Isolation and identification of metabolites from the gram-negative Proteobacteria of Burkholderia cenocepacia and Serratia marcescens

Burkholderia cenocepacia and Serratia marcescens are Gram-negative proteobacteria commonly found in the natural environment and are also opportunistic pathogens that caused a number of human diseases. The fermentation culture of Burkholderia cenocepacia yielded three compounds, 4-(2-hydroxyethoxy)-phenol (1), Maculosin (2) and methyl myristate (3). Compound 2 was also isolated together with cyclo(L-Leu-L-Pro) (4) from Serratia marcescens. Compound 1 was isolated from a natural source for the first time and the first isolation of compounds 2-4 was also reported from both Burkholderia cenocepacia and Serratia marcescens

Global landscape of mouse and human cytokine transcriptional regulation

Cytokines are cell-to-cell signaling proteins that play a central role in immune development, pathogen responses, and diseases. Cytokines are highly regulated at the transcriptional level by combinations of transcription factors (TFs) that recruit cofactors and the transcriptional machinery. Here, we mined through three decades of studies to generate a comprehensive database, CytReg, reporting 843 and 647 interactions between TFs and cytokine genes, in human and mouse respectively. By integrating CytReg with other functional datasets, we determined general principles governing the transcriptional regulation of cytokine genes. In particular, we show a correlation between TF connectivity and immune phenotype and disease, we discuss the balance between tissue-specific and pathogen-activated TFs regulating each cytokine gene, and cooperativity and plasticity in cytokine regulation. We also illustrate the use of our database as a blueprint to predict TF–disease associations and identify potential TF–cytokine regulatory axes in autoimmune diseases. Finally, we discuss research biases in cytokine regulation studies, and use CytReg to predict novel interactions based on co-expression and motif analyses which we further validated experimentally. Overall, this resource provides a framework for the rational design of future cytokine gene regulation studies.National Institutes of Health (NIH) [R00 GM114296 and R35 GM128625 to J.I.F.B., 5T32HL007501-34 to J.A.S.]; National Science Foundation [NSF-REU BIO-1659605 to M.M.]. Funding for open access charge: NIH [R35 GM128625]. (R00 GM114296 - National Institutes of Health (NIH); R35 GM128625 - National Institutes of Health (NIH); 5T32HL007501-34 - National Institutes of Health (NIH); NSF-REU BIO-1659605 - National Science Foundation; R35 GM128625 - NIH)Published versio

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

synZiFTR2.0: the development of improved synthetic human transcription activation factors

The advent of synthetic transcriptional regulators built mainly on human-derived proteins, namely synthetic Zinc Finger Transcription Regulators (synZiFTRs), has enabled fine-tuned control of therapeutically significant genes in primary T cells. However, their clinical relevance could be enhanced by amplifying synthetic gene circuit activation and expanding the synZiFTR toolkit with standardized compo-nents for the construction of more complex circuits. This study describes the de-velopment of the next iteration of synZiFTR, the synZiFTR2.0, incorporating the human-derived transcription elongation domain, IWS1. We present an engi-neered version 2.0 of GZV- and 4OHT/TMX-regulated gene switches, exhibiting a robust increase in transcriptional output upon drug induction. Furthermore, the synZiFTR toolkit was expanded and utilized to examine the feasibility of con-structing a two-input AND logic gate. Interestingly, the integration of IWS1 un-veiled a potential role of PP1-NUTS phosphatase in enhancing synthetic circuit output, though the precise mechanism warrants further investigation. The intro-duction of synZiFTR2.0 is projected to boost its clinical applicability, particularly in settings where circuit output strength is contingent on disease context that is often uncertain.2025-10-03T00:00:00

A new oxolane from <i>Enterobacter cloacae</i>

<p><i>Enterobacter cloacae</i> is a highly pathogenic Gram-negative proteobacterium which is responsible for a wide array of infections. In the present study, the fermentation culture of <i>E. cloacae</i> has yielded one new oxolane compound, Rimboxo (<b>1</b>) in addition to three known compounds, i.e. Maculosine (<b>2</b>), phenylacetic acid (<b>3</b>) and methyl myristate (<b>4</b>). These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods, and were subjected to cytotoxicity evaluations.</p

Aiding Virtual Organization (Semester Unknown) EnPRO 353: Aiding Virtual Organization EnPRO 353 Midterm Report Sp08

The objective for IPRO 353 is to evaluate the business opportunities for iGroups. We will do this by drafting a business plan, which will be evaluated for feasibility and a final report will be issued, for suggestions as to the next steps the iGroups project should take. Included in the business plan and recommendation shall be: Description of iGroups Market data Financial data Projections for income, cash flow, sales Analysis of different business models for iGroups, and final recommendation.Deliverable

Aiding Virtual Organization (Semester Unknown) EnPRO 353: Aiding Virtual Organization EnPRO 353 Final Presentation Sp08_redacted

The objective for IPRO 353 is to evaluate the business opportunities for iGroups. We will do this by drafting a business plan, which will be evaluated for feasibility and a final report will be issued, for suggestions as to the next steps the iGroups project should take. Included in the business plan and recommendation shall be: Description of iGroups Market data Financial data Projections for income, cash flow, sales Analysis of different business models for iGroups, and final recommendation.Deliverable