How does Recent Understanding of Molecular Mechanisms in Botulinum Toxin Impact Therapy?

Botulinum toxin, one of the most lethal toxins identified, is also used as a therapeutic agent for a variety of human conditions. The history of the discovery of botulinum toxin, an understanding of its function at the molecular level and its development into a therapeutic reagent are instructive and allow the reader to build a conceptual framework around which to understand its current therapeutic uses and consider potential further uses of botulinum toxin

Performance Analysis of Iterative IDMA Scheme in Power Line Communication Using Random Interleaver

Power line distribution networks are mainly used for electrical power supply.  The ever-increasing demand of low cost telecommunication, broadband and access to internet services has applied a driven force leading to further research in the field of power-line communication. Different multiplexing techniques, OFDM, CDMA, MC-CDMA, has been already used with power line communication. In this paper coded IDMA is being used with power line communication also the simulation and result has been described. Keywords: CDMA.IDMA,MC-CDMA,OFDM,Power line communication

Prevalence and incrimination of Anopheles fluviatilis species S (Diptera: Culicidae) in a malaria endemic forest area of Chhattisgarh state, central India

BACKGROUND: Chhattisgarh state in central India is highly endemic for malaria and contributes about 13% of annually reported malaria cases in the country with predominance of P. falciparum. Entomological investigations were carried out in a tribal forested area of district Bastar located in the southern part of Chhattisgarh state to record the prevalence of sibling species of Anopheles fluviatilis and An. culicifacies complexes. The vector species complexes were investigated at sibling species level for their biology in terms of resting and feeding behavior and malaria transmission potential. METHODS: Indoor resting vector mosquitoes collected during 2010–2011 were identified to sibling species by cytotaxonomy and polymerase chain reaction (PCR) assay. The blood meal source analysis and incrimination studies were done at sibling species level by counter current immunoelectrophoresis and enzyme linked immunosorbent assay (ELISA) respectively. RESULTS: Analysis of sibling species composition revealed predominance of An. fluviatilis species S in the study area, which was found to be highly anthropophagic and rested in human dwellings whereas the sympatric species T was primarily zoophagic. Incrimination studies showed high sporozoite rate in species S, thereby confirming its vectorial efficiency. An. culicifacies was encountered in low numbers and comprised species B and C in almost equal proportion. Both these species were found to be exclusively zoophagic. CONCLUSION: The observations made strongly suggest that species S of Fluviatilis Complex is the principal vector of malaria in certain forest areas of district Bastar, Chhattisgarh state and should be the target species for vector control operation. Vector control strategies based on biological characteristics of Fluviatilis S will lead to substantial decline in malaria incidence in such areas

Correlation of mitotic activity and Ki 67 with BR score and molecular classification in carcinoma breast

Background: To determine if mitotic activity played a role in classifying breast cancer in terms of its biological behaviour. We investigated the prospect of identifying a more meaningful cell proliferation marker for categorising treatment-naive breast cancer. Methods: The 150 cases diagnosed as invasive breast carcinoma in the histopathology section were systematically studied for the clinical, gross, and microscopic features. Results: the 50% patients were grade 2 (75), 41% were grade 3 (71) and 9% (14) were grade 1 in present study. The distribution of intrinsic subtypes was luminal A 25% (38), luminal B 59% (88), HER2 enriched 10% (15), basal 6% (9). Out of 150 cases, 29% (43) cases were T1, T2 were 65% (97), T3 were 2% (4), T4 were 4% (6). Mean Ki 67 was 15.6±8.8 in grade 1, 23.3±15.4 and 38.2± in grade 3. There was significant difference between I and III, and II and III (p<0.05). Mean mitotic count in grade 1 was 5.4±2.7, in grade 2 it was 9.7±13.5, in grade 3 it was 16.1±6.9. There was significant difference between grade 1 and 2, grade 2 and 3, grade 1 and 3 (p<0.05). There was significant difference between T stages (p<0.05). Conclusions: Ki 67 showed a more significant statistical correlation with prognostic factors as compared to mitotic count; we feel Ki 67 is more superior to mitotic count as a prognostic factor.

Dopamine Receptor and Gα(olf) Expression in DYT1 Dystonia Mouse Models during Postnatal Development

Background: DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated. Methodology/Principal Findings We used Dyt1 knock out (Dyt1 KO), Dyt1 ΔGAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT) or human ΔGAG mutant allele (DYT1 hMT). D1R, D2R, and Gα(olf) protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60) male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf) protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice. Conclusion/Significance We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology

Endophytic microbes modulate plant responses to abiotic stresses: a review

Many groups of microorganisms have been studied for their benefits towards humankind due to their capacity to produce natural compounds that can be valorized in many economic sectors such as agriculture. Due to the extensive use of chemicals pesticides and fertilizers, current agriculture systems facing several major problems such as emergence of resistant in pathogens and pests, soil infertility and bioaccumulation of toxic residues in the environment and particularly in foods which negatively affects human health. The use of natural products harmless to plants, humans and biodegradable constitute a promising way to overcome these problems. Modern agriculture systems are moving toward the use of beneficial microorganisms isolated from the soil, plant surfaces and inside tissues for developing eco-friendly products such as biofertilizers and biopesticides. Recent literatures show that colonization of plants by endophytes is the rule in nature and endophyte-free plant is a rare exception. Endophytes are microbes living inside plant tissues and supporting them in growth and development, as well as stresses tolerance without causing any apparent disease symptom. Abiotic stresses have a great impact on growth, production and health of plants. Many literatures show the role of endophytes in abiotic stress tolerance as well as mechanisms involved to cope with these constraints via the induction of stress-related genes and molecules. This review provides a summary of literature on how endophytes modulate plant growth and responses to abiotic stresses which may help to better understand their role in plant adaptation to environmental constraints and valorize their use in agriculture

Dopa-Responsive Dystonia: Functional Analysis of Single Nucleotide Substitutions within the 5’ Untranslated GCH1 Region

Background: Mutations in the GCH1 gene are associated with childhood onset, dopa-responsive dystonia (DRD). Correct diagnosis of DRD is crucial, given the potential for complete recovery once treated with L-dopa. The majority of DRD associated mutations lie within the coding region of the GCH1 gene, but three additional single nucleotide sequence substitutions have been reported within the 5’ untranslated (5’UTR) region of the mRNA. The biologic significance of these 5’UTR GCH1 sequence substitutions has not been analyzed. Methodology/Principal Findings Luciferase reporter assays, quantitative real time PCR and RNA decay assays, combined with bioinformatics, revealed a pathogenic 5’UTR GCH1 substitution. The +142C>T single nucleotide 5’UTR substitution that segregates with affected status in DRD patients, substantially attenuates translation without altering RNA expression levels or stability. The +142C>T substitution disrupts translation most likely by creating an upstream initiation start codon (uAUG) and an upstream open reading frame (uORF). Conclusions/Significance: This is the first GCH1 regulatory substitution reported to act at a post-transcriptional level, increasing the list of genetic diseases caused by abnormal translation and reaffirming the importance of investigating potential regulatory substitutions in genetic diseases