Possible involvement of DNA breaks in epigenetic regulation of cell differentiation

The review summarizes the authors’ and literature data on accumulation of DNA breaks in differentiating cells. Large 50-kb free DNA fragments were observed by several research teams in non-apoptotic insect, mammal, and plant cells. More intense DNA breakage was observed during maturation of spermatides, embryo development, and differentiation of myotubes, epidermal cells, lymphocytes, and neutrophils. In general, accumulation of DNA breaks in differentiating cells cannot be attributed to a decrease in the DNA repair efficiency. Poly(ADP)ribose synthesis often follows the DNA breakage in differentiating cells. We hypothesize that DNA fragmentation is an epigenetic tool for regulating the differentiation process. Scarce data on localization of the differentiation-associated DNA breaks indicate their preferable accumulation in specific DNA sequences including the nuclear matrix attachment sites. The same sites are degraded at early stages of apoptosis. Recent data on non-apoptotic function of caspases provide more evidence for possible existence of a DNA breakage mechanism in differentiating cells, resembling the initial stage of apoptosis. Excision of methylated cytosine and recombination are other possible explanations of the phenomenon. Elucidation of mechanisms of differentiation-induced DNA breaks appears to be a prospective research direction.     

Diversity,Community Composition,and Dynamics of Nonpigmented and Late-Pigmenting Rapidly Growing Mycobacteria in an Urban Tap Water Production and Distribution System

Nonpigmented and late-pigmenting rapidly growing mycobacteria (RGM) have been reported to commonly colonize water production and distribution systems. However, there is little information about the nature and distribution of RGM species within the different parts of such complex networks or about their clustering into specific RGM species communities. We conducted a large-scale survey between 2007 and 2009 in the Parisian urban tap water production and distribution system. We analyzed 1,418 water samples from 36 sites, covering all production units, water storage tanks, and distribution units; RGM isolates were identified by using rpoB gene sequencing. We detected 18 RGM species and putative new species, with most isolates being Mycobacterium chelonae and Mycobacterium llatzerense. Using hierarchical clustering and principal-component analysis, we found that RGM were organized into various communities correlating with water origin (groundwater or surface water) and location within the distribution network. Water treatment plants were more specifically associated with species of the Mycobacterium septicum group. On average, M. chelonae dominated network sites fed by surface water, and M. llatzerense dominated those fed by groundwater. Overall, the M. chelonae prevalence index increased along the distribution network and was associated with a correlative decrease in the prevalence index of M. llatzerense, suggesting competitive or niche exclusion between these two dominant species. Our data describe the great diversity and complexity of RGM species living in the interconnected environments that constitute the water production and distribution system of a large city and highlight the prevalence index of the potentially pathogenic species M. chelonae in the distribution network.     

Spongelike alginate nanoparticles as a new potential system for the delivery of antisense oligonucleotides.

The aim of this study was to design a new antisense oligonucleotide (ON) carrier system based on alginate nanoparticles and to investigate its ability to protect ON from degradation in the presence of serum. Pharmacokinetics and tissue distribution of ON-loaded nanoparticles have been determined after intravenous administration. An original and dynamic process for ON loading into polymeric nanoparticles has been applied. It is based on the diffusion of ON or ON/polylysine complex into the nanoparticle or the alginate gel, respectively. Indeed, the single coincubation of ON with nanoparticles led, within a few days, to an extremely efficient association. The diffusion kinetic of ON was shown to be dependent on several parameters, incubation temperature, ON concentration, presence or absence of polylysine, polylysine molecular weight, and nanoparticle preparation procedure. This new alginate-based system was found to be able to protect [33P]-radiolabeled ON from degradation in bovine serum medium and to modify their biodistribution, as an important accumulation of radioactivity was observed in the lungs, in the liver, and in the spleen after intravenous administration into mice. ON may be associated efficiently with calcium alginate in a colloidal state. Such nanosponges are promising carriers for specific delivery of ON to lungs, liver, and spleen.     

Erosion of the foramen transversarium of the axis. Anatomical observations

Six hundred foramina transversaria (FT) of the axis vertebrae of 4 population groups were examined for the presence of erosion of the lateral articular mass. Of these, 127 (21%) and 72 (12%) presented with moderate and marked erosion, respectively. Evidence is presented incriminating the tortuosity of the vertebral artery as well as congenital factors in the etiology of the erosion of the FT. Attention is drawn to the possible correlation between angulation of the transverse process of the axis and erosion of the FT.     

Exocoelomic internal hernia: elucidation of Papez's concept.

Two internal herinias of the intestines were found in adult males. One was a large translucent avascular membranous sac contining the small intestine from the duodenojejunal flexure to a point 6 in. proximal to the ileocaecal junction. The other was a peritoneal sac enclosing the small intestine, appendix, caecum and 6 in. of the ascending colon. The mesenteric and colic vessels were normal. Both hernias conformed to PAPEZ's concept of the so-called paraduodenal hernia that the hernial sac is derived from the umbilical coelom. The authors suggest that most of the so-called paraduodenal hernias are derived from the embryonic umbilical peritoneal diverticulum rather than from the peritoneal recesses or mesentery of the colon.     

Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat.

The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney.