Herbage Mass and Chemical Composition of the Heterogeneous Grasslands Affected by Harvesting TIME in Subtropical Terrain Nepal

A study was carried out to evaluate the productivity and chemical composition of heterogeneous grasslands at Agriculture and Forestry University (AFU) livestock farm. The four grassland ecotypes were chosen as upland north, upland south, lowland south and lowland north. The dominating herbage species and cover abundance by the botanical groups were studied on day before the harvesting. Later, the herbage dry matter productivity was estimated by quadrat cutting during May and June, 2017. Chemical analysis was done by using the proximate method for dry matter (DM), crude protein (CP), crude fiber (CF) and ether extract (EE) content. Research results showed that the AFU grassland dominated by perennial grasses and sedges followed by the forbs. The mean coverage of grasses and sedges was about 55%, whilst that of forbs was about 29% and the least was for legumes (about 4%). The cumulative herbage mass was about 1.53 t/ ha on the DM basis, whilst the highest DM was found in the upland-south (1.74 t/ha) and the least was in the upland-north (1.334 t/ha). The proximate analysis further revealed that the site had no effect on CF content, whilst the CP was significant only at the second harvest for the lowland north (8.34%).  Data revealed that the herbage composition might depend upon the soil moisture availability and geographical aspect. The dominance of perennial grasses at AFU grasslands revealed the yield stability, but needs the improvement through inoculation with leguminous forages for improved feed quality

Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation

<p>Abstract</p> <p>Background</p> <p>Clinical malaria has proven an elusive burden to enumerate. Many cases go undetected by routine disease recording systems. Epidemiologists have, therefore, frequently defaulted to actively measuring malaria in population cohorts through time. Measuring the clinical incidence of malaria longitudinally is labour-intensive and impossible to undertake universally. There is a need, therefore, to define a relationship between clinical incidence and the easier and more commonly measured index of infection prevalence: the "parasite rate". This relationship can help provide an informed basis to define malaria burdens in areas where health statistics are inadequate.</p> <p>Methods</p> <p>Formal literature searches were conducted for <it>Plasmodium falciparum </it>malaria incidence surveys undertaken prospectively through active case detection at least every 14 days. The data were abstracted, standardized and geo-referenced. Incidence surveys were time-space matched with modelled estimates of infection prevalence derived from a larger database of parasite prevalence surveys and modelling procedures developed for a global malaria endemicity map. Several potential relationships between clinical incidence and infection prevalence were then specified in a non-parametric Gaussian process model with minimal, biologically informed, prior constraints. Bayesian inference was then used to choose between the candidate models.</p> <p>Results</p> <p>The suggested relationships with credible intervals are shown for the Africa and a combined America and Central and South East Asia regions. In both regions clinical incidence increased slowly and smoothly as a function of infection prevalence. In Africa, when infection prevalence exceeded 40%, clinical incidence reached a plateau of 500 cases per thousand of the population <it>per annum</it>. In the combined America and Central and South East Asia regions, this plateau was reached at 250 cases per thousand of the population <it>per annum</it>. A temporal volatility model was also incorporated to facilitate a closer description of the variance in the observed data.</p> <p>Conclusion</p> <p>It was possible to model a relationship between clinical incidence and <it>P. falciparum </it>infection prevalence but the best-fit models were very noisy reflecting the large variance within the observed opportunistic data sample. This continuous quantification allows for estimates of the clinical burden of <it>P. falciparum </it>of known confidence from wherever an estimate of <it>P. falciparum </it>prevalence is available.</p

Allelic dimorphism of Plasmodium vivax gam-1 in the Indian subcontinent

BACKGROUND: Genetic polymorphism is an inevitable component of a complex organism especially in multistage infectious organisms such as malaria parasites. Understanding the population genetic structure of the parasites would provide valuable information for effective malaria control strategies. Recently, the development of molecular tools like PCR has made analysis of field samples possible and easier and research on Plasmodium vivax has also been strengthened. Not many reports are available on the genetic polymorphism of P. vivax from the Indian sub-continent. This study evaluates the extent of diversity in field isolates of India with respect to Pvgam-1. METHODS: A study was designed to assess the diversity of Pvgam-1 among field isolates from India, using a nested PCR assay. Field isolates were collected from different regions of the country and the observed variability was confirmed by sequencing data. RESULTS: Both Belem and Chesson type alleles were present either exclusively or in mixed form among isolates of all 10 study sites. The Belem type allele was predominant, occurring in 67% of isolates. The proportion of isolates showing the mixed form (both Belem and Chesson type alleles occurring together in the same isolate) was about 13 overall (up to 38.5% in some isolates). Sequencing of the PCR-amplified Belem and Chesson type alleles confirmed the PCR results. Among the 10 study sequences, 11 polymorphic sites and four singleton variations were observed. All the nucleotide substitutions were non-synonymous. CONCLUSION: Study shows limited diversity of Pvgam-1 marker in Indian isolates with well representation of both Belem and Chesson type alleles

Polymorphisms of TNF-enhancer and gene for FcγRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population

<p>Abstract</p> <p>Background</p> <p>Susceptibility/resistance to <it>Plasmodium falciparum </it>malaria has been correlated with polymorphisms in more than 30 human genes with most association analyses having been carried out on patients from Africa and south-east Asia. The aim of this study was to examine the possible contribution of genetic variants in the <it>TNF </it>and <it>FCGR2A </it>genes in determining severity/resistance to <it>P. falciparum </it>malaria in Indian subjects.</p> <p>Methods</p> <p>Allelic frequency distribution in populations across India was first determined by typing genetic variants of the <it>TNF </it>enhancer and the <it>FCGR2A </it>G/A SNP in 1871 individuals from 55 populations. Genotyping was carried out by DNA sequencing, single base extension (SNaPshot), and DNA mass array (Sequenom). Plasma TNF was determined by ELISA. Comparison of datasets was carried out by Kruskal-Wallis and Mann-Whitney tests. Haplotypes and LD plots were generated by PHASE and Haploview, respectively. Odds ratio (OR) for risk assessment was calculated using EpiInfo™ version 3.4.</p> <p>Results</p> <p>A novel single nucleotide polymorphism (SNP) at position -76 was identified in the <it>TNF </it>enhancer along with other reported variants. Five <it>TNF </it>enhancer SNPs and the <it>FCGR2A </it>R131H (G/A) SNP were analyzed for association with severity of <it>P. falciparum </it>malaria in a malaria-endemic and a non-endemic region of India in a case-control study with ethnically-matched controls enrolled from both regions. <it>TNF </it>-1031C and -863A alleles as well as homozygotes for the TNF enhancer haplotype CACGG (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) correlated with enhanced plasma TNF levels in both patients and controls. Significantly higher TNF levels were observed in patients with severe malaria. Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria. The high-affinity IgG2 binding FcγRIIa AA (131H) genotype was significantly associated with protection from disease manifestation, with stronger association observed in the malaria non-endemic region. These results represent the first genetic analysis of the two immune regulatory molecules in the context of <it>P. falciparum </it>severity/resistance in the Indian population.</p> <p>Conclusion</p> <p>Association of specific <it>TNF </it>and <it>FCGR2A </it>SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India.</p

Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL), a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h) was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required.</p> <p>Methods</p> <p>One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa) were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers <it>msp</it>-<it>1 </it>and <it>msp</it>-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in <it>pfmdr</it>1 was also carried out in the samples obtained from patients before and after the treatment.</p> <p>Results</p> <p>The PCR corrected cure rates were high at both the sites viz. 100% (n = 53) in Assam and 98.6% (n = 71) in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91) and 184 (91.3%, n = 91) of <it>pfmdr1 </it>gene.</p> <p>Conclusion</p> <p>AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria in India. The polymorphism in <it>pfmdr</it>1 gene is not co-related with clinical outcome. However, treatment failure can also occur due to incomplete absorption of the drug as is suspected in one case of failure at D7 in the study. AL can be a viable alternative of artesunate plus sulphadoxine/pyrimethamine (AS + SP), however, the drug should be used rationally and efficacy needs to be monitored periodically.</p

Mechanistic insights into the early life stage microbiota of silver pompano (Trachinotus blochii)

Deep investigations of host-associated microbiota can illuminate microbe-based solutions to improve production in an unprecedented manner. The poor larval survival represents the critical bottleneck in sustainable marine aquaculture practices. However, little is known about the microbiota profiles and their governing eco-evolutionary processes of the early life stages of marine teleost, impeding the development of suitable beneficial microbial management strategies. The study provides first-hand mechanistic insights into microbiota and its governing eco-evolutionary processes in early life stages of a tropical marine teleost model, Trachinotus blochii

Mechanistic insights into the early life stage microbiota of silver pompano (Trachinotus blochii)

IntroductionDeep investigations of host-associated microbiota can illuminate microbe-based solutions to improve production in an unprecedented manner. The poor larval survival represents the critical bottleneck in sustainable marine aquaculture practices. However, little is known about the microbiota profiles and their governing eco-evolutionary processes of the early life stages of marine teleost, impeding the development of suitable beneficial microbial management strategies. The study provides first-hand mechanistic insights into microbiota and its governing eco-evolutionary processes in early life stages of a tropical marine teleost model, Trachinotus blochii.MethodsThe microbiota profiles and their dynamics from the first day of hatching till the end of metamorphosis and that of fingerling’s gut during the routine hatchery production were studied using 16S rRNA amplicon-based high-throughput sequencing. Further, the relative contributions of various external factors (rearing water, live feed, microalgae, and formulated feed) to the microbiota profiles at different ontogenies was also analyzed.ResultsA less diverse but abundant core microbial community (~58% and 54% in the whole microbiota and gut microbiota, respectively) was observed throughout the early life stages, supporting ‘core microbiota’ hypothesis. Surprisingly, there were two well-differentiated clusters in the whole microbiota profiles, ≤10 DPH (days post-hatching) and &gt; 10 DPH samples. The levels of microbial taxonomic signatures of stress indicated increased stress in the early stages, a possible explanation for increased mortality during early life stages. Further, the results suggested an adaptive mechanism for establishing beneficial strains along the ontogenetic progression. Moreover, the highly transient microbiota in the early life stages became stable along the ontogenetic progression, hypothesizing that the earlier life stages will be the best window to influence the microbiota. The egg microbiota also crucially affected the microbial community. Noteworthily, both water and the feed microbiota significantly contributed to the early microbiota, with the feed microbiota having a more significant contribution to fish microbiota. The results illustrated that rotifer enrichment would be the optimal medium for the early larval microbiota manipulations.ConclusionThe present study highlighted the crucial foundations for the microbial ecology of T. blochii during early life stages with implications to develop suitable beneficial microbial management strategies for sustainable mariculture production

Genetic structure of Plasmodium falciparum field isolates in eastern and north-eastern India

<p>Abstract</p> <p>Background</p> <p>Molecular techniques have facilitated the studies on genetic diversity of <it>Plasmodium </it>species particularly from field isolates collected directly from patients. The <it>msp-1 </it>and <it>msp-2 </it>are highly polymorphic markers and the large allelic polymorphism has been reported in the block 2 of the <it>msp-1 </it>gene and the central repetitive domain (block3) of the <it>msp-2 </it>gene. Families differing in nucleotide sequences and in number of repetitive sequences (length variation) were used for genotyping purposes. As limited reports are available on the genetic diversity existing among <it>Plasmodium falciparum </it>population of India, this report evaluates the extent of genetic diversity in the field isolates of <it>P. falciparum </it>in eastern and north-eastern regions of India.</p> <p>Methods</p> <p>A study was designed to assess the diversity of <it>msp-1 </it>and <it>msp-2 </it>among the field isolates from India using allele specific nested PCR assays and sequence analysis. Field isolates were collected from five sites distributed in three states namely, Assam, West Bengal and Orissa.</p> <p>Results</p> <p><it>P. falciparum </it>isolates of the study sites are highly diverse in respect of length as well as sequence motifs with prevalence of all the reported allelic families of <it>msp-1 </it>and <it>msp-2</it>. Prevalence of identical allelic composition as well as high level of sequence identity of alleles suggest a considerable amount of gene flow between the <it>P. falciparum </it>populations of different states. A comparatively higher proportion of multiclonal isolates as well as multiplicity of infection (MOI) was observed among isolates of highly malarious districts Karbi Anglong (Assam) and Sundergarh (Orissa). In all the five sites, R033 family of <it>msp-1 </it>was observed to be monomorphic with an allele size of 150/160 bp. The observed 80–90% sequence identity of Indian isolates with data of other regions suggests that Indian <it>P. falciparum </it>population is a mixture of different strains.</p> <p>Conclusion</p> <p>The present study shows that the field isolates of eastern and north-eastern regions of India are highly diverse in respect of <it>msp-1 </it>(block 2) and <it>msp-2 </it>(central repeat region, block 3). As expected Indian isolates present a picture of diversity closer to southeast Asia, Papua New Guinea and Latin American countries, regions with low to meso-endemicity of malaria in comparison to African regions of hyper- to holo-endemicity.</p

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma