30 research outputs found
Association of Intronic Single Nucleotide Polymorphism (SNP) of CALM 1 gene with Osteoarthritis of the Knee in Indian Population: A Case-control Study
Osteoarthritis knee is one of the most prevalent disorders in the Indian subcontinent. The wide prevalence and varying features makes it a disease of disguise. Multiple etiological factors have been described. The most recent is genetic contribution in the causation of the disease. This case control study was conducted in the Department of Orthopaedic Surgery, CSM Medical University, Lucknow in collaboration with IIT, Kanpur. 120 cases and 120 controls were enrolled. Clinico-radiological features were noted and symptomatic clinical scoring was done. Genetic polymorphism in relation to intronic region of CALM 1 gene was studied by DNA extraction, Polymerase chain reaction (PCR) and Restriction fragment length polymorphism (RFLP) method. Statistical analysis was done using Stata software. There was no significant difference between age, sex and BMI among cases and controls (p value > .05). ESR (p value =0.0000), fasting blood sugar (p value= 0.0004) and serum uric acid (p value=0.0001) were significantly different among cases and controls. SNP was found in significantly higher number in cases than controls (p value = .0022). Heterozygosity was found only in 5 cases. Logistic regression has also proved significant association of occurrence of Single Nucleotide Polymorphism (SNP) with disease. CALM-1 gene intronic SNP (rs3213718) is present in Indian population. Occurrence of this SNP is significantly affecting the disease
The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system
Lafora disease (LD), a progressive form of inherited epilepsy, is associated with widespread neurodegeneration and the formation of polyglucosan bodies in the neurons. Laforin, a protein phosphatase, and malin, an E3 ubiquitin ligase, are two of the proteins that are defective in LD. We have shown recently that laforin and malin (referred together as LD proteins) are recruited to aggresome upon proteasomal blockade, possibly to clear misfolded proteins through the ubiquitin–proteasome system (UPS). Here we test this possibility using a variety of cytotoxic misfolded proteins, including the expanded polyglutamine protein, as potential substrates. Laforin and malin, together with Hsp70 as a functional complex, suppress the cellular toxicity of misfolded proteins, and all the three members of this complex are required for this function. Laforin and malin interact with misfolded proteins and promote their degradation through the UPS. LD proteins are recruited to the polyglutamine aggregates and reduce the frequency of aggregate-positive cells. Taken together, our results suggest that the malin–laforin complex is a novel player in the neuronal response to misfolded proteins and could be potential therapeutic targets for neurodegenerative disorders associated with cytotoxic proteins
Co-Administration of IL-1+IL-6+TNF-α with Mycobacterium tuberculosis Infected Macrophages Vaccine Induces Better Protective T Cell Memory than BCG
BCG has been administered globally for more than 75 years, yet tuberculosis (TB) continues to kill more than 2 million people annually. Further, BCG protects childhood TB but is quite inefficient in adults. This indicates that BCG fails to induce long-term protection. Hence there is a need to explore alternative vaccination strategies that can stimulate enduring T cell memory response. Dendritic cell based vaccination has attained extensive popularity following their success in various malignancies. In our previous study, we have established a novel and unique vaccination strategy against Mycobacterium tuberculosis (M. tb) and Salmonella typhimurium by utilizing infected macrophages (IM). In short-term experiments (30 days), substantial degree of protection was observed. However, remarkable difference was not observed in long-term studies (240 days) due to failure of the vaccine to generate long-lasting memory T cells. Hence, in the present study we employed T cell memory augmenting cytokines IL-1+IL-6+TNF-α and IL-7+IL-15 for the induction of the enhancement of long-term protection by the vaccine. We co-administered the M. tb infected macrophages vaccine with IL-1+IL-6+TNF-α (IM-1.6.α) and IL-7+IL-15 (IM-7.15). The mice were then rested for a reasonably large period (240 days) to study the bona fide T cell memory response before exposing them to aerosolized M. tb. IM-1.6.α but not IM-7.15 significantly improved memory T cell response against M. tb, as evidenced by recall responses of memory T cells, expansion of both central as well as effector memory CD4 and CD8 T cell pools, elicitation of mainly Th1 memory response, reduction in the mycobacterial load and alleviated lung pathology. Importantly, the protection induced by IM-1.6.α was significantly better than BCG. Thus, this study demonstrates that not only antigen-pulsed DCs can be successfully employed as vaccines against cancer and infectious diseases but also macrophages infected with M. tb can be utilized with great efficacy especially in protection against TB
Assessment of phagosomes infected with <i>Mycobacterium tuberculosis</i><span style="mso-bidi-font-style:italic"> as a vaccine candidate against tuberculosis </span>
1090-1097The present study describes a novel and
simple vaccination strategy that involve culturing of<i style="mso-bidi-font-style:
normal"> M. tuberculosis in the macrophage cells. Isolation of phagosome
from macrophage (cell line J774) infected with <i style="mso-bidi-font-style:
normal">M. tuberculosis (H37) and
M. bovis (BCG) at early and late
phase of infection was done ensuing the identification and characterization of
these phagosome. In vitro study of
apoptosis induced by phagosome infected with (H37) and (BCG) was performed. The
vaccine candidate with H37 MOI- 1:10 at 3 h, MOI- 1:20 at 1, 1.5, 2.5 and 3 h
and BCG MOI- 1:20 at 3.5 h showed percentage apoptosis as 38.64, 39.93, 34.66,
22.56,34.59 and 37.81% respectively. The results designates that macrophages provide
cellular niche during infection and illustrate considerable immunogenic
property. Novel antigens expressed or secreted by H37 in infected macrophages
can provide evidence to be a successful vaccine candidate as it endures
enhanced immune response than BCG
Attacks in Wireless Networks
Communications in wireless networks has been facilitating numerous emerging applications that require packet delivery from one or more senders to multiple receivers. Communications are susceptible to various kinds of attacks due to insecure wireless channels. Communications in wireless networks remains a challenging and critical issue. This paper presents recent advances in security requirements and services in communications in wireless networks. Wireless networks are being used in many commercial and military applications to collect event driven and real time data. Deployment nature of networks makes them vulnerable to security threats. Due to the resource limitations traditional security measures are not more enough to keep safe the nodes. Research in network security domains has produced several security solutions. In this paper we have observed security mechanisms. We have studied these security mechanisms with respect to packet overheads and compared the packet transmission time, average latency and energy consumption. The comparison shows that the packet overheads are lesser as compared to other schemes. It have been observed that packet delivery ratio decreases when we increase number of nodes while energy and latency increases
Evaluation of different generic in silico methods for predicting HLA class I binding peptide vaccine candidates using a reverse approach
Since CD8+ T cell response is crucial to combat intracellular infections and cancer, identification of class I HLA binding peptides is of immense clinical value. The experimental identification of such peptides is protracted and laborious. Exploiting in silico tools to discover such peptides is an attractive alternative. However, this approach needs a thorough assessment before its elaborate application. We have adopted a reverse approach to evaluate the reliability of eight different servers (inclusive of 55 predictors) by exploiting experimentally proven data. A comprehensive data set of more than 960 peptides was employed to test the efficacy of the programs. We have validated commonly used strategies to predict peptides that bind to seven most prevalent HLA class I alleles. We conclude that four of the eight servers are more adept in predictions. Although the overall predictions for class I MHC binders were superior to class II MHC binders, individual predictors for different alleles belonging to the same program were highly variable in their efficiencies. We have also addressed whether a consensus approach can yield better prediction efficiency. We observed that combining the results from different in silico programs could not increase the efficiency significantly