bluuebunny/crossref_metadata_2025_split huggingface dataset:
How the embryo makes a limb: determination, polarity and identity
Authors: Tickle Cheryll 
Published: August 2015

AbstractThe vertebrate limb with its complex anatomy develops from a small bud of undifferentiated mesoderm cells encased in ectoderm. The bud has its own intrinsic polarity and can develop autonomously into a limb without reference to the rest of the embryo. In this review, recent advances are integrated with classical embryology, carried out mainly in chick embryos, to present an overview of how the embryo makes a limb bud. We will focus on how mesoderm cells in precise locations in the embryo become determined to form a limb and express the key transcription factors Tbx4 (leg/hindlimb) or Tbx5 (wing/forelimb). These Tbx transcription factors have equivalent functions in the control of bud formation by initiating a signalling cascade involving Wnts and fibroblast growth factors (FGFs) and by regulating recruitment of mesenchymal cells from the coelomic epithelium into the bud. The mesoderm that will form limb buds and the polarity of the buds is determined with respect to both antero‐posterior and dorso‐ventral axes of the body. The position in which a bud develops along the antero‐posterior axis of the body will also determine its identity – wing/forelimb or leg/hindlimb. Hox gene activity, under the influence of retinoic acid signalling, is directly linked with the initiation of Tbx5 gene expression in the region along the antero‐posterior axis of the body that will form wings/forelimbs and determines antero‐posterior polarity of the buds. In contrast, Tbx4 expression in the regions that will form legs/hindlimbs is regulated by the homeoprotein Pitx1 and there is no evidence that Hox genes determine antero‐posterior polarity of the buds. Bone morphogenetic protein (BMP) signalling determines the region along the dorso‐ventral axis of the body in which both wings/forelimbs and legs/hindlimbs develop and dorso‐ventral polarity of the buds. The polarity of the buds leads to the establishment of signalling regions – the dorsal and ventral ectoderm, producing Wnts and BMPs, respectively, the apical ectodermal ridge producing fibroblast growth factors and the polarizing region, Sonic hedgehog (Shh). These signals are the same in both wings/forelimbs and legs/hindlimbs and control growth and pattern formation by providing the mesoderm cells of the limb bud as it develops with positional information. The precise anatomy of the limb depends on the mesoderm cells in the developing bud interpreting positional information according to their identity – determined by Pitx1 in hindlimbs – and genotype. The competence to form a limb extends along the entire antero‐posterior axis of the trunk – with Hox gene activity inhibiting the formation of forelimbs in the interlimb region – and also along the dorso‐ventral axis.
Realising skilled companionship in nursing: a utopian idea or difficult challenge?
Authors: Dierckx de Casterlé Bernadette 
Published: August 2015

Aims and objectivesThe question being considered in this discussion article is whether nurses' practice can be usefully characterised in terms of skilled companionship.BackgroundA nurse's role might be characterised as one of a ‘skilled companion,’ a concept that brings together the scientific and moral basis of nursing practice. It is this focus on integrating both ‘skill’ and ‘companionship’ characteristics of nurses' practice that largely determines their effectiveness as care providers and their specific contribution to health care outcomes.MethodsDiscursive article that invites readers to explore and arrive at a more comprehensive understanding of nurses' daily practice, one from an ethical perspective that is based on empirical data from the study of patients' caring experiences, nurses' caring experiences and nurses' ethical practice in daily care.ConclusionsResearch in this era of health care highlights an important dilemma that the nursing profession is confronted with daily: realising nurses' role as a skilled companion in an environment where this concept of nursing care is discouraged, or even thwarted. Although the ethical dimension is explicitly and universally recognised as a core dimension of nursing care, research clearly highlights nurses' difficulties in translating this element into daily practice. Most disturbing in these findings is that both patients and nurses feel compelled to reach a compromise to ‘survive’ in this often‐chaotic caring environment.Relevance to clinical practiceIt appears today that nurses' intrinsic strengths and potential are largely underutilised in daily practice. More than ever, the nursing profession is challenged to reflect on the future position, aspirations and responsibilities of nurses, to make clear choices, and to act accordingly. Viewing and implementing the nurse's role as one of a skilled companion promise better health care delivery in a postmodern world.
Exome and genome sequencing: a revolution for the discovery and diagnosis of monogenic disorders
Authors: Stranneheim H. , Wedell A. 
Published: August 2015

AbstractMassively parallel DNA sequencing has revolutionized analyses of human genetic variation. From having been out of reach for individual research groups and even more so for clinical diagnostic laboratories until recently, it is now possible to analyse complete human genomes within reasonable time frames and at a reasonable cost using technologies that are becoming increasingly available. This represents a huge advance in our ability to provide correct diagnoses for patients with rare inherited disorders and their families. This paradigm shift is especially dramatic within the area of monogenic disorders. Not only can rapid and safe diagnostics of virtually all known single‐gene defects now be established, but novel causes of disease in previously unsolved cases can also be identified, illuminating novel pathways important for normal physiology. This greatly increases the capability not only to improve management of rare disorders, but also to improve understanding of pathogenetic mechanisms relevant for common, complex diseases.
Leucine metabolism regulates TRI6 expression and affects deoxynivalenol production and virulence in Fusarium graminearum
Authors: Subramaniam Rajagopal , Narayanan Swara , Walkowiak Sean , Wang Li , Joshi Manisha , Rocheleau Hélène , Ouellet Thérèse , Harris Linda J. 
Published: August 2015

SummaryTRI6 is a positive regulator of the trichothecene gene cluster and the production of trichothecene mycotoxins [deoxynivalenol (DON)] and acetylated forms such as 15‐Acetyl‐DON) in the cereal pathogen Fusarium graminearum. As a global transcriptional regulator, TRI6 expression is modulated by nitrogen‐limiting conditions, sources of nitrogen and carbon, pH and light. However, the mechanism by which these diverse environmental factors affect TRI6 expression remains underexplored. In our effort to understand how nutrients affect TRI6 regulation, comparative digital expression profiling was performed with a wild‐type F. graminearum and a Δtri6 mutant strain, grown in nutrient‐rich conditions. Analysis showed that TRI6 negatively regulates genes of the branched‐chain amino acid (BCAA) metabolic pathway. Feeding studies with deletion mutants of MCC, encoding methylcrotonyl‐CoA‐carboxylase, one of the key enzymes of leucine metabolism, showed that addition of leucine specifically down‐regulated TRI6 expression and reduced 15‐ADON accumulation. Constitutive expression of TRI6 in the Δmcc mutant strain restored 15‐ADON production. A combination of cellophane breach assays and pathogenicity experiments on wheat demonstrated that disrupting the leucine metabolic pathway significantly reduced disease. These findings suggest a complex interaction between one of the primary metabolic pathways with a global regulator of mycotoxin biosynthesis and virulence in F. graminearum.
Use of Transparent Film Dressing for Dermoscopy of Mucosal Lesions
Authors: Sorrell Jennifer , Lauren Christine T. 
Published: August 2015

AbstractGenital and mucosal nevi are not uncommonly encountered in children. These type of nevi highlight challenges in performing a thorough dermoscopic examination. Contact dermoscopy can provide additional information about a nevus that non‐contact dermoscopy cannot. We propose applying a sterile transparent film dressing over the dermatoscope to act as a waterproof barrier that is also impermeable to bacteria and viruses. This provides a sanitary way to evaluate nevi in genital skin as well as on other mucosal surfaces.
Efficacy of pediatric acute pancreatitis scores at a Japanese tertiary center
Authors: Hashimoto Naoya , Yotani Nobuyuki , Michihata Nobuaki , Tang Julian , Sakai Hirokazu , Ishiguro Akira 
Published: August 2015

AbstractBackgroundPediatric acute pancreatitis (AP) is a rare but important clinical entity associated with significant morbidity. Predicting the severity and outcome of AP in pediatric patients can be challenging because there are few validated severity scoring systems. Moreover, the etiology of pediatric AP in the Japanese population is different from that of Western populations. The performance of severity scores in pediatric AP with a high prevalence of severe cases is still unknown. The aim of this study was to assess the performance of existing severity scoring systems when used for Japanese children at a tertiary care center.MethodsWe reviewed the electronic medical records of all children (≤18 years) treated for AP at between 2002 and 2012 at National Center for Child Health and Development, Tokyo. The modified Glasgow acute pancreatitis severity score (modified Glasgow), Ranson criteria (Ranson), Balthazar computed tomography severity index (CTSI), and pediatric acute pancreatitis severity (PAPS) score were assessed for their ability to distinguish severe pancreatitis from the milder forms.ResultsThirty‐three Japanese children with AP were identified. Among them, 37 episodes were analyzed for the performance of the scoring systems and 33 for the etiology. The most common etiology of AP was structural abnormality (n = 8). Sensitivity for the modified Glasgow, Ranson, PAPS, and CTSI was 42.9%, 52.4%, 81.0%, and 50.0%, respectively, while specificity was 81.3%, 81.3%, 37.5%, and 76.9%, respectively.ConclusionWe found PAPS to be the most reliable when used for discriminating the severe form of AP from the milder forms at a Japanese tertiary pediatric care center.
The Impact of a Nurse‐Led Home Visitation Program on Hypertension Self‐Management among Older Community‐Dwelling Koreans
Authors: Park Eunok , Kim JinShil 
Published: August 2015

AbstractObjectivesTo examine the impact of a nurse‐led home visitation program for hypertension self‐management among older community‐dwelling Koreans.Design and SampleAs part of a larger community‐based home visitation project aimed at behavioral change in this vulnerable population, a single group pre‐ and posttest design was used.MeasuresVisiting nurses affiliated to public health center assisted vulnerable elders with hypertension self‐management tailored according to their health problems through home visits for a period of 2–4 months.ResultsA total of 13,452 hypertensive persons over the age of 65 completed the intervention. All outcomes were significantly improved and included hypertension knowledge, blood pressure monitoring, dietary management, medication adherence, and self‐confidence in hypertension self‐management (p < .001). Changes in hypertension knowledge, medication adherence, and self‐confidence varied by gender with women showing greater knowledge improvement than men but less improvement in medication adherence and confidence in hypertension self‐management. There was a marginal interaction effect for gender and age on dietary management (F = 3.55, p = .063), with men (≥75 years) showing greater improvement than their female counterparts after the intervention.ConclusionsThis nurse‐led home visitation intervention can be helpful in self‐management skill building among hypertensive Korean elders. The program may improve medication adherence and health‐promoting behavioral changes.
The inflammasome and danger molecule signaling: at the crossroads of inflammation and pathogen persistence in the oral cavity
Authors: Yilmaz Özlem , Lee Kyu Lim 
Published: August 2015

AbstractInflammasomes are an oligomeric assembly of multiprotein complexes that activate the caspase‐1‐dependent maturation and the subsequent secretion of inflammatory interleukin‐1beta and interleukin‐18 cytokines in response to a ‘danger signal’ in vertebrates. The assessment of their significance continues to grow rapidly as the complex biology of various chronic inflammatory conditions is better dissected. Increasing evidence strongly links inflammasomes and host‐derived small ‘danger molecule ATP’ signaling with the modulation of the host immune response by microbial colonizers as well as with potential altering of the microbiome structure and intermicrobial interactions in the host. All of these factors eventually lead to the destructive chronic inflammatory disease state. In the oral cavity, a highly dynamic and multifaceted interplay takes place between the signaling of endogenous danger molecules and colonizing microbes on the mucosal surfaces. This interaction may redirect the local microenvironment to favor the conversion of the resident microbiome toward pathogenicity. This review outlines the major components of the known inflammasome complexes/mechanisms and highlights their regulation, in particular, by oral microorganisms, in relation to periodontal disease pathology. Better characterization of the cellular and molecular biology of the inflammasome will probably identify important potential therapeutic targets for the treatment and prevention of periodontal disease, as well as for other debilitating chronic diseases.
Neutrophil activation and periodontal tissue injury
Authors: Herrmann Jens Martin , Meyle Jörg 
Published: August 2015

AbstractNeutrophilic polymorphonuclear leukocytes (PMNL) track, engage and eliminate foreign entities, including bacteria, fungi and subcellular particles. PMNL are the major host‐cell line involved in the acute response during the early stages of infections, including those in the oral cavity. Rather short lived, they are among the fastest moving cells in the human body and travel great distances only to be immolated after encountering and neutralizing antigens. Although their role as the first line of host defense is well established, their role in chronic granulomatous inflammations, diseases and infections remains poorly understood, and many questions on the activation, motility, bactericidity and termination of PMNL in these conditions remain unanswered. This review aims to summarize our current understanding of the molecular mechanisms of PMNL activation and signaling events. Recent evidence indicates the presence of collateral tissue damage caused by poorly regulated PMNL pursuits of periodontal bacteria. Imbalances between the antigenic challenge and the primary host response may augment periodontal tissue breakdown. Thereafter, orchestrated regulation of the resolution of inflammation fails in the presence of a pathogenic periodontal biofilm.
Local inflammatory reactions in patients with diabetes and periodontitis
Authors: Sonnenschein Sarah K. , Meyle Joerg 
Published: August 2015

AbstractThe impact of diabetes mellitus on the prevalence, severity and progression of periodontal disease has been known for many years and intense efforts have been made to elucidate the underlying mechanisms. It is widely reported that hyperglycemia causes numerous systemic changes, including altered innate immune‐cell function and metabolic changes. The aim of this review was to summarize and discuss the evidence for mechanisms that probably play a role in the altered local inflammatory reactions in the periodontium of patients with diabetes, focusing on local changes in cytokine levels, matrix metalloproteinases, reactive oxygen species, advanced glycation end‐products, immune‐cell functions, the RANKL/osteoprotegerin axis and toll‐like receptors. Apart from the systemic effects of diabetes, recent evidence suggests that local changes in the periodontal tissues are characterized by enhanced interactions between leukocytes and endothelial cells and by altered leukocyte functions [resulting in increased levels of reactive oxygen species and of proinflammatory cytokines (interleukin‐1β, interleukin‐6 and tumor necrosis factor‐α)]. These local changes are amplified by the enhanced accumulation of advanced glycation end‐products and their interaction with receptors for advanced glycation end‐products. Furthermore, the increased levels of proinflammatory cytokines lead to an up‐regulation of RANKL in periodontal tissues, stimulating further periodontal tissue breakdown.
Activation and resolution of periodontal inflammation and its systemic impact
Authors: Hasturk Hatice , Kantarci Alpdogan 
Published: August 2015

AbstractInflammation is a highly organized event impacting upon organs, tissues and biological systems. Periodontal diseases are characterized by dysregulation or dysfunction of resolution pathways of inflammation that results in failure to heal and in a dominant chronic, progressive, destructive and predominantly unresolved inflammation. The biological consequences of inflammatory processes may be independent of the etiological agents, such as trauma, microbial organisms and stress. The impact of the inflammatory pathological process depends upon the tissues or organ system affected. Whilst mediators are similar, there is tissue specificity for the inflammatory events. It is plausible that inflammatory processes in one organ could directly lead to pathologies in another organ or tissue. Communication between distant parts of the body and their inflammatory status is also mediated by common signaling mechanisms mediated via cells and soluble mediators. This review focuses on periodontal inflammation, its systemic associations and advances in therapeutic approaches based on mediators acting through orchestration of natural pathways to resolution of inflammation. We also discuss a new treatment concept in which natural pathways of resolution of periodontal inflammation can be used to limit systemic inflammation and promote healing and regeneration.
Globalization and the Retreat of Citizen Participation in Collective Action: A Challenge for Public Administration
Authors: Adres Eitan , Vashdi Dana R. , Zalmanovitch Yair 
Published: August 2015

AbstractGlobalization challenges the ability of contemporary public administration to encourage citizen participation in collective action through behaviors such as tax compliance and contributions to public goods. The authors introduce a new individual‐level approach to globalization, arguing that people vary in the extent to which they are globalized and that an individual's level of globalism (ILG) reflects attitudes and dispositions that influence the way he or she resolves the social dilemma of participation in collective action (i.e., the decision to contribute versus follow a “free‐ride” strategy). Using a four‐country sample, the article examines the relationship betweenILGand collective action participation decisions in three behavioral experiments. Findings support the hypothesis that regardless of country‐level globalization, a more globalized individual complies less willingly with tax codes, donates less to local nongovernmental organizations, and prefers to adopt a free‐ride strategy in a public goods game. The consequences for public administration are discussed.
Epstein–Barr virus encephalitis in a renal transplant recipient manifesting as hemorrhagic, ring‐enhancing mass lesions
Authors: Babik J.M. , Katrak S. , Miller S. , Shah M. , Chin‐Hong P. 
Published: August 2015

AbstractEpstein–Barr virus (EBV) encephalitis has been infrequently described in immunocompromised patients. Here, we report a unique case of biopsy‐proven EBV encephalitis in a renal transplant recipient presenting with altered mental status, prominent visual disturbances, and hemorrhagic, ring‐enhancing mass lesions on magnetic resonance imaging. The patient was successfully treated with a prolonged course of antivirals. This case illustrates the difficulty in interpretation of cerebrospinal fluid EBV polymerase chain reaction assay, given the lack of specificity in immunocompromised patients.
A genome‐wide survey reveals abundant rice blast R genes in resistant cultivars
Authors: Zhang Xiaohui , Yang Sihai , Wang Jiao , Jia Yanxiao , Huang Ju , Tan Shengjun , Zhong Yan , Wang Ling , Gu Longjiang , Chen Jian‐Qun , Pan Qinghua , Bergelson Joy , Tian Dacheng 
Published: August 2015

SummaryPlant resistance genes (R genes) harbor tremendous allelic diversity, constituting a robust immune system effective against microbial pathogens. Nevertheless, few functional R genes have been identified for even the best‐studied pathosystems. Does this limited repertoire reflect specificity, with most R genes having been defeated by former pests, or do plants harbor a rich diversity of functional R genes, the composite behavior of which is yet to be characterized? Here, we survey 332 NBS‐LRR genes cloned from five resistant Oryza sativa (rice) cultivars for their ability to confer recognition of 12 rice blast isolates when transformed into susceptible cultivars. Our survey reveals that 48.5% of the 132 NBS‐LRR loci tested contain functional rice blast R genes, with most R genes deriving from multi‐copy clades containing especially diversified loci. Each R gene recognized, on average, 2.42 of the 12 isolates screened. The abundant R genes identified in resistant genomes provide extraordinary redundancy in the ability of host genotypes to recognize particular isolates. If the same is true for other pathogens, many extant NBS‐LRR genes retain functionality. Our success at identifying rice blast R genes also validates a highly efficient cloning and screening strategy.
INDUCER OF CBF EXPRESSION 1 integrates cold signals into FLOWERING LOCUS C‐mediated flowering pathways in Arabidopsis
Authors: Lee Jae‐Hyung , Jung Jae‐Hoon , Park Chung‐Mo 
Published: August 2015

SummaryPlants constantly monitor changes in photoperiod and temperature throughout the year to synchronize flowering with optimal environmental conditions. In the temperate zones, both photoperiod and temperature fluctuate in a somewhat predictable manner through the seasons, although a transient shift to low temperature is also encountered during changing seasons, such as early spring. Although low temperatures are known to delay flowering by inducing the floral repressor FLOWERING LOCUS C (FLC), it is not fully understood how temperature signals are coordinated with photoperiodic signals in the timing of seasonal flowering. Here, we show that the cold signaling activator INDUCER OF CBF EXPRESSION 1 (ICE1), FLC and the floral promoter SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) constitute an elaborate signaling network that integrates cold signals into flowering pathways. The cold‐activated ICE1 directly induces the gene encoding FLC, which represses SOC1 expression, resulting in delayed flowering. In contrast, under floral promotive conditions, SOC1 inhibits the binding of ICE1 to the promoters of the FLC gene, inducing flowering with a reduction of freezing tolerance. These observations indicate that the ICE1‐FLC‐SOC1 signaling network contributes to the fine‐tuning of flowering during changing seasons.