Early transcriptome profile of goat peripheral blood mononuclear cells (PBMCs) infected with peste des petits ruminant's vaccine virus (Sungri/96) revealed induction of antiviral response in an interferon independent manner

Sungri/96 vaccine strain is considered the most potent vaccine providing long-term immunity against peste des petits ruminants (PPR) in India. Previous studies in our laboratory highlighted induction of robust antiviral response in an interferon independent manner at 48 h and 120 h post infection (p.i.). However, immune response at the earliest time point 6 h p.i. (time taken to complete one PPRV life cycle), in PBMCs infected with Sungri/96 vaccine virus has not been investigated. This study was taken up to understand the global gene expression profiling of goat PBMCs after Sungri/96 PPRV vaccine strain infection at 6 h post infection (p.i.). A total of 1926 differentially expressed genes (DEGs) were identified with 616 - upregulated and 1310 - downregulated. TLR7/TLR3, IRF7/IRF1, ISG20, IFIT1/IFIT2, IFITM3, IL27 and TREX1 were identified as key immune sensors and antiviral candidate genes. Interestingly, type I interferons (IFNα/β) were not differentially expressed at this time point as well. TREX1, an exonuclease which inhibits type I interferons at the early stage of virus infection was found to be highly upregulated. IL27, an important antiviral host immune factor was significantly upregulated. ISG20, an antiviral interferon induced gene with exonuclease activity specific to ssRNA viruses was highly expressed. Functional profiling of DEGs showed significant enrichment of immune system processes with 233 genes indicating initiation of immune defense response in host cells. Protein interaction network showed important innate immune molecules in the immune network with high connectivity. The study highlights important immune and antiviral genes at the earliest time point

Dysregulated miRNAome and Proteome of PPRV Infected Goat PBMCs Reveal a Coordinated Immune Response

In this study, the miRNAome and proteome of virulent Peste des petits ruminants virus (PPRV) infected goat peripheral blood mononuclear cells (PBMCs) were analyzed. The identified differentially expressed miRNAs (DEmiRNAs) were found to govern genes that modulate immune response based on the proteome data. The top 10 significantly enriched immune response processes were found to be governed by 98 genes. The top 10 DEmiRNAs governing these 98 genes were identified based on the number of genes governed by them. Out of these 10 DEmiRNAs, 7 were upregulated, and 3 were downregulated. These include miR-664, miR-2311, miR-2897, miR-484, miR-2440, miR-3533, miR-574, miR-210, miR-21-5p, and miR-30. miR-664 and miR-484 with proviral and antiviral activities, respectively, were upregulated in PPRV infected PBMCs. miR-210 that inhibits apoptosis was downregulated. miR-21-5p that decreases the sensitivity of cells to the antiviral activity of IFNs and miR-30b that inhibits antigen processing and presentation by primary macrophages were downregulated, indicative of a strong host response to PPRV infection. miR-21-5p was found to be inhibited on IPA upstream regulatory analysis of RNA-sequencing data. This miRNA that was also highly downregulated and was found to govern 16 immune response genes in the proteome data was selected for functional validation vis-a-vis TGFBR2 (TGF-beta receptor type-2). TGFBR2 that regulates cell differentiation and is involved in several immune response pathways was found to be governed by most of the identified immune modulating DEmiRNAs. The decreased luciferase activity in Dual Luciferase Reporter Assay indicated specific binding of miR-21-5p and miR-484 to their target thus establishing specific binding of the miRNAs to their targets.This is the first report on the miRNAome and proteome of virulent PPRV infected goat PBMCs

Comparative and temporal transcriptome analysis of peste des petits ruminants virus infected goat peripheral blood mononuclear cells

Peste des petits ruminanats virus (PPRV), a morbillivirus causes an acute, highly contagious disease – peste des petits ruminants (PPR), affecting goats and sheep. Sungri/96 vaccine strain is widely used for mass vaccination programs in India against PPR and is considered the most potent vaccine providing long-term immunity. However, occurrence of outbreaks due to emerging PPR viruses may be a challenge. In this study, the temporal dynamics of immune response in goat peripheral blood mononuclear cells (PBMCs) infected with Sungri/96 vaccine virus was investigated by transcriptome analysis. Infected goat PBMCs at 48 h and 120 h post infection revealed 2540 and 2000 differentially expressed genes (DEGs), respectively, on comparison with respective controls. Comparison of the infected samples revealed 1416 DEGs to be altered across time points. Functional analysis of DEGs reflected enrichment of TLR signaling pathways, innate immune response, inflammatory response, positive regulation of signal transduction and cytokine production. The upregulation of innate immune genes during early phase (between 2-5 days) viz. interferon regulatory factors (IRFs), tripartite motifs (TRIM) and several interferon stimulated genes (ISGs) in infected PBMCs and interactome analysis indicated induction of broad-spectrum anti-viral state. Several Transcription factors – IRF3, FOXO3 and SP1 that govern immune regulatory pathways were identified to co-regulate the DEGs. The results from this study, highlighted the involvement of both innate and adaptive immune systems with the enrichment of complement cascade observed at 120 h p.i., suggestive of a link between innate and adaptive immune response. Based on the transcriptome analysis and qRT-PCR validation, an in vitro mechanism for the induction of ISGs by IRFs in an interferon independent manner to trigger a robust immune response was predicted in PPRV infection

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Fish Physiology and Biochemistry

Not AvailableThe present study aims to delineate the effect of exogenous enzyme supplementation of fermented or non-fermented de-oiled rice bran (DORB) on haematology, histology and expression of IGF I gene expression of Labeo rohita. Four test diets, namely, T1 (DORB), T2 (fermented DORB), T3 (DORB+exogenous enzyme) and T4 (fermented DORB+exogenous enzyme) were formulated and fed to the L. rohita for a period of 60 days. The test diets T3 and T4 were supplemented with 0.1 g kg-1 xylanase (16,000 U kg?1) and 0.1 g kg-1 phytase (500 U kg?1) enzymes. A total of 120 juveniles of L. rohita (average weight 5.01 ? 0.02 g) were stocked in 12 rectangular tanks with 10 fish per tank in triplicates. At the end of the experiment, haematology, histology and IGF I gene expression of the different groups were analysed. The haemoglobin (Hb) content, RBC count and WBC count of L. rohita varied significantly (p 0.05) effect on MCH, MCHC and lymphocyte content of the cultured fish. The group which were fed T3 diet had significantly (p < 0.05) higher IGF-I gene expression as compared to other groups. The histological examination of liver revealed no pathological alteration of this organ. Similarly, there were no pathological changes observed in intestinal tissue in any dietary treatment group. Based on the findings of the present study, it is concluded that exogenous enzyme supplementation of DORB-based diets improves the physiological status and growth performances of Labeo rohita

PPAR-&gamma; Partial Agonists in Disease-Fate Decision with Special Reference to Cancer

Peroxisome proliferator-activated receptor-&gamma; (PPAR-&gamma;) has emerged as one of the most extensively studied transcription factors since its discovery in 1990, highlighting its importance in the etiology and treatment of numerous diseases involving various types of cancer, type 2 diabetes mellitus, autoimmune, dermatological and cardiovascular disorders. Ligands are regarded as the key determinant for the tissue-specific activation of PPAR-&gamma;. However, the mechanism governing this process is merely a contradictory debate which is yet to be systematically researched. Either these receptors get weakly activated by endogenous or natural ligands or leads to a direct over-activation process by synthetic ligands, serving as complete full agonists. Therefore, fine-tuning on the action of PPAR-&gamma; and more subtle modulation can be a rewarding approach which might open new avenues for the treatment of several diseases. In the recent era, researchers have sought to develop safer partial PPAR-&gamma; agonists in order to dodge the toxicity induced by full agonists, akin to a balanced activation. With a particular reference to cancer, this review concentrates on the therapeutic role of partial agonists, especially in cancer treatment. Additionally, a timely examination of their efficacy on various other disease-fate decisions has been also discussed

Tree species diversity, distribution and soil nutrient status along altitudinal gradients in Saptasajya hill range, Eastern Ghats, India

This study analysed the diversity of tree species, their distribution and soil nutrient status along altitudinal gradients of Saptasajya hill range, Eastern Ghats, India. Thirty quadrats of 10m×10m size for trees across the altitude ranges between 81m and 450m were laid. Field sampling were conducted at 3 different elevation sites of the hill range: Site 1- Low Elevation Forest (LEF), Site 2- Middle Elevation Forest (MEF) and Site 3- High Elevation Forest (HEF). A total of 368 individuals which belongs to 48 species among 42 genera and 27 families were recorded in 0.3 ha sampling areas. Maximum numbers of tree species occurred at LEF (35) followed by MEF (34) and HEF (14). The density of tree species varied from 433 ha-1 to 390 ha-1 with average basal area of 30.64 m2/ha. The Shannon diversity index (H′) varied among the three sites was 2.19 (LEF), 1.84 (MEF) and 1.29 (HEF). The soil parameters of three forest sites were analysed and correlated with tree species richness, diversity and density. Species richness and tree diversity index were positively correlated with pH (r=0.743 and r=0.829 respectively; p<0.05), whereas tree density was negatively correlated with pH (r= -0.597), phosphorous (r= -0.401), organic carbon (r= -0.543) and tree diversity index (r= -0.364). It could be helpful to understand the pattern of vegetation and its relation to soil nutrients in Eastern Ghats of India implicating conservation plan for tree species in tropical moist deciduous forests

Dietary flavonoids as modulators of non-coding RNAs in hormone-associated cancer

Non-coding RNA (ncRNAs) is greatly known to be involved in many cellular processes such as growth and development including tumorigenesis. Alterations in expression of ncRNAs are observed in several cancers. Therefore, they are regarded as potential players in carcinogenesis. In a broader view, it has been documented that ncRNAs are also involved in hormone-associated cancers (HACs) by regulating their epigenetic processes. Hence, HACs emerge on the radar of scientific community and cancer research as they are widely influenced by hormone levels and latter promotes cancer growth. Although various risk factors point to HACs, findings are inconsistent and not uniform. Dietary flavonoids are amongst the natural compounds that are capable of repressing the proliferation and growth of numerous cancer cells. This could be rewarding and might open new avenues for cancer treatment. In addition, flavonoids seem to have anti-hormone like properties in HACs. However, there are no direct assessment of flavonoids and their effects in HACs. The studies are not stringent enough to evaluate the intake of these dietary flavonoids. Herein, the present review highlights the role of numerous dietary flavonoids as ncRNA modulators in HACs. Mechanisms of ncRNA regulation and the role of hormones associated with hormone-specific cancer has also been discussed

Modulation of key enzymes of glycolysis, gluconeogenesis, amino acid catabolism, and TCA cycle of the tropical freshwater fish Labeo rohita fed gelatinized and non-gelatinized starch diet

A 60-day experiment was conducted to study the effect of dietary gelatinized (G) and non-gelatinized (NG) starch on the key metabolic enzymes of glycolysis (hexokinase, glucokinase, pyruvate kinase, and lactate dehydrogenase), gluconeogenesis (glucose-6 phosphatase and fructose-1,6 bisphosphatase), protein metabolism (aspartate amino transferase and alanine amino transferase), and TCA cycle (malate dehydrogenase) in Labeo rohita juveniles. In the analysis, 234 juveniles (2.53 +/- A 0.04 g) were randomly distributed into six treatment groups each with three replicates. Six semi-purified diets containing NG and G cornstarch, each at six levels of inclusion (0, 20, 40, 60, 80, and 100) were prepared viz., T1 (100% NG, 0% G starch), T2 (80% NG, 20% G starch), T3 (60% NG, 40% G starch), T4 (40% NG, 60% G starch), T5 (20% NG, 80% G starch), and T6 (0% NG, 100% G starch). Dietary G:NG starch ratio had a significant (P 0.05) influenced by the type of dietary starch. The alanine amino transferase activity in both liver and muscle showed an increasing trend with the decrease in the dietary G level. The liver and muscle malate dehydrogenase activities were lowest in the T6 group and highest in the T1 group. Results suggest that NG (100%) starch diet significantly induced more the enzyme activities of amino acid metabolism, gluconeogenesis, and TCA cycle, whereas partial or total replacement of raw starch by gelatinized starch increased the glycolytic enzyme activity

Transcriptome analysis reveals common differential and global gene expression profiles in bluetongue virus serotype 16 (BTV-16) infected peripheral blood mononuclear cells (PBMCs) in sheep and goats

Bluetongue is an economically important infectious, arthropod borne viral disease of domestic and wild ruminants, caused by Bluetongue virus (BTV). Sheep are considered the most susceptible hosts, while cattle, buffalo and goats serve as reservoirs. The viral pathogenesis of BTV resulting in presence or absence of clinical disease among different hosts is not clearly understood. In the present study, transcriptome of sheep and goats peripheral blood mononuclear cells infected with BTV-16 was explored. The differentially expressed genes (DEGs) identified were found to be significantly enriched for immune system processes - NFκB signaling, MAPK signaling, Ras signaling, NOD signaling, RIG signaling, TNF signaling, TLR signaling, JAK-STAT signaling and VEGF signaling pathways. Greater numbers of DEGs were found to be involved in immune system processes in goats than in sheep. Interestingly, the DEHC (differentially expressed highly connected) gene network was found to be dense in goats than in sheep. Majority of the DEHC genes in the network were upregulated in goats but down-regulated in sheep. The network of differentially expressed immune genes with the other genes further confirmed these findings. Interferon stimulated genes - IFIT1 (ISG56), IFIT2 (ISG54) and IFIT3 (ISG60) responsible for antiviral state in the host were found to be upregulated in both the species. STAT2 was the TF commonly identified to co-regulate the DEGs, with its network showing genes that are downregulated in sheep but upregulated in goats. The genes dysregulated and the networks perturbed in the present study indicate host variability with a positive shift in immune response to BTV in goats than in sheep