Safety vs price in the generic drug market: metformin.

Objectives: Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been recalled due to the presence of carcinogens, predominantly N-nitrosodimethylamine (NDMA), including an extensive recall of extended-release (ER) metformin products in 2020.

Study Design: Primary pharmaceutical quality testing and database analysis.

Presence of unsafe chemical impurities, accelerated evaporation of alcohol, and lack of key labeling requirements are risks and concerns for some alcohol-based hand sanitizers and dispenser practices during the COVID-19 pandemic.

Alcohol-based hand sanitizers (ABHS) have been an important hand hygiene tool during the COVID-19 pandemic. Recently, ABHS from non-traditional drug manufacturers have entered the market, triggered by a lack of ABHS availability. Some of these ABHS contain high levels of chemical impurities that may be harmful with frequent exposure.

Course-based prefaculty training program introduces instructional methods, increases instructor self-efficacy, and promotes professional development.

Graduate student and postdoctoral teaching assistants receive highly variable preparation for instructional methods because providing such training is often expensive. Therefore, we conducted an intensive, pedagogical boot camp followed by classroom observations, structured professional development discussions about leveraging the experience on the job market, individual exit interviews, and a letter of recommendation. Our data show the participants implemented new pedagogical techniques in their classrooms, showed increased self-efficacy, and reported appreciation for the training experience.

Identification and Characterization of JAK2 Pseudokinase Domain Small Molecule Binders.

Janus kinases (JAKs) regulate hematopoiesis via the cytokine-mediated JAK-STAT signaling pathway. JAKs contain tandem C-terminal pseudokinase (JH2) and tyrosine kinase (JH1) domains. The JAK2 pseudokinase domain adopts a protein kinase fold and, despite its pseudokinase designation, binds ATP with micromolar affinity.

Genome of Diaporthe sp. provides insights into the potential inter-phylum transfer of a fungal sesquiterpenoid biosynthetic pathway.

Fungi have highly active secondary metabolic pathways which enable them to produce a wealth of sesquiterpenoids that are bioactive. One example is Δ6-protoilludene, the precursor to the cytotoxic illudins, which are pharmaceutically relevant as anticancer therapeutics. To date, this valuable sesquiterpene has only been identified in members of the fungal division Basidiomycota.

Pyrrolocin A, a 3-Decalinoyltetramic Acid with Selective Biological Activity, Isolated from Amazonian Cultures of the Novel Endophyte Diaporthales sp. E6927E.

Natural products remain an important source of new therapeutics for emerging drug-resistant pathogens like Candida albicans, which particularly affects immunocompromised patients. A bioactive 3-decalinoyltetramic acid, pyrrolocin A, was isolated from extracts of a novel Amazonian fungal endophyte, E6927E, of the Diaporthales family. The structure of the natural product was solved using NMR and CD spectroscopy and it is structurally related to the fungal setins, equisetin and phomasetin, which are well-characterized tetramic acid antibiotics specific for Gram-positive organisms.

Stelliosphaerols A and B, Sesquiterpene-Polyol Conjugates from an Ecuadorian Fungal Endophyte.

Endophytic fungi are plant tissue-associated fungi that represent a rich resource of unexplored biological and chemical diversity. As part of an ongoing effort to characterize Amazon rainforest-derived endophytes, numerous fungi were isolated and cultured from plants collected in the Yasuní National Park in Ecuador. Of these samples, phylogenetic and morphological data revealed a previously undescribed fungus in the order Pleosporales that was cultured from the tropical tree Duroia hirsuta.

Fusaric acid induces a notochord malformation in zebrafish via copper chelation.

Over a thousand extracts were tested for phenotypic effects in developing zebrafish embryos to identify bioactive molecules produced by endophytic fungi. One extract isolated from Fusarium sp., a widely distributed fungal genus found in soil and often associated with plants, induced an undulated notochord in developing zebrafish embryos.

Biodegradation of polyester polyurethane by endophytic fungi.

Bioremediation is an important approach to waste reduction that relies on biological processes to break down a variety of pollutants. This is made possible by the vast metabolic diversity of the microbial world. To explore this diversity for the breakdown of plastic, we screened several dozen endophytic fungi for their ability to degrade the synthetic polymer polyester polyurethane (PUR).

Ancylostoma ceylanicum excretory-secretory protein 2 adopts a netrin-like fold and defines a novel family of nematode proteins.

Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A.

Structure-based analysis of Toxoplasma gondii profilin: a parasite-specific motif is required for recognition by Toll-like receptor 11.

Profilins promote actin polymerization by exchanging ADP for ATP on monomeric actin and delivering ATP-actin to growing filament barbed ends. Apicomplexan protozoa such as Toxoplasma gondii invade host cells using an actin-dependent gliding motility. Toll-like receptor (TLR) 11 generates an innate immune response upon sensing T.

Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion.

Dengue virus relies on a conformational change in its envelope protein, E, to fuse the viral lipid membrane with the endosomal membrane and thereby deliver the viral genome into the cytosol. We have determined the crystal structure of a soluble fragment E (sE) of dengue virus type 1 (DEN-1). The protein is in the postfusion conformation even though it was not exposed to a lipid membrane or detergent.