bluuebunny/crossref_metadata_2025 huggingface dataset:
Hunting the genes in male‐pattern alopecia: how important are they, how close are we and what will they tell us?
Authors: Heilmann‐Heimbach Stefanie , Hochfeld Lara M. , Paus Ralf , Nöthen Markus M.
Published: February 2016

Androgenetic alopecia (AGA) is a highly heritable condition, and the most common form of hair loss in men. The phenotype is characterized by an androgen‐dependent, progressive loss of hair from the scalp, which may commence during puberty. Up to 80% of European men experience some degree of androgen‐dependent hair loss during their lifetime. Current treatment options for AGA have limited efficacy, and improved understanding of the underlying biological causes is required to facilitate novel therapeutic approaches. To date, molecular genetic studies have implicated 12 genomic regions in AGA and identified a number of candidate genes. The latter include those encoding the androgen receptor (AR), the histone deacetylases (HDAC) 4 and 9, and the WNT molecule WNT10A. However, the majority of contributing genetic risk factors still await identification. This review describes the current status of AGA genetic research. We discuss the strength of the genetic approach and anticipated developments in the field, and how these will facilitate the systematic unravelling of AGA pathobiology, a process which may lead to the identification of new therapeutic targets.
Water use of a multigenotype poplar short‐rotation coppice from tree to stand scale
Authors: Bloemen Jasper , Fichot Régis , Horemans Joanna A. , Broeckx Laura S. , Verlinden Melanie S. , Zenone Terenzio , Ceulemans Reinhart
Published: February 2016

Short‐rotation coppice (SRC) has great potential for supplying biomass‐based heat and energy, but little is known about SRC's ecological footprint, particularly its impact on the water cycle. To this end, we quantified the water use of a commercial scale poplar (Populus) SRC plantation in East Flanders (Belgium) at tree and stand level, focusing primarily on the transpiration component. First, we used the AquaCrop model and eddy covariance flux data to analyse the different components of the stand‐level water balance for one entire growing season. Transpiration represented 59% of evapotranspiration (ET) at stand scale over the whole year. Measured ET and modelled ET were lower as compared to the ET of reference grassland, suggesting that the SRC only used a limited amount of water. Secondly, we compared leaf area scaled and sapwood area scaled sap flow (Fs) measurements on individual plants vs. stand scale eddy covariance flux data during a 39‐day intensive field campaign in late summer 2011. Daily stem diameter variation (∆D) was monitored simultaneously with Fs to understand water use strategies for three poplar genotypes. Canopy transpiration based on sapwood area or leaf area scaling was 43.5 and 50.3 mm, respectively, and accounted for 74%, respectively, 86%, of total ecosystem ET measured during the intensive field campaign. Besides differences in growth, the significant intergenotypic differences in daily ∆D (due to stem shrinkage and swelling) suggested different water use strategies among the three genotypes which were confirmed by the sap flow measurements. Future studies on the prediction of SRC water use, or efforts to enhance the biomass yield of SRC genotypes, should consider intergenotypic differences in transpiration water losses at tree level as well as the SRC water balance at stand level.
Value for Open Space: Protection and Access Level
Authors: Metz Neil
Published: February 2016

This paper analyzes the value for the fundamental properties of open space: protection and access, using home sales from Colorado. Several measures are used: adjacency, distance to the nearest tract of open space, and percentage of open space area. Results indicate protected land with access (e.g., public park) has the greatest value, followed closely by protected land without access (e.g., conservation land), while unprotected land (e.g., agricultural land) has little to no value. Nearest neighbor matching is used as an improved control for unobservable neighborhood effects, and results indicate previous studies may overestimate the small‐scale value of open space.
C‐terminal acidic domain of histone chaperone human NAP1 is an efficient binding assistant for histone H2A‐H2B, but not H3‐H4
Authors: Ohtomo Hideaki , Akashi Satoko , Moriwaki Yoshihito , Okuwaki Mitsuru , Osakabe Akihisa , Nagata Kyosuke , Kurumizaka Hitoshi , Nishimura Yoshifumi
Published: February 2016

Nucleosome assembly protein 1 (NAP1) binds both the (H3‐H4)2 tetramer and two H2A‐H2B dimers, mediating their sequential deposition on DNA. NAP1 contains a C‐terminal acidic domain (CTAD) and a core domain that promotes dimer formation. Here, we have investigated the roles of the core domain and CTAD of human NAP1 in binding to H2A‐H2B and H3‐H4 by isothermal calorimetry and native mass spectrometry and compared them with the roles of yeast NAP1. We show that the hNAP1 and yNAP1 dimers bind H2A‐H2B by two different modes: a strong endothermic interaction and a weak exothermic interaction. A mutant hNAP1, but not yNAP1, dimer lacking CTAD loses the exothermic interaction and shows greatly reduced H2A‐H2B binding activity. The isolated CTAD of hNAP1 binds H2A‐H2B only exothermically with relatively stronger binding as compared with the exothermic interaction observed for the full‐length hNAP1 dimer. Thus, the two CTADs in the hNAP1 dimer seem to provide binding assistance for the strong endothermic interaction of the core domain with H2A‐H2B. By contrast, in the relatively weaker binding of hNAP1 to H3‐H4 as compared with yNAP1, CTAD of hNAP1 has no significant role. To our knowledge, this is the first distinct role identified for the hNAP1 CTAD.
Mesenchymal/radioresistant traits in granular astrocytomas: evidence from a combined clinical and molecular approach
Authors: Senetta Rebecca , Mellai Marta , Manini Claudia , Castellano Isabella , Bertero Luca , Pittaro Alessandra , Schiffer Davide , Boldorini Renzo , Cassoni Paola
Published: February 2016

Aims

Granular‐cell astrocytomas (GCAs) are morphologically characterized by a prominent component of granular periodic acid–Schiff‐positive cells, and show increased aggressiveness as compared with ‘ordinary’ astrocytomas. The aim of this study was to investigate, in a small series of three GCAs, the expression of mesenchymal/radioresistance‐associated biomarkers [such as chitinase‐3‐like protein 1 (YKL‐40), hepatocyte growth factor receptor (c‐Met), and caveolin 1 (Cav1)] that could contribute to the poor outcome associated with this glioma subgroup.

Methods and results

Our results show that GCAs, according to the new molecular glioma classifications, consistently show a prognostically negative molecular trait (IDH1wt‐ATRX noloss‐1p/19q nocodeletion). Furthermore, GCAs significantly differed from a control series of 33 ‘conventional’ astrocytomas, because of diffuse and strong immunohistochemical coexpression of YKL‐40, c‐Met, and Cav1.

Conclusions

Our findings show that specific morphological traits, such as a granular‐cell component, could represent useful features in guiding the search for prognostic and predictive biomarkers that could eventually be therapy‐targetable (e.g. Met inhibitors aimed at reducing radioresistance).
Air‐abrasive debridement with glycine powder versus manual debridement and chlorhexidine administration for the maintenance of peri‐implant health status: a six‐month randomized clinical trial
Authors: Lupi SM , Granati M , Butera A , Collesano V , Rodriguez Y Baena R
Published: February 2016

Study design

This single‐masked, randomized and six‐month clinical intervention trial including two study groups was planned to evaluate the efficacy of maintenance treatment with glycine powder on the periodontal health of peri‐implant tissues.

Methods

A total of 46 patients with partial or total edentulism, carrying a total of 88 implants, were assigned either to an air abrasive with the glycine powder treatment group (AAD) or to a manual debridement and clorexidine administration treatment group (MDA). Clinical data were collected before treatment and at 3 and 6 months after the treatment. Plaque index (PI), bleeding index (BOP), probing depth (PD), clinical attachment level (CAL) and bleeding score (BS) were analysed.

Results

After 3 months,AADtreatment statistically significantly improvedBS(P< 0.05); at 6 months,AADtreatment statistically significantly improved indexesPD,PI,BOPandBS(P< 0.05). In addition, theAADtreatment proved to be more effective thanMDAin maintaining the peri‐implant health ofPDat three and 6 months, and ofPIat 6 months (P< 0.05). There were no significant changes ofCALin both groups, and all the indexes remained within the physiological levels.

Conclusions

Within the limits of the study, treatment with glycine seems appropriate in the maintenance of peri‐implant health and more effective than the traditional treatment with plastic curette and chlorhexidine.
Vitamin D supplementation trial in infancy: body composition effects at 3 years of age in a prospective follow‐up study from Montréal
Authors: Hazell T. J. , Gallo S. , Vanstone C. A. , Agellon S. , Rodd C. , Weiler H. A.
Published: February 2016

Background

The impact of vitamin D status on body composition is not well understood.

Objectives

Evaluate how vitamin D supplementation in infancy affects body composition at 3 years of age.

Methods

Double‐blind randomized trial of 132, 1‐month‐old healthy, breastfed infants randomly assigned to receive oral vitamin D3 supplements of 400, 800, 1200 or 1600 IU d−1 for 11 months. In the present analysis, 87 (66%) returned at 3 years of age. Body composition was measured using dual‐energy x‐ray absorptiometry and plasma 25‐hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography tandem mass spectrometry.

Results

Anthropometry, body composition, diet, activity and demographics were similar across dosage groups at 3 years. Mean 25(OH)D concentration from 1 month to 3 years was higher (P < 0.001) in the 1200 IU group than 800 and 400 IU groups. Children with 25(OH)D concentrations above 75 nmol L−1 had lower fat mass (~450 g; P = 0.049). In multiple linear regression, mean 25(OH)D was associated with lean mass percent (β = 0.06; CI: 0.00, 0.12; P = 0.042), fat mass (β = −11.29; CI: −22.06, −0.52; P = 0.048) and body fat percent (β = −0.06; CI: −0.12, −0.01; P = 0.045).

Conclusions

Higher vitamin D status from infancy through to 3 years of age associates with leaner body composition.
Sugar‐sweetened beverage intake and its associations with cardiometabolic risks among adolescents
Authors: Loh D. A. , Moy F. M. , Zaharan N. L. , Jalaludin M. Y. , Mohamed Z.
Published: February 2016

Background

Investigations on sugar‐sweetened beverage (SSB) intake and cardiometabolic risks among Asians are scant.

Objectives

This study aimed to examine associations between SSB intake and cardiometabolic risks among Malaysian adolescents.

Methods

Anthropometric data, blood pressure (BP), fasting blood glucose (FBG), lipid profiles and insulin levels measured involved 873 adolescents (aged 13 years). SSB intake, dietary patterns and physical activity level (PAL) were self‐reported.

Results

Mean SSB consumption was 177.5 mL day−1 with significant differences among ethnicities (Malay, Chinese, Indians and Others) (p < 0.05). SSB intake was deleteriously associated with increased waist circumference, elevated triglycerides, FBG, insulin, insulin resistance and low HDL‐cholesterol, independent of PAL, body mass index and dietary patterns. Significant U‐shaped and inverse trends were noted between SSB intake and LDL‐cholesterol and BP, respectively.

Conclusion

Sugar‐sweetened beverage intake was unfavourably associated with cardiometabolic health outcomes among young adolescents. Concerted efforts towards healthy hydration are imperative to mitigate risk of cardiometabolic events.
Salt Intakes, Knowledge, and Behavior in Samoa: Monitoring Salt‐Consumption Patterns Through the World Health Organization's Surveillance of Noncommunicable Disease Risk Factors (STEPS)
Authors: Webster Jacqui , Su'a Sarah Asi Faletoese , Ieremia Merina , Bompoint Severine , Johnson Claire , Faeamani Gavin , Vaiaso Miraneta , Snowdon Wendy , Land Mary‐Anne , Trieu Kathy , Viali Satu , Moodie Marj , Bell Colin , Neal Bruce , Woodward Mark
Published: February 2016

This project measured population salt intake in Samoa by integrating urinary sodium analysis into the World Health Organization's (WHO's) STEPwise approach to surveillance of noncommunicable disease risk factors (STEPS). A subsample of the Samoan Ministry of Health's 2013 STEPS Survey collected 24‐hour and spot urine samples and completed questions on salt‐related behaviors. Complete urine samples were available for 293 participants. Overall, weighted mean population 24‐hour urine excretion of salt was 7.09 g (standard error 0.19) to 7.63 g (standard error 0.27) for men and 6.39 g (standard error 0.14) for women (P=.0014). Salt intake increased with body mass index (P=.0004), and people who added salt at the table had 1.5 g higher salt intakes than those who did not add salt (P=.0422). A total of 70% of the population had urinary excretion values above the 5 g/d cutoff recommended by the WHO. A reduction of 30% (2 g) would reduce average population salt intake to 5 g/d, in line with WHO recommendations. While challenging, integration of salt monitoring into STEPS provides clear logistical and cost benefits and the lessons communicated here can help inform future programs.
Prognostic value of polarized macrophages in patients with hepatocellular carcinoma after curative resection
Authors: Shu Qing‐Hua , Ge Yong‐Sheng , Ma Hua‐Xing , Gao Xiao‐Qiang , Pan Jing‐Jing , Liu Dong , Xu Ge‐Liang , Ma Jin‐Liang , Jia Wei‐Dong
Published: February 2016

As the most predominant tumour‐infiltrating immune cells, tumour‐associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68‐positive TAMs display dissimilarly polarized programmes comprising CD11c‐positive pro‐inflammatory macrophages (M1) and CD206‐positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c‐positive TAM density (P = 0.005) and low versus high CD206‐positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68‐positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence‐free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c‐positive and CD206‐positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.
Ledipasvir/sofosbuvir fixed‐dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus
Authors: Chuang Wan‐Long , Chien Rong‐Nan , Peng Cheng‐Yuan , Chang Ting‐Tsung , Lo Gin‐Ho , Sheen I‐Shyan , Wang Horng‐Yuan , Chen Jyh‐Jou , Yang Jenny C. , Knox Steven J. , Gao Bing , Garrison Kimberly L. , Mo Hongmei , Pang Phillip S. , Hsu Yu‐Chun , Hu Tsung‐Hui , Chu Chi‐Jen , Kao Jia‐Horng
Published: February 2016

Background and Aim:

Pegylated‐interferon‐alpha plus ribavirin is the current standard‐of‐care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon‐based regimens can be poorly tolerated. The interferon‐free, two‐drug, fixed‐dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients.

Methods:

In this multicenter, open‐label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment‐naïve; n = 43, treatment‐experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed‐dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected.

Results:

The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment‐naïve and treatment‐experienced patients, respectively, achieving SVR12. There were no on‐treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment‐emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3–4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir.

Conclusions:

Data from this phase 3b study suggest that 12 weeks of once‐daily treatment with the interferon‐free, ribavirin‐free regimen ledipasvir/sofosbuvir is effective and well‐tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
Effects of the Addition of Titanium Dioxide and Silaned Silica Nanoparticles on the Mechanical Properties of Maxillofacial Silicones
Authors: Cevik Pinar , Eraslan Oguz
Published: February 2016

Purpose

Silicone‐based elastomeric materials are commonly used to fabricate maxillofacial prostheses. The aim of this study was to evaluate the effect of different types of silica and nanosized titanium dioxide addition on the mechanical properties of two RTV silicone elastomers.

Materials and Methods

A‐2000 and A‐2006 silicone elastomers were used, and each was divided into four subgroups (n = 5). The first group was the control without additives. Other groups were titanium dioxide, fumed silica, and silaned silica. Each specimen was prepared in compliance with the manufacturer's instructions for the tensile strength, percent elongation, tear resistance, and the hardness tests according to ISO and ASTM standards. A factorial ANOVA with pairwise interaction indicated that the pattern for all four outcomes of the materials was different for A‐2000 and A‐2006 (p < 0.05). Therefore, the average outcome values for the materials within silicone elastomers were then analyzed by Tukey HSD. For the hardness test results, Kruskal‐Wallis and Mann‐Whitney U test methods were used. The level of statistical significance was p < 0.05.

Results

There was a statistically significant interaction (p < 0.05) between materials and silicone type for all four tests (tensile strength, tear, hardness, percent elongation). The hydrophobic silica group had significantly higher tensile strength than TiO2 for A‐2000. The fumed hydrophilic silica group had significantly higher tensile strength than TiO2 for A‐2006. Most of silica specimens had higher tensile strength when compared with the control and TiO2 groups for A‐2000 and A‐2006 silicones. The TiO2 group had the highest hardness value for A‐2000 while the lowest hardness value for A‐2006 (p < 0.05). There was no significant difference of tear strength among the type of additives (p > 0.05) for A‐2000. The fumed silica and TiO2 groups had significantly higher tear strength than the control group for A‐2006. The fumed silica and the hydrophobic silica groups had significantly higher percent elongation than the control group (p < 0.05) for A‐2000. The TiO2 group had the lowest percent elongation for A‐2006.

Conclusions

Results in this in vitro study may clarify future studies about the effect of different additives on the physical and mechanical properties of maxillofacial elastomers. There is a great interest in the effect of a new‐generation hydrophobic silica incorporation into A‐2000 silicone as well as the effect of fumed hydrophilic silica incorporation into A‐2006 silicone. Future research should be supported with more in vitro trials in different percentages of such additives used in this study.
Signaling by the heavy‐metal sensor CusS involves rearranged helical interactions in specific transmembrane regions
Authors: Fung Danny Ka Chun , Ma Yongzheng , Xia Tingying , Luk Jakson Chak Hon , Yan Aixin
Published: February 2016

Two‐component systems (TCSs) play important roles in the adaptation of bacteria to stress. Despite their increasingly well understood mechanistic features, it remains poorly understood how TCSs transduce signals across membranes. Here, we use the E. coli Cu/Ag‐responsive CusSR TCS as a model to investigate the roles of CusS transmembrane (TM) residues. Proline scanning of TM1 domain led to identification of the T17P, F18P, and S21P variants, which display higher kinase activities relative to wild type. A single point mutation, V202G, in the adjacent TM2 domain specifically suppresses the hyperactivities of these mutants. Disulfide crosslinking analysis demonstrated that T17 and V202 are situated in close proximity, and Cys residues substituted at those two positions form exclusive intramolecular crosslinks when CusS is in the signaling‐inactive state. In the signaling‐active variant of CusS, however, only intermolecular crosslinking between the two Cys residues could be observed, suggesting that destabilization of an intramolecular constraint and a subsequent rearrangement of helical interactions in this TM region is involved in the activation of CusS. An analogous TM helical interface in the P. aeruginosa heavy metal sensor kinase CzcS is also observed. Together, these results suggested a conserved transmembrane signal transduction mechanism in the heavy metal sensing TCSs.
A mass stranding of seven Longman's beaked whales (Indopacetus pacificus) in New Caledonia, South Pacific
Authors: Garrigue Claire , Oremus Marc , Dodémont Rémi , Bustamante Paco , Kwiatek Olivier , Libeau Geneviève , Lockyer Christina , Vivier Jean Christophe , Dalebout Merel L.
Published: February 2016

Seven Longman's beaked whales (Indopacetus pacificus) stranded together in southern New Caledonia on 16 November 2013 (one adult male, two adult females, two subadult females, one calf, and one unknown). At this time, we have no evidence to suggest that this event was an “atypical” mass stranding associated with active naval sonar or other anthropogenic activities. The adult females were slightly larger (618–640 cm) than the adult male (590 cm). The length of the calf (ca. 300 cm) suggests it was less than a year old. Five of the whales were sampled for mitochondrial (mt) DNA analysis to confirm species identification. All shared the same haplotype over 680 bp of the mtDNA control region. High concentrations of Hg, Fe, Se, Zn (all in the liver), and Cd (in the kidneys) were detected. Necropsies revealed plastic debris in the stomach of two of the whales. One of these same whales had chronic gastritis while the other had acute pleurisy and also tested positive for morbillivirus. This infection may have been a major factor behind this mass stranding event.
Epithelial discrimination of commensal and pathogenic Candida albicans
Authors: Tang SX , Moyes DL , Richardson JP , Blagojevic M , Naglik JR
Published: February 2016

All mucosal surfaces are lined by epithelial cells and are colonised by opportunistic microbes. In health, these opportunistic microbes remain commensal and are tolerated by the immune system. However, when the correct environmental conditions arise, these microbes can become pathogenic and need to be controlled or cleared by the immune system to prevent disease. The mechanisms that enable epithelial cells to initiate the ‘danger’ signals activated specifically by pathogenic microbes are critical to mucosal defence and homeostasis but are not well understood. Deciphering these mechanisms will provide essential understanding to how mucosal tissues maintain health and activate immunity, as well as how pathogens promote disease. This review focuses on the interaction of the human fungal pathogen Candida albicans with epithelial cells and the epithelial mechanisms that enable mucosal tissues to discriminate between the commensal and pathogenic state of this medically important fungus.
Dust mite allergen Der f 4: Expression, characterization, and IgE binding in pediatric asthma
Authors: Cui Yu‐bao , Yu Li‐li , Teng Fei‐xiang , Wang Nan , Zhou Ying , Yang Li , Zhang Cheng‐bo
Published: February 2016

Background

House dust mite hypersensitivity affects millions of people worldwide, and although many allergens produced by house dust mite species have been identified, some of the less potent allergens remain to be studied.

Methods

The full‐length cDNA encoding the group 4 allergen of the house dust mite species Dermatophagoides farinae (Der f 4) was generated through degenerate primer‐based PCR, 5′ RACE, and 3′ RACE, and the cDNA fragment was cloned into an expression vector for nucleotide sequencing. Following codon optimization and removal of the signal peptide sequence, the mature gene fragment was subcloned into pET‐28b (+) and transfected into E. coli BL21 cells for expression. The recombinant protein was purified by nickel affinity chromatography, identified by SDS‐PAGE, Western blotting, and MALDI‐TOF, and tested by ELISA for IgE reactivity with sera from individuals with asthma. Bioinformatics analyses were used to identify features of Der f 4.

Results

SDS‐PAGE and Western blotting of the codon‐optimized expression product showed a specific band. The mature recombinant Der f 4 was characterized as a stable and hydrophilic 57.9‐kDa protein, and its secondary structure comprised alpha helix (25.3%), extended strand (22.51%), and random coils (52.19%). The structure of the recombinant protein was consistent with that of α‐amylase. Among 27 pediatric asthma patients, 40.74% exhibited reactivity to rDer f 4 by ELISA.

Conclusions

This initial cloning and characterization of the Der f 4 allergen serves as a foundation for future studies into the clinical importance and application of this protein for house dust mite allergy.
The effect of internalization and other psychologic factors on the remission and severity of wheeze in children
Authors: Feitosa Caroline A. , Santos Darci N. , Barreto Maurício L. , Rodrigues Laura C.
Published: February 2016

Background

Asthma prevalence in Latin America is high and continues to increase. There is evidence that the psychologic characteristics of the child are associated with greater asthma morbidity. This study aimed to investigate the independent effect of internalizing/externalizing problems on two asthma/wheeze outcomes: (i) remission and (ii) progression to severity on Latin American children with mild asthma symptoms at baseline.

Methods

This was a prospective study in a cohort of 371 asthmatic children living in a poor urban area in Salvador, Brazil. The psychologic characteristics of the child were assessed using the Child Behavior Checklist (CBCL), and wheezing was defined using the ISAAC questionnaire at the start and end of follow‐up. A multiple logistic regression model with random effects was used to examine the association between the psychologic components and both outcomes.

Results

Remission of symptoms of wheeze was observed among 229 (61.73%) children. Remission was 56% lower among children with internalizing problems (OR = 0.54, 95% CI 0.33–0.87, p = 0.01). In addition, we found that 19 (8.76%) of the children acquired severe symptoms during follow‐up and there was strong evidence of the effect of internalizing problems in increasing the risk of progression to severe wheeze symptoms (OR = 4.03, 95% CI 1.39–11.70, p = 0.01).

Conclusions

Children with internalizing problems but not externalizing had less remission of wheezing, and a higher risk of acquiring severe symptoms. These results highlight the importance of psychologic care for children with asthma, to improve the prognosis of this condition.
Non‐typeable Haemophilus influenzae purulent pericarditis in a child with cystic fibrosis
Authors: Downes Kevin J , Abulebda Kamal , Siracusa Christopher , Moore Ryan , Staat Mary A , Poynter Sue E
Published: February 2016

Early airway colonization and infection with Haemophilus influenzae in children with cystic fibrosis (CF) is common. Although the pathogenicity of non‐typeable H. influenzae (NTHi) in patients with CF is controversial, this organism can cause both upper and lower respiratory tract infections. Extra‐pulmonary disease, however, is rare. Purulent pericarditis is a suppurative complication of bacterial infection of the pericardial space that can arise as a result of direct extension from an adjacent infection. We describe a case of purulent pericarditis due to NTHi in a young child with CF that developed as a complication of inadequately treated bronchopneumonia.
A creative collaboration between the science of ecosystem restoration and art for sustainable stormwater management on an urban college campus
Authors: Ahn Changwoo
Published: February 2016

This article presents an interdisciplinary, on‐campus, student project, titled “The Rain Project” that I designed as an urban ecosystem restoration model as well as a collaborative pedagogical approach between ecological science and art at George Mason University (GMU), Virginia, U.S.A. A group of students from several disciplines (e.g. environmental science, art, civil engineering, biology, communication, and film/media) participated in designing and constructing a floating wetland for a campus stormwater pond as part of sustainable stormwater management. The Rain Project has numerous implications for college education, scholarship, and service while presenting a novel way of building a sense of community among undergraduate students for ecological awareness and literacy. The work of Jackie Brookner, a renowned eco‐artist who worked extensively on stormwater, and its relevance to the project is discussed. I strongly suggest the need for linking art and the science of ecosystem restoration to best obtain improvements in much‐needed communication for the success of community participatory restoration projects. I also believe that this kind of interdisciplinary, campus project can facilitate the changes we need to train higher education students to be able to both think differently and communicate effectively. The Rain Project introduced students to new learning strategies that connected “systems thinking” with art, ecological science, and restoration practices.
A method for estimating microporosity of fine‐grained sediments and sedimentary rocks via scanning electron microscope image analysis
Authors: Nole Michael , Daigle Hugh , Milliken Kitty L. , Prodanović Maša
Published: February 2016

This study presents a method of two‐dimensional scanning electron microscope image analysis that directly quantifies microporosity abundance in clay‐rich, fine‐grained sediments. The method is novel in that it is specifically designed to circumvent the challenge to porosity quantification posed by mineral surface charging and topographical artifacts created during Ar‐ion cross‐section polishing. It utilizes the finding that differences in circularity values can be used to distinguish micropores from blemishes in a thresholded image. This method is powerful because it is fast and provides a direct microporosity estimation technique to augment or replace experimental data. The pore size range to which the method is applicable is clear and can be selected depending on the application of the analysis. When used appropriately, the method can be implemented on microporous sediments and sedimentary rock in general. The method is developed using marine muds of Pliocene and Miocene ages from the Nankai margin (burial depths from approximately 200 to 1100 m). The close match between imaging‐derived microporosity and bulk N2 microporosity measurements shows that porosity in these young and relatively shallowly buried sediments is dominated by pores of sizes that can be imaged by scanning electron microscopy. In Kumano, forearc basin sediments of the Nankai Trough, results of this method show a significant increase in microporosity with burial depth, probably due to microporosity preservation during compaction and possibly early volcanic ash diagenesis.
Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained
Authors: Nokia Miriam S. , Lensu Sanna , Ahtiainen Juha P. , Johansson Petra P. , Koch Lauren G. , Britton Steven L. , Kainulainen Heikki
Published: February 2016

Key points

Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.

Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.

Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.

We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.

Our results confirm that sustained aerobic exercise is key in improving AHN.

Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult‐born hippocampal neurons in adult male Sprague–Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise.
Lumped Capacitance and Three-Dimensional Computational Fluid Dynamics Conjugate Heat Transfer Modeling of an Automotive Turbocharger
Authors: Burke R. D. , Copeland C. D. , Duda T. , Rayes-Belmote M. A.
Published: February 2016

One-dimensional wave-action engine models have become an essential tool within engine development including stages of component selection, understanding system interactions, and control strategy development. Simple turbocharger models are seen as a weak link in the accuracy of these simulation tools, and advanced models have been proposed to account for phenomena including heat transfer. In order to run within a full engine code, these models are necessarily simple in structure yet are required to describe a highly complex 3D problem. This paper aims to assess the validity of one of the key assumptions in simple heat transfer models, namely, that the heat transfer between the compressor casing and intake air occurs only after the compression process. Initially, a sensitivity study was conducted on a simple lumped capacity thermal model of a turbocharger. A new partition parameter was introduced αA, which divides the internal wetted area of the compressor housing into pre- and postcompression. The sensitivity of heat fluxes to αA was quantified with respect to the sensitivity to turbine inlet temperature (TIT). At low speeds, the TIT was the dominant effect on compressor efficiency, whereas at high speed αA had a similar influence to TIT. However, modeling of the conduction within the compressor housing using an additional thermal resistance caused changes in heat flows of less than 10%. Three-dimensional computational fluid dynamics (CFD) analysis was undertaken using a number of cases approximating different values of αA. It was seen that when considering a case similar to αA = 0, meaning that heat transfer on the compressor side is considered to occur only after the compression process, significant temperature could build up in the impeller area of the compressor housing, indicating the importance of the precompression heat path. The 3D simulation was used to estimate a realistic value for αA which was suggested to be between 0.15 and 0.3. Using a value of this magnitude in the lumped capacitance model showed that at low speed there would be less than 1% point effect on apparent efficiency which would be negligible compared to the 8% point seen as a result of TIT. In contrast, at high speeds, the impact of αA was similar to that of TIT, both leading to approximately 1% point apparent efficiency error.
Collaborative Design Principles From Minecraft With Applications to Multi-User Computer-Aided Design
Authors: French David J. , Stone Brett , Nysetvold Thomas T. , Hepworth Ammon , Edward Red W.
Published: February 2016

Synchronous collaborative (“multi-user”) computer-aided design (CAD) is a current topic of academic and industry interest due to its potential to reduce design lead times and improve design quality through enhanced collaboration. Minecraft, a popular multiplayer online game in which players can use blocks to design structures, is of academic interest as a natural experiment in a collaborative 3D design of very complex structures. Virtual teams of up to 40 simultaneous designers have created city-scale models with total design times in the thousands of hours. Using observation and a survey of Minecraft users, we offer insights into how virtual design teams might effectively build, communicate, and manage projects in a multi-user CAD design environment. The results suggest that multi-user CAD will be useful and practical in an engineering setting with several simultaneous contributors. We also discuss the effects of multi-user CAD on team organization, planning, design concurrency, communication, and mentoring.
U.S. Ebola Treatment Center Clinical Laboratory Support
Authors: Jelden Katelyn C. , Iwen Peter C. , Herstein Jocelyn J. , Biddinger Paul D. , Kraft Colleen S. , Saiman Lisa , Smith Philip W. , Hewlett Angela L. , Gibbs Shawn G. , Lowe John J.
Published: February 2016

Fifty-five hospitals in the United States have been designated Ebola treatment centers (ETCs) by their state and local health authorities. Designated ETCs must have appropriate plans to manage a patient with confirmed Ebola virus disease (EVD) for the full duration of illness and must have these plans assessed through a CDC site visit conducted by an interdisciplinary team of subject matter experts. This study determined the clinical laboratory capabilities of these ETCs. ETCs were electronically surveyed on clinical laboratory characteristics. Survey responses were returned from 47 ETCs (85%). Forty-one (87%) of the ETCs planned to provide some laboratory support (e.g., point-of-care [POC] testing) within the room of the isolated patient. Forty-four (94%) ETCs indicated that their hospital would also provide clinical laboratory support for patient care. Twenty-two (50%) of these ETC clinical laboratories had biosafety level 3 (BSL-3) containment. Of all respondents, 34 (72%) were supported by their jurisdictional public health laboratory (PHL), all of which had available BSL-3 laboratories. Overall, 40 of 44 (91%) ETCs reported BSL-3 laboratory support via their clinical laboratory and/or PHL. This survey provided a snapshot of the laboratory support for designated U.S. ETCs. ETCs have approached high-level isolation critical care with laboratory support in close proximity to the patient room and by distributing laboratory support among laboratory resources. Experts might review safety considerations for these laboratory testing/diagnostic activities that are novel in the context of biocontainment care.
Evaluation of Polymorphic Locus Sequence Typing for Candida glabrata Epidemiology
Authors: Katiyar Santosh , Shiffrin Eric , Shelton Celeste , Healey Kelley , Vermitsky John-Paul , Edlind Tom
Published: February 2016

The opportunistic yeast
Candida glabrata
is increasingly refractory to antifungal treatment or prophylaxis and relatedly is increasingly implicated in health care-associated infections. To elucidate the epidemiology of these infections, strain typing is required. Sequence-based typing provides multiple advantages over length-based methods, such as pulsed-field gel electrophoresis (PFGE); however, conventional multilocus sequence typing (targeting 6 conserved loci) and whole-genome sequencing are impractical for routine use. A commercial sequence-based typing service for
C. glabrata
that targets polymorphic tandem repeat-containing loci has recently been developed. These CgMT-J and CgMT-M services were evaluated with 56 epidemiologically unrelated isolates, 4 to 7 fluconazole-susceptible or fluconazole-resistant isolates from each of 5 center A patients, 5 matched pairs of fluconazole-susceptible/resistant isolates from center B patients, and 7 isolates from a center C patient who responded to then failed caspofungin therapy. CgMT-J and CgMT-M generated congruent results, resolving isolates into 24 and 20 alleles, respectively. Isolates from all but one of the center A patients shared the same otherwise rare alleles, suggesting nosocomial transmission. Unexpectedly, Pdr1 sequencing showed that resistance arose independently in each patient. Similarly, most isolates from center B also clustered together; however, this may reflect a dominant clone since their alleles were shared by multiple unrelated isolates. Although distinguishable by their echinocandin susceptibilities, all isolates from the center C patient shared alleles, in agreement with the previously reported relatedness of these isolates based on PFGE. Finally, we show how phylogenetic clusters can be used to provide surrogate parents to analyze the mutational basis for antifungal resistance.
Controlled Evaluation of the New BacT/Alert Virtuo Blood Culture System for Detection and Time to Detection of Bacteria and Yeasts
Authors: Altun Osman , Almuhayawi Mohammed , Lüthje Petra , Taha Rubina , Ullberg Måns , Özenci Volkan
Published: February 2016

We compared the newly approved BacT/Alert Virtuo blood culture system to the BacT/Alert 3D system using 115 clinical bacterial and fungal isolates in 784 simulated blood culture bottles. The time to detection was reduced by roughly 20% in the Virtuo system (
P
< 0.0001) while the detection rate did not differ.
The Barrier to Autointegration Factor: Interlocking Antiviral Defense with Genome Maintenance
Authors: Wiebe Matthew S. , Jamin Augusta
Published: February 2016

Intrinsic defenses targeting foreign DNA are one facet of the cellular armament tasked with protecting host genomic integrity. The DNA binding protein BAF (barrier to autointegration factor) contributes to multiple aspects of genome maintenance and intercepts retrovirus, poxvirus, and herpesvirus genomes during infection. In this gem, we discuss the unique position BAF occupies at the virus-host interface and how both viral and cellular mechanisms may regulate its capacity to act as a pro- or antiviral effector targeting viral DNA.
Virus and Host Mechanics Support Membrane Penetration and Cell Entry
Authors: Greber Urs F.
Published: February 2016

Viruses are quasi-inert macromolecular assemblies. Their metastable conformation changes during entry into cells, when chemical and mechanical host cues expose viral membrane-interacting proteins. This leads to membrane rupture or fusion and genome uncoating. Importantly, virions tune their physical properties and enhance penetration and uncoating. For example, influenza virus softens at low pH to uncoat. The stiffness and pressure of adenovirus control uncoating and membrane penetration. Virus and host mechanics thus present new opportunities for antiviral therapy.
Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein
Authors: Zhang Junsong , Huang Feng , Tan Likai , Bai Chuan , Chen Bing , Liu Jun , Liang Juanran , Liu Chao , Zhang Shaoying , Lu Gen , Chen Yuan , Zhang Hui
Published: February 2016

The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP) and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent of its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex.

IMPORTANCE
The interaction between the influenza virus vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for the influenza virus life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza virus transmission and pathogenicity. Importantly, as an interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.
Tuberculous epididymo-orchitis masquerading as acute scrotum
Authors: Kinnear Ned , Hoh Ivan , Campillo Pedro , Bolt John
Published: February 2016

An 18-year-old boy, a refugee from Afghanistan, with no significant medical history, presented after 1 day of severe left testicular pain. History, clinical examination and scrotal ultrasound suggested the diagnosis of epididymo-orchitis. He was discharged on a 2-week course of amoxicillin/clavulanic acid. Six weeks later, he re-presented with a testicular abscess, continuous with the epididymal head. Incision and drainage led to laboratory confirmation of tuberculous infection. He was treated with isoniazid, rifampicin, ethambutol, pyrazinamide and vitamin B6for 9 months, with good response. Despite meeting high-risk criteria for tuberculosis, our patient had a delayed diagnosis. We present the case and discuss the lessons learned.