bluuebunny/crossref_metadata_2025_split huggingface dataset:
How, When, and Where Relic DNA Affects Microbial Diversity
Authors: Lennon J. T. , Muscarella M. E. , Placella S. A. , Lehmkuhl B. K. 
Published: June 2018

ABSTRACT
Extracellular or “relic” DNA is one of the largest pools of nucleic acids in the biosphere. Relic DNA can influence a number of important ecological and evolutionary processes, but it may also affect estimates of microbial abundance and diversity, which has implications for understanding environmental, engineered, and host-associated ecosystems. We developed models capturing the fundamental processes that regulate the size and composition of the relic DNA pools to identify scenarios leading to biased estimates of biodiversity. Our models predict that bias increases with relic DNA pool size, but only when the species abundance distributions (SADs) of relic and intact DNA are distinct from one another. We evaluated our model predictions by quantifying relic DNA and assessing its contribution to bacterial diversity using 16S rRNA gene sequences collected from different ecosystem types, including soil, sediment, water, and the mammalian gut. On average, relic DNA made up 33% of the total bacterial DNA pool but exceeded 80% in some samples. Despite its abundance, relic DNA had a minimal effect on estimates of taxonomic and phylogenetic diversity, even in ecosystems where processes such as the physical protection of relic DNA are common and predicted by our models to generate bias. Our findings are consistent with the expectation that relic DNA from different taxa degrades at a constant and equal rate, suggesting that it may not fundamentally alter estimates of microbial diversity.

IMPORTANCE
The ability to rapidly obtain millions of gene sequences and transcripts from a range of environments has greatly advanced understanding of the processes that regulate microbial communities. However, nucleic acids extracted from complex samples do not come only from viable microorganisms. Dead microorganisms can generate large pools of relic DNA that distort insight into the ecology and evolution of microbial systems. Here, we develop a conceptual and quantitative framework for understanding how relic DNA influences the structure of microbiomes. Our theoretical models and empirical results demonstrate that a large relic DNA pool does not automatically lead to biased estimates of microbial diversity. Rather, relic DNA effects emerge in combination with microscale processes that alter the commonness and rarity of sequences found in heterogeneous DNA pools.
The Pearling Transition Provides Evidence of Force-Driven Endosomal Tubulation during
Salmonella
Infection
Authors: Gao Yunfeng , Spahn Christoph , Heilemann Mike , Kenney Linda J. 
Published: June 2018

ABSTRACT

Bacterial pathogens exploit eukaryotic pathways for their own end. Upon ingestion,
Salmonella enterica
serovar Typhimurium passes through the stomach and then catalyzes its uptake across the intestinal epithelium. It survives and replicates in an acidic vacuole through the action of virulence factors secreted by a type three secretion system located on
Salmonella
pathogenicity island 2 (SPI-2). Two secreted effectors, SifA and SseJ, are sufficient for endosomal tubule formation, which modifies the vacuole and enables
Salmonella
to replicate within it. Two-color, superresolution imaging of the secreted virulence factor SseJ and tubulin revealed that SseJ formed clusters of conserved size at regular, periodic intervals in the host cytoplasm. Analysis of SseJ clustering indicated the presence of a pearling effect, which is a force-driven, osmotically sensitive process. The pearling transition is an instability driven by membranes under tension; it is induced by hypotonic or hypertonic buffer exchange and leads to the formation of beadlike structures of similar size and regular spacing. Reducing the osmolality of the fixation conditions using glutaraldehyde enabled visualization of continuous and intact tubules. Correlation analysis revealed that SseJ was colocalized with the motor protein kinesin. Tubulation of the endoplasmic reticulum is driven by microtubule motors, and in the present work, we describe how
Salmonella
has coopted the microtubule motor kinesin to drive the force-dependent process of endosomal tubulation. Thus, endosomal tubule formation is a force-driven process catalyzed by
Salmonella
virulence factors secreted into the host cytoplasm during infection.

IMPORTANCE
This study represents the first example of using two-color, superresolution imaging to analyze the secretion of
Salmonella
virulence factors as they are secreted from the SPI-2 type three secretion system. Previous studies imaged effectors that were overexpressed in the host cytoplasm. The present work reveals an unusual force-driven process, the pearling transition, which indicates that
Salmonella
-induced filaments are under force through the interactions of effector molecules with the motor protein kinesin. This work provides a caution by highlighting how fixation conditions can influence the images observed.
Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels: Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment
Authors: Pavlova Olga , Shirokov Alexander , Fomin Alexander , Navolokin Nikita , Terskov Andrey , Khorovodov Alexander , Namykin Anton , Pavlov Alexey , Tuchin Valery , Semyachkina-Glushkovskaya Oxana 
Published: June 2018

Malignant gliomas are highly invasive tumors that use the cerebral vessels for invasion due to high vascular fragility of the blood–brain barrier (BBB). On one hand, glioma is characterized by the BBB disruption, on the other hand, drug brain delivery via the BBB is a big challenge in glioma therapy. The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development. Here, we present in vivo and ex vivo study of the BBB disruption and glioma cells (GCs) migration in rats using fluorescence and confocal microscopy. We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells, where the BBB was impermeable for high weight molecules. The migration of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration. The mechanisms underlying glioma progression remain unknown but there is an evidence that the sympathetic nervous system (SNS) via activation of vascular beta2-adrenoreceptors (B2-ADRs) can play an important role in tumor metastasis. Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta-arrestin-1 — co-factor of B2-ADRs signaling pathway in rats with glioma. Pharmacological blockade of B2-ADRs reduces the BBB disruption, macrophages infiltration, GCs migration and increases survival rate. These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis.
LncRNA–FEZF1-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling
Authors: Bian Zehua , Zhang Jiwei , Li Min , Feng Yuyang , Wang Xue , Zhang Jia , Yao Surui , Jin Guoying , Du Jun , Han Weifeng , Yin Yuan , Huang Shenglin , Fei Bojian , Zou Jian , Huang Zhaohui 
Published: June 2018

Abstract
Purpose: Long non-coding RNAs (lncRNAs) play key roles in human cancers. Here, FEZF1-AS1, a highly overexpressed lncRNA in colorectal cancer, was identified by lncRNA microarrays. We aimed to explore the roles and possible molecular mechanisms of FEZF1-AS1 in colorectal cancer.
Experimental Design: LncRNA expression in colorectal cancer tissues was measured by lncRNA microarray and qRT-PCR. The functional roles of FEZF1-AS1 in colorectal cancer were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down, RNA immunoprecipitation and luciferase analyses were used to demonstrate the potential mechanisms of FEZF1-AS1.
Results: We identified a series of differentially expressed lncRNAs in colorectal cancer using lncRNA microarrays, and revealed that FEZF1-AS1 is one of the most overexpressed. Further validation in two expanded colorectal cancer cohorts confirmed the upregulation of FEZF1-AS1 in colorectal cancer, and revealed that increased FEZF1-AS1 expression is associated with poor survival. Functional assays revealed that FEZF1-AS1 promotes colorectal cancer cell proliferation and metastasis. Mechanistically, FEZF1-AS1 could bind and increase the stability of the pyruvate kinase 2 (PKM2) protein, resulting in increased cytoplasmic and nuclear PKM2 levels. Increased cytoplasmic PKM2 promoted pyruvate kinase activity and lactate production (aerobic glycolysis), whereas FEZF1-AS1–induced nuclear PKM2 upregulation further activated STAT3 signaling. In addition, PKM2 was upregulated in colorectal cancer tissues and correlated with FEZF1-AS1 expression and patient survival.
Conclusions: Together, these data provide mechanistic insights into the regulation of FEZF1-AS1 on both STAT3 signaling and glycolysis by binding PKM2 and increasing its stability. Clin Cancer Res; 24(19); 4808–19. ©2018 AACR.
Importance of Variant Interpretation in Whole-Exome Molecular Autopsy
Authors: Shanks Garrett W. , Tester David J. , Ackerman Jaeger P. , Simpson Michael A. , Behr Elijah R. , White Steven M. , Ackerman Michael J. 
Published: June 2018

Background:
Potentially lethal cardiac channelopathies/cardiomyopathies may underlie a substantial portion of sudden unexplained death in the young (SUDY). The whole-exome molecular autopsy represents the latest approach to postmortem genetic testing for SUDY. However, proper variant adjudication in the setting of SUDY can be challenging.

Methods:
From January 2012 through December 2013, 25 consecutive cases of SUDY from 1 to 40 years of age (average age at death 27±5.7 years; 13 white, 12 black) from Cook County, Illinois, were referred after a negative (n=16) or equivocal (n=9) conventional autopsy. A whole-exome molecular autopsy with analysis of 99 sudden death-susceptibility genes was performed. The predicted pathogenicity of ultrarare, nonsynonymous variants was determined using the American College of Medical Genetics guidelines.

Results:
Overall, 27 ultrarare nonsynonymous variants were seen in 16/25 (64%) victims of SUDY. Among black individuals, 9/12 (75%) had an ultrarare nonsynonymous variant compared with 7/13 (54%) white individuals. Of the 27 variants, 10 were considered pathogenic or likely pathogenic in 7/25 (28%) individuals in accordance with the American College of Medical Genetics guidelines. Pathogenic/likely pathogenic variants were identified in 5/16 (31%) of autopsy-negative cases and in 2/6 (33%) victims of SUDY with equivocal findings of cardiomyopathy. Overall, 6 pathogenic/likely pathogenic variants in 4/25 (16%) cases were congruent with the phenotypic findings at autopsy and therefore considered clinically actionable.

Conclusions:
Whole-exome molecular autopsy with gene-specific surveillance is an effective approach for the detection of potential pathogenic variants in SUDY cases. However, systematic variant adjudication is crucial to ensure accurate and proper care for surviving family members.
Manufacturing Shintō as a “World Religion”
Authors: MacWilliams Mark 
Published: June 2018

Abstract
How is Shintō presented in Anglo-American world religions textbooks? While not included in the earliest of such survey courses, it regularly appears in such texts from the early 20th century to the present. Why is Shintō included as one of “great” or “world” religions given how greatly it differs from the likes of Christianity and Islam? Textbook authors include Shintō by constructing an image of it that reflects their own model of world religions, an image that is also based on the “Shintō” that Meiji Japanese officials and scholars invented for their own political-ideological purposes. The standard portrayal of Shintō in Western textbooks has remained more or less the same for a century: It is described as (1) an archaic religion; (2) centered on Japanese imperial mythology; (3) nature worship; (4) apolitical, emphasizing personal piety at shrines. While the most recent editions have tried to incorporate new scholarship in their portrayal, they still rely a world religions model of Shintō that is seriously misleading, failing to adequately present Shintō’s complexities as a tradition.
Severe Weather Watches and Risk Perception in a Hypothetical Decision Experiment
Authors: Gutter Barrett F. , Sherman-Morris Kathleen , Brown Michael E. 
Published: June 2018

AbstractA great deal of research has been conducted regarding tornado warnings and protective actions taken, including some studies in which respondents were presented with hypothetical tornado warning scenarios. Much less research has been conducted in which respondents were presented with tornado watch scenarios, even though they cover a larger area and longer time period, thus potentially disrupting a far greater number of people. To address this lack of research, surveys were used to determine the influence of severe weather watches on planned Saturday afternoon and evening activities away from the immediate vicinity of the respondent’s home. Respondents were presented a hypothetical watch scenario, in which they had some activity planned for later that afternoon or evening. Each respondent rated his or her likelihood to continue an activity depending on the severity of the watch and the length of the activity. Respondents were provided information about each hypothetical watch including duration and primary threats. Responses from the survey indicated that as the severity of the watch or the length of the activity increased, the likelihood of the respondent continuing the activity decreased. For a severe thunderstorm watch, a tornado watch, and a particularly dangerous situation (PDS) tornado watch, 36.1%, 51.2%, and 80.2% of the respondents, respectively, would not continue an activity lasting 30 min or longer.
The Status of the Church in North America
Authors: Burdick Brent H. 
Published: June 2018

The number of Christians in American churches is declining rapidly, and the number of people in America who claim no faith is increasing. This article examines the current context and the challenges that the American Church faces, which include cultural influences, generational replacement, non-adaptive leadership, discipleship, training, and the loss of mission within the American Church. Despite the loss of numbers, the American Church still wields significant global influence owing to its missionary sending and exporting of media, marketing, and technological influence. The global Church follows the leadership of the American Church, for good or ill. Aspects of the Church that are exported, however, often reflect American cultural values rather than traditionally held biblical ideals. Understanding the dynamics, issues, peculiarities, flaws, and successes of the Church in America is therefore imperative if negative trends are ever able to be stemmed in the American Church, and if the American Church hopes to continue contributing significantly to global Christianity. The Church in North America has many expressions, and is extremely varied. Thousands of denominations have been formed over the years, reflecting every theological persuasion, episcopal and leadership structure, worship style, ethnic identity, and geographic area. This article explores the context in which the American Church functions, examines some of the factors and trends affecting the Church in America, discusses why there is reason for hope, and suggests some ways for the Church to move forward in uncertain times.
Book review: Srimati Basu, The Trouble with Marriage––Feminists Confront Law and Violence in India and Malavika Rajkotia, Intimacy Undone Marriage, Divorce and Family Law in India
Authors: Ganneri Namrata R. 
Published: June 2018

Srimati Basu, The Trouble with Marriage––Feminists Confront Law and Violence in India. New Delhi: Orient BlackSwan, 2015, xiv+266 pp., ₹775, ISBN: 978-93-86050-56-4. Malavika Rajkotia, Intimacy Undone Marriage, Divorce and Family Law in India. New Delhi: Speaking Tiger, 2017, xiv+418 pp., ₹799, ISBN: 978-93-86050-56-4.
Intra-articular Injections in the Treatment of Symptoms from Ankle Arthritis: A Systematic Review
Authors: Vannabouathong Christopher , Del Fabbro Gina , Sales Brendan , Smith Christopher , Li Chuan Silvia , Yardley Darryl , Bhandari Mohit , Petrisor Bradley A. 
Published: June 2018

Background: Intra-articular (IA) injections are commonly used to treat knee arthritis pain; however, whether their efficacy generalizes to ankle arthritis remains debatable. We aimed to evaluate the evidence for IA therapies in the management of this patient population. Methods: We performed a literature search for observational and randomized controlled trials (RCTs). Treatments included corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSC). We extracted study details, patient demographics, treatment characteristics, efficacy outcomes, and safety. When feasible, data from RCTs were meta-analyzed using a random-effects model and 95% confidence intervals (CIs) were calculated. A P value <.05 was considered statistically significant. Results: We identified 27 studies (1085 patients). Ankle OA, rheumatoid arthritis (RA), and hemophilic arthropathy populations were examined. The majority of studies were observational (20 studies); the only RCTs were those evaluating HA. Case series demonstrated favorable results in terms of symptomatic relief with CS, HA, PRP, and MSC injections; however, the effects of CS may only be short term and the evidence on MSCs was limited to 1 study with 6 ankle OA patients. Pooled results (3 RCTs, 109 patients) suggested significantly improved Ankle Osteoarthritis Scale scores with HA over saline at 6 months, with a mean difference of 12.47 points (95% CI 1.18-23.77, P = .03). Conclusion: Evidence from small trials favors HA and PRP injections for the treatment of pain associated with ankle osteoarthritis. However, the relative efficacy of all injectable therapies is far from definitive and warrants further high-quality comparative trials. Level of Evidence: Level III, systematic review.
Remote ischaemic conditioning for myocardial infarction or elective PCI: systematic review and meta-analyses of randomised trials
Authors: Haller Paul M , Vargas Kris G , Haller Maria C , Piackova Edita , Wojta Johann , Gyöngyösi Mariann , Gersh Bernard J , Kiss Attila , Podesser Bruno K , Huber Kurt 
Published: June 2018

Background: The efficacy of remote ischaemic conditioning in clinical trials of ST-segment elevation myocardial infarction (STEMI) or elective percutaneous coronary intervention is controversial. We aimed to systematically review and meta-analyse whether remote ischaemic conditioning reduces myocardial damage in those patients. Methods: We searched PubMed, Embase and Web of Science from inception until December 2017 for randomised clinical trials evaluating remote ischaemic conditioning versus a control group. Two independent reviewers extracted data of 23 trials (2118 patients with STEMI; 2048 patients undergoing elective percutaneous coronary intervention) which were meta-analysed using random-effects models. Results: Remote ischaemic conditioning reduced infarct size in STEMI patients when assessed by imaging (mean difference of infarct size as percentage of left ventricle −2.43, 95% confidence interval (CI) –4.37 to −0.48; P=0.01; I2=44%; n=925) or biomarkers related to myocardial injury (peak values of cardiac biomarker release reported as standardised mean difference −0.19, 95% CI −0.37 to −0.02; P=0.03; I2=58%; n=1483) and increased myocardial salvage index (mean difference 0.07, 95% CI 0.01 to 0.13; P=0.02; I2=49%; n= 636). Left ventricular ejection fraction was increased when assessed during the first days after STEMI (mean difference 1.53, 95% CI 0.23 to 2.83; P=0.02; I2=28%; n=1192). Remote ischaemic conditioning had no influence on biomarker values after elective percutaneous coronary intervention (standardised mean difference 0.06, 95% CI −0.17 to 0.30; P=0.59). Conclusions: Despite a statistically significant reduction of myocardial damage in STEMI patients, the magnitude of the reduction was small and a significant impact on clinical events is unlikely. With respect to elective percutaneous coronary intervention, remote ischaemic conditioning had no influence on myocardial injury and its use is not supported by our analysis.
Brief interventions to address substance use among patients presenting to emergency departments in resource poor settings: a cost-effectiveness analysis
Authors: Dwommoh Rebecca , Sorsdahl Katherine , Myers Bronwyn , Asante Kwaku Poku , Naledi Tracey , Stein Dan J. , Cleary Susan 
Published: June 2018

Abstract
Background
There are limited data describing the cost-effectiveness of brief interventions for substance use in resource-poor settings. Using a patient and provider perspective, this study investigates the cost-effectiveness of a brief motivational interviewing (MI) intervention versus a combined intervention of MI and problem solving therapy (MI-PST) for reducing substance use among patients presenting to emergency departments, in comparison to a control group.

Methods
Effectiveness data were extracted from Project STRIVE (Substance use and Trauma InterVention) conducted in South Africa. Patients were randomised to either receive 1 session of MI (n = 113) or MI in addition to four sessions of PST (n = 109) or no intervention [control (n = 110)]. Costs included the direct health care costs associated with the interventions. Patient costs included out of pocket payments incurred accessing the MI-PST intervention. Outcome measures were patients’ scores on the Alcohol, Smoking and Substance Use Involvement Screening Test (ASSIST) and the Centre for Epidemiological Studies Depression Scale (CES-D).

Results
Cost per patient was low in all three groups; US$16, US$33 and US$11, and for MI, MI-PST and control respectively. Outcomes were 0.92 (MI), 1.06 (MI-PST) and 0.88 (control) for ASSIST scores; and 0.74 (MI), 1.27 (MI-PST) and 0.53 (control) for CES-D scores. In comparison to the control group, the MI intervention costs an additional US$119 per unit reduction in ASSIST score, (US$20 for CES-D); MI-PST in comparison to MI costs US$131 or US$33 per unit reduction in ASSIST or CES-D scores respectively. The sensitivity analyses showed that increasing the number of patients who screened positive and thus received the intervention could improve the effectiveness and cost-effectiveness of the interventions.

Conclusion
MI or MI-PST interventions delivered by lay counsellors have the potential to be cost-effective strategies for the reduction of substance use disorder and depressive symptoms among patients presenting at emergency departments in resource poor settings. Given the high economic, social and health care cost of substance use disorders in South Africa, these results suggest that these interventions should be carefully considered for future implementation.
Trial registration This study is part of a trial registered with the Pan African Clinical Trial Registry (PACTR201308000591418)