RNA Vaccine: novel approach for cancer treatment

Cancer is still an unsolved puzzle and a major cause of mortality and morbidity in the world. Today, about one in every thousand people is dying due to cancer. No effective agent has yet been found which can cure cancer in its metastatic stage. However, attempts in the shape of chemotherapy, immunotherapy and vaccines are made worldwide to find a remedy through a proper regimen. In continuation, tumor specific mRNA has been introduced as part of vaccines in recent days. It is mostly used in transfection with Dendritic Cells (DCs) for better effectiveness and safety. The DCs are selected for transfection because they are highly potent Antigen Presenting Cells (APCs) with the ability to take up & process tumor antigen in peripheral blood & tissues and can also migrate to the draining lymph nodes to present antigen to naïve T lymphocytes & induce the immune response.
Although initially the RNA vaccination was administered alone, due to its unstable and easily degradable nature, it was found to be quite less effective, which led it to be used in combination with some stability enhancers’ viz. RNA packaging in liposomes. They not only increased its stability, but even worked as active immune stimulators as well. RNA could remain stable. Although it showed significant promise in cancer treatment, immune suppression was noticed after vaccination. To enhance the effectiveness it is now being used in combination with few drugs viz. SUNITINIB which can reduce the suppressive effect of suppressor cells. It might be a good choice for combined therapy with RNA vaccine.
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Manned flying systems /mfs/ cryogenic engine

Comparison of performance of cryogenic propulsion system with earth storable propulsion system for manned flying syste

Performance Assessment of Six Public Health Programs in Katsina State, Nigeria

This research aimed to evaluate the performance of six ongoing public health programs through core performance indicators in Katsina State, Nigeria. The healthcare delivery in Africa is mostly program-based. This requires that such programs need to be evaluated which may in turn help to identify any existing gaps towards the improvement of patients' access and coverage to their given service. We identified all active health facilities where our programs on malaria, Routine Immunization (RI), Family Planning (FP), Tuberculosis and Leprosy (TBL), HIV/AIDS, and Free Medicare (FMC) were being carried out. After that, a representative sample was derived to obtain data regarding five key performance indicators by using a Logistics Indicators Assessment Tool. Of 1,718 facilities, a total of 983 (57.22%) were visited, In other words, by assuming a normal distribution; each facility expectedly covers only 3,371 individuals. All programs provided different and diverse results on each indicator; however, the most obvious challenge was in the stock-out and demand vs. receipt of required medications. These are particularly for malaria, FMC, FP, and HIV. For instance, the stock-out lasted 222 days for malaria and 135 days for FP. Despite this, none of the programs had a lower than gold-standard near-term availability of required products. Program-based healthcare delivery is inadequate and ineffective unless the local system gets simultaneously developed. If required medications are not becoming available, optimal access, coverage, and benefits cannot be expected to be obtained. Clearly, Nigeria experiences a push system of meeting term supplies. Nigeria needs to strengthen its pharmaceutical system

Simultaneous solution of non-linear algebraic equations Technical memorandum no. 163

Digital computer program for nonlinear equation sets characteristic of filter circuit analysi

Enhanced Critical parameters of nano-Carbon doped MgB2 Superconductor

The high field magnetization and magneto transport measurements are carried out to determine the critical superconducting parameters of MgB2-xCx system. The synthesized samples are pure phase and the lattice parameters evaluation is carried out using the Rietveld refinement. The R-T(H) measurements are done up to a field of 140 kOe. The upper critical field values, Hc2 are obtained from this data based upon the criterion of 90% of normal resistivity i.e. Hc2=H at which Rho=90%Rho; where RhoN is the normal resistivity i.e., resistivity at about 40 K in our case. The Werthamer-Helfand-Hohenberg (WHH) prediction of Hc(0) underestimates the critical field value even below than the field up to which measurement is carried out. After this the model, the Ginzburg Landau theory (GL equation) is applied to the R-T(H) data which not only calculates the Hc2(0) value but also determines the dependence of Hc2 on temperature in the low temperature high field region. The estimated Hc(0)=157.2 kOe for pure MgB2 is profoundly enhanced to 297.5 kOe for the x=0.15 sample in MgB2-xCx series. Magnetization measurements are done up to 120 kOe at different temperatures and the other parameters like irreversibility field, Hirr and critical current density Jc(H) are also calculated. The nano carbon doping results in substantial enhancement of critical parameters like Hc2, Hirr and Jc(H) in comparison to the pure MgB2 sample.Comment: 25 pages with 9 Figs: comments/suggestions([email protected]

Mapping of IgE-binding regions on recombinant Cyn d 1, a major allergen from Bermuda Grass Pollen (BGP)

<p>Abstract</p> <p>Background</p> <p>Bermuda grass (<it>Cynodon dactylon</it>; subfamily Chloridoideae) is an important source of seasonal aeroallergens in warm tropical and sub-tropical areas worldwide. Improved approaches to diagnosis and therapy of allergic diseases require a thorough understanding of the structure and epitopes on the allergen molecule that are crucial for the antigen-antibody interaction. This study describes the localization of the human IgE-binding regions of the major group 1 pollen allergen Cyn d 1 from Bermuda grass.</p> <p>Methods</p> <p>A cDNA library was constructed from Bermuda grass pollen (BGP) using a Lambda gt11 expression vector. The gene encoding the Cyn d 1 allergen was isolated by screening the library with a mouse monoclonal antibody raised against grass group 1 allergen. In order to characterize the IgE epitopes on Cyn d 1, seven overlapping fragments and three deletion mutants were cloned and over-expressed in E. coli. The recombinant fragments and deletion mutants were evaluated for their comparative IgE reactivity with sera of non atopic individuals and grass pollen allergic patients by ELISA and a dot-blot assay.</p> <p>Results</p> <p>Analysis of IgE binding regions by overlapping fragments and deletion mutants identified two major allergenic regions corresponding to amino acids 120–170 and 224–244. Deletion of either or both regions led to a significant reduction in IgE binding, emphasizing the importance of the C-terminal region on Cyn d 1 in epitope-IgE interaction.</p> <p>Conclusion</p> <p>Anti-Cyn d 1 IgE antibodies from allergic human sera recognize two epitopes located at the C-terminal end of the molecule. These data will enable the design of improved diagnostic and therapeutic approaches for BGP hypersensitivity.</p

The role of endoplasmic reticulum stress response in pollen development and heat stress tolerance

Endoplasmic reticulum (ER) stress is defined by a protracted disruption in protein folding and accumulation of unfolded or misfolded proteins in the ER. This accumulation of unfolded proteins can result from excessive demands on the protein folding machinery triggered by environmental and cellular stresses such as nutrient deficiencies, oxidative stress, pathogens, and heat. The cell responds to ER stress by activating a protective pathway termed unfolded protein response (UPR), which comprises cellular mechanisms targeted to maintain cellular homeostasis by increasing the ER’s protein folding capacity. The UPR is especially significant for plants as being sessile requires them to adapt to multiple environmental stresses. While multiple stresses trigger the UPR at the vegetative stage, it appears to be active constitutively in the anthers of unstressed plants. Transcriptome analysis reveals significant upregulation of ER stress-related transcripts in diploid meiocytes and haploid microspores. Interestingly, several ER stress-related genes are specifically upregulated in the sperm cells. The analysis of gene knockout mutants in Arabidopsis has revealed that defects in ER stress response lead to the failure of normal pollen development and enhanced susceptibility of male gametophyte to heat stress conditions. In this mini-review, we provide an overview of the role of ER stress and UPR in pollen development and its protective roles in maintaining male fertility under heat stress conditions

Pattern of antimicrobial usage for prophylaxis of surgical site infection in a tertiary care hospital of Western Uttar Pradesh

Background: The practice of giving antibiotic prophylaxis has resulted in the reduction of surgical site infections (SSI), thus reducing cost, morbidity, and mortality. Common nosocomial infections in surgical patients include SSIs, urinary tract infections (UTIs), pneumonias and blood stream infections (BSIs). The present study was, therefore, designed to analyze the efficacy of antimicrobials used for prophylaxis during surgery in a tertiary care hospital in India.Methods: Total 100 patients were enrolled. Name, timing, route, dose of antimicrobials given were recorded. All the relevant data was taken from the patient’s medication charts and medical records. Chi-square test and t-test were applied.Results: The optimal time of giving antimicrobial prophylaxis in present study was 1 hour before the surgery. A total of 8 different antimicrobials were prescribed to 100 patients, out of which most commonly prescribed were cephalosporin i.e. 82%. Majority of SSI (57.12%) occurred when the duration of surgical antimicrobial prophylaxis (SAP) was for ≥2 hours (p value <0.05). Common organisms seen in SSI were E. coli, S. aureus, Pseudomonas and Kleibsella species. The hospital stay of patients with SSI was more as compared to patients without SSI in present study (p value <0.05).Conclusions: It has been observed that inappropriate selection and timing of giving SAP play an important role in developing SSI, which can be adequately controlled by adopting SAP guidelines, good infection control practices and risk factor analysis

Biological parts for engineering abiotic stress tolerance in plants

It is vital to ramp up crop production dramatically by 2050 due to the increasing global population and demand for food. However, with the climate change projections showing that droughts and heatwaves becoming common in much of the globe, there is a severe threat of a sharp decline in crop yields. Thus, developing crop varieties with inbuilt genetic tolerance to environmental stresses is urgently needed. Selective breeding based on genetic diversity is not keeping up with the growing demand for food and feed. However, the emergence of contemporary plant genetic engineering, genome-editing, and synthetic biology offer precise tools for developing crops that can sustain productivity under stress conditions. Here, we summarize the systems biology-level understanding of regulatory pathways involved in perception, signalling, and protective processes activated in response to unfavourable environmental conditions. The potential role of noncoding RNAs in the regulation of abiotic stress responses has also been highlighted. Further, examples of imparting abiotic stress tolerance by genetic engineering are discussed. Additionally, we provide perspectives on the rational design of abiotic stress tolerance through synthetic biology and list various bioparts that can be used to design synthetic gene circuits whose stress-protective functions can be switched on/off in response to environmental cues

RNA-seq highlights molecular events associated with impaired pollen-pistil interactions following short-term heat stress in Brassica napus

The global climate change is leading to increased frequency of heatwaves with crops getting exposed to extreme temperature events. Such temperature spikes during the reproductive stage of plant development can harm crop fertility and productivity. Here we report the response of short-term heat stress events on the pollen and pistil tissues in a commercially grown cultivar of Brassica napus. Our data reveals that short-term temperature spikes not only affect pollen fitness but also impair the ability of the pistil to support pollen germination and pollen tube growth and that the heat stress sensitivity of pistil can have severe consequences for seed set and yield. Comparative transcriptome profiling of non-stressed and heat-stressed (40°C for 30 min) pollen and pistil (stigma + style) highlighted the underlying cellular mechanisms involved in heat stress response in these reproductive tissues. In pollen, cell wall organization and cellular transport-related genes possibly regulate pollen fitness under heat stress while the heat stress-induced repression of transcription factor encoding transcripts is a feature of the pistil response. Overall, high temperature altered the expression of genes involved in protein processing, regulation of transcription, pollen-pistil interactions, and misregulation of cellular organization, transport, and metabolism. Our results show that short episodes of high-temperature exposure in B. napus modulate key regulatory pathways disrupted reproductive processes, ultimately translating to yield loss. Further investigations on the genes and networks identified in the present study pave a way toward genetic improvement of the thermotolerance and reproductive performance of B. napus varieties