Understanding Miro GTPases: Implications in the Treatment of Neurodegenerative Disorders

The Miro GTPases represent an unusual subgroup of the Ras superfamily and have recently emerged as important mediators of mitochondrial dynamics and for maintaining neuronal health. It is now well-established that these enzymes act as essential components of a Ca²⁺-sensitive motor complex, facilitating the transport of mitochondria along microtubules in several cell types, including dopaminergic neurons. The Miros appear to be critical for both anterograde and retrograde mitochondrial transport in axons and dendrites, both of which are considered essential for neuronal health. Furthermore, the Miros may be significantly involved in the development of several serious pathological processes, including the development of neurodegenerative and psychiatric disorders. In this review, we discuss the molecular structure and known mitochondrial functions of the Miro GTPases in humans and other organisms, in the context of neurodegenerative disease. Finally, we consider the potential human Miros hold as novel therapeutic targets for the treatment of such disease.     

Lead‐induced DNA damage and cell apoptosis in human renal proximal tubular epithelial cell: Attenuation via N‐acetyl cysteine and tannic acid

This study investigates the exposure of lead‐induced reactive oxygen species (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic intervention using antioxidants in human renal proximal tubular cells (HK‐2 cells). Following treatment of HK‐2 cells with an increasing concentration of lead nitrate (0–50 μM) for 24 h, the intracellular ROS level increased whereas the GSH level decreased significantly in a dose‐dependent manner. Comet assay results revealed that lead nitrate showed the ability to increase the levels of DNA strand breaks in HK‐2 cells. Lead exposure also induced apoptosis through caspase‐3 activation at 30 μg/mL. Pretreatment with N‐acetylcysteine (NAC) and tannic acid showed a significant ameliorating effect on lead‐induced ROS, DNA damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the DNA damage and apoptosis via caspase‐3 activation. Additionally, supplementation of antioxidants such as NAC and tannic acid may be used as salvage therapy for lead‐induced DNA damage and apoptosis in an exposed person.     

Reverse Genetics for Peste des Petits Ruminants Virus: Current Status and Lessons to Learn from Other Non-segmented Negative-Sense RNA Viruses

Peste des petits ruminants (PPR) is a highly contagious transboundary animal disease with a severe socio-economic impact on the livestock industry, particularly in poor countries where it is endemic. Full understanding of PPR virus (PPRV) pathobiology and molecular biology is critical for effective control and eradication of the disease. To achieve these goals, establishment of stable reverse genetics systems for PPRV would play a key role. Unfortunately, this powerful technology remains less accessible and poorly documented for PPRV. In this review, we discussed the current status of PPRV reverse genetics as well as the recent innovations and advances in the reverse genetics of other non-segmented negative-sense RNA viruses that could be applicable to PPRV. These strategies may contribute to the improvement of existing techniques and/or the development of new reverse genetics systems for PPRV.     

Coil embolization of intralobar pulmonary sequestration - an alternative to surgery: a case report

Background

Pulmonary sequestration is a congenital lung disease characterized by nonfunctioning pulmonary tissue that lacks normal communication with the bronchial tree and is supplied by a nonpulmonary systemic artery. Symptomatic bronchopulmonary sequestration is uncommon, seen more frequently in the pediatric population than in adults. It has traditionally been treated with surgical resection; however, a limited but growing number of cases have been treated with angiographic embolization. Given the inherent risks of cardiothoracic surgery, embolization of the anomalous vessel is an enticing alternative treatment. We present a case of a 56-year-old woman with known, symptomatic, intralobar pulmonary sequestration that was successfully treated with coil embolization.

Case presentation

A 56-year-old Pacific Islander woman with a history of chronic myeloid leukemia was admitted to the hospital with an episode of hemoptysis. Computed tomography of the chest demonstrated left lower lobe intralobar pulmonary sequestration fed by a large tortuous vessel branching off of the descending thoracic aorta. Surgical resection of the sequestration is the current standard treatment strategy of symptomatic intralobar pulmonary sequestration. The cardiothoracic surgeon noted that given the size and location of arterial blood supply, intervention would involve thoracotomy and lobectomy. The interventional radiologist offered embolization of the lesion as an alternative to surgery. Multiple coils, 6–13 mm in size, were used to embolize the sequestration. No considerable flow distal to the coils was noted postembolization.

Conclusions

Intralobar pulmonary sequestration is a rare condition that typically requires surgical management. This case demonstrates the efficacy of coil embolization as an alternative management strategy. To date, limited case reports of adults treated with endovascular embolization exist. Treatment of symptomatic pulmonary sequestration with embolization can be considered as an alternative to surgical resection.

     

Sodium chloride induced changes in leaf growth, and pigment and protein contents in two rice cultivars

Rice (Oryza sativa L.) seedlings were grown under NaCl stress. The leaf growth of resistant cv. Damodar was less affected than that of the susceptible cv. Jaya. The leaf protein content showed no distinct cultivar or age dependent differences under NaCl salinity. There was a significant increase in chlorophyll (Chl) and carotenoid (Car) contents of 25-d-oldseedlings of both cv. Jaya and cv. Damodar. However, Chl and Car content of 15-d-old seedlings of cv. Jaya decreased and that of cv. Damodar increased, under NaCl stress. This revised version was published online in July 2006 with corrections to the Cover Date.     

Rapid detection of 6-phosphogluconate dehydrogenase variants by electrophoresis on cellulose acetate gel

A procedure, suitable even under field conditions for the rapid detection of 6-phosphogluconate dehydrogenase electrophoretic variants, is described.Work supported by N.I.H.—grant no. ROI GM 13415.     

Biochemical aspects of the developing and ripening banana

The peel and pulp of the banana fruit and the pseudostem were examined for glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and aldolase activities and protein, phenolics, chlorophyll and starch. The peel-pulp ratio at various stages of fruit development on the plant and in detached fruits showing incipient ripening were used as an index of the physiological age of the fruit. The enzymes exhibited maximum activity at a stage corresponding to the initiation of the climacteric. GPT level at this stage was higher than that of GOT. An initial increase in the protein content was followed by a decline in both peel and pulp, the level reaching a minimum in climacteric fruits. Astringency, measured in terms of total phenolics, decreased with development; in mature fruits, peel contained 4–5 × as much phenolics as pulp. Chlorophyll in mature fruits was 10 × higher than in young fruits and decreased in ripe fruits. The onset of ripening was attended with a pronounced decrease in the starch. The various analyses were carried out also on the pseudostem removed from the plant soon after flower formation.     

Molecular analysis of the role of streptococcal pyrogenic exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes

Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (SPEA), in the pathogenesis of necrotizing soft-tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. SPEA can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild-type spea gene in an M1 streptococcal isolate. Supernatants from toxin-negative mutant bacteria demonstrated a 50% reduction in pro-mitogenic activity in HLA DQ-positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild-type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain-induced mortality was seen after intravenous infection. Intramuscular infection with the SPEA-negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified SPEA led to a dose-dependent increase in peritoneal neutrophils 6 h after administration. SPEA is not a critical virulence factor in invasive soft-tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.