bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific impact of inbreeding on pathogen load in the striped dolphin
Authors: Gkafas Georgios A. , de Jong Menno , Exadactylos Athanasios , Raga Juan Antonio , Aznar Francisco J. , Hoelzel A. Rus
Published: March 2020

The impact of inbreeding on fitness has been widely studied and provides consequential inference about adaptive potential and the impact on survival for reduced and fragmented natural populations. Correlations between heterozygosity and fitness are common in the literature, but they rarely inform about the likely mechanisms. Here, we investigate a pathology with a clear impact on health in striped dolphin hosts (a nematode infection that compromises lung function). Dolphins varied with respect to their parasite burden of this highly pathogenic lung nematode (Skrjabinalius guevarai). Genetic diversity revealed by high-resolution restriction-associated DNA (43 018 RADseq single nucleotide polymorphisms) analyses showed a clear association between heterozygosity and pathogen load, but only for female dolphins, for which the more heterozygous individuals had lowerSk. guevaraiburden. One locus identified by RADseq was a strong outlier in association with parasite load (heterozygous in all uninfected females, homozygous for 94% of infected females), found in an intron of the citron rho-interacting serine/threonine kinase locus (associated with milk production in mammals). Allelic variation at the Class II major histocompatability complex DQB locus was also assessed and found to be associated with both regional variation and with pathogen load. Both sex specificity and the identification of associating functional loci provide insight into the mechanisms by which more inbred individuals may be more susceptible to the infection of this parasite. This provides important insight towards our understanding of the impact of inbreeding in natural populations, relevant to both evolutionary and practical conservation considerations.
Nine novel psychrotolerant species of the genus Pedobacter isolated from Arctic soil with potential antioxidant activities
Authors: Dahal Ram Hari , Chaudhary Dhiraj Kumar , Kim Dong-Uk , Kim Jaisoo
Published: March 2020

Fifteen isolates of the genus

Pedobacter

were obtained from Arctic soil samples. All isolates were Gram-stain-negative and rod-shaped. Cells were strictly aerobic, psychrotolerant and grew optimally at 15–20 °C. Phylogenetic analysis based on 16S rRNA gene sequences revealed that all the isolated strains formed a lineage within the family

Sphingobacteriaceae

and clustered as members of the genus

Pedobacter

. The sole respiratory quinone was MK-7 and the major polar lipid was phosphatidylethanolamine. The major cellular fatty acids were summed feature 3 (iso-C15 : 02-OH/C16 : 1ω7c/ω6c), iso-C15 : 0 and iso-C17 : 0 3-OH. The DNA G+C content of the novel strains was 33.9–41.8 mol%. In addition, the average nucleotide identity and in silico DNA–DNA hybridization relatedness values between the novel type strains and phylogenetically related type strains were below the threshold values used for species delineation. Based on genomic, chemotaxonomic, phenotypic, phylogenetic and phylogenomic analyses, the isolated strains represent novel species in the genus

Pedobacter

, for which the names Pedobacter cryotolerans sp. nov. (type strain AR-2-6T=KEMB 9005-717T=KACC 19998T=NBRC 113826T), Pedobacter cryophilus sp. nov. (type strain AR-3-17T=KEMB 9005-718T=KACC 19999T=NBRC 113827T), Pedobacter frigiditerrae sp. nov. (type strain RP-1-13T=KEMB 9005-720T=KACC 21147T=NBRC 113829T), Pedobacter psychroterrae sp. nov. (type strain RP-1-14T=KEMB 9005-721T=KACC 21148T=NBRC 113830T), Pedobacter hiemivivus sp. nov. (type strain RP-3-8T=KEMB 9005-724T=KACC 21152T=NBRC 113833T), Pedobacter frigidisoli sp. nov. (type strain RP-3-11T=KEMB 9005-725T=KACC 21153T=NBRC 113927T), Pedobacter frigoris sp. nov. (type strain RP-3-15T=KEMB 9005-726T=KACC 21154T=NBRC 113834T), Pedobacter psychrodurus sp. nov. (type strain RP-3-21T=KEMB 9005-728T=KACC 21156T=NBRC 113835T) and Pedobacter polaris sp. nov. (type strain RP-3-22T=KEMB 9005-729T=KACC 21157T=NBRC 113836T) are proposed.
Salmonella Typhimurium encoded cold shock protein E is essential for motility and biofilm formation
Authors: Ray Semanti , Da Costa Rochelle , Thakur Samriddhi , Nandi Dipankar
Published: March 2020

The ability of bacteria to form biofilms increases their survival under adverse environmental conditions. Biofilms have enormous medical and environmental impact; consequently, the factors that influence biofilm formation are an important area of study. In this investigation, the roles of two cold shock proteins (CSP) during biofilm formation were investigated in

Salmonella

Typhimurium, which is a major foodborne pathogen. Among all CSP transcripts studied, the expression of cspE (STM14_0732) was higher during biofilm growth. The cspE deletion strain (ΔcspE) did not form biofilms on a cholesterol coated glass surface; however, complementation with WT cspE, but not the F30V mutant, was able to rescue this phenotype. Transcript levels of other CSPs demonstrated up-regulation of cspA (STM14_4399) in ΔcspE. The cspA deletion strain (ΔcspA) did not affect biofilm formation; however, ΔcspEΔcspA exhibited higher biofilm formation compared to ΔcspE. Most likely, the higher cspA amounts in ΔcspE reduced biofilm formation, which was corroborated using cspA over-expression studies. Further functional studies revealed that ΔcspE and ΔcspEΔcspA exhibited slow swimming but no swarming motility. Although cspA over-expression did not affect motility, cspE complementation restored the swarming motility of ΔcspE. The transcript levels of the major genes involved in motility in ΔcspE demonstrated lower expression of the class III (fliC, motA, cheY), but not class I (flhD) or class II (fliA, fliL), flagellar regulon genes. Overall, this study has identified the interplay of two CSPs in regulating two biological processes: CspE is essential for motility in a CspA-independent manner whereas biofilm formation is CspA-dependent.
Gaps in Sexually Transmitted Infection Screening among Men who Have Sex with Men in PrEP Care in the United States
Authors: Chandra Christina , Weiss Kevin M. , Kelley Colleen F. , Marcus Julia L. , Jenness Samuel M.
Published: March 2020

Background

The U.S. Centers for Disease Control and Prevention (CDC) recommends comprehensive sexually transmitted infection (STI) screening every 3–6 months for men who have sex with men (MSM) using HIV preexposure prophylaxis (PrEP). The gaps between these recommendations and clinical practice by region have not been quantified.

Methods

We used survey data collected from the internet-based ARTnet study between 2017 and 2019 on STI screening among MSM across the U.S., stratified by current, prior, and never PrEP use. Poisson regression models with robust error variance were used to model factors, including residence in the Southeast, associated with consistent (“always” or “sometimes”) exposure site-specific STI screening during PrEP care.

Results

Of 3259 HIV-negative MSM, 19% were currently using PrEP, 6% had used PrEP in the past, and 75% had never used PrEP. Among ever PrEP users, 87%, 78%, 57%, and 64% reported consistent screening for STIs by blood sample, urine sample or urethral swab, rectal swab, or pharyngeal swab, respectively, during PrEP care. Compared to PrEP users in all other regions, PrEP users in the Southeast were significantly less likely to be consistently screened for urogenital (adjusted prevalence ratio [aPR], 0.86; 95% confidence interval [CI], 0.76–0.98) and rectal STIs (aPR, 0.76; 95% CI, 0.62–0.93) during PrEP care.

Conclusions

Substantial gaps exist between CDC recommendations for STI screening during PrEP care and current clinical practice, particularly for rectal and pharyngeal exposure sites that can harbor asymptomatic infections and for MSM in Southeast states where the STI burden is substantial.

Nearly half of U.S. men who have sex with men in PrEP care are not receiving consistent bacterial STI screening at sites of sexual exposure, and levels are worse in the Southeast region where the burden of STI is highest.
Rapid Detection of 2019 Novel Coronavirus SARS-CoV-2 Using a CRISPR-based DETECTR Lateral Flow Assay
Authors: Broughton James P. , Deng Xianding , Yu Guixia , Fasching Clare L. , Singh Jasmeet , Streithorst Jessica , Granados Andrea , Sotomayor-Gonzalez Alicia , Zorn Kelsey , Gopez Allan , Hsu Elaine , Gu Wei , Miller Steve , Pan Chao-Yang , Guevara Hugo , Wadford Debra A. , Chen Janice S. , Chiu Charles Y.
Published: March 2020

An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (∼30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.
The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China
Authors: Gao Qijun , Hu Yingfu , Dai Zhiguo , Xiao Feng , Wang Jing , Wu Jing
Published: March 2020

Background

There is currently a global outbreak of coronavirus disease 2019 (COVID-19),and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported.

Objective

Describe the epidemic characteristics of COVID-19 in Jingmen,Hubei,introduce the local prevention and control experience,and observe the impact of various prevention and control measures on the number of new cases.

Methods

All the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29,2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic.

Findings

Of the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range,2-88 years;IQR,35-60). Thirty-three severe patients with a median age of 66 years(range,33-82 years,IQR,57-76) were treated in intensive care units; out of these patients, 66.7 %(22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures.

Interpretation

In conclusion,all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious,control measures have proven to be very effective, particularly wearing masks,which could prevent most infections.

Funding

Supported by the Major Program of Technological Innovation of Hubei Province.
Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population
Authors: Xu Yang , Li Yi-rong , Zeng Qiang , Lu Zhi-bing , Li Yong-zhe , Wu Wei , Dong Sheng-yong , Huang Gang , Wang Xing-huan
Published: March 2020

Background

In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in the Chinese Han population.

Methods

Retrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia, from February 7 to February 28, 2020; final date of follow-up was February 29, 2020.

Results

The study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n=44), severe or critical patients (n=25) were significantly older (median age, 67 years [IQR, 58-79] vs. 49 years [IQR, 36-60]; p<0.01). Fever was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue (58.0%), sputum (39.1%), and headache (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion (PLD) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury (troponin I >28 pg/mL) and 4.4% patients were diagnosed fungal infections or shock. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery.

Conclusions

In this multicenter case series of 69 patients without comorbidities, the full spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died.
Smartphone-Based Symbol-Digit Modalities Test Reliably Measures Cognitive Function in Multiple Sclerosis Patients
Authors: Pham Linh , Harris Thomas , Varosanec Mihael , Kosa Peter , Bielekova Bibiana
Published: March 2020

Limited time for patient encounters prevents reliable evaluation of all neurological functions in routine clinical practice. Quantifying neurological disability in a patient-autonomous manner via smartphones may remedy this problem, if such tests provide reliable, disease-relevant information.

We developed a smartphone version of the cognitive processing speed test, the Symbol-Digit Modalities Test (SDMT), and assessed its clinical utility. The traditional SDMT uses identical symbol-number codes, allowing memorization after repeated trials. In the phone app, the symbol-number codes are randomly generated.

In 154 multiple sclerosis (MS) patients and 39 healthy volunteers (HV), traditional and smartphone SDMT have good agreement (Lin’s coefficient of concordance [CCC] = 0.84) and comparable test-retest variance. In subjects with available volumetric MRI and digitalized neurological examinations (112 MS, 12 HV), the SDMT scores were highly associated with T2 lesion load and brain parenchymal fraction, when controlled for relevant clinical characteristics. The smartphone SDMT association with clinical/imaging features was stronger (R2 = 0.75, p < 0.0001) than traditional SDMT (R2 = 0.65, p < 0.0001). In the longitudinal subcohort, improvements from testing repetition (learning effects), were identifiable using non-linear regression in 14/16 subjects and, on average, peaked after 8 trials. Averaging several post-learning SDMT results significantly lowers the threshold for detecting true decline in test performance.

In conclusion, smartphone, self-administered SDMT is a reliable substitute of the traditional SDMT for measuring processing speed in MS patients. Granular measurements at home increase sensitivity to detect true performance decline in comparison to sporadic assessments in the clinic.
Ancient and modern genomes reveal microsatellites maintain a dynamic equilibrium through deep time
Authors: McComish Bennet J. , Charleston Michael A. , Parks Matthew , Baroni Carlo , Salvatore Maria Cristina , Li Ruiqiang , Zhang Guojie , Millar Craig D. , Holland Barbara R. , Lambert David M.
Published: March 2020

Microsatellites are widely used in population genetics, but their evolutionary dynamics remain poorly understood. It is unclear whether microsatellite loci drift in length over time. We identify more than 27 million microsatellites using a novel and unique dataset of modern and ancient Adélie penguin genomes along with data from 63 published chordate genomes. We investigate microsatellite evolutionary dynamics over two time scales: one based on the Adélie penguin samples dating to approximately 46.5 kya, the other dating to the diversification of chordates more than 500 Mya. We show that the process of microsatellite allele length evolution is at dynamic equilibrium; while there is length polymorphism among individuals, the length distribution for a given locus remains stable. Many microsatellites persist over very long time scales, particularly in exons and regulatory sequence. These often retain length variability, suggesting that they may play a role in the maintenance of evolutionary plasticity.
Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration
Authors: Bolado-Carrancio Alfonso , Rukhlenko Oleksii S. , Nikonova Elena , Tsyganov Mikhail A. , Wheeler Anne , Munoz Amaya Garcia , Kolch Walter , von Kriegsheim Alex , Kholodenko Boris N.
Published: March 2020

Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at the rear whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells.
Sprouty2 limits intestinal tuft and goblet cell numbers through GSK3β-mediated restriction of epithelial IL-33
Authors: Schumacher Michael A. , Hsieh Jonathan J. , Liu Cambrian Y. , Appel Keren L. , Waddell Amanda , Almohazey Dana , Katada Kay , Bernard Jessica K. , Bucar Edie B. , Gadeock Safina , Maselli Kathryn M. , Washington M. Kay , Grikscheit Tracy C. , Warburton David , Rosen Michael J. , Frey Mark R.
Published: March 2020

Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we asked whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion led to expanded goblet and tuft cell populations. Sprouty2 loss induced PI3K/Akt signaling, leading to GSK3β inhibition and epithelial interleukin (IL)-33 expression. In vivo, this resulted in increased stromal IL-13+ cells. IL-13 in turn induced tuft and goblet cell expansion in vitro and in vivo. Sprouty2 was downregulated by inflammation; this appeared to be a protective response, as VillinCre;Sprouty2F/Fmice were resistant to DSS colitis. In contrast, Sprouty2 was elevated in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.
Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Endosomal Sensing by Dendritic Cells in Psoriasis
Authors: Lou Fangzhou , Sun Yang , Xu Zhenyao , Niu Liman , Wang Zhikai , Deng Siyu , Liu Zhaoyuan , Zhou Hong , Bai Jing , Yin Qianqian , Cai Xiaojie , Sun Libo , Wang Hong , Wu Zhouwei , Chen Xiang , Shi Yuling , Tao Wufan , Ginhoux Florent , Wang Honglin
Published: March 2020

The mechanisms underlying tissue-specific chronic inflammation are elusive. Here we report that mice lacking Protein Phosphatase 6 in keratinocytes are predisposed to psoriasis-like skin inflammation, with an inordinate urea cycle and enhanced oxidative phosphorylation that supports hyperproliferation. This phenotype is mediated by increased Arginase-1 production resulting from CCAAT/enhancer-binding protein beta activation. Single-cell RNA-seq of the psoriatic epidermis revealed that the rate-limiting enzyme for Arginine biosynthesis, Argininosuccinate synthetase 1, maintains the Arginine pool, which is indispensable for immune responses. Accumulated polyamines branched from the urea cycle promote endosomal Tlr7-dependent self-RNA sensing by myeloid dendritic cells. This process is achieved with the assistance of an RNA-binding peptide that originates from the heterogeneous nuclear ribonucleoprotein A1, a probable autoantigen in psoriasis. Finally, targeting urea cycle wiring with an arginase inhibitor markedly improved skin inflammation in murine and non-human primate models of psoriasis. Our findings suggest that urea cycle alteration and excessive polyamine production by psoriatic keratinocytes promote self-RNA sensing by dendritic cells, which links the hyperproliferation of stationary cells with innate-immune activation in an auto-inflammatory condition.
Nonalcoholic fatty liver disease is associated with decreased hepatocyte mitochondrial respiration, but not mitochondrial number
Authors: Sinton MC , Ripolles J Meseguer , Villarin B Lucendo , Lyall MJ , Carter RN , Morton NM , Hay DC , Drake AJ
Published: March 2020

Nonalcoholic fatty liver disease (NAFLD) is currently the most prevalent form of liver disease worldwide. This term covers a spectrum of pathologies, from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH). As the disease progresses, NASH can develop into cirrhosis and hepatocellular carcinoma. However, the underlying mechanisms and the factors which predispose an individual to disease progression remain poorly understood. Whilst NAFLD appears to be associated with mitochondrial dysfunction, it is unclear whether this is due to respiratory impairment, changes in mitochondrial mass, or mitochondrial fragmentation. Using a human pluripotent stem cell-based model of NAFLD we show that exposure to lactate, pyruvate and octanoic acid results in the development of macrovesicular steatosis. We do not observe changes in mitochondrial mass or fragmentation but do find decreases in maximal respiration and reserve capacity, suggesting impairment in the electron transport chain (ETC). Taken together, these findings indicate that the development of macrovesicular steatosis in NAFLD may be linked to the impairment of the ETC in mitochondria.
MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas
Authors: Oldrini Barbara , Vaquero-Siguero Nuria , Mu Quanhua , Kroon Paula , Zhang Ying , Galán-Ganga Marcos , Bao Zhaoshi , Wang Zheng , Liu Hanjie , Sa Jason K , Zhao Junfei , Kim Hoon , Rodriguez-Perales Sandra , Nam Do-Hyun , Verhaak Roel GW , Rabadan Raul , Jiang Tao , Wang Jiguang , Squatrito Massimo
Published: March 2020

Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion.MGMTpromoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carriesMGMTgenomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of theseMGMTrearrangements in glioma cells and demonstrated that theMGMTgenomic rearrangements contribute to TMZ resistance bothin vitroandin vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.
Disease Risk Analysis in sea turtles: A baseline study to inform conservation efforts
Authors: Mashkour Narges , Jones Karina , Hipolito Teresa Valerio , Kophamel Sara , Ahasan Shamim , Walker Grant , Jakob-Hoff Richard , Whittaker Maxine , Hamann Mark , Bell Ian , Elliman Jennifer , Owens Leigh , Saladin Claire , Crespo-Picazo Jose Luis , Gardner Brett , Loganathan Aswini Leela , Bowater Rachel , Young Erina , Barnes Andrew , Robinson David , Baverstock Warren , Blyde David , March Duan , Eghbali Maryam , Mohammadi Maryam , Freggi Daniela , Giliam Jane , Hale Mike , Nicolle Nicholas , Spiby Kevin , Wrobel Daphne , Parga Mariluz , Mobaraki Asghar , Rajakaruna Rupika , Hyland Kevin P. , Read Mark , Ariel Ellen
Published: March 2020

The impact of a range of different threats has resulted in the listing of six out of seven sea turtle species on the IUCN Red List of endangered species. Disease risk analysis (DRA) tools are designed to provide objective, repeatable and documented assessment of the disease risks for a population and measures to reduce these risks through management options. To the best of our knowledge, DRAs have not previously been published for sea turtles, although disease is reported to contribute to sea turtle population decline. Here, a comprehensive list of health hazards is provided for all seven species of sea turtles. The possible risk these hazards pose to the health of sea turtles were assessed and “One Health” aspects of interacting with sea turtles were also investigated. The risk assessment was undertaken in collaboration with more than 30 experts in the field including veterinarians, microbiologists, social scientists, epidemiologists and stakeholders, in the form of two international workshops and one local workshop. The general finding of the DRA was the distinct lack of knowledge regarding a link between the presence of pathogens and diseases manifestation in sea turtles. A higher rate of disease in immunocompromised individuals was repeatedly reported and a possible link between immunosuppression and environmental contaminants as a result of anthropogenic influences was suggested. Society based conservation initiatives and as a result the cultural and social aspect of interacting with sea turtles appeared to need more attention and research. A risk management workshop was carried out to acquire the insights of local policy makers about management options for the risks relevant to Queensland and the options were evaluated considering their feasibility and effectiveness. The sea turtle DRA presented here, is a structured guide for future risk assessments to be used in specific scenarios such as translocation and head-starting programs.
Long-read sequencing to interrogate strain-level variation among adherent-invasiveEscherichia coliisolated from human intestinal tissue
Authors: Wang Jeremy , Bleich Rachel , Zarmer Sandra , Zhang Shiying , Dogan Belgin , Simpson Kenneth W , Arthur Janelle
Published: March 2020

Adherent-invasiveEscherichia coli(AIEC) is a pathovar linked to inflammatory bowel diseases (IBD), especially Crohn’s disease, and colorectal cancer. AIEC are genetically diverse, and in the absence of a universal molecular signature, are defined byin vitrofunctional attributes. The relative ability of difference AIEC strains to colonize, persist, and induce inflammation in an IBD-susceptible host is unresolved. To evaluate strain-level variation among tissue-associatedE. coliin the intestines, we develop a long-read sequencing approach to identify AIEC by strain that excludes host DNA. We use this approach to distinguish genetically similar strains and assess their fitness in colonizing the intestine. Here we have assembled complete genomes using long-read nanopore sequencing for a model AIEC strain, NC101, and seven strains isolated from the intestinal mucosa of Crohn’s disease and non-Crohn’s tissues. We show these strains can colonize the intestine of IBD susceptible mice and induce inflammatory cytokines from cultured macrophages. We demonstrate that these strains can be quantified and distinguished in the presence of 99.5% mammalian DNA and from within a fecal population. Analysis of global genomic structure and specific sequence variation within the ribosomal RNA operon provides a framework for efficiently tracking strain-level variation of closely-relatedE. coliand likely other commensal/pathogenic bacteria impacting intestinal inflammation in experimental settings and IBD patients.
Insulin-like Growth Factor-1 Regulates the Mechanosensitivity of Chondrocytes by Modulating TRPV4
Authors: Trompeter Nicholas , Gardinier Joseph D. , DeBarros Victor , Boggs Mary , Gangadharan Vimal , Cain William J. , Hurd Lauren , Duncan Randall L.
Published: March 2020

Both mechanical and IGF-1 stimulation are required for normal articular cartilage development and maintenance of the extracellular matrix. While much effort has been made to define the signaling pathways associated with these anabolic stimuli, we focused on how these pathways interact to regulate chondrocyte function. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. However, the mechanism by which TRPV4 is mechanically gated or regulated is not clear. In this study we propose that insulin-like growth factor 1 (IGF-1), which is important in regulating matrix production during mechanical load, modulates TRPV4 channel activity. Our studies indicate that IGF-1 reduces hypotonic-induced TRPV4 currents, and intracellular calcium flux by increasing stress fiber formation and apparent cell stiffness. Disruption of F-actin following IFG-1 treatment results in the return of the intracellular calcium response to hypotonic swelling. Furthermore, we highlight that IGF-1 suppresses TRPV4 mediated calcium flux through the MAP7 binding domain (aa. 798-809), where actin binds to the TRPV4 channel. IGF-1 treatment differentially influences the intracellular calcium flux of HEK 293 cells stably expressing either wild-type or mutant (P799L or G800D) TRPV4 during hypotonic challenge. A key down-stream response to mechanical stimulation of chondrocytes is ATP release. Data here indicate that activation of TRPV4 through hypotonic swelling induces ATP release, but this release is greatly reduced with IGF-1 treatment. Taken together this study indicates that IGF-1 modulates TRPV4 channel response to mechanical stimulation by increasing cell stiffness. As chondrocyte response to mechanical stimulation is greatly altered during OA progression, IGF-1 presents as a promising candidate for prevention and treatment of articular cartilage damage.
Capital structure decisions in a period of economic intervention
Authors: Neves Maria Elisabete , Serrasqueiro Zélia , Dias António , Hermano Cristina
Published: March 2020

Purpose

This paper aims to analyse the Portuguese companies’ determinants of capital structure. To reach this objective, the authors used data from 37 non-financial Portuguese large enterprises and from 4,233 non-financial small and medium enterprises for the period 2010-2016. Additionally, the authors selected a sub-period from 2010 to 2014 for a deeper understanding of the impact of the sovereign debt crisis and the Economic Adjustment Programme of Troika on the capital structure of those companies.

Design/methodology/approach

Three dependent variables were tested according to debt maturity, and a dynamic panel data model, namely, the generalised method of moments system estimator, was used to test the formulated research hypotheses following Arellano and Bover (1995) and Blundell and Bond (1998) to capture the dynamic nature of the firm’s capital structure decisions.

Findings

In general, the results point out that the capital structure decisions depend on a set of firm-specific factors, and that the effects of the determinants of the debt maturity ratios differ according to the type of firm, i.e. large/small firms, and the economic cycle.

Originality/value

To the best of the authors’ knowledge, this is the first study that has been carried out in Portugal by using two samples of large and small companies for analysing the effects of the Economic Adjustment Programme of Troika on the capital structure of companies. The authors seek to understand which type of companies suffered more because of the effects of the Economic Adjustment Programme of Troika during this period, and which are the capital structure determinants that present greater change. Contrary to what might be expected, large companies are the firms that suffer most from the Economic Adjustment Programme. Probably, because these companies are the most immediate, most scrutinised and those that must show abroad that the bank did not fund them in the long term, because of the imposition and limits to grant credit faced by the banks themselves.
Content marketing capability building: a conceptual framework
Authors: Ho John , Pang Christopher , Choy Crisann
Published: March 2020

Purpose

The purpose of this study is to develop a conceptual framework that identifies engaging CM practices, specifically how compelling content is created. Content marketing (CM) is fast becoming a key pillar in a company's marketing mix. It is also a requisite for companies seeking to modernise their marketing practices through digitalisation to enhance online branding. However, overlapping definitions and interchangeable terms arising from different perspectives and methodological practices confound what exactly constitutes CM. Although CM is generally accepted as sharing brand content via owned media to gain earned media, a strategic approach, based on evidence-driven research, is needed to navigate through the overwhelming confusion so that companies can better plan and implement CM.

Design/methodology/approach

This paper addresses the scarcity of work with regard to CM practices in Asia. To address this research gap, the study examines content creation practices of five successful companies, based in Singapore, through case studies, interviews and content analyses, to propose a CM capability development framework.

Findings

The findings point to the need for content creation to align with brand values and value creation to create and socialise compelling content for positive impact. Content created for audiences and marketed by brands can generate value when it is consumed and shared. The paper also provided much needed clarity in terms of how CM capability can be gained to minimise costly trial and error.

Research limitations/implications

The study is limited to companies operating in Asia. The framework will require implementation in other regions. Another limitation of the study was that it did not extend to how consumers responded to CM posts. This is an area for further research that can help validate the proposed framework.

Practical implications

The analytical framework adopted in this study can also be used as a functional CM model for marketing managers to construct better CM strategies and informed standards of practice by growing capabilities.

Social implications

CM is also a requisite for companies seeking to modernise their marketing practices through digitalisation to enhance online branding, particularly for small- and medium-sized companies.

Originality/value

This paper addresses the scarcity of work with regard to CM practices in Asia.
Species detection and delineation in the marine planktonic diatoms Chaetoceros and Bacteriastrum through metabarcoding: making biological sense of haplotype diversity
Authors: Gaonkar Chetan C. , Piredda Roberta , Sarno Diana , Zingone Adriana , Montresor Marina , Kooistra Wiebe H. C. F.
Published: March 2020

High‐throughput sequencing (HTS) metabarcoding is commonly applied to assess phytoplankton diversity. Usually, haplotypes are grouped into operational taxonomic units (OTUs) through clustering, whereby the resulting number of OTUs depends on chosen similarity thresholds. We applied, instead, a phylogenetic approach to infer taxa among 18S rDNA V4‐metabarcode haplotypes gathered from 48 time‐series samples using the marine planktonic diatoms Chaetoceros and Bacteriastrum as test case. The 73 recovered taxa comprised both solitary haplotypes and polytomies, the latter composed each of a highly abundant, dominant haplotype and one to several minor, peripheral haplotypes. The solitary and dominant haplotypes usually matched reference sequences, enabling species assignation of taxa. We hypothesise that the super‐abundance of reads in dominant haplotypes results from the homogenization effect of concerted evolution. Reads of populous peripheral haplotypes and dominant haplotypes show comparable distribution patterns over the sample dates, suggesting that they are part of the same population. Many taxa revealed marked seasonality, with closely related ones generally showing distinct periodicity, whereas others occur year‐round. Phylogenies inferred from metabarcode haplotypes enable delineation of biologically meaningful taxa, whereas OTUs resulting from clustering algorithms often deviate markedly from such taxa.
Changes in texture, composition and sensory characteristics of Camembert cheese made from a mixture of goat milk and cow milk during ripening
Authors: Gebreyowhans Solomon , Zhang Shuwen , Pang Xiaoyang , Yang Baoyu , Wang Tong , Wu Zheng , Lu Jing , Lv Jiaping
Published: March 2020

The study was conducted to evaluate the nutritional, textural and sensory characteristics of Camembert cheese made from goat milk, cow milk and their blends. The type of milk used affected yield, physicochemical properties and fatty acid profile of the cheeses. The percentages of C6:0, C8:0 and C10:0 acids were higher in the cheeses containing ≥ 75% goat milk. The sensory evaluation results showed differences in texture, colour, aroma and flavour among the cheeses. Cheeses made with the mixture of cow and goat milk particularly 50% goat milk mixed with 50% cow milk (50G:50C) maintained particular positive nutritional characteristics especially with respect to the mineral contents, fatty acids and consumer acceptability.
Inhibition of histone acetyltransferase GCN5 extends lifespan in both yeast and human cell lines
Authors: Huang Boyue , Zhong Dandan , Zhu Jie , An Yongpan , Gao Miaomiao , Zhu Shuai , Dang Weiwei , Wang Xin , Yang Baoxue , Xie Zhengwei
Published: March 2020

Histone acetyltransferases (HATs) are important enzymes that transfer acetyl groups onto histones and thereby regulate both gene expression and chromosomal structures. Previous work has shown that the activation of sirtuins, which are histone deacetylases, can extend lifespan. This suggests that inhibiting HATs may have a similar beneficial effect. In the present study, we utilized a range of HAT inhibitors or heterozygous Gcn5 and Ngg1 mutants to demonstrate marked yeast life extension. In human cell lines, HAT inhibitors and selective RNAi‐mediated Gcn5 or Ngg1 knockdown reduced the levels of aging markers and promoted proliferation in senescent cells. Furthermore, this observed lifespan extension was associated with the acetylation of histone H3 rather than that of H4. Specifically, it was dependent upon H3K9Ac and H3K18Ac modifications. We also found that the ability of caloric restriction to prolong lifespan is Gcn5‐, Ngg1‐, H3K9‐, and H3K18‐dependent. Transcriptome analysis revealed that these changes were similar to those associated with heat shock and were inversely correlated with the gene expression profiles of aged yeast and aged worms. Through a bioinformatic analysis, we also found that HAT inhibition activated subtelomeric genes in human cell lines. Together, our results suggest that inhibiting the HAT Gcn5 may be an effective means of increasing longevity.
Plasma proteomic signature of the risk of developing mobility disability: A 9‐year follow‐up
Authors: Osawa Yusuke , Semba Richard D. , Fantoni Giovanna , Candia Julián , Biancotto Angélique , Tanaka Toshiko , Bandinelli Stefania , Ferrucci Luigi
Published: March 2020

Introduction

Mobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data‐driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability in community‐dwelling older adults without mobility disability at baseline.

Methods

We investigated 660 women and men, aged 71.9 ± 6.0 (60–94) years, who participated in the Invecchiare in Chianti, “Aging in the Chianti Area” study and completed the 400‐m walk at fast pace (400‐m walk) at enrollment. Median follow‐up time was 8.57 [interquartile, 3.20–9.08] years. SOMAscan technology was used to measure 1,301 plasma proteins at enrollment. The incident of mobility disability was defined as inability to complete the 400‐m walk. Protein‐specific Cox proportional hazard model was adjusted for sex, age, and other important covariates.

Results

Plasma levels of 75 proteins predicted mobility disability (p < .05). Significant proteins were enriched for the KEGG “PI3K‐Akt signaling,” “phagosomes,” and “cytokine–cytokine receptor interaction” pathways. After multiple comparison adjustment, plasma cathepsin S (CTSS; hazard ratio [HR] 1.33, 95% CI: 1.17, 1.51, q = 0.007), growth/differentiation factor 15 (GDF15; HR: 1.45, 95% CI: 1.23, 1.72, q = 0.007), and thrombospondin‐2 (THBS2; HR: 1.44, 95% CI: 1.22, 1.69, q = 0.007) remained significantly associated with high risk of losing mobility.

Conclusion

CTSS, GDF15, and THBS2 are novel blood biomarkers associated with new mobility disability in community‐dwelling individuals. Overall, our analysis suggests that cellular senescence and inflammation should be targeted for prevention of mobility disability.
Antenatal models of care for women with gestational diabetes mellitus: Vignettes from an international meeting
Authors: Sina Maryam , Cade Thomas J. , Flack Jeff , Nolan Christopher J. , Rajagopal Rohit , Wong Vincent , Burcher Linda , Barry Alison , Gianatti Emily , McCarthy Ana , McNamara Catharine , Mickelson Marina , Hughes Ruth , Jones Tara , Latino Cathy , McIntyre David , Price Sarah , Simmons David
Published: March 2020

Background

Gestational diabetes (GDM) is one of the commonest pregnancy complications and is placing an increasing burden on diabetes and obstetric resources.

Aims

To describe different antenatal models of care that have developed to address the increasing proportion of pregnancies complicated by GDM.

Materials and Methods

Narrative review with thematic analysis from 15 volunteer antenatal diabetes in pregnancy services from Australia and New Zealand identified through a national diabetes organisation. Main outcomes were approaches to patient education, medical nutrition therapy (MNT), ongoing management and escalation of therapy for women with GDM.

Results

All clinics provided at least one group education and one MNT session within 1–2 weeks of GDM diagnosis. Women from culturally and linguistically diverse communities usually required 1:1 education. Ongoing management of women with GDM was through either all women being seen in the GDM clinic, a step‐up approach (ongoing management by the primary antenatal team with diabetes team referral if self‐blood glucose monitoring (SBGM) or insulin therapy dosage criteria are reached) or step‐down approach (ongoing management by the diabetes team with step‐down to the primary antenatal team if SBGM criteria are reached). Telehealth was used to reduce the burden of clinic attendance, particularly in rural areas.

Conclusions

Increasing numbers, earlier diagnoses, the need to provide care to women in rural, remote areas, and cultural/language differences, have generated a range of different antenatal models of care, allowed better workload accommodation and probably reduced costs. Randomised controlled trials of different models of care, with associated health economic analyses, are urgently needed.
Novel prognostic score for outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with metachronous peritoneal carcinomatosis
Authors: Chin Ken Min , Tan Grace Hwei Ching , Chia Claramae Shulyn , Ong Johnny Chin Ann , Teo Melissa Ching Ching
Published: March 2020

Background

This study aimed to determine pre‐ and peri‐operative parameters with significant predictive value for post‐operative outcomes in patients with recurrent colorectal cancer presenting as peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC), and to develop a novel prognostic scoring system for prediction of survival outcomes.

Methods

A single‐institution review of prospectively collected data from all patients who underwent CRS‐HIPEC between October 2005 and October 2017 was conducted. Univariate and multivariate analyses were used to identify significant parameters for prediction of post‐CRS‐HIPEC disease‐free survival and overall survival (OS).

Results

A total of 278 patients underwent CRS‐HIPEC, of whom 72 were for peritoneal carcinomatosis from recurrent colorectal cancer. Disease‐free interval (DFI; P = 0.006), peritoneal cancer index (PCI; P = 0.001) and left upper quadrant disease (P = 0.023) were significant independent predictors of 3‐year OS. DFI (0.007), PCI (P < 0.001) and intraoperative blood loss (BL; P = 0.001) were significant independent predictors of 5‐year OS. PCI and BL were significant independent predictors of both 3‐year (P = 0.026, PCI; P = 0.009, BL) and 5‐year (P = 0.002, PCI; P = 0.011, BL) disease‐free survival. Predictive models were developed for risk stratification of OS.

Conclusion

PCI, DFI, left upper quadrant disease and BL have significant predictive value for post‐CRS‐HIPEC outcomes. Risk stratification models allow for more prudent patient selection and ultimately more accurate prognostication of post‐operative outcomes.
Complex care pathways for children with multiple referrals demonstrated in a retrospective population‐based study
Authors: Heggestad Torhild , Greve Gottfried , Skilbrei Birger , Elgen Irene
Published: March 2020

Aim

To identify children with complex medical needs by examining their patterns of hospital care.

Methods

We conducted a retrospective population‐based study on 18 577 patients aged 6‐12 years from the Haukeland University Hospital register over a 3‐year period (from 2013 to 2015). Data were structured to examine the temporal patterns and sequences of referrals, care episodes and diagnoses, including flow across medical specialties.

Results

Over a third of patients had repeated referrals, and 14.9% of all had three or more. Furthermore, 9.3% of patients were referred to both somatic and mental healthcare services. Patients with such combined referrals had a higher number of referrals as well as a higher number of different diagnoses. Overall, there was a high frequency of non‐specific diagnoses, and 34.8% of patients still had a non‐specific main diagnosis at the end of their hospital contact.

Conclusion

This study demonstrates an increased risk for complex care pathways in children with multiple referrals. Interdisciplinary patterns of referrals were relatively common, particularly for patients in mental health care. These findings highlight the importance of developing interdisciplinary‐based approaches for patients with complex complaints.