bluuebunny/crossref_metadata_2025 huggingface dataset:
Culture beats gender? The importance of controlling for identity‐ and parenting‐related risk factors in adolescent psychopathology☆
Authors: Seiffge‐Krenke Inge , Persike Malte , Besevegis Elias , Chau Cecilia , Karaman Neslihan Güney , Lannegrand‐Willems Lyda , Lubiewska Katharzyna , Rohail Iffat
Published: January 2018

This study analyzed the unique effects of gender and culture on psychopathology in adolescents from seven countries after controlling for factors which might have contributed to variations in psychopathology. In a sample 2259 adolescents (M = 15 years; 54% female) from France, Germany, Turkey, Greece, Peru, Pakistan, and Poland identity stress, coping with identity stress, maternal parenting (support, psychological control, anxious rearing) and psychopathology (internalizing, externalizing and total symptomatology) were assessed. Due to variations in stress perception, coping style and maternal behavior, these covariates were partialed out before the psychopathology scores were subjected to analyses of variance with gender and country as factors. These analyses leveled out the main effect of country and revealed country‐specific gender effects. In four countries, males reported higher internalizing and total symptomatology than females. Partialing out the covariates resulted in a clearer picture of culture‐specific and gender‐dependent effects on psychopathology, which is helpful in designing interventions.
Topological attractors of contracting Lorenz maps
Authors: Brandão Paulo
Published: January 2018

We study the non-wandering set of contracting Lorenz maps. We show that if such a map
f
doesn't have any attracting periodic orbit, then there is a unique topological attractor. Furthermore, we classify the possible kinds of attractors that may occur.
Predictors of length of stay in psychiatric inpatient units: Does their effect vary across countries?
Authors: Dimitri Giorgia , Giacco Domenico , Bauer Michael , Bird Victoria Jane , Greenberg Lauren , Lasalvia Antonio , Lorant Vincent , Moskalewicz Jacek , Nicaise Pablo , Pfennig Andrea , Ruggeri Mirella , Welbel Marta , Priebe Stefan
Published: January 2018

Background

Previous studies in individual countries have identified inconsistent predictors of length of stay (LoS) in psychiatric inpatient units. This may reflect methodological inconsistencies across studies or true differences of predictors. In this study we assessed predictors of LoS in five European countries and explored whether their effect varies across countries.

Methods

Prospective cohort study. All patients admitted over 14 months to 57 psychiatric inpatient units in Belgium, Germany, Italy, Poland and United Kingdom were screened. Putative predictors were collected from medical records and in face-to-face interviews and tested for their association with LoS.

Results

Average LoS varied from 17.9 days in Italy to 55.1 days in Belgium. In the overall sample being homeless, receiving benefits, social isolation, diagnosis of psychosis, greater symptom severity, substance use, history of previous admission and being involuntarily admitted predicted longer LoS. Several predictors showed significant interaction effects with countries in predicting LoS. One variable, homelessness, predicted a different LoS even in opposite directions, whilst for other predictors the direction of the association was the same, but the strength of the association with LoS varied across countries.

Conclusions

The same patient characteristics have a different impact on LoS in different contexts. Thus, although some predictor variables related to clinical severity and social dysfunction appear of generalisable relevance, national studies on LoS are required to understand the complex influence of different patient characteristics on clinical practice in the given contexts.
A real world study on the genetic, cognitive and psychopathological differences of obese patients clustered according to eating behaviours
Authors: Caroleo Mariarita , Primerano Amedeo , Rania Marianna , Aloi Matteo , Pugliese Valentina , Magliocco Fabio , Fazia Gilda , Filippo Andrea , Sinopoli Flora , Ricchio Marco , Arturi Franco , Jimenez-Murcia Susana , Fernandez-Aranda Fernando , De Fazio Pasquale , Segura-Garcia Cristina
Published: January 2018

Background

Considering that specific genetic profiles, psychopathological conditions and neurobiological systems underlie human behaviours, the phenotypic differentiation of obese patients according to eating behaviours should be investigated. The aim of this study was to classify obese patients according to their eating behaviours and to compare these clusters in regard to psychopathology, personality traits, neurocognitive patterns and genetic profiles.

Methods

A total of 201 obese outpatients seeking weight reduction treatment underwent a dietetic visit, psychological and psychiatric assessment and genotyping for SCL6A2 polymorphisms. Eating behaviours were clustered through two-step cluster analysis, and these clusters were subsequently compared.

Results

Two groups emerged: cluster 1 contained patients with predominantly prandial hyperphagia, social eating, an increased frequency of the long allele of the 5-HTTLPR and low scores in all tests; and cluster 2 included patients with more emotionally related eating behaviours (emotional eating, grazing, binge eating, night eating, post-dinner eating, craving for carbohydrates), dysfunctional personality traits, neurocognitive impairment, affective disorders and increased frequencies of the short (S) allele and the S/S genotype.

Conclusions

Aside from binge eating, dysfunctional eating behaviours were useful symptoms to identify two different phenotypes of obese patients from a comprehensive set of parameters (genetic, clinical, personality and neuropsychology) in this sample. Grazing and emotional eating were the most important predictors for classifying obese patients, followed by binge eating. This clustering overcomes the idea that ‘binging’ is the predominant altered eating behaviour, and could help physicians other than psychiatrists to identify whether an obese patient has an eating disorder. Finally, recognising different types of obesity may not only allow a more comprehensive understanding of this illness, but also make it possible to tailor patient-specific treatment pathways.
Driving cessation over a 24‐year period: Dementia severity and cerebrospinal fluid biomarkers
Authors: Stout Sarah H. , Babulal Ganesh M. , Ma Chunyu , Carr David B. , Head Denise M. , Grant Elizabeth A. , Williams Monique M. , Holtzman David M. , Fagan Anne M. , Morris John C. , Roe Catherine M.
Published: January 2018

Introduction

With 36 million older adult U.S. drivers, safety is a critical concern, particularly among those with dementia. It is unclear at what stage of Alzheimer's disease (AD) older adults stop driving and whether preclinical AD affects driving cessation.

Methods

Time to driving cessation was examined based on Clinical Dementia Rating (CDR) and AD cerebrospinal fluid biomarkers. 1795 older adults followed up to 24 years received CDR ratings. A subset (591) had cerebrospinal fluid biomarker measurements and was followed up to 17 years. Differences in CDR and biomarker groups as predictors of time to driving cessation were analyzed using Kaplan‐Meier curves and Cox proportional models.

Results

Higher CDR scores and more abnormal biomarker measurements predicted a shorter time to driving cessation.

Discussion

Higher levels of AD biomarkers, including among individuals with preclinical AD, lead to earlier driving cessation. Negative functional outcomes of preclinical AD show a nonbenign phase of the disease.
Onset of transient natural convection in porous media due to porosity perturbations
Authors: Tilton Nils
Published: January 2018

Onset of natural convection due to transient diffusion in porous media has attracted considerable attention for its applications to CO$_{2}$ sequestration. Stability analyses typically investigate the onset of such convection using an initial value problem approach in which a perturbation is introduced to the concentration field at an initial time $t=t_{p}$. This leads to debate concerning physically appropriate perturbations, the critical time $t_{c}$ for linear instability and the counter-intuitive notion of an optimal initial time $t_{p}$ that maximizes perturbation growth. We propose an alternate approach in which transient diffusion is continuously perturbed by small porosity variations. With this approach, instability occurs immediately ($t_{c}=0$) without violating any physical constraints, such that the concepts of initial time $t_{p}$ and critical time $t_{c}$ become irrelevant. We also argue that the onset time for nonlinear convection is a more physically relevant parameter, and show that it can be predicted using a simple asymptotic expansion. Using the expansion, we explore the onset of nonlinear convection due to porosity perturbations that vary sinusoidally in the horizontal and vertical directions, and show there are optimal wavelengths that minimize the onset time. Finally, we find simple relationships for these wavelengths as functions of perturbation magnitude. These show that even small porosity perturbations, typically considered negligible in previous literature, are sufficient to trigger nonlinear convection and thereby influence the rate of CO$_{2}$ dissolution within time scales comparable to previous analyses.
Audience Experience in an Anti-expert Age: A Survey of Theatre Audience Research
Authors: SEDGMAN KIRSTY
Published: January 2018

Researchers who seek to capture and analyse audiences’ responses are facing a dilemma. In a political climate beleaguered by efforts to delegitimize expertise, what are the implications for a research tradition that seeks to understand cultural value from a range of diverse perspectives? In light of visibility generated by the 2009 publication of Helen Freshwater'sTheatre & Audienceand the subsequent launch in January 2017 of the international Network for Audience Research in the Performing Arts (iNARPA), the time seems ripe for a detailed critical overview of the audience studies discipline as it has been applied to theatre. In providing that survey, this article contends that the early decades of the new millennium have seen research into arts participation becoming trapped between two colliding agendas. Whereas on the one hand there is a growing pressure to celebrate cultural engagement in all its contradictory forms, there has on the other hand been a simultaneous imperative within the arts to push back against the encroaching de-hierarchization of cultural value beyond critical and scholarly perspectives. By revealing the potentials for and limitations of the field, this article queries how future audience research projects might productively investigate audience experience without diminishing the legitimacy of expert knowledge.
Evidence for the age-specific relationship of food insecurity and key dietary outcomes among US children and adolescents
Authors: Eicher-Miller Heather A. , Zhao Yanling
Published: January 2018

Approximately 6·5 million US children live in food-insecure households, meaning that they have restrained access to the types and amounts of foods they usually eat. The nutrient demands of growth and general sub-par dietary intake of US children by age highlight the importance and difficulty of attaining recommended amounts of critical dietary components to promote health and prevent disease. Evaluation of the evidence for a relationship of food insecurity with key dietary outcomes for the specific stages of child growth at 1–5 years, 6–11 years and 12–19 years has not been previously documented. Bradford Hill criteria of strength, consistency and dose–response were applied to aid evaluation. A comprehensive search of original research on US children using food-security assessment measures indexed to January 2017 was completed and identified sixteen studies that evaluated the relationship of food insecurity with key dietary outcomes. Evidence for a strong, consistent and dose–response relationship of food insecurity with lower vegetable intake compared with food security was determined among children aged 1–5 years and strong and consistent evidence of higher added sugar intake among food-insecure children aged 6–11 years compared with food-secure children was apparent. Adolescent-focused evidence was sparse but revealed adolescence as the paediatric age stage where food insecurity has the most potential for negative impact on child dietary intake. A discussion of future research opportunities includes strengthening the evidence through longitudinal study designs, inclusion of additional nutrients of concern, and stronger mitigation of bias and error.
Magnesium homeostasis in cattle: absorption and excretion
Authors: Martens Holger , Leonhard-Marek Sabine , Röntgen Monika , Stumpff Friederike
Published: January 2018

Magnesium (Mg2+) is an essential mineral without known specific regulatory mechanisms. In ruminants, plasma Mg2+concentration depends primarily on the balance between Mg2+absorption and Mg2+excretion. The primary site of Mg2+absorption is the rumen, where Mg2+is apically absorbed by both potential-dependent and potential-independent uptake mechanisms, reflecting involvement of ion channels and electroneutral transporters, respectively. Transport is energised in a secondary active manner by a basolateral Na+/Mg2+exchanger. Ruminal transport of Mg2+is significantly influenced by a variety of factors such as high K+concentration, sudden increases of ammonia, pH, and the concentration of SCFA. Impaired Mg2+absorption in the rumen is not compensated for by increased transport in the small or large intestine. While renal excretion can be adjusted to compensate precisely for any surplus in Mg2+uptake, a shortage in dietary Mg2+cannot be compensated for either via skeletal mobilisation of Mg2+or via up-regulation of ruminal absorption. In such situations, hypomagnesaemia will lead to decrease of a Mg2+in the cerebrospinal fluid and clinical manifestations of tetany. Improved knowledge concerning the factors governing Mg2+homeostasis will allow reliable recommendations for an adequate Mg2+intake and for the avoidance of possible disturbances. Future research should clarify the molecular identity of the suggested Mg2+transport proteins and the regulatory mechanisms controlling renal Mg excretion as parameters influencing Mg2+homeostasis.
Displacement convexity for the entropy in semi-discrete non-linear Fokker–Planck equations
Authors: CARRILLO JOSÉ A. , JÜNGEL ANSGAR , SANTOS MATHEUS C.
Published: January 2018

The displacement λ-convexity of a non-standard entropy with respect to a non-local transportation metric in finite state spaces is shown using a gradient flow approach. The constant λ is computed explicitly in terms ofa prioriestimates of the solution to a finite-difference approximation of a non-linear Fokker–Planck equation. The key idea is to employ a new mean function, which defines the Onsager operator in the gradient flow formulation.
A full-term healthy neonate with respiratory distress
Authors: Nederlof I. , Roest A. A. W. , Starreveld J. S.
Published: January 2018

Pneumopericardium, defined as air in the pericardial cavity, is a rare condition with potentially severe complications and mortality. In the neonatal period, pneumopericardium is associated with prematurity, very low birth weight, and assisted ventilation. We report the occurrence of spontaneous pneumopericardium in a healthy full-term neonate who did not receive any supportive ventilation.
A randomised trial of early palliative care for maternal stress in infants prenatally diagnosed with single-ventricle heart disease
Authors: Hancock Hayley S. , Pituch Ken , Uzark Karen , Bhat Priya , Fifer Carly , Silveira Maria , Yu Sunkyung , Welch Suzanne , Donohue Janet , Lowery Ray , Aiyagari Ranjit
Published: January 2018

Children with single-ventricle disease experience high mortality and complex care. In other life-limiting childhood illnesses, paediatric palliative care may mitigate maternal stress. We hypothesised that early palliative care in the single-ventricle population may have the same benefit for mothers. In this pilot randomised trial of early palliative care, mothers of infants with prenatal single-ventricle diagnoses completed surveys measuring depression, anxiety, coping, and quality of life at a prenatal visit and neonatal discharge. Infants were randomised to receive early palliative care – structured evaluation, psychosocial/spiritual, and communication support before surgery – or standard care. Among 56 eligible mothers, 40 enrolled and completed baseline surveys; 38 neonates were randomised, 18 early palliative care and 20 standard care; and 34 postnatal surveys were completed. Baseline Beck Depression Inventory-II and State-Trait Anxiety Index scores exceeded normal pregnant sample scores (mean 13.76±8.46 versus 7.0±5.0 and 46.34±12.59 versus 29.8±6.35, respectively; p=0.0001); there were no significant differences between study groups. The early palliative care group had a decrease in prenatal to postnatal State-Trait Anxiety Index scores (−7.6 versus 0.3 in standard care, p=0.02), higher postnatal Brief Cope Inventory positive reframing scores (p=0.03), and a positive change in PedsQL Family Impact Module communication and family relationships scores (effect size 0.46 and 0.41, respectively). In conclusion, these data show that mothers of infants with single-ventricle disease experience significant depression and anxiety prenatally. Early palliative care resulted in decreased maternal anxiety, improved maternal positive reframing, and improved communication and family relationships.
Coronary artery spasm due to intravenous atropine infusion in a child: possible Kounis syndrome
Authors: Castellano-Martinez Ana , Rodriguez-Gonzalez Moises
Published: January 2018

Coronary vasospasm can result from silent myocardial ischaemia to sudden death. There are many precipitant factors including different pharmacological agents. Kounis syndrome is defined by acute coronary syndromes associated with anaphylactic or anaphylactoid reactions. We report, to the best of our knowledge, the first paediatric case of Kounis syndrome due to intravenous atropine.
Prehospital Identification of Patients with a Final Hospital Diagnosis of Stroke
Authors: Andersson Elin , Bohlin Linda , Herlitz Johan , Sundler Annelie J. , Fekete Zoltán , Andersson Hagiwara Magnus
Published: January 2018

Introduction

the early phase of stroke, minutes are critical. Since the majority of patients with stroke are transported by the Emergency Medical Service (EMS), the early handling and decision making by the EMS clinician is important.

Problem

The study aim was to evaluate the frequency of a documented suspicion of stroke by the EMS nurse, and to investigate differences in the clinical signs of stroke and clinical assessment in the prehospital setting among patients with regard to if there was a documented suspicion of stroke on EMS arrival or not, in patients with a final hospital diagnosis of stroke.

Methods

The study had a retrospective observational design. Data were collected from reports on patients who were transported by the EMS and had a final diagnosis of stroke at a single hospital in western Sweden (630 beds) in 2015. The data sources were hospital and prehospital medical journals.

Results

In total, 454 patients were included. Among them, the EMS clinician suspected stroke in 52%. The findings and documentation on patients with a suspected stroke differed from the remaining patients as follows:

a)

More frequently documented symptoms from the face, legs/arms, and speech;

b)

More frequently assessments of neurology, face, arms/legs, speech, and eyes;

c)

More frequently addressed the major complaint with regard to time and place of onset, duration, localization, and radiation;

d)

Less frequently documented symptoms of headache, vertigo, and nausea; and

e)

More frequently had an electrocardiogram (ECG) recorded and plasma glucose sampled.

In addition to the 52% of patients who had a documented initial suspicion of stroke, seven percent of the patients had an initial suspicion of transitory ischemic attack (TIA) by the EMS clinician, and a neurologist was approached in another 10%.

Conclusion

Among 454 patients with a final diagnosis of stroke who were transported by the EMS, an initial suspicion of stroke was not documented in one-half of the cases. These patients differed from those in whom a suspicion of stroke was documented in terms of limited clinical signs of stroke, a less extensive clinical assessment, and fewer clinical investigations.

AnderssonE, BohlinL, HerlitzJ, SundlerAJ, FeketeZ, Andersson HagiwaraM. Prehospital identification of patients with a final hospital diagnosis of stroke. Prehosp Disaster Med. 2018;33(1):63–70.
Associations between sedentary behaviours and dietary intakes among adolescents
Authors: Fletcher Elly A , McNaughton Sarah A , Crawford David , Cleland Verity , Della Gatta Jacqueline , Hatt Jennifer , Dollman James , Timperio Anna
Published: January 2018

Objective

The purpose of the current study was to examine associations of individual and aggregated screen-based behaviours, and total sitting time, with healthy and unhealthy dietary intakes among adolescents.

Design

Cross-sectional study of adolescents. Participants self-reported durations of television viewing, computer use, playing electronic games (e-games), total sitting time, daily servings of fruits and vegetables, and frequency of consumption of sugar-sweetened beverages (SSB), diet beverages, fast foods and discretionary snacks. Logistic regression models were conducted to identify associations of screen-based behaviours, total screen time and total sitting time with dietary intakes.

Setting

Victoria, Australia.

Subjects

Adolescents (n 939) in School Year 11 (mean age 16·8 years).

Results

The results showed that watching television (≥2 h/d) was positively associated with consuming SSB and diet beverages each week and consuming discretionary snacks at least once daily, whereas computer use (≥2 h/d) was inversely associated with daily fruit and vegetable intake and positively associated with weekly fast-food consumption. Playing e-games (any) was inversely associated with daily vegetable intake and positively associated with weekly SSB consumption. Total screen (≥2 h/d) and sitting (h/d) times were inversely associated with daily fruit and vegetable consumption, with total screen time also positively associated with daily discretionary snack consumption and weekly consumption of SSB and fast foods.

Conclusions

Individual and aggregated screen-based behaviours, as well as total sitting time, are associated with a number of indicators of healthy and unhealthy dietary intake. Future research should explore whether reducing recreational screen time improves adolescents’ diets.
Mobile produce market influences access to fruits and vegetables in an urban environment
Authors: Hsiao Bi-sek , Sibeko Lindiwe , Wicks Kathy , Troy Lisa M
Published: January 2018

Objective

To assess the influence of a mobile produce market (MPM) on fruit and vegetable access.

Design

Novel application of a structured assessment (five dimensions of access framework) to examine fruit and vegetable access through self-administered surveys on shopping behaviours, and perceptions and experiences of shopping at the MPM.

Setting

Low-income neighbourhoods with limited access to fruits and vegetables.

Subjects

Older (≥60 years) and younger (18–59·9 years) shoppers.

Results

Participants were more likely to be women and non-White, one-third lived alone and nearly half were older adults. Compared with younger, older participants had different shopping behaviours: tended to purchase food for one person (P< 0·001), be long-term shoppers (P=0·002) and use electronic benefit transfer (EBT) cards (P=0·012). Older adults were more likely to like the market location (P=0·03), while younger adults were more likely to want changes in location (P=0·04), more activities (P=0·04), taste sampling (P=0·05) and nutritional counselling (P=0·01). The MPM captured all dimensions of access: availability, indicated by satisfaction with the produce variety for nearly one-third of all participants; accessibility, indicated by participants travelling <1 mile (<1·6 km; 72·2 %) and appreciation of location (72·7 %); affordability, indicated by satisfaction with price (47·6 %); acceptability, indicated by appreciation of produce quality (46·2 %); and accommodation, indicated by satisfaction with safety of location (30·1 %) and high EBT use among older adults (41·8 %).

Conclusions

MPM may influence fruit and vegetable access in low-income urban neighbourhoods by facilitating the five dimensions of access and may especially benefit older adults and individuals living alone.
Stories from the Front Lines: Making Sense of Gender Mainstreaming in Canada
Authors: Scala Francesca , Paterson Stephanie
Published: January 2018

Gender mainstreaming (GM) is a strategy used by governments to promote gender equality. It entails integrating gender and intersectional considerations into all aspects of policy work, including policy formulation, implementation, and evaluation. However, its success in achieving gender equality and social transformation has been limited. Drawing on implementation research and narrative analysis, this article explores the micro-level dynamics and the local actors that help shape the character and outcome of gender mainstreaming. Using narrative analysis, we explore how GM specialists within the Canadian public service make sense of their role, and we identify the strategies they use to make gender matter in policy work. By examining their stories of isolation, disempowerment, and resistance, we uncover the administrative and political forces that shape not only the “space” for gender work but also the opportunities for individual activism and resistance. These stories convey how, by engaging in these micro-level strategies, GM specialists both challenge and reinscribe, at the macro level, technocratic representations of GM and of policy work in general. We conclude with some reflections on the insights that micro-level analysis and implementation research can bring to the study of gender mainstreaming.
Modern Chemicals from Mystery Source Taint Fish in Utah Lake
Authors: Montanari Shaena
Published: January 2018

Utah Lake’s fish contain high levels of a potential carcinogen. Could removing some bottom-feeders reduce this contamination?
Essential thrombocythemia treatment algorithm 2018
Authors: Tefferi Ayalew , Vannucchi Alessandro M. , Barbui Tiziano
Published: January 2018

Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e.g., ruxolitinib). Furthermore, the main indication for treatment in ET and PV is to prevent thrombosis and, in that regard, none of the newer drugs have been shown to be superior to the time-tested older drugs (e.g., hydroxyurea). We currently consider three major risk factors for thrombosis (history of thrombosis, JAK2/MPL mutations, and advanced age), in order to group ET patients into four risk categories: “very low risk” (absence of all three risk factors); “low risk” (presence of JAK2/MPL mutations); “intermediate-risk” (presence of advanced age); and “high-risk” (presence of thrombosis history or presence of both JAK2/MPL mutations and advanced age). Herein, we provide a point-of-care treatment algorithm that is risk-adapted and based on evidence and decades of experience.
Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells
Authors: Page Brent D. G. , Valerie Nicholas C. K. , Wright Roni H. G. , Wallner Olov , Isaksson Rebecka , Carter Megan , Rudd Sean G. , Loseva Olga , Jemth Ann-Sofie , Almlöf Ingrid , Font-Mateu Jofre , Llona-Minguez Sabin , Baranczewski Pawel , Jeppsson Fredrik , Homan Evert , Almqvist Helena , Axelsson Hanna , Regmi Shruti , Gustavsson Anna-Lena , Lundbäck Thomas , Scobie Martin , Strömberg Kia , Stenmark Pål , Beato Miguel , Helleday Thomas
Published: January 2018

With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells. We confirm the involvement of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in breast cancer cells. We herein present TH5427 as a promising, targeted inhibitor that can be used to further study NUDT5 activity and ADP-ribose metabolism.
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2
Authors: Neumann Philipp , Jaé Nicolas , Knau Andrea , Glaser Simone F. , Fouani Youssef , Rossbach Oliver , Krüger Marcus , John David , Bindereif Albrecht , Grote Phillip , Boon Reinier A. , Dimmeler Stefanie
Published: January 2018

Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial–mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.
Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1α
Authors: Kilic Sinan , Felekyan Suren , Doroshenko Olga , Boichenko Iuliia , Dimura Mykola , Vardanyan Hayk , Bryan Louise C. , Arya Gaurav , Seidel Claus A. M. , Fierz Beat
Published: January 2018

The dynamic architecture of chromatin fibers, a key determinant of genome regulation, is poorly understood. Here, we employ multimodal single-molecule Förster resonance energy transfer studies to reveal structural states and their interconversion kinetics in chromatin fibers. We show that nucleosomes engage in short-lived (micro- to milliseconds) stacking interactions with one of their neighbors. This results in discrete tetranucleosome units with distinct interaction registers that interconvert within hundreds of milliseconds. Additionally, we find that dynamic chromatin architecture is modulated by the multivalent architectural protein heterochromatin protein 1α (HP1α), which engages methylated histone tails and thereby transiently stabilizes stacked nucleosomes. This compacted state nevertheless remains dynamic, exhibiting fluctuations on the timescale of HP1α residence times. Overall, this study reveals that exposure of internal DNA sites and nucleosome surfaces in chromatin fibers is governed by an intrinsic dynamic hierarchy from micro- to milliseconds, allowing the gene regulation machinery to access compact chromatin.
Global and regional importance of the direct dust-climate feedback
Authors: Kok Jasper F. , Ward Daniel S. , Mahowald Natalie M. , Evan Amato T.
Published: January 2018

Feedbacks between the global dust cycle and the climate system might have amplified past climate changes. Yet, it remains unclear what role the dust–climate feedback will play in future anthropogenic climate change. Here, we estimate the direct dust–climate feedback, arising from changes in the dust direct radiative effect (DRE), using a simple theoretical framework that combines constraints on the dust DRE with a series of climate model results. We find that the direct dust–climate feedback is likely in the range of −0.04 to +0.02 Wm −2 K−1, such that it could account for a substantial fraction of the total aerosol feedbacks in the climate system. On a regional scale, the direct dust–climate feedback is enhanced by approximately an order of magnitude close to major source regions. This suggests that it could play an important role in shaping the future climates of Northern Africa, the Sahel, the Mediterranean region, the Middle East, and Central Asia.
Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11
Authors: Lagrange Brice , Benaoudia Sacha , Wallet Pierre , Magnotti Flora , Provost Angelina , Michal Fanny , Martin Amandine , Di Lorenzo Flaviana , Py Bénédicte F. , Molinaro Antonio , Henry Thomas
Published: January 2018

Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our results indicate functional differences between human caspase-4 and murine caspase-11. We further establish that human Guanylate-binding proteins promote inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a broader reactivity of caspase-4 to under-acylated LPS than caspase-11, which may have important clinical implications for management of sepsis.
Skin-inspired highly stretchable and conformable matrix networks for multifunctional sensing
Authors: Hua Qilin , Sun Junlu , Liu Haitao , Bao Rongrong , Yu Ruomeng , Zhai Junyi , Pan Caofeng , Wang Zhong Lin
Published: January 2018

Mechanosensation electronics (or Electronic skin, e-skin) consists of mechanically flexible and stretchable sensor networks that can detect and quantify various stimuli to mimic the human somatosensory system, with the sensations of touch, heat/cold, and pain in skin through various sensory receptors and neural pathways. Here we present a skin-inspired highly stretchable and conformable matrix network (SCMN) that successfully expands the e-skin sensing functionality including but not limited to temperature, in-plane strain, humidity, light, magnetic field, pressure, and proximity. The actualized specific expandable sensor units integrated on a structured polyimide network, potentially in three-dimensional (3D) integration scheme, can also fulfill simultaneous multi-stimulus sensing and achieve an adjustable sensing range and large-area expandability. We further construct a personalized intelligent prosthesis and demonstrate its use in real-time spatial pressure mapping and temperature estimation. Looking forward, this SCMN has broader applications in humanoid robotics, new prosthetics, human–machine interfaces, and health-monitoring technologies.
Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition
Authors: Liu Xia , Mo Wei , Ye Jian , Li Lingyun , Zhang Yanping , Hsueh Eddy C. , Hoft Daniel F. , Peng Guangyong
Published: January 2018

Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence. Human Treg-induced T-cell senescence can be prevented via inhibition of the DNA damage response and/or STAT signaling in T-cell adoptive transfer mouse models. These studies identify molecular mechanisms of human Treg cell suppression and indicate that targeting Treg-induced T-cell senescence is a checkpoint for immunotherapy against cancer and other diseases associated with Treg cells.
A prebiotic template-directed peptide synthesis based on amyloids
Authors: Rout Saroj K. , Friedmann Michael P. , Riek Roland , Greenwald Jason
Published: January 2018

The prebiotic replication of information-coding molecules is a central problem concerning life’s origins. Here, we report that amyloids composed of short peptides can direct the sequence-selective, regioselective and stereoselective condensation of amino acids. The addition of activated DL-arginine and DL-phenylalanine to the peptide RFRFR-NH2 in the presence of the complementary template peptide Ac-FEFEFEFE-NH2 yields the isotactic product FRFRFRFR-NH2, 1 of 64 possible triple addition products, under conditions in which the absence of template yields only single and double additions of mixed stereochemistry. The templating mechanism appears to be general in that a different amyloid formed by (Orn)V(Orn)V(Orn)V(Orn)V-NH2 and Ac-VDVDVDVDV-NH2 is regioselective and stereoselective for N-terminal, L-amino-acid addition while the ornithine-valine peptide alone yields predominantly sidechain condensation products with little stereoselectivity. Furthermore, the templating reaction is stable over a wide range of pH (5.6–8.6), salt concentration (0–4 M NaCl), and temperature (25–90 °C), making the amyloid an attractive model for a prebiotic peptide replicating system.
Zika Virus in Salivary Glands of Five Different Species of Wild-Caught Mosquitoes from Mexico
Authors: Elizondo-Quiroga Darwin , Medina-Sánchez Aarón , Sánchez-González Jorge M. , Eckert Kristen Allison , Villalobos-Sánchez Erendira , Navarro-Zúñiga Antonio Rigoberto , Sánchez-Tejeda Gustavo , Correa-Morales Fabián , González-Acosta Cassandra , Arias Carlos F. , López Susana , del Ángel Rosa María , Pando-Robles Victoria , Elizondo-Quiroga Armando E.
Published: January 2018

Zika virus (ZIKV) is a mosquito-borne pathogen, and Aedes aegypti has been identified as the main vector of the disease. Other mosquito species in the Aedes and Culex genera have been suggested to have the potential for being competent vectors based on experimental exposition of mosquitoes to an infectious blood meal containing ZIKV. Here, we report the isolation in cell culture of ZIKV obtained from different body parts of wild-caught female mosquitoes (Ae. aegypti, Ae. vexans, Cx. quinquefasciatus, Cx. coronator, and Cx. tarsalis) and whole male mosquitoes (Ae. aegypti and Cx. quinquefasciatus) in Mexico. Importantly, this is the first report that shows the presence of the virus in the salivary glands of the wild-caught female mosquitoes species, Cx. coronator, Cx. tarsalis, and Ae. vexans. Our findings strongly suggest that all the species reported herein are potential vectors for ZIKV.
Mesoscale Dzyaloshinskii-Moriya interaction: geometrical tailoring of the magnetochirality
Authors: Volkov Oleksii M. , Sheka Denis D. , Gaididei Yuri , Kravchuk Volodymyr P. , Rößler Ulrich K. , Fassbender Jürgen , Makarov Denys
Published: January 2018

Crystals with broken inversion symmetry can host fundamentally appealing and technologically relevant periodical or localized chiral magnetic textures. The type of the texture as well as its magnetochiral properties are determined by the intrinsic Dzyaloshinskii-Moriya interaction (DMI), which is a material property and can hardly be changed. Here we put forth a method to create new artificial chiral nanoscale objects with tunable magnetochiral properties from standard magnetic materials by using geometrical manipulations. We introduce a mesoscale Dzyaloshinskii-Moriya interaction that combines the intrinsic spin-orbit and extrinsic curvature-driven DMI terms and depends both on the material and geometrical parameters. The vector of the mesoscale DMI determines magnetochiral properties of any curved magnetic system with broken inversion symmetry. The strength and orientation of this vector can be changed by properly choosing the geometry. For a specific example of nanosized magnetic helix, the same material system with different geometrical parameters can acquire one of three zero-temperature magnetic phases, namely, phase with a quasitangential magnetization state, phase with a periodical state and one intermediate phase with a periodical domain wall state. Our approach paves the way towards the realization of a new class of nanoscale spintronic and spinorbitronic devices with the geometrically tunable magnetochirality.
Role of Macromolecular Crowding on the Intracellular Diffusion of DNA Binding Proteins
Authors: Dey Pinki , Bhattacherjee Arnab
Published: January 2018

Recent experiments suggest that cellular crowding facilitates the target search dynamics of proteins on DNA, the mechanism of which is not yet known. By using large scale computer simulations, we show that two competing factors, namely the width of the depletion layer that separates the crowder cloud from the DNA molecule and the degree of protein-crowder crosstalk, act in harmony to affect the target search dynamics of proteins. The impacts vary from nonspecific to specific target search regime. During a nonspecific search, dynamics of a protein is only minimally affected, whereas, a significantly different behaviour is observed when the protein starts forming a specific protein-DNA complex. We also find that the severity of impacts largely depends upon physiological crowder concentration and deviation from it leads to attenuation in the binding kinetics. Based on extensive kinetic study and binding energy landscape analysis, we further present a comprehensive molecular description of the search process that allows us to interpret the experimental findings.
JmjC domain proteins modulate circadian behaviors and sleep in Drosophila
Authors: Shalaby Nevine A. , Pinzon Jorge H. , Narayanan Anjana S. , Jin Eugene Jennifer , Ritz Morgan P. , Dove Rachel J. , Wolfenberg Heike , Rodan Aylin R. , Buszczak Michael , Rothenfluh Adrian
Published: January 2018

Jumonji (JmjC) domain proteins are known regulators of gene expression and chromatin organization by way of histone demethylation. Chromatin modification and remodeling provides a means to modulate the activity of large numbers of genes, but the importance of this class of predicted histone-modifying enzymes for different aspects of post-developmental processes remains poorly understood. Here we test the function of all 11 non-lethal members in the regulation of circadian rhythms and sleep. We find loss of every Drosophila JmjC gene affects different aspects of circadian behavior and sleep in a specific manner. Together these findings suggest that the majority of JmjC proteins function as regulators of behavior, rather than controlling essential developmental programs.
A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge
Authors: Domi Arban , Feldmann Friederike , Basu Rahul , McCurley Nathanael , Shifflett Kyle , Emanuel Jackson , Hellerstein Michael S. , Guirakhoo Farshad , Orlandi Chiara , Flinko Robin , Lewis George K. , Hanley Patrick W. , Feldmann Heinz , Robinson Harriet L. , Marzi Andrea
Published: January 2018

Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013–2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective immune responses. In this study, we report 100% protection against lethal EBOV infection in guinea pigs after prime/boost vaccination with MVA-EBOV. Furthermore, this MVA-EBOV protected macaques from lethal disease after a single dose or prime/boost vaccination. The vaccine elicited a variety of antibody responses to both antigens, including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. This is the first report that a replication-deficient MVA vector can confer full protection against lethal EBOV challenge after a single dose vaccination in macaques.
Development and optimization of a differentiated airway epithelial cell model of the bovine respiratory tract
Authors: Cozens Daniel , Grahame Edward , Sutherland Erin , Taylor Geraldine , Berry Catherine C. , Davies Robert L.
Published: January 2018

Cattle are subject to economically-important respiratory tract infections by various bacterial and viral pathogens and there is an urgent need for the development of more realistic in vitro models of the bovine respiratory tract to improve our knowledge of disease pathogenesis. In the present study, we have optimized the culture conditions in serum-free medium that allow bovine bronchial epithelial cells (BBECs) grown at an air-liquid interface to differentiate into a three-dimensional epithelium that is highly representative of the bovine airway. Epidermal growth factor was required to trigger both proliferation and differentiation of BBECs whilst retinoic acid was also essential for mucociliary differentiation. Triiodothyronine was demonstrated not to be important for the differentiation of BBECs. Oxygen concentration had a minimal effect although optimal ciliation was achieved when BBECs were cultured at 14% oxygen tension. Insert pore-density had a significant effect on the growth and differentiation of BBECs; a high-pore-density was required to trigger optimum differentiation. The established BBEC model will have wide-ranging applications for the study of bacterial and viral infections of the bovine respiratory tract; it will contribute to the development of improved vaccines and therapeutics and will reduce the use of cattle in in vivo experimentation.