A5072889556- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
- Probiotics and Fermented Foods
- Retirement, Disability, and Employment
- Bacterial biofilms and quorum sensing
- Allergic Rhinitis and Sensitization
- Chemical Synthesis and Analysis
- Global Public Health Policies and Epidemiology
- Porphyrin Metabolism and Disorders
- Transportation Safety and Impact Analysis
- Vaccine Coverage and Hesitancy
- Microbial Metabolic Engineering and Bioproduction
- Food Allergy and Anaphylaxis Research
- Global Maternal and Child Health
- Fluorine in Organic Chemistry
- Immune responses and vaccinations
- Asthma and respiratory diseases
- Healthcare Systems and Reforms
- Employment and Welfare Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Agriculture and Farm Safety
- Posttraumatic Stress Disorder Research
- Biotin and Related Studies
University of Wisconsin–Madison
2015-2025
Yale University
2021-2024
Stanford University
2023-2024
Nationwide Children's Hospital
2023
Indiana State Department of Health
2021
Frederick S. Pardee RAND Graduate School
2015-2020
RAND Europe
2016
University of Freiburg
2016
Napa State Hospital
2015
RAND Corporation
2015
The bacterial stringent response (SR) is a conserved stress tolerance mechanism that orchestrates physiological alterations to enhance cell survival. This mediated by the intracellular accumulation of alarmones pppGpp and ppGpp, collectively called (p)ppGpp. In Enterococcus faecalis, (p)ppGpp metabolism carried out bifunctional synthetase/hydrolase E. faecalis Rel (RelEf) small alarmone synthetase (SAS) RelQEf. Although main enzyme responsible for SR activation in Firmicutes, there emerging...
ABSTRACT Gluconeogenesis, the reciprocal pathway of glycolysis, is an energy-consuming process that generates glycolytic intermediates from non-carbohydrate sources. In this study, we demonstrate robust and efficient gluconeogenesis in bacteria relies on allosteric inactivation pyruvate kinase, enzyme responsible for irreversible final step glycolysis. Using model bacterium Bacillus subtilis as example, discovered kinase activity inhibited during via its extra C-terminal domain (ECTD), which...
Abstract The alarmone nucleotides guanosine tetraphosphate and pentaphosphate, commonly referred to as (p)ppGpp, regulate bacterial responses nutritional other stresses. There is evidence for potential existence of a third alarmone, guanosine-5′-monophosphate-3′-diphosphate (pGpp), with less-clear functions. Here, we demonstrate the presence pGpp in cells, perform comprehensive screening identify proteins that interact respectively pGpp, ppGpp pppGpp Bacillus species. Both involved...
Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over past decade. Despite this progress, there remain substantial inequalities health outcomes, access, quality medical care between within countries. Poor, indigenous, rural populations have considerably worse indicators than national or regional averages. In an effort to address these inequalities, Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was...
The alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal inhibits purine salvage enzyme HPRT sharing a conserved motif with substrate PRPP. Intriguingly, regulation varies across organisms correlates oligomeric forms. (p)ppGpp-sensitive exists as PRPP-bound dimer or an apo- (p)ppGpp-bound tetramer, where dimer-dimer interface triggers allosteric structural rearrangements to enhance...
Purpose of review This aims to explore role emerging biologics, including ligelizumab, UB-221, dupilumab, and antialarmins, in food allergy management. With a focus on recent developments, we evaluate their promise mitigating adverse events during oral immunotherapy (OIT), reducing allergic reactions, addressing the limitations current therapeutic options. Recent findings Antiimmunoglobulin E mAbs, exemplified by omalizumab, demonstrate efficacy desensitization safety improvement...
ABSTRACT Guanosine triphosphate (GTP) is essential for macromolecular biosynthesis, and its intracellular levels are tightly regulated in bacteria. Loss of the alarmone (p)ppGpp disrupts GTP regulation Bacillus subtilis , causing cell death presence exogenous guanosine underscoring critical importance homeostasis. To investigate basis toxicity, we performed a genetic selection spontaneous mutations that suppress this effect, uncovering an unexpected link between synthesis glycolysis. In...
The nucleotide messenger (p)ppGpp allows bacteria to adapt fluctuating environments by reprogramming the transcriptome. Despite its well-recognized role in gene regulation, is only known directly affect transcription Proteobacteria binding RNA polymerase. Here, we reveal a different mechanism of regulation Firmicutes: binds factor PurR downregulate purine biosynthesis expression upon amino acid starvation. We first identified as receptor Bacillus anthracis. A co-structure with subtilis...
Timely and accurate measurement of population protection against measles is critical for decision-making prevention outbreaks. However, little known about how survey-based estimates immunization (crude coverage) compare to the seroprevalence antibodies (effective coverage), particularly in low-resource settings. In poor areas Mexico Nicaragua, we used household surveys gather information on from child health cards caregiver recall. We also collected dried blood spots (DBS) children aged 12...
Metformin is among the most prescribed medications worldwide and first-line therapy for type 2 diabetes. However, gastrointestinal side effects are common can be dose limiting. The total daily metformin frequently reaches several grams, poor absorption results in high intestinal drug concentrations. Here, we report that inhibits activity of enteropeptidase other digestive enzymes at concentrations predicted to occur human duodenum. Treatment mouse tissue with reduces activity; further,...
Abstract Glycolysis and gluconeogenesis are reciprocal metabolic pathways that utilize different carbon sources. Pyruvate kinase catalyzes the irreversible final step of glycolysis, yet physiological function its regulation is poorly understood. Through metabolomics enzyme kinetics studies, we discovered pyruvate activity inhibited during in soil bacterium Bacillus subtilis . This involves an extra C-terminal domain (ECTD) kinase, which essential for autoinhibition by effectors. Introducing...
The human intestine harbors a highly complex microbial community; interpersonal variation in this community can impact pathogen susceptibility, metabolism, and other aspects of health. Here, we identified characterized commensal-targeting antibacterial protein encoded the gut microbiome.
The American Cancer Society, Inc. (ACS) estimates that 37,940 Indiana residents were diagnosed with cancer in 2020, which remains the leading cause of death state. Across continuum, national goals have been established targeting recommended benchmarks for states prevention, screening, treatment, and survivorship. consistently falls below most each these targeted categories.To address disparities, we implemented Project ECHO (Extension Community Healthcare Outcomes) as a virtual telehealth...
Individual income and poverty are associated with poor health outcomes. The face unique challenges related to access, education, financial capacity, environmental effects, other factors that threaten their outcomes.We examined the variation in outcomes behaviors among poorest quintile eight countries of Mesoamerica using data from Salud Mesomérica 2015 baseline household surveys. We used multivariable logistic regression measure association between delivering a child facility select maternal...
Abstract The alarmones pppGpp and ppGpp (collectively (p)ppGpp) protect bacterial cells from nutritional other stresses. Here we demonstrate the physiological presence of pGpp as a third closely related alarmone in also characterize compare proteomic targets pGpp, Gram-positive Bacillus species. We revealed two regulatory pathways for that are highly conserved across species: inhibition purine nucleotide biosynthesis control ribosome assembly/activity through GTPases. Strikingly, potently...
Experimental research in education and training programs typically involves administering treatment to whole groups of individuals. As such, researchers rely on the estimation design parameter values conduct power analyses efficiently plan their studies detect desired effects. In this study, we present estimates from a compilation 11 involving teacher-level outcomes. These results expand upon what little is known about clustering variance among The findings inform intervention which nest...
ABSTRACT The nucleotide messenger (p)ppGpp allows bacteria to adapt fluctuating environments by reprogramming the transcriptome. Yet despite its well-recognized role in gene regulation, is only known directly affect transcription Proteobacteria. Here we reveal a different mechanism of regulation Firmicutes from soil pathogens: serves as co-repressor factor PurR downregulate purine biosynthesis. We identified receptor Bacillus anthracis and revealed that strongly enhances binding regulon...