transportation, the development of an in vitro human BBB model has been in demand. Previous models were unable to fully represent the complex threedimensional (3D) anatomical structure or specific barrier phenotypes of the matured BBB. In this study, we present a physiological 3D microfluidic model of the human BBB that mimics its developmental process including CNS angiogenesis and subsequent maturation in concert with perivascular cells. We used microfluidic hydrogel patterning to precisely and sequentially load perivascular cells into the model, investigate the role of each cell type on BBB phenotypes. We confirmed the necessity of the tri-culture system (brain endothelium with pericytes and astrocytes) to attain the characteristic BBB vascular morphology such as minimized diameter and maximized junction expression. In addition, endothelial-perivascular cell interaction was also critical in reconstituting p-glycoprotein (p-gp), efflux transporter in our model that works as metabolic barrier of BBB and blocks drug to enter CNS. The 3D hydrogel matrix was tuned with hyaluronic acid (HA) to optimize the interaction between endothelial cells and astrocytes. Our in vitro BBB system mimics CNS angiogenesis and characteristic features of BBB. We expect the model will contribute to deeper understanding of neurodegenerative diseases and cost-efficient development of effective CNS medications.
Early divergence of mutational mechanisms drives genetic heterogeneity of fetal tissues
Authors: Kuijk Ewart , Blokzijl Francis , Jager Myrthe , Besselink Nicolle , Boymans Sander , Chuva de Sousa Lopes Susana M. , van Boxtel Ruben , Cuppen Edwin
Published: November 2018

A developing human fetus needs to balance rapid cellular expansion with maintaining genomic stability. Here, we accurately quantified and characterized somatic mutation accumulation in fetal tissues by analyzing individual stem cells from human fetal liver and intestine. Fetal mutation rates were ~5-fold higher than in tissue-matched adult stem cells. The mutational landscape of fetal intestinal stem cells resembled that of adult intestinal stem cells, while the mutation spectrum of fetal liver stem cells is distinct from stem cells of the fetal intestine and the adult liver. Our analyses indicate that variation in mutational mechanisms, including oxidative stress and spontaneous deamination of methylated cytosines, contribute to the observed divergence in mutation accumulation patterns and drive genetic mosaicism in humans.

One Sentence Summary

Liver and intestinal cells accumulate elevated amounts and diverged types of somatic DNA mutations during early human fetal development
Contribution of Retrotransposition to Developmental Disorders
Authors: Gardner Eugene J. , Prigmore Elena , Gallone Giuseppe , Danecek Petr , Samocha Kaitlin E. , Handsaker Juliet , Gerety Sebastian S. , Ironfield Holly , Short Patrick J. , Sifrim Alejandro , Singh Tarjinder , Chandler Kate E. , Clement Emma , Lachlan Katherine L. , Prescott Katrina , Rosser Elisabeth , FitzPatrick David R. , Firth Helen V. , Hurles Matthew E. ,   on behalf of the Deciphering Developmental Disorders study
Published: November 2018

Mobile genetic Elements (MEs) are segments of DNA which, through an RNA intermediate, can generate new copies of themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. As such, we have identified RT-derived events in 9,738 exome sequenced trios with DD-affected probands as part of the Deciphering Developmental Disorders (DDD) study. We have ascertained 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04% of probands), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we have estimated genome-wide germline ME mutagenesis and constraint and demonstrated that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.
Boost-HiC : Computational enhancement of long-range contacts in chromosomal contact maps
Authors: Carron L. , Morlot J.B. , V. Matthys , Lesne A. , Mozziconacci J.
Published: November 2018

Genome-wide chromosomal contact maps are widely used to uncover the 3D organisation of genomes. They rely on the collection of millions of contacting pairs of genomic loci. Contact frequencies at short range are usually well measured in experiments, while there is a lot of missing information about long-range contacts.

We propose to use the sparse information contained in raw contact maps to determine high-confidence contact frequency between all pairs of loci. Our algorithmic procedure, Boost-HiC, enables the detection of Hi-C patterns such as chromosomal compartments at a resolution that would be otherwise only attainable by sequencing a hundred times deeper the experimental Hi-C library. Boost-HiC can also be used to compare contact maps at an improved resolution.

Boost-HiC is available at https://github.com/LeopoldC/Boost-HiC
ATR function is indispensable to allow proper mammalian follicle development
Authors: Pacheco Sarai , Garcia-Caldés Montserrat , Roig Ignasi
Published: November 2018

Mammalian female fertility relies on the proper development of follicles. Right after birth in mouse, oocytes associate with somatic ovarian cells to form follicles. These follicles grow during adult lifetime to produce viable gametes. In this study, we analyzed the role of the ATM and rad3-related (ATR) kinase in mouse oogenesis and folliculogenesis using a hypomorphic mutation of the Atr gene (Murga et al., 2009). Female mice homozygote for this allele have been reported to be sterile. Our data show that female meiotic prophase is not grossly altered when ATR levels are reduced. However, follicle development is majorly compromised since Atr mutant ovaries present a decrease of growing follicles. Comprehensive analysis of follicular cell death and proliferation suggest that wild-type levels of ATR are required to achieve optimal follicular development. Altogether, these findings suggest that reduced ATR expression causes sterility due to defects in follicular progression rather than in meiotic recombination. We discuss the implication of these findings for the use of ATR inhibitors as anti-cancer drugs and its possible side effects on female fertility.
Genome-wide analysis reveals signatures of selection for gait traits in Yili horse
Authors: Liu Ling-Ling , Fang Chao , Meng Jun , Detilleux Johann , Liu Wu-Jun , Yao Xin-Kui
Published: November 2018

High quality gaits play an important role in many breeding programs, but the genes of gait were limited at the moment. Here, we present an analysis of genomic selection signatures in 53 individuals from two breeds, using genotype data from the Affymetrix Equine 670K SNP genotyping array. The 11 selection regions of Yili horse were identified using anFSTstatistic and XP-EHH calculated in 200-kb windows across the genome. In total, 50 genes could be found in the 11 regions, and two candidate genes related to locomotory behavior (CLN6, FZD4). The genome of Yili horse and Russian horse were shaped by natural and artificial selection. Our results suggest that gait trait of Yili horse may related to two genes. This is the first time when whole genome array data is utilized to study genomic regions affecting gait in Yili horse breed.
A databank for intracellular electrophysiological mapping of the adult somatosensory cortex
Authors: da Silva Lantyer Angelica , Calcini Niccolò , Bijlsma Ate , Kole Koen , Emmelkamp Melanie , Peeters Manon , Scheenen Wim J. J. , Zeldenrust Fleur , Celikel Tansu
Published: November 2018

Background

Neurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in the adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration.

Findings

Here we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9-45 weeks old) from both sexes (females, N=195; males, N=120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N=257; VC, N=46), frozen noise injections (CC, N=104) and triangular voltage sweeps (VC, 10 (N=132), 50 (N=146) and 100 ms (N=152)), from regular spiking (N=169) and fast-spiking neurons (N=66).

Conclusions

The data can be used to systematically study the properties of somatic integration, and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.
Genomic analysis of dingoes identifies genomic regions under reversible selection during domestication and feralization
Authors: Zhang Shao-jie , Wang Guo-Dong , Ma Pengcheng , Zhang Liang-liang , Yin Ting-Ting , Liu Yan-hu , Otecko Newton O. , Wang Meng , Ma Ya-ping , Wang Lu , Mao Bingyu , Savolainen Peter , Zhang Ya-ping
Published: November 2018

Dingoes(Canis dingo)are wild canids living in Australia. They have lived isolated from both the wild and the domestic ancestor and are a unique model for studying feralization, the process in which a domestic species escapes human control, adapts to the wild, and diverges from the domestic ancestor into a genetically distinct population. Here, we sequenced the genomes of 10 dingoes and 2 New Guinea Singing Dogs, to study the origins and feralization process of the dingo. Phylogenetic and demographic analyses show that dingoes originate from domestic dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia 4300-5000 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identified 99 positively selected genes enriched in starch and fat metabolism pathways, indicating a diet change during feralization of dingoes. Interestingly, we found that 14 genes have shifted allele frequencies compared to dogs but not compared to wolves. This suggests that the selection affecting these genes during domestication of the wolf was reversed in the feralization process. One of these genes,ARHGEF7,may promote the formation of neural spine and synapses in hippocampal neurons. Functional assays showed that an A to G mutation inARHGEF7,located in a transcription factor-binding site, decreases the endogenous expression. This suggests thatARHGEF7may have been under selection for behavioral adaptations related to the transitions in environment both from wild to domestic and from domestic back to wild. Our results indicate that adaptation to domestication and feralization primarily affected different genomic regions, but that some genes, related to neurodevelopment, metabolism and reproduction, may have been reversibly affected in the two processes.
A well-ordered nanoflow LC-MS/MS approach for proteome profiling using 200 cm long micro pillar array columns
Authors: De Beeck Jeff Op , Pauwels Jarne , Van Landuyt Natalie , Jacobs Paul , De Malsche Wim , Desmet Gert , Argentini Andrea , Staes An , Martens Lennart , Impens Francis , Gevaert Kris
Published: November 2018

In bottom-up proteomics, capillaries up to 75 cm long with internal diameters of 50 to 100 µm packed with sub-2-µm C18-functionalized particles are routinely used in combination with high-resolution mass spectrometry. Unlike such conventional liquid chromatography (LC) columns, micro pillar array columns (µPAC™) are fabricated using micromachining technology, resulting in perfectly ordered chromatographic separation beds, leading to a minimized analyte dispersion while column permeability is increased by one order of magnitude. This allows using very long columns (up to 200 cm) at only a fraction of the pressure needed to operate packed bed columns. To validate µPAC™ column performances, different amounts of tryptic digests of HEK293T cell lysates were prepared and separated using a 200 cm µPAC™ column or a 40 cm long conventional column. Using an Orbitrap Elite instrument, on average 25% more proteins were identified with the µPAC™ column. Moreover, the rate at which the peak width increases with gradient time is much lower on the µPAC™ column. For a 10-hour long gradient, average peak widths below 0.5 min were observed, resulting in consistent identification of over 5,000 proteins. Combining long solvent gradients and this new type of LC column, substantial improvements in proteome coverage could be obtained. Finally, we demonstrated high reproducibility and durability of the µPAC™ column. Data are available via ProteomeXchange with identifiers PXD011547 and PXD013235.
Biophysical Studies of Some Bee Products as Radioprotectors
Authors: Hamieda Shimaa F. , Hassan Amal I. , Abdou Mona I. , Khalil Wafaa A. , Abd-El Nour Kamal N.
Published: November 2018

The study had been planned to evaluate some antioxidant ingredients in honey and propolis. Also, a study on ionizing gamma irradiated rats was done to assess these antioxidants as radioprotectors. Bioactive ingredients, such as phenols, flavonoids and trace elements, were explored using FTIR, UV-Vis and AAS spectroscopic techniques. Animals were exposed to fractionated gamma radiation doses. Honey, propolis and their combination were administrated before and during the irradiation period. Serum levels of total protein, albumin and uric acid were estimated. Also, the osmotic fragility of Red Blood Corpuscles (RBCs) membranes and a microscopic examination of blood films were investigated. The analysis demonstrated that the level of phenolic, flavonoid and trace elements are higher in propolis than honey. The levels of total protein and albumin decreased post irradiation while the level of uric acid increased. Likewise, osmotic fragility of RBCs membranes was increased with a sticking forming RBCs aggregation. It had been found that administration of the natural antioxidants induced amelioration in most of the studied parameters. It can be concluded that natural antioxidants produced a modulation against oxidative stress induced by ionizing radiation.

Summary Statement

Assessment of some antioxidant ingredients in honey and propolis. Also, a study on ionizing gamma irradiated rats was done to assess these antioxidants as radioprotectors.
Robust estimation of recent effective population size from number of independent origins in soft sweeps
Authors: Khatri Bhavin S. , Burt Austin
Published: November 2018

Estimating recent effective population size is of great importance in characterising and predicting the evolution of natural populations. Methods based on nucleotide diversity may underestimate current day effective population sizes due to historical bottlenecks, whilst methods that reconstruct demographic history typically only detect long-term variations. However, soft selective sweeps, which leave a fingerprint of mutational history by recurrent mutations on independent haplotype backgrounds, holds promise of an estimate more representative of recent population history. Here we present a simple and robust method of estimation based only on knowledge of the number of independent recurrent origins and the current frequency of the beneficial allele in a population sample, independent of the strength of selection and age of the mutation. Using a forward time theoretical framework, we show the mean number of origins is a function ofθ= 2Nμand current allele frequency, through a simple equation, and the distribution is approximately Poisson. This estimate is robust to whether mutants pre-existed before selection arose, and is equally accurate for diploid populations with incomplete dominance. For fast (e.g., seasonal) demographic changes compared to time scale for fixation of the mutant allele, and for moderate peak-to-trough ratios, we show our constant population size estimate can be used to bound the maximum and minimum population size. Applied to the Vgsc gene ofAnopheles gambiae, we estimate an effective population size of roughly 6 × 107, and including seasonal demographic oscillations, a minimum effective population size greater than 6 × 106and a maximum less than 3 × 109.
A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle
Authors: Iso-Touru Terhi , Wurmser Christine , Venhoranta Heli , Hiltpold Maya , Savolainen Tujia , Sironen Anu , Fischer Konrad , Flisikowski Krzysztof , Fries Ruedi , Vicente-Carrillo Alejandro , Alvarez-Rodriguez Manuel , Nagy Szabolcs , Mutikainen Mervi , Peippo Jaana , Taponen Juhani , Sahana Goutam , Guldbrandtsen Bernt , Simonen Henri , Rodriguez-Martinez Heriberto , Andersson Magnus , Pausch Hubert
Published: November 2018

Background

Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for many artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected.

Results

Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8,557 fertile bulls although five homozygous haplotype carriers were expected (P=0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5’ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle.

Conclusions

Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).
Efficient Construction of a Complete Index for Pan-Genomics Read Alignment
Authors: Kuhnle Alan , Mun Taher , Boucher Christina , Gagie Travis , Langmead Ben , Manzini Giovanni
Published: November 2018

While short read aligners, which predominantly use the FM-index, are able to easily index one or a few human genomes, they do not scale well to indexing databases containing thousands of genomes. To understand why, it helps to examine the main components of the FM-index in more detail, which is a rank data structure over the Burrows-Wheeler Transform (BWT) of the string that will allow us to find the interval in the string’s suffix array (SA) containing pointers to starting positions of occurrences of a given pattern; second, a sample of the SA that — when used with the rank data structure — allows us access the SA. The rank data structure can be kept small even for large genomic databases, by run-length compressing the BWT, but until recently there was no means known to keep the SA sample small without greatly slowing down access to the SA. Now that Gagie et al. (SODA 2018) have defined an SA sample that takes about the same space as the run-length compressed BWT — we have the design for efficient FM-indexes of genomic databases but are faced with the problem of building them. In 2018 we showed how to build the BWT of large genomic databases efficiently (WABI 2018) but the problem of building Gagie et al.’s SA sample efficiently was left open. We compare our approach to state-of-the-art methods for constructing the SA sample, and demonstrate that it is the fastest and most space-efficient method on highly repetitive genomic databases. Lastly, we apply our method for indexing partial and whole human genomes, and show that it improves over Bowtie with respect to both memory and time.

Availability

We note that the implementation of our methods can be found here:https://github.com/alshai/r-index.
Evaluation of S1PR1/pSTAT3 and S1PR2/FOXP1 Expression in Aggressive, Mature B Cell Lymphomas
Authors: Al-Kawaaz Mustafa , Sanchez Teresa , Kluk Michael J
Published: November 2018

Aggressive, mature B-cell lymphomas represent a heterogeneous group of diseases including Burkitt Lymphoma (BL), High Grade B Cell Lymphomas (HGBL) (eg, Double-Hit B cell lymphomas (HGBL-DH: HGBL with MYC and BCL2 and/or BCL6 translocations)), HGBL, Not Otherwise Specified (HGBL, NOS) and Diffuse Large B Cell Lymphoma. The overlapping morphologic and immunohistochemical features of these lymphomas may pose diagnostic challenges in some cases, and a better understanding of potential diagnostic biomarkers and possible therapeutic targets is needed. Sphingosine 1 Phosphate Receptors (S1PR1-5) represent a family of G-protein coupled receptors that bind the sphingolipid (S1P) and influence migration and survival pathways in a variety of cell types, including lymphocytes. S1PRs are emerging as biomarkers in B cell biology and interaction between S1PR pathways and STAT3 or FOXP1 has been reported, especially in DLBCL. Our aim was to extend the understanding of the S1PR1, STAT3 and S1PR2, FOXP1 expression beyond DLBCL, into additional aggressive, mature B cell lymphomas such as BL, HGBL-DH and HGBL,NOS.

Herein, we report that S1PR1 and S1PR2 showed different patterns of expression in mantle zones and follicle centers in reactive lymphoid tissue and, among the lymphomas in this study, Burkitt lymphomas showed a unique pattern of expression compared to HGBL and DLBCL. Additionally, we found that S1PR1 and S1PR2 expression was typically mutually exclusive and were expressed in a low proportion of cases (predominantly HGBL involving extranodal sites). Lastly, FOXP1 was expressed in a high proportion of the various case types and pSTAT3 was detected in a significant proportion of HGBL and DLBCL cases. Taken together, these findings provide further evidence that S1PR1, pSTAT3, S1PR2 and FOXP1 play a role in a subset of aggressive mature B cell lymphomas.
Targeting IDH1 as a pro-senescent therapy in high-grade serous ovarian cancer
Authors: Dahl Erika S. , Buj Raquel , Leon Kelly E. , Newell Jordan M. , Bitler Benjamin G. , Snyder Nathaniel W. , Aird Katherine M.
Published: November 2018

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer. High-grade serous carcinoma (HGSC) is the most frequently diagnosed and lethal histosubtype of EOC. A significant proportion of HGSC patients relapse with chemoresistant disease. Therefore, there is an urgent need for novel therapeutic strategies for HGSC. Metabolic reprogramming is a hallmark of cancer cells, and targeting metabolism for cancer therapy may be beneficial. Here we found that in comparison to normal fallopian tube epithelial cells, HGSC cells preferentially utilize glucose in the TCA cycle and not for aerobic glycolysis. This correlated with universally increased TCA cycle enzyme expression in HGSC cells under adherent conditions. To further differentiate the necessity of TCA cycle enzymes in ovarian cancer progression, we found that only wildtype isocitrate dehydrogenase I (IDH1) is both significantly increased in HGSC cells in spheroid conditions and is associated with reduced progression-free survival. IDH1 protein expression is also increased in primary HGSC patient tumors. Pharmacological inhibition or knockdown of IDH1 decreased proliferation of multiple HGSC cell lines by inducing senescence. Mechanistically, suppression of IDH1 increased the repressive histone mark H3K9me2 at proliferation promoting gene loci (PCNAandMCM3), which led to decreased mRNA expression. Altogether, these data suggest that increased IDH1 activity is an important metabolic adaptation in HGSC and that targeting wildtype IDH1 in HGSC alters the repressive histone epigenetic landscape to induce senescence. Therefore, inhibition of IDH1 may act as a novel therapeutic approach to alter both the metabolism and epigenetics of HGSC as a pro-senescent therapy.