Tools to make Stachybotrys chartarum genetically amendable: Key to unlocking cryptic biosynthetic gene clusters.

The soil and indoor fungus Stachybotrys chartarum can induce respiratory disorders, collectively referred to as stachybotryotoxicosis, owing to its prolific production of diverse bioactive secondary metabolites (SMs) or mycotoxins. Although many of these toxins responsible for the harmful effects on animals and humans have been identified in the genus Stachybotrys, however a number of SMs remain elusive. Through in silico analyses, we have identified 37 polyketide synthase (PKS) genes, highlighting that the chemical profile potential of Stachybotrys is far from being fully explored.

Diverse bacteria elicit distinct neutrophil responses in a physiologically relevant model of infection.

An efficient neutrophil response is critical for fighting bacterial infections, which remain a significant global health concern; therefore, modulating neutrophil function could be an effective therapeutic approach. While we have a general understanding of how neutrophils respond to bacteria, how neutrophil function differs in response to diverse bacterial infections remains unclear. Here, we use a microfluidic infection-on-a-chip device to investigate the neutrophil response to four bacterial species: , , , and We find enhanced neutrophil extravasation to , a limited overall response to , and identify IL-6 as universally important for neutrophil extravasation.

Disparities in Mpox Vaccination Among Priority Populations During the 2022 Outbreak.

Background: The 2022 mpox outbreak disproportionately affected men who have sex with men and persons living with HIV (PLWH). A 2-dose mpox vaccine series was deployed in mid-2022. Structural racism and insurance status may have affected equitable vaccination.

Concurrent Sexually Transmitted Infection Testing Among Patients Tested for Mpox at a Tertiary Healthcare System.

Coinfection with sexually transmitted infections (STIs) and mpox is common. We evaluated concurrent STI testing among Duke Health patients tested for mpox. We found that most patients tested for mpox were not comprehensively tested for STIs, despite concurrent STIs being diagnosed in 15% of patients when testing was performed.

PhageBox: An Open Source Digital Microfluidic Extension With Applications for Phage Discovery.

Objective: Recent advancements demonstrate the significant role of digital microfluidics in automating laboratory work with DNA and on-site viral testing. However, since commercially available instruments are limited to droplet manipulation, our work addresses the need for accelerated integration of other components, such as temperature control, that can expand the application domain.

Methods: We developed PhageBox-an accessible device that can be used as a biochip extension.

Ensuring a safe(r) harbor: Excising personally identifiable information from structured electronic health record data.

Recent findings have shown that the continued expansion of the scope and scale of data collected in electronic health records are making the protection of personally identifiable information (PII) more challenging and may inadvertently put our institutions and patients at risk if not addressed. As clinical terminologies expand to include new terms that may capture PII (e.g.

Synergies between centralized and federated approaches to data quality: a report from the national COVID cohort collaborative.

Objective: In response to COVID-19, the informatics community united to aggregate as much clinical data as possible to characterize this new disease and reduce its impact through collaborative analytics. The National COVID Cohort Collaborative (N3C) is now the largest publicly available HIPAA limited dataset in US history with over 6.4 million patients and is a testament to a partnership of over 100 organizations.

Identification of the polyketide synthase PKS7 responsible for the production of lecanoric acid and ethyl lecanorate in Claviceps purpurea.

Claviceps purpurea is a plant pathogenic fungus which is still highly relevant in modern agriculture as it infects grasses such as rye and wheat. The disease caused by the consumption of contaminated grain or flour has been known since the Middle Ages and is termed ergotism. The main cause for the toxicity of this fungus is attributed to the ergot alkaloids.

Disparity in Quality of Infectious Disease vs Addiction Care Among Patients With Injection Drug Use-Associated Bacteremia.

Evidence-based interventions for bacteremia (SAB) are well known, but it is unclear how they are implemented among patients with injection drug use-associated (IDU) SAB. Of 46 patients with IDU-SAB identified, all received high-quality SAB management; however, few received appropriate recognition or treatment of their underlying substance use disorder.

Smartphone geospatial apps for dengue control, prevention, prediction, and education: MOSapp, DISapp, and the mosquito perception index (MPI).

India has the largest number of dengue cases in the world, contributing approximately 34% of the global burden. The framework for a geospatially enabled early warning and adaptive response system (EWARS) was first proposed in 2008. It was meant to be a decision support system for enhancing traditional surveillance methods for preventing mosquito-borne diseases in India by utilizing remote sensing data and fuzzy logic-based mathematical predictive modeling.

Production and Role of Hormones During Interaction of Species With Maize ( L.) Seedlings.

It has long been known that hormones affect the interaction of a phytopathogen with its host plant. The pathogen can cause changes in plant hormone homeostasis directly by affecting biosynthesis or metabolism in the plant or by synthesizing and secreting the hormone itself. We previously demonstrated that pathogenic fungi of the species complex are able to produce three major types of hormones: auxins, cytokinins, and gibberellins.

Realizing the Potential of International Education in Leadership Learning.

This chapter explores how study abroad and the presence of international students contributes to students' leadership development, key challenges preventing that potential from being realized, and offers suggestions for improving access to and implementing leadership-focused study abroad and international student programs.

Analysis of the global regulator Lae1 uncovers a connection between Lae1 and the histone acetyltransferase HAT1 in Fusarium fujikuroi.

The fungus Fusarium fujikuroi causes "bakanae" disease of rice due to its ability to produce gibberellins (GAs), a family of plant hormones. Recent genome sequencing revealed the genetic capacity for the biosynthesis of 46 additional secondary metabolites besides the industrially produced GAs. Among them are the pigments bikaverin and fusarubins, as well as mycotoxins, such as fumonisins, fusarin C, beauvericin, and fusaric acid.

Comparative genomics of geographically distant Fusarium fujikuroi isolates revealed two distinct pathotypes correlating with secondary metabolite profiles.

Fusarium fujikuroi causes bakanae ("foolish seedling") disease of rice which is characterized by hyper-elongation of seedlings resulting from production of gibberellic acids (GAs) by the fungus. This plant pathogen is also known for production of harmful mycotoxins, such as fusarins, fusaric acid, apicidin F and beauvericin. Recently, we generated the first de novo genome sequence of F.

The GATA-Type Transcription Factor Csm1 Regulates Conidiation and Secondary Metabolism in .

GATA-type transcription factors (TFs) such as the nitrogen regulators AreA and AreB, or the light-responsive TFs WC-1 and WC-2, play global roles in fungal growth and development. The conserved GATA TF NsdD is known as an activator of sexual development and key repressor of conidiation in , and as light-regulated repressor of macroconidia formation in In the present study, we functionally characterized the NsdD ortholog in , named Csm1. Deletion of this gene resulted in elevated microconidia formation in the wild-type (WT) and restoration of conidiation in the non-sporulating velvet mutant Δ demonstrating that Csm1 also plays a role as repressor of conidiation in .

Comparative "Omics" of the Fusarium fujikuroi Species Complex Highlights Differences in Genetic Potential and Metabolite Synthesis.

Species of the Fusarium fujikuroi species complex (FFC) cause a wide spectrum of often devastating diseases on diverse agricultural crops, including coffee, fig, mango, maize, rice, and sugarcane. Although species within the FFC are difficult to distinguish by morphology, and their genes often share 90% sequence similarity, they can differ in host plant specificity and life style. FFC species can also produce structurally diverse secondary metabolites (SMs), including the mycotoxins fumonisins, fusarins, fusaric acid, and beauvericin, and the phytohormones gibberellins, auxins, and cytokinins.

Gibepyrone Biosynthesis in the Rice Pathogen Fusarium fujikuroi Is Facilitated by a Small Polyketide Synthase Gene Cluster.

The 2H-pyran-2-one gibepyrone A and its oxidized derivatives gibepyrones B-F have been isolated from the rice pathogenic fungus Fusarium fujikuroi already more than 20 years ago. However, these products have not been linked to the respective biosynthetic genes, and therefore, their biosynthesis has not yet been analyzed on a molecular level. Feeding experiments with isotopically labeled precursors clearly supported a polyketide origin for the formal monoterpenoid gibepyrone A, whereas the terpenoid pathway could be excluded.

Sound of silence: the beauvericin cluster in Fusarium fujikuroi is controlled by cluster-specific and global regulators mediated by H3K27 modification.

In this study, we compared the secondary metabolite profile of Fusarium fujikuroi and the histone deacetylase mutant ΔHDA1. We identified a novel peak in ΔHDA1, which was identified as beauvericin (BEA). Going in line with a 1000-fold increased BEA production, the respective non-ribosomal peptide synthetase (NRPS)-encoding gene (BEA1), as well as two adjacent genes (BEA2-BEA3), were significantly up-regulated in ΔHDA1 compared to the wild type.

Two separate key enzymes and two pathway-specific transcription factors are involved in fusaric acid biosynthesis in Fusarium fujikuroi.

Fusaric acid (FSA) is a mycotoxin produced by several fusaria, including the rice pathogen Fusarium fujikuroi. Genes involved in FSA biosynthesis were previously identified as a cluster containing a polyketide synthase (PKS)-encoding (FUB1) and four additional genes (FUB2-FUB5). However, the biosynthetic steps leading to FSA as well as the origin of the nitrogen atom, which is incorporated into the polyketide backbone, remained unknown.

Isolation and Structure Elucidation of Fujikurins A-D: Products of the PKS19 Gene Cluster in Fusarium fujikuroi.

Fusarium fujikuroi is a member of the Gibberella fujikuroi species complex and well known for the production of gibberellins and mycotoxins including fusarins and fusaric acid. A recent genome sequencing study revealed that the fungus has the genetic potential to produce many more secondary metabolites than have been reported. This paper describes the structure elucidation of the products of the cryptic and silent PKS19 gene cluster that were recently identified (fujikurins A-D).

Repletion of Iron Stores With the Use of Oral Iron Supplementation in Patients With Systolic Heart Failure.

Background: Iron deficiency is associated with reduced functional capacity and increased mortality in patients with heart failure with reduced ejection fraction (HFrEF). Correction of iron deficiency in HFrEF patients with the use of intravenous iron improves symptoms, quality of life, and exercise performance. Whether oral iron improves iron stores in HFrEF patients is unknown.