Analgesic, anti-inflammatory and antipyretic activities of the ethanolic extract and its fractions of Cleome rutidosperma

Oral administration of the ethanolic extract (200 and 400 mg/kg, p.o) and its fractions (200 mg/kg each) of the aerial parts of Cleome rutidosperma produced significant analgesic activity in acetic acid-induced writhing and tail immersion tests, anti-inflammatory effect against carrageenin induced inflammation and adjuvant induced polyarthritis and antipyretic activity against yeast-induced pyrexia. Fractionation of the ethanolic extract potentiated the activities.     

Qualitative risk assessment of transmission pathways of highly pathogenic avian influenza (HPAI) virus at live poultry markets in Dhaka city,Bangladesh

Analysis of environmental samples obtained from the Live Poultry Markets (LPMs) of Dhaka City, Bangladesh, has revealed that the highest degree of prevalence of highly pathogenic avian influenza A (HPAI, H5N1), besides other subtypes of the LPAI virus, poses the plausible risk of transmission of these viruses between human and poultry species. The present study was conducted using the OIE risk analysis framework to assess the risk level of each pathway successively. The estimated risk parameters were integrated towards to obtain the overall risk level for each specific HPAI transmission pathway using the matrix adapted by Cristobel Zepeda accompanying other expert consultations. The relevant data obtained from published and unpublished sources, together with survey data of field observations, were used to formulate and confirm the risk pathways and their associated risks. The results revealed that the risk of the release of the HPAI virus was medium when exposure was high. Additionally, the consequence would be considered very high with a medium degree of uncertainty for all parameters. Ultimately, the overall risk for transmission was estimated as medium with a medium degree of uncertainty. The findings of this study reveal that there is a significant threat that HPAI virus transmission could occur among poultry and humans and effectively sustain within the environment of the LPMs. Our findings are primarily focused on public health considerations, the hygienic slaughter of poultry and the relevant cleaning and sanitation practices conducted in the LPMs to support evidence‐based decision‐making processes. The findings of the study have the potential to be used to formulate effective risk reduction measures and can be further adapted in low‐resource settings without major infrastructural changes required of the LPMs. All of which would reduce the risk of HPAI virus release and further lessen the degree of exposure and transmission in established LPMs.     

Cofilin promotes actin polymerization and defines the direction of cell motility

A general caging method for proteins that are regulated by phosphorylation was used to study the in vivo biochemical action of cofilin and the subsequent cellular response. By acute and local activation of a chemically engineered, light-sensitive phosphocofilin mimic, we demonstrate that cofilin polymerizes actin, generates protrusions, and determines the direction of cell migration. We propose a role for cofilin that is distinct from its role as an actin-depolymerizing factor.     

Neurofibromas in NF1: Schwann cell origin and role of tumor environment

Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (cre/lox) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.     

Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence

Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the approximately 3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.     

Modification of the active site of alkaline phosphatase by site-directed mutagenesis

The catalytically essential amino acid in the active site of bacterial alkaline phosphatase (Ser-102) has been replaced with a cysteine by site-directed mutagenesis. The resulting thiol enzyme catalyzes the hydrolysis of a variety of phosphate monoesters. The rate-determining step of hydrolysis, however, is no longer the same for catalysis when the active protein nucleophile is changed from the hydroxyl of serine to the thiol of cysteine. Unlike the steady-state kinetics of native alkaline phosphatase, those of the mutant show sensitivity to the leaving group of the phosphate ester.     

Development of an agricultural crops spectral library and classification of crops at cultivar level using hyperspectral data

In the context of a growing interest in remote sensing for precision agriculture applications, the utility of space-borne hyperspectral imaging for the development of a crop-specific spectral library and automatic identification and classification of three cultivars for each of rice (Oryza sativa L.), chilli (Capsicum annuum L.), sugarcane (Saccharum officinarum L.) and cotton (Gossipium hirsutum L.) crops have been investigated in this study. The classification of crops at cultivar level using two spectral libraries developed using hyperspectral reflectance data at canopy scale (in-situ hyperspectral measurements) and at pixel scale (Hyperion data) has shown promising results with 86.5 and 88.8% overall classification accuracy, respectively. This observation highlights the possible integration of in-situ hyperspectral measurements with space-borne hyperspectral remote sensing data for automatic identification and discrimination of various crop cultivars. However, considerable spectral similarity is observed between cultivars of rice and sugarcane crops which may pose problems in the accurate identification of various crop cultivars.     

Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor

Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.