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

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

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

Implications of Extreme Climatic Events on Marine Fisheries Sector

Implications of Extreme Climatic Events on Marine Fisheries Secto

The RNA helicase Dhh1p cooperates with Rbp1p to promote porin mRNA decay via its non-conserved C-terminal domain

The yeast RNA helicase Dhh1p has been shown to associate with components of mRNA decay and is involved in mRNA decapping and degradation. An RNA-binding protein, Rbp1p, is known to bind to the 3′-UTR of porin (POR1) mRNA, and induces mRNA decay by an uncharacterized mechanism. Here, we show that Dhh1p can associate with POR1 mRNA and specifically promote POR1 mRNA decay via its interaction with Rbp1p. As compared to its mammalian homolog RCK/p54/DDX6, Dhh1p has a unique and long extension at its C-terminus. Interestingly, this non-conserved C-terminal region of Dhh1p is required for interaction with Rbp1p and modulating Rbp1p-mediated POR1 mRNA decay. Notably, expression of a C-terminal 81-residue deleted Dhh1p can fully complement the growth defect of a dhh1Δ strain and retains its function in regulating the mRNA level of an RNA-binding protein Edc1p. Moreover, mammalian DDX6 became capable of interacting with Rbp1p and could confer Rbp1p-mediated POR1 mRNA decay in the dhh1Δ strain upon fusion to the C-terminal unique region of Dhh1p. Thus, we propose that the non-conserved C-terminus of Dhh1p plays a role in defining specific interactions with mRNA regulatory factors that promote distinct mRNA decay

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

The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered

Evaluation of A2BP1 as an Obesity Gene

OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS-Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392) (Meyre et al. Nat Genet 2009;41:157-159). Selected variants were genotyped in two additional samples of Caucasians (Amish, n = 1,149, and German children case/control subjects, n = 998) and one additional Native American (n = 2,531) sample. Small interfering RNA was used to knockdown A2bp1 message levels in mouse embryonic hypothalamus cells. RESULTS-No single variant in A2BP1 was reproducibly associated with obesity across the different populations. However, different variants within intron 1 of A2BP1 were associated with BMI in full-heritage Pima Indians (rs10500331, P = 1.9 x 10(-7)) and obesity in French Caucasian adult (rs4786847, P = 1.9 x 10(-10)) and children (rs8054147, P = 9.2 x 10(-6)) case/control subjects. Reduction of A2bp1 in mouse embryonic hypothalamus cells decreased expression of Atxn2, Insr, and Mc4r. CONCLUSIONS-Association analysis suggests that variation in A2BP1 influences obesity, and functional studies suggest that A2BP1 could potentially affect adiposity via the hypothalamic MC4R pathway. Diabetes 59:2837-2845, 201