Cross Dehydrogenative Coupling of SF4-Alkyne with Tetrahydroisoquinolines.

This study introduces a dual-catalytic method for cross-dehydrogenative coupling (CDC) between tetrahydroisoquinolines and Py-SF4-alkyne using visible-light photoredox catalysis. This protocol enables selective C(sp3)-H alkynylation, expanding the synthetic toolkit for SF4-based molecules. Demonstrating efficiency and substrate versatility, this approach opens new avenues in hexacoordinated tetrafluorinated sulfur chemistry and CDC strategies and holds significant promise for drug discovery and materials science.

A computational study on structural and functional consequences of nsSNPs in human dopa decarboxylase.

The Dopa Decarboxylase (DDC) gene plays an important role in the synthesis of biogenic amines such as dopamine, serotonin, and histamine. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the DDC gene have been linked with various neurodegenerative disorders. In this study, a comprehensive in silico analysis of nsSNPs in the DDC gene was conducted to assess their potential functional consequences and associations with disease outcomes. Using publicly available databases, a complete list of nsSNPs in the DDC gene was obtained. 29 computational tools and algorithms were used to characterise the effects of these nsSNPs on protein structure, function, and stability. In addition, the population-based association studies were performed to investigate possible associations between specific nsSNPs and arthritis. Our research identified four novel DDC gene nsSNPs that have a major impact on the structure and function of proteins. Through molecular dynamics simulations (MDS), we observed changes in the stability of the DDC protein induced by specific nsSNPs. Furthermore, population-based association studies have revealed potential associations between certain DDC nsSNPs and various neurological disorders, including Parkinson's disease and dementia. The in silico approach used in this study offers insightful information about the functional effects of nsSNPs in the DDC gene. These discoveries provide insight into the cellular processes that underlie cognitive disorders. Furthermore, the detection of disease-associated nsSNPs in the DDC gene may facilitate the development of tailored and targeted therapy approaches.Communicated by Ramaswamy H. Sarma.

CstMYB1R1, a REVEILLE-8-like transcription factor, regulates diurnal clock-specific anthocyanin biosynthesis and response to abiotic stress in Crocus sativus L.

KEY MESSAGE: CstMYB1R1 acts as a positive regulator of Crocus anthocyanin biosynthesis and abiotic stress tolerance which was experimentally demonstrated through molecular analysis and over-expression studies in Crocus and Nicotiana. Regulatory mechanics of flavonoid/anthocyanin biosynthesis in Crocus floral tissues along the diurnal clock has not been studied to date. MYB proteins represent the most dominant, functionally diverse and versatile type of plant transcription factors which regulate key metabolic and physiological processes in planta. Transcriptome analysis revealed that MYB family is the most dominant transcription factor family in C. sativus. Considering this, a MYB-related REVEILLE-8 type transcription factor, CstMYB1R1, was explored for its possible role in regulating Crocus flavonoid and anthocyanin biosynthetic pathway. CstMYB1R1 was highly expressed in Crocus floral tissues, particularly tepals and its expression was shown to peak at dawn and dusk time points. Anthocyanin accumulation also peaked at dawn and dusk and was minimum at night. Moreover, the diurnal expression pattern of CstMYB1R1 was shown to highly correlate with Crocus ANS/LDOX gene expression among the late anthocyanin pathway genes. CstMYB1R1 was shown to be nuclear localized and transcriptionally active. CstMYB1R1 over-expression in Crocus tepals enhanced anthocyanin levels and upregulated transcripts of Crocus flavonoid and anthocyanin biosynthetic pathway genes. Yeast one hybrid (Y1H) and GUS reporter assay confirmed that CstMYB1R1 interacts with the promoter of Crocus LDOX gene to directly regulate its transcription. In addition, the expression of CstMYB1R1 in Nicotiana plants significantly enhanced flavonoid and anthocyanin levels and improved their abiotic stress tolerance. The present study, thus, confirmed positive role of CstMYB1R1 in regulating Crocus anthocyanin biosynthetic pathway in a diurnal clock-specific fashion together with its involvement in the regulation of abiotic stress response.

Computational approach for assessing the involvement of SMYD2 protein in human cancers using TCGA data.

BACKGROUND: SMYD2 is a protein of the SET and MYND domain-containing family SMYD. It can methylate the lysine residue of various histone and nonhistone cancer-related proteins and plays a critical role in tumorigenesis. Although emerging evidence supports the association of SMYD2 in the progression of cancers, but its definitive effect is not yet clear. Therefore, further study of the gene in relation with cancer progression needs to be conducted. In the current study, investigators used TCGA data to determine the potential carcinogenic effect of SMYD2 in 11 cancer types. The transcriptional expression, survival rate, mutations, enriched pathways, and Gene Ontology of the SMYD2 were explored using different bioinformatics tools and servers. In addition, we also examined the correlation between SMYD2 gene expression and immunocyte infiltration in multiple cancer types. RESULTS: Findings revealed that higher expression of SMYD2 was significantly correlated with cancer incidents. In CESC and KIRC, the mRNA expression of SMYD2 was significantly correlated with overall survival (OS). In BRCA, KIRC, COAD, and HNSC, the mRNA expression of SMYD2 was significantly correlated with disease-free survival (DFS). We detected 15 missense, 4 truncating, 4 fusions, and 1 splice type of mutation. The expression of SMYD2 was significantly correlated with tumor purity and immunocyte infiltration in six cancer types. The gene GNPAT was highly associated with SMYD2. Significant pathways and Gene Ontology (GO) terms for co-expressed genes were associated to various processes linked with cancer formation. CONCLUSION: Collectively, our data-driven results may provide reasonably comprehensive insights for understanding the carcinogenic effect of SMYD2. It suggests that SMYD2 might be used as a significant target for identifying new biomarkers for various human tumors.

CstPIF4 Integrates Temperature and Circadian Signals and Interacts with CstMYB16 to Repress Anthocyanins in Crocus.

Crocus sativus has emerged as an important crop because it is the only commercial source of saffron that contains unique apocarotenoids. Saffron is composed of dried stigmas of Crocus flower and constitutes the most priced spice of the world. Crocus floral organs are dominated by different classes of metabolites. While stigmas are characterized by the presence of apocarotenoids, tepals are rich in flavonoids and anthocyanins. Therefore, an intricate regulatory network might play a role in allowing different compounds to dominate in different organs. Work so far done on Crocus is focussed on apocarotenoid metabolism and its regulation. There are no reports describing the regulation of flavonoids and anthocyanins in Crocus tepals. In this context, we identified an R2R3 transcription factor, CstMYB16, which resembles subgroup 4 (SG4) repressors of Arabidopsis. CstMYB16 is nuclear localized and acts as a repressor. Overexpression of CstMYB16 in Crocus downregulated anthocyanin biosynthesis. The C2/EAR motif was responsible for the repressor activity of CstMYB16. CstMYB16 binds to the promoter of the anthocyanin biosynthetic pathway gene (LDOX) and reduces its expression. CstMYB16 also physically interacts with CstPIF4, which in turn is regulated by temperature and circadian clock. Thus, CstPIF4 integrates these signals and forms a repressor complex with CstMYB16, which is involved in the negative regulation of anthocyanin biosynthesis in Crocus. Independent of CstPIF4, CstMYB16 also represses CstPAP1 expression, which is a component of the MYB-bHLH-WD40 (MBW) complex and positively controls anthocyanin biosynthesis. This is the first report on identifying and describing regulators of anthocyanin biosynthesis in Crocus.

Morphological, phytochemical, and transcriptome analyses provide insights into the biosynthesis of monoterpenes in Monarda citriodora.

MAIN CONCLUSION: Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.

Computational screening of pathogenic missense nsSNPs in heme oxygenase 1 (HMOX1) gene and their structural and functional consequences.

Heme Oxygenase 1 (HMOX1) is a cytoprotective enzyme, exhibiting the highest activity in the spleen, catalyzing the heme ring breakdown into products of biological significance- biliverdin, CO, and Fe2+. In vascular cells, HMOX1 possesses strong anti-apoptotic, antioxidant, anti-proliferative, anti-inflammatory, and immunomodulatory actions. The majority of these activities are crucial for the prevention of atherogenesis. Single amino acid substitutions in proteins generated by missense non-synonymous single nucleotide polymorphism (nsSNPs) in the protein-encoding regions of genes are potent enough to cause significant medical challenges due to the alteration of protein structure and function. The current study aimed at characterizing and analyzing high-risk nsSNPs associated with the human HMOX1 gene. Preliminary screening of the total available 288 missense SNPs was performed through the lens of deleteriousness and stability prediction tools. Finally, a total of seven nsSNPs (Y58D, A131T, Y134H, F166S, F167S, R183S and M186V) were found to be most deleterious by all tools that are present at highly conserved positions. Molecular dynamics simulations (MDS) analysis explained the mutational effects on the dynamic action of the wild-type and mutant proteins. In a nutshell, R183S (rs749644285) was identified as a highly detrimental mutation that could significantly render the enzymatic activity of HMOX1. The finding of this computational analysis might help subject the experimental confirmatory analysis to characterize the role of nsSNPs in HMOX1.Communicated by Ramaswamy H. Sarma.

Comprehensive bioinformatics analysis of structural and functional consequences of deleterious missense mutations in the human QDPR gene.

Quinonoid dihydropteridine reductase (QDPR) is an enzyme that regulates tetrahydrobiopterin (BH4), a cofactor for enzymes involved in neurotransmitter synthesis and blood pressure regulation. Reduced QDPR activity can cause dihydrobiopterin (BH2) accumulation and BH4 depletion, leading to impaired neurotransmitter synthesis, oxidative stress, and increased risk of Parkinson's disease. A total of 10,236 SNPs were identified in the QDPR gene, with 217 being missense SNPs. Over 18 different sequence-based and structure-based tools were employed to assess the protein's biological activity, with several computational tools identifying deleterious SNPs. Additionally, the article provides detailed information about the QDPR gene and protein structure and conservation analysis. The results showed that 10 mutations were harmful and linked to brain and central nervous system disorders, and were predicted to be oncogenic by Dr. Cancer and CScape. Following conservation analysis, the HOPE server was used to analyse the effect of six selected mutations (L14P, V15G, G23S, V54G, M107K, G151S) on the protein structure. Overall, the study provides insights into the biological and functional impact of nsSNPs on QDPR activity and the potential induced pathogenicity and oncogenicity. In the future, research can be conducted to systematically evaluate QDPR gene variation through clinical studies, investigate mutation prevalence across different geographical regions, and validate computational results with conclusive experiments.Communicated by Ramaswamy H. Sarma.

Genetic diversity, population structure, and genome-wide association study for the flowering trait in a diverse panel of 428 moth bean (Vigna aconitifolia) accessions using genotyping by sequencing.

BACKGROUND: Moth bean (Vigna aconitifolia) is an underutilized, protein-rich legume that is grown in arid and semi-arid areas of south Asia and is highly resistant to abiotic stresses such as heat and drought. Despite its economic importance, the crop remains unexplored at the genomic level for genetic diversity and trait mapping studies. To date, there is no report of SNP marker discovery and association mapping of any trait in this crop. Therefore, this study aimed to dissect the genetic diversity, population structure and marker-trait association for the flowering trait in a diversity panel of 428 moth bean accessions using genotyping by sequencing (GBS) approach. RESULTS: A total of 9078 high-quality single nucleotide polymorphisms (SNPs) were discovered by genotyping of 428 moth bean accessions. Model-based structure analysis and PCA grouped the moth bean accessions into two subpopulations. Cluster analysis revealed accessions belonging to the Northwestern region of India had higher variability than accessions from the other regions suggesting that this region represents its center of diversity. AMOVA revealed more variations within individuals (74%) and among the individuals (24%) than among the populations (2%). Marker-trait association analysis using seven multi-locus models including mrMLM, FASTmrEMMA FASTmrEMMA, ISIS EM-BLASSO, MLMM, BLINK and FarmCPU revealed 29 potential genomic regions for the trait days to 50% flowering, which were consistently detected in three or more models. Analysis of the allelic effect of the major genomic regions explaining phenotypic variance of more than 10% and those detected in at least 2 environments showed 4 genomic regions with significant phenotypic effect on this trait. Further, we also analyzed genetic relationships among the Vigna species using SNP markers. The genomic localization of moth bean SNPs on genomes of closely related Vigna species demonstrated that maximum numbers of SNPs were getting localized on Vigna mungo. This suggested that the moth bean is most closely related to V. mungo. CONCLUSION: Our study shows that the north-western regions of India represent the center of diversity of the moth bean. Further, the study revealed flowering-related genomic regions/candidate genes which can be potentially exploited in breeding programs to develop early-maturity moth bean varieties.

A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics.

Polymorphisms of Thiopurine S-methyltransferase (TPMT) are known to be associated with leukemia, inflammatory bowel diseases, and more. The objective of the present study was to identify novel deleterious missense SNPs of TPMT through a comprehensive in silico protocol. The initial SNP screening protocol used to identify deleterious SNPs from the pool of all TPMT SNPs in the dbSNP database yielded an accuracy of 83.33% in identifying extremely dangerous variants. Five novel deleterious missense SNPs (W33G, W78R, V89E, W150G, and L182P) of TPMT were identified through the aforementioned screening protocol. These 5 SNPs were then subjected to conservation analysis, interaction analysis, oncogenic and phenotypic analysis, structural analysis, PTM analysis, and molecular dynamics simulations (MDS) analysis to further assess and analyze their deleterious nature. Oncogenic analysis revealed that all five SNPs are oncogenic. MDS analysis revealed that all SNPs are deleterious due to the alterations they cause in the binding energy of the wild-type protein. Plasticity-induced instability caused by most of the mutations as indicated by the MDS results has been hypothesized to be the reason for this alteration. While in vivo or in vitro protocols are more conclusive, they are often more challenging and expensive. Hence, future research endeavors targeted at TPMT polymorphisms and/or their consequences in relevant disease progressions or treatments, through in vitro or in vivo means can give a higher priority to these SNPs rather than considering the massive pool of all SNPs of TPMT.

Seroprevalence of anti SARS-CoV-2 IgG antibodies among adults in Jammu district, India: A community-based study.

Background & objectives: Serology testing is essential for immunological surveillance in the population. This serosurvey was conducted to ascertain the cumulative population immunity against SARS-CoV-2 among adults in Jammu district and to understand the association of seropositivity with sociodemographic and clinical correlates. Methods: On September 30 and October 1, 2020, a household survey was done in 20 villages/wards chosen from 10 health blocks in district Jammu, India. Demographic, clinical and exposure information was collected from 2000 adults. Serum samples were screened for IgG antibodies using COVID Kavach MERILISA kit. Tests of association were used to identify risk factors associated with IgG positivity. Crude odds ratio with 95 per cent confidence intervals (CIs) was calculated during univariate analysis followed by logistic regression. Results: Overall adjusted seroprevalence for SARS-CoV-2 was 8.8 per cent (95% CI: 8.78-8.82); it varied from 4.1 per cent in Chauki choura to 16.7 per cent Pallanwalla across 10 blocks in the district. Seropositivity was observed to be comparatively higher in 41-50 and 61-70 yr age groups, among males and in rural areas. Fever, sore throat, cough, dyspnoea, myalgias, anosmia, ageusia, fatigue, seizures, history of exposure, medical consultation, hospitalization and missing work showed significant association with seropositivity on univariate analysis. On logistic regression, only sore throat, myalgia and missing work showed significant adjusted odds of IgG positivity. Extrapolation to adult population suggested that exposure to SARS-CoV-2 was 14.4 times higher than reported cases, translating into Infection fatality rate of 0.08 per cent. Interpretation & conclusions: Since a major part of population was immunologically naive, all efforts to contain COVID-19 need to be vigorously followed while these baseline results provide an important yardstick to monitor the trends of COVID-19 and guide locally appropriate control strategies in the region.

Impacts, Tolerance, Adaptation, and Mitigation of Heat Stress on Wheat under Changing Climates.

Heat stress (HS) is one of the major abiotic stresses affecting the production and quality of wheat. Rising temperatures are particularly threatening to wheat production. A detailed overview of morpho-physio-biochemical responses of wheat to HS is critical to identify various tolerance mechanisms and their use in identifying strategies to safeguard wheat production under changing climates. The development of thermotolerant wheat cultivars using conventional or molecular breeding and transgenic approaches is promising. Over the last decade, different omics approaches have revolutionized the way plant breeders and biotechnologists investigate underlying stress tolerance mechanisms and cellular homeostasis. Therefore, developing genomics, transcriptomics, proteomics, and metabolomics data sets and a deeper understanding of HS tolerance mechanisms of different wheat cultivars are needed. The most reliable method to improve plant resilience to HS must include agronomic management strategies, such as the adoption of climate-smart cultivation practices and use of osmoprotectants and cultured soil microbes. However, looking at the complex nature of HS, the adoption of a holistic approach integrating outcomes of breeding, physiological, agronomical, and biotechnological options is required. Our review aims to provide insights concerning morpho-physiological and molecular impacts, tolerance mechanisms, and adaptation strategies of HS in wheat. This review will help scientific communities in the identification, development, and promotion of thermotolerant wheat cultivars and management strategies to minimize negative impacts of HS.

In-silico screening of plant-derived antivirals against main protease, 3CLpro and endoribonuclease, NSP15 proteins of SARS-CoV-2.

Novel Coronavirus or SARS-CoV-2 outbreak has developed a pandemic condition all over the world. The virus is highly infectious and spreads by human to human local transmission mode. Till date, there is no vaccination or drugs been approved for the treatment by the World Health Organisation. Henceforth, the discovery of the potential drugs is an urgent and utmost requirement for the medical fraternity. Since, the side effects of plant-derived compounds will be lower compared to synthetic/chemical drugs. The Main protease (3CLpro or NSP5) and endoribonuclease (NSP15) proteins are necessity for viral replication and its survival in the host cell. In the present study, in-silico approach of drug development was used to search for potential antiviral plant-derived compounds as inhibitors against SARS-CoV-2 replication proteins. Eight plant-derived compounds of which the antiviral activity was known and available, and two reported drugs against SARS-CoV-2 selected for the molecular docking analysis. The docking results suggested that bisdemethoxycurcumin, demethoxycurcumin, scutellarin, quercetin and myricetin showed least binding energy, i.e., greater than -6.5 Kcal/mol against 3CLpro and endoribonuclease of SARS-CoV-2. Further studies of ADME-Tox and bioavailability of drugs were also performed that exhibited efficient parameters of drug likeness. Molecular dynamics simulation calculations were performed for the most negative binding affinity of the compound to evaluate the dynamic behavior,and stability of protein-ligand complex. Our findings suggest that these compounds could be potential inhibitors of SARS-CoV-2 main protease and endoribonuclease. However, further in-vitro and pre-clinical experiments would validate the potential inhibitors of SARS-CoV-2 proteins.

Enhanced recovery protocol after single-stage bilateral primary total knee arthroplasty decreases duration of hospital stay without increasing complication rates.

PURPOSE: With an increasing number of total knee arthroplasty (TKA), protocols for better standard of patient care and shorter duration of hospital stay are necessary. Enhanced recovery (ER) protocols are becoming popular to meet these objectives. The current study aims to evaluate the clinical outcome of fast-track TKA using ER protocol in terms of length of hospital stay, perioperative complications and functional outcomes. METHODS: Patients undergoing single-stage bilateral primary TKA were prospectively included in the study. All patients went through a pre-defined ER protocol of TKA. Length of hospital stay, readmission rates, pain scores and functional scores of patients operated under ER protocol were compared with another matched historical control-group. Factors delaying the discharge of the patients by 48 h after the surgery were noted. RESULTS: We compared 275 patients undergoing single-stage bilateral primary TKA through ER protocol (Group 1) with 190 patients who had undergone bilateral primary TKA before the ER protocol was initiated (Group 2). The length of hospital stay (3.9 ± 2.1 days in group 1 and 7.5 ± 3.2 days in group 2, p 0.0001) and post-operative pain scores at 12 h (5.2 ± 2.9 in group 1 and 5.7 ± 2.1 in group 2, p 0.03) and 24 h (4.1 ± 1.6 in group 1 and 4.6 ± 1.4 in group 2, p 0.0005) were found to be significantly better with ER protocol. There was no difference in Oxford knee scores, infection rates, readmissions or mortality between the two groups. CONCLUSION: ER protocol in single-stage bilateral primary TKA resulted in decreased length of hospital stay without increasing complications and compromising the clinical outcome. It requires an integrated approach and adherence to clinical pathways. LEVEL OF EVIDENCE: Level II, Prospective comparative study.

Association between functional outcome scores and MRI-based structural integrity after rotator cuff repair: a prospective cohort study.

PURPOSE: Natural history of rotator cuff tears is poorly understood. Repair of rotator cuff tears has shown to improve functional outcomes in full-thickness tears. However, high re-tear rates have been reported in literature, which does not correlate with poorer outcomes. Primary aim of this study was to explore association between functional outcome scores and structural integrity of rotator cuff, using magnetic resonance imaging (MRI)-based grading. METHODS: Patients with MRI-proven full-thickness rotator cuff tears, undergoing mini-open rotator cuff repair, were assessed for shoulder abduction strength and functional outcome scores before the surgery and 2 years after the procedure. Association between functional outcome scores and MRI grading for rotator cuff healing (Sugaya grading) was analyzed. RESULTS: A total of 38 patients (18 females and 20 males), with a mean age of 50.6 years (SD: 10.9), were included in the study. Mean duration of symptoms was 6.05 months (SD: 4.2). On postoperative MRI, healing of the cuff was categorized as Sugaya grade 1 in 12 patients, grade 2 in 20 patients and grade 3 in 6 patients. Higher Sugaya grades (T: 13.48, p: 0.001) and grades of fatty degeneration (T: 14.05, p: 0.001) were found to be associated with longer duration of symptoms. Improvement in shoulder abduction strength correlated negatively with the duration of symptoms (r: -0.39, p: 0.01). There was a significant improvement in functional outcome scores after the surgery. There was no association between postoperative structural integrity of the repaired tendon (Sugaya grading) and functional outcome scores. CONCLUSION: Early repair of rotator cuff results in better functional outcomes and shoulder strength. The findings from this study suggest there is a dissociation between MRI-based grades of healing of repaired rotator cuff and function of the shoulder. STUDY DESIGN: Level II, Prospective cohort study.

Key drivers of consumption-based carbon emissions: empirical evidence from SAARC countries.

To devise an appropriate climate policy dealing with environmental degradation, reliable measurement of CO2 emissions is essential. In the recent past, most researchers have utilized production-based emissions in their studies, ignoring the important role of consumption-based emissions in environmental degradation. Therefore, the present research examines the drivers of consumption-based CO2 emissions in SAARC nations over the period 1990 to 2018. By employing traditional and second-generation panel cointegration methodologies, the study, more specifically, explores the link between consumption-based CO2 emissions and its five macroeconomic determinants, namely, GDP growth, energy consumption, FDI, trade openness (measured by composite trade share index), and urbanization. The study also applies the FMOLS and DOLS techniques for calculating the long-run elasticities of regressors with respect to the explained variable. The results establish a cointegration relationship between the variables and validate an "N-shaped EKC" for the SAARC region. It is also found that in the long run, energy consumption and urbanization amplify the consumption-based CO2 emissions while FDI and trade openness improve the environmental quality by plummeting emissions. Most importantly, the study rejects the "pollution-haven hypothesis" for the SAARC region based on the outcomes of FDI and trade openness. Lastly, based on the results, some policies are recommended for the abatement of environmental degradation in SAARC countries. As the SAARC nations rely heavily on fossil-based energy, it is suggestive for these economies to enhance the level of energy efficiency and augment the share of renewable energy sources in the energy mix. Furthermore, the policy designers in this region should encourage trade openness and liberalize inward FDI for containing consumption-based emissions.

Effect of prolonged storage at 2°C-6°C for 120 h on the coagulation factors of thawed cryoprecipitate: Can we extend its shelf life post thaw beyond 4 h?

BACKGROUND: Cryoprecipitate helps in replenishing important coagulation factors like fibrinogen, Factor VIII and von Willebrand factor without running the risk of volume overload. It is very useful in the treatment of trauma patients with active bleeding and works best when administered early. Extending the shelf life of thawed cryoprecipitate beyond 4 hours enables us to manage inventory better, reduces the burden of demand vs supply as well as minimizes wastage. It can also help in logistically supporting the transfusion services in making cryoprecipitate readily available in mass casualty scenarios (war, natural calamity) in remote locations by reducing the time required for thawing cryoprecipitate and the need for costly storage equipment. AIM: The aim of this study was to compare the levels of Factor VIII, Fibrinogen and von Willebrand factor on thawed cryoprecipitate after prolonged storage for 5 days at a temperature of 2-6°C. METHODOLOGY: The above mentioned coagulation factors were analyzed in cryoprecipitate at the time of product thaw and again after 120 hours of 2 to 6°C storage using fully automated coagulation analyser (STA Compact Max). All parameters were expressed as Mean ± Standard deviation and were analyzed using paired t-test with level of significance, P < 0.05. RESULTS: There was a significant decrease in the level of Factor VIII, whereas the levels of fibrinogen and von Willebrand Factor remained stable during the storage period. All the cryoprecipitate units retained factor activities above therapeutic range even after 5 days of storage at 2-6°C. CONCLUSION: Although the levels of clotting factors are reduced during storage, they are still maintained above the therapeutic range. In scenarios where maintaining frozen cryoprecipitate inventory is a logistical challenge and emergency massive demands of cryoprecipitate are foreseen, the use of pre-thawed cryoprecipitate can be considered as a viable option.

Effect of Women's and Partners' Education on Maternal Health-care Services Utilization in Five Empowered Action Group States of India: An analysis of 13,443 Women of Reproductive Age.

BACKGROUND: Suboptimal utilization of maternal health-care services is a perennial problem in Empowered Action Group (EAG) states. This study examines role of women's and partners' education on usage of antenatal, postnatal care (PNC), and skilled birth attendance in these states. METHODOLOGY: National Family Health Survey-4 (2015-2016) data for 13,443 women in reproductive age group of 15-49 years in Bihar, Madhya Pradesh (MP), Odisha, Rajasthan, and Uttar Pradesh (UP) were analyzed using logistic regression. RESULTS: Increasing level of education had a significant impact on utilization of antenatal services in all states, highest and lowest odds being observed with higher and primary level of partner's education, respectively. Skilled birth attendance universally showed rising trend with increasing women education, while it remained substantially low even at higher level of partner's education. For PNC, utilization increased with increasing level of maternal education. While significantly lower odds of PNC were seen with primary level of partner education in Rajasthan and UP, partner's secondary education showed positive and significant association in Bihar, Rajasthan, and UP. At higher level of partner education, positive and significant effects on PNC were observed only in Bihar, MP, and UP. CONCLUSIONS: Universal education is vital to attain sustainable development goals at the grassroot level, which is happening relatively slowly in the EAG states.

Structural and functional analysis of disease-associated mutations in GOT1 gene: An in silico study.

Disease-associated single nucleotide polymorphisms (SNPs) alter the natural functioning and the structure of proteins. Glutamic-oxaloacetic transaminase 1 (GOT1) is a gene associated with multiple cancers and neurodegenerative diseases which codes for aspartate aminotransferase. The present study involved a comprehensive in-silico analysis of the disease-associated SNPs of human GOT1. Four highly deleterious nsSNPs (L36R, Y159C, W162C and L345P) were identified through SNP screening using several sequence-based and structure-based tools. Conservation analysis and oncogenic analysis showed that most of the nsSNPs are at highly conserved residues, oncogenic in nature and cancer drivers. Molecular dynamics simulations (MDS) analysis was performed to understand the dynamic behaviour of native and mutant proteins. PTM analysis revealed that the nsSNP Y159C is at a PTM site and will mostly affect phosphorylation at that site. Based on the overall analyses carried out in this study, L36R is the most deleterious mutation amongst the aforementioned deleterious mutations of GOT1.

Iodine-catalyzed thioallylation of indoles using Bunte salts prepared from Baylis-Hillman bromides.

Metal-free iodine-catalyzed regioselective thioallylation of indoles has been accomplished at room temperature using Bunte salts prepared from Baylis-Hillman bromides. The resulting multi-functional C3 thioallylated indoles exhibit ample structural diversity and good functional group tolerance.