bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal cholesterol depletion during Fcγ receptor-mediated phagocytosis contributes to Lyn kinase regulation
Authors: Lu Stella M. , Volchuk Allen , Fairn Gregory D. 
Published: August 2018

AbstractCholesterol-rich nanodomains, historically referred to as lipid rafts, have previously been reported to be critical for proper Fcγ Receptor and Lyn kinase signaling during phagocytosis. Throughout the initial stages of phagocytosis, the nascent phagosome is actively remodeled by localized lipid metabolism and exocytosis. However, to date, little is known about the dynamics of cholesterol during this stage of particle engulfment. Using a genetically-encoded biosensor for cholesterol, we find that cholesterol is depleted from the nascent phagosome prior to sealing. Additionally, protein markers of both cholesterol-rich and cholesterol-poor nanodomains also clear from the site of phagocytosis arguing against the selective depletion of specific membrane domains. Consistent with previous studies we find that exocytosis contributes to the remodeling of the nascent phagosome. The displacement of cholesterol from the forming phagosome was paralleled by Lyn kinase helping to explain the reduction of phosphotyrosine signal in the nascent phagosome. This diminution of cholesterol and Lyn from the base of the cup may aid in the processivity of the phagocytic signal during pseudopod extension, and provide an unappreciated mechanism by which Lyn kinase signaling is regulated during phagocytosis.Summary Statement: Localized exocytosis dilutes cholesterol from the phagocytic cup leading to the displacement of Lyn kinase and an attenuation of signaling.
Proton Conductivity of Glycosaminoglycans
Authors: Selberg John , Jia Manping , Rolandi Marco 
Published: August 2018

AbstractProton (H+) conductivity is important in many natural phenomena including oxidative phosphorylation in mitochondria and archea, uncoupling membrane potentials by the antibiotic Gramicidin, and proton actuated bioluminescence in dinoflagellate. In all of these phenomena, the conduction of H+ occurs along chains of hydrogen bonds between water and hydrophilic residues. These chains of hydrogen bonds are also present in many hydrated biopolymers and macromolecule including collagen, keratin, chitosan, and various proteins such as reflectin. All of these materials are also proton conductors. Recently, our group has discovered that the jelly found in the Ampullae of Lorenzini-shark’s electrosensing organs- is the highest naturally occurring proton conducting substance. The jelly has a complex composition, but we attributed the conductivity to the glycosaminoglycan keratan sulfate (KS). Here, we have measured the proton conductivity of hydrated keratan sulfate using PdHx contacts to be 0.50 ± 0.11 mS cm -1- consistent to that of Ampullae of Lorenzini jelly, 2 ± 1 mS cm -1. Proton conductivity, albeit with lower values, is also shared by other glycosaminoglycans with similar chemical structures including dermatan sulfate, chondroitin sulfate A, heparan sulfate, and hyaluronic acid. This observation confirms the structure property relationship between proton conductivity and the chemical structure of biopolymers.
Real time monitoring of transtibial elevated vacuum prostheses: a case series on socket air pressure
Authors: Schoepp Katherine R. , Schofield Jonathon S. , Home David , Dawson Michael R. , Lou Edmond , Keri McNiel , Marasco Paul D. , Hebert Jacqueline S. 
Published: August 2018

AbstractElevated vacuum is a prosthetic suspension method used to reduce slippage between the prosthetic socket and the residual limb. Evaluation of the effectiveness of these systems is limited due to a lack of correlation to actual socket air pressure, particularly during unconstrained movements. This may explain some of the variability in functional outcomes reported in the literature. We developed a light-weight portable socket measurement system to quantify internal socket air pressure, temperature, and acceleration. We implemented the system onto the sockets of three transtibial prosthesis users with mechanical elevated vacuum pumps. Participants completed five functional tasks with and without the vacuum pumps actively connected, including the 2-Minute Walk test, 5-Times Sit-to-Stand test, 4-Square Step test, L-Test, and Figure-8 test. Results demonstrated that the use of elevated vacuum pumps produced different gait profiles and pressure ranges for each user, with significant differences between pump conditions. Two of the participants demonstrated substantially lower air pressure (higher vacuum) over time while the pump was active compared to inactive. The minimum air pressure measured at the completion of the 2-Minute Walk test was −34.6 ± 7.7 kPa, which is not as low as pressures reported in literature during benchtop experiments. One participant did not show substantial changes in pressure over time for either pump condition. Functional task performance was not significantly different between pump conditions. Correlation with accelerometer readings allowed air pressure data to be aligned with the gait cycle; peak positive pressures occurred just following initial contact of the foot in early stance, and the most negative pressures (vacuum) were observed throughout swing. This study has demonstrated the use of a portable data logging tool that may serve the clinical and research communities to quantify the operation of elevated vacuum systems, and better understand the variability of mechanical pump operation and overall system performance.
Health-seeking behavior and associated factors among community in Southern Ethiopia:Community based cross-sectional study guided by Health belief model
Authors: Asfaw Likawunt Samuel , Ayanto Samuel Yohannes , Aweke Yitagessu Habtu 
Published: August 2018

AbstractBackgroundHealth-seeking behavior is a sequence of actions taken to promote health and prevent disease. Governments’ expenditure to health is being improved in Ethiopia. In contrast, high disease burden and low health service utilization is observed. The low health service utilization could be due to low health-seeking behavior of the community. Thus, this studywas aimed to determine the level of health-seeking behavior and associated factors in Hosanna town, Southern Ethiopia.MethodsWe used communitybased cross-sectional study design among community (n= 443) in Hosanna town. The overall health-seeking behavior of study participants was assessed using the mean score of each of the dimensions (health promotion and disease prevention activities) as a cut-off value. Having a score above the mean on each of the target dimensions was equated with having a high level of health seeking behaviour. STATA 12 soft-ware package (Stata Corporation, College Station, Texas, 77845, USA)was used for descriptive and logistic regression analysis.ResultsAbout eighty five percent of (85.4%) participants had low level of health-seeking behavior. Males were about two folds more likely to have low level of health-seeking behavior than females (AOR: 1.8; CI 1.03–3.42). Widowed participants were about five times more likely to have low health-seeking behavior (AOR: 4.8; CI 2.1–17.1) when compared to married participants. Those participants who are illiterate were about five times more likely to have low health-seeking behavior than who completed higher education (AOR: 4.5; CI 1.16–17.8).ConclusionThe study revealed low health-seeking behavior among the study participants in the study area. This finding suggested the need forurgent interventions to the health literacy packages of Ethiopia to enhance the health seeking behavior of the country.
Individual-Based Network Model for Rift Valley Fever in Kabale District, Uganda, to Guide Mitigation Measures: A One Health Model
Authors: Sekamatte Musa , Riad Mahbubul H. , Tekleghiorghis Tesfaalem , Linthicum Kenneth J. , Britch Seth C. , Richt Juergen A. , Gonzalez J. P. , Scoglio Caterina M 
Published: August 2018

AbstractRift Valley fever (RVF) is a zoonotic disease which causes significant morbidity and mortality among ungulate livestock and humans in endemic regions. In the major RVF epizootic regions of East Africa, the causative agent of the disease, Rift Valley fever virus (RVFV), is primarily transmitted by multiple mosquito species in Aedes, Culex, and Mansonia genera during both epizootic and enzootic periods in a complex transmission cycle largely driven by the environment. However, recent RVFV activity in Uganda demonstrated that RVFV could also spread into new regions through livestock movements, and underscored the need to develop effective mitigation strategies to reduce transmission and prevent spread among cattle operations. We simulated RVFV transmission among cattle in different sub counties of Kabale District in Uganda using real world livestock data in a network-based model. This model considered livestock as spatially explicit factors in different sub-counties subjected to specific vector mosquito and environmental factors, and was configured to investigate and quantitatively evaluate the relative impacts of mosquito control, livestock movement regulations, and diversity in cattle populations on the spread of the RVF epizootic. We concluded that cattle movement should be restricted during periods of high vector mosquito abundance to control the epizootic spreading among sub-counties. On the other hand we found that mosquito control would only be sufficient to control the epizootic when mosquito abundance was low. Importantly, simulation results also showed that cattle populations with a higher diversity with regard to indigenous combined with exotic breeds led to reduced numbers of infected cattle compared to more homogenous cattle populations.
Monocyte depletion attenuates the development of posttraumatic hydrocephalus and preserves white matter integrity after traumatic brain injury
Authors: Makinde Hadijat M. , Just Talia B. , Cuda Carla M. , Bertolino Nicola , Procissi Daniele , Schwulst Steven J. 
Published: August 2018

AbstractMonocytes are amongst the first cells recruited into the brain after traumatic brain injury (TBI). We have shown monocyte depletion 24 hours prior to TBI reduces brain edema, decreases neutrophil infiltration and improves behavioral outcomes. Additionally, both lesion and ventricle size correlate with poor neurologic outcome after TBI. Therefore, we aimed to determine the association between monocyte infiltration, lesion size, and ventricle volume. We hypothesized that monocyte depletion would attenuate lesion size, decrease ventricle enlargement, and preserve white matter in mice after TBI. C57BL/6 mice underwent pan monocyte depletion via intravenous injection of liposome-encapsulated clodronate. Control mice were injected with liposome-encapsulated PBS. TBI was induced via an open-head, controlled cortical impact. Mice were imaged using magnetic resonance imaging (MRI) at 1, 7, and 14 days post-injury to evaluate progression of lesion and to detect morphological changes associated with injury (3D T1- weighted MRI) including regional alterations in white matter patterns (multi-direction diffusion MRI). Lesion size and ventricle volume were measured using semi-automatic segmentation and active contour methods with the software program ITK-SNAP. Data was analyzed with the statistical software program PRISM. No significant effect of monocyte depletion on lesion size was detected using MRI following TBI (p=0.4). However, progressive ventricle enlargement following TBI was observed to be attenuated in the monocyte-depleted cohort (5.3 ± 0.9mm3) as compared to the sham-depleted cohort (13.2 ± 3.1mm3;p=0.02). Global white matter integrity and regional patterns were evaluated and quantified for each mouse after extracting fractional anisotropy maps from the multi-direction diffusion-MRI data using Siemens Syngo DTI analysis package. Fractional anisotropy values were preserved in the monocyte-depleted cohort (123.0 ± 4.4mm3) as compared to sham-depleted mice (94.9 ± 4.6mm3;p=0.025) by 14 days post-TBI. The MRI derived data suggests that monocyte depletion at the time of injury may be a novel therapeutic strategy in the treatment of TBI. Furthermore, non-invasive longitudinal imaging allows for the evaluation of both TBI progression as well as therapeutic response over the course of injury.
Understanding narwhal diving behaviour using Hidden Markov Models with dependent state distributions and long range dependence
Authors: Ngôe Manh Cuong , Heide-Jørgensen Mads Peter , Ditlevsen Susanne 
Published: August 2018

AbstractDiving behaviour of narwhals is still largely unknown. We build three-state Hidden Markov models (HMM) to describe the diving behaviour of a narwhal and fit the models to a three-dimensional response vector of maximum dive depth, duration of dives and post-dive surface time of 8,609 dives measured in East Greenland over 83 days, an extraordinarily long and rich data set. In particular, diurnal patterns in diving behaviour for a marine mammal is being inferred, by using periodic B-splines with boundary knots in 0 and 24 hours. Several HMMs with covariates are used to characterize dive patterns. Narwhal diving patterns have not been analysed like this before, but in studies of other whale species, response variables have been assumed independent. We extend the existing models to allow for dependence between state distributions, and show that the dependence has an impact on the conclusions drawn about the diving behaviour. It is thus paramount to relax this strong and biologically unrealistic assumption to obtain trustworthy inferences.Author summaryNarwhals live in pristine environments. However, the increase in average temperatures in the Arctic and the concomitant loss of summer sea ice, as well as increased human activities, such as ship traffic and mineral exploration leading to increased noise pollution, are changing the environment, and therefore probably also the behavior and well-being of the narwhal. Here, we use probabilistic models to unravel the diving and feeding behavior of a male narwhal, tagged in East Greenland in 2013, and followed for nearly two months. The goal is to gain knowledge of the whales’ normal behavior, to be able to later detect possible changes in behavior due to climatic changes and human influences. We find that the narwhal uses around two thirds of its time searching for food, it typically feeds during deep dives (more than 350 m), and it can have extended periods, up to 3 days, without feeding activity.
tudor-domain containing protein 5-primepromotes male sexual identity in theDrosophilagermline and is repressed in females bySex lethal
Authors: Primus Shekerah , Pozmanter Caitlin , Baxter Kelly , Van Doren Mark 
Published: August 2018

AbstractFor sexually reproducing organisms, production of male or female gametes depends on specifying the correct sexual identity in the germline. InD. melanogaster, Sex lethal(Sxl) is the key gene that controls sex determination in both the soma and the germline, but how it does so in the germline is unknown, other than that it is different than in the soma. We conducted an RNA expression profiling experiment to identify direct and indirect germline targets of Sxl specifically in the undifferentiated germline. We find that, in these cells,Sxlloss does not lead to a global masculinization observed at the whole-genome level. In contrast,Sxlappears to affect a discrete set of genes required in the male germline, such asPhf7. We also identifytudor domain containing protein 5-prime(tdrd5p) as a target for Sxl regulation that is important for male germline identity.tdrd5pis repressed by Sxl in female germ cells, but is highly expressed in male germ cells where it promotes proper male fertility and germline differentiation. Additionally, Tdrd5p localizes to cytoplasmic granules with some characteristics of RNA Processing (P-) Bodies, suggesting that it promotes male identity in the germline by regulating post-transcriptional gene expression.Author summaryLike humans, all sexually reproducing organisms require gametes to reproduce. Gametes are made by specialized cells called germ cells, which must have the correct sexual identity information to properly make sperm or eggs. In fruit flies, germ cell sexual identity is controlled by the RNA-binding protein Sxl, which is expressed only in females. To better understand howSxlpromotes female identity, we conducted an RNA expression profiling experiment to identify genes whose expression changes in response to the loss ofSxlfrom germ cells. Here, we identifytudor domain containing protein 5-prime (tdrd5p), which is expressed 17-fold higher in ovaries lackingSxlcompared to control ovaries. Additionally,tdrd5pplays an important role in males as male flies that are mutant for this gene cannot make sperm properly and thus are less fertile. Moreover, we find thattdrd5ppromotes male identity in the germline, as several experiments show that it can shift the germ cell developmental program from female to male. This study tells us thatSxlpromotes female identity in germ cells by repressing genes, liketdrd5p, that promote male identity. Future studies into the function oftdrd5pwill provide mechanistic insight into how this gene promotes male identity.
Single-domain antibodies represent novel alternatives to monoclonal antibodies as targeting agents against the human papillomavirus 16 E6 protein
Authors: Togtema Melissa , Hussack Greg , Dayer Guillem , Teghtmeyer Megan , Raphael Shalini , Tanha Jamshid , Zehbe Ingeborg 
Published: August 2018

AbstractApproximately one-fifth of all malignancies worldwide are etiologically-associated with a persistent viral or bacterial infection. Thus, there is particular interest in therapeutic molecules which utilize components of a natural immune response to specifically inhibit oncogenic microbial proteins, as it is anticipated they will elicit fewer off-target effects than conventional treatments. This concept has been explored in the context of human papillomavirus type 16 (HPV16)-related cancers, through the development of monoclonal antibodies and fragments thereof against the viral E6 oncoprotein. However, challenges related to the biology of E6 as well as the functional properties of the antibodies themselves appear to have precluded their clinical translation. In this study, we attempted to address these issues by exploring the utility of the variable domains of camelid heavy-chain-only antibodies (denoted as VHHs). Through the construction and panning of two llama immune VHH phage display libraries, a pool of potential VHHs was isolated. The interactions of these VHHs with recombinant E6 protein were further characterized using ELISA, Western blotting under both denaturing and native conditions, as well as surface plasmon resonance, and three antibodies were identified that bound recombinant E6 with affinities in the nanomolar range. Our results now lead the way for subsequent studies into the ability of these novel molecules to inhibit HPV16-infected cellsin vitroandin vivo.
Identification of Key Differentially Expressed MicroRNAs in Cancer Patients Through Pan-cancer Analysis
Authors: Hu Yu , Dingerdissen Hayley , Gupta Samir , Kahsay Robel , Shanker Vijay , Wan Quan , Yan Cheng , Mazumder Raja 
Published: August 2018

AbstractA number of microRNAs (miRNAs) functioning in gene silencing have been associated with cancer progression. However, common expression patterns of abnormally expressed miRNAs and their potential roles in multiple cancer types have not yet been evaluated. To minimize the difference of patients, we collected miRNA sequencing data of 575 patients with tumor and adjacent non-tumorous tissues from 14 cancer types from The Cancer Genome Atlas (TCGA), and performed differential expression analysis using DESeq2 and edgeR. The results showed that cancer types can be grouped based on the distribution of miRNAs with different expression patterns. We found 81 significantly differentially expressed miRNAs (SDEmiRNAs) unique to one of the 14 cancers may affect patient survival rate, and 21 key SDEmiRNAs (nine overexpressed and 12 under-expressed) associated with at least eight cancers and enriched in more than 60% of patients per cancer, including four newly identified SDEmiRNAs (hsa-mir-4746, hsa-mir-3648, hsa-mir-3687, and hsa-mir-1269a). The downstream effect of these 21 SDEmiRNAs on cellular functions was evaluated through enrichment and pathway analysis of 7,186 protein-coding gene targets from literature mining with known differential expression profiles in cancers. It enables identification of their functional similarity in cell proliferation control across a wide range of cancers and to build common regulatory networks over cancer-related pathways. This is validated by construction of a regulatory network in PI3K pathway. This study provides evidence of the value of further analysis on SDEmiRNAs as potential biomarkers and therapeutic targets for cancer diagnosis and treatment.
Imperfect Linkage Disequilibrium Generates Phantom Epistasis (& Perils of Big Data)
Authors: de los Campos G. , Sorensen D. , Toro M. A. 
Published: August 2018

ABSTRACTThe genetic architecture of complex human traits and diseases is affected by large number of possibly interacting genes, but detecting epistatic interactions can be challenging. In the last decade, several studies have alluded to problems that linkage disequilibrium can create when testing for epistatic interactions between DNA markers. However, these problems have not been formalized nor have their consequences been quantified in a precise manner. Here we use a conceptually simple three locus model involving a causal locus and two markers to show that imperfect LD can generate the illusion of epistasis, even when the underlying genetic architecture is purely additive. We describe necessary conditions for such “phantom epistasis” to emerge and quantify its relevance using simulations. Our empirical results demonstrate that phantom epistasis can be a very serious problem in GWAS studies (with rejection rates against the additive model greater than 0.2 for nominal p-values of 0.05, even when the model is purely additive). Some studies have sought to avoid this problem by only testing interactions between SNPs with R-sq. <0.1. We show that this threshold is not appropriate and demonstrate that the magnitude of the problem is even greater with large sample size. We conclude that caution must be exercised when interpreting GWAS results derived from very large data sets showing strong evidence in support of epistatic interactions between markers.
Powerful and interpretable behavioural features for quantitative phenotyping ofC. elegans
Authors: Javer Avelino , Ripoll-Sanchez Lidia , Brown André E.X. 
Published: August 2018

AbstractBehaviour is a sensitive and integrative readout of nervous system function and therefore an attractive measure for assessing the effects of mutation or drug treatment on animals. Video data provides a rich but high-dimensional representation of behaviour and so the first step of analysis is often some form of tracking and feature extraction to reduce dimensionality while maintaining relevant information. Modern machine learning methods are powerful but notoriously difficult to interpret, while handcrafted features are interpretable but do not always perform as well. Here we report a new set of handcrafted features to compactly quantifyC. elegansbehaviour. The features are designed to be interpretable but to capture as much of the phenotypic differences between worms as possible. We show that the full feature set is more powerful than a previously defined feature set in classifying mutant strains. We then use a combination of automated and manual feature selection to define a core set of interpretable features that still provides sufficient power to detect behavioural differences between mutant strains and the wild type. Finally, we apply the new features to detect time-resolved behavioural differences in a series of optogenetic experiments targeting different neural subsets.