bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety Considerations in Pharmacotherapy of Bipolar Disorder
Authors: Masand Prakash S. , Fazal Farhan S. , Patkar Ashwin A. 
Published: August 2016

AbstractBipolar disorder is a chronic, frequently relapsing illness with a prevalence of 1.2% to 3.4% in the general population. It is associated with high disability, higher comorbidity due to medical illnesses, and significant social and economical consequences for patients, their families, and society. The episodic nature of this disease warrants rational use of medications and proper monitoring for adverse events. Various drug classes, such as mood stabilizers, antipsychotics, benzodiazepines, and antidepressants, are used for the acute and maintenance treatment of bipolar disorder. Each group of drugs is associated with wide array of adverse events and drug interactions, which are the main hurdles in treatment outcome and compliance. Common side effects seen with several agents, particularly antipsychotics, are somnolence, weight gain, extrapyramidal symptoms, dyslipidemia, type-2 diabetes, and hyperprolactinemia. Major drug interactions are seen with drugs such as carbamazepine, due to hepatic enzyme induction. Adverse effects such as somnolence are tolerability concerns and can be managed easily; others, such as diabetes mellitus, are safety concerns. It is prudent to have precise knowledge of the individual drug's side-effect profile, pharmacokinetics, and pharmacodynamics, to plan a treatment regimen. More research is needed to understand potential rish of various drugs and to devise and incorporate monitoring protocols in the treatment regimen.
Il Symptom Questionnaire come strumento di screening nei contesti sanitari di base
Authors: Rucci Paola , de Marco Piero , Bivi Raffaella 
Published: August 2016

SummaryObjective. - To test by means of ROC analysis the performance of the Symptom Questionnaire (SQ) of Kellner and Fava against an interview designed for making DSM-III diagnoses in 517 subjects. To analyse the trend of SQ scores at 3 months, 1 year and 2 years after the first interview in a sample of 112 persons. Design. - Cross-sectional and longitudinal analysis of the distributions of SQ scores in DSM-III cases and in non-cases. Setting. - General practice, hospital medical wards and emergency departments of Regione Emilia Romagna. Main outcome measures. - Symptom Questionnaire, Bech Mini-compendium to formulate DSM-III diagnoses. Results. - The SQ reached high sensitivity and specificity levels (80%, 76% in general practice, 86%, 74% in hospital medical wards, 83%, 85% in emergency departments with the cut-off scores of 24, 24 and 26, respectively). SQ scores show a similar trend in cases and in non-cases, with a significant drop at three months. Conclusions. - The SQ seems to be an adequate screening tool in the above-mentioned settings, but its length and the assistance sometimes needed during the compilation make its use in the emergency departments problematic.
Mechanistic stratification in electroactive biofilms of Geobacter sulfurreducens mediated by pilus nanowires
Authors: Steidl Rebecca J. , Lampa-Pastirk Sanela , Reguera Gemma 
Published: August 2016

AbstractElectricity generation by Geobacter sulfurreducens biofilms grown on electrodes involves matrix-associated electron carriers, such as c-type cytochromes. Yet, the contribution of the biofilm’s conductive pili remains uncertain, largely because pili-defective mutants also have cytochrome defects. Here we report that a pili-deficient mutant carrying an inactivating mutation in the pilus assembly motor PilB has no measurable defects in cytochrome expression, yet forms anode biofilms with reduced electroactivity and is unable to grow beyond a threshold distance (∼10 μm) from the underlying electrode. The defects are similar to those of a Tyr3 mutant, which produces poorly conductive pili. The results support a model in which the conductive pili permeate the biofilms to wire the cells to the conductive biofilm matrix and the underlying electrode, operating coordinately with cytochromes until the biofilm reaches a threshold thickness that limits the efficiency of the cytochrome pathway but not the functioning of the conductive pili network.
Ancient landscapes and the relationship with microbial nitrification
Authors: Jenkins Sasha N. , Murphy Daniel V. , Waite Ian S. , Rushton Steven P. , O’Donnell Anthony G. 
Published: August 2016

AbstractAmmonia oxidizing archaea (AOA) and bacteria (AOB) drive nitrification and their population dynamics impact directly on the global nitrogen cycle. AOA predominate in the majority of soils but an increasing number of studies have found that nitrification is largely attributed to AOB. The reasons for this remain poorly understood. Here,amoAgene abundance was used to study the distribution of AOA and AOB in agricultural soils on different parent materials and in contrasting geologic landscapes across Australia (n = 135 sites). AOA and AOB abundances separated according to the geologic age of the parent rock with AOB higher in the more weathered, semi-arid soils of Western Australia. AOA dominated the younger, higher pH soils of Eastern Australia, independent of any effect of land management and fertilization. This differentiation reflects the age of the underlying parent material and has implications for our understanding of global patterns of nitrification and soil microbial diversity. Western Australian soils are derived from weathered archaean laterite and are acidic and copper deficient. Copper is a co-factor in the oxidation of ammonia by AOA but not AOB. Thus, copper deficiency could explain the unexpectedly low populations of AOA in Western Australian soils.
The differential short- and long-term effects of HIV-1 latency-reversing agents on T cell function
Authors: Clutton G. , Xu Y. , Baldoni P. L. , Mollan K. R. , Kirchherr J. , Newhard W. , Cox Kara , Kuruc J. D. , Kashuba A. , Barnard R. , Archin N. , Gay C. L. , Hudgens M. G. , Margolis D. M. , Goonetilleke N. 
Published: August 2016

AbstractDespite the extraordinary success of HIV-1 antiretroviral therapy in prolonging life, infected individuals face lifelong therapy because of a reservoir of latently-infected cells that harbor replication competent virus. Recently, compounds have been identified that can reverse HIV-1 latency in vivo. These latency- reversing agents (LRAs) could make latently-infected cells vulnerable to clearance by immune cells, including cytolytic CD8+ T cells. We investigated the effects of two leading LRA classes on CD8+ T cell phenotype and function: the histone deacetylase inhibitors (HDACis) and protein kinase C modulators (PKCms). We observed that relative to HDACis, the PKCms induced much stronger T cell activation coupled with non-specific cytokine production and T cell proliferation. When examining antigen-specific CD8+ T cell function, all the LRAs except the HDACi Vorinostat reduced, but did not abolish, one or more measurements of CD8+ T cell function. Importantly, the extent and timing of these effects differed between LRAs. Panobinostat had detrimental effects within 10 hours of drug treatment, whereas the effects of the other LRAs were observed between 48 hours and 5 days. These observations suggest that scheduling of LRA and CD8+ T cell immunotherapy regimens may be critical for optimal clearance of the HIV-1 reservoir.
Lysine-specific histone demethylase 1 inhibition promotes reprogramming by facilitating the expression of exogenous transcriptional factors and metabolic switch
Authors: Sun Hao , Liang Lining , Li Yuan , Feng Chengqian , Li Lingyu , Zhang Yixin , He Songwei , Pei Duanqing , Guo Yunqian , Zheng Hui 
Published: August 2016

AbstractLysine-specific histone demethylase 1 (LSD1) regulates histone methylation and influences the epigenetic state of cells during the generation of induced pluripotent stem cells (iPSCs). Here we reported that LSD1 inhibition via shRNA or specific inhibitor, tranylcypromine, promoted reprogramming at early stage via two mechanisms. At early stage of reprogramming, LSD1 inhibition increased the retrovirus-mediated exogenous expression of Oct4, Klf4 and Sox2 by blocking related H3K4 demethylation. Since LSD1 inhibition still promoted reprogramming even when iPSCs were induced with small-molecule compounds in a virus-free system, additional mechanisms should be involved. When RNA-seq was used for analysis, it was found that LSD1 inhibition reversed some gene expression changes induced by OKS, which subsequently promoted reprogramming. For example, by partially rescuing the decreased expression of Hif1α, LSD1 inhibition reversed the up-regulation of genes in oxidative phosphorylation pathway and the down-regulation of genes in glycolysis pathway. Such effects facilitated the metabolic switch from oxidative phosphorylation to glycolysis and subsequently promoted iPSCs induction. In addition, LSD1 inhibition also promoted the conversion from pre-iPSCs to iPSCs by facilitating the similar metabolic switch. Therefore, LSD1 inhibition promotes reprogramming by facilitating the expression of exogenous transcriptional factors and metabolic switch.
Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease
Authors: Rey Martial , Yang Menglin , Lee Linda , Zhang Ye , Sheff Joey G. , Sensen Christoph W. , Mrazek Hynek , Halada Petr , Man Petr , McCarville Justin L , Verdu Elena F. , Schriemer David C. 
Published: August 2016

AbstractCeliac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1.
Bad faith in All’s Well That Ends Well
Authors: Hadfield Andrew 
Published: August 2016

AbstractAll’s Well That Ends Wellis a complicated and disturbing play that has a comic ending, but which seems anything but a comedy with a forced marriage based on bed-trickery between the reluctant Bertram and the feisty and witty Helena. Unsurprisingly, audiences have tended to side with Helena and the play has been classified as a “problem comedy” ever since William Lawrence identified this particular group of Shakespeare plays nearly a century ago. I want to argue in this essay that the play might better be classified as an “equivocation” play alongsideMacbeth, Othello, andTroilus and Cressidaand that the anxieties about fidelity, honesty and truthfulness in marriage need to be read in terms of the fear of religious tolerance/intolerance which dominated religious politics in the early years of James’s reign before the passing of the Oath of Allegiance (1606). The play is notable for its interest in chop logic, which the clown in particular displays throughout the play, a counterpoint to the arguments of Bertram and Helena who want very different things, but who are bound together as future husband and wife. Although the language of treason and treachery is used throughout, the play is less interested in answering the question of how far one can trust a stranger within than the issue of how far one can accommodate the needs of others. This article is published as part of a collection to commemorate the 400th anniversary of William Shakespeare’s death.
Cross-linguistic patterns in the acquisition of quantifiers
Authors: Katsos Napoleon , Cummins Chris , Ezeizabarrena Maria-José , Gavarró Anna , Kuvač Kraljević Jelena , Hrzica Gordana , Grohmann Kleanthes K. , Skordi Athina , Jensen de López Kristine , Sundahl Lone , van Hout Angeliek , Hollebrandse Bart , Overweg Jessica , Faber Myrthe , van Koert Margreet , Smith Nafsika , Vija Maigi , Zupping Sirli , Kunnari Sari , Morisseau Tiffany , Rusieshvili Manana , Yatsushiro Kazuko , Fengler Anja , Varlokosta Spyridoula , Konstantzou Katerina , Farby Shira , Guasti Maria Teresa , Vernice Mirta , Okabe Reiko , Isobe Miwa , Crosthwaite Peter , Hong Yoonjee , Balčiūnienė Ingrida , Ahmad Nizar Yanti Marina , Grech Helen , Gatt Daniela , Cheong Win Nee , Asbjørnsen Arve , Torkildsen Janne von Koss , Haman Ewa , Miękisz Aneta , Gagarina Natalia , Puzanova Julia , Anđelković Darinka , Savić Maja , Jošić Smiljana , Slančová Daniela , Kapalková Svetlana , Barberán Tania , Özge Duygu , Hassan Saima , Chan Cecilia Yuet Hung , Okubo Tomoya , van der Lely Heather , Sauerland Uli , Noveck Ira 
Published: August 2016

Significance
Although much research has been devoted to the acquisition of number words, relatively little is known about the acquisition of other expressions of quantity. We propose that the order of acquisition of quantifiers is related to features inherent to the meaning of each term. Four specific dimensions of the meaning and use of quantifiers are found to capture robust similarities in the order of acquisition of quantifiers in similar ways across 31 languages, representing 11 language types.
Transition path theory analysis of c-Src kinase activation
Authors: Meng Yilin , Shukla Diwakar , Pande Vijay S. , Roux Benoît 
Published: August 2016

SignificanceProteins often exhibit large-scale collective motions that are essential for biological macromolecules to perform their functions. To understand the nature of the large-scale conformational dynamics, we applied transition path theory to analyze the Markovian microstates that are obtained from extensive unrestrained molecular dynamics simulations, using the activating conformational changes in the kinase domain of c-Src nonreceptor tyrosine kinase as an example. These results elucidate the fine details of the conformational transition and offer a perspective for the interpretation of the conformational transition. Microstates that are not crucial to the thermodynamics but are important for the kinetics can be identified by transition path theory, explaining why extensive conformational sampling is needed to reproduce the accurate kinetics.
Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death
Authors: Aiba Isamu , Wehrens Xander H. T. , Noebels Jeffrey L. 
Published: August 2016

Significance
Gain-of-function “leaky” ryanodine receptor-2 (RyR2) mutations are detected in many cases of human sudden cardiac death and sudden unexpected death in epilepsy. The early lethality is considered to be due to arrhythmogenic behavior of cardiomyocytes caused by excess intracellular calcium ions released from internal stores. In this study, we find that the leaky RyR2 mutation also modulates neurotransmitter release from neurons in brainstem autonomic centers and facilitates spreading depolarization, which when provoked silences autonomic microcircuitry in the dorsal medulla. When seizures were generated in mice carrying a leaky RyR2 mutation, the mice experienced sudden cardiorespiratory collapse concomitant with brainstem spreading depolarization. These findings indicate that in addition to the myocardium, the brainstem is a target of leaky RyR2 mutations.
Learning to soar in turbulent environments
Authors: Reddy Gautam , Celani Antonio , Sejnowski Terrence J. , Vergassola Massimo 
Published: August 2016

Significance
Thermals are ascending currents that typically extend from the ground up to the base of the clouds. Birds and gliders piggyback thermals to fly with a reduced expenditure of energy, for example, during migration, and to extend their flying range. Flow in the thermals is highly turbulent, which poses the challenge of the orientation in strongly fluctuating environments. We combine numerical simulations of atmospheric flow with reinforcement learning methods to identify strategies of navigation that can cope with and even exploit turbulent fluctuations. Specifically, we show how the strategies evolve as the level of turbulent fluctuations increase, and we identify those sensorimotor cues that are effective at directing turbulent navigation.
Contrasting climate change impact on river flows from high-altitude catchments in the Himalayan and Andes Mountains
Authors: Ragettli Silvan , Immerzeel Walter W. , Pellicciotti Francesca 
Published: August 2016

Significance
Changes in the hydrology of high-altitude catchments may have major consequences for downstream water supply. Based on model projections with a higher spatiotemporal resolution and degree of process complexity than any previous intercontinental comparative study, we show that the impacts of climate change cannot be generalized. These impacts range from a high climatic sensitivity, decreasing runoff, and significant seasonal changes in the Central Andes of Chile to increasing future runoff, limited seasonal shifts, but increases in peak flows in the Nepalese Himalaya. This study constrains uncertainty about response times and mechanisms controlling glacier and runoff response to climate and sets a benchmark for process-based modeling of the climate change impact on the hydrology of high-altitude catchments.
Early gut colonizers shape parasite susceptibility and microbiota composition in honey bee workers
Authors: Schwarz Ryan S. , Moran Nancy A. , Evans Jay D. 
Published: August 2016

Significance
Using a social insect model, we tested how supplementing young adult bees with a resident microbiota species affects host physiology and microbiome composition. This supplementation had significant consequences for host development and detoxification responses, parasite susceptibility, and microbiome community structure. Our results show that early perturbation of the microbiota composition can have sustained consequences for hosts. Additionally, this work provides a cautionary tale to the arbitrary use of probiotics in animal health management and highlights the importance of experimental research addressing factors that shape animal microbiome communities.
Unhealthy Alcohol use in Primary Care Patients who Screen Positive for Drug Use
Authors: Maynié-François Christine , Cheng Debbie M. , Samet Jeffrey H. , Lloyd-Travaglini Christine , Palfai Tibor , Bernstein Judith , Saitz Richard 
Published: August 2016

Background Unhealthy alcohol use (UAU) is common among people who use other drugs; however, little information is available about UAU among patients who screen positive for drugs in primary care, where the clinical priority might be assumed to be drug use. This study aimed at describing the occurrence of UAU and its association with substance use–related outcomes in such patients. Methods This cohort study is a secondary analysis of data from a randomized trial of brief intervention for primary care patients screening positive for drug use. UAU was assessed at baseline; the main independent variable was any heavy drinking day in the past month. Outcomes including drug use characteristics and substance use–related consequences were assessed at baseline and 6 months later. Results Of 589 primary care patients with drug use, 48% had at least 1 past-month heavy drinking day. The self-identified main drug was marijuana for 64%, cocaine for 18%, and an opioid for 16%. Any heavy drinking at baseline was negatively associated with number of days use of the main drug at 6 months (incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI]: 0.62–0.91), but positively associated with the use of more than 1 drug (IRR = 1.73, 95% CI: 1.17–2.55) and unsafe sex (odds ratio [OR] = 1.90, 95% CI: 1.21–2.98). Conclusion Unhealthy alcohol use is common among patients identified by screening in primary care as using other drugs. Unexpectedly, UAU was negatively associated with days of main drug use. But, as expected, it was positively associated with other drug use characteristics and substance use–related consequences. These findings suggest that attention should be given to alcohol use among primary care patients who use other drugs.
Censusing marine eukaryotic diversity in the twenty-first century
Authors: Leray Matthieu , Knowlton Nancy 
Published: August 2016

The ocean constitutes one of the vastest and richest biomes on our planet. Most recent estimations, all based on indirect approaches, suggest that there are millions of marine eukaryotic species. Moreover, a large majority of these are small (less than 1 mm), cryptic and still unknown to science. However, this knowledge gap, caused by the lack of diagnostic morphological features in small organisms and the limited sampling of the global ocean, is currently being filled, thanks to new DNA-based approaches. The molecular technique of PCR amplification of homologous gene regions combined with high-throughput sequencing, routinely used to census unculturable prokaryotes, is now also being used to characterize whole communities of marine eukaryotes. Here, we review how this methodological advancement has helped to better quantify the magnitude and patterns of marine eukaryotic diversity, with an emphasis on taxonomic groups previously largely overlooked. We then discuss obstacles remaining to achieve a global understanding of marine eukaryotic diversity. In particular, we argue that 18S variable regions do not provide sufficient taxonomic resolution to census marine life, and suggest combining broad eukaryotic surveys targeting the 18S rRNA region with more taxon-focused analyses of hypervariable regions to improve our understanding of the diversity of species, the functional units of marine ecosystems.
This article is part of the themed issue ‘From DNA barcodes to biomes’.
Scaling up discovery of hidden diversity in fungi: impacts of barcoding approaches
Authors: Yahr Rebecca , Schoch Conrad L. , Dentinger Bryn T. M. 
Published: August 2016

The fungal kingdom is a hyperdiverse group of multicellular eukaryotes with profound impacts on human society and ecosystem function. The challenge of documenting and describing fungal diversity is exacerbated by their typically cryptic nature, their ability to produce seemingly unrelated morphologies from a single individual and their similarity in appearance to distantly related taxa. This multiplicity of hurdles resulted in the early adoption of DNA-based comparisons to study fungal diversity, including linking curated DNA sequence data to expertly identified voucher specimens. DNA-barcoding approaches in fungi were first applied in specimen-based studies for identification and discovery of taxonomic diversity, but are now widely deployed for community characterization based on sequencing of environmental samples. Collectively, fungal barcoding approaches have yielded important advances across biological scales and research applications, from taxonomic, ecological, industrial and health perspectives. A major outstanding issue is the growing problem of ‘sequences without names’ that are somewhat uncoupled from the traditional framework of fungal classification based on morphology and preserved specimens. This review summarizes some of the most significant impacts of fungal barcoding, its limitations, and progress towards the challenge of effective utilization of the exponentially growing volume of data gathered from high-throughput sequencing technologies.This article is part of the themed issue ‘From DNA barcodes to biomes’.