In , the Bld (Bald) regulators control formation of the reproductive aerial hyphae. The functions of some of these regulators have been well characterized, but BldB has remained enigmatic. In addition to the gene itself, Streptomyces venezuelae has 10 paralogs of that sit next to paralogs of and . Transcriptome sequencing (RNA-seq) revealed that loss of BldB function causes the dramatic transcriptional upregulation of the paralogs and a novel inhibitor of sporulation, , and that cooverexpression of just two of these genes, and , was sufficient to recapitulate the mutant phenotype. Further RNA-seq analysis showed that the transcription factor WhiJ9 is required for the activation of seen in the mutant, and biochemical studies showed that WhiJ9 mediates the activation of expression by binding to direct repeats in the intergenic region. BldB and BldB9 hetero-oligomerize, providing a potential link between BldB and the locus. This work greatly expands our overall understanding of the global effects of the BldB developmental regulator. To reproduce and disperse, the filamentous bacterium develops specialized reproductive structures called aerial hyphae. The formation of these structures is controlled by the (bald) genes, many of which encode transcription factors whose functions have been characterized. An exception is BldB, a protein whose biochemical function is unknown. In this study, we gain insight into the global effects of BldB function by examining the genome-wide transcriptional effects of deleting . We identify a small set of genes that are dramatically upregulated in the absence of BldB. We show that their overexpression causes the phenotype and characterize a transcription factor that mediates the upregulation of one of these target genes. Our results provide new insight into how BldB influences development.
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http://dx.doi.org/10.1128/jb.00135-23 | DOI Listing |
Environ Sci Technol
January 2025
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Air pollution is a leading contributor to the global disease burden. However, the complex nature of the chemicals to which humans are exposed through inhalation has obscured the identification of the key compounds responsible for diseases. Here, we develop a network topology-based framework to identify key toxic compounds in the airborne chemical exposome.
View Article and Find Full Text PDFCurr Opin Crit Care
January 2025
The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Purpose Of Review: To review the evidence that supports the implementation of goal-directed care bundle protocols to improve outcomes from neurocritical conditions, and of the possible advantage of specific over generalized protocols.
Recent Findings: Articles from January 1, 2023 to July 31, 2024 were searched to evaluate the effectiveness of standardized management in neurological emergencies. The use of care bundles and standardized protocols with time- and target-related metrics has shown benefit in patients with acute stroke and traumatic brain injury.
J Med Syst
January 2025
Department of Computing, University of North Florida, 1 UNF Dr., Jacksonville, 32246, FL, USA.
The "no-show" problem in healthcare refers to the prevalent phenomenon where patients schedule appointments with healthcare providers but fail to attend them without prior cancellation or rescheduling. In addressing this issue, our study delves into a multivariate analysis over a five-year period involving 21,969 patients. Our study introduces a predictive model framework that offers a holistic approach to managing the no-show problem in healthcare, incorporating elements into the objective function that address not only the accurate prediction of no-shows but also the management of service capacity, overbooking, and idle resource allocation resulting from mispredictions.
View Article and Find Full Text PDFCurr Nutr Rep
January 2025
Research and Development cell, Department of Intellectual property Rights, Lovely Professional University, Jalandhar- Delhi Grand Trunk Rd., Phagwara, Punjab, 144411, India.
Purpose Of Review: This review explores the mechanistic pathways and clinical implications of phytochemicals in obesity management, addressing the global health crisis of obesity and the pressing need for effective, natural strategies to combat this epidemic.
Recent Findings: Phytochemicals demonstrate significant potential in obesity control through various molecular mechanisms. These include the modulation of adipogenesis, regulation of lipid metabolism, enhancement of energy expenditure, and suppression of appetite.
Clin Exp Rheumatol
January 2025
UMass Chan Medical School and UMass Memorial Medical Center, Boston, MA, USA.
Objectives: To assess the efficacy and safety of an intra-articular (IA) CLK/DYRK inhibitor, lorecivivint (LOR), for the treatment of moderate to severe symptomatic knee osteoarthritis (OA).
Methods: This was a Phase 3, 28-week, multicentre, double-blind, placebo-controlled study evaluating the efficacy and safety of a single IA injection of LOR. Patients with ACR-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and pain Numeric Rating Scale (NRS) ≥4 and ≤8 in the target knee were randomised (1:1) to receive LOR 0.
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