Insight towards the conserved water mediated recognition of catalytic and structural Zn+2 ions in human Matrix Metalloproteinase-8 enzyme: A study by MD-simulation methods

Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC – W_H (W₁)…..W₂ ….H₁₆₂ - ZnS) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn⁺² ions in the enzyme through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic drug design protocol.     

Metal Chelates as Fungicides

A remarkable improvement in the emulsifying properties of proteins was observed in mixtures of serum albumin-dextran sulfate, lysozyme-dextran sulfate, serum albumin-chondroitin sulfate, α-lactalbumin-chondroitin sulfate and lysozyme-chondroitin sulfate. The emulsifying properties of these protein-polysaccharide complexes were affected by the molecular size of the polysaccharide and by such conditions as the presence of salt, acidic or alkaline pH, and heating. On the other hand, the emulsifying properties of ovalbumin-dextran hybrids prepared by covalent attachment were more enhanced in alkaline pH or by heating. The molecular size of the ovalbumin-dextran hybrids greatly affected the emulsifying properties.     

Competitive interactions between entomopathogenic nematodes and parasitoid venom

Entomopathogenic nematodes and parasitoid larvae of some wasps play important roles in the natural control of the pest insects. However, it has not been excluded that competition between nematodes and wasps may in some cases reduce their efficacy in the pest control. Using caterpillars of Spodoptera littoralis, we examined interactions between the nematode Steinernema carpocapsae and the venom of the parasitoid Habrobracon hebetor. The survival of S. littoralis caterpillars was reduced in a dose-dependent manner when 5 to 500 nematodes or 0.005–0.1 venom units were applied to single caterpillars. High doses of either nematodes or the venom caused death within 1–3 days in all treated hosts. The low doses of nematodes killed caterpillars within a week, in some cases when they attempted to pupate. Caterpillars receiving low venom doses were characterized by extended survival time terminated with death due to starvation. Combined treatment of nematodes and the venom were mutually synergistic and elicited severe lethal effects. The nematodes were fully resistant to the venom and can feed and grow on the symbiotic bacteria in vitro. The venom impairs food processing and causes death of caterpillars due to starvation. Disruption of the hormonal regulation of metamorphosis by ecdysteroids and juvenile hormone could be responsible for defective moults block at different stages of the moulting process, regionally restricted moulting, moults to “intermediates” combining regions of newly secreted larval and pupal cuticles.     

SARS-CoV-2 cell receptor gene ACE2 -mediated immunomodulation in breast cancer subtypes

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has impacted the world severely. The binding of the SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) and its intake by the host cell is a necessary step for infection. ACE2 has garnered widespread therapeutic possibility as it is entry/interactive point for SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19) pandemic and providing a critical regulator for immune modulation in various disease. Patients with suffering from cancer always being on the verge of being immune compromised therefore gaining knowledge about how SARS-CoV-2 viruses affecting immune cells in human cancers will provides us new opportunities for preventing or treating virus-associated cancers. Despite COVID-19 pandemic got center stage at present time, however very little research being explores, which increase our knowledge in context with how SARS-CoV-2 infection affect cancer a cellular level. Therefore, in light of the ACE-2 as an important contributor of COVID-19 global, we analyzed correlation between ACE2 and tumor immune infiltration (TIL) level and the type markers of immune cells were investigated in breast cancer subtypes by using TIMER database. Our findings shed light on the immunomodulatory role of ACE2 in the luminal A subtype which may play crucial role in imparting therapeutic resistance in this cancer subtype.     

Mice with dysfunctional TGF-β signaling develop altered intestinal microbiome and colorectal cancer resistant to 5FU

Emerging data show a rise in colorectal cancer (CRC) incidence in young men and women that is often chemoresistant. One potential risk factor is an alteration in the microbiome. Here, we investigated the role of TGF-β signaling on the intestinal microbiome and the efficacy of chemotherapy for CRC induced by azoxymethane and dextran sodium sulfate in mice. We used two genotypes of TGF-β-signaling-deficient mice (Smad4^+/? and Smad4^+/?Sptbn1^+/?), which developed CRC with similar phenotypes and had similar alterations in the intestinal microbiome. Using these mice, we evaluated the intestinal microbiome and determined the effect of dysfunctional TGF-β signaling on the response to the chemotherapeutic agent 5-Fluoro-uracil (5FU) after induction of CRC. Using shotgun metagenomic sequencing, we determined gut microbiota composition in mice with CRC and found reduced amounts of beneficial species of Bacteroides and Parabacteroides in the mutants compared to the wild-type (WT) mice. Furthermore, the mutant mice with CRC were resistant to 5FU. Whereas the abundances of E. boltae, B.dorei, Lachnoclostridium sp., and Mordavella sp. were significantly reduced in mice with CRC, these species only recovered to basal amounts after 5FU treatment in WT mice, suggesting that the alterations in the intestinal microbiome resulting from compromised TGF-β signaling impaired the response to 5FU. These findings could have implications for inhibiting the TGF-β pathway in the treatment of CRC or other cancers.     

Release of Mediator Enzyme β-Hexosaminidase and Modulated Gene Expression Accompany Hemocyte Degranulation in Response to Parasitism in the Silkworm Bombyx mori

In insects infections trigger hemocyte-mediated immune reactions including degranulation by exocytosis; however, involvement of mediator enzymes in degranulation process is unknown in insects. We report here that in silkworm Bombyx mori, infection by endoparasitoid Exorista bombycis and microsporidian Nosema bombycis activated granulation in granulocytes and promoted degranulation of accumulated structured granules. During degranulation the mediator lysosomal enzyme β-hexosaminidase showed increased activity and expression of β-hexosaminidase gene was enhanced. The events were confirmed in vitro after incubation of uninfected hemocytes with E. bombycis larval tissue protein. On infection, cytotoxicity marker enzyme lactate dehydrogenase (LDH) was released from the hemocytes illustrating cell toxicity. Strong positive correlation (R²?=?0.71) between LDH activity and β-hexosaminidase released after the infection showed parasitic–protein-induced hemocyte damage and accompanied release of the enzymes. Expression of β-hexosaminidase gene was enhanced in early stages after infection followed by down regulation. The expression showed positive correlation (R²?=?0.705) with hexosaminidase activity pattern. B. mori hexosaminidase showed 98% amino acid similarity with that of B. mandarina showing origin from same ancestral gene; however, 45–60% varied from other lepidopterans showing diversity. The observation signifies the less known association of hexosaminidase in degranulation of hemocytes induced by parasitic infection in B. mori and its divergence in different species.

     

A new species of the genus Cirrhimuraena (Anguilliformes: Ophichthidae) from the Bay of Bengal,India

A new species of the genus Cirrhimuraena (Anguilliformes: Ophichthidae), Cirrhimuraena indica sp. nov., is described based on eight specimens collected from the Paradip (Odisha) and Petuaghat harbours (West Bengal) along the Bay of Bengal. The species is distinct in having the upper jaw fringed with 16–17 cirri before posterior nostril and 4–5 in between the anterior and posterior nostrils on the side; dorsal fin originates above the level of gill opening, predorsal length is 9.3–10.9 in total length; the head is relatively large, the length is 9.3–9.8 in total length; no infraorbital pores are observed between the nostrils; teeth are numerous, small, conical and in bands on each jaw; pores are present before the gill opening 10–11 and before anus 47–48; pectoral-fin length is 2.4–2.8 in head length; predorsal vertebrae are 8–10, pre-anal vertebrae 43–47 and total vertebrae 164–169. In the maximum likelihood tree analysis for COI gene, the new species belongs to the same clade as the other congener of Cirrhimuraena chinensis and is separated from the species morphologically and genetically.     

Dynamic large branching hash tree based secure and efficient dynamic auditing protocol for cloud environment

Cluster Computing - Cloud computing model offers various platforms services and provides a scalable, on-demand service at any time-anywhere manner. However, in the outsourcing strategy, users no...     

Alkaline phosphatase and acid phosphatase levels in saliva and serum of patients with healthy periodontium,gingivitis, and periodontitis before and after scaling with root planing: A clinico-biochemical study

Periodontitis is commonly diagnosed based on clinical parameters. However, the analysis of a few unique biomarkers of the disease process present in the saliva and blood can further assist the estimation of the rate of disease progression.AimThe present study attempted to correlate the alkaline phosphatase (ALP) and acid phosphatase (ACP) levels in saliva and serum between patients with healthy periodontium, gingivitis, and chronic periodontitis.Materials and methodsThe present study was conducted in 135 subjects between 20 and 55 years of age. The subjects were divided into three groups, namely healthy (Group A), gingivitis (Group B), and chronic periodontitis (Group C). The clinical parameters were recorded using the plaque index (PI), gingival index (GI), and probing depth (PD). Saliva and serum were analyzed for ALP and ACP levels using an auto analyzer. All patients underwent scaling and root planning (SRP) along with oral hygiene instructions. Patients were then recalled after four weeks, and blood and saliva samples were collected to estimate ALP and ACP levels prior to clinical examination.ResultsThe clinical parameters exhibited a statistically significant decrease in the PI and GI in both group B and group C after SRP. A significant change in the PD and attachment levels (AL) was observed in the periodontitis group after SRP. The mean salivary & serum ALP levels exhibited a statistically significant decrease in group B & C after SRP. The mean serum ACP levels exhibited a statistically significant decrease in group B & C after SRP However, the salivary ACP levels decrease after SRP was only statistically significant in group C.ConclusionSerum and salivary ALP and ACP levels were markedly decreased in the gingivitis and periodontitis groups after SRP and were positively correlated with the clinical parameters.