Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis

The managerial skills in the game of roll ball: an indigenous game of India

  Roll Ball is an indigenous game of India.  Roll Ball is a dynamic game blending roller skates, basketball, handball, and throwball, played between two teams of twelve players. The objective is to score goals within a set timeframe. It allows ball handling with one or both hands, bouncing repeatedly. Invented by Raju Dabhade in 2003, it\u27s governed by the International Roll Ball Federation, emphasizing balance, speed, accuracy, and teamwork. With six World Cup matches held, Roll Ball has garnered global attention and become a beloved sport among youth.   In roll ball, referees have the authority to make decisions on the field, according to the rule of Roll Ball.  The good or bad decision of a referee could change the result of the game. Refereeing is a very critical task. The role of referees and players on the field of play demonstrates many more managerial skills.  Management is a term is meant not only for companies, but also for sports. This conceptual paper describes the managerial skills being utilized either knowingly or unknowingly by the players and referee

Role of probiotics in prevention of necrotizing enterocolitis in preterm neonates

Background: Necrotizing enterocolitis (NEC) is one of the common emergencies in preterm neonates which are associated with high morbidity and mortality despite recent advances in neonatal care. Probiotics may be one of the most effective therapies for the prevention of NEC. Objective: The objective of this study is to evaluate the role of probiotics in reducing the incidence of NEC in preterm newborns. Methods: This was a prospective randomized control study conducted at tertiary care teaching hospital. A total of 140 preterm newborns of gestation ≤34 weeks of age were enroled in the final analysis. The recruited newborns were randomized into intervention group and control group by simple random sampling method. The intervention group was fed probiotics mixed with expressed breast milk, and the control group was fed with milk alone. Result: The incidence of NEC in probiotics group was significantly lower than in the control group (2.86% vs. 11.43%), (p=0.04). Although there were no significant differences in the initial presentation of NEC between the two groups, those in the study group who developed NEC had less severe disease, based on Bell’s staging criteria. There was no significant difference in terms of age in diagnosis of NEC and in age at which birth weight is gained between the two groups. However, there was a statistically significant difference in duration of hospital stay (15.62±2.84 vs. 23.54±3.43 days; p<0.001) and time to reach full feed (15.82±3.15 vs. 20.22±2.14; p<0.001). There was no significant difference in incidence of overall mortality (p=0.209; relative risk [RR] 0.25, 95% confidence interval [CI]: 0.029–2.18) and sepsis rate (p=0.673; RR 1.15, 95% CI: 0.593–2.243) between the two groups. Conclusion: Probiotics supplementation reduced the incidence and severity of NEC in the preterm neonates. This resulted in shorter duration of hospital stay and faster achievement of full oral feeds

PHYTOCHEMICAL SCREENING AND ANTIMICROBIAL ACTIVITY OF AZADIRACHTA INDICA AND PLECTRANTHUS AMBOINICUS EXTRACT

Objective: In the present research, a clear systematic investigation of phytochemical screening and antibacterial activity of herbal plants such as Azadirachta indica and Plectranthus amboinicus has been carried out. Methods: The aqueous and alcoholic extract was prepared in soxhlet apparatus and phytochemical analysis of extracts was performed and analysed. The in vitro antimicrobial activity was performed by cup plate method. These extracts were studied under agar diffusion method against three bacterial species such as Bacillussubtills, Staphylococcus aureus, and Escherichia coli at 5µg, 50 µg and 250 µg concentration. Results: The combine extract showed a predominant activity against these bacteria, which confirmed antimicrobial activity in AEAI and AEPA Conclusion: The results obtained in this study clearly indicate that AEAI and AEPA has a significant potential to use as an antimicrobial agen

Auto-Platoon : Freight by example

The work introduces a bio-inspired leader-follower system based on an innovative mechanism proposed as software latching that aims to improve collaboration and coordination between a leader agent and the associated autonomous followers. The system utilizes software latching to establish real-time communication and synchronization between the leader and followers. A layered architecture is proposed, encompassing perception, decision-making, and control modules. Challenges such as uncertainty, dynamic environments, and communication latency are addressed using Deep learning and real-time data processing pipelines. The follower robot is equipped with sensors and communication modules that enable it to track and trace the agent of interest or avoid obstacles. The followers track the leader and dynamically avoid obstacles while maintaining a safe distance from it. The experimental results demonstrate the proposed system's effectiveness, making it a promising solution for achieving success in tasks that demand multi-robot systems capable of navigating complex dynamic environments

Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer

Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations. Understanding how these mutations impact on ER function is a prerequisite for identifying methods to treat breast cancer patients featuring such mutations. Towards this end, we used CRISPR-Cas9 genome editing to make a single allele knock-in of the most commonly mutated amino acid residue, tyrosine 537, in the estrogen-responsive MCF7 breast cancer cell line. Genomic analyses using RNA-seq and ER ChIP-seq demonstrated that the Y537S mutation promotes constitutive ER activity globally, resulting in estrogen-independent growth. MCF7-Y537S cells were resistant to the anti-estrogen tamoxifen and fulvestrant. Further, we show that the basal transcription factor TFIIH is constitutively recruited by ER-Y537S, resulting in ligand-independent phosphorylation of Serine 118 (Ser118) by the TFIIH kinase, cyclin-dependent kinase (CDK)7. The CDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growth of MCF7-Y537S cells. These studies confirm the functional importance of ER mutations in endocrine resistance, demonstrate the utility of knock-in mutational models for investigating alternative therapeutic approaches and highlight CDK7 inhibition as a potential therapy for endocrine-resistant breast cancer mediated by ER mutations

An mRNA decapping mutant deficient in P body assembly limits mRNA stabilization in response to osmotic stress

Yeast is exposed to changing environmental conditions and must adapt its genetic program to provide a homeostatic intracellular environment. An important stress for yeast in the wild is high osmolarity. A key response to this stress is increased mRNA stability primarily by the inhibition of deadenylation. We previously demonstrated that mutations in decapping activators (edc3∆ lsm4∆C), which result in defects in P body assembly, can destabilize mRNA under unstressed conditions. We wished to examine whether mRNA would be destabilized in the edc3∆ lsm4∆C mutant as compared to the wild-type in response to osmotic stress, when P bodies are intense and numerous. Our results show that the edc3∆ lsm4∆C mutant limits the mRNA stability in response to osmotic stress, while the magnitude of stabilization was similar as compared to the wild-type. The reduced mRNA stability in the edc3∆ lsm4∆C mutant was correlated with a shorter PGK1 poly(A) tail. Similarly, the MFA2 mRNA was more rapidly deadenylated as well as significantly stabilized in the ccr4∆ deadenylation mutant in the edc3∆ lsm4∆C background. These results suggest a role for these decapping factors in stabilizing mRNA and may implicate P bodies as sites of reduced mRNA degradation

Physiology of bridging stent grafts after fenestrated/branched endovascular aortic repair: Where translational science meets the clinical profile

Fenestrated/branched endovascular aortic repair emerges as the primary therapeutic modality for intricate aortic pathologies encompassing the paravisceral and thoracoabdominal segments, where bridging stent grafts (BSGs) play a vital role in linking the primary aortic endograft with target vessels. Bridging stent grafts can be categorized mainly into self‐expanding stent grafts (SESGs) and balloon‐expandable stent grafts (BESGs). Physiological factors significantly influence post‐complex endovascular aortic repair BSG behaviour, impacting clinical outcomes of SESGs and BESGs in different but overlapping ways. Crucial prerequisites for BSGs encompass not only flexibility but also resilience against mechanical stress and compliance mismatch, especially when bridging the rigid aortic main body with dynamic target vessels. The significance of considering these physiological factors in clinical decision‐making is underscored by recognizing the interplay between SESG and BESG characteristics, vessel physiology and patient haemorheology. Such factors include the anatomy and tortuosity of the vessel, diameter of the vessel and BSG, deployment and durability, extrinsic stenosis and respiratory motion. Haemorheological factors, such as anti‐thrombotic therapy and hydration status, need to be considered. This narrative review examines both in vitro and in vivo evidence regarding the impact of physiological factors on the behaviour of BSGs and assesses the consequences for clinical outcomes following complex endovascular aortic repair

Nanomagnet-facilitated pharmaco-compatibility for cancer diagnostics: Underlying risks and the emergence of ultrasmall nanomagnets

Article summarizes various progressive aspects of nanomagnets pertaining to their production with an emphasis on sustainable biomimetic approaches, particularly cancer therapy

How oceanography influences Fishery Biology? - A Case of distribution differences in carnivorous and planktivorous fishes along the Coastal Waters of Eastern Arabian Sea In: ICAR Sponsored Winter School on Recent Advances in Fishery Biology Techniques for Biodiversity Evaluation and Conservation, 1-21 December 2018, Kochi.

Understanding the link between physical oceanographic events and seasonality in catch composition is a critical component in the accurate assessment of climate change impacts in context of fisheries. This remains elusive owing to the lack of synoptic-level datasets on the relevant oceanographic variables. The advent of satellite remote sensing that can measure oceanographic variables at high spatial and temporal resolution has helped to address this challenge. Prior studies have communicated the puzzling dominance of carnivores (fish groups) in North East Arabian Sea (NEAS) whereas planktivores appear to thrive in South East Arabian Sea (SEAS). The study attempts to address this conundrum by taking cues from the influence of oceanographic forcing upon seasonal trends in catch composition using remotely-sensed oceanographic variables and mean standardized catch. The anoxic conditions associated with intense seasonal upwelling in SEAS waters leads to the reduction in the vertical extent of demersal carnivore habitats. The demersal habitats in NEAS waters have a higher likelihood of entraining oxygen rich (>0.5 ml/L) water column when compared with its southern counterpart especially from August to November. Moreover, NEAS waters cater to the nutritional requirements of juvenile demersal carnivore population as it supports primary production both during summer and winter monsoon months. The perpetual presence of chlorophyll biomass allows for the persistence of a prey base that maximizes the likelihood of demersal adult population being well-fed. The poleward directed West India Coastal Current facilitates the passive drift of juveniles towards productive and oxygen rich habitats in NEAS waters. For demersal/pelagic carnivores that undergo recruitment over a long span of time (> 6 months), NEAS waters provide the best spawning ground capable of meeting their long-term nutritional demands. Pelagic planktivores thrive in SEAS, where seasonal upwelling supported primary production remains the norm, owing to their relatively short recruitment span (< 4 months). Unlike SEAS, NEAS waters are found to provide suitable environment geared towards the successful larval recruitment, sustenance and survival of the demersal carnivore group. This could act as a forcing function in driving the annual catch composition of landing data registered in NEAS waters toward carnivore spectrum