bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of tyrosine kinase receptor Ephb2 impairs proliferation and stem cell activity of spermatogonia in culture†
Authors: N’Tumba-Byn Thierry , Yamada Makiko , Seandel Marco
Published: December 2019

Germline stem and progenitor cells can be extracted from the adult mouse testis and maintained long-term in vitro. Yet, the optimal culture conditions for preserving stem cell activity are unknown. Recently, multiple members of the Eph receptor family were detected in murine spermatogonia, but their roles remain obscure. One such gene, Ephb2, is crucial for maintenance of somatic stem cells and was previously found enriched at the level of mRNA in murine spermatogonia. We detected Ephb2 mRNA and protein in primary adult spermatogonial cultures and hypothesized that Ephb2 plays a role in maintenance of stem cells in vitro. We employed CRISPR-Cas9 targeting and generated stable mutant SSC lines with complete loss of Ephb2. The characteristics of Ephb2-KO cells were interrogated using phenotypic and functional assays. Ephb2-KO SSCs exhibited reduced proliferation compared to wild-type cells, while apoptosis was unaffected. Therefore, we examined whether Ephb2 loss correlates with activity of canonical pathways involved in stem cell self-renewal and proliferation. Ephb2-KO cells had reduced ERK MAPK signaling. Using a lentiviral transgene, Ephb2 expression was rescued in Ephb2-KO cells, which partially restored signaling and proliferation. Transplantation analysis revealed that Ephb2-KO SSCs cultures formed significantly fewer colonies than WT, indicating a role for Ephb2 in preserving stem cell activity of cultured cells. Transcriptome analysis of wild-type and Ephb2-KO SSCs identified Dppa4 and Bnc1 as differentially expressed, Ephb2-dependent genes that are potentially involved in stem cell function. These data uncover for the first time a crucial role for Ephb2 signaling in cultured SSCs.
“They’re in My Heart, Mind, and Cells”: What Continuing Bonds Reveal About Social Networks
Authors: Stemen Sara E
Published: December 2019

Background and Objectives

Research suggests that robust social networks have positive effects on peoples’ well-being. An instrumental methodology for studying networks is the social convoy model, a diagram of concentric circles that illustrate network size, structure, and satisfaction. Convoys have been described as dynamic. Specifically, as people age, their convoys become stronger and smaller due to focusing on what matters most and accumulating losses. Therefore, convoys only include meaningful, living persons. The continuing bonds model posits that it is normal for people to maintain connections with the deceased. The objective of the current study was to integrate the social convoy and continuing bonds models in order to examine the presence of deceased loved ones in convoys.

Research Design and Methods

Eighteen individuals (M = 66 years), recruited via fliers and snowball sampling, participated in one semistructured interview regarding the death of a loved one and their convoy. Participants also completed a convoy model, identifying where the deceased fit (if anywhere) when they were alive and at present. Interviews were transcribed, coded, and analyzed for themes.

Results

Three themes emerged: communication (i.e., writing or speaking to the deceased), continuity (i.e., a continuing relationship), and reciprocity (i.e., perceived exchange of support(s)). Eighty-nine percent of participants felt their loved one’s death did not change their convoy presence and 88% reported that their positioning in the convoy remained unchanged.

Discussion and Implications

This research offers a new way to think about convoys and may prompt the development of supportive interventions for bereaved individuals.
The Jacobian, Reflection Arrangement and Discriminant for Reflection Hopf Algebras
Authors: Kirkman E , Zhang J J
Published: December 2019

We study finite-dimensional semisimple Hopf algebra actions on noetherian connected graded Artin–Schelter regular algebras and introduce definitions of the Jacobian, the reflection arrangement, and the discriminant in a noncommutative setting.
Genetic parameter estimates for plasma oxidative status traits in slaughter pigs
Authors: Ntawubizi Martin , Raes Katleen , De Smet Stefaan
Published: December 2019

The aim of the present study was to assess the effect of sex and to estimate genetic parameters for several traits related to plasma oxidative status in slaughter pigs, i.e., ferric reducing ability of plasma (FRAP), concentrations of α-tocopherol and malondialdehyde (MDA), and glutathione peroxidase (GPx) activity. Blood samples were collected at slaughter from 477 Piétrain × (Landrace × Large White intercross) pigs of 2 performance test stations. Heritabilities (±SE) of plasma oxidative status traits as well as their phenotypic and additive genetic correlations with animal performance traits were estimated with multiple-trait REML animal models using VCE software. Results displayed no significant difference between barrows and gilts for FRAP and α-tocopherol in plasma. However, gilts had a significantly higher concentration of MDA and lower GPx activity compared with barrows. Heritability estimates were high for GPx (0.55 ± 0.05), and medium to low for α-tocopherol (0.30 ± 0.06), FRAP (0.22 ± 0.05), and MDA (0.15 ± 0.04). Estimated additive genetic and phenotypic correlations between these four traits were generally low, except for a negative additive genetic correlation between FRAP and GPx of −0.45 (±0.23). Additive genetic correlations between plasma oxidative status traits and animal performance traits were also generally absent or low with maximum values of ~0.3. Parameter estimates in this study have to be interpreted with caution because of the small size of the dataset. Nevertheless, it may be concluded that there is considerable additive genetic variance for plasma oxidative status traits in slaughter pigs. More research is warranted on the genetic determination of oxidative stress in farm animals and its relevance in breeding programs.
Identification of Volatiles From Plants Infested With Honeydew-Producing Insects, and Attraction of House Flies (Diptera: Muscidae) to These Volatiles
Authors: Hung Kim Y , McElfresh J Steven , Zou Yunfan , Wayadande Astri , Gerry Alec C
Published: December 2019

House flies (Musca domestica L.) are mechanical vectors of food-borne pathogens including Salmonella spp., Escherichia coli O157:H7, and Shigella spp., resulting in increased risk of diarrheal disease in areas where flies are abundant. Movement of house flies into food crops may be increased by the presence of honeydew-producing insects feeding on these crops. Using gas chromatography-electroantennogram detection (GC-EAD) and gas chromatography-mass spectrometry (GC-MS), volatile odors that elicited house fly antennal response were identified from naval orange (Osbeck) (Sapindales: Rutaceae) and Marsh grapefruit (Macfad.) (Sapindales: Rutaceae) leaves infested with whitefly (Hemiptera: Aleyrodidae) and from whole faba (L.) (Fabales: Fabaceae) bean plants infested with aphids (Hemiptera: Aphididae). Volatiles identified included benzaldehyde, butyl hexanoate, β-caryophyllene, Δ3-carene, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), (Z)-3-hexenyl acetate, myrcene, limonene, linalool, and naphthalene. This was followed by semifield bioassays of volatile blends and individual volatiles to determine house fly attraction to these volatiles. Although fly capture rates in the semifield setting were low, benzaldehyde and (Z)-3-hexenyl acetate were consistently attractive to house flies as individual compounds and as components of volatile blends.
Toward a standard pathological and molecular characterization of recurrent glioma in adults: a Response Assessment in Neuro-Oncology effort
Authors: Haider Ali S , van den Bent Martin , Wen Patrick Y , Vogelbaum Michael A , Chang Susan , Canoll Peter D , Horbinski Craig M , Huse Jason T
Published: December 2019

Regardless of subtype, diffuse gliomas of adulthood are characterized by inexorable progression through treatment. Cancer recurrence in the context of therapy is by no means unique to gliomas. For many tumors residing outside the central nervous system (CNS), tissue-based analyses are routinely employed to document the molecular and cellular features of disease recurrence. Such interventions are inconsistently applied for gliomas, however, and lack rigorous standardization when they are. While many of the reasons underlying these discrepancies reflect pragmatic realities inherent to CNS disease, the suboptimal employment of histological and molecular assessment at recurrence nevertheless represents a missed opportunity to proactively guide patient management and increase knowledge. Herein, we address this quandary by pairing a succinct description of the histological, biological, and molecular characteristics of recurrent glioma with recommendations for how to better standardize and implement quality pathological assessment into patient management. We hope this review will prompt thoughtful revision of standard operating procedures to maximize the utility of glioma re-biopsy.
Irregular sleep and event schedules are associated with poorer self-reported well-being in US college students
Authors: Fischer Dorothee , McHill Andrew W , Sano Akane , Picard Rosalind W , Barger Laura K , Czeisler Charles A , Klerman Elizabeth B , Phillips Andrew J K
Published: December 2019

Study Objectives

Sleep regularity, in addition to duration and timing, is predictive of daily variations in well-being. One possible contributor to changes in these sleep dimensions are early morning scheduled events. We applied a composite metric—the Composite Phase Deviation (CPD)—to assess mistiming and irregularity of both sleep and event schedules to examine their relationship with self-reported well-being in US college students.

Methods

Daily well-being, actigraphy, and timing of sleep and first scheduled events (academic/exercise/other) were collected for approximately 30 days from 223 US college students (37% females) between 2013 and 2016. Participants rated well-being daily upon awakening on five scales: Sleepy–Alert, Sad–Happy, Sluggish–Energetic, Sick–Healthy, and Stressed–Calm. A longitudinal growth model with time-varying covariates was used to assess relationships between sleep variables (i.e. CPDSleep, sleep duration, and midsleep time) and daily and average well-being. Cluster analysis was used to examine relationships between CPD for sleep vs. event schedules.

Results

CPD for sleep was a significant predictor of average well-being (e.g. Stressed–Calm: b = −6.3, p < 0.01), whereas sleep duration was a significant predictor of daily well-being (Stressed–Calm, b = 1.0, p < 0.001). Although cluster analysis revealed no systematic relationship between CPD for sleep vs. event schedules (i.e. more mistimed/irregular events were not associated with more mistimed/irregular sleep), they interacted upon well-being: the poorest well-being was reported by students for whom both sleep and event schedules were mistimed and irregular.

Conclusions

Sleep regularity and duration may be risk factors for lower well-being in college students. Stabilizing sleep and/or event schedules may help improve well-being.

Clinical Trial Registration

NCT02846077.
Informing Pharmacokinetic Models with Physiological Data: Oral Population Modeling of L-Serine in Humans
Authors: Bosley J. R. , Björnson Elias , Zhang Cheng , Turkez Hasan , Nielsen Jens , Uhlen Mathias , Boren Jan , Mardinoglu Adil
Published: December 2019

To determine how to set optimal oral L-serine (serine) dose levels for a clinical trial, existing literature was surveyed. Data sufficient to set the dose was inadequate, and so a (n=10) Phase I-A calibration trial was performed, administering serine with and without other oral agents. We analyzed the trial and the literature data using pharmacokinetic (PK) modeling and statistical analysis. The therapeutic goal is to modulate specific serine-related metabolic pathways in the liver using the lowest possible dose which gives the desired effect since the upper bound was expected to be limited by toxicity. In this paper, we first review relevant literature, describe the calibration trial and resulting data, and present the results of modeling from the trial. Serine is a non-essential amino acid that is nonetheless present at a base level in blood from both dietary sources and endogenous production. Serine is consumed by several pathways. A standard PK approach, in which a common model structure was selected using a fit to data, yielded a model with a single central compartment corresponding to plasma, clearance from that compartment, and an endogenous source of serine. The lack of intravenous data normally prevents independent determination of bioavailability and volume of distribution, however, under some assumptions about endogenous synthesis and use, values could be estimated. The model was poorly conditioned but did give consistent estimates. To improve conditioning, a parametric structure was changed to estimate ratios (bioavailability over volume, for example). Model fit quality was improved and the uncertainty in estimated parameters was reduced. Because of the particular interest in the fate of serine, the model was used to estimate whether serine is consumed in the gut, absorbed by the liver, or entered the blood in either a free state, or in a protein- or tissue-bound state that is not measured by our assay. The PK model structure was set up to represent relevant physiology, and this quantitative systems biology approach allowed a broader set of physiological data to be used to narrow parameter and prediction confidence intervals, and to better understand the biological meaning of the data. The model results allowed us to determine the optimal human dose for future trials, including a trial design component including IV and tracer studies. A key contribution is that we were able to use human physiological data from the literature to inform the PK model and to set reasonable bounds on parameters, and to improve model conditioning. Leveraging literature data produced a more predictive, useful model.
Heterogeneity and targeted therapy-induced adaptations in lung cancer revealed by longitudinal single-cell RNA sequencing
Authors: Maynard Ashley , McCoach Caroline E. , Rotow Julia K. , Harris Lincoln , Haderk Franziska , Kerr Lucas , Yu Elizabeth A. , Schenk Erin L. , Tan Weilun , Zee Alexander , Tan Michelle , Gui Philippe , Lea Tasha , Wu Wei , Urisman Anatoly , Jones Kirk , Sit Rene , Kolli Pallav K. , Seeley Eric , Gesthalter Yaron , Le Daniel D. , Yamauchi Kevin A. , Naeger David , Thomas Nicholas J. , Gupta Anshal , Gonzalez Mayra , Do Hien , Tan Lisa , Gomez-Sjoberg Rafael , Gubens Matthew , Jahan Thierry , Kratz Johannes R. , Jablons David , Neff Norma , Doebele Robert C. , Weissman Jonathan , Blakely Collin M. , Darmanis Spyros , Bivona Trever G.
Published: December 2019

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNAseq) of metastatic lung cancer was performed using 44 tumor biopsies obtained longitudinally from 27 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNAseq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNAseq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.
Precision Multiparameter Tracking of Inflammation on Timescales of Hours to Years Using Serial Dried Blood Spots
Authors: Anderson N. Leigh , Razavi Morteza , Pope Matthew E. , Yip Richard , Cameron L. C. , Bassini-Cameron Adriana , Pearson Terry W.
Published: December 2019

High-frequency longitudinal tracking of inflammation using dried blood microsamples provides a new window for personalized monitoring of infections, chronic inflammatory disease, and clinical trials of anti-inflammatory drugs. Using 1,662 dried blood spot samples collected by 16 subjects over periods of weeks to years, we studied the behavior of 12 acute phase response (APR) and related proteins in inflammation events correlated with infection, vaccination, surgery, intense exercise and Crohn’s disease. Proteins were measured using SISCAPA mass spectrometry and normalized to constant plasma volume using low-variance proteins, generating high precision within-person biomarker trajectories with well-characterized personal baselines. The results shed new light on the dynamic regulation of APR proteins and offer a new approach to visualization of multidimensional inflammation trajectories.
Risk of schizophrenia and bipolar disorder in patients with multiple sclerosis: record-linkage studies
Authors: Meier Ute-Christiane , Ramagopalan Sreeram V , Goldacre Michael J , Goldacre Raph
Published: December 2019

Background

The epidemiology of psychiatric comorbidity in multiple sclerosis (MS) remains poorly understood.

Objective

We aimed to determine the risk of schizophrenia and bipolar disorder in MS patients.

Material and Methods

Retrospective cohort analyses were performed using an all-England national linked Hospital Episode Statistics (HES) dataset (1999-2016) and to determine whether schizophrenia or bipolar disorder are more commonly diagnosed subsequently in people with MS (n=128,194), and whether MS is more commonly diagnosed subsequently in people with schizophrenia (n=384,188) or bipolar disorder (n=203,592), than would be expected when compared with a reference cohort (∼15 million people) after adjusting for age and other factors. Adjusted hazard ratios (aHRs) were calculated using Cox proportional hazards models.

Results

Findings were dependent on whether the index and subsequent diagnoses were selected as the primary reason for hospital admission or were taken from anywhere on the hospital record. When searching for diagnoses anywhere on the hospital record, there was a significantly elevated risk of subsequent schizophrenia (aHR 1.51, 95% confidence interval (CI) 1.40 to 1.60) and of bipolar disorder (aHR 1.14, 95% CI 1.04 to 1.24) in people with prior-recorded MS and of subsequent MS in people with prior-recorded schizophrenia (aHR 1.26, 1.15-1.37) or bipolar disorder (aHR 1.73, 1.57-1.91), but most of these associations were reduced to null when analyses were confined to diagnoses recorded as the primary reason for admission.

Conclusion

Further research is needed to investigate the potential association between MS and schizophrenia and/or bipolar disorder as it may shed light on underlying pathophysiology and help identify potential shared risk factors.
What is the best evidence for graft choice in ACL reconstruction? Protocol for a systematic review and network meta-analysis
Authors: Habibi Junaid , Zakharia Alexander , Woolnough Taylor , Axelrod Daniel , de SA Darren
Published: December 2019

Introduction

Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed sports medicine procedures. A variety of grafts are currently used for reconstruction, including both allograft and autograft. Despite numerous meta-analyses, there exists no high-quality quantitative synthesis of all randomized controlled trial (RCT) data on graft choice.

Objective

To identify the optimal graft choice for ACL reconstruction by performing the first systematic review and network meta-analysis (NMA) to include both functional outcomes and complications.

Methods

Multiple digital databases including MEDLINE, Embase, and CENTRAL will be searched independently and in duplicate for RCTs randomizing graft choice in ACL reconstruction in skeletally mature patients. A Bayesian framework with a random-effects model will be used for NMA. Surface under the cumulative ranking curve (SUCRA) values will be used to generate a rank list for each outcome. Results will be reported as mean differences (MD) (or standardized mean difference, if necessary) or relative risk (RR) with 95% credible intervals (CI). Comparisons will be inferred to be statistically significant if the 95% CI of MD does not cross zero or if the 95% CI of relative risk does not cross one. Studies will be assessed for quality using the Cochrane risk of bias assessment tool. Quality of evidence for each network comparison will be determined as per the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach for network meta-analyses. This NMA will be reported according to the PRISMA extension statement for network meta-analyses

Outcomes of interest

Functional outcomes of interest including range of motion, return to activity/sport, and IKDC, Lysholm, Tegner, ACL-QOL, and KOOS scores. Persistent laxity as measured by Lachman, Pivot-shift, side-to-side, and measured laxity (e.g. KT-1000) will also be analyzed. Complications (e.g. infection, graft failure, donor site pain), tunnel osteolysis, and failure (including but not limited to graft rupture and/or persistent laxity) will be compared between grafts.

Relevance/Impact

This NMA will be the first high-quality syntheses of all randomized evidence regarding graft choice in ACL reconstruction. As the first analysis to compare all major graft choices independently, it will be used to inform surgeon-patient decision making. It has the reasonable possibility of changing clinical practice.
Clustering of susceptible individuals within households can drive an outbreak: an individual-based model exploration
Authors: Kuylen Elise , Willem Lander , Broeckhove Jan , Beutels Philippe , Hens Niel
Published: December 2019

When estimating important measures such as the herd immunity threshold, and the corresponding efforts required to eliminate measles, it is often assumed that susceptible individuals are uniformly distributed throughout populations. However, unvaccinated individuals may be clustered in a variety of ways, including by geographic location, by age, in schools, or in households. Here, we investigate to which extent different levels of within-household clustering of susceptible individuals may impact the risk and persistence of measles outbreaks. To this end, we apply an individual-based model, Stride, to a population of 600,000 individuals, using data from Flanders, Belgium. We compare realistic scenarios regarding the distribution of susceptible individuals within households in terms of their impact on epidemiological measures for outbreak risk and persistence. We find that higher levels of within-household clustering of susceptible individuals increase the risk, size and persistence of measles outbreaks. Ignoring within-household clustering thus leads to underestimations of measles elimination and outbreak mitigation efforts.
Probability waves: pattern-based p-value correction in mass univariate analysis between two event-related potential waves
Authors: Abramov Dimitri Marques
Published: December 2019

Background

Methods for p-value correction are criticized for either increasing Type II error or improperly reducing Type I error. This problem is worse when dealing with hundreds or thousands of paired comparisons between waves or images which are performed point-to-point. This text considers patterns in probability vectors resulting from multiple point-to-point comparisons between two ERP waves (mass univariate analysis) to correct p-values. These patterns (probability waves) mirror ERP waveshapes and might be indicators of consistency in statistical differences.

New method

In order to compute and analyze these patterns, we convoluted the decimal logarithm of the probability vector (p’) using a Gaussian vector with size compatible to the ERP periods observed. For verify consistency of this method, we also calculated mean amplitudes of late ERPs from Pz (P300 wave) and O1 electrodes in two samples, respectively of typical and ADHD subjects.

Results

the present method reduces the range of p’-values that did not show covariance with neighbors (that is, that are likely random differences, type I errors), while preserving the amplitude of probability waves, in accordance to difference between respective mean amplitudes.

Comparison with existing methods

the positive-FDR resulted in a different profile of corrected p-values, which is not consistent with expected results or differences between mean amplitudes of the analyzed ERPs.

Conclusion

the present new method seems to be biological and statistically more suitable to correct p-values in mass univariate analysis of ERP waves.
Honeybees adjust colour preferences in response to concurrent social information from conspecifics and heterospecifics
Authors: Romero-González José E , Solvi Cwyn , Chittka Lars
Published: December 2019

Bees efficiently learn asocial and social cues to optimise foraging from fluctuating floral resources. However, it remains unclear how bees respond to divergent sources of social information, and whether such social cues might modify bees’ natural preferences for non-social cues (e.g. flower colour), hence affecting foraging decisions. Here, we investigated honeybees’ (Apis mellifera) inspection and choices of unfamiliar flowers based on both natural colour preferences and simultaneous foraging information from conspecifics and heterospecifics. Individual honeybees’ preferences for flowers were recorded when the reward levels of a learned flower type had declined and novel-coloured flowers were available where they would find either no social information or one conspecific and one heterospecific (Bombus terrestris), each foraging from a different coloured flower (magenta or yellow). Honeybees showed a natural preference for magenta flowers. Honeybees modified their inspection of both types of flowers in response to conspecific and heterospecific social information. The presence of either demonstrator on the less-preferred yellow flower increased honeybees’ inspection of yellow flowers. Conspecific social information influenced observers’ foraging choices of yellow flowers, thus outweighing their original preference for magenta flowers. This effect was not elicited by heterospecific social information. Our results indicate that flower colour preferences of honeybees are rapidly adjusted in response to conspecific social information, which in turn is preferred over heterospecific information, possibly favouring the transmission of adaptive foraging information within species.
Detection for suspected Genetically Modified Maize and Soybean crops in the selcted places of Ethiopia using PCR machine
Authors: Admas Adugnaw , Melese Smegnew , Genetu Amare
Published: December 2019

Detection of genetically modified organisms (GMOs) in crops is an important issue for all the subjects involved in seed quality control and customer’s right. Due to the increasing number of GMOs research and development activity in the globe during the past few years, it has become necessary to screen and regulate highely practiced GMO crops. In this study, following the extraction of genomic DNA from agriculture farming land and commercial areas collected samples that suspected for GMOs such as Soybean and maize crops, the recombinant DNA target sequences were targeted to detect for transgene such as CaMV35s gene using thermal cycler Polymerase Chain Reaction (PCR). In addition, for positive control taxone specficInvertaseandLectinegene of maize and soybean have done. Based on the gel electrophoresis results,Invertase and Lectinegene events were detected in all maize and soybean samples respectively. How ever, fortunately in all collected samples of maize and soybean in different places of the countery trans-genes were not detected. Finally, this reserch result concludes that in the studied area soybean and maize crops are GMO free.
Cortical control of virtual self-motion using task-specific subspaces
Authors: Schroeder Karen E , Perkins Sean M , Wang Qi , Churchland Mark M
Published: December 2019

Brain-machine interfaces (BMIs) for reaching have enjoyed continued performance improvements, yet there remains significant need for BMIs that control other movement classes. Recent scientific findings suggest that the intrinsic covariance structure of neural activity depends strongly on movement class, potentially necessitating different decode algorithms across classes. To address this, we developed a self-motion BMI based on cortical activity as monkeys performed non-reaching arm movements: cycling a hand-held pedal to progress along a virtual track. Unlike during reaching, we found no high-variance dimensions that directly correlated with to-be-decoded variables. Yet we could decode a single variable – self-motion – by non-linearly leveraging structure that spanned many high-variance neural dimensions. Resulting online BMI-control success rates approached those during manual control. These findings make two broad points regarding how to build decode algorithms that harmonize with the empirical structure of neural activity in motor cortex. First, even when decoding from the same cortical region (e.g., arm-related motor cortex) different movement classes may need to employ very different strategies. Although correlations between neural activity and hand velocity are prominent during reaching tasks, they are not a fundamental property of motor cortex and cannot be counted on to be present in general. Second, although one generally desires a low-dimensional readout, it can be beneficial to leverage a multi-dimensional high-variance subspace. Fully embracing this approach requires highly non-linear approaches tailored to the task at hand, but can produce near-native levels of performance.

Significance Statement

Many BMI decoders have been constructed for controlling movements normally performed with the arm. Yet it is unclear how these will function beyond the reach-like scenarios where they were developed. Existing decoders implicitly assume that neural covariance structure, and correlations with to-be-decoded kinematic variables, will be largely preserved across tasks. We find that the correlation between neural activity and hand kinematics, a feature typically exploited when decoding reach-like movements, is essentially absent during another task performed with the arm: cycling through a virtual environment. Nevertheless, the use of a different strategy, one focused on leveraging the highest-variance neural signals, supported high performance real-time BMI control.
Functional genomics of the parasitic habits of blowflies and botflies
Authors: Cardoso Gisele Antoniazzi , Deszo Marina , Torres Tatiana Teixeira
Published: December 2019

Infestation by dipterous larvae – myiasis - is a major problem for livestock industries worldwide and can cause severe economic losses. The Oestroidea superfamily is an interesting model to study the evolution of myiasis-causing flies because of the diversity of parasitism strategies among closely-related species. These flies are saprophagous, obligate parasites, or facultative parasites and can be subdivided into cutaneous, nasopharyngeal, traumatic, and furuncular. We expect that closely-related species have genetic differences that lead to the diverse parasitic strategies. To identify genes with such differences, we used gene expression and coding sequence data from five species (Cochliomyia hominivorax, Chrysomya megacephala, Lucilia cuprina, Dermatobia hominis, andOestrus ovis). We tested whether 1,287 orthologs have different expression and evolutionary constraints under different scenarios. We found two up-regulated genes; one in species causing cutaneous myiasis that is involved in iron transportation/metabolization (ferritin), and another in species causing traumatic myiasis that responds to reduced oxygen levels (anoxia up-regulated-like). Our evolutionary analysis showed a similar result. In theCh. hominivoraxbranch, we found one gene with the same function as ferritin that may be evolving under positive selection, spook. This is the first step towards understanding origins and evolution of parasitic strategy diversity in Oestroidea.
Intravital quantification of absolute cytoplasmic B cell calcium reveals dynamic signaling across B cell differentiation stages
Authors: Ulbricht Carolin , Leben Ruth , Rakhymzhan Asylkhan , Kirchhoff Frank , Nitschke Lars , Radbruch Helena , Niesner Raluca A , Hauser Anja E
Published: December 2019

Development, function and maintenance of lymphocytes largely depend upon the cellular mobilization and storage of Ca2+ions. In B lymphocytes, the absolute amount of calcium mobilized and retained after cell signaling remains unknown, athough it is a crucial part of their selection within germinal centers and differentiation into plasma cells. Here, we introduce the novel reporter mouse strain YellowCaB that expresses the genetically encoded calcium indicator TN-XXL in CD19+lymphocytes. The construct consists of the electrondonor fluorophore eCFP and the acceptor citrine, linked by a calcium sensitive domain. Its conformation and therefore donor quenching is directly linked to cytosolic calcium concentrations. By combining intravital two-photon fluorescence lifetime microscopy with our numerical approach for phasor-based analysis, we are able to extract absolute cytoplasmic calcium concentrations in activated B cells for the first timein vivo. We show that calcium concentrations in B cells are highly dynamic and fluctuations persist in extrafollicular B cells with functional relevance.
HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread
Authors: Aggarwal Anupriya , Ospina Stella Alberto , Henry Catherine , Narayan Kedar , Turville Stuart G.
Published: December 2019

F-Actin remodelling is important for the spread of HIV via cell-cell contacts, yet the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM), we observed F-Actin structures that exhibit strong positive curvature to be enriched for HIV buds. Virion proteomics, gene silencing, and viral mutagenesis supported a Cdc42-IQGAP1-Arp2/3 pathway as the primary intersection of HIV budding, membrane curvature and F-Actin regulation. Whilst HIV egress activated the Cdc42-Arp2/3 filopodial pathway, this came at the expense of cell-free viral release. Importantly, release could be rescued by cell-cell contact, provided Cdc42 and IQGAP1 were present. From these observations we conclude that a proportion out-going HIV has corrupted a central F-Actin node that enables initial coupling of HIV buds to cortical F-Actin to place HIV at the leading cell edge. Whilst this initially prevents particle release, maturation of cell-cell contacts signals back to this F-Actin node to enable viral release & subsequent infection of the contacting cell.
HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice
Authors: Samardzija Marijana , Corna Andrea , Gomez-Sintes Raquel , Jarboui Mohamed Ali , Armento Angela , Roger Jerome E. , Petridou Eleni , Haq Wadood , Paquet-Durand Francois , Zrenner Eberhart , Zeck Günther , Grimm Christian , Boya Patricia , Ueffing Marius , Trifunović Dragana
Published: December 2019

Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors while cones remain initially unaffected. Cone death follows rod death secondarily due to increased oxidative stress, inflammation, and loss of structural and nutritional support provided by rods. Here, we show that secondary cone cell death in animal models for RP was associated with an increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at a late stage of the disease, when majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival. Moreover, the surviving cones remained light sensitive and initiated light-driven ganglion cell responses. RNA-seq analysis of protected cones demonstrated that HDAC inhibition led to multi-level protectionviaregulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique possibility for a targeted pharmacological protection of both primary degenerating rods and secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients independent of the disease stage.
Epigenetically bistable regions across neuron-specific genes govern neuron eligibility to a coding ensemble in the hippocampus
Authors: Odell S. C. , Taki F. , Klein S. , Chen R. J. , Levine O. B. , Skelly M.J. , Nabila A. , Brindley E. , Gal Toth J. , Dündar F. , Sheridan C. K. , Fetcho R. N. , Alonso A. , Liston C. , Landau D. A. , Pleil K. E , Toth M.
Published: December 2019

Episodic memories are stored in distributed neurons but how eligibility of individual neurons to coding ensembles is determined remains elusive. We identified thousands of predominantly bistable (CpG methylated or unmethylated) regions within neuronal gene bodies, established during the development of the mouse hippocampal dentate gyrus. Reducing DNA methylation and the proportion of the methylated epialleles at bistable regions compromised novel context-induced neuronal activation and spatial memory. Conversely, increasing methylation and the frequency of the methylated epialleles at bistable regions enhanced intrinsic excitability and spatial memory but impaired spatial working memory, indicating that the developmentally established methylated-unmethylated epiallelic balance at bistable regions is essential for proper neuronal excitability and hippocampal cognitive functions. Single-nucleus profiling revealed the enrichment of specific epialleles from a subset of bistable regions, primarily exonic, in encoding neurons. We propose a model in which epigenetically bistable regions create neuron heterogeneity, and specific constellations of exonic epialleles dictate, via modulating neuronal excitability, eligibility to a coding ensemble.
A waveguide imaging platform for live-cell TIRF imaging of neurons over large fields of view
Authors: Opstad Ida S. , Ströhl Florian , Fantham Marcus , Hockings Colin , Vanderpoorten Oliver , van Tartwijk Francesca W. , Lin Julie Qiaojin , Tinguely Jean-Claude , Dullo Firehun T. , Kaminski-Schierle Gabriele S. , Ahluwalia Balpreet S. , Kaminski Clemens F.
Published: December 2019

Large fields of view (FOVs) in total internal reflection fluorescence microscopy (TIRFM) via waveguides have been shown to be highly beneficial for single molecule localisation microscopy on fixed cells [1, 2] and have also been demonstrated for short-term live-imaging of robust cell types [3–5], but not yet for delicate primary neurons nor over extended periods of time. Here, we present a waveguide-based TIRFM set-up for live-cell imaging of demanding samples. Using the developed microscope, referred to asthe ChipScope, we demonstrate successful culturing and imaging of fibroblasts, primary rat hippocampal neurons and axons ofXenopusretinal ganglion cells (RGC). The high contrast and gentle illumination mode provided by TIRFM coupled with the exceptionally large excitation areas and superior illumination homogeneity offered by photonic waveguides have potential for a wide application span in neuroscience applications.
Estimates of abundance and change in abundance of the Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa
Authors: Vargas-Fonseca OA , Kirkman SP , Oosthuizen WC , Bouveroux T , Cockcroft V , Conry D , Pistorius PA
Published: December 2019

We investigated the abundance of Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa, from the Goukamma Marine Protected Area (MPA) to the Tsitsikamma MPA, between 2014 and 2016. During this period, 662.3h of boat-based photo-identification survey effort was carried out, and the sighting histories of 817 identified individuals were used to estimate abundance using mark-recapture modelling. The selected open population model (POPAN) provided an estimate of 2,295 individuals (95% CI: 1,157-4,553) for the entire study area. A model estimate was produced for a subset of the study area, Plettenberg Bay, which could be compared with a past estimate for this location (2002-2003). The comparison suggested a 72.3% decrease in abundance, from 6,997 (95% CI: 5,230-9,492) in 2002-2003 to 1,940 (95% CI: 1,448-2,600) in 2014-2016. The decline in abundance was supported by a 72% reduction in mean group size for Plettenberg Bay between the periods. It is essential to be able to assess abundance changes at other locations to inform revision ofT. aduncusconservation status in South Africa.
Overprecision Increases Subsequent Surprise
Authors: Schatz Derek , Moore Don A.
Published: December 2019

Overconfident people should be surprised that they are so often wrong. Are they? Three studies examined the relationship between confidence and surprise in order to shed light on the psychology of overprecision in judgment. Participants reported ex-ante confidence in their beliefs, and after receiving accuracy feedback, they then reported ex-post surprise. Results show that more ex-ante confidence produces less ex-post surprise for correct answers; this relationship reverses for incorrect answers. However, this sensible pattern only holds for some measures of confidence; it fails for confidence-interval measures. The results can help explain the robust durability of overprecision in judgment.
Anillin/Mid1p interacts with the ECSRT-associated protein Vps4p and mitotic kinases to regulate cytokinesis in fission yeast
Authors: Rezig Imane M. , Gould Gwyn W. , McInerny Christopher J.
Published: December 2019

Cytokinesis is the final stage of the cell cycle which separates cellular constituents to produce two daughter cells. UsingSchizosaccharomyces pombewe have investigated the role of various classes of proteins involved in this process. Central to these is anillin/Mid1p which forms a ring-like structure at the cell equator that predicts the site of cell separation through septation in fission yeast. Here we demonstrate a direct physical interaction between Mid1p and the endosomal sorting complex required for transport (ESCRT)-associated protein Vps4p. The interaction is essential for cell viability, and Vps4p is required for the correct cellular localization of Mid1p. Furthermore, we show that Mid1p is phosphorylated by the aurora kinase Aurora A, that the interaction ofmid1andark1genes is essential for cell viability, and that Ark1p is also required for the correct cellular localization of Mid1p. We mapped the sites of phosphorylation of Mid1p by Aurora A and the polo kinase Plk1 and assessed their importance by mutational analysis. Mutational analysis revealed S332, S523 and S531 to be required for Mid1p function and its interaction with Vps4p, Ark1p and Plo1p. Combined our data suggest a physical interaction between Mip1p and Vps4p important for cytokinesis, and identify phosphorylation of Mid1p by aurora and polo kinases as being significant for this process.

Author summary

Replication is a property of all living cells, with cell separation, so-called cytokinesis, the final step in the process. A large number of proteins have been identified that are required for cytokinesis, but in many cases it is not understand how they interact and regulate each other. In this research we have analysed two classes of proteins founds in all eukaryotic cells with central roles in cytokinesis: the endosomal sorting complex required for transport (ESCRT) proteins and the anillin protein Mid1p. We identify a direct physical interaction between the ESCRT protein Vps4 and anillin/Mid1p, and explore how it regulates cytokinesis. Midp1 activity is shown to controlled by the protein kinase Ark1p by direct phosphorylation, and this phosphorylation is important for Mid1p function. These observations identify new ways in which ESCRT and anillin/Mid1p control cell separation.
Investigations into the declining health of alder (Alnus glutinosa) along the river Lagan in Belfast, including the first report ofPhytophthora lacustriscausing disease ofAlnusin Northern Ireland
Authors: Hanlon Richard O , Wilson Julia , Cox Deborah
Published: December 2019

Common alder (Alnus glutinosa) is an important tree species, especially in riparian and wet habitats. Alder is very common across Ireland and Northern Ireland, and provides a wide range of ecosystem services. Surveys along the river Lagan in Belfast, Northern Ireland led to the detection of several diseasedAlnustrees. As it is known that Alnus suffers from aPhytophthorainduced decline, this research set out to identify the presence and scale of the risk toAlnushealth fromPhytophthoraand other closely related oomycetes. Sampling and a combination of morphological and molecular testing of symptomatic plant material and river baits identified the presence of severalPhytophthoraspecies, includingPhytophthora lacustris. A survey of the tree vegetation along an 8.5 km stretch of the river revealed that of the 166Alnustrees counted, 28 were severely defoliated/diseased and 9 were dead. Inoculation studies using pottedAlnussaplings demonstrate thatP. lacustriswas able to cause disease, and Koch’s postulates for this pathogen-host combination were completed, which suggests a future risk toAlnushealth fromP. lacustrisin Northern Ireland.
Prevalence, risk factors and health seeking behaviour of pulmonary tuberculosis in four tribal dominated districts of Odisha: comparison with studies in other regions of India
Authors: Hussain Tahziba , Tripathy Sushri Shanta , Das Shritam , Das Dasarathi , Thomas Beena
Published: December 2019

Aim

To determine the prevalence of pulmonary tuberculosis, socio-cultural practices and health seeking behaviour of tribal people in four districts of Odisha.

Methodology

This was an action research study with qualitative and quantitative design following a sequential approach implemented in a 4-phased manner. It was carried out in the 6 selected villages from July,2015 to June,2017. The screening for active TB among chest symptomatics is followed as per the guidelines of the (RNTCP) Revised National Tuberculosis Control Program in India.

Results

In all, 1455 households were surveyed in the 6 tribal dominated villages of 4 districts, namely Balangir, Dhenkanal, Kandhmal and Mayurbhanj. Total population of the villages was 6681. Based on the eligibility, 5144 (97.7%) individuals were screened. About 139 (2.3%) could not be screened due to non-availability in their households during day time. Out of these, 126 chest symptomatic individuals were identified. Sputum samples were collected from these and sent to the National Reference Laboratory, RMRC, Bhubaneswar using public transport and maintaining cold chain. 35 patients were found to be having active TB disease. 18 were culture positive. The prevalence of pulmonary TB is 0.68%. The risk factors seemed to be ignorance about TB symptoms, addiction to alcoholic drinks, difficulty reaching the health facilities owing to the long distances, lack of communication and transport. In addition, other morbidities like Malaria, diabetes, hypertension, malnutrition, etc. were observed in the tribes of the study sites.

Conclusion

Observed prevalence suggests further strengthening of TB control program. This study is the first of its kind in this State.