AR-V7 expression facilitates accelerated G2/M phase transition in castration-resistant prostate cancer.

The emergence of AR-V7, a truncated isoform of AR upon androgen deprivation therapy treatment, leads to the development of castration resistant prostate cancer (CRPC). Understanding mechanisms that regulate AR-V7 expression is critical for developing newer therapeutic strategies. In this study, we have investigated the regulation of AR-V7 during cell cycle and identified a distinct pattern of periodic fluctuation, peaking during G2/M phase. This fluctuation correlates with the expression of Cdc-2 like kinase 1 (CLK1) and phosphorylated serine/arginine-rich splicing factor 1 (p-SRSF1) during these phases, pointing towards their role in AR-V7 generation. Functional assays reveal that CLK1 knockdown prolongs the S phase, leading to altered cell cycle distribution and increased accumulation of AR-V7 and pSRSF1 in G1/S phase. Conversely, CLK1 overexpression rescues AR-V7 and p-SRSF1 levels in the G2/M phase, consistent with observed cell cycle alterations upon AR-V7 knockdown and overexpression in CRPC cells. Furthermore, overexpression of kinase-deficient CLK1 mutant leads to diminished AR-V7 levels during G2/M, underlining the essential contribution of CLK1's kinase activity in modulating AR-V7 expression. Collectively, our findings, for the first time, show periodic regulation of AR-V7 expression, its effect on cell cycle progression and the critical role of CLK1-pSRSF1 axis in modulating AR-V7 expression throughout the cell cycle.

Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.

Foot-and-Mouth Disease Virus Serotype O Exhibits Phenomenal Genetic Lineage Diversity in India during 2018-2022.

In India, widespread foot-and-mouth disease (FMD) outbreaks occurred in 2021. The objective of this study was to identify genetic lineages and evaluate the antigenic relationships of FMD virus (FMDV) isolates gathered from outbreaks reported between 2019 and 2022. Our study shows that the lineages O/ME-SA/Ind2001e and the O/ME-SA/Cluster-2018 were both responsible for the FMD outbreaks on an epidemic scale during 2021. This observation is in contrast to earlier findings that suggested epidemic-scale FMD outbreaks in India are often connected to a single genetic lineage. Additionally, we report here the identification of the O/ME-SA/PanAsia-2/ANT10 sub-lineage in India for the first time, which was connected to two intermittent outbreaks in Jammu and Kashmir. The current study demonstrates that the O/ME-SA/ind2001e lineage has a strong presence outside of the Indian subcontinent. Furthermore, the O/ME-SA/Cluster-2018 was observed to have a wider geographic distribution than previously, and like the O/ME-SA/Ind2001d and O/ME-SA/Ind2001e lineages in the past, it may eventually spread outside of its geographic niche. For O/ME-SA/Ind2001e and O/ME-SA/Cluster-2018, the predicted substitution rate for the VP1 region was 6.737 × 10-3 and 8.257 × 10-3 nt substitutions per site per year, respectively. The time of the most recent common ancestor of the O/ME-SA/Ind2001e and O/ME-SA/Cluster-2018 strains suggests that the viruses possibly emerged during 2003-2011 and 2009-2017, respectively. Recent sightings of the O/ME-SA/PanAsia2/ANT10 virus in India and the O/ME-SA/Ind2001e virus in Pakistan point to possible cross-border transit of the viruses. The results of a two-dimensional viral neutralization test revealed that all of the field isolates were antigenically matched to the currently used Indian vaccine strain O INDR2/1975. These results suggest that the serotype O vaccine strain can protect against outbreaks brought on by all three circulating lineages.

Emergence of a novel genetic lineage 'A/ASIA/G-18/2019' of foot and mouth disease virus serotype A in India: A challenge to reckon with.

Foot and mouth disease (FMD) has engendered large scale socioeconomic crises on numerous occasions owing to its extreme contagiousness, transboundary nature, complicated epidemiology, negative impact on productivity, trade embargo, and need for intensive surveillance and expensive control measures. Emerging FMD virus variants have been predicted to have originated and spread from endemic Pool 2, native to South Asia, to other parts of the globe. In this study, 26 Indian serotype A isolates sampled between the year 2015 and 2022 were sequenced for the VP1 region. BLAST and maximum likelihood phylogeny suggest emergence of a novel genetic group within genotype 18, named here as 'A/ASIA/G-18/2019' lineage, that is restricted so far only to India and its eastern neighbour, Bangladesh. The lineage subsequent to its first appearance in 2019 seems to have displaced all other prevalent strains, in support of the phenomenon of 'genotype/lineage turnover'. It has diversified into two distinct sub-clusters, reflecting a phase of active evolution. The rate of evolution of the VP1 region for the Indian serotype A dataset was estimated to be 6.747 × 10-3 substitutions/site/year. India is implementing a vaccination centric FMD control programme. The novel lineage showed good antigenic match with the proposed vaccine candidate A IND 27/2011 when tested in virus neutralization test, while the existing vaccine strain A IND 40/2000 showed homology with only 31% of the isolates. Therefore, in order to combat this challenge of antigenic divergence, A IND 27/2011 could be the preferred strain in the Indian vaccine formulations.

An overview of remote monitoring methods in biodiversity conservation.

Conservation of biodiversity is critical for the coexistence of humans and the sustenance of other living organisms within the ecosystem. Identification and prioritization of specific regions to be conserved are impossible without proper information about the sites. Advanced monitoring agencies like the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) had accredited that the sum total of species that are now threatened with extinction is higher than ever before in the past and are progressing toward extinct at an alarming rate. Besides this, the conceptualized global responses to these crises are still inadequate and entail drastic changes. Therefore, more sophisticated monitoring and conservation techniques are required which can simultaneously cover a larger surface area within a stipulated time frame and gather a large pool of data. Hence, this study is an overview of remote monitoring methods in biodiversity conservation via a survey of evidence-based reviews and related studies, wherein the description of the application of some technology for biodiversity conservation and monitoring is highlighted. Finally, the paper also describes various transformative smart technologies like artificial intelligence (AI) and/or machine learning algorithms for enhanced working efficiency of currently available techniques that will aid remote monitoring methods in biodiversity conservation.

Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: insights from computational studies.

The recent outbreak of the coronavirus (SARS-CoV2) is an unprecedented threat to human health and society across the globe. In this context, development of suitable interventions is the need of the hour. The viral spike protein (S Protein) and the cognate host cell receptor ACE2 can be considered as effective and appropriate targets for interventions. It is evident from the present computational study, that catechin and curcumin, not only exhibit strong binding affinity to viral S Protein and host receptor ACE2 but also to their complex (receptor-binding domain (RBD) of the spike protein of SARS-CoV2 and ACE2; RBD/ACE2-complex). The binding affinity values of catechin and curcumin for the S protein, ACE2 and RBD/ACE2-complex are - 10.5 and - 7.9 kcal/mol; - 8.9 and - 7.8 kcal/mol; and - 9.1 and - 7.6 kcal/mol, respectively. Curcumin directly binds to the receptor binding domain (RBD) of viral S Protein. Molecular simulation study over a period of 100 ns further substantiates that such interaction within RBD site of S Protein occurs during 40-100 ns out of 100 ns simulation trajectory. Contrary to this, catechin binds with amino acid residues present near the RBD site of S Protein and causes fluctuation in the amino acid residues of the RBD and its near proximity. Both catechin and curcumin bind the interface of 'RBD/ACE2-complex' and intervene in causing fluctuation of the alpha helices and beta-strands of the protein complex. Protein-protein interaction studies in presence of curcumin or catechin also corroborate the above findings suggesting the efficacy of these two polyphenols in hindering the formation of S Protein-ACE2 complex. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols for therapeutic strategy against SARS-CoV2.

Comparison of continuous cardiac output monitoring derived from regional impedance cardiography with continuous thermodilution technique in cardiac surgical patients.

Background: Cardiac output (CO) assessment is a corner stone in advanced haemodynamic management, especially in critical ill patients. The present study was conducted to validate cardiac index and cardiac output by NICaS™ with the thermodilution technique using pulmonary artery catheter in post-operative cardiac surgical patients. Materials and Methods: This was a prospective observational clinical study conducted at a tertiary care hospital. 23 adult patients in the age range of 18-65 years who had undergone for elective coronary artery bypass grafting were included in the study. Results: Spearman's correlation coefficient of cardiac index between continuous Thermodilution (cTD) and Non-Invasive Cardiac System (NICaS™) showed a good correlation (r = 0.765, 95% confidence interval 0.70 to 0.82, P < 0.0001). There was a good correlation between cTD and NICaS™ for cardiac output (r = 0.759, 95% confidence interval 0.69 to 0.81, P < 0.0001), Bland-Altman plot for cardiac index between cTD and NICaS™ showed a mean bias of -0.66 ± 0.6919 with limits of agreement being -2.02 to 0.6936. Bland-Altman plot for cardiac output between cTD and NICaS™ showed a mean bias of -1.0386 ± 1.17 with limits of agreement being -3.34 to + 1.26. Percentage error for cardiac index and cardiac output were 64.78% and 64% respectively. Polar plot analysis showed an angular bias of 6.32° with radial limits of agreement being -8.114° to 20.75° for cardiac index and angular bias of 5.6682° with radial limits of agreement being -9.1422° to 20.4784° for cardiac output. Conclusion: NICaS™ demonstrated a good trending ability for both CI and CO. However, NICaS™ derived parameters are not interchangeable with the values derived from continuous thermodilution technique.

Characterization of antibiotic resistant and enzyme producing bacterial strains isolated from the Arabian Sea.

Marine bacteria are known to produce many bioactive molecules and extracellular enzymes of commercial importance. We have investigated the bacterial diversity of the coastal area of Karwar, Karnataka State, India. Among these bacterial isolates, five bacterial strains were selected and identified by their morphological, biochemical characteristics and phylogenetic analysis based on 16S rRNA gene sequences. The identified bacterial isolates, Bacillus toyonensis PNTB1, Lysinibacillus sphaericus PTB, Vibrio vulnificus PMD, Shewanella MPTDBS, and Pseudomonas chlororaphis PNTB were characterized for their tolerance to salt and antibiotics. Vibrio vulnificus PMD showed maximum tolerance at higher concentration of salt than other bacteria. These bacterial strains were screened for the production of extracellular enzymes such as lipase, cellulase, pectinase, tannase, chitinase, and L-glutaminase. Vibrio vulnificus showed maximum production of L-glutaminase enzyme. Bacillus toyonensis PNTB1 shows lipase, CM-cellulase and chitinase activities. These isolated bacterial cultures were also utilized most of the aromatic compounds at 7 mM. These findings indicate the organisms present in this zone may have more potential applications in bioremediation, agricultural, industrial, and therapeutics.