bluuebunny/crossref_metadata_2025_split huggingface dataset:
SYSTEMS BIOLOGY AND PREDICTIVE NEUROSCIENCE: A DOUBLE HELICAL APPROACH
Authors: Wiseman Harris 
Published: May 2017

AbstractThis article explores the overlap between systems biology and predictive neuroscience, placing them in their larger context, the contemporary trend of bioinformatic convergence across the sciences. These two domains overlap with respect to their interest in data accumulation and data integration; their reliance on computational statistical correlation; and their translational goals, that is, producing practical fruits and applications from the interscientific cross‐pollination that contemporary data‐integrative approaches make possible. The interventions that such translational conversations generate are medical and social in nature, and are aimed at both prevention (through prediction) and treatment. It will be argued that such approaches, socially and medically applied, contain potential for conveying both agency‐enhancing and agency‐diminishing social messages. The article concludes with a call to balance the overwhelmingly quantitative focus characteristic of predictive neuroscience with more qualitative empirical methodologies. This would represent a double helical approach.
EPIGENETICS, REPRESENTATION, AND SOCIETY
Authors: Gadjev Ilya 
Published: May 2017

AbstractIn recent decades, advances in the life sciences have created an unprecedentedly detailed picture of heredity and the formation of the phenotype where clusters of simplistic reductionist and deterministic views and interpretations have begun to lose ground to more complex and holistic notions. The developments in gene regulation and epigenetics have become a vivid emblem of the ongoing ‘softening’ of heredity. Despite this headway, the outlook and rhetoric widely popular in the twentieth century favoring the ‘gene’ in the ‘gene↔genetic plasticity↔phenotype↔environment’ tetrad have not been successfully tackled but continue to exist in parallel with a new, equally monochromatic, viewpoint championing genetic plasticity. An examination of epigenetics and its presentation in the public sphere, open to a conversation with the social disciplines and philosophy, could address this dichotomy and contribute to the discourse. This article outlines key biological aspects of epigenetics and discusses the language, presentation and wider resonance of this field of life science research.
THE EXPLORATION OF ECOSPACE: EXTENDING OR SUPPLEMENTING THE NEO‐DARWINIAN PARADIGM?
Authors: Gregersen Niels Henrik 
Published: May 2017

AbstractThe neo‐Darwinian paradigm, focusing on natural selection of genes responsible for differential adaption, provides the foundation for explaining evolutionary processes. The modern synthesis is broader, however, focusing on organisms rather than on gene transmissions per se. Yet, strands of current biology argue for further supplementation of Darwinian theory, pointing to nonbiotic drivers of evolutionary development, for example, self‐organization of physical structures, and the interaction between individual organisms, groups of organisms, and their nonbiotic environments. According to niche construction theory, when organisms and groups develop, they not only adapt to their environments but modify their environments, creating new habitats for later generations. Insofar as ecological niches persist beyond the lifecycle of individual organisms, an ecological inheritance system exists alongside genetic inheritance. Such ecological structures may even facilitate the development of a cultural inheritance system, as we see in humans. The article discusses theological perspectives of such new developments within holistic biology.
Genetic Determinants of the Pharmacokinetic Variability of Rifampin in Malawian Adults with Pulmonary Tuberculosis
Authors: Sloan Derek J. , McCallum Andrew D. , Schipani Alessandro , Egan Deirdre , Mwandumba Henry C. , Ward Steve A. , Waterhouse David , Banda Gertrude , Allain Theresa J. , Owen Andrew , Khoo Saye H. , Davies Geraint R. 
Published: May 2017

ABSTRACT

Variable exposure to antituberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the
SLCO1B1
locus on the plasma area under the concentration-time curve (AUC) of rifampin. We evaluated the contribution of single nucleotide polymorphisms (SNPs) in
SLCO1B1
and other candidate genes (
AADAC
and
CES-1
) to interindividual pharmacokinetic variability in Malawi. A total of 174 adults with pulmonary TB underwent sampling of plasma rifampin concentrations at 2 and 6 h postdose. Data from a prior cohort of 47 intensively sampled, similar patients from the same setting were available to support population pharmacokinetic model development in NONMEM v7.2, using a two-stage strategy to improve information during the absorption phase. In contrast to recent studies in South Africa and Uganda, SNPs in
SLCO1B1
did not explain variability in AUC
0–∞
of rifampin. No pharmacokinetic associations were identified with
AADAC
or
CES-1
SNPs, which were rare in the Malawian population. Pharmacogenetic determinants of rifampin exposure may vary between African populations.
SLCO1B1
and other novel candidate genes, as well as nongenetic sources of interindividual variability, should be further explored in geographically diverse, adequately powered cohorts.
Esx Systems and the Mycobacterial Cell Envelope: What's the Connection?
Authors: Bosserman Rachel E. , Champion Patricia A. 
Published: May 2017

ABSTRACTMycobacterial 6-kDa early secreted antigenic target (ESAT-6) system (ESX) exporters transport proteins across the cytoplasmic membrane. Many proteins transported by ESX systems are then translocated across the mycobacterial cell envelope and secreted from the cell. Although the mechanism underlying protein transport across the mycolate outer membrane remains elusive, the ESX systems are closely connected with and localize to the cell envelope. Links between ESX-associated proteins, cell wall synthesis, and the maintenance of cell envelope integrity have been reported. Genes encoding the ESX systems and those required for biosynthesis of the mycobacterial envelope are coregulated. Here, we review the interplay between ESX systems and the mycobacterial cell envelope.
The Response to 2-Aminoacrylate Differs in Escherichia coli and Salmonella enterica, despite Shared Metabolic Components
Authors: Borchert Andrew J. , Downs Diana M. 
Published: May 2017

ABSTRACT

The metabolic network of an organism includes the sum total of the biochemical reactions present. In microbes, this network has an impeccable ability to sense and respond to perturbations caused by internal or external stimuli. The metabolic potential (i.e., network structure) of an organism is often drawn from the genome sequence, based on the presence of enzymes deemed to indicate specific pathways.
Escherichia coli
and
Salmonella enterica
are members of the
Enterobacteriaceae
family of Gram-negative bacteria that share the majority of their metabolic components and regulatory machinery as the “core genome.” In
S. enterica
, the ability of the enamine intermediate 2-aminoacrylate (2AA) to inactivate a number of pyridoxal 5′-phosphate (PLP)-dependent enzymes has been established
in vivo
. In this study, 2AA metabolism and the consequences of its accumulation were investigated in
E. coli
. The data showed that despite the conservation of all relevant enzymes,
S. enterica
and
E. coli
differed in both the generation and detrimental consequences of 2AA. In total, these findings suggest that the structure of the metabolic network surrounding the generation and response to endogenous 2AA stress differs between
S. enterica
and
E. coli
.

IMPORTANCE
This work compared the metabolic networks surrounding the endogenous stressor 2-aminoacrylate in two closely related members of the
Enterobacteriaceae
. The data showed that despite the conservation of all relevant enzymes in this metabolic node, the two closely related organisms diverged in their metabolic network structures. This work highlights how a set of conserved components can generate distinct network architectures and how this can impact the physiology of an organism. This work defines a model to expand our understanding of the 2-aminoacrylate stress response and the differences in metabolic structures and cellular milieus between
S. enterica
and
E. coli
.
A Mutation in the Bacillus subtilis rsbU Gene That Limits RNA Synthesis during Sporulation
Authors: Rothstein David M. , Lazinski David , Osburne Marcia S. , Sonenshein Abraham L. 
Published: May 2017

ABSTRACT

Mutants of
Bacillis subtilis
that are temperature sensitive for RNA synthesis during sporulation were isolated after selection with a
32
P suicide agent. Whole-genome sequencing revealed that two of the mutants carried an identical lesion in the
rsbU
gene, which encodes a phosphatase that indirectly activates SigB, the stress-responsive RNA polymerase sigma factor. The mutation appeared to cause RsbU to be hyperactive, because the mutants were more resistant than the parent strain to ethanol stress. In support of this hypothesis, pseudorevertants that regained wild-type levels of sporulation at high temperature had secondary mutations that prevented expression of the mutant
rsbU
gene. The properties of these RsbU mutants support the idea that activation of SigB diminishes the bacterium's ability to sporulate.

IMPORTANCE
Most bacterial species encode multiple RNA polymerase promoter recognition subunits (sigma factors). Each sigma factor directs RNA polymerase to different sets of genes; each gene set typically encodes proteins important for responses to specific environmental conditions, such as changes in temperature, salt concentration, and nutrient availability. A selection for mutants of
Bacillus subtilis
that are temperature sensitive for RNA synthesis during sporulation unexpectedly yielded strains with a point mutation in
rsbU
, a gene that encodes a protein that normally activates sigma factor B (SigB) under conditions of salt stress. The mutation appears to cause RsbU, and therefore SigB, to be active inappropriately, thereby inhibiting, directly or indirectly, the ability of the cells to transcribe sporulation genes.
eIF2α Phosphorylation Mediates IL24-Induced Apoptosis through Inhibition of Translation
Authors: Persaud Leah , Zhong Xuelin , Alvarado Giselle , Do Winchie , Dejoie Jordan , Zybtseva Anna , Aktas Bertal Huseyin , Sauane Moira 
Published: May 2017

AbstractIL24 is an immunomodulatory cytokine that also displays broad cancer-specific suppressor effects. The tumor-suppressor activities of IL24 include inhibition of angiogenesis, sensitization to chemotherapy, and cancer-specific apoptosis. Supra-physiologic activation and/or overexpression of translation initiation factors are implicated in the initiation and progression of cancer animal models as well as a subset of human cancers. Activation and/or overexpression of translation initiation factors correlate with aggressiveness of cancer and poor prognosis. Two rate-limiting translation initiation complexes, the ternary complex and the eIF4F complex, are regulated by eIF2α and 4E-BP1 phosphorylation, respectively. The work reported here provides direct evidence that IL24 induces inhibition of translation initiation leading to apoptosis in squamous cell carcinoma. A dominant constitutively active mutant of eIF2α, which is resistant to phosphorylation, was used to determine the involvement of eIF2α in IL24-induced apoptosis. Treatment with IL24 resulted in inhibition of protein synthesis, expression of downstream biomarkers of ternary complex depletion such as CHOP, and induction of apoptosis in cancer cells. The constitutively active nonphosphorylatable mutant of eIF2α, eIF2α-S51A, reversed both the IL24-mediated translational block and IL24-induced apoptosis. Intriguingly, IL24 treatment also caused hypophosphorylation of 4E-BP1, which binds to eIF4E with high affinity, thus preventing its association with eIF4G and therefore preventing elF4F complex assembly.Implications: These results demonstrate a previously unrecognized role of IL24 in inhibition of translation, mediated through both phosphorylation of eIF2α and dephosphorylation of 4E-BP1, and provide the first direct evidence for translation control of gene-specific expression by IL24. Mol Cancer Res; 15(8); 1117–24. ©2017 AACR.
当代中国宗教研究∶对话中国社会科学领域的基督教研究者
Authors: Thurston Naomi 
Published: May 2017

This article, based on qualitative fieldwork among Chinese scholars of Christianity whom I interviewed between 2011 and 2015, explores the nexus between scholarly inquiry, cross-disciplinary negotiation, and religious belonging, specifically among the first generation of scholars researching Christianity after the launch of Deng Xiaoping’s policy of reform and opening-up. The article presents a typology of the researchers that is informed by interviewees’ disciplinary, religious, and discursive alignments. It also addresses the question of how the academic discipline of theology might find new anchorage in the landscape of “Sino-Christian studies,” with its many voices and varied interests.
本论文的资料来自笔者从2011至2015年在中国学术界进行的田野研究，探讨的重点是学术研究、跨文化协调与宗教身份的勾连，尤其针对学者中的“前辈”，即改革开放以来第一代学人。此外，此项研究将呈现一个按照学者专业、宗教归属与话语路径来划分的的类型图。本文探索的问题是：在充满不同观点与多种目标的知识话语领域中，学术性神学在当代语境中能否找到一个新的位置？ (This article is in English.)
The Reconfiguration of Guanxi in a Twentieth-Century Indigenous Chinese Protestant Group
Authors: Zimmerman-Liu Teresa 
Published: May 2017

Guanxiis the Chinese system of ideas and practices constituting social relationships and can be considered the foundation of Chinese societies. Protestant Christianity spread overguanxinetworks from its first introduction to China, changing bothguanxiand Christianity in the process. This paper proposes a causal model ofguanxiand then analyzes how it was reconstituted in the indigenous Chinese Protestant group, the Local Churches. It is based on published writings by Local Church founders and members and on the author’s thirty years of experience with the group. This case contributes to the academic understanding ofguanxiand Chinese Christianity, finding that extension of family, supply of resources, and social interaction are the core aspects ofguanxi, but that specific practices change in the Christian context to preserve biblical commandments. Becauseguanxinetworks are bonding rather than bridging, Chinese Christian groups will tend to diverge more than they converge.關係是中國人構成社會交往的思想和實踐體系，可以說是中國社會的基礎。基督新教在中国的发展依赖于关系网络，在其传播过程中二者都发生了变化。本文先提出一个关于關係的因果模型，再分析關係如何在一個中國本土的新教團體—地方教會—中被重新構造。本項研究是基於地方教會創辦人和成員的寫作，也基於作者與該團體三十年的接触。這項個案研究 有助于擴展對關係與中國基督教的學術理解。關係最重要方面是家庭关系的延展，供應資源，以及社會交流，不過，基督徒為了遵守聖經的教訓， 改变了關係的某些实践。地方教会的关系网络强调内部团结，而不是对外开放，所以与其他基督教团体关系疏离，而不是趨向匯合。 (This article is in English.)
Mental disorders in Australian 4- to 17- year olds: Parent-reported need for help
Authors: Johnson Sarah E , Lawrence David , Sawyer Michael , Zubrick Stephen R 
Published: May 2017

Objective: To describe the extent to which parents report that 4- to 17-year-olds with symptoms meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for mental disorders need help, the types of help needed, the extent to which this need is being met and factors associated with a need for help. Method: During 2013–2014, a national household survey of the mental health of Australia’s young people (Young Minds Matter) was conducted, involving 6310 parents (and carers) of 4- to 17-year-olds. The survey identified 12-month mental disorders using the Diagnostic Interview Schedule for Children – Version IV ( n = 870) and asked parents about the need for four types of help – information, medication, counselling and life skills. Results: Parents of 79% of 4- to 17-year-olds with mental disorders reported that their child needed help, and of these, only 35% had their needs fully met. The greatest need for help was for those with major depressive disorder (95%) and conduct disorder (93%). Among these, 39% of those with major depressive disorder but only 19% of those with conduct disorder had their needs fully met. Counselling was the type of help most commonly identified as being needed (68%). In multivariate models, need for counselling was higher when children had autism or an intellectual disability, in blended families, when parents were distressed, and in the most advantaged socioeconomic areas. Conclusions: Many children and adolescents meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for mental disorders have a completely unmet need for help, especially those with conduct disorders. Even with mild disorders, lack of clinical assessment represents an important missed opportunity for early intervention and treatment.
Systematic Review of Ossicular Chain Anatomy: Strategic Planning for Development of Novel Middle Ear Prostheses
Authors: Kamrava Brandon , Roehm Pamela C. 
Published: May 2017

ObjectiveTo systematically review the anatomy of the ossicular chain.Data SourcesGoogle Scholar, PubMed, and otologic textbooks.Review MethodsA systematic literature search was performed on January 26, 2015. Search terms used to discover articles consisted of combinations of 2 keywords. One keyword from both groups was used: [ossicular, ossicle, malleus, incus, stapes] and [morphology, morphometric, anatomy, variation, physiology], yielding more than 50,000 hits. Articles were then screened by title and abstract if they did not contain information relevant to human ossicular chain anatomy. In addition to this search, references of selected articles were studied as well as suggested relevant articles from publication databases. Standard otologic textbooks were screened using the search criteria.ResultsThirty‐three sources were selected for use in this review. From these studies, data on the composition, physiology, morphology, and morphometrics were acquired. In addition, any correlations or lack of correlations between features of the ossicular chain and other features of the ossicular chain or patient were noted, with bilateral symmetry between ossicles being the only important correlation reported.ConclusionThere was significant variation in all dimensions of each ossicle between individuals, given that degree of variation, custom fitting, or custom manufacturing of prostheses for each patient could optimize prosthesis fit. From published data, an accurate 3‐dimensional model of the malleus, incus, and stapes can be created, which can then be further modified for each patient’s individual anatomy.
The Impact of Tympanostomy Tubes on Speech and Language Development in Children with Cleft Palate
Authors: Shaffer Amber D. , Ford Matthew D. , Choi Sukgi S. , Jabbour Noel 
Published: May 2017

ObjectiveDescribe the impact of hearing loss, tympanostomy tube placement before palatoplasty, and number of tubes received on speech outcomes in children with cleft palate.Study DesignCase series with chart review.SettingTertiary care children’s hospital.Subjects and MethodsRecords from 737 children born between April 2005 and April 2015 who underwent palatoplasty at a tertiary children’s hospital were reviewed. Exclusion criteria were cleft repair at an outside hospital, intact secondary palate, absence of postpalatoplasty speech evaluation, sensorineural or mixed hearing loss, no tubes, first tubes after palatoplasty, or first clinic after 12 months of age. Data from 152 patients with isolated cleft palate and 166 patients with cleft lip and palate were analyzed using Wilcoxon rank‐sum, χ2, and Fisher exact test and logistic regression.ResultsMost patients (242, 76.1%) received tubes before palatoplasty. Hearing loss after tubes, but not before, was associated with speech/language delays at 24 months (P =. 005) and language delays (P =. 048) and speech sound production disorders (SSPDs, P =. 040) at 5 years. Receiving tubes before palatoplasty was associated with failed newborn hearing screen (P =. 001) and younger age at first posttubes type B tympanogram with normal canal volume (P =. 015). Hearing loss after tubes (P =. 021), language delays (P =. 025), SSPDs (P =. 003), and velopharyngeal insufficiency (P =. 032) at 5 years and speech surgery (P =. 022) were associated with more tubes.ConclusionContinued middle ear disease, reflected by hearing loss and multiple tubes, may impair speech and language development. Inserting tubes before palatoplasty did not mitigate these impairments better than later tube placement.
Comparing 30‐Day Morbidity and Mortality in Pediatric and Adult Otologic Surgery
Authors: Schwam Zachary G. , Michaelides Elias , Schwam Jennifer R. , Kuo Phoebe , Hajek Michael A. , Judson Benjamin L. , Schutt Christopher 
Published: May 2017

ObjectiveTo determine differences in timing and rate of postoperative adverse events among pediatric and adult populations undergoing specific otologic procedures.Study DesignAdministrative database study.SettingMulti‐institutional database.Subjects and MethodsThe National Surgical Quality Improvement Program (NSQIP) and NSQIP‐Pediatric (NSQIP‐P) were used to extract data from 819 adults (years 2005‐2010) and 7020 children (years 2012‐2014) undergoing tympanoplasty and (tympano)mastoidectomy, respectively. Simple summary statistics, χ2, and multivariable logistic regression analyses were performed.ResultsThere were no significant differences in overall adverse event rates between adults (2.9%) and children (2.3%) (P =. 233). Adults experienced infectious complications more frequently than did children (0.4% vs 0.0%, P =. 002). Postdischarge complications accounted for 83.7% of all complications. Children treated by pediatric otolaryngologists had higher readmission rates (odds ratio [OR], 2.80; 95% confidence interval [CI], 1.20‐3.60; P =. 002). Tympanomastoidectomy was associated with higher odds of reoperation (OR, 1.02; 95% CI, 1.01‐1.03; P <. 001), as was undergoing a concurrent procedure that did not include myringotomy (OR, 3.38; 95% CI, 1.47‐7.79; P =. 004).ConclusionBoth adult and pediatric otologic surgery are safe, with patients experiencing similarly low complication rates. Most adverse events occur after discharge.
Long‐term Evaluation of Type 2 Thyroplasty with Titanium Bridges for Adductor Spasmodic Dysphonia
Authors: Sanuki Tetsuji , Yumoto Eiji 
Published: May 2017

ObjectivesStandard treatments of adductor spasmodic dysphonia (AdSD) provide temporary relief of symptoms. Type 2 thyroplasty offers a long‐term solution; however, long‐term voice outcome data are lacking. The objective of this study was to assess the long‐term voice outcomes of type 2 thyroplasty with titanium bridges through use of a validated voice questionnaire.Study DesignCase series with chart review.SettingUniversity hospital.Subjects and MethodsForty‐seven consecutively enrolled patients with AdSD underwent type 2 thyroplasty with titanium bridges between August 2006 and November 2014. Questionnaires were completed during regularly scheduled follow‐ups and, in some cases, were sent to patients who missed follow‐up appointments. In 2015, questionnaires were mailed to all 47 patients and included a Voice Handicap Index–10 evaluation, as well as questions on postoperative vocal symptoms, surgical site, and status of the implanted titanium bridges.ResultsOf 47 patients with AdSD, 31 (66%) completed the questionnaires. The average follow‐up interval was 41.3 months. No patient reported experiencing an adverse event around the surgical site, and almost all were satisfied with their voices postoperatively. The mean postoperative (>3 years) Voice Handicap Index–10 score improved significantly, from 26.3 to 9.4 (n = 17, P =. 0009).ConclusionsType 2 thyroplasty for AdSD significantly improved patient quality of life and voice symptoms and continued to do so long after the surgery. The results of this study suggest that type 2 thyroplasty provides relief from vocal symptoms in patients with AdSD for >3 years.