Bioinformatics

Background: About 41% of households globally, mainly in developing countries rely on solid fuels for cooking with consequences for fetal growth and development. Previous reviews were limited in scope, assessing only two outcomes (birth weight, stillbirth). With important evidence accumulating, there is a need to improve the previous estimates and assess additional outcomes. We conducted a systematic review and meta-analysis to evaluate the quality and strength of available evidence on household air pollution (HAP) and the whole range of adverse pregnancy outcomes. Methods: PubMed, Ovid Medline, Scopus and CINAHL were searched from their inception to the end of April 2013. All epidemiological study designs were eligible for inclusion in the review. The random-effects model was applied in computing the summary-effect estimates (EE) and their corresponding 95% confidence interval (CI). Results: Of 1505 studies screened, 19 studies satisfied the inclusion criteria. Household combustion of solid fuels resulted in an 86.43 g (95% CI: 55.49, 117.37) reduction in birth weight, and a 35% (EE51.35, 95% CI: 1.23, 1.48) and 29% (EE51.29, 95% CI: 1.18, 1.41) increased risk of LBW and stillbirth respectively. Conclusion: Combustion of solid fuels at home increases the risk of a wide range of adverse pregnancy outcomes. Access to clean household energy solutions is the surest way to combat HAP and mitigate their adverse effects.

Summary: The Helmholtz Network for Bioinformatics (HNB) is a joint venture of eleven German bioinformatics research groups that offers convenient access to numerous bioinformatics resources through a single web portal. The ‘Guided Solution Finder’ which is available through the HNB portal helps users to locate the appropriate resources to answer their queries by employing a detailed, tree-like questionnaire. Furthermore, automated complex tool cascades (‘tasks’), involving resources located on different servers, have been implemented, allowing users to perform comprehensive data analyses without the requirement of further manual intervention for data transfer and re-formatting. Currently, automated cascades for the analysis of regulatory DNA segments as well as for the prediction of protein functional properties are provided. Availability: The HNB portal is available at http://www.hnbioinfo.de

This review has been undertaken to investigate the role of histone deacetylases (HDACs) class II genes in various cancers. Efforts in cancer research mainly aims to identify the major drug targets, develop and improve treatment regimens which eventually helps into better prognosis. One of the major challenges is the determination and mapping of involvement of molecular pathways. So, there has been large interest in developing pathways and also determining driver genes and regulators. Bioinformatics helps to evaluate huge data from wetlab researches to explore biologically relevant interactions and pathways. Emerging evidence shows that many HDACs exists as biomarkers in cancers. The objective of this study is to present a review on the major and latest findings on class II HDACs and its association in cancers. Here, we summarize the current knowledge of class II HDACs, including their features and classification, biological mechanism as well as their function and reported clinical studies in cancers. In addition, we discuss various trials and clinically available inhibitors targeting them. These results provide valuable insights which helps to identify and develop cancer specific therapeutic options.

The present work investigates the efficacy of using Artemisia annua in traditional medicine in comparison with chemical extracts of its bioactive molecules. In addition, the effects of location (Egypt and Jericho) on the bioactivities of the plant were investigated. The results showed that water extracts of Artemisia annua from Jericho have stronger antibacterial activities than organic solvent extracts. In contrast, water and organic solvent extracts of the Artemisia annua from Egypt do not have anti-bacterial activity. Furthermore, while the methanol extract of EA displayed high anticancer affects, the water extract of Egypt and the extracts of Jericho did not show significant anticancer activity. Finally, the results showed that the methanol and water extracts of Jericho had the highest antioxidant activity, while the extracts of Egypt had none. The current results validate the scientific bases for the use of Artemisia annua in traditional medicine. In addition, our results suggest that the collection location of the Artemisia annua has an effect on its chemical composition and bioactivities.

Schizophrenia is a debilitating chronic disease that requires lifelong medical care and supervision. Even with treatment, the majority of patients relapse within 5 years, and suicide may occur in up to 10% of patients. Poor adherence to oral antipsychotics is the most common cause of relapse. The discontinuation rate for oral antipsychotics in schizophrenia ranges from 26% to 44%, and as many as two-thirds of patients are at least partially nonadherent, resulting in increased risk of hospitalization. A very helpful approach to improve adherence in schizophrenia is the use of long-acting injectable (LAI) antipsychotics, although only a minority of patients receive these. Reasons for underutilization may include negative attitudes, perceptions, and beliefs of both patients and health care professionals. Research shows, however, significant improvements in adherence with LAIs compared with oral drugs, and this is accompanied by lower rates of discontinuation, relapse, and hospitalization. In addition, LAIs are associated with better functioning, quality of life, and patient satisfaction. A need exists to encourage broader LAI use, especially among patients with a history of nonadherence with oral antipsychotics. This paper reviews the impact of nonadherence with antipsychotic drug therapy overall, as well as specific outcomes of the schizophrenia patient, and highlights the potential benefits of LAIs.

Biomarkers able to characterise and predict multifactorial diseases are still one of the most important targets for all the "omics" investigations. In this context, Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry Imaging (MALDI-MSI) has gained considerable attention in recent years, but it also led to a huge amount of complex data to be elaborated and interpreted. For this reason, computational and machine learning procedures for biomarker discovery are important tools to consider, both to reduce data dimension and to provide predictive markers for specific diseases. For instance, the availability of protein and genetic markers to support thyroid lesion diagnoses would impact deeply on society due to the high presence of undetermined reports (THY3) that are generally treated as malignant patients. In this paper we show how an accurate classification of thyroid bioptic specimens can be obtained through the application of a state-of-the-art machine learning approach (i.e., Support Vector Machines) on MALDI-MSI data, together with a particular wrapper feature selection algorithm (i.e., recursive feature elimination). The model is able to provide an accurate discriminatory capability using only 20 out of 144 features, resulting in an increase of the model performances, reliability, and computational efficiency. Finally, tissue areas rather than average proteomic profiles are classified, highlighting potential discriminating areas of clinical interest.

Grasses of the genus Setaria occur in natural and agricultural eco systems worldwide, from the tropical forage S. sphacelata (golden timothygrass) to the invasive S. viridis (green foxtail) and S. verticillata (hooked bristlegrass) populations that can be found in the farthest northern reaches of Canada. Five Setaria species, S. faberii (giant fox tail), S. viridis, S. pumila (yellow foxtail), S. geniculata (knotroot foxtail) and S. verticillata, are problematic weeds 1 . S. viridis is among the most widespread plant species on the planet, and is problematic for crop production due to its repeated evolution of herbicide resistance 2 . In Northern China, around 6,000 BC, foxtail millet was domesticated from S. viridis, and together with proso millet (Panicum miliaceum), became a major cereal crop 3 . Foxtail millet remains a significant crop and dietary staple in this region. It has been suggested, but not proven, that foxtail millet was independently domesticated in Europe a few millennia later . Although the flower structure of S. italica creates a strong bias for inbreeding, the great diversity in S. italica morphology and adaptation suggests that gene flow between S. italica and S. viridis may continue when these two species are grown in sympatry 9,10 . More recently, directed crosses between S. viridis and S. italica have been used for genetic mapping 11 and to introduce herbicide resistance from S. viridis into S. italica breeding germplasm . Recent interest in the S. italica-S. viridis pair (hereafter referred to as "Setaria") has centered on their potential as model species for understanding basic biological processes . Some accessions of S. viridis have short cycling times (6 weeks, seed to seed) and tiny statures (20 cm at maturity), and can be efficiently transformed using Agrobacteriumbased methods. Setaria is also a diploid, tractable model for polyploid biofuel crops like switchgrass (Panicum virgatum) and Napier grass (Pennisetum purpureum). Multiple mapping populations, fosmid libraries and mutagenized populations have been developed for the genus Setaria (some for S. italica, others for S. viridis). Here, the Setaria toolkit is expanded with a highquality, wellannotated reference genome sequence based on Sanger shotgun sequencing, a highresolution genetic map, an endsequenced bacterial artificial chromosome (BAC) library, expressed sequence tags (ESTs) from 13 cDNA libraries and 4 RNASeq libraries. We compared these sequences with the genomes of S. viridis, switchgrass, sorghum and rice to uncover both shared and unique properties of the independent adaptations of several grasses to life on earth. Detailed comparisons of the diploid S. italica with available polyploid switchgrass genome sequences demonstrated the utility of using a closely related diploid genome sequence to aid assembly of a polyploid plant genome.

Agradecer en primer lugar a mis Tutores, Eduardo Osinaga y Agustín Correa, por su dedicación y apoyo durante todo este camino, por compartir sus conocimientos y por siempre estar con buena disposición para sobrellevar dificultades propias del camino de la investigación. En segundo lugar, agradecer a todos los integrantes del laboratorio de Glicobiología e Inmunología Tumoral, por su constante apoyo y ayuda tanto en tareas de laboratorio, como en el apoyo motivacional. Todos han hecho el laboratorio un lugar de trabajo ameno y agradable. También agradecer a los integrantes de la Unidad de proteínas Recombinantes del Instituto Pasteur, quienes siempre estaban dispuestos a ayudar frente a dificultades técnicas o de laboratorio. Al grupo del Instituto de Radiología InRad, Hospital das Clínicas, HCFMUSP, por su colaboración en los trabajos in vivo y por sus aportes que fueron esenciales para el proyecto. Por último, agradecer a todas las personas que de una u otra manera transitaron este camino conmigo. Un especial agradecimiento a mis padres, Verónica Lima y Walker Flores, por siempre acompañar mis decisiones profesionales, y por regalarme un futuro. A Johann Schuller, por siempre alentarme a seguir creciendo y avanzando en lo que me gusta, y por siempre tener buena disposición para ayudarme. Y a mis amigas que siempre me acompañan, aunque sea desde la distancia. Gracias.

Sulfur mustard is a vesicant agent with severe irritating effects on living tissues, including skin, mucous membranes, eyes, and the respiratory tract. The eyes are the most susceptible tissue to mustard gas effects, and varying degrees of ocular involvement are seen in 75% to 90% of exposed individuals. Most cases resolve uneventfully; however, a minority of exposed patients will have a continuous process, which manifests clinically either as persistent smoldering inflammation (chronic form) or late-onset lesions appearing many years after a variable "silent" period (delayed form). Distinctive features common to most cases with chronic involvement include chronic blepharitis, meibomian gland dysfunction and dry eye, limbal ischemia, limbal stem cell deficiency, aberrant conjunctival vessels, corneal neovascularization, and secondary degenerative changes, including lipid and amyloid deposition and corneal irregularity, thinning and scarring. Herein, we will discuss medical and surgical management for a number of patients with chronic or delayed mustard gas induced ocular surface disorders. What is your general management strategy for patients with mustard gas induced ocular surface disorders?

The authors present the first use of the novel positron emission tomography (PET) apoptosis tracer 18 F-labeled 2-(5-fluoro-pentyl)-2-methylmalonic acid ( 18 F-ML-10) for early-therapy response assessment of a newly diagnosed glioblastoma multiforme (GBM) patient. Case report: A 71-year-old male with a newly diagnosed GBM received 18 F-ML-10 PET scans prior to therapy initiation (baseline) and after completing 3 weeks of whole-brain radiation therapy with concomitant temozolomide chemotherapy (early-therapy assessment, ETA). The baseline 18 F-ML-10 PET scan showed increased tracer uptake at the site of the GBM, with highest activity toward the central portion of the tumor. At the ETA time point, a new distribution of tracer uptake was observed compared to baseline. Normalized pixel-by-pixel subtraction of baseline from ETA was used to quantify change in tracer distribution between 18 F-ML-10 PET imaging time points. Results of this analysis showed reduction in 18 F-ML-10 uptake at the site of greatest baseline uptake, but increased uptake around the periphery of the tumor at the early-therapy time point. The changing patterns of 18 F-ML-10 uptake between baseline and ETA are suggestive for therapy-induced tumor cellular apoptosis.

Background: Paramedic education has evolved in recent times from vocational post-employment to tertiary pre-employment supplemented by clinical placement. Simulation is advocated as a means of transferring learned skills to clinical practice. Sole reliance of simulation learning using mannequin-based models may not be sufficient to prepare students for variance in human anatomy. In 2012, we trialled the use of fresh frozen human cadavers to supplement undergraduate paramedic procedural skill training. The purpose of this study is to evaluate whether cadaveric training is an effective adjunct to mannequin simulation and clinical placement. Methods: A multi-method approach was adopted. The first step involved a Delphi methodology to formulate and validate the evaluation instrument. The instrument comprised of knowledge-based MCQs, Likert for self-evaluation of procedural skills and behaviours, and open answer. The second step involved a pre-post evaluation of the 2013 cadaveric training. Results: One hundred and fourteen students attended the workshop and 96 evaluations were included in the analysis, representing a return rate of 84%. There was statistically significant improved anatomical knowledge after the workshop. Students' self-rated confidence in performing procedural skills on real patients improved significantly after the workshop: inserting laryngeal mask (MD 0.667), oropharyngeal (MD 0.198) and nasopharyngeal (MD 0.600) airways, performing Bag-Valve-Mask (MD 0.379), double (MD 0.344) and triple (MD 0.326,) airway manoeuvre, doing 12-lead electrocardiography (MD 0.729), using laryngoscope (MD 0.726), using Magill W forceps to remove foreign body (MD 0.632), attempting thoracocentesis (MD 1.240), and putting on a traction splint (MD 0.865). The students commented that the workshop provided context to their theoretical knowledge and that they gained an appreciation of the differences in normal tissue variation. Following engagement in/ completion of the workshop, students were more aware of their own clinical and non-clinical competencies. The paramedic profession has evolved beyond patient transport with minimal intervention to providing comprehensive both emergency and non-emergency medical care. With limited availability of clinical placements for undergraduate paramedic training, there is an increasing demand on universities to provide suitable alternatives. Our findings suggested that cadaveric training using fresh frozen cadavers provides an effective adjunct to simulated learning and clinical placements.

Neurofibromatosis type 1 is an autosomal dominant genetic disease and a common tumor predisposition syndrome that affects 1 in 3000 to 4000 patients in the USA. Although studies have been conducted to better understand and manage this disease, the underlying pathogenesis of neurofibromatosis type 1 has not been completely elucidated, and this disease is still associated with significant morbidity and mortality. Treatment options are limited to surgery with chemotherapy for tumors in cases of malignant transformation. In this review, we summarize the advances in the development of targeted pharmacological interventions for neurofibromatosis type 1 and related conditions.

Hearing loss from noise exposure is a leading occupational disease, with up to 5% of the population at risk world-wide. Here, we present a novel purine-based pharmacological intervention that can ameliorate noiseinduced cochlear injury. Wistar rats were exposed to narrow-band noise (8-12 kHz, 110 dB SPL, 2-24 h) to induce cochlear damage and permanent hearing loss. The selective adenosine A 1 receptor agonist, adenosine amine congener (ADAC), was administered intraperitoneally (100 µg/kg/day) at time intervals after noise exposure. Hearing thresholds were assessed using auditory brainstem responses and the hair cell loss was evaluated by quantitative histology. Free radical damage in the organ of Corti was assessed using nitrotyrosine immunohistochemistry. The treatment with ADAC after noise exposure led to a significantly greater recovery of hearing thresholds compared with controls. These results were upheld by increased survival of sensory hair cells and reduced nitrotyrosine immunoreactivity in ADAC-treated cochlea. We propose that ADAC could be a valuable treatment for noise-induced cochlear injury in instances of both acute and extended noise exposures.

Background: For last five years, as technological advancement occurs, novel kinds of human generation viruses’ discovery have been increased. A rare human cancer associated virus Merkel’s Cell polyomavirus (MCPyV or MCV) got remarkable attraction among the newly discovered viruses. As a common human virus MCPyV infection frequently found in skin and also occurs at other anatomical sites.  Methods:  In this study, the in-silico screening of miRNAs from MCPyV was done, as the computational screening procedures are functionally vital, efficient and inexpensive for the said purpose.  Results:  Primarily 52 sequences, possessing possible hairpin-like structures, were extracted from MCPyV genome by searching through VMir software using various filters. 17 nominees were confirmed with real pre-miRNA like hairpin organizations by iMiRNA-SSF program. Further seven nominees were excluded by free energy measurement and other parameters. 10 mature miRNAs were affirmed in 10 impending candidates...

The demand for interdisciplinary research is increasing in the new millennium to help us understand complex problems and find solutions by integrating the knowledge from different disciplines. The present review is an excellent example of this and shows how unique combination of physics, chemistry, and biological techniques can be used for the evaluation of Indian medicinal herbs used for treating diabetes mellitus. Laser-induced breakdown spectroscopy (LIBS) is a sensitive optical technique that is widely used for its simplicity and versatility. This review presents the most recent application of LIBS for detection of glycemic elements in medicinal plants. The characteristics of matrices, object analysis, use of laser system, and analytical performances with respect to Indian herbs are discussed.

We present pygenomics, a Python package for working with genomic intervals and bioinformatic data files. The package implements interval operations, provides both API and CLI, and supports reading and writing data in widely used bioinformatic formats, including BAM, BED, GFF3 and VCF. The source code of pygenomics is provided with in-source documentation and type annotations and adheres to the functional programming paradigm. These features facilitate seamless integration of pygenomics routines into scripts and pipelines. The package is implemented in pure Python using its standard library only and contains the property-based testing framework. Comparison of pygenomics with other Python bioinformatic packages with relation to features and performance is presented. The performance comparison covers operations with genomic intervals, read alignments, and genomic variants and demonstrates that pygenomics is suitable for computationally effective analysis.

Reactome () is an expertauthored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2975 human proteins, 2907 reactions and 4455 literature citations. A new entitylevel pathway viewer and improved search and data mining tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. Reactome has increased its utility to the model organism communities with improved orthology prediction methods allowing pathway inference for 22 species and through collaborations to create manually curated Reactome pathway datasets for species including Arabidopsis, Oryza sativa (rice), Drosophila and Gallus gallus (chicken). Reactome's data content and software can all be freely used and redistributed under open source terms.

A principal challenge currently facing biologists is how to connect the complete DNA sequence of an organism to its development and behaviour. Large-scale targeted-deletions have been successful in defining gene functions in the single-celled yeast Saccharomyces cerevisiae, but comparable analyses have yet to be performed in an animal. Here we describe the use of RNA interference to inhibit the function of ,86% of the 19,427 predicted genes of C. elegans. We identified mutant phenotypes for 1,722 genes, about two-thirds of which were not previously associated with a phenotype. We find that genes of similar functions are clustered in distinct, multi-megabase regions of individual chromosomes; genes in these regions tend to share transcriptional profiles. Our resulting data set and reusable RNAi library of 16,757 bacterial clones will facilitate systematic analyses of the connections among gene sequence, chromosomal location and gene function in C. elegans. The ability to inactivate a target gene transiently by RNAi 1 has greatly accelerated the analysis of loss-of-function phenotypes in C. elegans and other organisms. Although several large-scale RNAibased screens have been used to study gene function in C. elegans 2-4 , in total only about a third of the predicted genes have been analysed so far. Genome-wide RNAi analyses would not only provide a key resource for studying gene function in C. elegans but should also address important issues in functional genomics, such as the global organization of gene functions in a metazoan genome. In addition, because more than half of the genes in C. elegans have a human homologue, this kind of functional analysis in the worm should provide insights into human gene function.

Motivation: The SWISS-PROT group at the EBI has developed the Proteome Analysis Database utilizing existing resources and providing comprehensive and integrated comparative analysis of the predicted protein coding sequencesof the complete genomes of bacteria, archaea and eukaryotes. The Proteome Analysis Database is accompanied by a program that has been designed to carry out interactive InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database. Availability: http://www.ebi.ac.uk/proteome/comparisons.html Contact: alex@ebi.ac.uk; proteome@ebi.ac.uk * To whom all correspondence should be addressed.

Motivation: InterPro is a new integrated documentation resource for protein families, domains and functional sites, developed initially as a means of rationalising the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. Results: Merged annotations from PRINTS, PROSITE and Pfam form the InterPro core. Each combined InterPro entry includes functional descriptions and literature references, and links are made back to the relevant parent database(s), allowing users to see at a glance whether a particular family or domain has associated patterns, profiles, fingerprints, etc. Merged and individual entries (i.e. those that have no counterpart in the companion resources) are assigned unique accession numbers. Release 1.2 of InterPro (June 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification (PTMs) encoded by 6581 different regular expressions, profiles, fingerprints and Hidden Markov Models (HMMs)...

The paper presents the results of a study conducted at the Auschwitz-Birkenau State Museum in Os ´wie ˛cim on the occurrence of biodeterioration. Visual assessment of the buildings revealed signs of deterioration of the buildings in the form of dampness, bulging and crumbling plaster, and wood fiber splitting. The external surfaces, and especially the concrete strips and ground immediately adjoining the buildings, were colonized by bryophytes, lichens, and algae. These organisms developed most intensively close to the ground on the northern sides of the buildings. Inside the buildings, molds and bacteria were not found to develop actively, while algae and wood-decaying fungi occurred locally. The factors conducive to biological corrosion in the studied buildings were excessive dampness of structural partitions close to the ground and a relative air humidity of above 70%, which was connected to ineffective moisture insulation. The influence of temperature was smaller, as it mostly affected the quantitative composition of the microorganisms and the qualitative composition of the algae. Also the impact of light was not very strong, but it was conducive to algae growth.

Background: Under-prescription of antidepressants (ADs) among people meeting the criteria for major depressive episodes and excessive prescription in less symptomatic patients have been reported. The reasons influencing general practitioners' (GPs) prescription of ADs remain little explored. This study aimed at assessing the influence of GP and patient characteristics on AD prescription. Methods: This cross-sectional study was based on a sample of 816 GPs working within the main health care insurance system in the Seine-Maritime district of France during 2010. Only GPs meeting the criteria for full-time GP practice were included. The ratio of AD prescription to overall prescription volume, a relative measure of AD prescription level, was calculated for each GP, using the defined daily dose (DDD) concept. Associations of this AD prescription ratio with GPs' age, gender, practice location, number of years of practice, number of days of sickness certificates prescribed, number of home visits and consultations, number and mean age of registered patients, mean patient income, and number of patients with a chronic condition were assessed using univariate and multivariate analysis. Results: The high prescribers were middle-aged (40-59) urban GPs, with a moderate number of consultations and fewer low-income and chronic patients. GPs' workload (e.g., volume of prescribed drug reimbursement and number of consultations) had no influence on the AD prescription ratio. GPs with more patients with risk factors for depression prescribed fewer ADs, however, which could suggest the medications were under-prescribed among the at-risk population. Conclusions: Our study described a profile of the typical higher AD prescriber that did not include heavy workload. In future work, a more detailed assessment of all biopsychosocial components of the consultation and other influences on GP behavior such as prior training would be useful to explain AD prescription in GP's practice.

The purpose of this review is to conduct a detailed analysis of the literature on the use of myofunctional oral therapy tools for the treatment of Class II skeletal malocclusions. From March to May 2020, a comprehensive and systematic search was performed on the Medline (PubMed) and Google Scholar databases for works published since January 2010, using the following terms in the search: oral myofunctional tools; Class II skeletal malocclusions in children; treatment of class II bone malocclusion in children. Additional manual searches from other sources are also carried out. Only scientific articles in English are considered for this review. An electronic and manual search resulted in the identification of 61 articles. Based on the inclusion criteria, a full text copy of 30 articles was selected for analysis. Specific analysis was then made of 16 articles describing the effects produced using tools to treat Class II skeletal malocclusion and masticatory muscle dysfunction. Literatur...

Background Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported. Results In this study we describe 14 individuals with microdeletions of 3q29, including one family with a mildly affected mother and two affected children, identified among 14,698 individuals with idiopathic mental retardation who were analyzed by array CGH. Eleven individuals had typical 1.6-Mb deletions. Three individuals had deletions that flank, span, or partially overlap the commonly deleted region. Although the clinical presentations of individuals with typical-sized deletions varied, several features were present in multiple individuals, including mental retardation and mic...

Monilethrix is a rare autosomal dominant disease characterized by hair fragility and hyperkeratotic papules. Mutations in type‐II hair specific keratins hHb6 and hHb1 have recently been reported. We describe a large family with a E410D mutation in the evolutionary conserved helix termination motif of keratin hHb6 that was variably expressed among 12 heterozygous members, and severely expressed among 3 homozygous members. These 3 patients had essentially complete lack of scalp hair since the age of 2 months with no improvement over time as well as follicular keratotic involvement extensively expressed over the scalp and large body areas. The variability seen in heterozygous patients, along with seasonal and pregnancy‐related improvement suggest that other genetic or environmental factors may modify keratin gene expression. This represents the first report of a co‐dominant keratin hHb6 mutation resulting in severe disease.

New Pd–NHC complexes have been synthesized and employed for palladium-catalyzed direct arylation of pyrrole derivatives by using electron-deficient aryl chlorides as coupling partners. The desired coupling products were obtained in moderate to good yields by using 1 mol % of these air-stable palladium complexes. This is an advantage compared to the procedures employing air-sensitive phosphines, which have been previously shown to promote the coupling of aryl chlorides with heteroarenes.

A phylogenetic network is a generalization of a phylogenetic tree, allowing structural properties that are not tree-like. In a seminal paper, Wang et al.1studied the problem of constructing a phylogenetic network, allowing recombination between sequences, with the constraint that the resulting cycles must be disjoint. We call such a phylogenetic network a "galled-tree". They gave a polynomial-time algorithm that was intended to determine whether or not a set of sequences could be generated on galled-tree. Unfortunately, the algorithm by Wang et al.1is incomplete and does not constitute a necessary test for the existence of a galled-tree for the data. In this paper, we completely solve the problem. Moreover, we prove that if there is a galled-tree, then the one produced by our algorithm minimizes the number of recombinations over all phylogenetic networks for the data, even allowing multiple-crossover recombinations. We also prove that when there is a galled-tree for the da...

There are many critical situations when one needs to rapidly identify an unidentified pathogen from among a given set of previously sequenced pathogens. DNA or RNA hybridization chips can be designed for such identifications. Each cell in the chip can report the presence or absence of a specific substring of DNA in the unidentified pathogen. Properly designed, the collection of reports obtained from the cells can uniquely identify any pathogen in the set, or determine that the unidentified pathogen is not in the set. There is a limit to the number of cells on a chip, and a range of substring lengths that a cell can handle. So, given the full sequences of a set of pathogens, the problem is to design the chip by selecting the smallest set of substrings of the appropriate lengths, so that each pathogen in the set has a unique set of cells that report a substring. For any given pathogen, the set of reporting cells is its signature, and hence the entire system is a "barcode" system for the pathogens. Previous work addressed this problem [1], but focused on pathogens of bacterial size, and hence had to make many compromises for the sake of efficiency. The substrings lengths were severely restricted, and no optimality or near-optimality was guaranteed. In this paper, we focus on viral-size pathogens. We show that for genomes of this size, it is practical to solve the barcode design problem optimally, or near-optimally, without artificially constraining the problem. We also efficiently find barcodes that provide a level of redundancy, tolerating a number of errors or mutations. The key technical ideas are the use of suffix trees to identify the critical substrings, integer-linear programming (ILP) to express the minimization problem, and a simple idea that dramatically reduces the size of the ILP, allowing it to be solved efficiently by the commercial ILP solver CPLEX. We report extensive tests of our approach on various collections of virus DNA and RNA sequences.

Motivation: We are interested in studying the evolution of DNA single nucleotide polymorphism sequences which have undergone (meiotic) recombination. For a given set of sequences, computing the minimum number of recombinations needed to explain the sequences (with one mutation per site) is a standard question of interest, but it has been shown to be NPhard, and previous algorithms that compute it exactly work either only on very small datasets or on problems with special structure. Results: In this paper, we present efficient, practical methods for computing both upper and lower bounds on the minimum number of needed recombinations, and for constructing evolutionary histories that explain the input sequences. We study in detail the efficiency and accuracy of these algorithms on both simulated and real data sets. The algorithms produce very close upper and lower bounds, which match exactly in a surprisingly wide range of data. Thus, with the use of new, very effective lower bounding methods and an efficient algorithm for computing upper bounds, this approach allows the efficient, exact computation of the minimum number of needed recombinations, with high frequency in a large range of data. When upper and lower bounds match, evolutionary histories found by our algorithm correspond to the most parsimonious histories.

The occurrence of tuberculosis in the flat bones of the skull is very rare. Only eight cases of tuberculosis of the frontal bone have been reported in the literature. Case presentation: A 14-year-old girl of Asian ethnicity presented with gradual loss of vision. A computed tomography scan of her head showed a diffuse, homogeneously ill-defined hyperdense lesion of size 2.9 5.3 cm (anteroposterior thickness) involving the right orbit. Biopsy of the lesion confirmed the presence of epithelioid cells and Langerhans giant cells with caseous material. After surgical debridement with antitubercular treatment, the patient had an uneventful recovery. Although rare, tuberculosis can affect the flat bones of the skull. Tuberculosis of the frontal bone can be included in the differential diagnosis of blindness.

Programmed cell death (PCD) plays a pivotal role in plant development and defense. To investigate the interaction between PCD and R gene–mediated defense, we used the 22K Barley1 GeneChip to compare and contrast time-course expression profiles of Blumeria graminis f. sp hordei (Bgh) challenged barley (Hordeum  vulgare) cultivar C.I. 16151 (harboring the Mla6 powdery mildew resistance allele) and its fast neutron–derived Bgh-induced tip cell death1 mutant, bcd1. Mixed linear model analysis identified genes associated with the cell death phenotype as opposed to R gene–mediated resistance. One-hundred fifty genes were found at the threshold P value < 0.0001 and a false discovery rate <0.6%. Of these, 124 were constitutively overexpressed in the bcd1 mutant. Gene Ontology and rice (Oryza sativa) alignment-based annotation indicated that 68 of the 124 overexpressed genes encode ribosomal proteins. A deletion harboring six genes on chromosome 5H cosegregates with bcd1-specified cell...

Crucian carp are unusual among vertebrates in surviving extended periods in the complete absence of molecular oxygen. During this time cardiac output is maintained though these mechanisms are not well understood. Using a high-density cDNA microarray, we have defined the genome-wide gene expression responses of cardiac tissue after exposing the fish at two temperatures (8 and 13uC) to one and seven days of anoxia, followed by seven days after restoration to normoxia. At 8uC, using a false discovery rate of 5%, neither anoxia nor re-oxygenation elicited appreciable changes in gene expression. By contrast, at 13uC, 777 unique genes responded strongly. Up-regulated genes included those involved in protein turnover, the pentose phosphate pathway and cell morphogenesis while down-regulated gene categories included RNA splicing and transcription. Most genes were affected between one and seven days of anoxia, indicating gene regulation over the medium term but with few early response genes. Re-oxygenation for 7 days was sufficient to completely reverse these responses. Glycolysis displayed more complex responses with anoxia up-regulated transcripts for the key regulatory enzymes, hexokinase and phosphofructokinase, but with down-regulation of most of the non-regulatory genes. This complex pattern of responses in genomic transcription patterns indicates divergent cardiac responses to anoxia, with the transcriptionally driven reprogramming of cardiac function seen at 13uC being largely completed at 8uC.

Analytical approaches for the characterisation of the compound channels in transparent multihop relay transmissions over independent fading channels are considered in this paper. Compound channels with homogeneous links are considered first. Using Mellin transform technique, exact expressions are derived for the moments of cascaded Weibull distributions. Subsequently, two performance metrics, namely,coefficient of variationandamount of fade, are derived using the computed moments. These metrics quantify the possible variations in the channel gain and signal to noise ratio from their respective average values and can be used to characterise the achievable receiver performance. This approach is suitable for analysing more realistic compound channel models for scattering density variations of the environment, experienced in multihop relay transmissions. The performance metrics for suchheterogeneous compound channelshaving distinct distribution in each hop are computed and compared with...

Objective. To assess the incidence of adverse pregnancy outcome in native and nonnative Dutch women with pregestational type 2 diabetes (T2D) in a multicenter study in The Netherlands. Methods. Maternal characteristics and pregnancy outcome were retrospectively reviewed and the influence of ethnicity on outcome was evaluated using independent t-test, Mann-Whitney U-test, and chi-square test. Results. 272 pregnant women (80 native and 192 non-native Dutch) with pregestational T2D were included. Overall outcome was unfavourable, with a perinatal mortality of 4.8%, major congenital malformations of 6.3%, preeclampsia of 11%, preterm birth of 19%, birth weight >90th percentile of 32%, and a Caesarean section rate of 42%. In nonnative Dutch women, the glycemic control was slightly poorer and the gestational age at booking somewhat later as compared to native Dutch women. However, there were no differences in incidence of preeclampsia/HELLP, preterm birth, perinatal mortality, macrosom...

Thyroid dysfunction is a widespread and complex issue in the field of endocrine disorders. It has a significant impact on multiple physiological systems, particularly on the heart. This review explores the complex interaction between thyroid dysfunction and cardiac dynamics, examining the detailed network of molecular, cellular, and systemic changes that underlie the close connection between these two physiological areas. Thyroid dysfunction, which includes both hyperthyroidism and hypothyroidism, is a common endocrine condition that affects millions of people worldwide. The thyroid hormones thyroxine and triiodothyronine regulate various metabolic activities essential for maintaining cellular balance. Disruptions in thyroid function result in widespread consequences, affecting the cardiovascular system. Thyroid hormones directly impact cardiac muscle cells, controlling their ability to contract, their electrical properties, and their reaction to hypertrophy. Thyroid dysfunction goes beyond the level of individual cells and involves complex interactions among vascular dynamics, neurohormonal control, and endothelial function. These factors all contribute to the development of cardiovascular illness. The impact of thyroid dysfunction on cardiac structure, function, and outcomes is not limited to a one-way pattern. Instead, it involves a dynamic two-way interaction. The manifestations of this condition can vary from minor changes in the electrical activity of the heart to more obvious structural abnormalities, such as an increase in the size of the heart muscle and a decrease in its ability to relax during the filling phase. Furthermore, the correlation between thyroid dysfunction and adverse cardiovascular outcomes, such as heart failure and arrhythmias, highlights the clinical importance of this connection. This review provides a complete overview of the relationship between thyroid dysfunction and cardiac dynamics by analyzing a wide range of research from clinical, molecular, and epidemiological perspectives. This study seeks to enhance our comprehension of the comprehensive effects of thyroid dysfunction on the anatomy and function of the heart by explaining the complex molecular mechanisms and systemic consequences. The goal is to establish a basis for informed clinical treatment and future research efforts.

The NIST Recommended Practice Guide on Measurement Issues in Single Wall Carbon Nanotubes represents the output from the 2nd NASA-NIST workshop devoted to issues of nanotube purity, dispersion and measurement techniques held at NIST in 2005. In attendance were over 80 participants, representing private corporations, universities, and government laboratories. The primary purpose of the workshop was to bring together technical and business leaders in the field of single wall carbon nanotubes (SWNTs) to discuss measurement priorities and aid in the development of measurement protocols. This guide lays out written protocols to enable product developers to more rapidly assess as-received materials, prepare quality nanotube dispersions, and ultimately achieve both repeatability and high performance in their resulting value-added devices. The technical chapters in this guide were written by leading practitioners in the field and present standard methods currently used for characterization of single wall nanotubes in a straightforward fashion. techniques, and it has traditionally been the most popular tool to evaluate the quality of as-prepared SWNT soot. (7) Because a typical SEM frame visualizes less than 10 -12 g of an inhomogeneous sample for which there is no published algorithm with which to quantify the SWNT content, the use of these techniques to assess the purity of bulk SWNT samples is not recommended.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that exert their biological functions as negative regulators of gene expression. They are involved in the skin wound healing process with a dynamic expression pattern and can therefore potentially serve as biomarkers for skin wound age estimation. However, no reports have described any miRNAs as suitable reference genes (RGs) for miRNA quantification in wounded skin or samples with postmortem changes. Here, we aimed to identify specific miRNAs as RGs for miRNA quantification to support further studies of skin wound age estimation. Overall, nine miRNAs stably expressed in mouse skin at certain posttraumatic intervals (PTIs) were preselected by next-generation sequencing as candidate RGs. These nine miRNAs and the commonly used reference genes (comRGs: U6, GAPDH, ACTB,18S, 5S, LC-Ogdh) were quantitatively examined using qRT-PCR at different PTIs during skin wound healing in mice. The stabilities of these genes were evaluated usin...

A controlled fire burner was constructed where various natural vegetation species could be used as fuel. The burner was equipped with thermocouples to measure fuel surface temperature and used as a cavity for microwaves with a laboratory quality 2port vector network analyzer to determine electrical conductivity from S-parameters. Electrical conductivity for vegetation material flames is important for numerical prediction of flashover in high voltage power transmission faults research. Vegetation fires that burn under high voltage transmission lines reduce flashover voltage by increasing air electrical conductivity and temperature. Analyzer determined electrical conductivity ranged from 0.0058 -0.0079 mho/m for a fire with a maximum temperature of 1240 K.

Omega-3 fatty acids (n-3) has shown to improve neuromotor function. This study examined the effects of docosahexaenoic acid (DHA) on complex reaction time, precision and efficiency, in female elite soccer players. 24 players from two Spanish female soccer Super League teams were randomly selected and assigned to two experimental groups, then administered, in a double-blind manner, 3.5 g·day(-1) of either DHA-rich fish oil (FO =12) or olive oil (OO = 12) over 4 weeks of training. Two measurements (pre- and post-treatment) of complex reaction time and precision were taken. Participants had to press different buttons and pedals with left and right hands and feet, or stop responding, according to visual and auditory stimuli. Multivariate analysis of variance displayed an interaction between supplement administration (pre/post) and experimental group (FO/OO) on complex reaction time (FO pre = 0.713 ± 0.142 ms, FO post = 0.623 ± 0.109 ms, OO pre = 0.682 ± 1.132 ms, OO post = 0.715 ± 0.159...

Motivation: Protein–protein interaction networks provide insights into the relationships between the proteins of an organism thereby contributing to a better understanding of cellular processes. Nevertheless, large-scale interaction networks are available for only a few model organisms. Thus, interologs are useful for a systematic transfer of protein interaction networks between organisms. However, no standard tool is available so far for that purpose. Results: In this study, we present an automated prediction tool developed for all sequenced genomes available in Integr8. We also have developed a second method to predict protein–protein interactions in the widely used cyanobacterium Synechocystis. Using these methods, we have constructed a new network of 8783 inferred interactions for Synechocystis. Availability: InteroPORC is open-source, downloadable and usable through a web interface at http://biodev.extra.cea.fr/interoporc/ Contact:  michaut.bioinfo@gmail.com Supplementary infor...

Background: Identifying reliable oligonucleotide sequences for use in microarray experiments is a complex process. Two key issues are the accuracy of the input sequences and the specificity of the oligonucleotide sequences. We provide a suite of Perl scripts that facilitates the search for gene-specific oligonucleotides for microarray experiments. Genes of interest are first identified in the form of UniGene clusters. The sequences of these clusters were extracted and assembled into contigs to increase their accuracy. The 3' untranslated region (3'UTR) of the contig was parsed. Then, multiple 50mer oligonucleotide sequences with similar melting temperature were obtained from each 3'UTR. These sequences were analyzed for gene specificity. Five Cy3-labeled cDNAs were used to empirically verify the specificity of a set of 1814 50mers.

BACKGROUND: The integration of the rapidly expanding corpus of information about the genome, transcriptome, and proteome, engendered by powerful technological advances, such as microarrays, and the availability of genomic sequence from multiple species, challenges the grasp and comprehension of the scientific community. Despite the existence of text-mining methods that identify biological relationships based on the textual co-occurrence of gene/protein terms

The cellular heterogeneity of brain poses a particularly thorny issue in genome-wide gene expression studies. Because laser capture microdissection (LCM) enables the precise extraction of a small area of tissue, we combined LCM with neuronal track tracing to collect nucleus accumbens shell neurons that project to ventral pallidum, which are of particular interest in the study of reward and addiction. Four independent biological samples of accumbens projection neurons were obtained. Approximately 500 pg of total RNA from each sample was then amplified linearly and subjected to Affymetrix microarray and Applied Biosystems sequencing by oligonucleotide ligation and detection (SOLiD) transcriptome sequencing (RNA-seq). A total of 375 million 50-bp reads were obtained from RNA-seq. Approximately 57% of these reads were mapped to the rat reference genome (Baylor 3.4/rn4). Approximately 11,000 unique RefSeq genes and 100,000 unique exons were identified from each sample. Of the unmapped reads, the quality scores were 4.74 ± 0.42 lower than the mapped reads. When RNA-seq and microarray data from the same samples were compared, Pearson correlations were between 0.764 and 0.798. The variances in data obtained for the four samples by microarray and RNA-seq were similar for medium to high abundance genes, but less among low abundance genes detected by microarray. Analysis of 34 genes by real-time polymerase chain reaction showed higher correlation with RNA-seq (0.66) than with microarray (0.46). Further analysis showed 20-30 million 50-bp reads are sufficient to provide estimates of gene expression levels comparable to those produced by microarray. In summary, this study showed that picogram quantities of total RNA obtained by LCM of ∼700 individual neurons is sufficient to take advantage of the benefits provided by the transcriptome sequencing technology, such as low background noise, high dynamic range, and high precision.

Bipolar disorder (BD) is a debilitating condition associated with a high prevalence of medical comorbidities and premature mortality. This is the first study to explore, through high-throughput-omics combined with bioinformatics, molecular signatures, pathways, and main medical diseases related to different stages of BD. Blood samples from BD patients (n=10) classified into high (BD+) or poor functioning (BD-), based on functional and cognitive status, and healthy controls (n=5) were analyzed using mass spectrometry-based proteomic analysis. Bioinformatics was performed to detect biological processes, pathways, and diseases related to BD. Eight proteins exclusively characterized the molecular profile of patients with BD+ compared to HC, while 26 altered proteins were observed in the BD-group. These altered proteins were mainly enriched in biological processes related to lipid metabolism, complement system and coagulation cascade, and cardiovascular diseases; all these changes were more prominent in the BD-group. These findings may represent systemic alterations that occur with the progression of the illness and a possible link between BD and medical comorbidities. Such comprehensive understanding provides valuable insights for targeted interventions, addressing mental and physical health aspects in subjects with BD.

Respiratory infections with Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) are associated with a worse prognosis and increased risk of death. In this work, we assessed the virulence potential of three B. cenocepacia clonal isolates obtained from a CF patient between the onset of infection (isolate IST439) and before death with cepacia syndrome 3.5 years later (isolate IST4113 followed by IST4134), based on their ability to invade epithelial cells and compromise epithelial monolayer integrity. The two clonal isolates retrieved during late-stage disease were significantly more virulent than IST439. Proteomic profiling by 2-D DIGE of the last isolate recovered before the patient's death, IST4134, and clonal isolate IST439, was performed and compared with a prior analysis of IST4113 vs. IST439. The cytoplasmic and membrane-associated enriched fractions were examined and 52 proteins were found to be similarly altered in the two last isolates compared with IST439. These proteins are involved in metabolic functions, nucleotide synthesis, translation and protein folding, cell envelope biogenesis and iron homeostasis. Results are suggestive of the important role played by metabolic reprogramming in the virulence potential and persistence of B. cenocepacia, in particular regarding bacterial adaptation to microaerophilic conditions. Also, the content of the virulence determinant AidA was higher in the last 2 isolates. Significant levels of siderophores were found to be secreted by the three clonal isolates in an iron-depleted environment, but the two late isolates were more tolerant to low iron concentrations than IST439, consistent with the relative abundance of proteins involved in iron uptake.

Motivation: The ability to identify complex motifs, i.e. non-contiguous nucleotide sequences, is a key feature of modern motif finders. Addressing this problem is extremely important, not only because these motifs can accurately model biological phenomena but because its extraction is highly dependent upon the appropriate selection of numerous search parameters. Currently available combinatorial algorithms have proved to be highly efficient in exhaustively enumerating motifs (including complex motifs), which fulfill certain extraction criteria. However, one major problem with these methods is the large number of parameters that need to be specified. Results: We propose a new algorithm, MUSA (Motif finding using an UnSupervised Approach), that can be used either to autonomously find over-represented complex motifs or to estimate search parameters for modern motif finders. This method relies on a biclustering algorithm that operates on a matrix of co-occurrences of small motifs. The p...

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described ''SCA10 haplotype''. This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas.