On open-closed extension of boundary string field theory

We investigate a classical open-closed string field theory whose open string sector is given by boundary string field theory. The open-closed interaction is introduced by the overlap of a boundary state with a closed string field. With the help of the Batalin-Vilkovisky formalism, the closed string sector is determined to be the HIKKO closed string field theory. We also discuss the gauge invariance of this theory in both open and closed string sides.Comment: 25 pages, 2 figures, comments and a reference added, typos correcte

IMPECCABLE: Integrated Modeling PipelinE for COVID Cure by Assessing Better LEads

The drug discovery process currently employed in the pharmaceutical industry typically requires about 10 years and $2–3 billion to deliver one new drug. This is both too expensive and too slow, especially in emergencies like the COVID-19 pandemic. In silico methodologies need to be improved both to select better lead compounds, so as to improve the efficiency of later stages in the drug discovery protocol, and to identify those lead compounds more quickly. No known methodological approach can deliver this combination of higher quality and speed. Here, we describe an Integrated Modeling PipEline for COVID Cure by Assessing Better LEads (IMPECCABLE) that employs multiple methodological innovations to overcome this fundamental limitation. We also describe the computational framework that we have developed to support these innovations at scale, and characterize the performance of this framework in terms of throughput, peak performance, and scientific results. We show that individual workflow components deliver 100 × to 1000 × improvement over traditional methods, and that the integration of methods, supported by scalable infrastructure, speeds up drug discovery by orders of magnitudes. IMPECCABLE has screened ∼ 1011 ligands and has been used to discover a promising drug candidate. These capabilities have been used by the US DOE National Virtual Biotechnology Laboratory and the EU Centre of Excellence in Computational Biomedicine

Quality of Type 2 Diabetes Management in the States of The Co-Operation Council for the Arab States of the Gulf: A Systematic Review

Type 2 diabetes mellitus is a growing, worldwide public health concern. Recent growth has been particularly dramatic in the states of The Co-operation Council for the Arab States of the Gulf (GCC), and these and other developing economies are at particular risk. We aimed to systematically review the quality of control of type 2 diabetes in the GCC, and the nature and efficacy of interventions. We identified 27 published studies for review. Studies were identified by systematic database searches. Medline and Embase were searched separately (via Dialog and Ovid, respectively; 1950 to July 2010 (Medline), and 1947 to July 2010 (Embase)) on 15/07/2009. The search was updated on 08/07/2010. Terms such as diabetes mellitus, non-insulin-dependent, hyperglycemia, hypertension, hyperlipidemia and Gulf States were used. Our search also included scanning reference lists, contacting experts and hand-searching key journals. Studies were judged against pre-determined inclusion/exclusion criteria, and where suitable for inclusion, data extraction/quality assessment was achieved using a specifically-designed tool. All studies wherein glycaemic-, blood pressure- and/or lipid- control were investigated (clinical and/or process outcomes) were eligible for inclusion. No limitations on publication type, publication status, study design or language of publication were imposed. We found the extent of control to be sub-optimal and relatively poor. Assessment of the efficacy of interventions was difficult due to lack of data, but suggestive that more widespread and controlled trial of secondary prevention strategies may have beneficial outcomes. We found no record of audited implementation of primary preventative strategies and anticipate that controlled trial of such strategies would also be useful

Decreasing Prevalence of the Full Metabolic Syndrome but a Persistently High Prevalence of Dyslipidemia among Adult Arabs

A decade has passed since metabolic syndrome (MetS) was documented to be highly prevalent in the kingdom of Saudi Arabia. No follow-up epidemiologic study was done. This study aims to fill this gap. In this cross-sectional, observational study, a total of 2850 randomly selected Saudi adults aged 18–55 years were recruited. Subjects' information was generated from a database of more than 10,000 Saudi citizens from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort), Saudi Arabia. Anthropometrics included body mass index (BMI), blood pressure, as well as waist and hip circumferences. Fasting blood glucose and lipid profile were determined using routine laboratory procedures. The definition of ATP-III (NHANES III) was used for the diagnosis of the full MetS. The overall prevalence of complete MetS was 35.3% [Confidence-Interval (CI) 33.5–37.01]. Age-adjusted prevalence according to the European standard population is 37.0%. Low HDL-cholesterol was the most prevalent of all MetS risk factors, affecting 88.6% (CI 87.5–89.7) and hypertriglyceridemia the second most prevalent, affecting 34% (CI 32.3–35.7) of the subjects. The prevalence of the full MetS decreased from previous estimates but remains high, while dyslipidemia remains extremely high, affecting almost 90% of middle-aged Arabs. Screening for dyslipidemia among Saudi adults is warranted, especially among those most at risk. Scientific inquiry into the molecular causes of these manifestations should be pursued as a first step in the discovery of etiologic therapies

TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities.

The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders. TMX2 encodes one of the five TMX proteins of the protein disulfide isomerase family, hitherto not linked to human developmental brain disease. Our mechanistic studies on protein function show that TMX2 localizes to the ER mitochondria-associated membranes (MAMs), is involved in posttranslational modification and protein folding, and undergoes physical interaction with the MAM-associated and ER folding chaperone calnexin and ER calcium pump SERCA2. These interactions are functionally relevant because TMX2-deficient fibroblasts show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity. Intriguingly, under basal conditions TMX2 occurs in both reduced and oxidized monomeric form, while it forms a stable dimer under treatment with hydrogen peroxide, recently recognized as a signaling molecule in neural morphogenesis and axonal pathfinding. Exogenous expression of the pathogenic TMX2 variants or of variants with an in vitro mutagenized TRX domain induces a constitutive TMX2 polymerization, mimicking an increased oxidative state. Altogether these data uncover TMX2 as a sensor in the MAM-regulated redox signaling pathway and identify it as a key adaptive regulator of neuronal proliferation, migration, and organization in the developing brain

Recreational and occupational field exposure to freshwater cyanobacteria – a review of anecdotal and case reports, epidemiological studies and the challenges for epidemiologic assessment

Cyanobacteria are common inhabitants of freshwater lakes and reservoirs throughout the world. Under favourable conditions, certain cyanobacteria can dominate the phytoplankton within a waterbody and form nuisance blooms. Case reports and anecdotal references dating from 1949 describe a range of illnesses associated with recreational exposure to cyanobacteria: hay fever-like symptoms, pruritic skin rashes and gastro-intestinal symptoms are most frequently reported. Some papers give convincing descriptions of allergic reactions while others describe more serious acute illnesses, with symptoms such as severe headache, pneumonia, fever, myalgia, vertigo and blistering in the mouth. A coroner in the United States found that a teenage boy died as a result of accidentally ingesting a neurotoxic cyanotoxin from a golf course pond. This death is the first recorded human fatality attributed to recreational exposure to cyanobacteria, although uncertainties surround the forensic identification of the suspected cyanotoxin in this case. We systematically reviewed the literature on recreational exposure to freshwater cyanobacteria. Epidemiological data are limited, with six studies conducted since 1990. Statistically significant increases in symptoms were reported in individuals exposed to cyanobacteria compared to unexposed counterparts in two Australian cohort studies, though minor morbidity appeared to be the main finding. The four other small studies (three from the UK, one Australian) did not report any significant association. However, the potential for serious injury or death remains, as freshwater cyanobacteria under bloom conditions are capable of producing potent toxins that cause specific and severe dysfunction to hepatic or central nervous systems. The exposure route for these toxins is oral, from ingestion of recreational water, and possibly by inhalation. A range of freshwater microbial agents may cause acute conditions that present with features that resemble illnesses attributed to contact with cyanobacteria and, conversely, acute illness resulting from exposure to cyanobacteria or cyanotoxins in recreational waters could be misdiagnosed. Accurately assessing exposure to cyanobacteria in recreational waters is difficult and unreliable at present, as specific biomarkers are unavailable. However, diagnosis of cyanobacteria-related illness should be considered for individuals presenting with acute illness following freshwater contact if a description is given of a waterbody visibly affected by planktonic mass development

Expression analysis of asthma candidate genes during human and murine lung development

<p>Abstract</p> <p>Background</p> <p>Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function.</p> <p>Objective</p> <p>To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma.</p> <p>Methods</p> <p>Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6.</p> <p>Results</p> <p>In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. <it>NOD1, EDN1, CCL5, RORA </it>and <it>HLA-G</it>. Among the asthma genes identified in genome wide association studies, <it>ROBO1</it>, <it>RORA, HLA-DQB1, IL2RB </it>and <it>PDE10A </it>were differentially expressed during human lung development.</p> <p>Conclusions</p> <p>Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.</p

Novel insights into the genomic basis of citrus canker based on the genome sequences of two strains of Xanthomonas fuscans subsp. aurantifolii

Background: Citrus canker is a disease that has severe economic impact on the citrus industry worldwide. There are three types of canker, called A, B, and C. The three types have different phenotypes and affect different citrus species. The causative agent for type A is Xanthomonas citri subsp. citri, whose genome sequence was made available in 2002. Xanthomonas fuscans subsp. aurantifolii strain B causes canker B and Xanthomonas fuscans subsp. aurantifolii strain C causes canker C. Results: We have sequenced the genomes of strains B and C to draft status. We have compared their genomic content to X. citri subsp. citri and to other Xanthomonas genomes, with special emphasis on type III secreted effector repertoires. In addition to pthA, already known to be present in all three citrus canker strains, two additional effector genes, xopE3 and xopAI, are also present in all three strains and are both located on the same putative genomic island. These two effector genes, along with one other effector-like gene in the same region, are thus good candidates for being pathogenicity factors on citrus. Numerous gene content differences also exist between the three cankers strains, which can be correlated with their different virulence and host range. Particular attention was placed on the analysis of genes involved in biofilm formation and quorum sensing, type IV secretion, flagellum synthesis and motility, lipopolysacharide synthesis, and on the gene xacPNP, which codes for a natriuretic protein. Conclusion: We have uncovered numerous commonalities and differences in gene content between the genomes of the pathogenic agents causing citrus canker A, B, and C and other Xanthomonas genomes. Molecular genetics can now be employed to determine the role of these genes in plant-microbe interactions. The gained knowledge will be instrumental for improving citrus canker control.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientIfico e Tecnologico (CNPq)Coordenacao para Aperfeicoamento de Pessoal de Ensino Superior (CAPES)Fundo de Defesa da Citricultura (FUNDECITRUS

Diversity, distribution and conservation of the terrestrial reptiles of Oman (Sauropsida, Squamata)

All authors: Salvador Carranza , Meritxell Xipell, Pedro Tarroso, Andrew Gardner, Edwin Nicholas Arnold, Michael D. Robinson, Marc Simó-Riudalbas, Raquel Vasconcelos, Philip de Pous, Fèlix Amat, Jiří Šmíd, Roberto Sindaco, Margarita Metallinou †, Johannes Els, Juan Manuel Pleguezuelos, Luis Machado, David Donaire, Gabriel Martínez, Joan Garcia-Porta, Tomáš Mazuch, Thomas Wilms, Jürgen Gebhart, Javier Aznar, Javier Gallego, Bernd-Michael Zwanzig, Daniel Fernández-Guiberteau, Theodore Papenfuss, Saleh Al Saadi, Ali Alghafri, Sultan Khalifa, Hamed Al Farqani, Salim Bait Bilal, Iman Sulaiman Alazri, Aziza Saud Al Adhoobi, Zeyana Salim Al Omairi, Mohammed Al Shariani, Ali Al Kiyumi, Thuraya Al Sariri, Ahmed Said Al Shukaili, Suleiman Nasser Al Akhzami.In the present work, we use an exceptional database including 5,359 records of 101 species of Oman’s terrestrial reptiles together with spatial tools to infer the spatial patterns of species richness and endemicity, to infer the habitat preference of each species and to better define conservation priorities, with especial focus on the effectiveness of the protected areas in preserving this unique arid fauna. Our results indicate that the sampling effort is not only remarkable from a taxonomic point of view, with multiple observations for most species, but also for the spatial coverage achieved. The observations are distributed almost continuously across the two-dimensional climatic space of Oman defined by the mean annual temperature and the total annual precipitation and across the Principal Component Analysis (PCA) of the multivariate climatic space and are well represented within 17 out of the 20 climatic clusters grouping 10% of the explained climatic variance defined by PC1 and PC2. Species richness is highest in the Hajar and Dhofar Mountains, two of the most biodiverse areas of the Arabian Peninsula, and endemic species richness is greatest in the Jebel Akhdar, the highest part of the Hajar Mountains. Oman’s 22 protected areas cover only 3.91% of the country, including within their limits 63.37% of terrestrial reptiles and 50% of all endemics. Our analyses show that large areas of the climatic space of Oman lie outside protected areas and that seven of the 20 climatic clusters are not protected at all. The results of the gap analysis indicate that most of the species are below the conservation target of 17% or even the less restrictive 12% of their total area within a protected area in order to be considered adequately protected. Therefore, an evaluation of the coverage of the current network of protected areas and the identification of priority protected areas for reptiles using reserve design algorithms are urgently needed. Our study also shows that more than half of the species are still pending of a definitive evaluation by the International Union for Conservation of Nature (IUCN).This work was funded by grants CGL2012-36970, CGL2015-70390-P from the Ministerio de Economía y Competitividad, Spain (cofunded by FEDER) to SC, the project Field study for the conservation of reptiles in Oman, Ministry of Environment and Climate Affairs, Oman (Ref: 22412027) to SC and grant 2014-SGR-1532 from the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya to SC. MSR is funded by a FPI grant from the Ministerio de Economía y Competitividad, Spain (BES-2013-064248); RV, PT and LM were funded by Fundação para a Ciência e Tecnologia (FCT) through post-doc grants (SFRH/BPD/79913/2011) to RV, (SFRH/BPD/93473/2013) to PT and PhD grant (SFRH/BD/89820/2012) to LM, financed by Programa Operacional Potencial Humano (POPH) – Quadro de Referência Estrategico Nacional (QREN) from the European Social Fund and Portuguese Ministerio da Educação e Ciência