Antibacterial and mechanism of action studies of boxazomycin A.

Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors.

History and Prospects of Drug Discovery and Development Collaboration between Industry and Academia.

Research collaborations and licensing deals are critical for the discovery and development of life-saving drugs. This practice has been ongoing since the inception of the pharmaceutical industry. The current process of drug discovery and development is complex, regulated, and highly regimented, having evolved over time.

Discovery, synthesis, activities, structure-activity relationships, and clinical development of combretastatins and analogs as anticancer drugs. A comprehensive review.

Covering: 1982 to up to the end of 2022Bioassay guided purification of the extracts of led to the discovery of six series of combretastatins A-D with cytotoxic activities ranging from sub nM to >50 μM ED's against a wide variety of cancer cell lines. Of these, -stilbenes combretastatins A-4 and A-1 were the most potent, exhibiting efficacy against a wide variety of tumor types in murine models. These antimitotic agents inhibited tubulin polymerization by reversibly binding to the colchicine binding sites.

Impact of novel microbial secondary metabolites on the pharma industry.

Microorganisms are remarkable producers of a wide diversity of natural products that significantly improve human health and well-being. Currently, these natural products comprise half of all the pharmaceuticals on the market. After the discovery of penicillin by Alexander Fleming 85 years ago, the search for and study of antibiotics began to gain relevance as drugs.

Our microbes not only produce antibiotics, they also overproduce amino acids.

Fermentative production of amino acids is an important goal of modern biotechnology. Through fermentation, micro-organisms growing on inexpensive carbon and nitrogen sources can produce a wide array of valuable products including amino acids. The amino acid market is $8 billion and mainly impacts the food, pharmaceutical and cosmetics industries.

Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid.

Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models.

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.

Development of a semi-defined medium supporting production of platensimycin and platencin by Streptomyces platensis.

Platensimycin and platencin are compounds that were discovered at Merck Research Laboratories and have shown promising antibacterial activity. They are both produced in fermentation by the actinomycete Streptomyces platensis. Merck reported a crude, insoluble production medium to produce the antibiotics.

Essential role of genetics in the advancement of biotechnology.

Microorganisms are one of the greatest sources of metabolic and enzymatic diversity. In recent years, emerging recombinant DNA and genomic techniques have facilitated the development of new efficient expression systems, modification of biosynthetic pathways leading to new metabolites by metabolic engineering, and enhancement of catalytic properties of enzymes by directed evolution. Complete sequencing of industrially important microbial genomes is taking place very rapidly and there are already hundreds of genomes sequenced.

Penicillin: the medicine with the greatest impact on therapeutic outcomes.

The principal point of this paper is that the discovery of penicillin and the development of the supporting technologies in microbiology and chemical engineering leading to its commercial scale production represent it as the medicine with the greatest impact on therapeutic outcomes. Our nomination of penicillin for the top therapeutic molecule rests on two lines of evidence concerning the impact of this event: (1) the magnitude of the therapeutic outcomes resulting from the clinical application of penicillin and the subsequent widespread use of antibiotics and (2) the technologies developed for production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today.

Platensimycin and platencin: promising antibiotics for future application in human medicine.

Platensimycin and platencin are novel antibiotics produced by Streptomyces platensis. They are potent and non-toxic natural products active against Gram-positive pathogens, including antibiotic-resistant strains and Mycobacterium tuberculosis. They were isolated using an intriguing target-based whole-cell antisense differential sensitivity assay as inhibitors of fatty acid biosynthesis of type II.

Natural products for cancer chemotherapy.

For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti-tumour activity.

Effect of implementing a computerized system for bone mineral density storage and report preparation on result turnaround time and savings in cost, time, and space.

Objective: To evaluate whether introduction of a densitometry workflow, data-storage, and reporting software system would result in streamlined workflow with fewer expenses and quicker result turnaround time.

Methods: BoneStation was implemented March 30, 2009, in a large, urban, tertiary referral center performing more than 6000 bone mineral density studies annually at 3 different geographic sites. The times of scan acquisition, report preparation, and final signature in the online medical record were recorded, and the delays from scan to report and from scan to final signature in the online medical record were calculated for each patient during 2 representative weeks before (n = 274) and 2 weeks after (n = 235) implementation of BoneStation.

Biosolutions to the energy problem.

We are in an energy crisis caused by years of neglect to alternative energy sources. There are many possible solutions and a number of these are based on microorganisms. These include bioethanol, biobutanol, biodiesel, biohydrocarbons, methane, methanol, electricity-generating microbial fuel cells, and production of hydrogen via photosynthetic microbes.

Working-age persons with multiple sclerosis and access to disease-modifying medications.

US residents can face serious financial barriers to obtaining prescription medications, including disease-modifying medications for multiple sclerosis (MS). We conducted 30-min telephone surveys with 983 persons with MS nationwide, 21-64 years old, to explore how financial and health insurance concerns affect access to services including MS drugs. Almost everyone (96.

Relation between number of component views and accuracy of left ventricular mass determined by three-dimensional echocardiography.

Three-dimensional echocardiography (3DE) allows the accurate determination of left ventricular (LV) mass, but the optimal number of component or extracted 2-dimensional (2D) image planes that should be used to calculate LV mass is not known. This study was performed to determine the relation between the number of 2D image planes used for 3DE and the accuracy of LV mass, using cardiovascular magnetic resonance (CMR) imaging as the reference standard. Three-dimensional echocardiography data sets were analyzed using 4, 6, 8, 10 and 20 component 2D planes as well as biplane 2D echocardiography and CMR in 25 subjects with a variety of LV pathologies.

Disruption of neuronal migration by RNAi of Dyx1c1 results in neocortical and hippocampal malformations.

The brains of individuals with developmental dyslexia have neocortical neuronal migration abnormalities including molecular layer heterotopias, laminar dysplasias, and periventricular nodular heterotopias (PNH). RNA interference (RNAi) of Dyx1c1, a candidate dyslexia susceptibility gene, disrupts neuronal migration in developing embryonic neocortex. Using in utero electroporation, we cotransfected cells in the rat neocortical ventricular zone (VZ) at E14/15 with short hairpin RNA vectors targeting Dyx1c1 along with either plasmids encoding enhanced green fluorescent protein or plasmids encoding monomeric red fluorescent protein only.

Teaching medical students about communicating with patients with major mental illness.

Persons with major mental illness often have chronic diseases and poor physical health. Therefore, all practicing physicians should learn about communicating effectively with these patients. Few efforts to teach medical students communication skills have specifically targeted patients with major mental illness.

Involvement of nitrogen-containing compounds in beta-lactam biosynthesis and its control.

Biosynthesis of beta-lactam antibiotics by fungi and actinomycetes is markedly affected by compounds containing nitrogen. The different processes employed by the spectrum of microbes capable of making these valuable compounds are affected differently by particular compounds. Ammonium ions, except at very low concentrations, exert negative effects via nitrogen metabolite repression, sometimes involving the nitrogen regulatory gene nre.

Histometric changes and cell death in the thalamus after neonatal neocortical injury in the rat.

Freezing injury to the developing cortical plate results in a neocortical malformation resembling four-layered microgyria. Previous work has demonstrated that following freezing injury to the somatosensory cortex, males (but not females) have more small and fewer large cells in the medial geniculate nucleus. In the first experiment, we examined the effects of induced microgyria to the somatosensory cortex on neuronal numbers, neuronal size, and nuclear volume of three sensory nuclei: ventrobasal complex, dorsal lateral geniculate nucleus, and medial geniculate nucleus.

Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis.

The present study was designed to determine whether cardiac inflammation is important for the successful homing of stem cells to the heart after intravenous injection in a murine myocarditis model. Male Bagg albino/c mice were infected with encephalomyocarditis virus (EMCV) to produce myocarditis. Subgroups of mice received single injections by tail vein of embryonic stem cells (ESCs) transfected with green fluorescent protein (GFP) as a marker at days 3, 14, or 60 after infection; other subgroups without stem cell injections were killed at each of these time points to assess the degree of inflammation present.