bluuebunny/crossref_metadata_2025_split huggingface dataset:
GOOD VISUAL OUTCOME IN A BILATERAL MULTIFOCAL SYPHILITIC CHORIORETINITIS, DESPITE LATE DIAGNOSIS
Authors: de Aragao Ricardo Evangelista Marrocos , Barreira Ieda Maria Alexandre , Muccioli Cristina , Carneiro Gustavo Jose Arruda Mendes , de Araujo Cesar Pereira , de Almeida Everton Fernandes Vieira , Oria Talles Peterson Cavalcante , Pinto Nayara Queiroz Cardoso , Ferreira Jhonatan de Paula Araujo 
Published: January 2017

Purpose:
To report a case of a good visual outcome in a patient with bilateral multifocal syphilitic chorioretinitis, despite the late diagnosis.

Methods:
Ophthalmologic examination, multimodal imaging, including fundus photography, angiography, and optical coherence tomography.

Results:
The authors describe a 47-year-old heterosexual man with a bilateral multifocal syphilitic chorioretinitis that was lately diagnosed and despite that had a good visual outcome.

Conclusion:
The diagnosis of ocular syphilis is a challenge; however, once it has been made, even lately, it is eminently treatable.
The New York State Healthy Neighborhoods Program: Findings From an Evaluation of a Large-Scale, Multisite, State-Funded Healthy Homes Program
Authors: Reddy Amanda L. , Gomez Marta , Dixon Sherry L. 
Published: January 2017

Context:
A growing evidence base suggests that a comprehensive healthy homes approach may be an effective strategy for improving housing hazards that affect health, but questions remain about the feasibility of large-scale implementation.

Objective:
To evaluate the impact of a large-scale, multisite, state-funded healthy homes program.

Setting:
Homes in high-risk neighborhoods of 13 counties funded under the New York State Healthy Neighborhoods Program (NYS HNP) from 2008 to 2012.

Participants:
A total of 28 491 homes received an initial visit and 6436 dwellings received a revisit (follow-up assessment 3 to 6 months after the intervention). A majority of residents are low-income renters living in buildings built prior to 1950.

Intervention:
The NYS HNP is a low-intensity healthy homes program. Participating homes undergo a visual assessment to identify potential environmental health and safety hazards, and interventions (education, referrals, and products) are provided to address any hazards identified during the visit.

Main Outcome Measures:
The proportion of homes affected by several types of housing hazards, improvement in hazards among revisited homes, and the change in the overall number of hazards per home were assessed.

Results:
Among the homes that were revisited, there were significant improvements in the conditions assessed for tobacco control, fire safety, lead poisoning prevention, indoor air quality, and other hazards (including pests and mold). There was a significant reduction in the number of hazards per home (2.8 to 1.5; P < .001), but homes were not hazard-free at the revisit.

Conclusion:
This evaluation suggests that a comprehensive, low-intensity healthy housing approach can produce short-term impacts with public health significance. This evaluation provides information about hazards that are common, easily assessed, and easily corrected or improved, which may be of use to a variety of programs that already provide in-home services and are seeking to expand the scope of their visits or to inform the development of new programs.
An Evaluation of a State-Funded Healthy Homes Intervention on Asthma Outcomes in Adults and Children
Authors: Reddy Amanda L. , Gomez Marta , Dixon Sherry L. 
Published: January 2017

Context:
Reducing exposure to environmental triggers is a critical part of asthma management.

Objective:
To evaluate the impact of a healthy homes intervention on asthma outcomes and assess the impact of different targeting strategies.

Setting:
The New York State (NYS) Healthy Neighborhoods Program (HNP) operates in select communities with a higher burden of housing-related illness and associated risk factors.

Participants:
Residents with asthma were recruited through 3 mechanisms: door-to-door canvassing (CANVASSED), 752 residents in 457 dwellings; referrals from community partners (REFERRED), 573 residents in 307 dwellings; referrals of Medicaid enrollees with poorly controlled asthma (TARGETED), 140 residents in 140 dwellings.

Intervention:
The NYS HNP provides visual assessments and low-cost interventions to identify and address asthma triggers and trigger-promoting conditions in the home environment. Conditions are reassessed during a revisit conducted 3 to 6 months after the initial visit.

Main Outcome Measure(s):
The analysis compares improvements across the 3 groups for measures of asthma self-management, health care access, morbidity, and environmental conditions. An asthma trigger score characterizing the extent of multiple triggers in a dwelling was also calculated.

Results:
Among 1465 adults and children, there were significant improvements in environmental conditions and self-reported self-management, health care access, and asthma morbidity outcomes for each group. The improvement was greatest in the TARGETED group for most outcomes, but selected measures of self-management and health care access were greater in the other groups. The mean improvement was significantly greater in the TARGETED group.

Conclusion:
Targeting the intervention to people with poorly controlled asthma maximizes improvements in trigger avoidance and asthma morbidity; however, other recruitment strategies are effective for impacting endpoints related to health care access and self-management. This evaluation demonstrates that a low-intensity home-based environmental intervention is effective as well as practical and feasible. Health care payers, state and local health departments, and others should consider investing in these home-based services as part of a comprehensive asthma care package.
Gαq Mediates Clozapine Effects inCaenorhabditiselegans
Authors: Hao Limin , Tong Yongguang , Harrington Kristin , O’Neill Jessica L. , Sheikholeslami Afsaneh , Wang Xin , Freedman Jonathan H. , Cohen Bruce M. , Buttner Edgar A. 
Published: January 2017

ABSTRACTClozapine binds and has significant effects on multiple neurotransmitter receptors, notably including some dopamine receptors. Downstream of these receptors, clozapine affects the balance of Gi− and Gq-dependent second-messenger signaling. We usedCaenorhabiditis elegansas a genetic model to study further how clozapine affects both dopamine receptors and downstream Gq mediated signaling. Four of six worm dopamine receptor orthologs,dop-1, dop-2, dop-4, anddop-5produced resistance to clozapine induced developmental delay when mutated, suggesting that both type I and type II dopamine receptors mediate the behavioral effects of clozapine inC. elegans. Beyond these receptors, reduction of function of one of the G proteins,egl-30(Gαq), produced greatly increased susceptibility to clozapine. Gαq has multiple known downstream effects. Among these is the control of acetylcholine release, which is in balance with monoamines in the human brain and is another target of clozapine and other antipsychotic drugs. We tested for downstream effects on acetylcholine at the neuromuscular junction upon clozapine treatment but found no evidence for effects of clozapine. In contrast, modulation of Gαq upstream leads to worms that are either more resistant or more susceptible to clozapine, emphasizing the importance of Gαq proteins in mediating effects of clozapine. A genetic screen for suppressors ofegl-30recovered eight mutants. By characterizing the behavioral effects of these mutants, we found that clozapine exerts its function on development by affecting Gαq signaling through control of the pharyngeal pumping rate. A whole-genome sequencing technique was utilized and identified a list of candidate genes for these suppressor mutations. Further characterization of these mutants promises the discovery of novel components participating in Gαq signaling and a better understanding of the mechanisms of action of clozapine.
Spatial Attention Enhances the Neural Representation of Invisible Signals Embedded in Noise
Authors: Smout Cooper A. , Mattingley Jason B. 
Published: January 2017

AbstractRecent evidence suggests that voluntary spatial attention can affect neural processing of visual stimuli that do not enter conscious awareness (i.e. invisible stimuli), supporting the notion that attention and awareness are dissociable processes (Watanabe et al., 2011; Wyart, Dehaene, & Tallon-Baudry, 2012). To date, however, no study has demonstrated that these effects reflect enhancement of the neural representation of invisible stimuliper se, as opposed to other neural processes not specifically tied to the stimulus in question. In addition, it remains unclear whether spatial attention can modulate neural representations of invisible stimuli in direct competition with highly salient and visible stimuli. Here we developed a novel electroencephalography (EEG) frequency-tagging paradigm to obtain a continuous readout of human brain activity associated with visible and invisible signals embedded in dynamic noise. Participants (N= 23) detected occasional contrast changes in one of two flickering image streams on either side of fixation. Each image stream contained a visible or invisible signal embedded in every second noise image, the visibility of which was titrated and checked using a two-interval forced-choice detection task. Steady-state visual-evoked potentials (SSVEPs) were computed from EEG data at the signal and noise frequencies of interest. Cluster-based permutation analyses revealed significant neural responses to both visible and invisible signals across posterior scalp electrodes. Control analyses revealed that these responses did not reflect a subharmonic response to noise stimuli. In line with previous findings, spatial attention increased the neural representation of visible signals. Crucially, spatial attention also increased the neural representation of invisible signals. As such, the present results replicate and extend previous studies by demonstrating that attention can modulate the neural representation of invisible signals that are in direct competition with highly salient masking stimuli.
Initiation of DNA replication requires actin dynamics and formin activity
Authors: Nikolaos Parisis , Krasinska Liliana , Harker Bethany , Urbach Serge , Rossignol Michel , Camasses Alain , Dewar James , Morin Nathalie , Fisher Daniel 
Published: January 2017

AbstractNuclear actin influences transcription in a manner dependent on its dynamics of polymerisation and nucleocytoplasmic translocation. Using human somatic cells and transcriptionally-silentXenopusegg extracts, we show that actin dynamics is also required for DNA replication. We identify many actin regulators in replicating nuclei fromXenopusegg extracts, and show that in human cells, nuclear actin filaments form in early G1 and disassemble prior to S-phase. In either system, treatments that stabilise nuclear actin filaments abrogate nuclear transport and initiation of DNA replication. Mechanistically, actin directly binds RanGTP-importin complexes and disruption of its dynamics hinders cargo release. This prevents both nuclear pore complex (NPC) formation and active nuclear transport, which we show is required throughout DNA replication. Nuclear formin activity is required for two further steps: loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin and initiation of DNA replication. Thus, actin dynamics and formins are involved in several nuclear processes essential for cell proliferation.
The genomic basis of adaptation to the deep water ‘twilight zone’ in Lake Malawi cichlid fishes
Authors: Hahn Christoph , Genner Martin J , Turner George F , Joyce Domino A 
Published: January 2017

AbstractDeep water environments are characterized by low levels of available light at increasingly narrow spectra, great hydrostatic pressure and reduced dissolved oxygen - conditions predicted to exert highly specific selection pressures. In Lake Malawi over 800 cichlid species have evolved, and this adaptive radiation extends into the “twilight zone” below 100 metres. We use population-level RAD-seq data to investigate whether four endemic deep water species (Diplotaxodonspp.) have experienced divergent selection within this environment. We identify candidate genes including regulators of photoreceptor function, photopigments, lens morphology and haemoglobin, many not previously implicated in cichlid adaptive radiations. Co-localization of functionally linked genes suggests co-adapted “supergene” complexes. Comparisons ofDiplotaxodonto the broader Lake Malawi radiation using genome resequencing data revealed functional substitutions in candidate genes. Our data provide unique insights into genomic adaptation to life at depth, and suggest genome-level specialisation for deep water habitat as an important process in cichlid radiation.
DepEst: an R package of important dependency estimators for gene network inference algorithms
Authors: Altay Gökmen , Kurt Zeyneb , Altay Nejla , Aydin Nizamettin 
Published: January 2017

AbstractGene network inference algorithms (GNI) are popular in bioinformatics area. In almost all GNI algorithms, the main process is to estimate the dependency (association) scores among the genes of the dataset.We present a bioinformatics tool, DepEst (Dependency Estimators), which is a powerful and flexible R package that includes 11 important dependency score estimators that can be used in almost all GNI Algorithms. DepEst is the first bioinformatics package that includes such a large number of estimators that runs both in parallel and serial.DepEst is currently available athttps://github.com/altayg/Depest.Package access link, instructions, various workflows and example data sets are provided in the supplementary file.
Context-Aware Prediction of Pathogenicity of Missense Mutations Involved in Human Disease
Authors: Feinauer Christoph , Weigt Martin 
Published: January 2017

AbstractAmino-acid substitutions are implicated in a wide range of human diseases, many of which are lethal. Distinguishing such mutations from polymorphisms without significant effect on human health is a necessary step in understanding the etiology of such diseases. Computational methods can be used to select interesting mutations within a larger set, to corroborate experimental findings and to elucidate the cause of the deleterious effect. In this work, we show that taking into account the sequence context in which the mutation appears allows to improve the predictive and explanatory power of such methods. We present an unsupervised approach based on the direct-coupling analysis of homologous proteins. We show its capability to quantify mutations where methods without context dependence fail. We highlight cases where the context dependence is interpretable as functional or structural constraints and show that our simple and unsupervised method has an accuracy similar to state-of-the-art methods, including supervised ones.
Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types
Authors: Finucane Hilary K. , Reshef Yakir A. , Anttila Verneri , Slowikowski Kamil , Gusev Alexander , Byrnes Andrea , Gazal Steven , Loh Po-Ru , Lareau Caleb , Shoresh Noam , Genovese Giulio , Saunders Arpiar , Macosko Evan , Pollack Samuela ,   The Brainstorm Consortium, Perry John R.B. , Buenrostro Jason D. , Bernstein Bradley E. , Raychaudhuri Soumya , McCarroll Steven , Neale Benjamin M. , Price Alkes L. 
Published: January 2017

ABSTRACTGenetics can provide a systematic approach to discovering the tissues and cell types relevant for a complex disease or trait. Identifying these tissues and cell types is critical for following up on non-coding allelic function, developing ex-vivo models, and identifying therapeutic targets. Here, we analyze gene expression data from several sources, including the GTEx and PsychENCODE consortia, together with genome-wide association study (GWAS) summary statistics for 48 diseases and traits with an average sample size of 169,331, to identify disease-relevant tissues and cell types. We develop and apply an approach that uses stratified LD score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We detect tissue-specific enrichments at FDR < 5% for 34 diseases and traits across a broad range of tissues that recapitulate known biology. In our analysis of traits with observed central nervous system enrichment, we detect an enrichment of neurons over other brain cell types for several brain-related traits, enrichment of inhibitory over excitatory neurons for bipolar disorder but excitatory over inhibitory neurons for schizophrenia and body mass index, and enrichments in the cortex for schizophrenia and in the striatum for migraine. In our analysis of traits with observed immunological enrichment, we identify enrichments of T cells for asthma and eczema, B cells for primary biliary cirrhosis, and myeloid cells for Alzheimer's disease, which we validated with independent chromatin data. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signal.
Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury
Authors: Matthew MacManes 
Published: January 2017

AbstractAnimal living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. Indeed, these animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert adapted rodentP. eremicussurvives, we performed an experiment by which we subjected reproductively mature adults to profound acute dehydration, during which they lost on average 23% of their body weight. Animals react via a series of changes in the kidney, which include modulating expression of genes responsible for reducing the rate of transcription, and maintaining water and salt balance. Extracellular matrix turnover appears to be decreased, and apoptosis is limited. Serum Creatinine and other biomarkers of kidney injury are not elevated, which is different than the canonical human response, suggesting that transcriptional changes caused by acute dehydration effectively prohibit widespread kidney damage in the cactus mouse.
A Parallel Multiobjective Metaheuristic for Multiple Sequence Alignment
Authors: Rubio-Largo Álvaro , Vanneschi Leonardo , Castelli Mauro , Vega-Rodríguez Miguel A. 
Published: January 2017

AbstractThe alignment among three or more nucleotides/amino-acids sequences at the same time is known as Multiple Sequence Alignment (MSA), an NP-hard optimization problem. The time complexity of finding an optimal alignment raises exponentially when the number of sequences to align increases. In this work, we deal with a multiobjective version of the MSA problem where the goal is to simultaneously optimize the accuracy and conservation of the alignment. A parallel version of the Hybrid Multiobjective Memetic Metaheuristics for Multiple Sequence Alignment is proposed. In order to evaluate the parallel performance of our proposal, we have selected a pull of datasets with different number of sequences (up to 1000 sequences) and study its parallel performance against other well-known parallel metaheuristics published in the literature, such as MSAProbs, T-Coffee, Clustal Ω, and MAFFT. The comparative study reveals that our parallel aligner is around 25 times faster than the sequential version with 32 cores, obtaining a parallel efficiency around 80%.
Pure Correlates of Exploration and Exploitation in the Human Brain
Authors: Blanchard Tommy C. , Gershman Samuel J. 
Published: January 2017

AbstractBalancing exploration and exploitation is a fundamental problem in reinforcement learning. Previous neuroimaging studies of the exploration-exploitation dilemma could not completely disentangle these two processes, making it difficult to unambiguously identify their neural signatures. We overcome this problem using a task in which subjects can either observe (pure exploration) or bet (pure exploitation). Insula and dorsal anterior cingulate cortex showed significantly greater activity on observe trials compared to bet trials, suggesting that these regions play a role in driving exploration. A model-based analysis of task performance suggested that subjects chose to observe until a critical evidence threshold was reached. We observed a neural signature of this evidence accumulation process in ventromedial prefrontal cortex. These findings support theories positing an important role for anterior cingulate cortex in exploration, while also providing a new perspective on the roles of insula and ventromedial prefrontal cortex.Significance StatementSitting down at a familiar restaurant, you may choose to order an old favorite or sample a new dish. In reinforcement learning theory, this is known as the exploration-exploitation dilemma. The optimal solution is known to be intractable; therefore, humans must use heuristic strategies. Behavioral studies have revealed several candidate strategies, but identifying the neural mechanisms underlying these strategies is complicated due to the fact that exploration and exploitation are not perfectly dissociable in standard tasks. Using an “observe or bet” task, we identify for the first time pure neural correlates of exploration and exploitation in the human brain.
The Nucleosome Remodelling and Deacetylation complex restricts Mediator access to enhancers to control transcription
Authors: Xenophontos Maria , Reynolds Nicola , Gharbi Sarah , Johnstone Ewan , Signolet Jason , Floyd Robin , Ralser Meryem , Bornelöv Susanne , Dietmann Sabine , Loos Remco , Bertone Paul , Hendrich Brian 
Published: January 2017

AbstractA number of different chromatin remodelling complexes in mammalian cells are implicated in the control of gene expression. The genetic requirements for many such complex components have been described, and the biochemical activities of complex components characterised in vitro, yet the molecular mechanisms by which these biochemical activities impact transcriptional regulation in vivo remain ill-defined. Using an inducible system with fine temporal resolution, we show that the Nucleosome Remodelling and Deacetylation (NuRD) complex directly regulates chromatin architecture at enhancer regions in ES cells, in turn influencing the activity of RNA polymerase II via Mediator. Through this mechanism NuRD restricts Mediator access to enhancer chromatin during lineage commitment, thereby enabling appropriate transcriptional regulation. In contrast, acetylation levels of histone H3 lysine 27 are not immediately impacted by NuRD activity, correlating with transcriptional response only after expression levels have changed. These findings provide a detailed, molecular picture of genome-wide modulation of lineage-specific transcription by an abundant chromatin remodelling complex.
Cell-to-cell Modeling of the interface between Atrial and Sinoatrial Anisotropic Heterogeneous Nets II: Mechanisms Underlying Nets Dynamics
Authors: López Gabriel , Castellanos Norma P. , Godínez Rafael 
Published: January 2017

ABSTRACTIn [24] we studied the transitional zone between Sinoatrial cells and Atrial cells in the Heart. The present paper study the mechanisms underlying the dynamics of the modeled nets in that paper.