bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between the activities of daily living, oral health‐related quality of life and dementia
Authors: Cho Min‐Jeong , Jung Eun‐Kyung , Jung Yun‐Sook , Shin Hae‐Eun , Kim Eun‐Kyong , Kim Hyeon‐Chang , Choi Youn‐Hee , Song Keun‐Bae
Published: April 2018

Aim

The aim of the present study was to investigate the association between the activities of daily living and the oral health‐related quality of life and dementia in older adults.

Methods

Over a period of 18 months, we visited 12 elderly care facilities and recruited 375 participants, 345 of whom were selected to undergo oral health examinations and oral health‐related surveys. Each investigation was carried out face‐to‐face by a professional worker.

Results

Cognitive ability was found to be good when the results of the activities of daily living and the oral health‐related quality of life examinations were good. If the results of the activities of daily living examination were bad, the odds ratio of dementia was 2.66, and adjusted odds ratio for age, sex, residence type, education level and denture was 2.99, representing a significant difference (P < 0.05).

Conclusions

Most oral problems are not simply the outcome of aging, with oral hygiene management being the most important determining factor. Oral health problems can be prevented, and in order to improve the quality of life of older adults, attention must be paid to oral healthcare. Geriatr Gerontol Int 2018; 18: 943–949.
Role of autonomic nervous activity, as measured by heart rate variability, on the effect of mortality in disabled older adults with low blood pressure in long‐term care
Authors: Shibasaki Koji , Ogawa Sumito , Yamada Shizuru , Ouchi Yasuyoshi , Akishita Masahiro
Published: April 2018

Aim

Previous studies have shown the relationship between low blood pressure and high mortality in frail, disabled older adults in long‐term care. However, the mechanism of this relationship is still unclear. We hypothesized that autonomic nervous activity decline is involved in the relationship between low blood pressure and high mortality.

Methods

The present prospective cohort study recruited 61 participants aged ≥75 years. The data from 24‐h Holter monitoring and blood pressure recorded by ambulatory blood pressure monitoring were collected. Measured data were divided into three categories: 24‐h, daytime and night‐time. From power spectral density in the electrocardiogram, low frequency, high frequency and low frequency/high frequency ratio were calculated. The primary end‐point was death.

Results

High blood pressure was connected to both high daytime low frequency and high frequency (partial correlation coefficients: 0.42, P < 0.05 and 0.35, P < 0.05, respectively). In addition, the low blood pressure group had higher mortality than the high blood pressure group, and disabled older adults in long‐term care and those with elevated daytime systolic and diastolic blood pressure had less risk of mortality compared with those without (systolic: hazard ratio 0.89, 95% confidence interval 0.83–0.96, P = 0.003; diastolic: hazard ratio 0.98, 95% confidence interval 0.79–1.00, P = 0.049). The average blood pressures in the high blood pressure groups were approximately 140/80 mmHg and were connected to low mortality.

Conclusions

Attenuated autonomic nervous activity might lead to low blood pressure in the daytime and high mortality in disabled older adults in long‐term care. Geriatr Gerontol Int 2018; 18: 1153–1158.
Oncological impact of neoadjuvant hormonal therapy on permanent iodine‐125 seed brachytherapy in patients with low‐ and intermediate‐risk prostate cancer
Authors: Takamoto Atsushi , Tanimoto Ryuta , Bekku Kensuke , Araki Motoo , Sadahira Takuya , Wada Koichiro , Ebara Shin , Katayama Norihisa , Yanai Hiroyuki , Nasu Yasutomo
Published: April 2018

Objectives

To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy.

Methods

Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography‐guided permanent iodine‐125 seed brachytherapy. We retrospectively analyzed low‐ or intermediate‐risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence‐free survival, progression‐free survival, cancer‐specific survival and overall survival.

Results

A total of 484 patients with low‐risk (259 patients) or intermediate‐risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5‐year actuarial biochemical recurrence‐free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence‐free survival outcomes in low‐ (P = 0.8949) or intermediate‐risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate‐specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence‐free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression‐free survival, cancer‐specific survival or overall survival.

Conclusions

In patients with low‐ or intermediate‐risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.
SNP‐based susceptibility–resistance association and mRNA expression regulation analyses of tlr7 to grass carp Ctenopharyngodon idella reovirus
Authors: Su J. J. , Shang X. Y. , Wan Q. Y. , Su J. G.
Published: April 2018

Eleven single nucleotide polymorphisms (SNP) in Ctenopharyngodon idella toll‐like receptor 7 (citlr7) gene, containing two in the 5′‐flanking region, three within the single intron and six distributed in the coding sequence (CDS), were identified. A case–control study of 73 susceptible individuals and 67 resistant individuals was conducted to test the SNPs‐based susceptibility–resistance association and mRNA expression of citlr7 to grass carp reovirus (GCRV), showing that both 820 A/G and 1726 A/G were significantly correlative sites in genotype (P < 0·05). Multifactor dimensionality reduction (MDR) analysis suggested the exertion of antiviral effects of 820 A/G might rely on SNPs interactions of citlr7 and C. idella toll‐like receptor 8 (citlr8). Combining the mortality rate and citlr7 mRNA expression, it was suggested that 1726 GG‐genotyped individuals might be more resistant than 1726 A/G genotyped individuals, indicating the selection on synonymous mutations in 1726 A/G might be susceptibility–resistance‐type specific. In addition, haplotype analysis uncovered no significantly correlative haplotypes in citlr7. These findings may provide an in‐depth insight for the further functional research of citlr7. The potential genetic markers identified may contribute to the molecular and transgenic breeding of C. idella.
Acid‐suppressive drugs and risk of kidney disease: A systematic review and meta‐analysis
Authors: Qiu Tingting , Zhou Junwen , Zhang Chao
Published: April 2018

Background and Aim

More concerns had been raised about the risk of kidney disease (KD) associated with acid‐suppressive drugs. But whether they could directly increase such risk remained unclear. Meta‐analysis was conducted to comprehensively investigate this relationship.

Methods

PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and three Chinese databases were searched until April 2017 for observational studies investigating the associations between acid‐suppressive drugs and KD. Pooled log (odds ratios [ORs]) or log (hazard ratios [HRs]) with standard errors for KD risk were calculated using the generic inverse variance method and random‐effect model.

Results

Ten studies involving 128 020 KD patients were included. Proton pump inhibitor (PPI) therapy was associated with higher risks of acute interstitial nephritis (OR, 2.78; 95% confidence interval [CI], 1.25–6.17), acute kidney injury (AKI) (HR, 1.85; 95% CI, 1.33–2.59), chronic kidney disease (CKD) (HR, 1.47; 95% CI, 1.03–2.09), and end‐stage renal disease (ESRD) (HR, 1.61; 95% CI, 1.26–2.04) than non‐PPI therapy. Additionally, PPI significantly increased the risks of AKI (HR, 1.32; 95% CI, 1.16–1.51), CKD (HR, 1.28; 95% CI, 1.24–1.33), and ESRD (HR, 1.96; 95% CI, 1.21–3.17) compared with histamine 2 receptor antagonist (H2RA). Relationship between H2RA therapy and AKI (OR, 0.98; 95% CI, 0.90–1.07) or CKD (OR, 1.00; 95% CI, 0.89–1.11) was not found.

Conclusions

Proton pump inhibitor therapy significantly increased the risks of acute interstitial nephritis, AKI, CKD, and ESRD. Similar risks were not identified for H2RA therapy. More clinical trials are needed to confirm our findings.
A survey on author profiling, deception, and irony detection for the Arabic language
Authors: Rosso Paolo , Rangel Francisco , Farías Irazu Hernández , Cagnina Leticia , Zaghouani Wajdi , Charfi Anis
Published: April 2018

The possibility of knowing people traits on the basis of what they write is a field of growing interest named author profiling. To infer a user's gender, age, native language, language variety, or even when the user lies, simply by analyzing her texts, opens a wide range of possibilities from the point of view of security. In this paper, we review the state of the art about some of the main author profiling problems, as well as deception and irony detection, especially focusing on the Arabic language.
Correlation between novel 3D high‐resolution manometry esophagogastric junction metrics and pH‐metry in reflux disease patients
Authors: Xiao Y. , Lin Z. , Li Y. , Pandolfino J. E. , Chen M. , Kahrilas P. J.
Published: April 2018

Background and aims

We recently developed 2 novel 3D high‐resolution manometry (HRM) metrics of esophagogastric junction (EGJ) contractility to differentiate the lower esophageal sphincter (LES) and crural diaphragm (CD) elements of EGJ pressure. This study aimed to compare these metrics to the EGJ‐contractile integral (EGJ‐CI) and to analyze their correlation with esophageal acid exposure time (AET) on pH‐metry.

Methods

Thirty‐one gastro‐oesophageal reflux disease (GERD) patients and 20 control subjects underwent 24‐hour pH‐metry and HRM using a 3D‐HRM catheter. EGJ metrics were calculated during 3 consecutive respiratory cycles at rest. The EGJ‐CI was calculated using the DCI tool in the ManoView software. 3D LES pressure (3D‐LESP) and 3D‐DHA, a metric quantifying the CD component of the 3D‐HRM pressure topography, were calculated using a MATLAB program. Pearson correlation was used to calculate correlations with AET.

Key Results

3D‐LESP, 3D‐DHA, and EGJ‐CI were all significantly lower in GERD patients than in control subjects (P < .05) and all were significantly correlated with AET (R = −.48, −.42, −.52, respectively, all P < .01). The 3D‐DHA and EGJ‐CI also strongly correlated with each other (R = .84, P < .001).

Conclusions & Inferences

Both 3D‐EGJ metrics were correlated with AET emphasizing the importance of both LES and CD function as a determinant of EGJ competence. 3D‐DHA also strongly correlated with the EGJ‐CI suggesting that EGJ‐CI is strongly driven by the asymmetrical CD pressure component.
Salivary functions in mastication, taste and textural perception, swallowing and initial digestion
Authors: Pedersen AML , Sørensen CE , Proctor GB , Carpenter GH
Published: April 2018

Saliva exerts multiple functions in relation to the initial digestive processes taking place in the upper parts of the gastrointestinal tract. Ingestion of food and beverages, in turn, is a strong stimulus for secretion of saliva with a differential composition depending on the neuronal stimulation pattern. This review paper provides insight into the mechanisms by which saliva acts in relation to taste, mastication, bolus formation, enzymatic digestion and swallowing. Also, the protective functions of saliva including maintenance of dental and mucosal integrity will be discussed as they indirectly influence the digestive process. The final part of this study focuses on the implications of xerostomia and salivary gland dysfunction on gastrointestinal functions.
Arabidopsis ANGUSTIFOLIA3 (AN3) is associated with the promoter of CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) to regulate light‐mediated stomatal development
Authors: Meng Lai‐Sheng , Li Cong , Xu Meng‐Ke , Sun Xu‐Dong , Wan Wen , Cao Xiao‐Ying , Zhang Jin‐Lin , Chen Kun‐Ming
Published: April 2018

Light signals are perceived by multiple photoreceptors that converge to suppress the RING E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) for the regulation of stomatal development. Thus, COP1 is a point of integration between light signaling and stomatal patterning. However, how light signaling is collected into COP1 for the production and spacing of stomata is still unknown. Here, we report that the loss‐of‐function mutant of ANGUSTIFOLIA3 (AN3) delays asymmetric cell division, which leads to decreased stomatal index. Furthermore, overexpression of AN3 accelerates asymmetric cell division, which results in clusters of stomata. In addition, the stomatal development through AN3 regulation is mediated by light signaling. Finally, we find that an3 is a light‐signaling mutant, and that AN3 protein is light regulated. Self‐activation by AN3 contributes to the control of AN3 expression. Thus, AN3 is a point of collection between light signaling and stomatal patterning. Target‐gene analysis indicates that AN3 is associated with COP1 promoter for the regulation of light‐controlling stomatal development. Together, these components for regulating stomatal development form an AN3–COP1–E3 ubiquitin ligase complex, allowing the integration of light signaling into the production and spacing of stomata.
Insights to plant–microbe interactions provide opportunities to improve resistance breeding against root diseases in grain legumes
Authors: Wille Lukas , Messmer Monika M. , Studer Bruno , Hohmann Pierre
Published: April 2018

Root and foot diseases severely impede grain legume cultivation worldwide. Breeding lines with resistance against individual pathogens exist, but these resistances are often overcome by the interaction of multiple pathogens in field situations. Novel tools allow to decipher plant–microbiome interactions in unprecedented detail and provide insights into resistance mechanisms that consider both simultaneous attacks of various pathogens and the interplay with beneficial microbes. Although it has become clear that plant‐associated microbes play a key role in plant health, a systematic picture of how and to what extent plants can shape their own detrimental or beneficial microbiome remains to be drawn. There is increasing evidence for the existence of genetic variation in the regulation of plant–microbe interactions that can be exploited by plant breeders. We propose to consider the entire plant holobiont in resistance breeding strategies in order to unravel hidden parts of complex defence mechanisms. This review summarizes (a) the current knowledge of resistance against soil‐borne pathogens in grain legumes, (b) evidence for genetic variation for rhizosphere‐related traits, (c) the role of root exudation in microbe‐mediated disease resistance and elaborates (d) how these traits can be incorporated in resistance breeding programmes.
Interstitial Lung Diseases in the U.S. Mining Industry: Using MSHA Data to Examine Trends and the Prevention Effects of Compliance with Health Regulations, 1996–2015
Authors: Yorio Patrick L. , Laney A. Scott , Halldin Cara N. , Blackley David J. , Moore Susan M. , Wizner Kerri , Radonovich Lewis J. , Greenawald Lee A.
Published: April 2018

Given the recent increase in dust‐induced lung disease among U.S. coal miners and the respiratory hazards encountered across the U.S. mining industry, it is important to enhance an understanding of lung disease trends and the organizational contexts that precede these events. In addition to exploring overall trends reported to the Mine Safety and Health Administration (MSHA), the current study uses MSHA's enforcement database to examine whether or not compliance with health regulations resulted in fewer mine‐level counts of these diseases over time. The findings suggest that interstitial lung diseases were more prevalent in coal mines compared to other mining commodities, in Appalachian coal mines compared to the rest of the United States, and in underground compared to surface coal mines. Mines that followed a relevant subset of MSHA's health regulations were less likely to report a lung disease over time. The findings are discussed from a lung disease prevention strategy perspective.
Randomization‐based statistical inference: A resampling and simulation infrastructure
Authors: Dinov Ivo D. , Palanimalai Selvam , Khare Ashwini , Christou Nicolas
Published: April 2018

Statistical inference involves drawing scientifically‐based conclusions describing natural processes or observable phenomena from datasets with intrinsic random variation. We designed, implemented, and validated a new portable randomization‐based statistical inference infrastructure (http://socr.umich.edu/HTML5/Resampling_Webapp) that blends research‐driven data analytics and interactive learning, and provides a backend computational library for managing large amounts of simulated or user‐provided data.

We designed, implemented and validated a new portable randomization‐based statistical inference infrastructure (http://socr.umich.edu/HTML5/Resampling_Webapp) that blends research‐driven data analytics and interactive learning, and provides a backend computational library for managing large amounts of simulated or user‐provided data. The core of this framework is a modern randomization webapp, which may be invoked on any device supporting a JavaScript‐enabled web browser. We demonstrate the use of these resources to analyse proportion, mean and other statistics using simulated (virtual experiments) and observed (e.g. Acute Myocardial Infarction, Job Rankings) data. Finally, we draw parallels between parametric inference methods and their distribution‐free alternatives.

The Randomization and Resampling webapp can be used for data analytics, as well as for formal, in‐class and informal, out‐of‐the‐classroom learning and teaching of different scientific concepts. Such concepts include sampling, random variation, computational statistical inference and data‐driven analytics. The entire scientific community may utilize, test, expand, modify or embed these resources (data, source‐code, learning activity, webapp) without any restrictions.
Priming as a Process and as a Function in Agenda Setting
Authors: Chernov Gennadiy
Published: April 2018

This paper explores the priming mechanism in agenda setting in conjunction with information processing and other variables such as relevance and mental models. Over the years, certain confusion started to accumulate about what is a place of priming in the media effects realm in general and in agenda setting in particular. Moreover, new advances in the psychology studies of priming and in media priming were not accounted for in agenda setting. The paper aims at a) reviewing what developments in the field have taken place over the years, and b) revisiting and clarifying priming in its specific application to public agenda setting based on the new developments.The paper concludes with a new working definition of priming and describes a more complex theoretical framework of priming that shows how mental models and relevance explain priming effects better than accessibility only in deliberative information processes, and that even in more automatic, peripheral processing, accessibility plays a role as only an initial trigger for further issue or performance evaluations.
Central and peripheral chemoreceptors in sudden infant death syndrome
Authors: Porzionato Andrea , Macchi Veronica , De Caro Raffaele
Published: April 2018

The pathogenesis of sudden infant death syndrome (SIDS) has been ascribed to an underlying biological vulnerability to stressors during a critical period of development. This paper reviews the main data in the literature supporting the role of central (e.g. retrotrapezoid nucleus, serotoninergic raphe nuclei, locus coeruleus, orexinergic neurons, ventral medullary surface, solitary tract nucleus) and peripheral (e.g. carotid body) chemoreceptors in the pathogenesis of SIDS. Clinical and experimental studies indicate that central and peripheral chemoreceptors undergo critical development during the initial postnatal period, consistent with the age range of SIDS (<1 year). Most of the risk factors for SIDS (gender, genetic factors, prematurity, hypoxic/hyperoxic stimuli, inflammation, perinatal exposure to cigarette smoke and/or substance abuse) may structurally and functionally affect the developmental plasticity of central and peripheral chemoreceptors, strongly suggesting the involvement of these structures in the pathogenesis of SIDS. Morphometric and neurochemical changes have been found in the carotid body and brainstem respiratory chemoreceptors of SIDS victims, together with functional signs of chemoreception impairment in some clinical studies. However, the methodological problems of SIDS research will have to be addressed in the future, requiring large and highly standardized case series. Up‐to‐date autopsy protocols should be produced, involving substantial, and exhaustive sampling of all potentially involved structures (including peripheral arterial chemoreceptors). Morphometric approaches should include unbiased stereological methods with three‐dimensional probes. Prospective clinical studies addressing functional tests and risk factors (including genetic traits) would probably be the gold standard, allowing markers of intrinsic or acquired vulnerability to be properly identified.
The Reduced Space Shooting Method for Calculating the Peak Periodic Solutions of Nonlinear Systems
Authors: Liao Haitao , Wu Wenwang
Published: April 2018

A hybrid approach which combines the reduced sequential quadratic programing (SQP) method with the shooting method is proposed to search the worst resonance response of nonlinear systems. The shooting method is first employed to construct the nonlinear equality constraints for the constrained optimization problem. Then, the complex optimization problem is simplified and solved numerically by the reduced SQP method. By virtue of the coordinate basis decomposition scheme which exploits the gradients of nonlinear equality constraints, the nonlinear equality constraints are eliminated, resulting in a simple optimization problem subject to bound constraints. Moreover, the second-order correction (SOC) technique is adopted to overcome Maratos effect. The novelty of the approach described lies in the capability to efficiently handle nonlinear equality constraints. The effectiveness of the proposed algorithm is demonstrated by two benchmark examples seen in the literature.
Speaking rhythmically improves speech recognition under “cocktail-party” conditions
Authors: Wang Mengyuan , Kong Lingzhi , Zhang Changxin , Wu Xihong , Li Liang
Published: April 2018

This study examines whether speech rhythm affects speech recognition under “cocktail-party” conditions. Against a two-talker masker, but not a speech-spectrum noise masker, recognition of the last (third) keyword in a normal rhythmic sentence was significantly better than that of the first keyword. However, this word-position-related speech-recognition improvement disappeared for rhythmically hybrid target sentences that were constructed by grouping parts from different sentences with different artificially modulated rhythms (rates) (fast, normal, or slow). Thus, the normal rhythm with a constant rate plays a role in improving speech recognition against informational speech masking, probably through a build-up of temporal prediction for target words.
Defect imaging for plate-like structures using diffuse field
Authors: Hayashi Takahiro
Published: April 2018

Defect imaging utilizing a scanning laser source (SLS) technique produces images of defects in a plate-like structure, as well as spurious images occurring because of resonances and reverberations within the specimen. This study developed defect imaging by the SLS using diffuse field concepts to reduce the intensity of spurious images, by which the energy of flexural waves excited by laser can be estimated. The experimental results in the different frequency bandwidths of excitation waves and in specimens with different attenuation proved that clearer images of defects are obtained in broadband excitation using a chirp wave and in specimens with low attenuation, which produce diffuse fields easily.
Study questions animal efficacy data behind trials
Authors: Yasinski Emma
Published: April 2018

Information provided to ethical review panels may often be insufficient to judge a drug's therapeutic potential.
Free agents
Authors: Waldrop M. Mitchell
Published: April 2018

Monumentally complex models are gaming out disaster scenarios with millions of simulated people.
MitoCPR—A surveillance pathway that protects mitochondria in response to protein import stress
Authors: Weidberg Hilla , Amon Angelika
Published: April 2018

The mitoCPR unclogs mitochondria

The import of proteins into mitochondria is essential for cell viability. How cells respond when mitochondrial protein import is impaired is poorly understood. Weidberg and Amon showed that upon mitochondrial import stress, yeast cells mounted a response known as the mitoCPR. mitoCPR was activated when mitochondrial protein import was impaired and unimported precursors accumulated on the organelle's surface. mitoCPR restored mitochondrial functions by clearing stalled proteins from the import channels. It did this by inducing expression of Cis1, which recruited the adenosine triphosphatase Msp1 to import channels to remove unimported precursors and target them for degradation by the proteasome.

Science
, this issue p.
eaan4146
Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
Authors: Burnett Deborah L. , Langley David B. , Schofield Peter , Hermes Jana R. , Chan Tyani D. , Jackson Jennifer , Bourne Katherine , Reed Joanne H. , Patterson Kate , Porebski Benjamin T. , Brink Robert , Christ Daniel , Goodnow Christopher C.
Published: April 2018

Autoantibody redemption through rapid mutations

Antibodies distinguish foreign epitopes from closely related self-antigens by poorly understood mechanisms. In mice, Burnett
et al.
found that a proportion of B cells could cross-react with similar foreign and self-antigens (see the Perspective by Kara and Nussenzweig). Challenge with self-antigen resulted in anergy (i.e., a lack of immune response), which was reversed by exposure to high-density foreign antigen. Mutations that decreased self-affinity were rapidly selected for, whereas selection for epistatic mutations that enhanced foreign reactivity took longer. Self-reactivity, rather than being an impediment to immunization, resulted in higher affinities against a foreign immunogen.

Science
, this issue p.
223
; see also p.
152
RNA buffers the phase separation behavior of prion-like RNA binding proteins
Authors: Maharana Shovamayee , Wang Jie , Papadopoulos Dimitrios K. , Richter Doris , Pozniakovsky Andrey , Poser Ina , Bickle Marc , Rizk Sandra , Guillén-Boixet Jordina , Franzmann Titus M. , Jahnel Marcus , Marrone Lara , Chang Young-Tae , Sterneckert Jared , Tomancak Pavel , Hyman Anthony A. , Alberti Simon
Published: April 2018

RNA and membraneless organelles

Membraneless compartments can form in cells through liquidliquid phase separation (see the Perspective by Polymenidou). But what prevents these cellular condensates from randomly fusing together? Using the RNA-binding protein (RBP) Whi3, Langdon
et al.
demonstrated that the secondary structure of different RNA components determines the distinct biophysical and biological properties of the two types of condensates that Whi3 forms. Several RBPs, such as FUS and TDP43, contain prion-like domains and are linked to neurodegenerative diseases. These RBPs are usually soluble in the nucleus but can form pathological aggregates in the cytoplasm. Maharana
et al.
showed that local RNA concentrations determine distinct phase separation behaviors in different subcellular locations. The higher RNA concentrations in the nucleus act as a buffer to prevent phase separation of RBPs; when mislocalized to the cytoplasm, lower RNA concentrations trigger aggregation.

Science
, this issue p.
922
, p.
918
; see also p.
859
The future of artisanal fishing
Fishing Lessons: Artisanal Fisheries and the Future of Our Oceans
Kevin M. Bailey
University of Chicago Press, 2018. 252 pp.
Authors: Pauly Daniel
Published: April 2018

Declining fish populations and policies that favor large operations threaten small fisheries
How cleaner air changes the climate
Authors: Samset Bjørn Hallvard
Published: April 2018

Air quality improvements affect regional climate in complex ways
Plasticity of Aminoglycoside Binding to Antibiotic Kinase APH(2″)-Ia
Authors: Caldwell Shane J. , Berghuis Albert M.
Published: April 2018

The APH(2″)-Ia aminoglycoside resistance enzyme forms the C-terminal domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme and confers high-level resistance to natural 4,6-disubstituted aminoglycosides. In addition, reports have suggested that the enzyme can phosphorylate 4,5-disubstituted compounds and aminoglycosides with substitutions at the N1 position. Previously determined structures of the enzyme with bound aminoglycosides have not indicated how these noncanonical substrates may bind and be modified by the enzyme. We carried out crystallographic studies to directly observe the interactions of these compounds with the aminoglycoside binding site and to probe the means by which these noncanonical substrates interact with the enzyme. We find that APH(2″)-Ia maintains a preferred mode of binding aminoglycosides by using the conserved neamine rings when possible, with flexibility that allows it to accommodate additional rings. However, if this binding mode is made impossible because of additional substitutions to the standard 4,5- or 4,6-disubstituted aminoglycoside architecture, as in lividomycin A or the N1-substituted aminoglycosides, it is still possible for these aminoglycosides to bind to the antibiotic binding site by using alternate binding modes, which explains the low rates of noncanonical phosphorylation activities seen in enzyme assays. Furthermore, structural studies of a clinically observed arbekacin-resistant mutant of APH(2″)-Ia revealed an altered aminoglycoside binding site that can stabilize an alternative binding mode for N1-substituted aminoglycosides. This mutation may alter and expand the aminoglycoside resistance spectrum of the wild-type enzyme in response to newly developed aminoglycosides.
Treating Anthrax-Induced Meningitis in Rabbits
Authors: Ben-Shmuel Amir , Glinert Itai , Sittner Assa , Bar-David Elad , Schlomovitz Josef , Brosh Tal , Kobiler David , Weiss Shay , Levy Haim
Published: April 2018

Treatment of anthrax is challenging, especially during the advanced stages of the disease. Recently, the Centers for Disease Control and Prevention (CDC) updated its recommendations for postexposure prophylaxis and treatment of exposed populations (before and after symptom onset). These recommendations distinguished, for the first time, between systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic cases meningeal unless positively proven otherwise. The treatment of patients suffering from systemic anthrax with suspected or confirmed meningitis includes the combination of three antibiotics, i.e., a fluoroquinolone (levofloxacin or ciprofloxacin), a β-lactam (meropenem or imipenem), and a protein synthesis inhibitor (linezolid or clindamycin). In addition, treatment with an antitoxin (anti-protective antigen antibodies) and dexamethasone should be applied. Since the efficacy of most of these treatments has not been demonstrated, especially in animal meningitis models, we developed an anthrax meningitis model in rabbits and tested several of these recommendations. We demonstrated that, in this model, ciprofloxacin, linezolid, and meropenem were ineffective as single treatments, while clindamycin was highly effective. Furthermore, combined treatments of ciprofloxacin and linezolid or ciprofloxacin and dexamethasone failed in treating rabbits with meningitis. We demonstrated that dexamethasone actually hindered blood-brain barrier penetration by antibiotics, reducing the effectiveness of antibiotic treatment of anthrax meningitis in this rabbit model.
SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A
Authors: Luo Xinlong , Yang Wei , Gao Guangxia
Published: April 2018

Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells via passing through the nuclear pore complex. The nuclear membrane-imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here we report that overexpression of SUN1 specifically inhibited infection by HIV-1 but not that by simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription but led to reduced accumulation of the 2-long-terminal-repeat (2-LTR) circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import. HIV-1 CA was mapped as a determinant for viral sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine (CsA) significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant containing CA-G89A, which does not interact with cyclophilin A (CypA), was resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wild-type virus but not that of the G89A mutant. These results indicate that SUN1 participates in the HIV-1 nuclear entry process in a manner dependent on the interaction of CA with CypA.

IMPORTANCE
HIV-1 infects both dividing and nondividing cells. The viral preintegration complex (PIC) can enter the nucleus through the nuclear pore complex. It has been well known that the viral protein CA plays an important role in determining the pathways by which the PIC enters the nucleus. In addition, the interaction between CA and the cellular protein CypA has been reported to be important in the selection of nuclear entry pathways, though the underlying mechanisms are not very clear. Here we show that both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA played an important role in determining the sensitivity of the virus to SUN1: the regulatory activity of SUN1 toward HIV-1 relied on the interaction between CA and CypA. These results help to explain how SUN1 is involved in the HIV-1 nuclear entry process.
Neuronal Subtype Determines Herpes Simplex Virus 1 Latency-Associated-Transcript Promoter Activity during Latency
Authors: Cabrera Jorge Ruben , Charron Audra J. , Leib David A.
Published: April 2018

Herpes simplex virus (HSV) latency in neurons remains poorly understood, and the heterogeneity of the sensory nervous system complicates mechanistic studies. In this study, we used primary culture of adult trigeminal ganglion (TG) mouse neurons in microfluidic devices and an
in vivo
model to examine the subtypes of sensory neurons involved in HSV latency. HSV-infected neurofilament heavy-positive (NefH
+
) neurons were more likely to express latency-associated transcripts (LATs) than infected neurofilament heavy-negative (NefH
−
) neurons. This differential expression of the LAT promoter correlated with differences in HSV-1 early infection that manifested as differences in the efficiency with which HSV particles reached the cell body following infection at the distal axon.
In vivo
, we further identified a specific subset of NefH
+
neurons which coexpressed calcitonin gene-related peptide α (NefH
+
CGRP
+
neurons) as the sensory neuron subpopulation with the highest LAT promoter activity following HSV-1 infection. Finally, an early-phase reactivation assay showed HSV-1 reactivating in NefH
+
CGRP
+
neurons, although other sensory neuron subpopulations were also involved. Together, these results show that sensory neurons expressing neurofilaments exhibit enhanced LAT promoter activity. We hypothesize that the reduced efficiency of HSV-1 invasion at an early phase of infection may promote efficient establishment of latency in NefH
+
neurons due to initiation of the antiviral state preceding arrival of the virus at the neuronal cell body. While the outcome of HSV-1 infection of neurons is determined by a broad variety of factors
in vivo
, neuronal subtypes are likely to play differential roles in modulating the establishment of latent infection.

IMPORTANCE
Two pivotal properties of HSV-1 make it a successful pathogen. First, it infects neurons, which are immune privileged. Second, it establishes latency in these neurons. Together, these properties allow HSV to persist for the lifetime of its host. Neurons are diverse and highly organized cells, with specific anatomical, physiological, and molecular characteristics. Previous work has shown that establishment of latency by HSV-1 does not occur equally in all types of neurons. Our results show that the kinetics of HSV infection and the levels of latency-related gene expression differ in certain types of neurons. The neuronal subtype infected by HSV is therefore a critical determinant of the outcome of infection and latency.
Late Cretaceous to early Neogene tectonic development of the southern Sierra Nevada region, California
Authors: Chapman Alan D. , Wood David J. , Saleeby Jason B. , Saleeby Zorka
Published: April 2018

The Sierra Nevada batholith is an ~600-km-long, NNW-trending continental arc generally exposed from epizonal to mesozonal levels and showing a distinct strike-perpendicular zonation in structural, lithologic, petrologic, geochronologic, and isotopic patterns. South of 35.5° N, in the southern Sierra Nevada–northern Mojave Desert region, the depth of exposure increases markedly and a tectonostratigraphy consisting of three distinct, fault-bounded assemblages is observed. From high to low structural levels, these units are (1) fragments of shallow-level eastern Sierra Nevada batholith affinity rocks, (2) deeper-level western to axial zone rocks, and (3) subduction accretion assemblages (e.g., the Rand schist). This multi-tiered core complex is the product of shallow subduction that occurred over ~500 km of the plate margin in Late Cretaceous time. Slab shallowing was accompanied by intense contractile deformation within the crust and along the subduction megathrust; crustal thickening, uplift, and denudation of the residual arc to midcrustal levels; removal of the forearc and frontal arc by subduction erosion; and replacement of sub-batholithic mantle with underplated subduction assemblages. As the slab reverted to a “normal” trajectory, previously thickened crust no longer compensated at depth by a shallowly dipping slab became gravitationally unstable and underwent a profound phase of extensional collapse. Two subparallel shear zones, one separating assemblages 1 and 2 (the southern Sierra detachment) and the other juxtaposing units 2 and 3 (the Rand fault), comprise an integrated Late Cretaceous detachment system that accommodated extensional collapse. These Late Cretaceous events preconditioned the southern California crust for imprints of subsequent tectonic regimes. For example, subduction of the Pacific-Farallon slab window in early Neogene time created an extensional stress regime in the overriding plate, facilitating high-angle normal faulting across the previously extended region and volcanism associated with upwelling astheno-spheric material. The invasion of hot and buoyant asthenosphere destabilized dense sub-batholithic root material still affixed beneath the central Sierra Nevada batholith, leading to Pliocene–Quaternary delamination of the high-density rocks. Replacement of dense sub-batholithic root materials with asthenosphere has led to ~1 km of uplift across the southern Sierra Nevada and into the eastern San Joaquin Basin. The purpose of this trip is to highlight structural and petrologic records of multiple phases of tectonism in the southern Sierra Nevada–Mojave Desert region, illustrating the profound and lasting effect that shallow subduction may have on a continental margin.
Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7–9 years of age
Authors: Rowan Janet A , Rush Elaine C , Plank Lindsay D , Lu Jun , Obolonkin Victor , Coat Suzette , Hague William M
Published: April 2018

Objective

To compare body composition and metabolic outcomes at 7–9 years in offspring of women with gestational diabetes (GDM) randomized to metformin (±insulin) or insulin treatment during pregnancy.

Research design and methods

Children were assessed at 7 years in Adelaide (n=109/181) and 9 years in Auckland (n=99/396) by anthropometry, bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) (n=92/99) and fasting bloods (n=82/99).

Results

In the Adelaide subgroup, mothers were similar at enrollment. Women randomized to metformin versus insulin had higher treatment glycemia (p=0.002) and more infants with birth weight >90th percentile (20.7% vs 5.9%; p=0.029). At 7 years, there were no differences in offspring measures. In Auckland, at enrollment, women randomized to metformin had a higher body mass index (BMI) (p=0.08) but gained less weight during treatment (p=0.07). Offspring birth measures were similar. At 9 years, metformin offspring were larger by measures of weight, arm and waist circumferences, waist:height (p<0.05); BMI, triceps skinfold (p=0.05); DXA fat mass and lean mass (p=0.07); MRI abdominal fat volume (p=0.051). Body fat percent was similar between treatment groups by DXA and BIA. Abdominal fat percentages (visceral adipose tissue, subcutaneous adipose tissue and liver) were similar by MRI. Fasting glucose, triglyceride, insulin, insulin resistance, glycosylated hemoglobin (HbA1c), cholesterol, liver transaminases, leptin and adiponectin were similar.

Conclusions

Metformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7–9 years. Metformin-exposed children were larger at 9 years. Metformin may interact with fetal environmental factors to influence offspring outcomes.
Adherence to reporting guidelines and clinical trial registration policies in oncology journals: a cross-sectional review
Authors: Wayant Cole , Moore Gretchan , Hoelscher Mark , Cook Courtney , Vassar Matt
Published: April 2018

Reporting guidelines (RG) aim to improve research transparency and ensure high-quality study reporting. Similarly, clinical trial registration policies aim to reduce bias in results reporting by ensuring prospective registration of all trial outcomes. Failure to adhere to quality standards documented in RGs may result in low-quality and irreproducible research. Herein, we investigate the adherence to common RGs and trial registration policies in 21 oncology journals. We surveyed the Instructions for Authors page for each of the included oncology journals for adherence to common reporting guidelines and trial registration policies. We corresponded with editors to determine accepted study types and cross-referenced this information with a journal’s RGs and trial registration policies to calculate the per cent of journals that adhere to a specific guideline or policy. 76.2% (16/21) of oncology journals surveyed adhere to Consolidated Standards of Reporting Trials guidelines for clinical trials while only 33.3% (7/21) adhere to Strengthening the Reporting of Observational Studies in Epidemiology for observational studies. Similarly, 76.2% (16/21) of oncology journals adhere to clinical trial registration policies. We further demonstrate that journal adherence to RGs positively affects author reporting, despite adherence to trial registration policies showing no such benefit. Our results show that oncology journals adhere to RGs and trial registration policies at a higher rate than other specialties, but nonetheless show room for improvement. We conclude that oncology journal adherence to RGs and trial registration policies is encouraging, but nonetheless suboptimal. We recommend the adoption of RGs and trial registration policies by all oncology journals.
From the battlefield to the bedroom: a multilevel analysis of the links between political conflict and intimate partner violence in Liberia
Authors: Kelly Jocelyn T D , Colantuoni Elizabeth , Robinson Courtland , Decker Michele R
Published: April 2018

Objectives

Assess the link between levels of armed conflict and postconflict intimate partner violence (IPV) experienced by women in Liberia.

Methods

Armed Conflict Location and Event Data Project data were used to measure conflict-related fatalities in districts in Liberia during the country’s civil war from 1999 to 2003. These data were linked to individual-level data from the 2007 Demographic and Health Survey, including past-year IPV. Multilevel logistic models accounting for the clustering of women within districts evaluated the relationship of conflict fatalities with postconflict past-year IPV. Additional conflict measures, including conflict events and cumulative years of conflict, were assessed.

Results

After adjusting for individual-level characteristics correlated with IPV, residence in a conflict fatality-affected district was associated with a 50% increase in risk of IPV (adjusted OR (aOR): 1.55, 95% CI 1.26 to 1.92). Women living in a district that experienced 4–5 cumulative years of conflict were also more likely to experience IPV (aOR 1.88, 95% CI 1.29 to 2.75).

Conclusion

Residing in a conflict-affected district even 5 years after conflict was associated with postconflict IPV.

Policy implications

Recognising and preventing postconflict IPV violence is important to support long-term recovery in postconflict settings.