bluuebunny/crossref_metadata_2025 huggingface dataset:
SAAMP 2.0: An algorithm to predict genotype‐phenotype correlation of lysosomal storage diseases
Authors: Ou L. , Przybilla M.J. , Whitley C.B.
Published: February 2018

Lysosomal storage diseases (LSDs) are a group of genetic disorders, resulting from deficiencies of lysosomal enzyme. Genotype‐phenotype correlation is essential for timely and proper treatment allocation. Recently, by integrating prediction outcomes of 7 bioinformatics tools, we developed a SAAMP algorithm to predict the impact of individual amino‐acid substitution. To optimize this approach, we evaluated the performance of these bioinformatics tools in a broad array of genes. PolyPhen and PROVEAN had the best performances, while SNP&GOs, PANTHER and I‐Mutant had the worst performances. Therefore, SAAMP 2.0 was developed by excluding 3 tools with worst performance, yielding a sensitivity of 94% and a specificity of 90%. To generalize the guideline to proteins without known structures, we built the three‐dimensional model of iduronate‐2‐sulfatase by homology modeling. Further, we investigated the phenotype severity of known disease‐causing mutations of the GLB1 gene, which lead to 2 LSDs (GM1 gangliosidosis and Morquio disease type B). Based on the previous literature and structural analysis, we associated these mutations with disease subtypes and proposed a theory to explain the complicated genotype‐phenotype correlation. Collectively, an updated guideline for phenotype prediction with SAAMP 2.0 was proposed, which will provide essential information for early diagnosis and proper treatment allocation, and they may be generalized to many monogenic diseases.
Melanoma mimicking Rosai‐Dorfman disease
Authors: Xie Daniel Y. , Costello Collin M. , Liang Helen J. , Thomas Brett G. , DiCaudo David J. , Mangold Aaron R.
Published: February 2018

Despite well‐defined clinical and histopathological features of melanoma, atypical presentations mimicking other skin disorders can result in a delayed diagnosis or misdiagnosis and subsequent inappropriate treatment. Rosai‐Dorfman disease (RDD) is a rare histiocytic disorder with unique clinical and histopathological features. We report a case of melanoma treated with cryotherapy that mimicked RDD both clinically and histopathologically. We compare this RDD‐like melanoma to classic RDD, outlining the importance of clinicopathological correlation prior to treatment, as well as the potential pitfalls in diagnosis after cryotherapy of pigmented lesions.
In silico annotation of five candidate genes associated with pathogenicity in Fusarium circinatum
Authors: Muñoz‐Adalia E. J. , Fernández M. , Wingfield B. D. , Diez J. J.
Published: February 2018

The Pine Pitch Canker disease caused by the pathogenic fungus Fusarium circinatum is one of the most devastating diseases in pine forests, afforestation and nurseries around the world. Despite the importance of this phytopathogen, only a little is known about the genes that drive the infection traits and the virulence factors. In this work, five candidate genes (i.e. Fcfga1, Fcfgb1, Fcac, Fcrho1 and FcpacC) were in silico annotated using the whole genome of F. circinatum as reference. The similarity of these proposed genes at nucleotide and protein levels with genes previously described in other Fusarium species was > 90% of identity and > 90% query coverage in all cases. In addition, the gene ontology of each candidate gene was also investigated.
Can (Mg,Y)‐PSZ—Spinel composites be a valuable option for dental application?
Authors: De Portu Goffredo , Chevalier Jérôme , Douillard Thierry , Gremillard Laurent , Bonnefont Guillaume
Published: February 2018

Twenty‐year‐old samples of (Mg,Y)‐PSZ—Spinel composite were characterized to assess their microstructure and mechanical properties after such a long period of natural aging. The amount of the different phases was determined byXRD, whereas a detailed observation of the microstructural features was carried out by high‐resolutionSEMandFIB/SEM. Bending strength, hardness, and toughness were also measured. Translucency was quantified by measuring the contrast ratio (CR). After comparison of the results obtained in this study with those obtained 20 years ago, the studied material reveals a phase stability superior to that exhibited by conventional 3Y‐TZP, good strength, and hardness and a remarkable toughness. The value ofCRis comparable with those exhibited by the materials commonly used in dentistry. Thanks to the presence of spinel particles, grains are smaller than in conventional Mg‐PSZ. In addition, we show here that grains can be further refined through spark plasma sntering. For all these reasons (Mg,Y)‐PSZ‐spinel composite could be proposed as valid alternative to 3Y‐TZPfor dental applications.
Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy
Authors: Guerra L. , Castori M. , Didona B. , Castiglia D. , Zambruno G.
Published: February 2018

Hereditary palmoplantar keratodermas (PPKs) comprise a large and heterogeneous group of disorders characterized by persistent thickening of the epidermis at palmar and plantar surfaces. Clinical and genetic features of isolated and complex PPKs have been reviewed in part I of this 2‐part review. Here we focus on clinical and molecular classification of syndromic PPKs which are recognized by additional extracutaneous manifestations, in particular deafness, specific mucosal lesions, cardiomyopathy, inborn errors of metabolism, involvement of internal organs or disorders of sexual development. Other genetic diseases, which may show palmoplantar involvement, such as selected subtypes of hereditary epidermolysis bullosa, various hereditary ichthyoses and other keratinization disorders, several ectodermal dysplasias and some multisystem genetic disorders, are also briefly summarized. PPK diagnosis is based on inheritance pattern, age at onset, morphology, distribution and severity of hyperkeratosis, pattern of additional dermatological and systemic manifestations and laboratory findings. Molecular analysis is at present the gold standard to confirm the diagnosis in PPK forms due to mutations in known causative genes. No specific and curative therapy is currently available for PPKs which highly impair patients’ quality of life. Topical treatments are symptomatic and offer only temporary relief. Among systemic treatments, retinoids improve disease symptoms in the majority of patients.
Ethnocultural influences in how people prefer to obtain and receive health information
Authors: King‐Shier Kathryn , Lau Alyssa , Fung Sunny , LeBlanc Pamela , Johal Simran
Published: February 2018

Aims and objectives

To develop an understanding of south Asian and Chinese people's preferences about where to find health information and how best to receive health information, relative to their white counterparts.

Background

South Asian and Chinese ethnic groups represent the largest proportion of Canada's growing visible minorities. There may be challenges to ensuring that south Asian and Chinese people have access to health information in the same way that others do.

Design

Qualitative descriptive.

Methods

Fifty‐two participants (12 white, 16 south Asian and 24 Chinese) engaged in six focus groups (two for each ethnocultural group). Focus groups were conducted in English, Punjabi and Cantonese, with the assistance of Punjabi and Cantonese interpreters. Questions were focused on how participants have preferred or would prefer to receive health information (e.g., when, where, what format, from whom), as well as the facilitators and barriers to understanding the health information.

Results

Participants agreed that although physicians were their primary source for health information, they also used written materials, media and the Internet to glean information. Participants identified concerns regarding the use of technical jargon by healthcare providers. South Asians and Chinese referred to their English language fluency and the lack of ethnoculturally specific information as additional challenges to understanding information they were offered. Whether and how family members were included in the communication process, also varied by ethnocultural group.

Conclusions

As Canada welcomes immigrants from other countries, and its population becomes more diverse, healthcare providers need to have an understanding of the potential diversity in how to approach offering health information.

Relevance to clinical practice

Healthcare providers need to consider what people of different ethnocultural backgrounds need when developing effective health communication strategies.
Coping with interruptions in clinical nursing—A qualitative study
Authors: Laustsen Sussie , Brahe Liselotte
Published: February 2018

Aims and objectives

To gain knowledge on how nurses’ cope with interruptions in clinical practice.

Background

Interruptions may delay work routines and result in wasted time, disorganised planning and ineffective working procedures, affecting nurses’ focus and overview in different ways. Research has identified a growing problem linking errors or adverse events with interruptions. It may affect patient safety if nurses are not paying attention to interruptions. Little is known about how nurses cope with interruptions

Design

The study was inspired by ethnographic fieldwork with a hermeneutical phenomenological approach.

Methods

Observations were performed combined with semi‐structured qualitative interviews.

Results

Managing interruptions depend on level of competence, working environment, dialogue and matching of expectations, collegial roles and implicit rules. Working procedures impact on how nurses are exposed to unnecessary interruptions. The latter affects overview and the ability to put the foot down and decline being interrupted. Professional competencies for example prioritising, keeping focus and collaborating across disciplines are needed to cope with interruptions.

Conclusion

Culture work and matching of expectations are important to reflect on and discuss personal‐ and group behaviour caused by interruptions. We need to focus on the role of each nurse in the professional team, types of personality and unspoken rules. Professional competencies for example prioritising, keeping focus and cooperating across disciplines are needed to cope with interruptions.

Relevance to clinical practice

Coping with interruptions is important for the nursing profession, quality of care and patient safety. Changing practice requires multidisciplinary cooperation accepting different agendas at personal, group and organisational levels. Nurses must understand the meaning and nature of different types of interruptions to develop coping strategies and maintain quality in care and patient safety in multidisciplinary teamwork.
Predictive factors of satisfaction and quality of life after immediate breast reconstruction using the BREAST‐Q©
Authors: Cereijo‐Garea Carmen , Pita‐Fernández Salvador , Acea‐Nebril Benigno , Rey‐Villar Raquel , García‐Novoa Alejandra , Varela‐Lamas Cristina , Builes‐Ramirez Sergio , Seoane‐Pillado Teresa , Balboa‐Barreiro Vanesa
Published: February 2018

Aims and objectives

To analyse quality of life and satisfaction after immediate breast reconstruction due to cancer and its determining factors.

Background

Studying breast reconstruction is important because of its frequency and variability. In addition to the surgical results, it is necessary to analyse the quality of life and patient satisfaction using a specific tool.

Design methods

An ambispective design was used (n = 101; α = 0.05; precision = 10%), studying anthropometric, sociocultural data, Fagerström test and the BREAST‐Q© questionnaire. A logistic regression analysis was performed to identify variables associated with quality of life and satisfaction.

Results

Mean age of the patients on diagnosis was 44.87 ± 8.5 years. Forty‐one of the patients were carried out a skin‐sparing mastectomy (42.7%). Immediate reconstruction was performed with implant in 73 (74.5%). The domains on the BREAST‐Q© for quality of life with the lowest scores were physical well‐being chest (74) and sexual well‐being (61.5). The satisfaction domain with the lowest score was with the breast (59). The variables associated with the worst quality of life in the physical well‐being chest domain were the skin‐sparing mastectomy (OR, 4.2; 95% confidence interval (CI), 1.2–14.1) and lymphedema (OR, 12.9; 95% CI, 1.0–159.9). Antibody treatment was associated with a worse score on the psychosocial well‐being domain (OR, 4.25; 95% CI, 1.0–18.0) and sexual well‐being domain (OR, 7.34; 95% CI, 0.9–54.6). Satisfaction was associated with nicotine dependence on the breast and outcome scale. The higher the dependence on nicotine, the greater the dissatisfaction with the breasts (OR, 2.41; 95% CI, 1.1–5.3) and with the result (OR, 2.45; 95% CI, 1.0–5.9).

Conclusions

The type of treatment and lymphedema modify the patients’ quality of life. Nicotine dependence is associated with lower satisfaction with the breast and with the outcome.

Relevance to clinical practice

This study suggests the need for multidisciplinary attention during the first year of adjuvant treatment despite the benefits of immediate reconstruction. It shows the need for preoperative assessment of the level of nicotine dependence, anxiety and depression of smoking patients before preoperative counselling.
Organisational silence among nurses and physicians in public hospitals
Authors: Harmanci Seren Arzu Kader , Topcu İbrahim , Eskin Bacaksiz Feride , Unaldi Baydin Nihal , Tokgoz Ekici Emine , Yildirim Aytolan
Published: February 2018

Aims and objectives

To define the underlying reasons that lead physicians and nurses who provide patient care and treatment, to maintain silence in their work and how they perceive the consequences of such silence in public hospitals.

Background

The concept of organisational silence is described as employees’ avoidance of stating his/her opinions, thoughts and suggestions, which would improve the organisation and enable it to provide better processes or services. This concept has been examined more frequently in the international literature in the past decade, and it has drawn attention as one of the most important barriers to employees’ contributions to their organisation.

Design

Descriptive and cross‐sectional study.

Methods

The study sample consisted of 601 physicians and nurses who work in five hospitals with bed capacities of 100 or more. The data were collected using a two‐part form: an introductory information form and an organisational silence scale.

Results

Administrative and organisational topics were prominent among the reasons for employees of healthcare organisations to remain silent for both physicians and nurses.

Conclusions

The results of this study should be considered by physicians and nurses to realise and improve themselves. Also, decision makers and managers of public hospitals might evaluate and remove organisational and communicative barriers to employees’ contributions to their organisations based on these results.

Relevance to clinical practice

Physicians and nurses are responsible for the fulfilment of highly important tasks for their organisations. Their contributions help their organisations remain competitive, improve the health services, ensure and sustain patient safety. Hence, these results will provide information to facilitate an understanding of the topics, causes and consequences of organisational silence among physicians and nurses, two key healthcare professions, and will be helpful in the development of medical and nursing human resources in clinical settings.
A rating instrument for fear of hospitalisation
Authors: Jankovic Slobodan M , Antonijevic Gordana V , Vasic Ivana R , Zivkovic‐Radojevic Marija N , Mirkovic Snjezana N , Nikolic Bosko V , Opancina Valentina D , Putnik Srdjan S , Radoicic Ljiljana R , Raspopovic Katarina M , Stanojevic Dragan R , Teofilov Sladjana D , Tomasevic Katarina V , Radonjic Vesela
Published: February 2018

Aims and objectives

To develop and validate a reliable instrument that can measure fear of hospitalisation experienced by outpatients.

Background

After having a diagnosis established, some patients experience sense of fear, unpleasantness and embarrassment due to the possibility to be admitted to a hospital. Currently, there is no available instrument for measuring fear of hospitalisation.

Design

Cross‐sectional study for assessing reliability and validity of a questionnaire.

Method

The questionnaire with 17 items and answers according to the Likert scale was developed during two brainstorming sessions of the research team. Its reliability, validity and temporal stability were tested on the sample of 330 outpatients. The study was multicentric, involving patients from seven cities and three countries.

Results

Fear of hospitalisation scale showed satisfactory reliability, when rated both by the investigators (Cronbach's alpha .799) and by the patients themselves (Cronbach's alpha .760). It is temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed three domains: fear of being injured, trust to medical staff and fear of losing privacy or autonomy.

Conclusions

This study developed new reliable and valid instrument for measuring fear of hospitalisation.

Relevance to clinical practice

Identification of patients with high level of fear of hospitalisation by this instrument should help clinicians to administer measures which may decrease fear and prevent avoidance of healthcare utilisation.
Fundamental care guided by the Careful Nursing Philosophy and Professional Practice Model©
Authors: Meehan Therese Connell , Timmins Fiona , Burke Jacqueline
Published: February 2018

Aims and objectives

To propose the Careful Nursing Philosophy and Professional Practice Model© as a conceptual and practice solution to current fundamental nursing care erosion and deficits.

Background

There is growing awareness of the crucial importance of fundamental care. Efforts are underway to heighten nurses’ awareness of values that motivate fundamental care and thereby increase their attention to effective provision of fundamental care. However, there remains a need for nursing frameworks which motivate nurses to bring fundamental care values to life in their practice and strengthen their commitment to provide fundamental care.

Design

This descriptive position paper builds on the Careful Nursing Philosophy and Professional Practice Model© (Careful Nursing). Careful Nursing elaborates explicit nursing values and addresses both relational and pragmatic aspects of nursing practice, offering an ideal guide to provision of fundamental nursing care.

Method

A comparative alignment approach is used to review the capacity of Careful Nursing to address fundamentals of nursing care.

Conclusions

Careful Nursing provides a value‐based comprehensive and practical framework which can strengthen clinical nurses’ ability to articulate and control their practice and, thereby, more effectively fulfil their responsibility to provide fundamental care and measure its effectiveness.

Relevance to clinical practice

This explicitly value‐based nursing philosophy and professional practice model offers nurses a comprehensive, pragmatic and engaging framework designed to strengthen their control over their practice and ability to provide high‐quality fundamental nursing care.
Steroid therapy in children with fulminant hepatitis A
Authors: Zakaria H. M. , Salem T. A. , El‐Araby H. A. , Salama R. M. , Elbadry D. Y. , Sira A. M. , Ali M. A. , Salem M. E. , Abd‐Alaaty B. M. , Goda S. S. , Eltaras S. M. , Khalil F. O. , Abou‐Zeinah S. S. , Sira M. M.
Published: February 2018

Fulminant hepatic failure is a life‐threatening disease. Hepatitis A virus (HAV) can cause fulminant hepatic failure and death in about 0.2% of cases. Extensive destruction of infected hepatocytes by immune‐mediated lysis is thought to be the cause. We aimed to evaluate the use of steroid therapy in children with fulminant HAV. This study included 33 children with fulminant HAV in two groups. Steroid group: comprised of 18 children who received prednisolone (1 mg/kg/d) or its equivalent dose of methylprednisolone, and the nonsteroid group: comprised another 15 children who did not receive steroid therapy. Age and sex were matched for both groups (P > .05), and they were comparable regarding baseline clinical and laboratory characteristics. Of the steroid group, 15 patients survived and 3 died, while in the nonsteroid group, 4 patients survived and 11 died (P = .001). Of the living patients, 15 of 19 (78.9%) received steroids while only 3 of 14 (21.4%) of the dead patients received steroids (P = .001). Stepwise regression analysis showed that steroid therapy was the only independent variable associated with recovery (P = .001). Steroid therapy in children with fulminant HAV associated significantly with improved outcome and survival. Future studies on a larger population size are strongly recommended.
DNA gyrase activity regulates DnaA‐dependent replication initiation in Bacillus subtilis
Authors: Samadpour A. N. , Merrikh H.
Published: February 2018

In bacteria, initiation of DNA replication requires the DnaA protein. Regulation of DnaA association and activity at the origin of replication, oriC, is the predominant mechanism of replication initiation control. One key feature known to be generally important for replication is DNA topology. Although there have been some suggestions that topology may impact replication initiation, whether this mechanism regulates DnaA‐mediated replication initiation is unclear. We found that the essential topoisomerase, DNA gyrase, is required for both proper binding of DnaA to oriC as well as control of initiation frequency in Bacillus subtilis. Furthermore, we found that the regulatory activity of gyrase in initiation is specific to DnaA and oriC. Cells initiating replication from a DnaA‐independent origin, oriN, are largely resistant to gyrase inhibition by novobiocin, even at concentrations that compromise survival by up to four orders of magnitude in oriC cells. Furthermore, inhibition of gyrase does not impact initiation frequency in oriN cells. Additionally, deletion or overexpression of the DnaA regulator, YabA, significantly modulates sensitivity to gyrase inhibition, but only in oriC and not oriN cells. We propose that gyrase is a negative regulator of DnaA‐dependent replication initiation from oriC, and that this regulatory mechanism is required for cell survival.
Drought stress and tree size determine stem CO2 efflux in a tropical forest
Authors: Rowland Lucy , da Costa Antonio C. L. , Oliveira Alex A. R. , Oliveira Rafael S. , Bittencourt Paulo L. , Costa Patricia B. , Giles Andre L. , Sosa Azul I. , Coughlin Ingrid , Godlee John L. , Vasconcelos Steel S. , Junior João A. S. , Ferreira Leandro V. , Mencuccini Maurizio , Meir Patrick
Published: February 2018

CO2 efflux from stems (CO2_stem) accounts for a substantial fraction of tropical forest gross primary productivity, but the climate sensitivity of this flux remains poorly understood.

We present a study of tropical forest CO2_stem from 215 trees across wet and dry seasons, at the world's longest running tropical forest drought experiment site.

We show a 27% increase in wet season CO2_stem in the droughted forest relative to a control forest. This was driven by increasing CO2_stem in trees 10–40 cm diameter. Furthermore, we show that drought increases the proportion of maintenance to growth respiration in trees > 20 cm diameter, including large increases in maintenance respiration in the largest droughted trees, > 40 cm diameter. However, we found no clear taxonomic influence on CO2_stem and were unable to accurately predict how drought sensitivity altered ecosystem scale CO2_stem, due to substantial uncertainty introduced by contrasting methods previously employed to scale CO2_stem fluxes.

Our findings indicate that under future scenarios of elevated drought, increases in CO2_stem may augment carbon losses, weakening or potentially reversing the tropical forest carbon sink. However, due to substantial uncertainties in scaling CO2_stem fluxes, stand‐scale future estimates of changes in stem CO2 emissions remain highly uncertain.
Transplant‐related mortality and survival in children with malignancies treated with allogeneic hematopoietic stem cell transplantation. A multicenter analysis
Authors: Zaucha‐Prazmo Agnieszka , Gozdzik Jolanta , Debski Robert , Drabko Katarzyna , Sadurska Elzbieta , Kowalczyk Jerzy R.
Published: February 2018

The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant‐related reasons. The most frequently observed causes of TRM were toxic complications effecting with organ failure (38%), followed by infections (26%), PTLD (14.3%), and GvHD (16.7%). There was no statistical difference in the incidence of TRM depending on stem cell source (P = .209) and primary diagnosis (P = .301). According to TRM score, TRM was significantly higher in high‐risk group (P = .006). High‐risk patients had lower survival comparing to low/intermediate group (P = .0001). OS did not differ between ALL, AML, and MDS/JMML groups. The study confirmed the utility of factors included in TRM score stratification in assessing the risk of transplant procedure in pediatric patients transplanted for malignancies.
The Historical Presidency: Lost Confidence: The Democratic Party, the Vietnam War, and the 1968 Election
Authors: Nelson Michael
Published: February 2018

The 1968 election was a crucial turning point for the Democratic Party. Long‐standing confidence by Democrats in the ability and responsibility of the United States to spread liberal values across the globe gave way to diffidence and hesitancy in the international arena in the face of growing disillusionment within the party about the Vietnam War. John F. Kennedy, with resolve, and Lyndon B. Johnson, with reservations, unsuccessfully pursued victory in the war, thereby creating the conditions for a revolt within their party that doomed Hubert H. Humphrey's candidacy in 1968 and led Democrats to turn against liberal assertiveness on the world stage for nearly the next quarter century.
Production of moss‐dominated biocrusts to enhance the stability and function of the margins of artificial water bodies
Authors: Cruz de Carvalho Ricardo , dos Santos Patrícia , Branquinho Cristina
Published: February 2018

Margins of water reservoirs associated with dams can have high‐frequency tides, promoting soil erosion and nutrient leaching. We propose the use of biocrusts for restoration and ecological engineering purposes, due to their poikilohydric character, to stabilize reservoir margins. We promoted biocrust growth under controlled conditions, testing two types of substrate: native sand and organic substrate. After 2 months, biocrusts grew on organic substrate covering almost all the area, but not on native sand. This fast and easy nature‐based solution for soil stabilization can be used as an environmental engineering tool in highly degraded sites.
S‐Nitrosoglutathione works downstream of nitric oxide to mediate iron‐deficiency signaling in Arabidopsis
Authors: Kailasam Sakthivel , Wang Ying , Lo Jing‐Chi , Chang Hsin‐Fang , Yeh Kuo‐Chen
Published: February 2018

Iron (Fe) is essential for plant growth and development. Knowledge of Fe signaling, from the beginning of perception to activation of the uptake process, is critical for crop improvement. Here, by using chemical screening, we identified a small molecule 3‐amino‐N‐(3‐methylphenyl)thieno[2,3‐b]pyridine‐2‐carboxamide named R7 (‘R’ denoting repressor of IRON‐REGULATED TRANSPORTER 1), that modulates Fe homeostasis of Arabidopsis. R7 treatment led to reduced Fe levels in plants, thus causing severe chlorosis under Fe deficiency. Expression analysis of central transcription factors, FER‐LIKE IRON DEFICIENCY INDUCED TRANSCRIPTION FACTOR (FIT) and subgroup Ib basic helix–loop–helix (Ib bHLH) genes bHLH38/39/100/101, revealed that R7 targets the FIT‐dependent transcriptional pathway. Exogenously supplying S‐nitrosoglutathione (GSNO), but not other nitric oxide (NO) donors sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐dl‐penicillamine (SANP), alleviated the inhibitory effects of R7 on Fe homeostasis. R7 did not inhibit cellular levels of NO or glutathione but decreased GSNO level in roots. We demonstrate that NO is involved in regulating not only the FIT transcriptional network but also the Ib bHLH networks. In addition, GSNO, from S‐nitrosylation of glutathione, specifically mediates the Fe‐starvation signal to FIT, which is distinct from the NO to Ib bHLH signal. Our work dissects the molecular connection between NO and the Fe‐starvation response. We present a new signaling route whereby GSNO acts downstream of NO to trigger the Fe‐deficiency response in Arabidopsis.
The glycan‐dependent ERAD machinery degrades topologically diverse misfolded proteins
Authors: Shin Yun‐Ji , Vavra Ulrike , Veit Christiane , Strasser Richard
Published: February 2018

Many soluble and integral membrane proteins fold in the endoplasmic reticulum (ER) with the help of chaperones and folding factors. Despite these efforts, protein folding is intrinsically error prone and amino acid changes, alterations in post‐translational modifications or cellular stress can cause protein misfolding. Folding‐defective non‐native proteins are cleared from the ER and typically undergo ER‐associated degradation (ERAD). Here, we investigated whether different misfolded glycoproteins require the same set of ERAD factors and are directed to HRD1 complex‐mediated degradation in plants. We generated a series of glycoprotein ERAD substrates harboring a misfolded domain from Arabidopsis STRUBBELIG or the BRASSINOSTEROID INSENSITVE 1 receptor fused to different membrane anchoring regions. We show that single pass and multispanning ERAD substrates are subjected to glycan‐dependent degradation by the HRD1 complex. However, the presence of a powerful ER exit signal in the multispanning ERAD substrates causes competition with ER quality control and targeting of misfolded glycoproteins to the vacuole. Our results demonstrate that the same machinery is used for degradation of topologically different misfolded glycoproteins in the ER of plants.
Genome sequence of M6, a diploid inbred clone of the high‐glycoalkaloid‐producing tuber‐bearing potato species Solanum chacoense, reveals residual heterozygosity
Authors: Leisner Courtney P. , Hamilton John P. , Crisovan Emily , Manrique‐Carpintero Norma C. , Marand Alexandre P. , Newton Linsey , Pham Gina M. , Jiang Jiming , Douches David S. , Jansky Shelley H. , Buell C. Robin
Published: February 2018

Cultivated potato (Solanum tuberosum L.) is a highly heterozygous autotetraploid that presents challenges in genome analyses and breeding. Wild potato species serve as a resource for the introgression of important agronomic traits into cultivated potato. One key species is Solanum chacoense and the diploid, inbred clone M6, which is self‐compatible and has desirable tuber market quality and disease resistance traits. Sequencing and assembly of the genome of the M6 clone of S. chacoense generated an assembly of 825 767 562 bp in 8260 scaffolds with an N50 scaffold size of 713 602 bp. Pseudomolecule construction anchored 508 Mb of the genome assembly into 12 chromosomes. Genome annotation yielded 49 124 high‐confidence gene models representing 37 740 genes. Comparative analyses of the M6 genome with six other Solanaceae species revealed a core set of 158 367 Solanaceae genes and 1897 genes unique to three potato species. Analysis of single nucleotide polymorphisms across the M6 genome revealed enhanced residual heterozygosity on chromosomes 4, 8 and 9 relative to the other chromosomes. Access to the M6 genome provides a resource for identification of key genes for important agronomic traits and aids in genome‐enabled development of inbred diploid potatoes with the potential to accelerate potato breeding.
Combined Effects of Thermophoresis, Brownian Motion, and Nanofluid Variable Properties on CuO-Water Nanofluid Natural Convection in a Partially Heated Square Cavity
Authors: Astanina M. S. , Abu-Nada E. , Sheremet M. A.
Published: February 2018

Numerical investigation of natural convective heat transfer and fluid flow in a differentially heated square cavity filled with a CuO-water nanofluid having variable properties is performed. Governing partial differential equations formulated in nondimensional stream function, vorticity, temperature, and nanoparticles volume fraction are solved by the second-order accurate finite difference method and taking into account the Brownian diffusion and thermophoresis. The effects of Rayleigh number (Ra = 104–106), initial nanoparticles volume fraction (C0 = 0–0.09), location of the heater (Δ = 0.0–0.9), and dimensionless time (τ = 0–300) on flow patterns, isotherms, and concentration fields as well as the local and average Nusselt numbers at the heater surface are studied. The isoconcentrations reveal that for most of the cavity domain the nanoparticle concentration is around the initial average concentration of nanoparticles except for a very limited variation in a region close to the cavity walls that experiences minor deviation from the initial concentration. It was found that the flow strength within the cavity (i.e., ψmaxRa⋅Pr) is inversely proportional to the heater location Δ and is directly proportional to the Rayleigh number. Also, it was found that the best location of the heater, from a heat transfer perspective, is placing it entirely at the left wall of the cavity where a maximum average Nusselt number is registered. This study revealed that for all heater locations there is always an adverse impact of nanoparticles on the heat transfer and the worst case is registered for the Δ = 0 and the least deterioration is noticed for Δ = 0.9.
The Thermal Response of Intumescent Coating Under Different Combinations of External Heat Fluxes
Authors: Hsu Sheng-Yen
Published: February 2018

In this study, the heat-blocking performance of intumescent coating under various combinations of external radiative and convective heat fluxes is investigated numerically. The results show that the temperature distribution and heat fluxes near the coating surface are significantly affected by the heat-source combination, and consequently, the thermal responses of coating are different. For the same magnitude of convective heat source, the higher flame temperature (lower heat convection coefficient) has larger thermal effect on coating response. For the same magnitude of heat source, the radiative heat source generates more thermal response of coating than the convective one. Moreover, if the external heat flux is not intense enough to cause large expansion ratio (2 < xL/L < 11) in 3600 s, the combination of heat source can significantly affect the substrate temperature and the total heat flux at the coating surface. However, if the expansion ratio is sufficiently large (xL/L > 11) at the quasi-steady-state (3600 s), the substrate temperature and the total heat flux are independent of the combination of heat source, which only affects the temperature and the radiative and convective heat fluxes near the coating surface (∼3 mm in this study).
Ground Effect on the Vortex Flow and Aerodynamics of a Slender Delta Wing
Authors: Lee T. , Ko L. S.
Published: February 2018

The ground effect on the aerodynamic loading and leading-edge vortex (LEV) flow generated by a slender delta wing was investigated experimentally. Both the lift and drag forces were found to increase with reducing ground distance (up to 50% of the wing chord). The lift increment was also found to be the greatest at low angles of attack α and decreased rapidly with increasing ground distance and α. The ground effect-caused earlier wing stall was also accompanied by a strengthened LEV with an increased rotational speed and size compared to the baseline wing. The smaller the ground distance, the stronger the LEV and the earlier vortex breakdown became. Meanwhile, the vortex trajectory was also found to be located further inboard and above the delta wing in ground effect compared to its baseline-wing counterpart. Finally, for wing-in-ground effect (WIG) craft with delta-wing planform the most effective in-ground-effect flight should be kept within 10% of the wing chord.
Shear Layer Development, Separation, and Stability Over a Low-Reynolds Number Airfoil
Authors: Ziadé Paul , Feero Mark A. , Lavoie Philippe , Sullivan Pierre E.
Published: February 2018

The shear layer development for a NACA 0025 airfoil at a low Reynolds number was investigated experimentally and numerically using large eddy simulation (LES). Two angles of attack (AOAs) were considered: 5 deg and 12 deg. Experiments and numerics confirm that two flow regimes are present. The first regime, present for an angle-of-attack of 5 deg, exhibits boundary layer reattachment with formation of a laminar separation bubble. The second regime consists of boundary layer separation without reattachment. Linear stability analysis (LSA) of mean velocity profiles is shown to provide adequate agreement between measured and computed growth rates. The stability equations exhibit significant sensitivity to variations in the base flow. This highlights that caution must be applied when experimental or computational uncertainties are present, particularly when performing comparisons. LSA suggests that the first regime is characterized by high frequency instabilities with low spatial growth, whereas the second regime experiences low frequency instabilities with more rapid growth. Spectral analysis confirms the dominance of a central frequency in the laminar separation region of the shear layer, and the importance of nonlinear interactions with harmonics in the transition process.
Challenging Paradigms by Optimizing Combustible Dust Separator
Authors: Strasser Wayne , Strasser Alex
Published: February 2018

A computational study was carried out to investigate the effects of internal geometry changes on the likelihood of solids buildup within, and the efficiency of, an industrial dust collector. Combustible solids held up in the unit pose a safety risk. The dust collector serves multiple functions, so the design requires a delicate balance. Particles should be separated from the incoming mixture and collected in the bottom of the unit. This particulate material should freely flow into a high-speed ejector (Mach 0.4) underneath. Gas must also flow freely to the top outlet, but sufficient gas must flow down to the ejector so that its motive gas augments the transport of particles back to the reactor (recirculation). Computational design evaluations included: (1) rod spacing, (2) ledge removal, and (3) rod cover plates. Testing on particle size distribution and density was carried out in-house to provide inputs to the computational fluid dynamics (CFD) model. Rod spacing reduction had a mixed effect on flow distribution. Plates were found to induce a negative effect on recirculation and a mixed effect on combustible solids accumulation. Removal of the ledge, however, offered slightly more recirculation along with completely alleviating stagnant solids accumulation. It is shown that, without consideration of detailed fluid physics, general separator design principals might be misguiding.
Staphylococcus aureus
HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis
Authors: Choby Jacob E. , Grunenwald Caroline M. , Celis Arianna I. , Gerdes Svetlana Y. , DuBois Jennifer L. , Skaar Eric P.
Published: February 2018

Staphylococcus aureus
is responsible for a significant amount of devastating disease. Its ability to colonize the host and cause infection is supported by a variety of proteins that are dependent on the cofactor heme. Heme is a porphyrin used broadly across kingdoms and is synthesized
de novo
from common cellular precursors and iron. While heme is critical to bacterial physiology, it is also toxic in high concentrations, requiring that organisms encode regulatory processes to control heme homeostasis. In this work, we describe a posttranscriptional regulatory strategy in
S. aureus
heme biosynthesis. The first committed enzyme in the
S. aureus
heme biosynthetic pathway, glutamyl-tRNA reductase (GtrR), is regulated by heme abundance and the integral membrane protein HemX. GtrR abundance increases dramatically in response to heme deficiency, suggesting a mechanism by which
S. aureus
responds to the need to increase heme synthesis. Additionally, HemX is required to maintain low levels of GtrR in heme-proficient cells, and inactivation of
hemX
leads to increased heme synthesis. Excess heme synthesis in a Δ
hemX
mutant activates the staphylococcal heme stress response, suggesting that regulation of heme synthesis is critical to reduce self-imposed heme toxicity. Analysis of diverse organisms indicates that HemX is widely conserved among heme-synthesizing bacteria, suggesting that HemX is a common factor involved in the regulation of GtrR abundance. Together, this work demonstrates that
S. aureus
regulates heme synthesis by modulating GtrR abundance in response to heme deficiency and through the activity of the broadly conserved HemX.

IMPORTANCE
Staphylococcus aureus
is a leading cause of skin and soft tissue infections, endocarditis, bacteremia, and osteomyelitis, making it a critical health care concern. Development of new antimicrobials against
S. aureus
requires knowledge of the physiology that supports this organism’s pathogenesis. One component of staphylococcal physiology that contributes to growth and virulence is heme. Heme is a widely utilized cofactor that enables diverse chemical reactions across many enzyme families.
S. aureus
relies on many critical heme-dependent proteins and is sensitive to excess heme toxicity, suggesting
S. aureus
must maintain proper intracellular heme homeostasis. Because
S. aureus
provides heme for heme-dependent enzymes via synthesis from common precursors, we hypothesized that regulation of heme synthesis is one mechanism to maintain heme homeostasis. In this study, we identify that
S. aureus
posttranscriptionally regulates heme synthesis by restraining abundance of the first heme biosynthetic enzyme, GtrR, via heme and the broadly conserved membrane protein HemX.
Developing outcome measures assessing wound management and patient experience: a mixed methods study
Authors: Elliott Daisy
Published: February 2018

Objectives

To develop outcome measures to assess practical management of primary surgical wounds and patient experience.

Design

Mixed methods, including qualitative interviews and data extraction from published randomised controlled trials (RCTs).

Setting

Two university-teaching NHS hospitals and three district NHS hospitals in the South West and Midlands regions of England.

Participants

Sixty-four patients and 15 healthcare professionals from abdominal general surgical specialities and obstetrics (caesarean section).

Methods

Measures were developed according to standard guidelines to identify issues relevant to patients’ experiences of surgical wounds and dressings, including analysis of existing RCT outcomes and semi-structured interviews. These were written into provisional questionnaire items for a single outcome measure. Cognitive interviews with patients and healthcare professionals assessed face validity, acceptability and relevance. Findings from interviews were regularly shared with the study team who suggested amendments to modify and reword items to improve understanding before further iterative testing with patients and healthcare professionals.

Results

Analyses of existing RCT outcomes and interviews produced a total of 69 issues. Pretesting and iterative revision established the need for two separate measures. One measure addresses healthcare professionals’ experience of wound management in two key areas: exudate and its impact, and allergic reactions to the dressing. The other measure addresses patients’ experience of wounds in seven key areas: wound comfort, dressing removal, dressings to protect the wound, impact on daily activities, ease of movement, anxiety about the wound and satisfaction with dressing. Each measure took less than five min to complete and both were understood and acceptable to patients and healthcare professionals.

Conclusion

This in-depth study has developed two measures to assess practical management of primary surgical wounds and patient experience. Further work to test their validity, reliability and application to other settings is now required.

Trial registration number

HTA - 12/200/04; Pre-results.
Cohort profile: LIFEWORK, a prospective cohort study on occupational and environmental risk factors and health in the Netherlands
Authors: Reedijk Marije , Lenters Virissa , Slottje Pauline , Pijpe Anouk , Peeters Petra H , Korevaar Joke C , Bueno-de-Mesquita Bas , Verschuren W M Monique , Verheij Robert A , Pieterson Inka , van Leeuwen Flora E , Rookus Matti A , Kromhout Hans , Vermeulen Roel C H
Published: February 2018

Purpose

LIFEWORK is a large federated prospective cohort established in the Netherlands to quantify the health effects of occupational and environmental exposures. This cohort is also the Dutch contribution to the international Cohort Study of Mobile Phone Use and Health (COSMOS). In this paper, we describe the study design, ongoing data collection, baseline characteristics of participants and the repeatability of key questionnaire items.

Participants

88 466 participants were enrolled in three cohort studies in 2011–2012. Exposure information was collected by a harmonised core questionnaire, or modelled based on occupational and residential histories; domains include air pollution (eg, nitrogen dioxide (NO2), particulate matter with diameter ≤2.5 µm (PM2.5)), noise, electromagnetic fields (EMF), mobile phone use, shift work and occupational chemical exposures. Chronic and subacute health outcomes are assessed by self-report and through linkage with health registries.

Findings to date

Participants had a median age of 51 years at baseline (range 19–87), and the majority are female (90%), with nurses being over-represented. Median exposure levels of NO2, PM2.5, EMF from base stations and noise at the participants’ home addresses at baseline were 22.9 µg/m3, 16.6 µg/m3, 0.003 mWm2and 53.1 dB, respectively. Twenty-two per cent of participants reported to have started using a mobile phone more than 10 years prior to baseline. Repeatability for self-reported exposures was moderate to high (weighted kappa range: 0.69–1) for a subset of participants (n=237) who completed the questionnaire twice.

Future plans

We are actively and passively observing participants; we plan to administer a follow-up questionnaire every 4–5 years—the first follow-up will be completed in 2018—and linkage to cause-of-death and cancer registries occurs on a (bi)annual basis. This prospective cohort offers a unique, large and rich resource for research on contemporary occupational and environmental health risks and will contribute to the large international COSMOS study on mobile phone use and health.