Multiplexed activity metabolomics for isolation of filipin macrolides from a hypogean actinomycete.

Chemical and biological stimulus screening in a hypogean actinomycete was used to elicit secondary metabolism. Optimal biosynthesis of bioactive natural products was identified using Multiplexed Activity Profiling for determining dose-dependent activity via six single-cell biological readouts. Bioactive extracts were fractioned to establish candidate compounds for isolation using Multiplexed Activity Metabolomics by correlating microtiter well-isolated phenotypes and extracted ion current peaks.

Making the match and breaking it: values, perceptions, and obstacles of trainees applying into physician-scientist training programs.

Background: Replenishing the physician-scientist workforce constitutes a central mission of medical education, but the loss of qualified trainees to non-academic positions remains an ongoing threat. Among the barriers facing physician-scientists today is the game-like model of U.S.

Apoptolidin family glycomacrolides target leukemia through inhibition of ATP synthase.

Cancer cells have long been recognized to exhibit unique bioenergetic requirements. The apoptolidin family of glycomacrolides are distinguished by their selective cytotoxicity towards oncogene-transformed cells, yet their molecular mechanism remains uncertain. We used photoaffinity analogs of the apoptolidins to identify the F subcomplex of mitochondrial ATP synthase as the target of apoptolidin A.

DebarcodeR increases fluorescent cell barcoding capacity and accuracy.

Fluorescent cell barcoding (FCB) enables efficient collection of tens to hundreds of flow cytometry samples by covalently marking cells with varying concentration of spectrally distinct dyes. A key consideration in FCB is to balance the density of dye barcodes, the complexity of cells in the sample, and the desired accuracy of the debarcoding. Unfortunately, barcoding bench and computational methods have not benefited from the high dimensional revolution in cytometry due to a lack of automated computational tools that effectively balance these common cytometry needs.

Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.

Reported here are novel formic-acid-mediated rearrangements of dearomatized acylphloroglucinols to access a structurally diverse group of synthetic acylphloroglucinol scaffolds (SASs). Density-functional theory (DFT) optimized orbital and stereochemical analyses shed light on the mechanism of these rearrangements. Products were evaluated by multiplexed activity profiling (MAP), an unbiased platform which assays multiple biological readouts simultaneously at single-cell resolution for markers of cell signaling, and can aid in distinguishing genuine activity from assay interference.

Bifunctional Nitrone-Conjugated Secondary Metabolite Targeting the Ribosome.

Many microorganisms possess the capacity for producing multiple antibiotic secondary metabolites. In a few notable cases, combinations of secondary metabolites produced by the same organism are used in important combination therapies for treatment of drug-resistant bacterial infections. However, examples of conjoined roles of bioactive metabolites produced by the same organism remain uncommon.

Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics.

Discovering bioactive metabolites within a metabolome is challenging because there is generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles and primary human tissue comprise a response platform used to discover novel microbial metabolites with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse effector mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling.

Sex differences in the corpus callosum of patients with schizophrenia.

The corpus callosum (CC) has been of interest in schizophrenia research because of its possible role in reduced lateralization and because of its sexually dimorphic characteristics. The literature has been replete with structural brain studies that have yielded equivocal results because of failure to address sex differences, handedness, and overall reductions in total brain volume (TBV) associated with schizophrenia. We performed midsagittal corpus callosum area MRI measurements on 71 chronically ill patients with schizophrenia (52 males, 19 females) and 67 controls (49 males, 18 females) using a semiautomated analytic technique subdividing the corpus callosum into five segments.

Making a difference for children: the medical community's role in improving child care.

The quality of child care for the majority of children in the United States is poor to mediocre. The lack of good quality child care has serious consequences for family stability, work force productivity, and child health and development. The medical community, especially pediatricians, family practitioners, nurses, and nurse practitioners, can play five key roles in helping to ensure that every child has a solid early foundation: 1) they can become trusted sources of support for parents, who are often isolated from their extended families and unsure about their new roles as parents; 2) they can give child care providers in the community information about health and safety practices; 3) they can provide preventive and diagnostic services to children in child care programs; 4) they can act as advocates for improved services to children and families; and 5) they can refer parents and siblings for care.

Cervicofacial mycobacterial adenitis in children: endemic to San Diego?

Nontuberculous mycobacteria (NTM) are an important cause of cervicofacial lymphadenitis in children. A dramatic increase has been seen in confirmed cases of NTM lymphadenitis in San Diego in the past few years. This report encompasses a span of 2 years 9 months, during which 22 children had confirmed NTM infection and another 14 had necrotizing granulomatous lymphadenitis in whom the specific diagnosis of NTM could not be made.