bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lectin Chaperone Calnexin Is Involved in the Endoplasmic Reticulum Stress Response by Regulating Ca
2+
Homeostasis in Aspergillus nidulans
Authors: Zhang Shenghua , Zheng Hailin , Chen Qiuyi , Chen Yuan , Wang Sha , Lu Ling , Zhang Shizhu 
Published: May 2017

ABSTRACT

The Ca
2+
-mediated signaling pathway is crucial for environmental adaptation in fungi. Here we show that calnexin, a molecular chaperone located in the endoplasmic reticulum (ER), plays an important role in regulating the cytosolic free calcium concentration ([Ca
2+
]
c
) in
Aspergillus nidulans
. Inactivation of calnexin (ClxA) in
A. nidulans
caused severe defects in hyphal growth and conidiation under ER stress caused by the ER stress-inducing agent dithiothreitol (DTT) or high temperature. Importantly, defects in the Δ
clxA
mutant were restored by the addition of extracellular calcium. Furthermore, the CchA/MidA complex (the high-affinity Ca
2+
channels), calcineurin (calcium/calmodulin-dependent protein phosphatase), and PmrA (secretory pathway Ca
2+
ATPase) were required for extracellular calcium-based restoration of the DTT/thermal stress sensitivity in the Δ
clxA
mutant. Interestingly, the Δ
clxA
mutant exhibited markedly reduced conidium formation and hyphal growth defects under the low-calcium condition, which is similar to defects caused by mutations in MidA/CchA. Moreover, the phenotypic defects were further exacerbated in the Δ
clxA
Δ
midA
Δ
cchA
mutant, which suggested that ClxA and MidA/CchA are both required under the calcium-limiting condition. Using the calcium-sensitive photoprotein aequorin to monitor [Ca
2+
]
c
in living cells, we found that ClxA and MidA/CchA complex synergistically coordinate transient increase in [Ca
2+
]
c
in response to extracellular calcium. Moreover, ClxA, in particular its luminal domain, plays a role in mediating the transient [Ca
2+
]
c
in response to DTT-induced ER stress in the absence of extracellular calcium, indicating ClxA may mediate calcium release from internal calcium stores. Our findings provide new insights into the role of calnexin in the regulation of calcium-mediated response in fungal ER stress adaptation.

IMPORTANCE
Calnexin is a well-known molecular chaperone conserved from yeast to humans. Although it contains calcium binding domains, little is known about the role of calnexin in Ca
2+
regulation. In this study, we demonstrate that calnexin (ClxA) in the filamentous fungus
Aspergillus nidulans
, similar to the high-affinity calcium uptake system (HACS), is required for normal growth and conidiation under the calcium-limiting condition. The ClxA dysfunction decreases the transient cytosolic free calcium concentration ([Ca
2+
]
c
) induced by a high extracellular calcium or DTT-induced ER stress. Our findings provide the direct evidence that calnexin plays important roles in regulating Ca
2+
homeostasis in addition to its role as a molecular chaperone in fungi. These results provide new insights into the roles of calnexin and expand knowledge of fungal stress adaptation.
Prevalence and Genomic Characterization of Escherichia coli O157:H7 in Cow-Calf Herds throughout California
Authors: Worley Jay N. , Flores Kristopher A. , Yang Xun , Chase Jennifer A. , Cao Guojie , Tang Shuai , Meng Jianghong , Atwill Edward R. 
Published: May 2017

ABSTRACT

Escherichia coli
serotype O157:H7 is a zoonotic food- and waterborne bacterial pathogen that causes a high hospitalization rate and can cause life-threatening complications. Increasingly,
E. coli
O157:H7 infections appear to originate from fresh produce. Ruminants, such as cattle, are a prominent reservoir of
E. coli
O157:H7 in the United States. California is one of the most agriculturally productive regions in the world for fresh produce, beef, and milk. The close proximity of fresh produce and cattle presents food safety challenges on a uniquely large scale. We performed a survey of
E. coli
O157:H7 on 20 farms in California to observe the regional diversity and prevalence of
E. coli
O157:H7. Isolates were obtained from enrichment cultures of cow feces. Some farms were sampled on two dates. Genomes from isolates were sequenced to determine their relatedness and pathogenic potential.
E. coli
O157:H7 was isolated from approximately half of the farms. The point prevalence of
E. coli
O157:H7 on farms was highly variable, ranging from zero to nearly 90%. Within farms, generally one or a few lineages were found, even when the rate of isolation was high. On farms with high isolation rates, a single clonal lineage accounted for most of the isolates. Farms that were visited months after the first visit might have had the same lineages of
E. coli
O157:H7. Strains of
E. coli
O157:H7 may be persistent for months on farms.

IMPORTANCE
This survey of 20 cow-calf operations from different regions of California provides an in depth look at resident
Escherichia coli
O157:H7 populations at the molecular level.
E. coli
O157:H7 is found to have a highly variable prevalence, and with whole-genome sequencing, high prevalences in herds were found to be due to a single lineage shed from multiple cows. Few repeat lineages were found between farms in this area; therefore, we predict that
E. coli
O157:H7 has significant diversity in this area beyond what is detected in this survey. All isolates from this study were found to have pathogenic potential based on the presence of key virulence gene sequences. This represents a novel insight into pathogen diversity within a single subtype and will inform future attempts to survey regional pathogen populations.
Translation, adaptation and validation of two versions of the Chronic Liver Disease Questionnaire in Malaysian patients for speakers of both English and Malay languages: a cross-sectional study
Authors: Khairullah Shasha , Mahadeva Sanjiv 
Published: May 2017

ObjectiveWe aimed to adapt, translate and validate the Chronic Liver Disease Questionnaire (CLDQ) in Malaysian patients with chronic liver diseases of various aetiologies.SettingTertiary level teaching institution in Malaysia.ParticipantsThe validation process involved 211 adult patients (English language n=101, Malay language n=110) with chronic liver disease. Characteristics of the study subjects were as follows: mean (SD) age was 56 (12.8) years, 58.3% were male and 41.7% female. The inclusion criteria were patients 18 years or older with chronic hepatitis and/or liver cirrhosis of any aetiology. The exclusion criteria were as follows: presence of hepatic encephalopathy, ongoing treatment with interferon and presence of other chronic conditions that have an impact on health-related quality of life (HRQOL).MethodsA cross-sectional study was conducted. Cultural adaptation of the English version of the CLDQ was performed, and a Malay version was developed following standard forward–backward translation by independent native speakers. Psychometric properties of both versions were determined by assessing their internal consistency, test–retest reliability and discriminant and convergent validity.ResultsCronbach’s alpha for internal consistency across the various domains of the CLDQ was 0.95 for the English version and 0.92 for the Malay version. Test–retest analysis showed excellent reliability with an intraclass correlation coefficient of 0.89 for the English version and 0.93 for the Malay version. The average scores of both the English and Malay versions of the CLDQ demonstrated adequate discriminant validity by differentiating between non-cirrhosis (English 6.3, Malay 6.1), compensated cirrhosis (English 5.6, Malay 6.0) and decompensated cirrhosis (English 5.1, Malay 4.9) (p<0.001). Convergent validity showed that correlation was fair between the English (ρ=0.59) and Malay (p=0.47) CLDQ versions with the EQ-5D, a generic HRQOL instrument.ConclusionThe English and Malay versions of the CLDQ are reliable and valid disease-specific instruments for assessing HRQOL in Malaysian patients with chronic liver disease.
Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial
Authors: Xu Huajun , Wang Hui , Guan Jian , Yi Hongliang , Qian Yingjun , Zou Jianyin , Xia Yunyan , Fu Yiqun , Li Xinyi , Jiao Xiao , Huang Hengye , Dong Pin , Yu Ziwei , Yang Jun , Xiang Mingliang , Li Jiping , Chen Yanqing , Wang Peihua , Sun Yizhou , Li Yuehua , Zheng Xiaojian , Jia Wei , Yin Shankai 
Published: May 2017

ObjectivesMany clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment.Methods/designThis study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences.Trial registration numberNCT02886156; pre-results.
Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study
Authors: Primavera Diego , Manchia Mirko , Deriu Luca , Tusconi Massimo , Collu Roberto , Scherma Maria , Fadda Paola , Fratta Walter , Carpiniello Bernardo 
Published: May 2017

IntroductionBrain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments.Methods and analysisLongitudinal assessment of BDNF in Sardinian psychotic patients (LABSP) is a 24-month observational prospective cohort study. Patients with SAD will be recruited at the Psychiatry Research Unit of the Department of Medical Science and Public Health, University of Cagliari and University of Cagliari Health Agency, Cagliari, Italy. We will collect BDNF serum levels as well as sociodemographic, psychopathological and neurocognitive measures. Structured, semistructured and self-rating assessment tools, such as the Positive and Negative Syndrome Scale for psychopathological measures and the Brief Assessment of Cognition in Schizophrenia for cognitive function, will be used.Ethics and disseminationThis study protocol was approved by the University of Cagliari Health Agency Ethics Committee (NP2016/5491). The study will be conducted in accordance with the principles of good clinical practice, in the Declaration of Helsinki in compliance with the regulations. Participation will be voluntary and written informed consent will be obtained for each participant upon entry into the study. We plan to disseminate the results of our study through conference presentations and publication in international peer-reviewed journals. Access to raw data will be available in anonymised form upon request to the corresponding author.
Chest pain and shortness of breath in cardiovascular disease: a prospective cohort study in UK primary care
Authors: Barnett Lauren A , Prior James A , Kadam Umesh T , Jordan Kelvin P 
Published: May 2017

ObjectiveTo determine characteristics associated with monthly chest pain and shortness of breath (SoB) during activity in cardiovascular disease (CVD) and trajectories of these symptoms over 10 months.Study design and settingBaseline questionnaire was sent to patients aged ≥40 years from 10 UK general practices. Responders were sent monthly questionnaires for 10 months. For patients with CVD (ischaemic heart disease and heart failure), the association of sociodemographic characteristics, pain elsewhere and anxiety and depression with monthly reports of chest pain and SoB during activity were determined using multilevel, multinomial logistic regression. Common symptom trajectories were determined using dual trajectory latent class growth analysis.Results661 patients with CVD completed at least 5 monthly questionnaires. Multiple other pain sites (relative risk ratio: 4.03; 95% CI 1.64 to 9.91) and anxiety or depression (relative risk ratio: 3.31; 95% CI 1.89 to 5.79) were associated with reporting weekly chest pain. Anxiety or depression (relative risk ratio: 4.10; 95% CI 2.72 to 6.17), obesity (relative risk ratio: 2.53; 95% CI 1.49 to 4.30), older age (80+: relative risk ratio: 2.51; 95% CI 1.19 to 5.26), increasing number of pain sites (4+: relative risk ratio: 4.64; 95% CI 2.35 to 9.18) and female gender (relative risk ratio: 1.81; 95% CI 1.20 to 2.75) were associated with reporting weekly SoB. Eight symptom trajectories were identified, with SoB symptoms more common than chest pain.ConclusionsPotentially modifiable characteristics are associated with the experience of chest pain and SoB. Identified symptom trajectories may facilitate tailored care to improve outcomes in patients with CVD.
Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease
Authors: Grander Christoph , Adolph Timon E , Wieser Verena , Lowe Patrick , Wrzosek Laura , Gyongyosi Benedek , Ward Doyle V , Grabherr Felix , Gerner Romana R , Pfister Alexandra , Enrich Barbara , Ciocan Dragos , Macheiner Sophie , Mayr Lisa , Drach Matthias , Moser Patrizia , Moschen Alexander R , Perlemuter Gabriel , Szabo Gyongyi , Cassard Anne Marie , Tilg Herbert 
Published: May 2017

ObjectiveAlcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD.DesignThe intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A. muciniphila abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of A. muciniphila on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed.ResultsPatients with ASH exhibited a decreased abundance of faecal A. muciniphila when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in A. muciniphila abundance. Ethanol-induced intestinal A. muciniphila depletion could be restored by oral A. muciniphila supplementation. Furthermore, A. muciniphila administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. A. muciniphila also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically ameliorated hepatic injury and neutrophil infiltration.ConclusionEthanol exposure diminishes intestinal A. muciniphila abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. A. muciniphila promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from A. muciniphila supplementation.
Active low-angle normal faults in the deep water Santos Basin, offshore Brazil: a geomechanical analogy between salt tectonics and crustal deformation
Authors: Fetter Marcos , Moraes Anderson , Muller Andre 
Published: May 2017

Abstract
We provide a structural analysis and propose a geomechanical model for an extensional fault system observed in seismic data from the deep water Santos Basin, offshore Brazil. The system includes low-angle normal faults (LANFs) associated with underlying listric faults and salt rollers. The LANFs cut through shallow sedimentary successions up to the seafloor, reaching displacements of 1 km during the last 5 myr, at least one order of magnitude larger than the displacement of the coeval Andersonian high-angle normal faults. We suggest that the LANFs were produced by clockwise rotation of the stress field caused by the presence of salt intruded along the footwall of the main listric normal faults of the extensional system. Numerical models indicate that the proposed geomechanical model can be attained with strain weakening and widespread plastic yielding along the main normal faults. We suggest that the studied LANFs are related to salt flow in the same way that the LANFs described in regional extensional provinces are related to flow of either the lower crust or the mantle. The rheological analogy is remarkable and therefore we suggest that this work will contribute to the solution of the LANFs paradox.
Reconstructing Palaeozoic and Mesozoic tectonic evolution of Novaya Zemlya: combing geochronology and thermochronology
Authors: Zhang Xiaojing , Pease Victoria , Carter Andrew , Scott Robert 
Published: May 2017

Abstract
To better understand the sediment provenance and exhumation history of Novaya Zemlya's Mesozoic fold–thrust belt, we apply detrital zircon U–Pb geochronology combined with zircon and apatite fission track analyses to samples from the Precambrian to late Permian siliciclastic successions of the southern and northern islands. The Silurian to early Devonian samples are dominated by zircons (1.14–0.9 Ga) characteristic of the Sveconorwegian Orogen. Zircon fission track ages for individual units are older than their stratigraphic ages and consistent with single-age population distributions. The zircon fission track results document no annealing after deposition and therefore preserve provenance information, which indicates that the source rock(s) of each sample most likely experienced the same thermal event. The results support the erosion and recycling of Sveconorwegian-aged zircon from the Fennoscandian shield during Caledonian orogenesis to the Barents Sea Shelf and Novaya Zemlya. Apatite fission track ages and thermal modelling identify a rapid cooling event at 220–210 Ma, consistent with late Triassic deformation on Novaya Zemlya.
Normal and Cancerous Tissues Release Extrachromosomal Circular DNA (eccDNA) into the Circulation
Authors: Kumar Pankaj , Dillon Laura W. , Shibata Yoshiyuki , Jazaeri Amir A. , Jones David R. , Dutta Anindya 
Published: May 2017

Abstract
Cell-free circulating linear DNA is being explored for noninvasive diagnosis and management of tumors and fetuses, the so-called liquid biopsy. Previously, we observed the presence of small extrachromosomal circular DNA (eccDNA), called microDNA, in the nuclei of mammalian tissues and cell lines. Now, we demonstrate that cell-free microDNA derived from uniquely mapping regions of the genome is detectable in plasma and serum from both mice and humans and that they are significantly longer (30%–60% &gt;250 bases) than cell-free circulating linear DNA (∼150 bases). Tumor-derived human microDNA is detected in the mouse circulation in a mouse xenograft model of human ovarian cancer. Comparing the microDNA from paired tumor and normal lung tissue specimens reveals that the tumors contain longer microDNA. Consistent with human cancers releasing microDNA into the circulation, serum and plasma samples (12 lung and 11 ovarian cancer) collected prior to surgery are enriched for longer cell-free microDNA compared with samples from the same patient obtained several weeks after surgical resection of the tumor. Thus, circular DNA in the circulation is a previously unexplored pool of nucleic acids that could complement miRNAs and linear DNA for diagnosis and for intercellular communication.
Implications: eccDNA derived from chromosomal genomic sequence, first discovered in the nuclei of cells, are detected in the circulation, are longer than linear cell-free DNA, and are released from normal tissue and tumors into the circulation. Mol Cancer Res; 15(9); 1197–205. ©2017 AACR.
Safety of Outpatient Initiation of Disopyramide for Obstructive Hypertrophic Cardiomyopathy Patients
Authors: Adler Arnon , Fourey Dana , Weissler‐Snir Adaya , Hindieh Waseem , Chan Raymond H. , Gollob Michael H. , Rakowski Harry 
Published: May 2017

Background
Disopyramide is effective in ameliorating symptoms in patients with hypertrophic cardiomyopathy; however, its potential for proarrhythmic effect has raised concerns about its use in the ambulatory setting. The risk of initiating disopyramide in this manner has never been evaluated.

Methods and Results

All charts of patients seen in the outpatient hypertrophic cardiomyopathy clinic between 2010 and 2014 were screened for initiation of disopyramide and data were extracted. Disopyramide in our clinic is usually initiated at a dose of 300 mg daily and titrated during follow‐up. A total of 2015 patients were seen in the clinic, including 168 who were started on disopyramide. There were no cardiac events within 3 months of disopyramide initiation. During long‐term follow‐up (255 patient‐years; mean, 447 days; interquartile range, 201–779), only 2 patients developed cardiac events (syncope of unknown cause in both). Thirty‐eight patients (23%) developed side effects of disopyramide and 18 (11%) stopped the drug because of these side effects. Of the patients continuing disopyramide long term, 63% remained free of septal reduction interventions at end of follow‐up. Disopyramide at a dose of 300 mg prolonged the mean
QT
c interval by 19±23 ms; however, increasing the dose to 600 mg had no further significant effect.

Conclusions

Initiation of disopyramide in the outpatient setting is safe and the risk of subsequent sudden cardiac death is low. Because of its
QT
‐prolonging effect, precautions may be necessary in patients at higher risk of torsades de pointes.