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Streptomyces produces diverse secondary metabolites of biopharmaceutical importance, yet the rate of biosynthesis of these metabolites is often hampered by complex transcriptional regulation. Therefore, a fundamental understanding of transcriptional regulation in Streptomyces is key to fully harness its genetic potential. Here, independent component analysis (ICA) of 454 high‐quality gene expression profiles of the model species Streptomyces coelicolor is performed, of which 249 profiles are newly generated for S. coelicolor cultivated on 20 different carbon sources and 64 engineered strains with overexpressed sigma factors. ICA of the transcriptome dataset reveals 117 independently modulated groups of genes (iModulons), which account for 81.6% of the variance in the dataset. The genes in each iModulon are involved in specific cellular responses, which are often transcriptionally controlled by specific regulators. Also, iModulons accurately predict 25 secondary metabolite biosynthetic gene clusters encoded in the genome. This systemic analysis leads to reveal the functions of previously uncharacterized genes, putative regulons for 40 transcriptional regulators, including 30 sigma factors, and regulation of secondary metabolism via phosphate‐ and iron‐dependent mechanisms in S. coelicolor. ICA of large transcriptomic datasets thus enlightens a new and fundamental understanding of transcriptional regulation of secondary metabolite synthesis along with interconnected metabolic processes in Streptomyces. [ABSTRACT FROM AUTHOR]

Interfaith initiatives are seen as promising sites for societal change and personal transformation. However, many questions about the actual outcomes of such initiatives have remained unanswered. Therefore, a systematic review was conducted, focusing on 1) the outcomes of interfaith initiatives and 2) the methods used to evaluate these outcomes. This review analyses 47 empirical studies on interfaith initiatives. The review of the initiatives' outcomes indicates that interfaith initiatives can positively impact participants' knowledge about other worldviews, communication skills and appreciation for other worldviews. At the same time, it can be challenging for interfaith initiatives to positively impact participants' knowledge of socio-political challenges, awareness of power imbalance and privilege and behaviour as interfaith leaders. The analysis of the methods used to evaluate the impact of interfaith initiatives shows that most studies used qualitative methods. For studies using quantitative or mixed methods designs, a variety of measurement instruments were used, whereby there was little overlap or consensus regarding the concepts being used. The findings of this article will stimulate scholars to focus more on learning activities and evaluation methods that take societal learning outcomes into consideration. It emphasises the need to build on previous evaluation and research efforts. [ABSTRACT FROM AUTHOR]

Health care simulation experiences should provide clear feedback that students can understand and incorporate into future practice. Based on the literature, more research is needed regarding how health professional students use various types of feedback to establish rapport with clients, increase critical thinking skills, and work collaboratively. Various types of feedback may be useful in regular simulationbased education, but there is limited research on how students integrate various feedback to enhance skill development. This study aimed to examine how occupational therapy (OT) students incorporate realtime Simulated Patient (SP) feedback, numerical feedback, and instructor-written feedback to enhance their learning from the simulation experience. This mixed methods study collected learner assessment numerical data and qualitative data (SP feedback and instructor written feedback) in first-year OT students' simulation learning sessions. The students answered six debrief questions reflecting on the simulation process, explaining how they plan to incorporate the feedback in future OT practice. Quantitative results of student performance data were reported. Seven themes emerged from the thematic analysis of the debrief reflections. These themes provided information on students' perceptions of the experience and illustrated how they plan to use the feedback. The findings of this study provide instructors strategies that can be used to enhance student learning when designing simulations. This study found that numerical and written feedback from the instructor was more meaningful when combined with real-time SP feedback. Future studies should include a comparison of cohorts as well as interprofessional education. [ABSTRACT FROM AUTHOR]

Background: This systematic review aims to highlight the scope of pharmacogenomics research within global Indigenous populations. This review also explores the barriers and facilitators of pharmacogenomics research within this population. Methodology: A systematic review of literature was conducted to identify and present an understanding of current empirical evidence demonstrating the conduct of genomics or pharmacogenomics research within global Indigenous populations (PROSPERO registration: CRD42021257226). Using key search terms, relevant databases were searched for articles published between January 2010 and July 2022. Screening, data extraction, and analysis was conducted using well‐defined inclusion criteria. Quality assessment and risk of bias appraisal was conducted using the mixed methods appraisal tool. Indigenous community engagement and participation in genomics research was assessed using the social‐ecological framework. Results: From the 427 articles identified, 77 articles met inclusion criteria and underwent full‐text screening. Of these, 30 articles were included in the final review, with 16 being quantitative and 14 either qualitative or mixed methods studies. Most studies were conducted with native Indigenous populations from the United States of America (36%). Content analysis revealed that studies either explored genetic variations associated with disease in Indigenous populations (23%) or markers for drug metabolism (30%) or were designed to understand perspectives of genomics research within this population (47%). Perspectives included the exploration of the role of participants in research, benefits or outcomes achieved from participation in genomics research, and levels of Indigenous engagement and participation in genomics research. Conclusions: This review highlights a growing gap in Indigenous genomics research globally. It presents several important considerations from Indigenous participants, identifying how researchers can co‐create culturally safe and inclusive design, implementation, analysis, and subsequent outcomes of genomics research involving Indigenous people. Indigenous governance, self‐determination and leadership is essential, with researchers required to be responsive to such fundamental partnerships for research to progress. [ABSTRACT FROM AUTHOR]

Introduction: Developmental processes continue in organisms in which sensory systems have reached functional maturity, however, little research has focused on the influence of sensory input on cell and tissue development. Here, we explored the influence of visual system activity on the development of skin melanophores in Xenopus laevis. Methods: Melanophore number was measured in X. laevis larvae after the manipulation of visual input through eye removal (enucleation) and/or incubation on a white or black substrate at the time when the visual system becomes functional (stage 40). To determine the developmental process impacted by visual input, migration, proliferation and differentiation of melanophores was assessed. Finally, the role of melatonin in driving melanophore differentiation was explored. Results: Enucleating, or maintaining stage 40 larvae on a black background, results in a pronounced increase in melanophore number in the perioptic region within 24 h. Time lapse analysis revealed that in enucleated larvae new melanophores appear through gradual increase in pigmentation, suggesting unpigmented cells in the perioptic region differentiate into mature melanophores upon reduced visual input. In support, we observed increased expression of melanization genes tyr, tyrp1, and pmel in the perioptic region of enucleated or black background-reared larvae. Conversely, maintaining larvae in full light suppresses melanophore differentiation. Interestingly, an extra-pineal melatonin signal was found to be sufficient and necessary to promote the transition to differentiated melanophores. Discussion: In this study, we found that at the time when the visual system becomes functional, X. laevis larvae possess a population of undifferentiated melanophores that can respond rapidly to changes in the external light environment by undergoing differentiation. Thus, we propose a novel mechanism of environmental influence where external sensory signals influence cell differentiation in a manner that would favor survival. [ABSTRACT FROM AUTHOR]

Bacillus Calmette–Guérin (BCG) immunotherapy has been a cornerstone treatment for non-muscle-invasive bladder cancer for decades and still faces challenges, such as severe immune adverse reactions, which reduce its use as a first-line treatment. This review examines BCG therapy's history, mechanisms, and current status, highlighting how nanotechnology and bioengineering are revitalizing its application. We discuss novel nanocarrier systems aimed at enhancing BCG's efficacy while mitigating specific side effects. These approaches promise improved tumor targeting, better drug loading, and an enhanced stimulation of anti-tumor immune responses. Key strategies involve using materials such as liposomes, polymers, and magnetic particles to encapsulate BCG or functional BCG cell wall components. Additionally, co-delivering BCG with chemotherapeutics enhances drug targeting and tumor-killing effects while reducing drug toxicity, with some studies even achieving synergistic effects. While most studies remain experimental, this research direction offers hope for overcoming BCG's limitations and advancing bladder cancer immunotherapy. Further elucidation of BCG's mechanisms and rigorous safety evaluations of new delivery systems will be crucial for translating these innovations into clinical practice. [ABSTRACT FROM AUTHOR]

Covering: up to October 2023 Many bioactive natural products are synthesized by microorganisms that are either difficult or impossible to cultivate under laboratory conditions, or that produce only small amounts of the desired compound. By transferring biosynthetic gene clusters (BGCs) into alternative host organisms that are more easily cultured and engineered, larger quantities can be obtained and new analogues with potentially improved biological activity or other desirable properties can be generated. Moreover, expression of cryptic BGCs in a suitable host can facilitate the identification and characterization of novel natural products. Heterologous expression therefore represents a valuable tool for natural product discovery and engineering as it allows the study and manipulation of their biosynthetic pathways in a controlled setting, enabling innovative applications. Bacillus is a genus of Gram-positive bacteria that is widely used in industrial biotechnology as a host for the production of proteins from diverse origins, including enzymes and vaccines. However, despite numerous successful examples, Bacillus species remain underexploited as heterologous hosts for the expression of natural product BGCs. Here, we review important advantages that Bacillus species offer as expression hosts, such as high secretion capacity, natural competence for DNA uptake, and the increasing availability of a wide range of genetic tools for gene expression and strain engineering. We evaluate different strain optimization strategies and other critical factors that have improved the success and efficiency of heterologous natural product biosynthesis in B. subtilis. Finally, future perspectives for using B. subtilis as a heterologous host are discussed, identifying research gaps and promising areas that require further exploration. [ABSTRACT FROM AUTHOR]

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We study the size and structure of globular cluster (GC) systems of 118 early-type galaxies from the NGVS, MATLAS, and ACSVCS surveys. Fitting Sérsic profiles, we investigate the relationship between effective radii of GC systems (R e,gc) and galaxy properties. GC systems are 2–4 times more extended than host galaxies across the entire stellar mass range of our sample (108.3 M ⊙ < M * < 1011.6 M ⊙). The relationship between R e,gc and galaxy stellar mass exhibits a characteristic "knee" at a stellar mass of M p ≃ 1010.8, similar to the galaxy R e –stellar mass relationship. We present a new characterization of the traditional blue and red GC color subpopulations, describing them with respect to host galaxy (g ′ − i ′) color (Δgi): GCs with similar colors to their hosts have a "red" Δgi, and those significantly bluer GCs have a "blue" Δgi. The GC populations with red Δgi, even in dwarf galaxies, are twice as extended as the stars, suggesting that formation or survival mechanisms favor the outer regions. We find a tight correlation between R e,gc and the total number of GCs, with intrinsic scatter ≲0.1 dex spanning two and three orders of magnitude in size and number, respectively. This holds for both red and blue subpopulations, albeit with different slopes. Assuming that N GC,Total correlates with M 200, we find that the red GC systems have effective radii of roughly 1%–5% R 200, while the blue GC systems in massive galaxies can have sizes as large as ∼10% R 200. Environmental dependence on R e,gc is also found, with lower-density environments exhibiting more extended GC systems at fixed mass. [ABSTRACT FROM AUTHOR]

The quality of listening in interpersonal contexts was hypothesized to improve a variety of work outcomes. However, research of this general hypothesis is dispersed across multiple disciplines and mostly atheoretical. We propose that perceived listening improves job performance through its effects on affect, cognition, and relationship quality. To test our theory, we conducted a registered systematic review and multiple meta-analyses, using three-level meta-analysis models, based on 664 effect sizes and 400,020 observations. Our results suggest a strong positive correlation between perceived listening and work outcomes, r ¯ =.39, 95%CI = [.36,.43], ρ ¯ =.44, with the effect on relationship quality, r ¯ = .51, being stronger than the effect on performance, r ¯ = .36. These findings partially support our theory, indicating that perceived listening may enhance job performance by improving relationship quality. However, 75% of the literature relied on self-reports raising concerns about discriminant validity. Despite this limitation, removing data solely based on self-reports still produced substantial estimates of the association between listening and work outcomes (e.g., listening and job performance, r ¯ =.21, 95%CI = [.13,.29], ρ ¯ =.23). Our meta-analyses suggest further research into (a) the relationship between listening and job knowledge, (b) measures assessing poor listening behaviors, (c) the incremental validity of listening in predicting listeners' and speakers' job performance, and (d) listening as a means to improve relationships at work. [ABSTRACT FROM AUTHOR]

Observations in 2022 of intertidal and subtidal foraminiferalfaunas at four localities along the central-eastern side of Vancouver Island, British Columbia, Canada, and molecular analyses have documented the first occurrence of the nonindigenous Asian species Ammonia confertitesta Zheng in the northwestern Pacific Ocean. The species was present at three of these localities: Davis Lagoon south of Ladysmith (4% in the lagoon and 49% on the beach) and 0.6% in Nanaimo Harbor. The vector of introduction is thought to be the release of ballast water and associated sediment. These releases probably occurred in the Port of Vancouver, which were then transported by means of the cyclonic circulation across the Strait of Georgia, or from local anchorages close to the sampling sites. The timing of the introduction is impossible to determine because no stratigraphic record is presently available. However, foraminiferal studies in the late 1980s near the Port of Vancouver that recovered calcareous taxa did not report the presence of this species, nor was it found at 33 sites sampled from 1997 to 1999 throughout the Strait of Georgia. [ABSTRACT FROM AUTHOR]

Covering: up to the end of 2022 In recent years rare Actinobacteria have become increasingly recognised as a rich source of novel bioactive metabolites. Actinomadura are Gram-positive bacteria that occupy a wide range of ecological niches. This review highlights about 230 secondary metabolites produced by Actinomadura spp., reported until the end of 2022, including their bioactivities and selected biosynthetic pathways. Notably, the bioactive compounds produced by Actinomadura spp. demonstrate a wide range of activities, including antimicrobial, antitumor and anticoccidial effects, highlighting their potential in various fields. [ABSTRACT FROM AUTHOR]

To combat climate change, carbon dioxide must be prevented from entering the atmosphere or even removed from it. Biochar is one potential practice to sequester carbon, but its climate change mitigation potential depends on a multitude of parameters. Differentiating areas of low and high climate change mitigation through biochar addition is key to maximize its potential and effectively use the available feedstock for its production. This study models the realistic application of 1 metric tonne (t) per hectare (ha) of forest harvest residue derived biochar over the climatically and pedologically diverse agricultural area of British Columbia, Canada, and provides a framework and assumptions for reproducibility in other parts of the world. The model accounts for the direct (input of organic carbon) and indirect (enhanced plant biomass) effects of biochar on soil organic carbon stock, its impact on nitrous oxide emissions from soils, and the avoided emissions from the reduced lime requirement due to biochar's alkalinization potential. Impacts are modelled over 20‐year time horizon to account for the duration and magnitude variation over time of biochar effect on plant biomass and nitrous oxide emissions from soil and conform to the IPCC GWP 20‐year time horizon reporting. The results show that a single application of 1 t of biochar per ha−1 can mitigate between 3 and 5 t CO2e ha−1 over a 20‐year time frame. Applied to the 746,000 ha of agricultural land of British Columbia this translate to the mitigation of a total of 2.5 million metric tonnes (Mt) CO2e over a 20‐year time frame. Further, the results identify agricultural areas in the Lower Mainland region (the southwestern corner of British Columbia) as the area maximizing climate change mitigation potential through biochar addition due to a combination of relative high temperature, high precipitation, and crops with high nitrogen requirement. [ABSTRACT FROM AUTHOR]

Clinical multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is the leading cause of refractory bacterial keratitis (BK). However, the reported BK treatment methods lack biosecurity and bioavailability, which usually causes irreversible visual impairment and even blindness. Herein, for BK caused by clinically isolated MDR-PA infection, armed phages are modularized with the type I photosensitizer (PS) ACR-DMT, and an intelligent phage eyedrop is developed for combined phagotherapy and photodynamic therapy (PDT). These eyedrops maximize the advantages of bacteriophages and ACR-DMT, enabling more robust and specific targeting killing of MDR-PA under low oxygen-dependence, penetrating and disrupting biofilms, and efficiently preventing biofilm reformation. Altering the biofilm and immune microenvironments alleviates inflammation noninvasively, promotes corneal healing without scar formation, protects ocular tissues, restores visual function, and prevents long-term discomfort and pain. This strategy exhibits strong scalability, enables at-home treatment of ocular surface infections with great patient compliance and a favorable prognosis, and has significant potential for clinical application., (© 2024 Wiley‐VCH GmbH.)

The dystrophinopathies encompass the phenotypically variable forms of muscular dystrophy caused by pathogenic variants in the DMD gene. The dystrophinopathies include the most common inherited muscular dystrophy among 46,XY individuals, Duchenne muscular dystrophy, as well as Becker muscular dystrophy and other less common phenotypic variants. With increased access to and utilization of genetic testing in the diagnostic and carrier setting, genetic counselors and clinicians in diverse specialty areas may care for individuals with and carriers of dystrophinopathy. This practice resource was developed as a tool for genetic counselors and other health care professionals to support counseling regarding dystrophinopathies, including diagnosis, health risks and management, psychosocial needs, reproductive options, clinical trials, and treatment. Genetic testing efforts have enabled genotype/phenotype correlation in the dystrophinopathies, but have also revealed unexpected findings, further complicating genetic counseling for this group of conditions. Additionally, the therapeutic landscape for dystrophinopathies has dramatically changed with several FDA-approved therapeutics, an expansive research pathway, and numerous clinical trials. Genotype-phenotype correlations are especially complex and genetic counselors' unique skill sets are useful in exploring and explaining this to families. Given the recent advances in diagnostic testing and therapeutics related to dystrophinopathies, this practice resource is a timely update for genetic counselors and other healthcare professionals involved in the diagnosis and care of individuals with dystrophinopathies., (© 2024 National Society of Genetic Counselors.)

Objective: To examine the association between Body Mass Index (BMI) and self-rated health status among a representative sample of the Brazilian population., Methods: This study consists of a secondary analysis of the existing 2019 Brazilian National Health Survey (PNS). Logistic regression models were then used to examine the association between self-reported health status and BMI, while controlling for obesity-related medical conditions and socio-demographic characteristics., Results: The representative sample included 34,021 men and 34,430 women, comprising a total sample of 68,451. Men living with obesity (BMI ≥ 30 kg/m 2 ) had, on average, a lower self-reported health status score (OR = 0.69, p < 0.01) compared to men within a healthy weight BMI range (18.5-25 kg/m 2 ). Women living with obesity had, on average, a lower self-reported health status score (OR = 0.56, p < 0.01) compared to women within a healthy weight BMI range (18.5-25 kg/m 2 ). There was also a statistically significant negative association (p < 0.01) between our obesity-related medical conditions and self-reported health for men and women. We also find some evidence of a non-linear association between BMI and health status for men., Conclusions: The findings indicate that there is a statistically significant negative association between BMI and self-reported health for Brazilian men and women living with obesity. These findings reinforce the importance of addressing this growing public health challenge and the value of preventive measures and effective public health programs that focus on improving overall health and quality of life for individuals living with obesity., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Tuberculosis (TB) is a chronic respiratory infectious disease and is induced by Mycobacterium tuberculosis (M.tb) infection. Macrophages serve as the cellular home in immunoreaction against M.tb infection, which is tightly regulated through Toll-like receptor 4 (TLR4) expression. Therefore, this study is designed to explore the role and mechanism of TLR4 in mycobacterial injury in human macrophages (THP-1 cells) after M.tb infection. Cell proliferation and apoptosis were assessed using MTT, EdU, and flow cytometry assays. ELISA kits were utilized to assess the levels of Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor α (TNF-α). The binding between Yin-Yang-1 (YY1) and TLR4 promoter was predicted by JASPAR and verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. M.tb infection might repress THP-1 cell proliferation, and induce cell apoptosis and inflammatory response in a multiplicity of infection (MOI)-dependent manner. Moreover, M.tb infection increased the expression of TLR4 in HTP-1 cells in an MOI-dependent way, and its downregulation might overturn M.tb infection-mediated HTP-1 cell damage and inflammatory response. At the molecular level, YY1 was a transcription factor of TLR4 and promoted TLR4 transcription via binding to its promoter region. Besides, YY1 might activate the NF-kB signaling pathway via regulating TLR4. Meanwhile, TLR4 inhibitor BAY11-7082 might overturn the repression effect of TLR4 on M.tb-infected HTP-1 cell damage. YY1-activated TLR4 might aggravate mycobacterial injury in human macrophages after M.tb infection by the NF-kB pathway, providing a promising therapeutic target for TB treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)