bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Physiological Information and Home Security Information Collection System for the Elderly Based on LabVIEW
Authors: Qiaoping Su , Wenjuan Sun , Yuan Liu , Liqin Ji , Zhiwei Dai
Published: November 2019

Design of physiological information and home security information collection system for the elderly is based on LabVIEW. The main function is to receive data information from the hardware through serial communication, so that the upper computer can realize the conversion of data, and associate the data with the database. In the design of the system, module panels including “user management”, “personal information”, “physiological information”, “living home”, “history information”, “news media” are added. The data of the core module “physiological information” and “living home” is received by the serial port and stored in the database. The Microsoft Office Access database is selected on the database building. The database is accessed, read, written, newly created, deleted, etc. by creating a computer ODBC data source and using a LabSQL toolkit. It uses the VISA control on the serial port to configure the system serial port and other settings, selects the hexadecimal number of the system serial port receiving hardware to convert to a decimal number, and distinguish the delivery display panel.
A Fireworks-inspired Estimation of Distribution Algorithm
Authors: Hao Li
Published: November 2019

Estimation of distribution algorithm(EDA) is a popular evolutionary algorithm which is obtained widely attention. On the basis of EDA, combining with the idea of fireworks algorithm, we proposed a fireworks-inspired multi-model EDA(FMEDA). In FMEDA, multiple probabilistic models are used and generate different number of solutions by introducing the idea of firework explosion. Next, each model evolves by compared with its own best solution directly. The method of setting the limit of probability is taken to prevent from premature convergence. Applying this algorithm to the function optimization problem and the knapsack problem, the experimental result shows that the proposed algorithm has better performance than CGA and PBIL.
An Angle-expressed Quantum Evolutionary Algorithm for Quadratic Knapsack Problem
Authors: Hao Li
Published: November 2019

The quadratic knapsack problem(QKP) is a typical combinatorial optimization problem. It is arisen in many optimization fields, but there exist no pseudo-polynomial time algorithm to solve it. In this paper, we propose an angle-expressed quantum evolutionary algorithm to solve QKP. In this algorithm, the qubits are expressed in the angle and initialized according to the value densities of their corresponding items, the rotation angle of Q-gate is determined through an analytical formula, and Hε gate is used to prevent from premature convergence. For infeasible solution, a dynamic value density is introduced to choose item to be selected or dropped. Finally, experiment demonstrates the effectiveness of the algorithm.
Atomic insights in crystallization of liquid Cu on single crystal Ta and amorphous Ta
Authors: Gan Xianglai , Shu Longlong , Fei Linfeng , Wang Yu , Zhou Naigen
Published: November 2019

The crystallization processes of liquid Cu on single crystal Ta and amorphous Ta under different undercoolings were investigated with molecular dynamics simulation. As the undercooling is not greater than 350 K, only heteronucleation process occurred in both cases. However, at a larger undercooling (400 K), the nucleation transformed from a heteronucleation mode to a mix-mode of heteronucleation and homonucleation in both cases. Interestingly, we found that the heteronucleation of Cu embryos, in the amorphous-Ta/liquid-Cu samples, was always triggered by the recrystallization of amorphous Ta; it means that crystal Ta possesses a higher nucleation potency than amorphous Ta. Further analysis indicated that the higher nucleation potency of single crystal Ta originates from its ability to induce liquid Cu atoms ordering. Liquid Cu took a longer time, on average, to nucleate on amorphous Ta than on crystal Ta at different temperatures. In addition, microstructure analysis indicated that the crystallized region contained both stacking faults and twin crystals.
Is the fermionic exchange phase also acquired locally?
Authors: Marletto Chiara , Vedral Vlatko
Published: November 2019

We argue that the fermionic exchange phase could be detected by local means. We propose a simple experiment to test our idea. This leads us to speculate that there might be a deeper mechanism behind the notion of particle statistics in quantum physics that goes beyond the conventional argument based on the spin-statistics connections.
Pluripotential theory on Teichmüller space I: Pluricomplex Green function
Authors: Miyachi Hideki
Published: November 2019

This is the first paper in a series of investigations of the pluripotential theory on Teichmüller space. One of the main purposes of this paper is to give an alternative approach to the Krushkal formula of the pluricomplex Green function on Teichmüller space. We also show that Teichmüller space carries a natural stratified structure of real-analytic submanifolds defined from the structure of singularities of the initial differentials of the Teichmüller mappings from a given point. We will also give a description of the Levi form of the pluricomplex Green function using the Thurston symplectic form via Dumas’ symplectic structure on the space of holomorphic quadratic differentials.
Observational Study of the Associations of Participation in High School Football With Self-Rated Health, Obesity, and Pain in Adulthood
Authors: Gaulton Timothy G , Deshpande Sameer K , Small Dylan S , Neuman Mark D
Published: November 2019

American football is the most popular high school sport in the United States, yet its association with health in adulthood has not been widely studied. We investigated the association between high school football and self-rated health, obesity, and pain in adulthood in a retrospective cohort study of data from the Wisconsin Longitudinal Study (1957–2004). We matched 925 males who played varsity football in high school with 1,521 males who did not play football. After matching, playing football was not associated with poor or fair self-rated health (odds ratio (OR) = 0.88, 95% confidence interval (CI): 0.63, 1.24; P = 0.48) or pain that limited activities (OR = 0.86, 95% CI: 0.59, 1.25; P = 0.42) at age 65 years. Football was associated with obesity (body mass index (weight (kg)height (m)2) ≥30) in adulthood (OR = 1.32, 95% CI: 1.06, 1.64; P = 0.01). The findings suggest that playing football in high school was not significantly associated with poor or fair self-related health at age 65 years, but it was associated with the risk of being obese as an adult in comparison with not playing football in high school. Our findings provide needed information about the risk of playing football with regard to a broader set of health outcomes.
Metabolic Risk Factors as Differential Predictors of Profiles of Neurocognitive Impairment Among Older HIV+ and HIV− Adults: An Observational Study
Authors: Pasipanodya Elizabeth C , Montoya Jessica L , Campbell Laura M , Hussain Mariam A , Saloner Rowan , Paolillo Emily M , Jeste Dilip V , Letendre Scott L , McCutchan J Allen , Heaton Robert K , Moore David J
Published: November 2019

Objective

Neurocognitive performance among older persons, including those living with HIV (people living with HIV [PLWH]), exhibits significant heterogeneity, suggesting subpopulations with differing profiles of neurocognitive impairment (NCI). Metabolic factors are associated with NCI, but their relationships to cluster-derived NCI profiles are unknown.

Method

Participants (144 PLWH and 102 HIV uninfected) aged 50+ years completed a neuropsychological battery assessing seven cognitive domains. Latent class analysis (LCA) identified NCI profiles separately by HIV serostatus and in a combined sample. Obtained classes were examined against the Montreal Cognitive Assessment (MoCA) and diagnoses of HIV-associated neurocognitive disorders (HAND). Multinomial regression identified metabolic predictors of classification.

Results

LCA identified three latent classes in each participant sample: Class1Multidomain NCI (high probability of impairment across multiple domains), Class 2Learning & Recall NCI (high probability of impairment in learning and recall), and Class 3NC Unimpaired (low probability of NCI across all domains). Severity of NCI implied by classes corresponded with MoCA scores and HAND diagnoses. In analyses on the combined sample, compared to HIV-uninfected individuals, PLWH were more likely to be in Class1Multidomain NCI. Among PLWH, those with dyslipidemia and hypertension had greater odds of classification in Class 1Multidomain NCI while those with central obesity had higher odds of classification in Class 2Learning & Recall NCI; metabolic syndrome approached significance as a differential predictor. Regardless of HIV status, individuals with diabetes were more likely to be in Class 1Multidomain NCI.

Conclusions

Metabolic risk factors confer heightened risk of NCI in HIV infection. Interventions to reduce metabolic risk may improve neurocognitive outcomes among PLWH.
Towards a comparative approach to the structure of animal personality variation
Authors: White Stephen John , Pascall David John , Wilson Alastair James
Published: November 2019

Latent personality traits underpinning observed behavioral variation have been studied in a great many species. However, a lack of standardized behavioral assays, coupled to a common reliance on inferring personality from a single, observed, behavioral trait makes it difficult to determine if, when, and how conclusions can be directly compared across taxa. Here, we estimate the among-individual (co)variance structure (ID) for a set of four behaviors expressed in an open field trial, putatively indicative of boldness, in seven species of small freshwater fish. We show that the ID matrices differ in terms of the total amount of variation present, and crucially the orientation, and as a consequence, biological interpretation of the first eigenvector. Specifically, loading of observed traits on the main axis of variation in ID matched a priori expectations for a shy-bold continuum in only three of the seven cases. Nonetheless, when the “shape” of the matrices was compared in higher dimensions, there was a high level of similarity among species, and weak evidence of phylogenetic signal. Our study highlights the present difficulty of trying to compare empirical inferences about specific personality traits across studies. However, it also shows how multivariate data collection and analysis allows the structure of behavioral variation to be quantitatively compared across populations or species without reliance on ambiguous verbal labels. This suggests that the field may have much to gain from greater uptake of phylogenetically informed comparative approaches when seeking to test evolutionary hypotheses about the origin and maintenance of personality variation.
DrawGlycan-SNFG and gpAnnotate: rendering glycans and annotating glycopeptide mass spectra
Authors: Cheng Kai , Pawlowski Gabrielle , Yu Xinheng , Zhou Yusen , Neelamegham Sriram
Published: November 2019

This manuscript describes an open-source program, DrawGlycan-SNFG (version 2), that accepts IUPAC (International Union of Pure and Applied Chemist)-condensed inputs to render Symbol Nomenclature For Glycans (SNFG) drawings. A wide range of local and global options enable display of various glycan/peptide modifications including bond breakages, adducts, repeat structures, ambiguous identifications etc. These facilities make DrawGlycan-SNFG ideal for integration into various glycoinformatics software, including glycomics and glycoproteomics mass spectrometry (MS) applications. As a demonstration of such usage, we incorporated DrawGlycan-SNFG into gpAnnotate, a standalone application to score and annotate individual MS/MS glycopeptide spectrum in different fragmentation modes.

Availability and implementation

DrawGlycan-SNFG and gpAnnotate are platform independent. While originally coded using MATLAB, compiled packages are also provided to enable DrawGlycan-SNFG implementation in Python and Java. All programs are available from https://virtualglycome.org/drawglycan; https://virtualglycome.org/gpAnnotate.

Supplementary information

Supplementary data are available at Bioinformatics online.
Graph theory for EEG: can we learn to trust another black box?
Authors: Smith Garnett C , Stacey William C
Published: November 2019

This scientific commentary refers to ‘Virtual resection predicts surgical outcome for drug-resistant epilepsy’ by Kini et al. (doi:10.1093/brain/awz303).
miR-155 as a novel clinical target for hematological malignancies
Authors: Witten Lisa , Slack Frank J
Published: November 2019

MicroRNAs (miRNAs), small non-coding RNAs that repress target genes, are a promising new focus of targeted therapeutics for cancer. miR-155 is a well-studied miRNA involved in inflammation that acts oncogenically in many hematological malignancies. Like other miRNAs, its role in these diseases is complex and nuanced, which gives particular power to its inhibition in diseased cells. This, together with increasing understanding of its key targets in cancer and the use of powerful mouse models of miR-155 in cancer, makes miR-155 an ideal target for therapeutic inhibition. Here, we review the role of miRNAs, and particularly miR-155, in cancers, and discuss progress on therapeutically targeting it, including the ongoing clinical trial of anti-miR-155 molecule Cobomarsen (MRG-106).
Transcription Factor 4 Safeguards Hippocampal Dentate Gyrus Development by Regulating Neural Progenitor Migration
Authors: Wang Yafei , Lu Zhiheng , Zhang Yilan , Cai Yuqun , Yun Di , Tang Tianxiang , Cai Zheping , Wang Chunyang , Zhang Yandong , Fang Fang , Yang Zhengang , Behnisch Thomas , Xie Yunli
Published: November 2019

The dentate gyrus (DG) of the hippocampal formation plays essential roles in learning and memory. Defective DG development is associated with neurological disorders. Here, we show that transcription factor 4 (Tcf4) is essential for DG development. Tcf4 expression is elevated in neural progenitors of the dentate neuroepithelium in the developing mouse brain. We demonstrate that conditional disruption of Tcf4 in the dentate neuroepithelium leads to abnormal neural progenitor migration guided by disorganized radial glial fibers, which further leads to hypoplasia in the DG. Moreover, we reveal that Wnt7b is a key downstream effector of Tcf4 in regulating neural progenitor migration. Behavioral analysis shows that disruption of integrity of the DG impairs the social memory highlighting the importance of proper development of the DG. These results reveal a critical role for Tcf4 in regulating DG development. As mutations in TCF4 cause Pitt–Hopkins syndrome (PTHS) characterized by severe intellectual disability, our data also potentially provide insights into the basis of neurological defects linked to TCF4 mutations.
Does environmental stress affect cortisol biodistribution in freshwater mussels?
Authors: Binder A Ronja D , Pfaffl Michael W , Hiltwein Felix , Geist Juergen , Beggel Sebastian
Published: November 2019

Lay summaries:

Since little is known about invertebrate steroid hormones, we established a cortisol extraction and quantification protocol via ELISA in mussels, in the model organism Anodonta anatina. Additionally, we quantified cortisol biodistribution and redistribution in five different tissues after treatment with either copper (II) chloride, sodium chloride or algae feed.
Written Language Outcomes of Deaf Elementary Students Engaged in Authentic Writing
Authors: Wolbers Kimberly A , Dostal Hannah M , Cihak David , Holcomb Leala
Published: November 2019

This study explores the impact of Strategic and Interactive Writing Instruction (SIWI) on six students’ written language skills through the application of a multiple-baseline probe single case design with embedded condition. This was part of a larger Institute of Education Sciences (IES)-funded project focused on the development and feasibility of implementation of SIWI. For the majority of skills analyzed, there were improvements in the mean level of performance with the implementation of SIWI, as well as more consistent responding and positive trends in the data. The study also revealed that teachers are in need of additional tools to aid the systematic identification and tracking of syntax skills in children’s written language development, and to distinguish these from other writing skills such as conventions or handwriting.
Merger Policy in a Quantitative Model of International Trade*
Authors: Breinlich Holger , Nocke Volker , Schutz Nicolas
Published: November 2019

In a two-country international trade model with oligopolistic competition, we study the conditions on market structure and trade costs under which a merger policy designed to benefit domestic consumers is too tough or too lenient from the viewpoint of the foreign country. We calibrate the model to match industry-level data in the U.S. and Canada. Our results suggest that at present levels of trade costs, merger policy is too tough in the vast majority of sectors. We also quantify the resulting externalities and study the impact of different regimes of coordinating merger policies at varying levels of trade costs.
Cancer statistics: a comparison between World Health Organization (WHO) and Global Burden of Disease (GBD)
Authors: Mattiuzzi Camilla , Lippi Giuseppe
Published: November 2019

This study aims to define comparability of 2016 statistics between Global Health Estimates (GHE) and Global Health Data Exchange (GHDx) registries for disability-adjusted life years (DALYs) and mortality of the 25 most frequent worldwide malignancies. An excellent correlation can be found between the two registries for both cancer DALYs (r = 0.988) and mortality (r = 0.993). Cancer-related DALYs are substantially equivalent (mean bias, −1.9%; P = 0.603), while cancer mortality is modestly but significantly overestimated in GDHx (mean bias, 9.1%; P = 0.004). These results suggest that cancer DALYs estimate appear almost overlapping between GHE and GHDx registries, while cancer mortality is slightly overestimated in GDHx.
Key amino acid residues of neuraminidase involved in influenza A virus entry
Authors: Chen Fangzhao , Liu Teng , Xu Jiagui , Huang Yingna , Liu Shuwen , Yang Jie
Published: November 2019

Generally, influenza virus neuraminidase (NA) plays a critical role in the release stage of influenza virus. Recently, it has been found that NA may promote influenza virus to access the target cells. However, the mechanism remain unclear. Here, we reported that peramivir indeed possessed anti-influenza A virus (IAV) activity in the stage of viral entry. Importantly, we verified the critical residues of influenza NA involved in the viral entry. As a result, peramivir as an efficient NA inhibitor could suppress the initiation of IAV infection. Furthermore, mutational analysis showed NA might be associated with viral entry via amino acids residues R118, E119, D151, R152, W178, I222, E227, E276, R292 and R371. Our results demonstrated NA must contain the key amino acid residues can involve in IAV entry.
Partial anomalous pulmonary venous connection detected during right pneumonectomy
Authors: Yenigün Bülent Mustafa , Kocaman Gökhan , Gürsoy Çoruh Ayşegül , Akal Rıfat Murat
Published: November 2019

Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital anomaly. Generally, it is seen on the right side and is associated with an atrial septal defect. Herein, we present a case of a 50-year-old male patient with a supracardiac type PAPVC detected during pneumonectomy for a right hilar mass. This is the second case report in the literature presenting surgical treatment of both lung cancer and PAPVC using pneumonectomy. Thoracic surgeons should be aware of this anomaly when they are planning to perform a major lung resection. If PAPVC and lung cancer are in the same lobe, anatomical lung resections including pneumonectomy can be safely performed.
Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness
Authors: Castaño M Soledad , Aliee Maryam , Mwamba Miaka Erick , Keeling Matt J , Chitnis Nakul , Rock Kat S
Published: November 2019

Background

Gambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization’s goal of global elimination of transmission (EOT).

Methods

We used stochastic models of gHAT transmission fitted to DRC case data and explored patterns of regional reporting and extinction. The time to EOT at a health zone scale (~100 000 people) and how an absence of reported cases informs about EOT was quantified.

Results

Regional epidemiology and level of active screening (AS) both influenced the predicted time to EOT. Different AS cessation criteria had similar expected infection dynamics, and recrudescence of infection was unlikely. However, whether EOT has been achieved when AS ends is critically dependent on the stopping criteria. Two or three consecutive years of no detected cases provided greater confidence of EOT compared with a single year (~66%–75% and ~82%–84% probability of EOT, respectively, compared with 31%–51%).

Conclusions

Multiple years of AS without case detections is a valuable measure to assess the likelihood that the EOT target has been met locally.
Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics
Authors: Srivastava Shashikant , Deshpande Devyani , Magombedze Gesham , van Zyl Johanna , Cirrincione Kayle , Martin Katherine , Bendet Paula , Berg Alexander , Hanna Debra , Romero Klaus , Hermann Dave , Gumbo Tawanda
Published: November 2019

Objectives

Animal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3–4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB).

Methods

A series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen.

Results

Using linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13–0.23) versus 0.15 (95% credible interval=0.08–0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13–0.18) versus 0.11 (95% credible interval=0.09–0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1–41.34) and 72.30% (95% credible interval=71.41–73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18–94.13) at 6 months for standard therapy.

Conclusions

The kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.
Thinking outside the pelvis: benign peritoneal multicystic mesothelioma of the ascending colon
Authors: Murphy Brenda , Ismaeil Mohamed , Winter Des C
Published: November 2019

Benign peritoneal multicystic mesothelioma is a rare tumor of the visceral peritoneum. The authors present an atypical case of a 74-year-old man who presented with a multicystic mesothelioma of the ascending colon.
Extensive hidradenitis suppurativa with dorsal foot involvement: a case report
Authors: Nisar Saira , Roberson Jeffrey L , Travis Taryn E , Johnson Laura S , Shupp Jeffrey W
Published: November 2019

Hidradenitis suppurativa (HS) is a highly morbid chronic inflammatory skin disease resulting in painful and purulent lesions classically occurring in areas with a high density of apocrine glands such as the groin and axillae. This is the case of a 53-year-old male with medically refractory Hurley stage III HS affecting multiple anatomical sites including the dorsum of the right foot, an atypical location. Throughout his hospital course, he underwent a series of surgical excision and graft procedures to treat extensive HS lesions on various anatomical locations. In patients with a history of HS, mechanical stress may result in atypical lesion locations. In addition to the standard medical and surgical treatment, management should include optimizing nutritional parameters, smoking cessation, wound care and reducing friction and pressure at the affected area.
Turning sugar into oil: making photosynthesis blind to feedback inhibition
Authors: Paul Matthew J , Eastmond Peter J
Published: November 2019

This article comments on:

Beechey-Gradwell Z, Cooney L, Winichayakul S, Andrews M, Hea SY, Crowther T, Roberts N. 2020. Storing carbon in leaf lipid sinks enhanced perennial ryegrass carbon capture especially under high N and elevated CO2. Journal of Experimental Botany 71, 2351–2361.
The European Nucleotide Archive in 2019
Authors: Amid Clara , Alako Blaise T F , Balavenkataraman Kadhirvelu Vishnukumar , Burdett Tony , Burgin Josephine , Fan Jun , Harrison Peter W , Holt Sam , Hussein Abdulrahman , Ivanov Eugene , Jayathilaka Suran , Kay Simon , Keane Thomas , Leinonen Rasko , Liu Xin , Martinez-Villacorta Josue , Milano Annalisa , Pakseresht Amir , Rahman Nadim , Rajan Jeena , Reddy Kethi , Richards Edward , Smirnov Dmitriy , Sokolov Alexey , Vijayaraja Senthilnathan , Cochrane Guy
Published: November 2019

The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena) at the European Molecular Biology Laboratory’s European Bioinformatics Institute provides open and freely available data deposition and access services across the spectrum of nucleotide sequence data types. Making the world’s public sequencing datasets available to the scientific community, the ENA represents a globally comprehensive nucleotide sequence resource. Here, we outline ENA services and content in 2019 and provide an insight into selected key areas of development in this period.
Rapid in vitro production of single-stranded DNA
Authors: Minev Dionis , Guerra Richard , Kishi Jocelyn Y , Smith Cory , Krieg Elisha , Said Khaled , Hornick Amanda , Sasaki Hiroshi M , Filsinger Gabriel , Beliveau Brian J , Yin Peng , Church George M , Shih William M
Published: November 2019

There is increasing demand for single-stranded DNA (ssDNA) of lengths >200 nucleotides (nt) in synthetic biology, biological imaging and bionanotechnology. Existing methods to produce high-purity long ssDNA face limitations in scalability, complexity of protocol steps and/or yield. We present a rapid, high-yielding and user-friendly method for in vitro production of high-purity ssDNA with lengths up to at least seven kilobases. Polymerase chain reaction (PCR) with a forward primer bearing a methanol-responsive polymer generates a tagged amplicon that enables selective precipitation of the modified strand under denaturing conditions. We demonstrate that ssDNA is recoverable in ∼40–50 min (time after PCR) with >70% yield with respect to the input PCR amplicon, or up to 70 pmol per 100 μl PCR reaction. We demonstrate that the recovered ssDNA can be used for CRISPR/Cas9 homology directed repair in human cells, DNA-origami folding and fluorescent in-situ hybridization.
Contrasting diurnal patterns in antioxidant capacities, but not in expression of stress protein genes among copepod populations from clear versus glacially fed alpine and subalpine lakes
Authors: Tartarotti Barbara , Sommaruga Ruben , Saul Nadine
Published: November 2019

Short-term changes in environmental conditions largely influence planktonic organisms, but their responses will depend on the habitat characteristics. Here we studied diurnal patterns in antioxidative metabolites (lipophilic and hydrophilic antioxidant capacities) and in the expression of stress protein genes (heat shock proteins, hsp) of copepods to identify short-term stress responses in clear and turbid alpine lakes, as well as in less transparent subalpine ones. Cyclops abyssorum tatricus showed diurnal variation in antioxidant capacities with maxima around noon in clear, but not in glacially fed, turbid lakes. Low fluctuations of these metabolites were also observed in another copepod, Acanthodiaptomus denticornis. Although levels of hsp genes differed between populations living in clear or glacially fed lakes, there was no diurnal rhythmicity in gene expression. Our data show that when planktonic organisms may be at greatest risk of oxidative damage, such as during the daytime in high UV radiation environments, they activate antioxidant responses. Conversely, in less transparent lakes, the physiological response seems to be unnecessary. The difference in gene expression levels suggests an ecological, albeit not acute, role of these genes in copepods experiencing daily environmental fluctuations.
Identifying phenotypes of patients with antiphospholipid antibodies: results from a cluster analysis in a large cohort of patients
Authors: Sciascia Savino , Radin Massimo , Cecchi Irene , Bertolaccini Maria Laura , Bertero Maria Tiziana , Rubini Elena , Vaccarino Antonella , Bazzan Mario , Giachino Osvaldo , Baldovino Simone , Rossi Daniela , Mengozzi Giulio , Roccatello Dario
Published: November 2019

Objectives

To identify the aggregation of patients with aPL into different subgroups sharing common features in terms of clinical and laboratory phenotypes.

Methods

We applied a hierarchical cluster analysis from the multiple correspondence analysis to determine subgroups of patients according to clinical and laboratory characteristics in a cohort of subjects with confirmed aPL positivity who presented to our outpatient clinics from 2006 to 2018.

Results

A total of 486 patients [403 women; age 41.7 years (26)] were included, resulting in five clusters. Cluster 1 (n= 150) presented with thrombotic events (65.3% with venous thrombosis), with triple aPL positivity found in 34.7% of them (the highest rate among the different clusters). All the patients from cluster 2 (n = 91) had a confirmed diagnosis of SLE and the highest rate of anti-dsDNA positivity (91.7%). Cluster 3 included 79 women with pregnancy morbidity. Triple positivity was present in 3.8%, significantly lower when compared with Cluster 1 (34.7% versus 3.8%, P <0.01). Cluster 4 included 67 patients, 28 (41.8%) of whom with APS. Thrombotic events were observed in 23.9% patients. Cluster 4 had the highest rate of cytopenia, with thrombocytopenia as high 41.8% with no anti-dsDNA antibodies. Cluster 5 included 94 asymptomatic aPL carriers.

Conclusion

While clusters 1, 2, 3 and 5 corresponded to well-known entities, cluster 4 might represent a bridging condition between pure primary APS and defined SLE, with lower thrombotic risk when compared with primary APS but higher general features such as ANA and cytopenia (mainly thrombocytopenia).
The effect of calf jackets on the health, performance, and skin temperature of dairy origin beef calves
Authors: Rutherford Naomi H , Gordon Alan W , Arnott Gareth , Lively Francis O
Published: November 2019

Variations and extremities in climatic conditions can result in cold stress for dairy calves during the preweaning period. The objective of this study was to investigate the effect of calf jackets on the health, performance, and skin temperature of dairy-origin beef calves. This study took place in a designated calf rearing unit, spanned for a duration of 1 yr, and consisted of five batches of calves. Calves (30.9 ± 1.68 d of age; 55.9 ± 0.20 kg live weight) were assigned to one of four treatment groups on arrival at the rearing unit. Treatments consisted of control (no jacket), arrival (jacket for 2 wk postarrival), weight (jacket for a minimum of 2 wk and until 65 kg live weight), and wean (jacket until 5 d postweaning). Ambient conditions differed significantly (P < 0.001) during each of the five batches; batch 4 was the coldest with a mean ambient temperature of 6.16 °C. Significant differences were observed between the five batches for day 50 weight (P < 0.01) and disease incidence (P < 0.05). However, treatment had no significant effect on calf health or performance (P > 0.05) during any of the five batches. Skin temperature was significantly greater (P < 0.001) for calves wearing a jacket. Furthermore, there was a significant (P < 0.001) relationship between ambient temperature-humidity index and skin temperature for calves with and without a calf jacket. Therefore, although calf jackets had no benefit in terms of health or performance, they did act as a barrier to environmental conditions.
Reducing Older Workers’ Sickness Absence: The Moderating Role of Perceived Fairness
Authors: Goštautaitė Bernadeta , Shao Yiduo
Published: November 2019

Although aging is often associated with higher vulnerability for illness, research has reported mixed results regarding the relationship between workers’ age and sickness absence. Drawing on social exchange theory, we propose that perceived fairness may attenuate the positive association between employee age and sickness absence. We tested our hypotheses by matching employee survey data with organizational archival data on sickness absence from a public sector organization in Lithuania (n = 458). Our findings showed that perceived fairness buffered the negative effect of age on sickness absence, which provides important implications.
Paraconexibacter algicola gen. nov., sp. nov., a novel actinobacterium isolated from a eutrophic lake during the end of cyanobacterial harmful algal blooms, and proposal of Paraconexibacteraceae fam. nov. in the order Solirubrobacterales
Authors: Chun Seong-Jun , Cui Yingshun , Jin Chunzhi , Cho A Ra , Wong Shu-Kuan , Lee Hyung-Gwan , Oh Hee-Mock , Ahn Chi-Yong
Published: November 2019

A novel bacterium, strain Seoho-28T, was isolated from a shallow eutrophic lake during the end of cyanobacterial harmful algal blooms and was characterized taxonomically and phylogenetically. Strain Seoho-28T was a Gram-stain-negative, aerobic, rod-shaped and non-motile bacterium. The strain grew optimally with 0 % NaCl and at 25–30 °C on Reasoner's 2A medium. The phylogenetic analysis based on 16S rRNA gene sequences positioned the novel strain among the order

Solirubrobacterales

, but sequence similarities to known species were less than 94.7 %. The genomic DNA G+C content of the strain Seoho-28T was 74.2 mol%. Genomic comparisons of strain Seoho-28T with families in the order

Solirubrobacterales

were made using the Genome-to-Genome Distance Calculator, average nucleotide identity and average amino acid identity analyses (values indicated ≤14.9, ≤73.5 and ≤57.8 %, respectively). Strain Seoho-28T contained C16 : 0-iso, C18 : 1
 ω9c and C16 : 0 as major fatty acids and MK-7 (H4) as the major quinone. Strain Seoho-28T contained diphosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid as major polar lipids. Meso- and ll-diaminopimelic acids were the diagnostic diamino acids in the cell-wall peptidoglycan. Based on the genotypic, chemotaxonomic and phenotypic results, strain Seoho-28T represents a novel genus and species, Paraconexibacter algicola gen. nov., sp. nov., which belongs to a new family Paraconexibacteraceae in the order

Solirubrobacterales

and the class

Thermoleophilia

. The type strain is Seoho-28T (=KCTC 39791T=JCM 31881T).
Complete hybrid genome assembly of clinical multidrug-resistant Bacteroides fragilis isolates enables comprehensive identification of antimicrobial-resistance genes and plasmids
Authors: Sydenham Thomas V. , Overballe-Petersen Søren , Hasman Henrik , Wexler Hannah , Kemp Michael , Justesen Ulrik S.
Published: November 2019

Bacteroides fragilis

constitutes a significant part of the normal human gut microbiota and can also act as an opportunistic pathogen. Antimicrobial resistance (AMR) and the prevalence of AMR genes are increasing, and prediction of antimicrobial susceptibility based on sequence information could support targeted antimicrobial therapy in a clinical setting. Complete identification of insertion sequence (IS) elements carrying promoter sequences upstream of resistance genes is necessary for prediction of AMR. However, de novo assemblies from short reads alone are often fractured due to repeat regions and the presence of multiple copies of identical IS elements. Identification of plasmids in clinical isolates can aid in the surveillance of the dissemination of AMR, and comprehensive sequence databases support microbiome and metagenomic studies. We tested several short-read, hybrid and long-lead assembly pipelines by assembling the type strain

B. fragilis

CCUG4856T (=ATCC25285=NCTC9343) with Illumina short reads and long reads generated by Oxford Nanopore Technologies (ONT) MinION sequencing. Hybrid assembly with Unicycler, using quality filtered Illumina reads and Filtlong filtered and Canu-corrected ONT reads, produced the assembly of highest quality. This approach was then applied to six clinical multidrug-resistant

B. fragilis

isolates and, with minimal manual finishing of chromosomal assemblies of three isolates, complete, circular assemblies of all isolates were produced. Eleven circular, putative plasmids were identified in the six assemblies, of which only three corresponded to a known cultured

Bacteroides

plasmid. Complete IS elements could be identified upstream of AMR genes; however, there was not complete correlation between the absence of IS elements and antimicrobial susceptibility. As our knowledge on factors that increase expression of resistance genes in the absence of IS elements is limited, further research is needed prior to implementing AMR prediction for

B. fragilis

from whole-genome sequencing.
Spatiotemporal tools for emerging and endemic disease hotspots in small areas – an analysis of dengue and chikungunya in Barbados, 2013 – 2016
Authors: Lippi Catherine A. , Stewart-Ibarra Anna M. , Romero Moory , Hinds Avery Q.J. , Lowe Rachel , Mahon Roché , Meerbeeck Cedric J. Van , Rollock Leslie , Hilaire Marquita Gittens-St. , Trotman Adrian R. , Holligan Dale , Kirton Shane , Borbor-Cordova Mercy J. , Ryan Sadie J.
Published: November 2019

Objective

To detect potential hotspots of transmission of dengue and chikungunya in Barbados, and assess impact of input surveillance data and methodology on observed patterns of risk.

Methods

Using two methods of cluster detection, Moran’s I and spatial scan statistics, we analyzed the geospatial and temporal distribution of disease cases and rates across Barbados for dengue fever in 2013–2016, and a 2014 chikungunya outbreak.

Results

During years with high numbers of dengue cases, hotspots for cases were found with Moran’s I in south and central regions in 2013 and 2016, respectively. Using smoothed disease rates, clustering was detected every year for dengue. Hotspots were not detected via spatial scan statistics, but coldspots suggesting lower rates of disease activity were found in southwestern Barbados during high case years of dengue.

Conclusions

Spatial analysis of surveillance data is useful in identifying outbreak hotspots, complementing existing early warning systems. We caution that these methods should be used in a manner appropriate to available data, and reflecting explicit public health goals – managing for overall case numbers, or targeting anomalous rates for further investigation.
Characterization of the prion protein binding properties of antisense oligonucleotides
Authors: Reidenbach Andrew G , Minikel Eric Vallabh , Zhao Hien T , Guzman Stacy G , Leed Alison J , Mesleh Michael F , Kordasiewicz Holly B , Schreiber Stuart L , Vallabh Sonia M
Published: November 2019

Antisense oligonucleotides (ASOs) designed to lower prion protein (PrP) expression in the brain through RNAse H1-mediated degradation of PrP RNA are in development as prion disease therapeutics. ASOs were previously reported to sequence-independently interact with PrP and inhibit prion accumulation in cell culture, yetin vivostudies using a new generation of ASOs found that only PrP-lowering sequences were effective at extending survival. Cerebrospinal fluid (CSF) PrP has been proposed as a pharmacodynamic biomarker for trials of such ASOs, but is only interpretable if PrP lowering is indeed the relevant mechanism of actionin vivoand if measurement of PrP is unconfounded by any PrP-ASO interaction. Here we examine the PrP-binding and antiprion properties of ASOsin vitroand in cell culture. Binding parameters determined by isothermal titration calorimetry were similar across all ASOs tested, indicating that ASOs of various chemistries bind full-length recombinant PrP with low- to mid-nanomolar affinity in a sequence-independent manner. Nuclear magnetic resonance, dynamic light scattering, and visual inspection of ASO-PrP mixtures suggested, however, that this interaction is characterized by the formation of large aggregates, a conclusion further supported by the salt dependence of the affinity measured by isothermal titration calorimetry. Sequence-independent inhibition of prion accumulation in cell culture was observed. The inefficacy of non-PrP-lowering ASOs against prion diseasein vivomay be because their apparent activityin vitrois an artifact of aggregation, or because the concentration of ASOs in relevant compartments within the central nervous system (CNS) quickly drops below the effective concentration for sequence-independent antiprion activity after bolus dosing into CSF. ELISA-based measurements of PrP concentration in human CSF were not impacted by the addition of ASO. These findings support the further development of PrP-lowering ASOs and of CSF PrP as a pharmacodynamic biomarker.
Human URAT1/SLC22A12gene promoter is regulated by 27-hydroxycholesterol through estrogen response elements
Authors: Matsubayashi Masaya , Sakaguchi Yoshihiko M. , Sahara Yoshiki , Nanaura Hitoki , Kikuchi Sotaro , Ashari Arvand , Bui Linh , Kobashigawa Shinko , Nakanishi Mari , Nagata Riko , Matsui Takeshi K. , Kashino Genro , Hasegawa Masatoshi , Takasawa Shin , Eriguchi Masahiro , Tsuruya Kazuhiko , Nagamori Shushi , Sugie Kazuma , Nakagawa Takahiko , Takasato Minoru , Umetani Michihisa , Mori Eiichiro
Published: November 2019

Elevated levels of uric acid, a metabolite of purine in humans, is related to various diseases, such as gout, atherosclerosis and renal dysfunction. The excretion and reabsorption of uric acid to/from urine is tightly regulated by uric acid transporters. The amino acid sequences of uric acid reabsorption transporters, URAT1/SLC22A12, OAT4/SLC22A11, and OAT10/SLC22A13, share closer phylogenic relationship, whereas the gene promoter sequences are distant phylogenic relationship. Through the single-cell RNA-sequencing analysis of an adult human kidney, we found that only a small number of cells express these transporters, despite their role in the regulation of serum uric acid levels. Transcriptional motif analysis on these transporter genes, revealed that the URAT1/SLC22A12gene promoter displayed the most conserved estrogen response elements (EREs) among the three transporters. The endogenous selective estrogen receptor modulator (SERM) 27-hydroxycholesterol (27HC) had positive effects on the transcriptional activity of URAT1/SLC22A12. We also found that 27HC increased the protein and gene expression of URAT1/SLC22A12in mouse kidneys and human kidney organoids, respectively. These results strongly suggest the role of 27HC for URAT1/SLC22A12expression in renal proximal tubules and upregulation of serum uric acid levels and also show the relationship between cholesterol metabolism and serum uric acid regulation.

Significance Statement

The elevated levels of serum uric acid cause various diseases, and the excretion/reabsorption of uric acid to/from urine is tightly regulated by the uric acid transporters. We found that despite the role in serum uric acid regulation, only a small number of cells express URAT1/SLC22A12. We also found that URAT1/SLC22A12gene promoter region has effective estrogen response elements, and endogenous selective estrogen receptor (ER) modulator 27-hydroxycholesterol (27HC) increased URAT1/SLC22A12expression in the mice kidneys and human kidney organoids. These suggest that 27HC increases URAT1/SLC22A12expression and upregulate serum uric acid levels. Since 27HC connects cholesterol metabolism, our study indicates the important link between cholesterol metabolism and serum uric acid regulation, and also provides a novel therapeutic approach to hyperuricemia.
Induced pluripotent stem cell-derived primary proprioceptive neurons as Friedreich ataxia cell model
Authors: Dionisi Chiara , Rai Myriam , Chazalon Marine , Schiffmann Serge N. , Pandolfo Massimo
Published: November 2019

Human induced pluripotent stem cells (iPSCs) are used to generate models of human diseases that recapitulate the pathogenic process as it occurs in affected cells. Many differentiated cell types can currently be obtained from iPSCs, but no validated protocol is yet available to specifically generate primary proprioceptive neurons. Proprioceptors are affected in a number of genetic and acquired diseases, including Friedreich ataxia (FRDA).

FRDA is a recessive neurodegenerative and systemic disease due to epigenetic suppression of frataxin (FXN) expression caused by the presence of expanded GAA repeats at the FXN locus. The most characteristic early neuropathologic finding in FRDA is the loss of large primary proprioceptive neurons in the dorsal root ganglia (DRGs), with associated loss of large myelinated fibers in the dorsal roots and in the posterior columns of the spinal cord. Both a developmental deficit and progressive neurodegeneration are thought to underlie the loss of proprioceptors in FRDA, though the relative contribution of these two components is unclear. The basis of the high specific vulnerability of proprioceptors in FRDA is also unknown. In order to address these open questions about FRDA pathogenesis and at the same time develop a cell model that can be applied to other conditions primarily affecting proprioceptors, we set up a protocol to differentiate iPSCs into primary proprioceptive neurons. We modified the dual-SMAD inhibition/WNT activation protocol, previously used to generate nociceptor-enriched cultures of primary sensory neurons from iPSCs, to favor instead the generation of proprioceptors. We succeeded in substantially enriching iPSC-derived primary sensory neuron cultures in proprioceptors, largely exceeding the proportion normally represented by these cells in dorsal root ganglia. We also showed that almost pure populations of proprioceptors can be purified from these cultures by fluorescence-activated cell sorting. Finally, we demonstrated that iPSCs from a FRDA patient can generate normal appearing proprioceptors but have subtle differentiation deficits and more limited survival.