bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolving kinetic intermediates during the regulated assembly and disassembly of fusion pores
Authors: Das Debasis , Bao Huan , Courtney Kevin C. , Wu Lanxi , Chapman Edwin R. 
Published: January 2020

AbstractThe opening of a fusion pore during exocytosis creates the first aqueous connection between the lumen of a vesicle and the extracellular space. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate the formation of these dynamic structures, and their kinetic transitions are tightly regulated by accessory proteins at the synapse. Here, we utilize two single molecule approaches, nanodisc-based planar bilayer electrophysiology and single-molecule FRET, to address the relationship between SNARE complex assembly and rapid (micro-millisecond) fusion pore transitions, and to define the role of accessory proteins. Synaptotagmin (syt) 1, a major Ca2+-sensor for synaptic vesicle exocytosis, drove the formation of an intermediate: committed trans-SNARE complexes that form large, stable pores. Once open, these pores could only be closed by the action of the ATPase, NSF. Time-resolved measurements revealed that NSF-mediated pore closure occurred via a complex ‘stuttering’ mechanism. This simplified system thus reveals the dynamic formation and dissolution of fusion pores.
The evolution of sexual signaling is linked to odorant receptor tuning in perfume-collecting orchid bees
Authors: Brand Philipp , Hinojosa-Díaz Ismael A. , Ayala Ricardo , Daigle Michael , Yurrita Obiols Carmen L. , Eltz Thomas , Ramírez Santiago R. 
Published: January 2020

AbstractSexual signaling is an important reproductive barrier known to evolve early during the formation of new species, but the genetic mechanisms that facilitate the divergence of sexual signals remain elusive. Here we isolate a gene linked to the rapid evolution of a signaling trait in a pair of nascent neotropical orchid bee lineages, Euglossa dilemma and E. viridissima. Male orchid bees acquire chemical compounds from their environment to concoct species-specific perfumes to later expose during courtship. We find that the two lineages acquire chemically distinct perfumes and are reproductively isolated despite low levels of genome-wide differentiation. Remarkably, variation in perfume chemistry coincides with rapid divergence in few odorant receptor (OR) genes. Using functional assays, we demonstrate that the derived variant of Or41 in E. dilemma is specific towards its species-specific major perfume compound, whereas the ancestral variant in E. viridissima is broadly tuned to multiple odorants. Our results show that OR evolution likely played a role in the divergence of sexual communication in natural populations.
The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids
Authors: Ducastel Sarah , Touche Véronique , Trabelsi Mohamed-Sami , Boulinguiez Alexis , Butruille Laura , Nawrot Margaux , Peschard Simon , Chávez-Talavera Oscar , Dorchies Emilie , Vallez Emmanuelle , Annicotte Jean-Sébastien , Lancel Steve , Briand Olivier , Bantubungi Kadiombo , Caron Sandrine , Bindels Laure B. , Delzenne Nathalie M. , Tailleux Anne , Staels Bart , Lestavel Sophie 
Published: January 2020

AbstractThe gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown that activation of the nuclear Farnesoid X Receptor (FXR) decreases the L-cell response to glucose. Here, we investigated whether FXR also regulates the SCFA-induced GLP-1 secretion. GLP-1 secretion in response to SCFAs was evaluated ex vivo in murine colonic biopsies and in colonoids of wild-type (WT) and FXR knock-out (KO) mice, in vitro in GLUTag and NCI-H716 L-cells activated with the synthetic FXR agonist GW4064 and in vivo in WT and FXR KO mice after prebiotic supplementation. SCFA-induced GLP-1 secretion was blunted in colonic biopsies from GW4064-treated mice and enhanced in FXR KO colonoids. In vitro FXR activation inhibited GLP-1 secretion in response to SCFAs and FFAR2 synthetic ligands, mainly by decreasing FFAR2 expression and downstream Gαq-signaling. FXR KO mice displayed elevated colonic FFAR2 mRNA levels and increased plasma GLP-1 levels upon local supply of SCFAs with prebiotic supplementation. Our results demonstrate that FXR activation decreases L-cell GLP-1 secretion in response to inulin-derived SCFA by reducing FFAR2 expression and signaling. Inactivation of intestinal FXR using bile acid sequestrants or synthetic antagonists in combination with prebiotic supplementation may be a promising therapeutic approach to boost the incretin axis in type 2 diabetes.
Precision Medicine and Artificial Intelligence: A Pilot Study on Deep Learning for Hypoglycemic Events Detection based on ECG
Authors: Porumb Mihaela , Stranges Saverio , Pescapè Antonio , Pecchia Leandro 
Published: January 2020

AbstractTracking the fluctuations in blood glucose levels is important for healthy subjects and crucial diabetic patients. Tight glucose monitoring reduces the risk of hypoglycemia, which can result in a series of complications, especially in diabetic patients, such as confusion, irritability, seizure and can even be fatal in specific conditions. Hypoglycemia affects the electrophysiology of the heart. However, due to strong inter-subject heterogeneity, previous studies based on a cohort of subjects failed to deploy electrocardiogram (ECG)-based hypoglycemic detection systems reliably. The current study used personalised medicine approach and Artificial Intelligence (AI) to automatically detect nocturnal hypoglycemia using a few heartbeats of raw ECG signal recorded with non-invasive, wearable devices, in healthy individuals, monitored 24 hours for 14 consecutive days. Additionally, we present a visualisation method enabling clinicians to visualise which part of the ECG signal (e.g., T-wave, ST-interval) is significantly associated with the hypoglycemic event in each subject, overcoming the intelligibility problem of deep-learning methods. These results advance the feasibility of a real-time, non-invasive hypoglycemia alarming system using short excerpts of ECG signal.
Regulatory mechanisms involved in muscle and bone remodeling during refeeding in gilthead sea bream
Authors: Lavajoo F. , Perelló-Amorós M. , Vélez E. J. , Sánchez-Moya A. , Balbuena-Pecino S. , Riera-Heredia N. , Fernández-Borràs J. , Blasco J. , Navarro I. , Capilla E. , Gutiérrez J. 
Published: January 2020

AbstractThe tolerance of fish to fasting offers a model to study the regulatory mechanisms and changes produced when feeding is restored. Gilthead sea bream juveniles were exposed to a 21-days fasting period followed by 2 h to 7-days refeeding. Fasting provoked a decrease in body weight, somatic indexes, and muscle gene expression of members of the Gh/Igf system, signaling molecules (akt, tor and downstream effectors), proliferation marker pcna, myogenic regulatory factors, myostatin, and proteolytic molecules such as cathepsins or calpains, while most ubiquitin-proteasome system members increased or remained stable. In bone, downregulated expression of Gh/Igf members and osteogenic factors was observed, whereas expression of the osteoclastic marker ctsk was increased. Refeeding recovered the expression of Gh/Igf system, myogenic and osteogenic factors in a sequence similar to that of development. Akt and Tor phosphorylation raised at 2 and 5 h post-refeeding, much faster than its gene expression increased, which occurred at day 7. The expression in bone and muscle of the inhibitor myostatin (mstn2) showed an inverse profile suggesting an inter-organ coordination that needs to be further explored in fish. Overall, this study provides new information on the molecules involved in the musculoskeletal system remodeling during the early stages of refeeding in fish.
A Novel Cyanobacterium Synechococcus elongatus PCC 11802 has Distinct Genomic and Metabolomic Characteristics Compared to its Neighbor PCC 11801
Authors: Jaiswal Damini , Sengupta Annesha , Sengupta Shinjinee , Madhu Swati , Pakrasi Himadri B. , Wangikar Pramod P. 
Published: January 2020

AbstractCyanobacteria, a group of photosynthetic prokaryotes, are attractive hosts for biotechnological applications. It is envisaged that future biorefineries will deploy engineered cyanobacteria for the conversion of carbon dioxide to useful chemicals via light-driven, endergonic reactions. Fast-growing, genetically amenable, and stress-tolerant cyanobacteria are desirable as chassis for such applications. The recently reported strains such as Synechococcus elongatus UTEX 2973 and PCC 11801 hold promise, but additional strains may be needed for the ongoing efforts of metabolic engineering. Here, we report a novel, fast-growing, and naturally transformable cyanobacterium, S. elongatus PCC 11802, that shares 97% genome identity with its closest neighbor S. elongatus PCC 11801. The new isolate has a doubling time of 2.8 h at 1% CO2, 1000 µmole photons.m−2.s−1 and grows faster under high CO2 and temperature compared to PCC 11801 thus making it an attractive host for outdoor cultivations and eventual applications in the biorefinery. Furthermore, S. elongatus PCC 11802 shows higher levels of key intermediate metabolites suggesting that this strain might be better suited for achieving high metabolic flux in engineered pathways. Importantly, metabolite profiles suggest that the key enzymes of the Calvin cycle are not repressed under elevated CO2 in the new isolate, unlike its closest neighbor.
What is the clinical value of mHealth for patients?
Authors: Rowland Simon P. , Fitzgerald J. Edward , Holme Thomas , Powell John , McGregor Alison 
Published: January 2020

AbstractDespite growing interest from both patients and healthcare providers, there is little clinical guidance on how mobile apps should be utilized to add value to patient care. We categorize apps according to their functionality (e.g. preventative behavior change, digital self-management of a specific condition, diagnostic) and discuss evidence for effectiveness from published systematic reviews and meta-analyses and the relevance to patient care. We discuss the limitations of the current literature describing clinical outcomes from mHealth apps, what FDA clearance means now (510(k)/de novo FDA clearance) and in the future. We discuss data security and privacy as a major concern for patients when using mHealth apps. Patients are often not involved in the development of mobile health guidelines, and professionals’ views regarding high-quality health apps may not reflect patients’ views. We discuss efforts to develop guidelines for the development of safe and effective mHealth apps in the US and elsewhere and the role of independent app reviews sites in identifying mHealth apps for patient care. There are only a small number of clinical scenarios where published evidence suggests that mHealth apps may improve patient outcomes.
Modern Aspects of the Motivation of the Staff of a Commercial Enterprise Through the Social Menu System
Authors: Pecherskaya Evelina P. , Tarasova Tatiana M. 
Published: January 2020

At present, a very difficult situation is developing in the economy, which should be characterized as ‘personnel shortage’. Every year this situation is complicated by the deteriorating demographic situation. Moreover, at present, in most companies, the incentive process is imperfect, since in most cases it does not depend on the results of the employee’s work.
Well-thought-out stimulation helps to best manage the business behavior of staff, ensuring the welfare of the organization. Most domestic enterprises strive to create conditions to meet the needs of their employees and are very successful in this. Therefore, a high wage level and the offer of a full social package, training and career planning for employees, organizing corporate events, diagnosing the situation in a company with the involvement of external consultants and conducting surveys among staff gradually become familiar working conditions for employees of commercial organizations.
The article conducts a study of the incentive system for the labor activity of the ‘Fix Price’ sales department, which was carried out on the basis of an analysis of the company’s internal regulatory documents and by questioning the employees. This study revealed the main problems in the functioning of the current system of motivation, on the basis of which measures were proposed to improve the personnel incentive system and a model of external motivation of staff was proposed.
Zika Virus and Pregnancy: Association between Acute Infection and Microcephaly in Newborns in the State of Rio de Janeiro, Brazil
Authors: Pereira Alessandra Mendelski , Araujo Júnior Edward , Werner Heron , Monteiro Denise Leite Maia 
Published: January 2020

Abstract
Introduction Aim of the study was to evaluate the association between microcephaly and acute infection with Zika virus (ZIKV) in pregnant women in the state of Rio de Janeiro, Brazil. Infection was confirmed by laboratory testing.
Materials and Methods A cross-sectional retrospective study of pregnant women with symptoms occurring between 2015 and 2016 suggestive of acute ZIKV infection was carried out, with confirmation of infection done by blood or urine RT-PCR. The relative proportions of categorical variables were calculated for two distinct groups: pregnant women whose newborns had microcephaly and pregnant women who gave birth to infants without microcephaly. Confidence intervals with a 95% level of agreement were estimated for the relative ratios.
Results A total of 1609 pregnant women with a mean age of 26.4 ± 6.5 years were evaluated. As regards the time of acute infection, 19.6% (316) of cases occurred in the first trimester of pregnancy. Nineteen (76%) of the 25 cases with microcephaly (1.5%) were associated with an infection contracted in the first trimester of pregnancy (p < 0.001, OR = 13.7, 95% CI: 5.6 – 37.7). 48% (12/25) of the newborns with microcephaly had a birth weight of < 2500 grams, while only 7% (116/1597) of the group of newborns without microcephaly had a similarly low birth weight (p < 0.001, OR = 11.7, 95% CI: 5.2 – 26.2). Logistic regression showed that a birth weight of < 2500 g (OR = 12.54) and ZIKV infection in the first trimester of pregnancy (OR = 14.05) were associated with microcephaly (area under ROC curve = 0.86).
Conclusion Acute ZIKV infection in the first trimester of pregnancy and low birth weight are associated with microcephaly.
The Change in Attitudes Towards Abortion in Former West and East Germany After Reunification: A Latent Class Analysis and Implications for Abortion Access
Authors: Hanschmidt Franz , Kaiser Julia , Stepan Holger , Kersting Anette 
Published: January 2020

Abstract
Introduction The legal status of abortion has changed in the regions of former East Germany after reunification due to the adoption of restrictive West German abortion policies. The aim of this study was to evaluate the impact on attitudes towards abortion and the associated health care implications in Western and Eastern Germany.
Materials and Methods Nationally representative data on public support for legally restricting abortion access were taken from the German General Social Survey and included the surveys 1992, 1996, 2000, 2006 and 2012 (N = 14 459). Two indicators of barriers to access to abortion care were calculated for each federal state, based on the number of abortion facilities and the proportion of women seeking abortion outside their state of residency. Data were analysed using latent class analysis.
Results Results suggested that abortion attitudes could be classified into three distinct subgroups: 1) support for abortion access independent of womenʼs reason; 2) support on the basis of maternal or foetal health reasons but not for socio-economic reasons (e.g. financial restrictions); and 3) no support. The size of subgroups in favour of partial or complete restriction on abortion access increased in both regions over the study period and this trend could not be explained by changes in socio-demographic characteristics. Respondents living in a federal state with more barriers to access to abortion care were more likely to hold restrictive abortion attitudes.
Conclusion Negative attitudes towards abortion have increased in Western and Eastern Germany during the two decades following reunification and may harm women by limiting acceptability and accessibility of abortion care. Abortion policies, public discourse and provision of abortion care should be informed by international guidelines protecting womenʼs health and rights.
Single-nucleus RNA sequencing reveals transcriptional changes of hippocampal neurons in APP23 mouse model of Alzheimer’s disease
Authors: Zhong Shan , Wang Mengdi , Zhan Yaxi , Zhang Jie , Yang Xiaoli , Fu Shumei , Bi Danlei , Gao Feng , Shen Yong , Chen Zuolong 
Published: January 2020

Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that mostly strikes the elderly. However, the exact molecular and cellular pathogenesis of AD, especially the dynamic changes of neurons during disease progression, remains poorly understood. Here we used single-nucleus RNA sequencing (snRNA-seq) to access the transcriptional changes of hippocampal neurons in APP23 mouse model of AD. We performed snRNA-seq using a modified Smart-seq2 technique on 3,280 neuronal nuclei from the hippocampus of young and aged APP23 and control mice and identified four distinct subpopulations. Comparative transcriptional analysis showed multiple changes in different subtypes of hippocampal neurons of APP23 mice in comparison to control mice, as well as the transcriptional changes in these neurons during disease progression. Our findings revealed multiple neuronal subtype-specific transcriptional changes that may lead to targets for future studies of AD.
Nanostructured graphene for nanoscale electron paramagnetic resonance spectroscopy
Authors: Marie Luke St , El Fatimy Abdel , Hrubý Jakub , Nemec Ivan , Hunt James , Myers-Ward Rachael , Gaskill D Kurt , Kruskopf Mattias , Yang Yanfei , Elmquist Randolph , Marx Raphael , van Slageren Joris , Neugebauer Petr , Barbara Paola 
Published: January 2020

Abstract
The opening of a quantum confinement gap in nanostructured graphene yields extremely sensitive photodetectors, with electrical noise equivalent power lower than 10−15 W Hz−0.5 at temperatures below 3 K, for detection of radiation in a very broad frequency range, including ultraviolet, visible and terahertz. Here we demonstrate the operation of these detectors in the presence of magnetic field as high as 7 T, paving the way to in situ spectroscopy of molecular nanomagnets.
Antithrombotic therapy for postinterventional management of peripheral arterial disease
Authors: Zavgorodnyaya Daria , Knight Tamara B , Daley Mitchell J , Teixeira Pedro G 
Published: January 2020

Abstract

Purpose
Evidence on the use of antithrombotic pharmacotherapy in patients undergoing revascularization of lower extremities for symptomatic peripheral arterial disease (PAD) is reviewed.

Summary
Individuals with PAD can experience leg pain, intermittent claudication, critical limb ischemia, and acute limb ischemia. In such patients, revascularization may be indicated to improve the quality of life and to prevent amputations. Antithrombotic therapy is often intensified in the postrevascularization period to prevent restenosis of the index artery and to counteract the prothrombotic state induced by the intervention. Therapeutic modalities include dual antiplatelet therapy (DAPT), anticoagulation, a combination of antiplatelet and anticoagulation therapy, and addition of cilostazol to single antiplatelet therapy. Subgroup analyses of data from randomized clinical trials provided low-quality evidence for the use of DAPT in patients with a below-knee prosthetic bypass graft and anticoagulation for those with a venous bypass graft. Cilostazol, when added to aspirin therapy, has been shown to prevent index vessel reocclusion after an endovascular intervention in patients at low risk for thrombosis in several small randomized trials.

Conclusion
There is a considerable paucity of high-quality evidence on the optimal antithrombotic regimen for patients undergoing lower extremity revascularization, with no particular therapy shown to consistently improve patient outcomes. The decision to initiate intensified antithrombotic therapy should include a close examination of its risk–benefit profile. The demonstrated benefit of such treatment is restricted to the prevention of index artery reocclusion, while an increased risk of bleeding may lead to significant morbidity and mortality.
Language and Trauma: An Introduction
Authors: Busch Brigitta , McNamara Tim 
Published: January 2020

AbstractThis paper introduces the conceptual framing of studies of trauma. It considers how, on the one hand, applied linguistics may contribute to this study, responding to the suggestion that trauma ‘can be best understood through plural, multi-disciplinary perspectives’ (Luckhurst 2008: 214), and, on the other hand, the extent to which linguistic studies of trauma can contribute to a better understanding of what Coupland and Coupland (1997: 117) have called ‘discourses of the unsayable’. It argues that the tools of linguistic analysis may be used to understand the role of language in how individuals may experience, recount, and potentially recover from psychological trauma, in personal, literary, and institutional contexts, as exemplified by the papers in this volume.
Low factor H-related 5 levels contribute to infection-triggered haemolytic uraemic syndrome and membranoproliferative glomerulonephritis
Authors: Gómez Delgado Irene , Gutiérrez-Tenorio Josué , Fraga Rodríguez Gloria M , Cavero Teresa , Arjona Emilia , Sánchez-Corral Pilar 
Published: January 2020

Abstract
Dysregulation of the alternative complement pathway is a major pathogenic mechanism in two rare renal diseases: atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). We report on a 66-year-old male with chronic hepatitis C virus (HCV) infection and a combined liver–kidney transplant that was diagnosed with MPGN at the age of 63 years and a 5-year-old boy who presented with aHUS at the age of 21 months following a Streptococcus pneumoniae infection. Both patients carried similar frameshift variants in the complement CFHR5 gene that segregate with reduced levels of factor H–related 5 (FHR-5). We conclude that low FHR-5 levels may predispose to viral and bacterial infections that then trigger different renal phenotypes.
Cathepsin D concentration in breast cancer cytosols: correlation with biochemical, histological, and clinical findings
Authors: Duffy M J , Brouillet J P , Reilly D , McDermott E , O'Higgins N , Fennelly J J , Maudelonde T , Rochefort H 
Published: January 2020

Abstract
Cathepsin D (CD, EC 3.4.23.5) is a lysosomal protease induced by estrogen in certain estrogen receptor (ER)-positive breast cancer cell lines but produced constitutively by ER-negative cell lines. Our aims in this investigation were to study the distribution of CD in human breast cancers and to relate its concentrations to various biochemical, histological, and clinical characteristics. The concentrations of CD were significantly higher in breast carcinomas than in either normal breast tissues or benign breast tumors. In primary carcinomas, CD concentrations did not correlate with the concentrations of ER or with the estrogen-inducible protease t-PA. However, CD concentrations did correlate weakly but significantly with both UK-PA antigen and UK-PA activity. Also, CD concentrations did not correlate with either tumor stage or axillary node status but did correlate significantly with tumor grade. Patients with cancers containing high concentrations of CD had a significantly shorter overall survival than did patients with low concentrations of the enzyme.