A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Th2 cells are essential for modulation of vascular repair by allogeneic endothelial cells

Author Manuscript 2011 April 1.Background: Endothelial cells (ECs) embedded within 3-dimensional matrices (MEEC) control lumenal inflammation and intimal hyperplasia when placed in the vascular adventitia. Matrix embedding alters endothelial immunogenicity in vitro. T-helper (Th) cell-driven host immunity is an impediment of allogeneic grafts. We aimed to identify if modulation of Th balance would affect immune compatibility and endothelial regulation of vascular repair in vivo. Methods: Pigs (n = 4/group) underwent carotid artery balloon injury and were left untreated (Group 1) or received perivascular porcine MEEC implants (Group 2), 12 days of cyclosporine A (CsA; Group 3), or MEEC and CsA (Group 4). Host immune reactivity was analyzed after 28 and 90 days. Results: MEEC treatment induced formation of EC-specific immunoglobulin (Ig) G1 antibodies (41 ± 6 mean fluorescence intensity [MFI]) and differentiation of host splenocytes into Th2, but not Th1, cytokine-producing cells (interleukin [IL]-4, 242 ± 102; IL-10, 273 ± 114 number of spots). Concomitant CsA therapy reduced IgG1 antibody frequency (25 ± 2 MFI; p < 0.02) and Th2-cytokine producing splenocytes upon MEEC treatment (IL-4, 157 ± 19; IL-10, 124 ± 26 number of spots; p < 0.05). MEECs inhibited luminal occlusion 28 and 90 days after balloon injury (12 ± 7%) vs untreated controls (68 ± 14%; p < 0.001) but to a lesser extent with concomitant CsA treatment (34 ± 13%; p < 0.02 vs Group 2). Conclusions: MEECs do not induce a significant Th1-driven immune response but do enhance differentiation of splenocytes into cells producing Th2 cytokine. Reduction in this Th2 response reduces the vasoregulatory effects of allogeneic ECs after injury

Evaluation of the cutaneous microbiome in psoriasis

Psoriasis, a highly prevalent disease of humans of unknown cause, is a chronic inflammatory disorder primarily involving skin, with distinctive clinical characteristics. With the newly developed tools that facilitate microbiome research, it now is possible to assess whether the cutaneous microbiome plays a role in the pathogenesis of this disorder. Preliminary data from our studies suggest that the cutaneous microbiome in psoriasis is complex and possibly different from normal. To deal with this complexity, we propose to examine the cutaneous microbiome in relation to psoriasis with explorations at several taxonomic and informatic levels. Our overall objective is to examine how changes in the normal cutaneous microbiome contributes to the pathogenesis of psoriasis. Since causality is complex and often difficult to prove, our overall hypothesis is that there are alterations in the cutaneous microbiome in areas of skin affected by psoriasis in comparison with the range observed in clinically unaffected areas, or in healthy persons. We also hypothesize that the characteristics of the microbiome may affect clinical responses to the immunomodulatory agents used to treat psoriasis. An alternative hypothesis is that effective treatment of psoriasis with systemic immunomodulatory agents will not substantially affect the disordered microbial ecosystem. Such observations would provide evidence for the roles of the microbiota in this disorder. Since an important consideration in microbiome research is the optimal level (e.g. phylum, genus, species, strain, gene) at which to examine a scientific question, and we are not yet certain what are the optimal levels for psoriasis, this also will be examined. Our studies of psoriasis should allow development of both approaches and tools that will have general utility for microbiome research. To test our hypothesis, we propose the following specific aims: 1. To understand the cutaneous microbiome species composition overlaying psoriatic lesions; 2. To investigate differences in metagenome content for psoriatic lesions compared to normal skin; 3. To identify differences in the transcriptional profiles of the microbiome and the host between normal skin and psoriatic lesions using high-throughput sequencing; and 4. To estimate the effects of systemic immunomodulatory therapy for psoriasis on microbiome composition. In total, these studies should help us understand the role of the microbiome in psoriasis pathogenesis

Knowledge, attitudes and practice of condom use among the married women in Mirpur area of Dhaka city, Bangladesh

Background: Condom is an important method of family planning and prevention of sexually transmitted infections. Condom is the only contraceptive method that can protect against both pregnancy and sexually transmitted infections. Unprotected sex leads to many unintended pregnancies and sexually transmitted infections (STIs). The family planning saves lives of women and children and improves the quality of life. This study was aimed to assess the knowledge, attitudes and practice of condom use among the married women in Mirpur area of Dhaka city in Bangladesh.Methods: A descriptive cross-sectional study was conducted among the randomly selected sample of 101 women aged 15-49 years from selected areas of Mirpur in Dhaka city of Bangladesh. Pre-designed and pre-tested questionnaire was used to elicit the required information from the study participants using face to face interview. The collected data was analyzed using SPSS 21.0 version.Results: Only 5.9% of the study participants had ever used condom. Most of the study participants (93.1%) considered a condom as an effective method for birth control and prevention of sexually transmitted infections (10.9%). However, 36.6% of them believed that condom use had some harmful effects. The main reason for condom use among the users was for family planning (83.3%) and the rest (16.7%) mentioned that it was due to STIs prevention and family planning. The condom use was found significantly associated with age, educational level, partner’s educational level, socio-economic status, and perceived risk of STIs.Conclusions: The study revealed that the rate of condom use was very low among the study participants. This might be due to lack of knowledge about proper and effective use of condoms, low perception of risk of STIs, misperception about harmful effects of condoms and the use of other family planning methods by respondents

The influence of technology and demand factors on firm size and industrial structure in the DRAM market -- 1973-1988

The focus of this research is on the impact of the diffusion of innovations in integrated circuit technology on the market structure of that industry and the implications of firm strategy for both further innovation and market structure change. The study examines the effects of sustained product innovation over a fifteen-year-period in the DRAM segment of the integrated circuit industry. Assessments are made on first mover advantages, shape of the diffusion curve, and resource needs in a market characterized by an increasingly complex technology. Comparisons are made along the dimensions of number of firms in the market, continuity of the firms and market concentration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30210/1/0000600.pd

Knowledge and practice regarding prevention of puerperal sepsis among postpartum women attending a private hospital in Bangladesh

Background: Puerperal sepsis is a common pregnancy-related condition that could eventually lead to obstetric shock or sometimes death. In developing world, the puerperal sepsis is the second most cause of maternal mortality. Cases of Maternal mortality have not declined in spite of efforts by both the public and private sector to prevent such deaths.Methods: A descriptive cross-sectional study was conducted among 150 postpartum mothers who attended Ibn Sina Medical College Hospital (ISMCH) Bangladesh during August to December 2017. A non-probability purposive sampling technique was used to select the study participants and the data was collected using pre-tested semi-structured questionnaire by face to face interview. The collected information was analysed using SPSS 22.0 version.Results: About 50.7% of the study participants were in the age group 19-29 years and the mean age of the study participants was 29.6±15.9 years. More than seven-tenths (73.3%) of the study participants were Muslims and the majority (24.7%) of the study participants had senior secondary certificate. Most of the study participants (62%) were living in urban area and only 18.7% were service holders. Only 39.3% of the respondents think that they have sufficient knowledge regarding prevention of puerperal sepsis and about 78% of the study participants mentioned that getting immediate medical care for any wounds or even seasonal diseases prevents puerperal sepsis. About 37.4% were disagreed to avoid sexual intercourse during last 2 months of pregnancy prevents puerperal sepsis and about 51.3% were agreed to avoid appearances in crowded and unhygienic places, this will prevent from catching respiratory diseases.Conclusions: The findings reported that most of the study participants had poor level of knowledge regarding prevention of puerperal sepsis. However, the study participants had satisfactory practice level about prevention of puerperal sepsis. It further reveals that educational level and age of the study participants was found statistically significant with knowledge about prevention of puerperal sepsis

Adopting Evidence-Based Practices in Elementary School Math: The Collaborative for Improvement of Problem Solving (CIPS)

Two key activities in building and sustaining a change-based model are (a) enhancing buy-in for the change and (b) evaluating capacity to evaluate the change before, during, and after adoption. Unfortunately, the construct of buy-in is frequently used but poorly defined. Furthermore, adopting precise methods to evaluate implementation of evidence-based practices is challenging for schools. Partnerships with universities have been shown to help schools better understand the complexity of sustained change (Shernoff et al., 2011). This poster discusses methods used by the UMass-Boston and Burlington Public Schools Collaborative for the Improvement of Problem Solving (CIPS) to enhance the use of evidence-based practices (EBPs)

Enhanced T-Helper-1 Lymphocyte Activation Patterns in Acute Coronary Syndromes

ObjectivesWe sought to determine whether different stages of coronary artery disease (CAD) are associated with distinct differentiation patterns of activated T cells.BackgroundAtherosclerosis is an inflammatory disease. However, little is known about specific inflammatory cell activation in atherosclerosis, for example, the T-helper (Th)1/Th2-balance.MethodsWe studied 18 patients with stable angina (SA), 28 patients with acute coronary syndrome (ACS) (16 with unstable angina pectoris and 12 with ST-segment elevation myocardial infarction), 19 patients with unheralded myocardial infarction (UH), and 16 control patients. Cytokine patterns and transcription factor signaling pathways of circulating T cells were characterized using reverse transcription polymerase chain reaction and flow cytometry.ResultsAlthough interferon (IFN)-γ+/CD3+T cells were ∼2-fold greater in patients with SA or UH than in control subjects, there was a massive expansion of Th1 cells in patients with ACS (p < 0.001). This increase was paralleled by significantly increased mRNA transcript levels for signal-transducer-and-activator-4 (ACS 1.17 ± 0.14 relative units [RU]; control patients 0.44 ± 0.09 RU; SA 0.67 ± 0.12 RU; UH 0.61 ± 0.17 RU), interleukin-2 (ACS 1.55 ± 0.51 RU; control patients 0.21 ± 0.09 RU; SA 0.54 ± 0.18 RU; UH 0.45 ± 0.16 RU), and IFN-γ in ACS (1.27 ± 0.39 RU; control patients 0.35 ± 0.09 RU; SA 0.58 ± 0.11 RU; UH 0.53 ± 0.24 RU; p < 0.002). Th2 and Th0 cells were not different across patient subsets. The burden of CAD was identical between SA (1.4 ± 0.2 diseased vessels, 68 ± 13% diameter stenosis) and ACS (1.4 ± 0.2 diseased vessels, 64 ± 17% diameter stenosis) but significantly greater in patients with UH (2.5 ± 0.5 diseased vessels, 95 ± 7% diameter stenosis; p < 0.05).ConclusionsPatients with UH have a greater burden of obstructive CAD than SA but no greater T-cell activation. Patients with ACS have the same extent of CAD than SA but significantly greater activation of Th1 cells that may contribute to the increasing instability. Differences in circulating Th1 cells might indicate different pathogenic components, leading to ACS and UH

The positive role of the ecological community in the genomicrevolution

The exponential increase of genomic and metagenomic data,fueled in part by recent advancements in sequencing technology, aregreatly expanding our understanding of the phylogenetic diversity andmetabolic capacity present in the environment. Two of the centralchallenges that bioinformaticians and ecologists alike must face are thedesign of bioinformatic resources that facilitate the analysis of genomicand metagenomic data in a comparative context and the efficient captureand organization of the plethora of descriptive information required tousefully describe these data sets. In this commentary, we review threeinitiatives presented in the "new frontiers" session of the second SCOPEmeeting on Microbial Environmental Genomics (MicroEnGen-II, Shanghai,June 12-15, 2006). These are (1) the Integrated Microbial GenomesResources (IMG), (2) the Genomic Standards Consortium (GSC), and (3) theNatural Environment Research Council (NERC) Environmental BioinformaticsCentre (NEBC). These integrative bioinformatics and data managementinitiatives underscore the increasingly important role ecologists have toplay in the genomic (metagenomic) revolution

RNA Sequencing-Based Genome Reannotation of the Dermatophyte Arthroderma benhamiae and Characterization of Its Secretome and Whole Gene Expression Profile during Infection.

Dermatophytes are the most common agents of superficial mycoses in humans and animals. The aim of the present investigation was to systematically identify the extracellular, possibly secreted, proteins that are putative virulence factors and antigenic molecules of dermatophytes. A complete gene expression profile of Arthroderma benhamiae was obtained during infection of its natural host (guinea pig) using RNA sequencing (RNA-seq) technology. This profile was completed with those of the fungus cultivated in vitro in two media containing either keratin or soy meal protein as the sole source of nitrogen and in Sabouraud medium. More than 60% of transcripts deduced from RNA-seq data differ from those previously deposited for A. benhamiae. Using these RNA-seq data along with an automatic gene annotation procedure, followed by manual curation, we produced a new annotation of the A. benhamiae genome. This annotation comprised 7,405 coding sequences (CDSs), among which only 2,662 were identical to the currently available annotation, 383 were newly identified, and 15 secreted proteins were manually corrected. The expression profile of genes encoding proteins with a signal peptide in infected guinea pigs was found to be very different from that during in vitro growth when using keratin as the substrate. Especially, the sets of the 12 most highly expressed genes encoding proteases with a signal sequence had only the putative vacuolar aspartic protease gene PEP2 in common, during infection and in keratin medium. The most upregulated gene encoding a secreted protease during infection was that encoding subtilisin SUB6, which is a known major allergen in the related dermatophyte Trichophyton rubrum. IMPORTANCE Dermatophytoses (ringworm, jock itch, athlete's foot, and nail infections) are the most common fungal infections, but their virulence mechanisms are poorly understood. Combining transcriptomic data obtained from growth under various culture conditions with data obtained during infection led to a significantly improved genome annotation. About 65% of the protein-encoding genes predicted with our protocol did not match the existing annotation for A. benhamiae. Comparing gene expression during infection on guinea pigs with keratin degradation in vitro, which is supposed to mimic the host environment, revealed the critical importance of using real in vivo conditions for investigating virulence mechanisms. The analysis of genes expressed in vivo, encoding cell surface and secreted proteins, particularly proteases, led to the identification of new allergen and virulence factor candidates