bluuebunny/crossref_metadata_2025 huggingface dataset:
Physicians' Perceptions of Psychological Safety and Peer Performance Feedback
Authors: Scheepers Renée A. , van den Goor Myra , Arah Onyebuchi A. , Heineman Maas Jan , Lombarts Kiki M. J. M. H.
Published: October 2018

Introduction:

For continuous professional development, it is imperative that physicians regularly receive performance feedback from their peers. Research shows that professionals are more proactive in learning and knowledge sharing with peers in teams with more psychological safety. Psychological safety has however not been studied in relation to peers' performance feedback. This study investigated the association between physicians' perceptions of psychological safety and performance feedback received from their peers.

Methods:

We invited physicians of cardiology, gastroenterology, obstetrics and gynecology, otorhinolaryngology, pulmonology, neurology, and neurosurgery departments of an academic medical center to participate. Physicians evaluated psychological safety using Edmondson's seven-item validated scale and performance feedback using the adapted four-item feedback subscale of the validated System for Evaluation of Teaching Qualities, including corrective and positive feedback, explanations of feedback, and suggestions for improvement from peers. We analyzed the data using multilevel linear regression analyses adjusted for physicians' sex, years since being certified a medical specialist, and months working in the clinic under the study.

Results:

This study included 105 physicians (86.8% participated). Psychological safety was positively associated with physicians' perceptions of performance feedback from peers (B = 0.54, 95% confidence interval = 0.34–0.73, P-value <.001).

Conclusions:

Physicians who experienced more psychological safety were more likely to receive corrective and positive performance feedback from peers, explanations of feedback, and suggestions for improvement. Medical teams should consider investing in psychological safety to encourage performance feedback from peers, and thus support physicians' continuous professional development and their efforts to provide high-quality patient care.
Retrospective Single-Center Registry Study on Graft Thickness 1 Year After Descemet Stripping Automated Endothelial Keratoplasty
Authors: Gormsen Andreas , Ivarsen Anders , Hjortdal Jesper
Published: October 2018

Purpose:

To compare the graft thickness of eye bank precut grafts with graft thickness measured 1 year after Descemet stripping automated endothelial keratoplasty (DSAEK) and to correlate the graft thickness of eye bank precut grafts with best spectacle-corrected visual acuity (BSCVA) and endothelial cell density (ECD) 1 year after DSAEK.

Methods:

This was a retrospective registry study of 183 eyes of 179 DSAEK patients. Grafts were cut in the eye bank after 1 day in dextran-containing medium, and thickness was measured by optical coherence tomography immediately after precutting. Examinations 1 year after DSAEK included optical coherence tomography for graft thickness, BSCVA, and specular microscopy. Patients were divided into 2 groups based on the median graft thickness. The correlations between original graft thickness and graft thickness measured 1 year later, BSCVA, and ECD were analyzed by linear regression analyses.

Results:

Graft thickness decreased from 116 ± 36.8 μm before to 100 ± 36.8 μm 1 year after DSAEK (R2 =0.901, P <0.0001). Mean BSCVA 1 year after DSAEK was 0.24 logMAR in eyes without ocular comorbidity. BSCVA was 0.25 ± 0.16 (0.21–0.28) and 0.20 ± 0.11 (0.18–0.23) in eyes with a graft thickness above or below 111 μm, respectively (P = 0.04). ECD loss 1 year after surgery did not correlate with graft thickness (R2 = 0.0006, P <0.875).

Conclusions:

Graft thickness measured immediately after precutting correlates strongly with graft thickness measured 1 year after DSAEK. This study suggests that ultrathin grafts provide better visual acuity 1 year after DSAEK than regular grafts.
Existentially Oriented Group Intervention for Patients With Heart Failure: Intervention Development and Preliminary Assessment
Authors: Vilchinsky Noa , Horowitz Yaffit , Bar-Kalifa Eran , Hasson-Ohayon Ilanit , Berlin Tatiana , Mosseri Morris
Published: October 2018

Background:

Patients with heart failure (HF) cope with a chronic, life-threatening, particularly disabling medical condition. Their well-being is considered to be at a greater risk than that of patients with any other cardiovascular disease, and their psychological distress is associated with a worse prognosis. These patients are often preoccupied with existential concerns such as fear of death, loneliness, and a loss of sense of meaning. However, there is a dearth of literature regarding psychological interventions that address these issues among this population.

Aims:

We, the authors of the current pilot study, present the development and initial implementation of a novel protocol: “existentially oriented group intervention for patients with heart failure.” Our aims were to test the intervention's feasibility, as well as to explore patients' subjective experience of it.

Methods:

The intervention (consisting of seven 1-hour weekly sessions) was applied to 2 consecutive groups. Twelve patients coping with HF levels III and IV—according to the New York Heart Association classification—from a hospital-based HF clinic participated. The Narrative Evaluation of Intervention Interview was applied.

Results:

Although high dropout levels were detected, the patients who fully participated in the program reported on satisfaction and progress in the following 4 domains: personal growth, social support, self-worth, and mastery.

Conclusions:

On the basis of our preliminary findings, the “existentially oriented group intervention for patients with heart failure” is recommended to be further tested among patients coping with HF.
Transformational Leadership Practices and Work Engagement Among Nurse Leaders
Authors: Shaughnessy Marian K. , Quinn Griffin Mary T. , Bhattacharya Anand , Fitzpatrick Joyce J.
Published: October 2018

OBJECTIVE

The aim of this study was to develop better understanding of the leadership characteristics of clinical nurse leaders.

BACKGROUND

Transformational leaders are the essential to support nursing in taking control of patient and family care coordination. One prior study of leadership and work engagement among clinical nurse leaders was identified.

METHODS

This descriptive correlational study explored the relationship between transformational leadership practices and work engagement among nurse leaders in the United States. Sample consisted of clinical nursing leaders attending the 2016 Magnet® Conference.

RESULTS

A significant positive relationship was identified between leadership practices and work engagement. Differences were noted in areas of select leadership practices and work engagement among nurse leaders based on different levels of education. Nurse leaders underperform in inspiring a shared vision, support for innovation, and taking risks, while also showing relatively weak levels of engagement in areas of vigor and absorption.

CONCLUSION

There is a need for additional research to better understand the characteristics of clinical nurse leaders to promote the principles of transformational leadership.
Use of Simulation to Develop Teamwork Skills in Prelicensure Nursing Students
Authors: Foster Marva , Gilbert Marie , Hanson Darlene , Whitcomb Kathryn , Graham Crystal
Published: October 2018

Background

While use of simulation to improve teamwork skills has been established in a variety of clinical settings, it is unclear how teamwork skills of nursing students are developed using simulation.

Purpose

The purpose of this review was to synthesize literature on how simulation is used to teach teamwork skills to prelicensure nursing students.

Methods

The integrative review of the literature was conducted using the Whittemore and Knafl 5-stage methodology and the TeamSTEPPS framework.

Results

Twenty-one articles were included in the review. Each of the articles reviewed used a component of TeamSTEPPS. The most common TeamSTEPPS concept addressed in the simulations was communication followed by mutual support.

Conclusion

While simulation appears to be an appropriate methodology to teach teamwork skills to prelicensure nursing students, it is evident that some of those skills are not being taught using the TeamSTEPPS framework
Successful Treatment of a Subcutaneous Abscess Caused by Hyaluronic Acid Injection in Nasal Dorsum Augmentation Via a Scarless Incision
Authors: Liu Hai-Peng , Zhang Duo
Published: October 2018

We report a successful treatment of a subcutaneous abscess in a 24-year-old woman caused by hyaluronic acid injection in nasal dorsum augmentation using negative pressure drainage via nasal mucosal approach.
Repair of Cerebrospinal Fluid Leak in Cochlear Implantation
Authors: Karatas Erkan
Published: October 2018

Objective:

The aim of this study is to evaluate the treatment of cerebrospinal fluid (CSF) leaks from cochleostomy after cochlear implantation intraoperatively and postoperatively.

Methods:

Three hundred seven patients (age ranges 13 months to 18 years) were undergone cochlear implantation and 14 (4.56%) of them had CSF leakage intraoperatively (2 normal, 12 anomalous cochlea). Complete packing of the around electrode in cochleostomy with muscle had performed to control CSF leak intraoperatively for primary surgery in 10 patients. Cerebrospinal fluid leakage was observed in 3 patients after cochlear implantation postoperatively. Revision surgeries for CSF leakage with fat tissue sealing were performed for them also. Fat tissue packing was performed for the last 4 patients in primary surgery. Outcomes of management methods for sealing were evaluated.

Results:

Sealing the cochleostomy with muscle was performed for 10 patients. Fibrin glue applications were used for excessive leakage for 5 patients with cochlear anomalies and 3 of these patients had CSF leak from cochleostomy postoperatively (Patients I, II, III). Secondary surgeries with fat tissue sealing were performed. But CSF leakage also was occurred in Patient III. Subtotal petrosectomy and obliteration of cavity with fat tissue had been performed for Patient III. Cerebrospinal fluid leakage has not been seen in primary surgeries with fat tissue packing in other 5 patients.

Conclusion:

Cerebrospinal fluid leakage may occur in cochlear implantation patients with inner ear anomalies postoperatively. Sealing of the cochleostomy with fat tissue is more useful than muscle intraoperatively.
Biocompatibility Studies of Nanoengineered Polycaprolactone and Nanohydroxyapatite Scaffold for Craniomaxillofacial Bone Regeneration
Authors: Harikrishnan Pandurangan , Islam Hairul , Sivasamy Arumugam
Published: October 2018

Currently there is an increased demand for synthetic bone substitute materials (SBSMs) due to avoidance of donor-site surgery and morbidity. Attempts are done to create SBSM mimicking the bone microarchitecture for enhanced healing. In this study, the authors nanoengineered polycaprolactone (PCL) and nanohydroxyapatite (nHAp) composite scaffold by electrospinning. The nHAp is synthesized via hydrothermal process followed by microwave irradiation. In vitro biocompatibility evaluation with MG63 osteoblastic cell line showed enhanced cell proliferation in the PCL-nHAp scaffold than plain PCL by MTT assay and fluorescence microscopy. Increased osteogenesis in the PCL-nHAp scaffold was shown by the increased calcium load, alkaline phosphatase activity, and expression of osteogenic biomarkers namely osteocalcin, osteonectin, and osteopontin. In vivo studies conducted in rabbit femur bone defects showed increased bone regeneration in PCL-nHAp implanted defects. The results show that PCL-nHAp electrospun scaffold is biomimetic and highly osteogenic and thus a potential SBSM for critical size craniomaxillofacial bone defect applications.
Computational modelling unravels the precise clockwork of cyanobacteria
Authors: Schmelling Nicolas M. , Axmann Ilka M.
Published: October 2018

Precisely timing the regulation of gene expression by anticipating recurring environmental changes is a fundamental part of global gene regulation. Circadian clocks are one form of this regulation, which is found in both eukaryotes and prokaryotes, providing a fitness advantage for these organisms. Whereas many different eukaryotic groups harbour circadian clocks, cyanobacteria are the only known oxygenic phototrophic prokaryotes to regulate large parts of their genes in a circadian fashion. A decade of intensive research on the mechanisms and functionality using computational and mathematical approaches in addition to the detailed biochemical and biophysical understanding make this the best understood circadian clock. Here, we summarize the findings and insights into various parts of the cyanobacterial circadian clock made by mathematical modelling. These findings have implications for eukaryotic circadian research as well as synthetic biology harnessing the power and efficiency of global gene regulation.
The intrinsic and regulated proteomes of barley seeds in response to fungal infection
Authors: Kerr Edward D. , Phung Toan K. , Caboche Christopher H. , Fox Glen P. , Platz Greg J. , Schulz Benjamin L.
Published: October 2018

Barley is an important cereal grain used for beer brewing, animal feed, and human food consumption. Fungal disease can impact barley production, as it causes substantial yield loss and lowers seed quality. We used sequential window acquisition of all theoretical ions mass spectrometry (SWATH-MS) to measure and quantify the relative abundance of proteins within seeds of different barley varieties under various fungal pathogen burdens (ProteomeXchange Datasets PXD011303 and PXD014093). Fungal burden in the leaves and stems of barley resulted in changes to the seed proteome. However, these changes were minimal and showed substantial variation among barley samples infected with different pathogens. The limited effect of intrinsic disease resistance on the seed proteome is consistent with the main mediators of disease resistance being present in the leaves and stems of the plant. The seeds of barley varieties accredited for use as malt had higher levels of proteins associated with starch synthesis and beer quality. The proteomic workflows developed and implemented here have potential application in quality control, breeding and processing of barley, and other agricultural products.
Atlas-based classification algorithms for identification of informative brain regions in fMRI data
Authors: Arco Juan E. , Díaz-Gutiérrez Paloma , Ramírez Javier , Ruz María
Published: October 2018

Multi-voxel pattern analysis (MVPA) has been successfully applied to neuroimaging data due to its larger sensitivity compared to univariate traditional techniques. Searchlight is the most widely employed approach to assign functional value to different regions of the brain. However, its performance depends on the size of the sphere, which can overestimate the region of activation when a large sphere size is employed

In the current study, we examined the validity of two different alternatives to Searchlight: an atlas-based local averaging method (ABLA, Schrouff et al., 2013a) and a Multi-Kernel Learning (MKL, Rakotomamonjy et al., 2008) approach, in a scenario where the goal is to find the informative brain regions that support certain mental operations. These methods employ weights to measure the informativeness of a brain region and highly reduce the large computational cost that Searchlight entails. We evaluated their performance in two different scenarios where the differential BOLD activation between experimental conditions was large vs. small, and employed nine different atlases to assess the influence of diverse brain parcellations.

Results show that both methods were able to localize informative regions when differences between conditions were large, demonstrating a large sensitivity and stability in the identification of regions across atlases. Moreover, the sign of the weights reported by these methods provided the directionality of univariate approaches. However, when differences were small, only ABLA localized informative regions. Thus, our results show that atlas-based methods are useful alternatives to Searchlight, but that the nature of the classification to perform should be taken into account when choosing the specific method to implement.
Construction of a germline-specific RNAi tool inC. elegans
Authors: Zou Lina , Wu Di , Zang Xiao , Wang Zi , Wu Zixing , Chen Di
Published: October 2018

Analysis of complex biological functions usually requires tissue-specific genetic manipulations in multicellular organisms. TheC. elegansgermline plays regulatory roles not only in reproduction, but also in metabolism, stress response and aging. Previous studies have used mutants ofrrf-1, which encodes an RNA-directed RNA polymerase, as a germline-specific RNAi tool. However, therrf-1mutants showed RNAi efficiency in somatic tissues. Here we constructed a germline-specific RNAi strain by combining an indel mutation ofrde-1, which encodes an Argonaute protein that functions cell autonomously to ensure RNAi efficiency, and a single-copyrde-1transgene driven by thesun-1germlinespecific promoter. The germline RNAi efficiency and specificity are confirmed by RNAi phenocopy of known mutations, knockdown of GFP reporter expression, as well as quantitative RT-PCR measurement of tissue-specific mRNAs upon RNAi knockdown. The germline-specific RNAi strain shows no obvious deficiencies in reproduction, lipid accumulation, thermo-tolerance and life span compared to wild-type animals. By screening an RNAi sub-library of phosphatase genes, we identified novel regulators of thermo-tolerance. Together, we have created a useful tool that can facilitate the genetic analysis of germline-specific functions inC. elegans.
Social learning through associative processes: A computational theory
Authors: Lind Johan , Ghirlanda Stefano , Enquist Magnus
Published: October 2018

Social transmission of information is a key phenomenon in the evolution of behavior and in the establishment of traditions and culture. The diversity of social learning phenomena has engendered a diverse terminology and numerous ideas about underlying learning mechanisms, at the same time that some researchers have called for a unitary analysis of social learning in terms of associative processes. Leveraging previous attempts and a recent computational formulation of associative learning, we analyze the following learning scenarios in some generality: learning responses to social stimuli, including learning to imitate; learning responses to non-social stimuli; learning sequences of actions; learning to avoid danger. We conceptualize social learning as situations in which stimuli that arise from other individuals have an important role in learning. This role is supported by genetic predispositions that either cause responses to social stimuli or enable social stimuli to reinforce specific responses. Our explorations show that, when guided by such predispositions, associative processes can give rise to a wide variety of social learning phenomena, such as stimulus and local enhancement, contextual imitation and simple production imitation, observational conditioning, and social and response facilitation. In addition, we clarify how associative mechanisms can result in transfer of information and behavior from experienced to naïve individuals.
PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure
Authors: Hervera Arnau , Zhou Luming , Palmisano Ilaria , McLachlan Eilidh , Kong Guiping , Hutson Thomas Haynes , Danzi Matt C , Lemmon Vance P , Bixby John L , Matamoros-Angles Andreu , Forsberg Kirsi , De Virgiliis Francesco , Matheos Dina P , Kwapis Janine , Wood Marcelo A , Puttagunta Radhika , Del Rio Jose Antonio , Di Giovanni Simone
Published: October 2018

The molecular mechanisms discriminating between regenerative failure and success remain elusive. While a regeneration-competent peripheral nerve injury mounts a regenerative gene expression response in bipolar dorsal root ganglia (DRG) sensory neurons, a regeneration-incompetent central spinal cord injury does not. This dichotomic response offers a unique opportunity to investigate the fundamental biological mechanisms underpinning regenerative ability. Following a pharmacological screen with small molecule inhibitors targeting key epigenetic enzymes in DRG neurons we identified HDAC3 signalling as a novel candidate brake to axonal regenerative growth. In vivo, we determined that only a regenerative peripheral but not a central spinal injury induces an increase in calcium, which activates protein phosphatase 4 that in turn dephosphorylates HDAC3 thus impairing its activity and enhancing histone acetylation. Bioinformatics analysis of ex vivo H3K9ac ChIPseq and RNAseq from DRG followed by promoter acetylation and protein expression studies implicated HDAC3 in the regulation of multiple regenerative pathways. Finally, genetic or pharmacological HDAC3 inhibition overcame regenerative failure of sensory axons following spinal cord injury. Together, these data indicate that PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.
Evolution of empathetic moral evaluation
Authors: Radzvilavicius Arunas L. , Stewart Alexander J. , Plotkin Joshua B.
Published: October 2018

Social norms can promote cooperation in human societies by assigning reputations to individuals based on their past actions. A good reputation indicates that an individual is worthy of help and is likely to reciprocate. A large body of research has established the norms of moral assessment that promote cooperation and maximize social welfare, assuming reputations are objective. But if there is no centralized institution to provide objective moral evaluation, then opinions about an individual’s reputation may differ across a population. Here we use evolutionary game theory to study the effects of empathy – the capacity to make moral evaluations from the perspective of another person. We find that empathetic moral evaluation tends to foster cooperation by reducing the rate of unjustified defection. The norms of moral evaluation previously considered most socially beneficial depend on high levels of empathy, whereas different norms are required to maximize social welfare in populations unwilling or incapable of empathy. We demonstrate that empathy itself can evolve through social contagion and attain evolutionary stability under most social norms. We conclude that a capacity for empathetic moral evaluation represents a key component to sustaining cooperation in human societies: cooperation requires getting into the mindset of others whose views differ from our own.
A network module for the Perseus software for computational proteomics facilitates proteome interaction graph analysis
Authors: Rudolph Jan , Jürgen Cox
Published: October 2018

Proteomics data analysis strongly benefits from not studying single proteins in isolation but taking their multivariate interdependence into account. We introduce PerseusNet, the new Perseus network module for the biological analysis of proteomics data. Proteomics is commonly used to generate networks, e.g. with affinity purification experiments, but networks are also used to explore proteomics data. PerseusNet supports the biomedical researcher for both modes of data analysis with a multitude of activities. For affinity purification, a volcano plot-based statistical analysis method for network generation is featured which is scalable to large numbers of baits. For posttranslational modifications of proteins, such as phosphorylation, a collection of dedicated network analysis tools helps elucidating cellular signaling events. Co-expression network analysis of proteomics data adopts established tools from transcriptome co-expression analysis. PerseusNet is extensible through a plug-in architecture in a multi-lingual way, integrating analyses in C#, Python and R and is freely available at http://www.perseus-framework.org.
Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis
Authors: Võsa Urmo , Claringbould Annique , Westra Harm-Jan , Bonder Marc Jan , Deelen Patrick , Zeng Biao , Kirsten Holger , Saha Ashis , Kreuzhuber Roman , Kasela Silva , Pervjakova Natalia , Alvaes Isabel , Fave Marie-Julie , Agbessi Mawusse , Christiansen Mark , Jansen Rick , Seppälä Ilkka , Tong Lin , Teumer Alexander , Schramm Katharina , Hemani Gibran , Verlouw Joost , Yaghootkar Hanieh , Sönmez Reyhan , Brown Andrew , Kukushkina Viktorija , Kalnapenkis Anette , Rüeger Sina , Porcu Eleonora , Kronberg-Guzman Jaanika , Kettunen Johannes , Powell Joseph , Lee Bernett , Zhang Futao , Arindrarto Wibowo , Beutner Frank ,   BIOS Consortium, Brugge Harm ,   i2QTL Consortium, Dmitreva Julia , Elansary Mahmoud , Fairfax Benjamin P. , Georges Michel , Heijmans Bastiaan T. , Kähönen Mika , Kim Yungil , Knight Julian C. , Kovacs Peter , Krohn Knut , Li Shuang , Loeffler Markus , Marigorta Urko M. , Mei Hailang , Momozawa Yukihide , Müller-Nurasyid Martina , Nauck Matthias , Nivard Michel , Penninx Brenda , Pritchard Jonathan , Raitakari Olli , Rotzchke Olaf , Slagboom Eline P. , Stehouwer Coen D.A. , Stumvoll Michael , Sullivan Patrick , Hoen Peter A.C. ‘t , Thiery Joachim , Tönjes Anke , van Dongen Jenny , van Iterson Maarten , Veldink Jan , Völker Uwe , Wijmenga Cisca , Swertz Morris , Andiappan Anand , Montgomery Grant W. , Ripatti Samuli , Perola Markus , Kutalik Zoltan , Dermitzakis Emmanouil , Bergmann Sven , Frayling Timothy , van Meurs Joyce , Prokisch Holger , Ahsan Habibul , Pierce Brandon , Lehtimäki Terho , Boomsma Dorret , Psaty Bruce M. , Gharib Sina A. , Awadalla Philip , Milani Lili , Ouwehand Willem , Downes Kate , Stegle Oliver , Battle Alexis , Yang Jian , Visscher Peter M. , Scholz Markus , Gibson Gregory , Esko Tõnu , Franke Lude
Published: October 2018

While many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.

To identify these effects, we performedcis-andtrans-expressionquantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.

We observed thatcis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to usecis-eQTLs to pinpoint causal genes within susceptibility loci.

In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology.

We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.
The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K
Authors: Bushell Simon R. , Pike Ashley C.W. , Falzone Maria E. , Rorsman Nils J. G. , Ta Chau M , Corey Robin A. , Newport Thomas D. , Shintre Chitra A. , Tessitore Annamaria , Chu Amy , Wang Qinrui , Shrestha Leela , Mukhopadhyay Shubhashish M.M. , Love James D. , Burgess-Brown Nicola A. , Sitsapesan Rebecca , Stansfeld Phillip J. , Huiskonen Juha T. , Tammaro Paolo , Accardi Alessio , Carpenter Elisabeth P.
Published: October 2018

Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase and ion channel activity, or specific chloride channel activity. Although TMEM16K is widely distributed and associated with the neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location in cells, function and structure are largely uncharacterised. Here we show that TMEM16K is an ER-resident calcium-regulated lipid scramblase. Our crystal structures of TMEM16K show a scramblase fold, with an open lipid transporting groove. Additional structures solved by cryo-EM reveal extensive conformational changes extending from the cytoplasmic to the ER side of the membrane, giving a state with a closed lipid permeation pathway. Molecular dynamics simulations showed that the open-groove conformation is necessary for scramblase activity. Our results suggest mechanisms by which missense variants of TMEM16K could cause SCAR10 ataxia, providing new hypotheses to explore for therapy.
MEK/mTOR-dependent D1 dopamine receptor activation induces local protein synthesis via eEF2 dephosphorylation in neurons
Authors: David Orit , Barrera Iliana , Koltun Bella , Ironi Sivan , Gal-Ben-Ari Shunit , Rosenblum Kobi
Published: October 2018

Neuromodulators in general, and dopamine in particular, define brain and neuronal states in different ways including regulation of global and local mRNA translation. Yet, the signaling pathways underlying the effects of dopamine on mRNA translation are not clear. Here, using genetic, pharmacologic, biochemical, and imaging methods, we tested the hypothesis that dopamine regulates phosphorylation of the eukaryotic elongation factor 2 (eEF2). We found that activation of dopamine receptor D1 but not D2 leads to rapid dephosphorylation of eEF2 at Thr56 in cortical primary neuronal culture and in vivo in a time-dependent manner. Additionally, NMDA receptor, mTOR, and ERK pathways are upstream to the D1 receptor-dependent eEF2 dephosphorylation and essential for it. Furthermore, D1 receptor activation resulted in a major reduction in dendritic eEF2 phosphorylation levels together with a correlative increase in local mRNA translation. These results reveal the role of eEF2 in dopamine regulation of local mRNA translation in neurons.

One-sentence summary

D1 receptor activation increases protein synthesis in dendrites by inactivating eEF2K in an ERK2/mTOR-dependent manner.
Correlation between the epigenetic modification of histone H3K9 acetylation of NR2B gene promoter in rat hippocampus and ethanol withdrawal syndrome
Authors: Li Duan , Zhang Yanqing , Zhang Yanting , Wang Qi , Miao Qin , Xu Yahui , Soares Jair C , Zhang Xiangyang , zhang ruiling
Published: October 2018

Previous studies showed that an epigenetic modification of N-methyl-D-aspartate (NMDA) receptor, especially NMDA receptor 2B subunit (NR2B), was involved in the pathological process of ethanol withdrawal syndrome (EWS). However, the relationship between the epigenetic regulation of the NR2B gene in the rat hippocampus region and EWS were inconsistent. A rat model of chronic ethanol exposure was established. EWS score and the behavioral changes were recorded at different points in time. The NR2B expression levels and the histone H3K9 acetylation level in the NR2B gene promoter region were measured using qRT-PCR, Western blot, immunofluorescence and chromatin immunoprecipitation, respectively. Finally, the relationships between the epigenetic modification of histone H3K9 acetylation of NR2B gene promoter and EWS were examined. Our results showed that the EWS score was increased at 2 h, peaked at 6 h after withdrawal of ethanol, and reduced to the level parallel to the normal control group at day 3 after ethanol withdrawal. The NR2B mRNA expression and protein levels showed similar patterns. Further correlation analyses indicted that both histone H3K9 acetylation in NR2B gene promoter and the expression levels of NR2B were positively associated with EWS. Chronic ethanol exposure may result in epigenetic modification of histone H3K9 acetylation in NR2B gene promoter in rat hippocampus, and the expression levels of NR2B were found to be positively correlated with EWS.
Biochemical and physiological investigations on adenosine 5’ monophosphate deaminase from Plasmodium spp.
Authors: Nagappa Lakshmeesha Kempaiah , Balaram Hemalatha
Published: October 2018

Abbreviations:

HGXPRT - Hypoxanthine-guanine-xanthine phosphoribosyltransferase, ADSS - Adenylosuccinate synthetase, ASL - Adenylosuccinate lyase, GMPS - Guonosine monophosphate synthetase, IMPDH - Inosine monophosphate dehydrogenase, ISN1 - Inosine monophosphate specific nucleotidase, PNP - Purine nucleoside phosphorylase

Interplay between ATP generating and utilizing pathways in a cell is responsible for maintaining cellular ATP/energy homeostasis that is reflected by Adenylate Energy Charge (AEC) ratio. Adenylate kinase (AK), that catalyzes inter-conversion of ADP, ATP and AMP, plays a major role in maintaining AEC, and is regulated by cellular AMP levels. Hence, the enzymes AMP deaminase (AMPD) and nucleotidases, which catabolize AMP, indirectly regulate AK activity and in-turn affect AEC. Here, we present the first report on AMPD fromPlasmodium, the causative agent of malaria. The recombinant enzyme expressed inSaccharomyces cerevisiaewas studied using functional complementation assay and residues vital for enzyme activity have been identified. Similarities and differences betweenPlasmodium falciparumAMPD (PfAMPD) and its homologs from yeast,Arabidopsisand humans are also discussed. The AMPD gene was deleted in the murine malaria parasiteP. bergheiand was found to be non-essential for intra-erythrocytic growth of the knockout parasites. However, when episomal expression was attempted, viable parasites were not obtained, suggesting that perturbing AMP homeostasis by over-expressing AMPD might be lethal. As AMPD is known to be allosterically modulated by ATP, GTP and phosphate, allosteric activators of PfAMPD could be developed as anti-parasitic agents.
Genomic architecture of parallel ecological divergence: beyond a single environmental contrast
Authors: Morales Hernán E. , Faria Rui , Johannesson Kerstin , Larsson Tomas , Panova Marina , Westram Anja M. , Butlin Roger K.
Published: October 2018

The genetic basis of parallel ecological divergence provides important clues to the operation of natural selection and the predictability of evolution. Many examples exist where binary environmental contrasts seem to drive parallel divergence. However, this simplified view can conceal important components of parallel divergence because environmental variation is often more complex. Here, we disentangle the genetic basis of parallel divergence across two axes of environmental differentiation (crab-predation vs. wave-action and low-shore vs. high-shore habitat contrasts) in the marine snail Littorina saxatilis, a well established natural system of parallel ecological divergence. We used whole-genome resequencing across multiple instances of these two environmental axes, at local and regional scales from Spain to Sweden. Overall, sharing of genetic differentiation is generally low but it is highly heterogeneous across the genome and increases at smaller spatial scales. We identified genomic regions, both overlapping and non-overlapping with recently described candidate chromosomal inversions, that are differentially involved in adaptation to each of the environmental axis. Thus, the evolution of parallel divergence in L. saxatilis is largely determined by the joint action of geography, history, genomic architecture and congruence between environmental axes. We argue that the maintenance of standing variation, perhaps as balanced polymorphism, and/or the re-distribution of adaptive variants via gene flow can facilitate parallel divergence in multiple directions as an adaptive response to heterogeneous environments.
A Systematic Approach to Identify Recycling Endocytic Cargo Depending on the GARP Complex
Authors: Eising Sebastian , Thiele Lisa , Fröhlich Florian
Published: October 2018

Proteins and lipids of the plasma membrane underlie constant remodeling via a combination of the secretory- and the endocytic pathway. In the yeast endocytic pathway, cargo is sorted for recycling to the plasma membrane or degradation in vacuoles. In a previous paper we have shown a role for the GARP complex in sphingolipid sorting and homeostasis (Fröhlich et al. 2015). However, the majority of cargo sorted in a GARP dependent process remain largely unknown. Here we use auxin induced degradation of GARP combined with mass spectrometry based vacuolar proteomics and lipidomics to show that recycling of two specific groups of proteins, the amino-phospholipid flippases and cell wall synthesis proteins depends on a functional GARP complex. Our results suggest that mis-sorting of flippases and remodeling of the lipid composition are the first occurring defects in GARP mutants. Our assay can be adapted to systematically map cargo of the entire endocytic pathway.
A tool for analyzing electrode tracks from slice histology
Authors: Shamash Philip , Carandini Matteo , Harris Kenneth D , Steinmetz Nicholas A
Published: October 2018

It is now possible to record from hundreds of neurons across multiple brain regions in a single electrophysiology experiment. An essential step in the ensuing data analysis is to assign recorded neurons to the correct brain regions. Brain regions are typically identified after the recordings by comparing images of brain slices to a reference atlas by eye. This introduces error, in particular when slices are not cut at a perfectly coronal angle or when electrode tracks span multiple slices. Here we introduce SHARP-Track, a tool to localize regions of interest and plot the brain regions they pass through. SHARP-Track offers a MATLAB user interface to explore the Allen Mouse Brain Atlas, register asymmetric slice images to the atlas using manual input, and interactively analyze electrode tracks. We find that it reduces error compared to localizing electrodes in a reference atlas by eye. See github.com/cortex-lab/allenCCF for the software and wiki.
On the prevalence of uninformative parameters in statistical models applying model selection in applied ecology
Authors: Leroux Shawn J.
Published: October 2018

Research in applied ecology provides scientific evidence to guide conservation policy and management. Applied ecology is becoming increasingly quantitative and model selection via information criteria has become a common statistical modeling approach. Unfortunately, parameters that contain little to no useful information are commonly presented and interpreted as important in applied ecology. I review the concept of an uninformative parameter in model selection using information criteria and perform a literature review to measure the prevalence of uninformative parameters in model selection studies applying Akaike’s Information Criterion (AIC) in 2014 in four of the top journals in applied ecology(Biological Conservation,Conservation Biology,Ecological Applications,Journal of Applied Ecology).Twenty-one percent of studies I reviewed applied AIC metrics. Many (31.5 %) of the studies applying AIC metrics in the four applied ecology journals I reviewed had or were very likely to have uninformative parameters in a model set. In addition, more than 40 % of studies reviewed had insufficient information to assess the presence or absence of uninformative parameters in a model set. Given the prevalence of studies likely to have uninformative parameters or with insufficient information to assess parameter status (71.5 %), I surmise that much of the policy recommendations based on applied ecology research may not be supported by the data analysis. I provide warning signals and a decision tree to help reduce the prevalence of uninformative parameters in studies applying model selection with information criteria. The four warning signals and decision tree should assist authors, reviewers, and editors to screen for uninformative parameters in studies applying model selection with information criteria. In the end, careful thinking at every step of the scientific process and greater reporting standards are required to detect uninformative parameters in studies adopting an information criteria approach.
Determination of biophysical parameters for enhancement of human osteoblast proliferation by mechanical vibration in the infrasonic frequency range
Authors: Nahum Rosenberg , Jacob Halevi Politch , Orit Rosenberg , Haim Abramovich
Published: October 2018

Experimental methods for studying an enhancement of osteoblast proliferation in vitro provide tools for the research of biochemical processes involved in bone turnover in vivo. Some of the current methods used for this purpose are based on the ability of the osteoblasts to enhance proliferation by mechanical stimulation. We describe an experimental approach of biomechanical stimulation of cultured human osteoblast-like cells by vibration. This method is based on the specially designed controlled vibration setup that consists of an electric actuator, with horizontally mounted well plate containing cell cultures. Previously this method found to be effective to enhance cell proliferation, but the exact mechanical parameters of effective vibration were elusive. The current low friction system for mechanical stimulation of osteoblast-like cells in vitro provides recording of narrow range mechanical parameters in the infrasonic spectrum.

We exposed human osteoblast-like cells in explant monolayer culture to mechanical vibration in the 10-70Hz range of frequencies and found that 50-70 Hz of vibration frequency is optimal for inducing osteoblast proliferation that was deduced from interrelation between unchanged cell number in culture samples with significant decrease in cell death rate (decreased LDH activity in culture media, p<.05) and with parallel decrease of their maturation level (p<.01).

In this report we determined the optimal mechanical parameters and excitation protocol for induction of osteoblast proliferation in vitro by using a tunable and versatile mechanical platform, which can be used in the research of cell mechanotransduction.
Heat Shock in C. elegans Induces Downstream of Gene Transcription andAccumulation of Double-Stranded RNA
Authors: Melnick Marko , Gonzales Patrick , Cabral Joseph , Allen Mary A. , Dowell Robin D. , Link Christopher D.
Published: October 2018

We observed that heat shock of Caenorhabditis elegans leads to the formation of nuclear double-stranded RNA (dsRNA) foci, detectable with a dsRNA-specific monoclonal antibody. These foci significantly overlap with nuclear HSF-1 granules. To investigate the molecular mechanism(s) underlying dsRNA foci formation, we used RNA-seq to globally characterize total RNA and immunoprecipitated dsRNA from control and heat shocked worms. We find antisense transcripts are generally increased after heat shock, and a subset of both sense and antisense transcripts enriched in the dsRNA pool by heat shock overlap with dsRNA transcripts enriched by deletion of tdp-1, which encodes the C. elegans ortholog of TDP-43. Interestingly, transcripts involved in translation are over-represented in the dsRNAs induced by either heat shock or deletion of tdp-1. Also enriched in the dsRNA transcripts are sequences downstream of annotated genes (DoGs), which we globally quantified with a new algorithm. To validate these observations, we used fluorescence in situ hybridization (FISH) to confirm both antisense and downstream of gene transcription for eif-3.B, one of the affected loci we identified.
Stressed mothers, tolerant daughters: a case studyabout the physiological responses and growth of sugarcane plants under water deficit
Authors: Marcos Fernanda C. C. , Silveira Neidiquele M. , Marchiori Paulo E. R. , Machado Eduardo C. , Souza Gustavo M. , Landell Marcos G. A. , Ribeiro Rafael V.
Published: October 2018

Drought stress can imprint marks in plants after a previous exposure, leading to a permissive state that facilitates a more effective response to subsequent stress events. Such stress imprints would benefit plants obtained from progenitors previously exposed to drought. Herein, our hypothesis was that daughter plants obtained from mother plants previously exposed to water deficit will perform better under water deficit as compared to those obtained from mothers that did not face stressful conditions. Sugarcane mother plants were grown under well-hydrated conditions or subjected to three cycles of water deficit by water withholding. Then, daughter plants produced through vegetative propagation were subjected to water deficit. Leaf gas exchange was reduced under water deficit and daughters from mothers that experienced water deficit presented a faster recovery of CO2 assimilation and higher instantaneous carboxylation efficiency after rehydration as compared to daughters from mothers that did not face water deficit. Plants obtained from mother plants that faced water deficit showed the highest leaf proline concentration under water deficit as well as higher leaf H2O 2 concentration and leaf ascorbate peroxidase activity regardless of water regime. Under well-watered conditions, daughters from mothers that faced stressful conditions presented higher root H2O2 concentration and root catalase activity than ones from mothers that did not experience water shortage. Such physiological changes were associated with improvements in leaf area and shoot and root dry matter accumulation in daughters from stressed mothers. Our results suggest that root H2O2 concentration is a chemical signal associated with stress memory and improved sugarcane growth. Such findings bring a new perspective to sugarcane production systems, in which stress memory can be explored for improving drought tolerance in rainfed areas.