Using Current Data to Define New Approach in Age Related Macular Degeneration: Need to Accelerate Translational Research

Age related macular degeneration (AMD) is one of the major retinal degenerative disease of ageing whose complex genetic basis remains undeciphered. The involvement of various other factors like mitochondrial genes, cytoskeletal proteins and the role of epigenetics has been described in this review. Several population based AMD genetic studies have been carried out worldwide. Despite the increased publication of reports, clinical translation still eludes this davastating disease. We suggest models to address roadblocks in clinical translation hoping that these would be beneficial to drive AMD research towards innovative biomarkers and therapeutics Therefore, addressing the need large autopsy studies and combining it with efficient use of bioinformatic tools, statistical modeling and probing SNP-biomarker association are key to time bound resolution of this disease.     

Spiro Benzodiazepine Substituted Fluorocoumarins as Potent Anti-Anxiety Agents

Russian Journal of Bioorganic Chemistry - 1,5-Benzodiazepines are one of the important class of tranquilizers. The fusion of heterocyclic systems like coumarins and indolines with the...     

Insights into the mechanism of a novel shockwave-assisted needle-free drug delivery device driven by in situ-generated oxyhydrogen mixture which provides efficient protection against mycobacterial infections

Background

Needle-free, painless and localized drug delivery has been a coveted technology in the area of biomedical research. We present an innovative way of trans-dermal vaccine delivery using a miniature detonation-driven shock tube device. This device utilizes~2.5 bar of in situ generated oxyhydrogen mixture to produce a strong shockwave that accelerates liquid jets to velocities of about 94 m/s.

Method

Oxyhydrogen driven shock tube was optimized for efficiently delivering vaccines in the intradermal region in vivo. Efficiency of vaccination was evaluated by pathogen challenge and host immune response. Expression levels of molecular markers were checked by qRT-PCR.

Results

High efficiency vaccination was achieved using the device. Post pathogen challenge with Mycobacterium tuberculosis, 100% survival was observed in vaccinated animals. Immune response to vaccination was significantly higher in the animals vaccinated using the device as compared to conventional route of vaccination.

Conclusion

A novel device was developed and optimized for intra dermal vaccine delivery in murine model. Conventional as well in-house developed vaccine strains were used to test the system. It was found that the vaccine delivery and immune response was at par with the conventional routes of vaccination. Thus, the device reported can be used for delivering live attenuated vaccines in the future.

     

Development and Characterization of SSR Markers to Study Genetic Diversity and Population Structure of Horsegram Germplasm (<Emphasis Type="Italic">Macrotyloma uniflorum</Emphasis>)

Development of genomic resources in any crop is the pre-requisite for the construction of linkage map and implementation of molecular breeding strategies to develop superior cultivars. Large number of molecular markers are required to enrich the scanty information available in horsegram (Macrotyloma uniflorum).We employed the next-generation Illumina sequencing platform to develop a large number of microsatellite markers in this species. Of the total 23,305 potential SSRs motifs, 5755 primers were designed. Of these, 1425, 1310, 856, 1276, and 888 were of di-, tri-, tetra-, penta-, and hexa-nucleotide repeats respectively. Thirty polymorphic SSR primers and 24 morphological traits were used in 360 horsegram accessions to detect the genetic diversity and population structure. Thirty primers amplified 170 polymorphic alleles with an average of 5.6 alleles per primer having size 80 to 380 bp. The polymorphism information content (PIC) ranged from 0.15 to 0.76 with an average of 0.50, suggesting that SSR markers used in the study were polymorphic and suitable for characterization of horsegram germplasm. Dendrogram-based on Jaccard’s similarity coefficient and neighbor-joining tree grouped the horsegram accessions into two major clusters. Similarly, STRUCTURE analysis assigned genotypes into two gene pools namely Himalayan origin and Southern India. Diversity analysis based on 24 agro-morphological traits also suggested the presence of high level of diversity among the accessions.     

A density functional theory parameterised neural network model of zirconia

We have developed a Behler–Parrinello Neural Network (BPNN) that can be employed to calculate energies and forces of zirconia bulk structures with oxygen vacancies with similar accuracy as that of the density functional theory (DFT) calculations that were used to train the BPNN. In this work, we have trained the BPNN potential with a reference set of 2178 DFT calculations and validated it against a dataset of untrained data. We have shown that the bulk structural parameters, equation of states, oxygen vacancy formation energies and diffusion barriers predicted by the BPNN potential are in good agreement with the reference DFT data. The transferability of the BPNN potential has also been benchmarked with the prediction of structures that were not included in the reference set. The evaluation time of the BPNN is orders of magnitude less than corresponding DFT calculations, although the training process of the BPNN potential requires non-negligible amount of computational resources to prepare the dataset. The computational efficiency of the NN enabled it to be used in molecular dynamics simulations of the temperature-dependent diffusion of an oxygen vacancy and the corresponding diffusion activation energy.     

Comparative stemness and differentiation of luminal and basal breast cancer stem cell type under glutamine‐deprivation

Glutamine (gln) metabolism has emerged as a cancer therapeutic target in past few years, however, the effect of gln-deprivation of bCSCs remains elusive in breast cancer. In this study, effect of glutamine on stemness and differentiation potential of bCSCs isolated from MCF-7 and MDAMB-231 were studied. We have shown that bCSCs differentiate into CD24⁺ epithelial population under gln-deprivation and demonstrated increased expression of epithelial markers such as e-cadherin, claudin-1 and decreased expression of mesenchymal protein n-cadherin. MCF-7-bCSCs showed a decrease in EpCAM^high population whereas MDAMB-231-bCSCs increased CD44^high population in response to gln-deprivation. The expression of intracellular stem cell markers such sox-2, oct-4 and nanog showed a drastic decrease in gene expression under gln-deprived MDAMB-231-bCSCs. Finally, localization of β-catenin in MCF-7 and MDAMB-231 cells showed its accumulation in cytosol or perinuclear space reducing its efficiency to transcribe downstream genes. Conclusively, our study demonstrated that gln-deprivation induces differentiation of bCSCs into epithelial subtypes and also reduces stemness of bCSCs mediated by reduced nuclear localization of β-catenin. It also suggests that basal and luminal bCSCs respond differentially towards changes in extracellular and intracellular gln. This study could significantly affect the gln targeting regimen of breast cancer therapeutics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-020-00603-1.     

On the role of p53 in the cellular response to aneuploidy

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