bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV Testing and Epidemiology in a Hospital‐Based Surgical Cohort in Malawi
Authors: Haac Bryce E. , Charles Anthony G. , Matoga Mitch , LaCourse Sylvia M. , Nonsa Dominic , Hosseinipour Mina
Published: May 2013

Background

Despite the high prevalence of HIV in adults (11 %) in Malawi, testing among surgical patients is not routine. We examined the feasibility of universal opt‐out HIV testing and counseling (HTC) on the surgical wards of Kamuzu Central Hospital in Lilongwe, Malawi, and sought to further delineate the role of HIV in surgical presentation and outcome.

Methods

We reviewed HTC and surgical admission records from May to October 2011 and compared these data to data collected prospectively on patients admitted from November 2011 through April 2012, after universal HTC implementation.

Results

Prior to universal HTC, 270 of the 2,606 (10.4 %) surgical admissions were tested; 13 % were HIV‐infected. After universal HTC implementation, HTC counselors reviewed 1,961 of the 2,488 admissions (79 %): 310 (16 %) had known status (157 seropositive, 153 seronegative) and 1,651 had unknown status (81 %). Among those with unknown status, 97 % (1,598, of 64 % of all admissions) accepted testing, of whom 9 % were found to be HIV‐infected. Patients with longer lengths of stay (LOS) (mean = 11 vs. 5 days, p < 0.01) and those who underwent surgical intervention (odds ratio [OR] 2.5; confidence interval [CI] 2.0–3.1) were more likely to have a known status on discharge. HIV was more prevalence in patients with infection and genital/anal warts or ulcers and lower in trauma patients. HIV‐positive patients received less surgical intervention (OR 0.69; CI 0.52–0.90), but there was no association between HIV status and length of stay or mortality.

Conclusions

Universal opt‐out HTC on the surgical wards was well accepted and increased the proportion of patients tested. High HIV prevalence in this setting merits implementation of universal HTC.
Improved production of protease-resistant phytase by Aspergillus oryzae and its applicability in the hydrolysis of insoluble phytates
Authors: Sapna  , Singh Bijender
Published: May 2013

Among three hundred isolates of filamentous fungi, Aspergillus oryzae SBS50 secreted higher phytase activity at pH 5.0, 35 °C and 200 rpm after 96 h of fermentation. Starch and beef extract supported the highest phytase production than other carbon and nitrogen sources. A nine-fold improvement in phytase production was achieved due to optimization. Supplementation of the medium with inorganic phosphate repressed the enzyme synthesis. Among surfactants tested, Tween 80 increased fungal growth and phytase production, which further resulted in 5.4-fold enhancement in phytase production. The phytase activity was not much affected by proteases treatment. The enzyme resulted in the efficient hydrolysis of insoluble phytate complexes (metal- and protein–phytates) in a time dependent manner. Furthermore, the hydrolysis of insoluble phytates was also supported by scanning electron microscopy. The enzyme, being resistant to trypsin and pepsin, and able to hydrolyze insoluble phytates, can find an application in the animal food/feed industry for improving nutritional quality and also in combating environmental phosphorus pollution and plant growth promotion.
Human and mouse neuroinflammation markers in Niemann‐Pick disease, type C1
Authors: Cologna Stephanie M. , Cluzeau Celine V. M. , Yanjanin Nicole M. , Blank Paul S. , Dail Michelle K. , Siebel Stephan , Toth Cynthia L. , Wassif Christopher A. , Lieberman Andrew P. , Porter Forbes D.
Published: May 2013

Niemann‐Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post‐mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C‐X‐C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL‐3, IL‐10 and IL‐13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.
Physical activity is inversely related to drug consumption in elderly patients with cardiovascular events
Authors: Cacciatore Francesco , Mazzella Francesca , Viati Luisa , Longobardi Giancarlo , Magliocca Antonio , Basile Claudia , Guadagno Livia , Ferrara Nicola , Rengo Franco , Abete Pasquale
Published: May 2013

Elderly patients with cardiovascular events are characterized by high drug consumptions. Whether high drug consumptions are related to physical activity is not known. In order to examine whether physical activity is related to drug consumption in the elderly, patients older than 65 years (n = 250) with a recent cardiovascular event were studied. Physical activity was analyzed according to the Physical Activity Scale for the Elderly (PASE) score and related to drug consumption. PASE score was 72.4 ± 45.0 and drug consumption was 8.3 ± 2.2. Elderly patients with greater comorbidity took more drugs (8.7 ± 2.1) and are less active (PASE = 64.4 ± 50.6) than patients with Cumulative Illness Rating Scale severity score higher than 1.8 than those with a score lower than 1.8 (76.3 ± 41.4, p < 0.05, and 8.0 ± 2.0, p = 0.006, respectively). Multivariate analysis correlation confirmed that PASE score is negatively associated with drug consumption (β = −0.149, p = 0.031), independently of several variables including comorbidity. Thus, physical activity is inversely related to drug consumption in elderly patients with cardiovascular events. This inverse relationship may be attributable to the high degree of comorbidity observed in elderly patients in whom poor level of physical activity and high drug consumption are predominant.
Estimation of Docosahexaenoic Acid Glycerides in Schizochytrium sp. Oil by Open Column Chromatography and Reversed‐phase HPLC
Authors: Jiang Lu , Huang He , Lei Mingliu , Zheng Hongbo , Liang Jingrui , Zhang Hongman
Published: May 2013

Column chromatography and reversed‐phase HPLC using a Sepax BR‐C18 column were applied for the analysis of glycerides in the docosahexaenoic acid (DHA) oil by Schizochytrium sp. The oil was detected under UV light after isocratic elution with 20 % 2‐propanol/hexane (5:4, v/v) + 80 % acetonitrile. The correlation coefficients for the calibration of HPLC for DHA glycerides were in the range of 0.9958–0.9998. The accuracy was confirmed with recoveries of 93.47–102.25 %. DHA oil samples under different aeration rates were successfully analyzed and the content of the binding of DHA on the acylglycerol backbone was very low (1.81–4.21 %). However, the content of glycerides (tri‐, di‐, mono‐) separated by column chromatography was more than 87.22 %. The glycerides were largely composed of triacylglycerides (TAG) (82.29–89.54 %), where higher content of TAG correlated to higher contents of DHA and TAG of DHA (TriDHA). In addition, the optimal aeration rate of 250 m3/h was obtained for TAG, DHA, and TriDHA production by Schizochytrium sp. with the temperature 30 ± 0.5 °C, impeller speed 85 ± 5 rpm and pressure 0.04 Mpa.
Effects of Processing and Composition on the Crystallization and Mechanical Properties of Water‐in‐Oil Emulsions
Authors: Cisneros Estevez A. , Toro‐Vazquez J. F. , Hartel R. W.
Published: May 2013

This research investigated the role of agitation, high‐melting emulsifier and water content on the crystallization process and the texture of water‐in‐oil emulsions produced on a pilot plant scale using a scraped surface heat exchanger (SSHE). Our results indicated that shear affected the hardness of the emulsions as they exited the SSHE, with softer emulsions processed at higher shear; once the emulsions reached equilibrium temperature, no differences in texture due to shear were observed. The added emulsifier delayed the crystallization of emulsions processed in the SSHE with no further effect on the equilibrium solid fat content (SFC) or textural properties of emulsions after 24 h of storage. The texture of the crystallized emulsions at early stages of processing was influenced by the amount of water and water droplet size; the larger the amount of water and the smaller the droplets, the higher the hardness of emulsions. Once the emulsions reached equilibrium temperature, further crystallization took place, and the texture depended only on the SFC.
Entgrenzte Lebenswelten: Wohn- und Arbeitsmigration als Ausdruck transnationaler Lebensentwürfe im deutsch-luxemburgischen und deutsch-polnischen Grenzraum
Authors: Nienaber Birte , Kriszan Agnes
Published: May 2013

National borders inside the European Union are open contact zones of transnational everyday lives. The Schengen Agreement ensures the free movement of EU ci-tizens, leading to new forms of international migration and illustrating the European integration process on the local level. Migrants move to the neighbouring country to live or work there. Cross-border residential property and labour markets develop a transnationalisation of everyday lives between neighbouring countries. With the case study region of the municipality of Perl in the German federal state of Saarland and the municipality Amt Löcknitz-Penkun in the German federal state of Mecklenburg-Western Pomerania the article deals with these cross-border everyday lives. On the one side of the national state borders there is a booming region (Luxembourg or Szczecin) and on the other side there is a structural weak rural German region. This substantially influences these processes. Both case study regions show dealings with these cross-border phenomena and spatial implications.
Repeated evaluations of the quality of clinical teaching by residents
Authors: Fluit Cornelia R. M. G. , Feskens Remco , Bolhuis Sanneke , Grol Richard , Wensing Michel , Laan Roland
Published: May 2013

Many studies report on the validation of instruments for facilitating feedback to
clinical supervisors. There is mixed evidence whether evaluations lead to more effective
teaching and higher ratings. We assessed changes in resident ratings after an evaluation
and feedback session with their supervisors. Supervisors of three medical specialities
were evaluated, using a validated instrument (EFFECT). Mean overall scores (MOS) and
mean scale scores were calculated and compared using paired T-tests. 24 Supervisors from
three departments were evaluated at two subsequent years. MOS increased from 4.36 to
4.49. The MOS of two scales showed an increase >0.2: ‘teaching methodology’
(4.34–4.55), and ‘assessment’ (4.11–4.39). Supervisors with an MOS <4.0 at year 1
(n = 5) all demonstrated a strong increase in the MOS (mean overall increase 0.50, range
0.34–0.64). Four supervisors with an MOS between 4.0 and 4.5 (n = 6) demonstrated an
increase >0.2 in their MOS (mean overall increase 0.21, range −0.15 to 53). One
supervisor with an MOS >4.5 (n = 13) demonstrated an increase >0.02 in the MOS,
two demonstrated a decrease >0.2 (mean overall increase −0.06, range −0.42 to 0.42).
EFFECT-S was associated with a positive change in residents’ ratings of their
supervisors, predominantly in supervisors with relatively low initial scores.
Secretion of miraculin through the function of a signal peptide conserved in the Kunitz‐type soybean trypsin inhibitor family
Authors: Takai Ayako , Satoh Makiko , Matsuyama Tomomi , Ito Akane , Nakata Rieko , Aoyama Takashi , Inoue Hiroyasu
Published: May 2013

Miraculin, a glycoprotein that modifies sour tastes into sweet ones, belongs to the Kunitz‐type soybean trypsin inhibitor (STI) family. To clarify the functional relation of miraculin with Kunitz‐type STIs, we investigated its subcellular localization and trypsin inhibitory activity. In transgenic Arabidopsis thaliana, miraculin, fused to yellow fluorescent protein, localized to and outside the plasma membrane depending on the putative secretion signal peptide. When transgenic seedlings were cultured in liquid medium, miraculin was present in the supernatant only after cellulase treatment. No trypsin inhibitory activity was detected in native or recombinant miraculin. In conclusion, miraculin is secreted outside the plasma membrane through the function of a signal peptide, conserved in Kunitz‐type STIs, whereas its trypsin inhibitory activity may be lost during its evolution.
Mechanisms of cisplatin ototoxicity: theoretical review
Authors: Gonçalves M S , Silveira A F , Teixeira A R , Hyppolito M A
Published: May 2013

Introduction:

Cisplatin is an effective chemotherapeutic agent commonly used in the treatment of malignant tumours, but ototoxicity is a significant side effect.

Objectives:

To discuss the mechanisms of cisplatin ototoxicity and subsequent cell death, and to present the results of experimental studies.

Material and methods:

We conducted a systematic search for data published in national and international journals and books, using the Medline, SciELO, Bireme, LILACS and PubMed databases.

Results:

The nicotinamide adenine dinucleotide phosphate oxidase 3 isoform (also termed NOX3) seems to be the main source of reactive oxygen species in the cochlea. These reactive oxygen species react with other molecules and trigger processes such as lipid peroxidation of the plasma membrane and increases in expression of the transient vanilloid receptor potential 1 ion channel.

Conclusion:

Cisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence.
Peltigera wulingensis, a new lichen (Ascomycota) from north China
Authors: HAN Liu-Fu , ZHANG Ya-Ya , GUO Shou-Yu
Published: May 2013

The terricolous lichen Peltigera wulingensis sp. nov. is described from Wuling Mountain, North China. It can be distinguished from other members of the P. rufescens group by its phyllidia along the margin or laminal cracks, scabrose upper surface, lobe extremities with tufts of tiny grey-whitish to pale brown hairs, and its slender, scattered and simple rhizines. Comparisons of the ITS sequences of the nuclear ribosomal DNA repeat tandem support the taxonomic distinctness of this species.
Collema fasciculare belongs in Arctomiaceae
Authors: OTÁLORA Mónica A. G. , WEDIN Mats
Published: May 2013

The phylogenetic placement of Collema fasciculare (L.) F. H. Wigg, the most deviating species within Collema (Collemataceae, Lecanoromycetidae), was studied using maximum likelihood and Bayesian analysis of three molecular loci (mitochondrial SSU rDNA, and the protein-coding, nuclear RPB1 and MCM7 genes). Collema fasciculare belongs to Arctomiaceae (Ostropomycetidae) forming a strongly supported monophyletic group with members of Arctomia. The spores, paraphyses, asci and hymenial reactions in Collema fasciculare are similar to other Arctomia, but the ascoma ontogeny is somewhat different. Also C. leptosporum Malme, another species in the Fasciculare group, shows similarities with Arctomia regarding spores and asci. Arctomia is morphologically heterogeneous and the genus is in need of revision. Until then, the species of the Fasciculare group fit best in Arctomia s. lat. and the combinations Arctomia fascicularis (L.) Otálora & Wedin, Arctomia leptospora (Malme) Otálora & Wedin, Arctomia papuanarum (Degel.) Otálora & Wedin and Arctomia uviformis (Hue) Otálora & Wedin are proposed.
New lichen species of the genera Porina and Byssoloma from an urban Atlantic rainforest patch in Sergipe, NE Brazil
Authors: CÁCERES Marcela Eugenia da Silva , SANTOS Marlon Wendell Oliveira dos , MENDONÇA Cléverton de Oliveira , MOTA Danyelle Andrade , APTROOT André
Published: May 2013

The new species Byssoloma catillariosporum and Porina isidioambigua are described from NE Brazil. The first is reminiscent of B. leucoblepharum but differs by the consistently uniseptate ascospores. The second is characterized by tiny isidia and black perithecia with relatively large, 3-septate ascospores. Both species were found at the Área de Proteço Ambiental (APA) Morro do Urubu, an area of c. 214 hectares in the large (500 000 inhabitants) city of Aracaju. It is the only urban Mata Atlântica remnant in Aracaju, with mesophytic deciduous and semi-deciduous forest, and cerrado enclaves in isolated points.
Jews or Germans? Nationality Legislation and the Restoration of Liberal Democracy in Western Europe after the Holocaust
Authors: Fraser David , Caestecker Frank
Published: May 2013

Statelessness continues to trouble today's international legal and political spheres. Despite the International Convention Relating to the Status of Stateless Persons, the stateless remain an unwelcome presence and awkward anomaly within an international human rights regime still fundamentally dominated by the nation state structure. In 1945, Marc Vishniak wrote that the stateless were “… restricted in their rights more than any other people and constitute the weakest chain in the link of human rights.” Hannah Arendt, who was herself a Jewish refugee from Germany, placed the enigma of the stateless in an even more central philosophical position. Whereas Visniak emphasized the problematic and marginalized legal status of the stateless within the dominant international paradigm, Arendt proposed a re-imagining of the international legal order, a vision that would prioritize a solution to the situation of the stateless, especially stateless Jews, by “somehow or other restoring to them the inalienable rights of man.” For Arendt, Jewish former citizens of Germany, stripped of their nationality by the Nazi regime, occupied a newly paradoxical situation as empowered and voluntaryHeimatlos,precisely because they now rejected the standard legal normativity of the state/citizen template. Arendt found historical support for her argument about statelessness as both abnormal within dominant international legal thinking, and at the same time strangely empowering, with regard to the situation of the mainly Jewish refugees displaced during World War I. They had fallen outside the protections offered by new succession countries at the end of that conflict, very often by their own decision to refuse incorporation as citizens of the emergent nation states. These Jewishapatridesdiscovered “privileges and juridical advantages in statelessness.” For Arendt, Jewish former citizens of Germany at the end of World War II further embodied a move toward conceptualizing a new international paradigm wherein rights could be sought beyond the traditional bounds of a state-based legal order, precisely because those bounds had been irrevocably shattered by the state itself.
“Our Militancy is in Our Openness”: Gay Employment Rights Activism in California and the Question of Sexual Orientation in Sex Equality Law
Authors: Turk Katherine
Published: May 2013

On Good Friday of 1973, members of San Francisco's homosexual community staged a public demonstration amidst the skyscrapers in the business district. Shen Hayes, described as a “frail nineteen-year-old,” claimed to embody the suffering of the city's gay population. Hayes dragged a telephone pole “cross” on his back while throngs of protesters cheered and chanted. The local minister leading the action likened gays’ lack of rights to murder, and the caption accompanying Hayes’ photo in the newspaper claimed that he and other gay Californians had been “crucified.” Despite, despite the protest's religious intensity, its objective was secular. Activists had convened to oppose discrimination against those workers whom Pacific Telephone & Telegraph (PT&T) had labeled “manifest homosexuals”: employees and job applicants who either claimed orseemedto be gay.
Crew and Patient Safety in Ambulances: Results of a Personnel Survey and Experimental Side Impact Crash Test
Authors: Fournier Marc , Chenaitia Hichem , Masson Catherine , Michelet Pierre , Behr Michel , Auffray Jean-Pierre
Published: May 2013

Introduction

Ambulance drivers often travel under stressful conditions at high speed while using vehicles with poor high-speed maneuverability. The occupant safety of ambulance vehicles has not yet been addressed by the automotive safety paradigm; particularly for the rear patient compartment. This study had two objectives: (1) to assess by survey the French Emergency Medical Services (EMS) to determine the layout of the vehicle most often used and the EMS personnel's behavior during transport; and (2) to conduct a crash test to analyze the injuries which may affect EMS personnel and patients in the rear patient compartment.

Method

Firstly, a survey was distributed to the 50 largest metropolitan French EMS programs. Secondly, a crash test was performed with a Mobile Intensive Care Unit (MICU) in conditions closest to reality.

Results

Forty-nine of the 50 biggest metropolitan French EMS programs responded to the survey. This represents 108 French MICUs. During the last three years, 12 of 49 EMS programs (24%) identified at least one accident with an MICU, and six of these 12 (50%) suffered at least one death in those accidents. A crash test using a typical French EMS MICU showed that after impact of a collision, the ambulance was moved more than five meters with major consequences for all passengers. A study-approved human cadaver placed in the position of a potential patient was partially thrown from the stretcher with a head impact. The accelerometric reaction of the anthropomorphic manikin head was measured at 48G.

Conclusion

The crash test demonstrated a lack of safety for EMS personnel and patients in the rear compartment. It would be preferable if each piece of medical equipment were provided with a quick release system resistant to three-dimensional 10G forces. The kinetic changes undergone by the “patient” substitute on the stretcher would probably have an effect of causing injury pathology. This study highlights the need for more research and development in this area.

FournierM,ChenaitiaH,MassonC,MicheletP,BehrM,AuffrayJP.Crew and patient safety in ambulances: results of a personnel survey and experimental side impact crash test.Prehosp Disaster Med.2013;28(4):1-6.
A food desert in Detroit: associations with food shopping and eating behaviours, dietary intakes and obesity
Authors: Budzynska Katarzyna , West Patricia , Savoy-Moore Ruth T , Lindsey Darlene , Winter Michael , Newby PK
Published: May 2013

Objective

Currently 67 % of the US population is overweight or obese and obesity is associated with several chronic medical conditions. Geographic areas where individuals lack access to healthy foods have been termed ‘food deserts’. The study aim was to examine if area of residence within Metro Detroit was associated with dietary intake, food and shopping behaviours, and BMI.

Design

Cross-sectional study.

Settings

Participants were recruited in the waiting area of four primary-care clinics.

Subjects

Individuals (n 1004) completed a questionnaire comprising four sections: demographics; personal health status including self-reported height and weight; a modified diet, transportation and shopping survey; and a subscale from the Diet and Health Knowledge Survey.

Results

Seventy-four per cent of participants were female and the mean age was 46·7 (sd 15·0) years. In univariate analyses, living in Detroit was associated with being African American, unemployment, less education, no regular exercise, worse health self-rating and obesity (P < 0·0005 for all). Participants living in Detroit had a 3·06 (95 % CI 1·91, 4·21) kg/m2 larger BMI compared with people living outside the city (P < 0·0005) in univariate analyses, but the effect was attenuated when adjusted for demographics, disease status, shopping and eating behaviours, dietary intakes and diet knowledge (β = −0·46 kg/m2, 95 % CI −2·23, 1·30 kg/m2, P = 0·60).

Conclusions

Overweight and obesity are highly prevalent both inside (82·9 %) and outside (72·8 %) the city of Detroit, presenting a major public health problem. However, living in this food desert was not significantly associated with BMI after potential covariates were considered.
Development and Initial Validation of the Workplace Resilience Inventory
Authors: McLarnon Matthew J. W. , Rothstein Mitchell G.
Published: May 2013

This study sought to provide the initial psychometric evidence supporting a new measure of resiliency. In consideration of the shortcomings of previous measures, a more comprehensive measure was developed based on the theoretical model of King and Rothstein (2010) . The resulting measure, the Workplace Resilience Inventory (WRI), encompasses an individual’s personal characteristics, social support network, initial responses to a significant and life changing event, and self-regulatory processes. Following a rigorous, theoretically-based, and empirically-supported procedure for selecting items, the facets of the WRI demonstrated acceptable internal consistency, as well as adequate independence. The WRI demonstrates significant relations with important well-being criteria, such as satisfaction with life, depression, and perceived stress, and demonstrates incremental validity above and beyond a previously validated measure of resiliency, the Psychological Capital (PsyCap) questionnaire.
Immunological aspects of atherosclerosis
Authors: Woollard Kevin J.
Published: May 2013

Cardiovascular disease is the leading cause of death in several countries. The underlying process is atherosclerosis, a slowly progressing chronic disorder that can lead to intravascular thrombosis. There is overwhelming evidence for the underlying importance of our immune system in atherosclerosis. Monocytes, which comprise part of the innate immune system, can be recruited to inflamed endothelium and this recruitment has been shown to be proportional to the extent of atherosclerotic disease. Monocytes undergo migration into the vasculature, they differentiate into macrophage phenotypes, which are highly phagocytic and can scavenge modified lipids, leading to foam cell formation and development of the lipid-rich atheroma core. This increased influx leads to a highly inflammatory environment and along with other immune cells can increase the risk in the development of the unstable atherosclerotic plaque phenotype. The present review provides an overview and description of the immunological aspect of innate and adaptive immune cell subsets in atherosclerosis, by defining their interaction with the vascular environment, modified lipids and other cellular exchanges. There is a particular focus on monocytes and macrophages, but shorter descriptions of dendritic cells, lymphocyte populations, neutrophils, mast cells and platelets are also included.
Phenotypic diversity and relationships among a worldwide durum wheat (Triticum turgidum L. var. durum) germplasm collection under rainfed conditions of Iran
Authors: Mohammadi Reza , Amri Ahmed
Published: May 2013

Information on the variation available for different plant attributes has enabled germplasm collections to be effectively utilised in crop improvement. This study evaluated 380 durum wheat landraces, representing a worldwide durum wheat collection from 16 geographical origins, for several phenological and agronomic traits under rainfed conditions of Iran during three consecutive cropping seasons (2008–11). The experimental design was an unreplicated trial for all landraces, augmented by four repeated check cultivars. Best linear unbiased predictions (BLUPs) representing adjusted genotypic means were generated for individual trials using a mixed model. Multivariate analyses were used to measure the phenotypic diversity within the germplasm collection and relationships among landraces from different geographical regions. Combined analysis of variance indicated significant differences between years, landraces, and their interaction effects, indicating high variability among the germplasm across the years for each studied trait. Low heritability coupled with low genetic advance as a percentage of the mean was observed for days to heading (DTH) and days to maturity (DTM), whereas moderate heritability with moderate genetic advance as a percentage of the mean was exhibited for grain yield (YLD) followed by 1000-kernel weight (TKW) and plant height (PHT). According to Shannon’s phenotypic diversity index, collections from Iran (which represented a high percentage of germplasm tested) exhibited lower diversity in quantitative traits, especially for phenological traits, i.e. DTH and DTM, relative to landraces from other origins. Biplot analyses indicated several significant patterns among landraces from different geographical regions. The landraces with American and Australian origins were closely associated with each other and can be characterised by low yield productivity, high PHT, and high infestation by wheat stem sawfly (WSS). In contrast, the germplasm from Asian origins showed high yield potential and high TKW with good tolerance to WSS. The results indicated that the Iranian landraces with the lowest yield tend to be late in flowering and maturity. In conclusion, landraces with a wide genetic diversity were identified and can be used to achieve breakthrough in the durum wheat genetic improvement.
Structural basis of the relaxed state of a Ca
2+
-regulated myosin filament and its evolutionary implications
Authors: Woodhead John L. , Zhao Fa-Qing , Craig Roger
Published: May 2013

Myosin filaments of muscle are regulated either by phosphorylation of their regulatory light chains or Ca
2+
binding to the essential light chains, contributing to on–off switching or modulation of contraction. Phosphorylation-regulated filaments in the relaxed state are characterized by an asymmetric interaction between the two myosin heads, inhibiting their actin binding or ATPase activity. Here, we have tested whether a similar interaction switches off activity in myosin filaments regulated by Ca
2+
binding. Cryo-electron microscopy and single-particle image reconstruction of Ca
2+
-regulated (scallop) filaments reveals a helical array of myosin head-pair motifs above the filament surface. Docking of atomic models of scallop myosin head domains into the motifs reveals that the heads interact in a similar way to those in phosphorylation-regulated filaments. The results imply that the two major evolutionary branches of myosin regulation—involving phosphorylation or Ca
2+
binding—share a common structural mechanism for switching off thick-filament activity in relaxed muscle. We suggest that the Ca
2+
-binding mechanism evolved from the more ancient phosphorylation-based system to enable rapid response of myosin-regulated muscles to activation. Although the motifs are similar in both systems, the scallop structure is more tilted and higher above the filament backbone, leading to different intermolecular interactions. The reconstruction reveals how the myosin tail emerges from the motif, connecting the heads to the filament backbone, and shows that the backbone is built from supramolecular assemblies of myosin tails. The reconstruction provides a native structural context for understanding past biochemical and biophysical studies of this model Ca
2+
-regulated myosin.
Biopolymer-reinforced synthetic granular nanocomposites for affordable point-of-use water purification
Authors: Sankar Mohan Udhaya , Aigal Sahaja , Maliyekkal Shihabudheen M. , Chaudhary Amrita , Anshup  , Kumar Avula Anil , Chaudhari Kamalesh , Pradeep Thalappil
Published: May 2013

Creation of affordable materials for constant release of silver ions in water is one of the most promising ways to provide microbially safe drinking water for all. Combining the capacity of diverse nanocomposites to scavenge toxic species such as arsenic, lead, and other contaminants along with the above capability can result in affordable, all-inclusive drinking water purifiers that can function without electricity. The critical problem in achieving this is the synthesis of stable materials that can release silver ions continuously in the presence of complex species usually present in drinking water that deposit and cause scaling on nanomaterial surfaces. Here we show that such constant release materials can be synthesized in a simple and effective fashion in water itself without the use of electrical power. The nanocomposite exhibits river sand-like properties, such as higher shear strength in loose and wet forms. These materials have been used to develop an affordable water purifier to deliver clean drinking water at US $2.5/y per family. The ability to prepare nanostructured compositions at near ambient temperature has wide relevance for adsorption-based water purification.
Frequent adaptation and the McDonald–Kreitman test
Authors: Messer Philipp W. , Petrov Dmitri A.
Published: May 2013

Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald–Kreitman (MK) test to infer the rate of positive selection (
α
) from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimates of
α
severely underestimate the true rate of adaptation even if all polymorphisms with population frequencies under 50% are excluded. Furthermore, already under intermediate rates of adaptation, genetic draft substantially distorts the site frequency spectra at neutral and functional sites from the expectations under mutation–selection–drift balance. MK-type approaches that first infer demography from synonymous sites and then use the inferred demography to correct the estimation of α obtain almost the correct α in our simulations. However, these approaches typically infer a severe past population expansion although there was no such expansion in the simulations, casting doubt on the accuracy of methods that infer demography from synonymous polymorphism data. We propose a simple asymptotic extension of the MK test that yields accurate estimates of α in our simulations and should provide a fruitful direction for future studies.
Gene regulatory network for neurogenesis in a sea star embryo connects broad neural specification and localized patterning
Authors: Yankura Kristen A. , Koechlein Claire S. , Cryan Abigail F. , Cheatle Alys , Hinman Veronica F.
Published: May 2013

A great challenge in development biology is to understand how interacting networks of regulatory genes can direct the often highly complex patterning of cells in a 3D embryo. Here, we detail the gene regulatory network that describes the distribution of ciliary band-associated neurons in the bipinnaria larva of the sea star. This larva, typically for the ancestral deuterostome dipleurula larval type that it represents, forms two loops of ciliary bands that extend across much of the anterior-posterior and dorsal-ventral ectoderm. We show that the sea star first likely uses maternally inherited factors and the Wnt and Delta pathways to distinguish neurogenic ectoderm from endomesoderm. The broad neurogenic potential of the ectoderm persists throughout much of gastrulation. Nodal, bone morphogenetic protein 2/4 (Bmp2/4), and Six3-dependent pathways then sculpt a complex ciliary band territory that is defined by the expression of the forkhead transcription factor,
foxg
. Foxg is needed to define two molecularly distinct ectodermal domains, and for the formation of differentiated neurons along the edge of these two territories. Thus, significantly, Bmp2/4 signaling in sea stars does not distinguish differentiated neurons from nonneuronal ectoderm as it does in many other animals, but instead contributes to the patterning of an ectodermal territory, which then, in turn, provides cues to permit the final steps of neuronal differentiation. The modularity between specification and patterning likely reflects the evolutionary history of this gene regulatory network, in which an ancient module for specification of a broad neurogenic potential ectoderm was subsequently overlaid with a module for patterning.
Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site
Authors: Schifano Jason M. , Edifor Regina , Sharp Jared D. , Ouyang Ming , Konkimalla Arvind , Husson Robert N. , Woychik Nancy A.
Published: May 2013

The
Mycobacterium tuberculosis
genome contains an unusually high number of toxin–antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin–antitoxin loci belong to the
mazEF
family, encoding the intracellular toxin MazF and its antitoxin inhibitor MazE. Nearly every MazF ortholog recognizes a unique three- or five-base RNA sequence and cleaves mRNA. As a result, these toxins selectively target a subset of the transcriptome for degradation and are known as “mRNA interferases.” Here we demonstrate that a MazF family member from
M. tuberculosis,
MazF-mt6, has an additional role—inhibiting translation through targeted cleavage of 23S rRNA in the evolutionarily conserved helix/loop 70. We first determined that MazF-mt6 cleaves mRNA at
5
′
UU↓CCU
3′
sequences. We then discovered that MazF-mt6 also cleaves
M. tuberculosis
23S rRNA at a single UUCCU in the ribosomal A site that contacts tRNA and ribosome recycling factor. To gain further mechanistic insight, we demonstrated that MazF-mt6–mediated cleavage of rRNA can inhibit protein synthesis in the absence of mRNA cleavage. Finally, consistent with the position of 23S rRNA cleavage, MazF-mt6 destabilized 50S–30S ribosomal subunit association. Collectively, these results show that MazF toxins do not universally act as mRNA interferases, because MazF-mt6 inhibits protein synthesis by cleaving 23S rRNA in the ribosome active center.
Heterochromatin protein Sir3 induces contacts between the amino terminus of histone H4 and nucleosomal DNA
Authors: Wang Feng , Li Geng , Altaf Mohammed , Lu Chenning , Currie Mark A. , Johnson Aaron , Moazed Danesh
Published: May 2013

The regulated binding of effector proteins to the nucleosome plays a central role in the activation and silencing of eukaryotic genes. How this binding changes the properties of chromatin to mediate gene activation or silencing is not fully understood. Here we provide evidence that association of the budding yeast silent information regulator 3 (Sir3) silencing protein with the nucleosome induces a conformational change in the amino terminus of histone H4 that promotes interactions between the conserved H4 arginines 17 and 19 (R17 and R19) and nucleosomal DNA. Substitutions of H4R17 and R19 with alanine abolish silencing in vivo, but have little or no effect on binding of Sir3 to nucleosomes or histone H4 peptides in vitro. Furthermore, in both the previously reported crystal structure of the Sir3-bromo adjacent homology (BAH) domain bound to the
Xenopus laevis
nucleosome core particle and the crystal structure of the Sir3-BAH domain bound to the yeast nucleosome core particle described here, H4R17 and R19 make contacts with nucleosomal DNA rather than with Sir3. These results suggest that Sir3 binding generates a more stable nucleosome by clamping H4R17 and R19 to nucleosomal DNA, and raise the possibility that such induced changes in histone–DNA contacts play major roles in the regulation of chromatin structure.
Complex history of the amphibian-killing chytrid fungus revealed with genome resequencing data
Authors: Rosenblum Erica Bree , James Timothy Y. , Zamudio Kelly R. , Poorten Thomas J. , Ilut Dan , Rodriguez David , Eastman Jonathan M. , Richards-Hrdlicka Katy , Joneson Suzanne , Jenkinson Thomas S. , Longcore Joyce E. , Parra Olea Gabriela , Toledo Luís Felipe , Arellano Maria Luz , Medina Edgar M. , Restrepo Silvia , Flechas Sandra Victoria , Berger Lee , Briggs Cheryl J. , Stajich Jason E.
Published: May 2013

Understanding the evolutionary history of microbial pathogens is critical for mitigating the impacts of emerging infectious diseases on economically and ecologically important host species. We used a genome resequencing approach to resolve the evolutionary history of an important microbial pathogen, the chytrid
Batrachochytrium dendrobatidis
(Bd), which has been implicated in amphibian declines worldwide. We sequenced the genomes of 29 isolates of Bd from around the world, with an emphasis on North, Central, and South America because of the devastating effect that Bd has had on amphibian populations in the New World. We found a substantial amount of evolutionary complexity in Bd with deep phylogenetic diversity that predates observed global amphibian declines. By investigating the entire genome, we found that even the most recently evolved Bd clade (termed the global panzootic lineage) contained more genetic variation than previously reported. We also found dramatic differences among isolates and among genomic regions in chromosomal copy number and patterns of heterozygosity, suggesting complex and heterogeneous genome dynamics. Finally, we report evidence for selection acting on the Bd genome, supporting the hypothesis that protease genes are important in evolutionary transitions in this group. Bd is considered an emerging pathogen because of its recent effects on amphibians, but our data indicate that it has a complex evolutionary history that predates recent disease outbreaks. Therefore, it is important to consider the contemporary effects of Bd in a broader evolutionary context and identify specific mechanisms that may have led to shifts in virulence in this system.
Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels
Authors: Yu Haibo , Lin Zhihong , Mattmann Margrith E. , Zou Beiyan , Terrenoire Cecile , Zhang Hongkang , Wu Meng , McManus Owen B. , Kass Robert S. , Lindsley Craig W. , Hopkins Corey R. , Li Min
Published: May 2013

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1–KCNEx complexes. Mutations in either
KCNQ1
or
KCNE1
genes result in diseases in brain, heart, and the respiratory system. In addition to complexities arising from existence of five KCNE subunits, KCNE1 to KCNE5, recent studies in heterologous systems suggest unorthodox stoichiometric dynamics in subunit assembly is dependent on KCNE expression levels. The resultant KCNQ1–KCNE channel complexes may have a range of zero to two or even up to four KCNE subunits coassembling per KCNQ1 tetramer. These findings underscore the need to assess the selectivity of small-molecule KCNQ1 modulators on these different assemblies. Here we report a unique small-molecule gating modulator, ML277, that potentiates both homomultimeric KCNQ1 channels and unsaturated heteromultimeric (KCNQ1)
4
(KCNE1)
n
(
n
< 4) channels. Progressive increase of KCNE1 or KCNE3 expression reduces efficacy of ML277 and eventually abolishes ML277-mediated augmentation. In cardiomyocytes, the slowly activating delayed rectifier potassium current, or
I
Ks
, is believed to be a heteromultimeric combination of KCNQ1 and KCNE1, but it is not entirely clear whether
I
Ks
is mediated by KCNE-saturated KCNQ1 channels or by channels with intermediate stoichiometries. We found ML277 effectively augments
I
Ks
current of cultured human cardiomyocytes and shortens action potential duration. These data indicate that unsaturated heteromultimeric (KCNQ1)
4
(KCNE1)
n
channels are present as components of
I
Ks
and are pharmacologically distinct from KCNE-saturated KCNQ1–KCNE1 channels.
Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice
Authors: Martinod Kimberly , Demers Melanie , Fuchs Tobias A. , Wong Siu Ling , Brill Alexander , Gallant Maureen , Hu Jing , Wang Yanming , Wagner Denisa D.
Published: May 2013

Deep vein thrombosis and pulmonary embolism are major health problems associated with high mortality. Recently, DNA-based neutrophil extracellular traps (NETs) resulting from the release of decondensed chromatin, were found to be part of the thrombus scaffold and to promote coagulation. However, the significance of nuclear decondensation and NET generation in thrombosis is largely unknown. To address this, we adopted a stenosis model of deep vein thrombosis and analyzed venous thrombi in peptidylarginine deiminase 4 (PAD4)-deficient mice that cannot citrullinate histones, a process required for chromatin decondensation and NET formation. Intriguingly, less than 10% ofPAD4−/−mice produced a thrombus 48 h after inferior vena cava stenosis whereas 90% of wild-type mice did. Neutrophils were abundantly present in thrombi formed in both groups, whereas extracellular citrullinated histones were seen only in thrombi from wild-type mice. Bone marrow chimera experiments indicated that PAD4 in hematopoietic cells was the source of the prothrombotic effect in deep vein thrombosis. Thrombosis could be rescued by infusion of wild-type neutrophils, suggesting that neutrophil PAD4 was important and sufficient. Endothelial activation and platelet aggregation were normal inPAD4−/−mice, as was hemostatic potential determined by bleeding time and platelet plug formation after venous injury. Our results show that PAD4-mediated chromatin decondensation in the neutrophil is crucial for pathological venous thrombosis and present neutrophil activation and PAD4 as potential drug targets for deep vein thrombosis.
Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2
Authors: Acunzo Mario , Romano Giulia , Palmieri Dario , Laganá Alessandro , Garofalo Michela , Balatti Veronica , Drusco Alessandra , Chiariello Mario , Nana-Sinkam Patrick , Croce Carlo M.
Published: May 2013

In the past decade, we have observed exciting advances in lung cancer therapy, including the development of targeted therapies. However, additional strategies for early detection and tumor-based therapy are still essential in improving patient outcomes. EGF receptor (EGFR) and MET (the receptor tyrosine kinase for hepatocyte growth factors) are cell-surface tyrosine kinase receptors that have been implicated in diverse cellular processes and as regulators of several microRNAs (miRNAs), thus contributing to tumor progression. Here, we demonstrate a biological link between EGFR, MET, and the miRNA cluster
23a∼27a∼24–2
. We show that miR-27a regulates MET, EGFR, and Sprouty2 in lung cancer. In addition, we identify both direct and indirect mechanisms by which miR-27a can regulate both MET and EGFR. Thus, we propose a mechanism for MET and EGFR axis regulation that may lead to the development of therapeutics in lung cancer.