Alternative Livelihood for Scheduled Caste Population in Cuddalore District through Sustainable Utilization of Marine Waste for Oyster Mushroom Cultivation

Edible mushroom cultivation is a profitable cottage industry, in which oyster mushroom occupies a prominent place in India. A good substrate is a key factor that determines the profitability of the mushroom cultivation. Marine waste were evaluated for the production of oyster mushroom as a means of managing the vast amount of organic waste that are being generated by fast growing seafood industries. In the present study, sustainable utilization of marine bio-waste for the cultivation of oyster mushroom (Pleurotus florida) and the standardized technology was transferred to scheduled caste population in and around Parangipettai, Tamil Nadu, India. The participants have collected marine wastes from the landing centre and processed as per the procedure taught during the lectures as well as demonstration. The experimental work was designed with Completely Randomized Design (CRD) with four treatments (375 g of paddy straw with 125 g of fish waste, shell waste, seaweed and seagrass amended separately) and a control (500 g of paddy straw) with three replications. Continuous hands on training were given for a period of one month to the participants on cultivation of oyster mushroom using marine bio-wastes as supplementary substrate along with paddy straw. During this one month training, the participants understand the technology thoroughly starting from the substrate preparation and processing, spawn handling, mushroom bed preparation, continuous monitoring of the culture environment, harvest, value addition and marketing etc. Further, the nutritive value and biological activities of oyster mushroom cultured on different marine waste were evaluated. Average yield was tested in three flushes of P.florida on four different substrates with control. Among various substrates, maximum yield (498.11±7.80 g) was recorded in fish waste. However, minimum average yield (266.91±4.35 g) was recorded in seaweed. The biological efficiency was recorded in four different substrates along with control. Among these, fish waste exhibited highest biological efficiency (99.62±1.56%). Very least efficiency was observed in control (53.38333±0.86784%). The proximate composition such as moisture, protein, carbohydrate, total lipid, crude fiber, amino acids and vitamins were estimated in P. florida which harvested from five different substrates. The highest moisture content (90.71%) was recorded in paddy straw and the least value (82.97%) was recorded in shell waste. The highest content of protein was found in fish waste (23.52%) and the lowest protein was found in seaweed (17.18%). The lowest lipid percentage was observed in fish waste (4%) and the highest lipid percentage was observed in paddy straw (8%). The lowest percentage (22.09%) of carbohydrate was observed in seaweed substrate and the highest carbohydrate percentage was observed in fish waste (36.54%). The maximum percentage of crude fiber was observed in fish waste (14.67%) and minimum in seaweed (8.75%). Three training programmes were successfully conducted to scheduled caste women population with the financial support of Department Science and Technology, Government of India. Micro funding was provided to the two self help groups belong to SC population and they became a small entrepreneur in that area. It is interesting to note that the oyster mushroom cultivation using marine waste as supplementary substrate along with paddy straw not only increase the yield and nutritional quality but it could be an alternative livelihood for scheduled caste population.Keywords: Mushroom, Marine waste, Culture, Proximate composition, Biomolegule

Glass forming ability and soft-magnetic properties of Fe-based glassy alloys developed using high phosphorous pig Iron

Glass forming ability (GFA) and soft-magnetic behaviour of melt-spun Fe69C5.5P11.5Mn0.4Si2.3Cr1.8Mo1B8.5 (alloy 2) and Fe68C9P12Mn1Si3Nb2B5, (alloy 3) alloys prepared using high phosphorous pig iron (h-PI, Fe80C14P2.2Mn0.4Si3.4) has been studied. The glass formation, thermo-physical and soft-magnetic properties of the alloys were analyzed for different quenching rates by varying wheel speed as 23, 26, 33, 39 and 43 m/s. The simultaneous incorporation of alloying elements (Cr, Mo, Nb) and metalloids (C, B, P, Si) transforms h-PI to complete glassy alloy, even at low quenching rates. The melt quenching rate influences the thermal parameters and Curie temperature of glassy ribbons in an opposite way. Amongst all, FeCPMnSiCrMoB glassy alloy show superior combination of higher glass transition temperature of 788 K, super cooled region of 34 K, glass Curie temperature of 552 K, coercivity less than 13 A/m and maximum saturation magnetization of 1.1 T. In addition, the annealing treatment at 758 K improves magnetic softness (1.7 A/m) of the alloy by relaxation of quenched-in stresses. The comparison of developed glassy alloy with similar Fe-glassy alloys and SENNTIX type alloys show best combination of thermo-physical and magnetic properties. The glassy alloy prepared using blast furnace high phosphorous pig iron can be used for uniformly gapped soft-magnetic cores

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

Src Kinases Are Required for a Balanced Production of IL-12/IL-23 in Human Dendritic Cells Activated by Toll-Like Receptor Agonists

BACKGROUND: Pathogen recognition by dendritic cells (DC) is crucial for the initiation of both innate and adaptive immune responses. Activation of Toll-like Receptors (TLRs) by microbial molecular patterns leads to the maturation of DC, which present the antigen and activate T cells in secondary lymphoid tissues. Cytokine production by DC is critical for shaping the adaptive immune response by regulating T helper cell differentiation. It was previously shown by our group that Src kinases play a key role in cytokines production during TLR4 activation in human DC. PRINCIPAL FINDINGS: In this work we investigated the role of Src kinases during different TLRs triggering in human monocyte-derived DC (MoDC). We found that Src family kinases are important for a balanced production of inflammatory cytokines by human MoDC upon stimulation of TLR3 and 8 with their respective agonists. Disruption of this equilibrium through pharmacological inhibition of Src kinases alters the DC maturation pattern. In particular, while expression of IL-12 and other inflammatory cytokines depend on Src kinases, the induction of IL-23 and co-stimulatory molecules do not. Accordingly, DC treated with Src inhibitors are not compromised in their ability to induce CD4 T cell proliferation and to promote the Th17 subset survival but are less efficient in inducing Th1 differentiation. CONCLUSIONS: We suggest that the pharmacological modulation of DC maturation has the potential to shape the quality of the adaptive immune response and could be exploited for the treatment of inflammation-related diseases

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Activated Human CD4+CD45RO+ Memory T-Cells Indirectly Inhibit NLRP3 Inflammasome Activation through Downregulation of P2X7R Signalling

Inflammasomes are multi-protein complexes that control the production of pro-inflammatory cytokines such as IL-1β. Inflammasomes play an important role in the control of immunity to tumors and infections, and also in autoimmune diseases, but the mechanisms controlling the activation of human inflammasomes are largely unknown. We found that human activated CD4+CD45RO+ memory T-cells specifically suppress P2X7R-mediated NLRP3 inflammasome activation, without affecting P2X7R-independent NLRP3 or NLRP1 inflammasome activation. The concomitant increase in pro-IL-1β production induced by activated memory T-cells concealed this effect. Priming with IFNβ decreased pro-IL-1β production in addition to NLRP3 inflammasome inhibition and thus unmasked the inhibitory effect on NLRP3 inflammasome activation. IFNβ suppresses NLRP3 inflammasome activation through an indirect mechanism involving decreased P2X7R signaling. The inhibition of pro-IL-1β production and suppression of NLRP3 inflammasome activation by IFNβ-primed human CD4+CD45RO+ memory T-cells is partly mediated by soluble FasL and is associated with down-regulated P2X7R mRNA expression and reduced response to ATP in monocytes. CD4+CD45RO+ memory T-cells from multiple sclerosis (MS) patients showed a reduced ability to suppress NLRP3 inflammasome activation, however their suppressive ability was recovered following in vivo treatment with IFNβ. Thus, our data demonstrate that human P2X7R-mediated NLRP3 inflammasome activation is regulated by activated CD4+CD45RO+ memory T cells, and provide new information on the mechanisms mediating the therapeutic effects of IFNβ in MS

Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites

CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

Background: A functional polymorphism located at 21 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves’ disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves’ disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn’s disease (CD) lesions. Methodology: Genotyping of rs1883832C.T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings: The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p= 0.025; OR (95% CI)= 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p= 0.002; OR (95% CI)= 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p= 0.5; OR (95% CI)= 1.04 (0.93–1.17)]. Conclusion: The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.Peer reviewe

The Myeloid Receptor PILRβ Mediates the Balance of Inflammatory Responses through Regulation of IL-27 Production

Paired immunoglobulin-like receptors beta, PILRβ, and alpha, PILRα, are related to the Siglec family of receptors and are expressed primarily on cells of the myeloid lineage. PILRβ is a DAP12 binding partner expressed on both human and mouse myeloid cells. The potential ligand, CD99, is found on many cell types, such as epithelial cells where it plays a role in migration of immune cells to sites of inflammation. Pilrb deficient mice were challenged with the parasite Toxoplasma gondii in two different models of infection induced inflammation; one involving the establishment of chronic encephalitis and a second mimicking inflammatory bowel disease in order to understand the potential role of this receptor in persistent inflammatory responses. It was found that in the absence of activating signals from PILRβ, antigen-presenting cells (APCs) produced increased amounts of IL-27, p28 and promoted IL-10 production in effector T cells. The sustained production of IL-27 led ultimately to enhanced survival after challenge due to dampened immune pathology in the gut. Similar protection was also observed in the CNS during chronic T. gondii infection after i.p. challenge again providing evidence that PILRβ is important for regulating aberrant inflammatory responses