Biotechnological applications of microbial bioconversions

Modern research has focused on the microbial transformation of a huge variety of organic compounds to obtain compounds of therapeutic and/or industrial interest. Microbial transformation is a useful tool for producing new compounds, as a consequence of the variety of reactions for natural products. This article describes the production of many important compounds by biotransformation. Emphasis is placed on reporting the metabolites that may be of special interest to the pharmaceutical and biotechnological industries, as well as the practical aspects of this work in the field of microbial transformations.     

A Study of Maternal and Maternal Interaction Effects in Diallel Crosses

The analysis of diallel crosses by including the components due to maternal effect and maternal interaction effects have been presented for Griffing method—1 (random effect model) and Griffing method—3 (fixed and random effect model). Wherever exact test of significance is not possible, testing procedure using Satterthwaite (1946) approximation has been presented.     

Gadopentatic acid affects in vitro proliferation and doxorubicin response in human breast adenocarcinoma cells

Contrasting agents (CAs) that are administered to patients during magnetic resonance imaging to facilitate tumor identification are generally considered harmless. However, gadolinium (Gd) based contrast agents can be retained in the body, inflicting specific cell line cytotoxicity. We investigate the effect of Gadopentatic acid (Gd-DTPA) on human breast adenocarcinoma MCF-7 cells. These cells exhibit a toggle switch response: exposure to 0.1 and 1 mM concentrations of Gd-DTPA enhances proliferation, which is hindered at a higher 10 mM concentration. Proliferation is enhanced when cells transition to 3D morphologies in post confluent conditions. The proliferation dependence on the concentration of CA is absent for Hs 578T and MDA-MB-231 triple negative cell lines. MCF-7 cells reveal a double toggle switch related to the expression of VEGF, which goes through high–low–high downregulation when cells are exposed to 0.1, 1, and 10 mM Gd-DTPA, respectively. Finally, doxorubicin drug response is assessed, which also reveals a double toggle switch behavior, where drug cytotoxicity exhibits a nonlinear dependence on the CA concentration. A toggle switch in cell characteristics that are exposed to 1 mM of Gd-DTPA amplifies the importance of this threshold, affecting several cell behaviors if surpassed. This work emphasizes the important effects that CAs can have on cells, specifically Gd-DTPA on MCF-7 cells, and the implications for cell growth and drug response during clinical and synthetic biology procedures.     

Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis

1. Download high-res image (111KB)
2. Download full-size image

     

Indole acids as a novel PDE2 inhibitor chemotype that demonstrate pro-cognitive activity in multiple species

An internal HTS effort identified a novel PDE2 inhibitor series that was subsequently optimized for improved PDE2 activity and off-target selectivity. The optimized lead, compound 4, improved cognitive performance in a rodent novel object recognition task as well as a non-human primate object retrieval task. In addition, co-crystallization studies of close analog of 4 in the PDE2 active site revealed unique binding interactions influencing the high PDE isoform selectivity.