Effect of skill on work productivity and physical body dimensions of the Oraon tea garden labourers of the Jalpaiguri district, West Bengal, India

Skill is one of the factors influencing labour productivity of manual labour. The present study aims to find out the possible relationship between skill and productivity and between skill and physical body dimension among the tea garden labourers of Northern West Bengal, India. Skill was measured by indigenously devised test protocols developed only for this purpose. Productivity or labour output was measured in terms of amount of tea leaves (in weight) plucked in a day by an individual. Physical body dimension was recorded in terms of a list of anthropometric traits. The results show an inconsistent relationship between skill and productive output and a non-significant relationship between skill and physical body dimensions. However, there are some trends that skill is high in younger individuals and low skill in females is associated with relatively high fat accumulation in the body.     

Phospholipase A2 as a target protein for nonsteroidal anti-inflammatory drugs (NSAIDS): crystal structure of the complex formed between phospholipase A2 and oxyphenbutazone at 1.6 A resolution

Phospholipase A(2) (PLA(2); EC 3.1.1.4) is a key enzyme involved in the production of proinflammatory mediators known as eicosanoids. The binding of the substrate to PLA(2) occurs through a well-formed hydrophobic channel. To determine the viability of PLA(2) as a target molecule for the structure-based drug design against inflammation, arthritis, and rheumatism, the crystal structure of the complex of PLA(2) with a known anti-inflammatory compound oxyphenbutazone (OPB), which has been determined at 1.6 A resolution. The structure has been refined to an R factor of 0.209. The structure contains 1 molecule each of PLA(2) and OPB with 2 sulfate ions and 111 water molecules. The binding studies using surface plasmon resonance show that OPB binds to PLA(2) with a dissociation constant of 6.4 x 10(-8) M. The structure determination has revealed the presence of an OPB molecule at the binding site of PLA(2). It fits well in the binding region, thus displaying a high level of complementarity. The structure also indicates that OPB works as a competitive inhibitor. A large number of hydrophobic interactions between the enzyme and the OPB molecule have been observed. The hydrophobic interactions involving residues Tyr(52) and Lys(69) with OPB are particularly noteworthy. Other residues of the hydrophobic channel such as Leu(3), Phe(5), Met(8), Ile(9), and Ala(18) are also interacting extensively with the inhibitor. The crystal structure clearly reveals that the binding of OPB to PLA(2) is specific in nature and possibly suggests that the basis of its anti-inflammatory effects may be due to its binding to PLA(2) as well.     

Expression and characterization of a novel CD6 ligand in cells derived from joint and epithelial tissues

CD6 is a T cell surface glycoprotein that plays an important role in interactions of thymocytes with thymic epithelial cells and in mature T cell interactions with selected nonprofessional tissue APCs. We describe a novel CD6 ligand (CD6L) 3A11 Ag that is distinct from the known CD6L (CD166). The 3A11 protein is expressed on cells derived from human thymus, skin, synovium, and cartilage, and its expression is enhanced by IFN-gamma. mAbs directed against the 3A11 Ag and CD166 exhibit distinct patterns of binding to a panel of cell lines. Confocal microscopy shows that both CD166 and the 3A11 Ag are expressed at the cell surface, and that these proteins colocalize. The 3A11 Ag has a molecular mass of 130 kDa and is immunoprecipitated using either mAb 3A11 or soluble CD6-Ig fusion protein. mAbs directed against individual CD6L were less potent than was soluble CD6-Ig fusion protein in reducing adhesion of T cells to adherent 3A11-positive epithelial cells in vitro, suggesting that these Abs recognize epitopes on the 3A11 Ag and CD166 that are distinct from CD6 binding sites. Finally, transfection of epithelial cells with CD166-specific small interfering RNAs significantly decreased CD166 expression without alteration in 3A11 Ag levels, and thus confirmed that these two CD6L are distinct. Taken together, our data identifies a novel 130-kDa CD6L that may mediate interactions of synovial and epithelial cells with T lymphocytes.     

Crystal structure of schistatin, a disintegrin homodimer from saw-scaled viper (Echis carinatus) at 2.5 A resolution

This is the first structure of a biological homodimer of disintegrin. Disintegrins are a class of small (4-14 kDa) proteins that bind to transmembrane integrins selectively. The present molecule is the first homodimer that has been isolated from the venom of Echis carinatus. The monomeric chain contains 64 amino acid residues. The three-dimensional structure of schistatin has been determined by the multiple isomorphous replacement method. It has been refined to an R-factor of 0.190 using all the data to 2.5 A resolution. The two subunits of the disintegrin homodimer are related by a 2-fold crystallographic symmetry. Thus, the crystallographic asymmetric unit contains a monomer of disintegrin. The monomer folds into an up-down topology with three sets of antiparallel beta-strands. The structure is well ordered with four intramolecular disulfide bonds. the two monomers are firmly linked to each other through two intermolecular disulfide bridges at their N termini together with several other interactions. This structure has corrected the error in the disulfide bond pattern of the two intermolecular disulfide bridges that was reported earlier using chemical methods. Unique sequence and structural features of the schistatin monomers suggest that they have the ability to bind well with both alphaIIb beta3 and alphav beta3 integrins. The N termini anchored two chains of the dimer diverge away at their C termini exposing the Arg-Gly-Asp motif into opposite directions thus enhancing their binding efficiency to integrins. This is one of the unique features of the present disintegrin homodimer and seems to be responsible for the clustering of integrin molecules. The homodimer binds to integrins apparently with a higher affinity than the monomers and also plays a role in the signaling pathway.     

Crystal structure of a highly acidic neurotoxin from scorpion Buthus tamulus at 2.2A resolution reveals novel structural features

The crystal structure of a highly acidic neurotoxin from the scorpion Buthus tamulus has been determined at 2.2A resolution. The amino acid sequence determination shows that the polypeptide chain has 64 amino acid residues. The pI measurement gave a value of 4.3 which is one of the lowest pI values reported so far for a scorpion toxin. As observed in other alpha-toxins, it contains four disulphide bridges, Cys12-Cys63, Cys16-Cys36, Cys22-Cys46, and Cys26-Cys48. The crystal structure reveals the presence of two crystallographically independent molecules in the asymmetric unit. The conformations of two molecules are identical with an r.m.s. value of 0.3A for their C(alpha) tracings. The overall fold of the toxin is very similar to other scorpion alpha-toxins. It is a betaalphabetabeta protein. The beta-sheet involves residues Glu2-Ile6 (strand beta1), Asp32-Trp39 (strand beta3) and Val45-Val55 (strand beta4). The single alpha-helix formed is by residues Asn19-Asp28 (alpha2). The structure shows a trans peptide bond between residues 9 and 10 in the five-membered reverse turn Asp8-Cys12. This suggests that this toxin belongs to classical alpha-toxin subfamily. The surface features of the present toxin are highly characteristic, the first (A-site) has residues, Phe18, Trp38 and Trp39 that protrude outwardly presumably to interact with its receptor. There is another novel face (N-site) of this neurotoxin that contains several negatively charged residues such as, Glu2, Asp3, Asp32, Glu49 and Asp50 which are clustered in a small region of the toxin structure. On yet another face (P-site) in a triangular arrangement, with respect to the above two faces there are several positively charged residues, Arg58, Lys62 and Arg64 that also protrude outwardly for a potentially potent interaction with other molecules. This toxin with three strong features appears to be one of the most toxic molecules reported so far. In this sense, it may be a new subclass of neurotoxins with the largest number of hot spots.     

Lens specification is the ground state of all sensory placodes, from which FGF promotes olfactory identity

The sense organs of the vertebrate head comprise structures as varied as the eye, inner ear, and olfactory epithelium. In the early embryo, these assorted structures share a common developmental origin within the preplacodal region and acquire specific characteristics only later. Here we demonstrate a fundamental similarity in placodal precursors: in the chick all are specified as lens prior to acquiring features of specific sensory or neurogenic placodes. Lens specification becomes progressively restricted in the head ectoderm, initially by FGF and subsequently by signals derived from migrating neural crest cells. We show that FGF8 from the anterior neural ridge is both necessary and sufficient to promote olfactory fate in adjacent ectoderm. Our results reveal that placode precursors share a common ground state as lens and progressive restriction allows the full range of placodal derivatives to form.     

Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson''s r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.African Americans in the United States have been affected disproportionately by the human immunodeficiency virus type 1 (HIV-1) epidemic. They accounted for only 13% of the U.S. population but for 47% of AIDS cases diagnosed in the United States in 2006 (14, 17). An HIV-1 vaccine would be of enormous benefit to this subpopulation. One strategy for HIV-1 vaccine development seeks to capitalize on the recognition and destruction of HIV-1-infected cells by cytotoxic T lymphocytes (CTLs) (32, 33, 35).CTL recognition is critically dependent on binding, presentation, and cell surface display of a variety of antigenic peptides (epitopes) by extremely polymorphic human leukocyte antigen (HLA) molecules. As the relative importance of increasing numbers of HIV-1 epitopes for individual HLA class I molecules has been recognized (9, 16), the feasibility of developing a vaccine tailored to every epitope and HLA specificity has come to seem more remote. Conceptualization of epitope specificity in terms of broad groupings (supertypes) of HLA molecules may provide a rational but simpler approach to this challenge.Several efforts have succeeded at consolidating the huge spectrum of individual HLA class I alleles into four HLA-A and five HLA-B supertype categories (37-39), based on the ability of different HLA class I molecules to present similar epitopes. Unlike individual allele frequencies, which vary greatly across ethnic groups, all nine supertypes (comprising most, but not all, HLA-A and HLA-B alleles) are present in all human populations. This more uniform representation of allele groups may confer an advantage in the form of balancing selection (38).HLA alleles within one supertype that share epitope binding specificities might be expected to demonstrate similar associations with HIV-1 outcomes or vaccine response; conversely, alleles within a supertype that differ substantially in function might be expected to show differential responses to natural infection or vaccines designed on the basis of supertype (2). Functional heterogeneity of alleles within the supertypes could be due to differences in the class I alleles themselves (e.g., variable epitope avidity or tolerance to viral mutations), in host background (genetic epistasis), or in the virus (e.g., clade-related epitope specificities or viral escape).Previous work has detected associations between the HLA class I supertypes and HIV-1 outcomes for Caucasians with clade B infections (34, 44) and for native Africans with clade A or C infections (23, 28). We are unaware of studies among African Americans in the context of clade B HIV-1 infection or of any systematic attempt to tease apart the independent contributions of supertypes and their individual class I alleles to HIV-1 outcomes. Here we document the frequencies of the HLA class I alleles and supertypes in the Reaching for Excellence in Adolescent Care and Health (REACH) and HIV Epidemiologic Research Study (HERS) cohorts, and we report the relative effects of those alleles and supertypes on the degree of HIV-1 disease control.     

A cybernetic model to predict the effect of freely available nitrogen substrate on rifamycin B production in complex media

It is well-known that secondary metabolite production is repressed by excess nitrogen substrate available in the fermentation media. Although the nitrogen catabolite repression has been known, quantitative process models have not been reported to represent this phenomenon in complex medium. In this paper, we present a cybernetic model for rifamycin B production via Amycolatopsis mediterranei S699 in complex medium, which is typically used in industry. Nitrogen substrate is assumed to be present in two forms in the medium; available nitrogen (S _ANS) such as free amino acids and unavailable nitrogen (S _UNS) such as peptides and proteins. The model assumes that an inducible enzyme catalyzes the conversion of S _UNS to S _ANS. Although S _ANS is required for growth and product formation, high concentrations were found to inhibit rifamycin production. To experimentally validate the model, five different organic nitrogen sources were used that differ in the ratio of S _ANS/S _UNS. The model successfully predicts higher rifamycin B productivity for nitrogen sources that contain lower initial S _ANS. The higher productivity is attributed to the sustained availability of S _ANS at low concentration via conversion of S _UNS to S _ANS, thereby minimizing the effects of nitrogen catabolite repression on rifamycin production. The model can have applications in model-based optimization of substrate feeding recipe and in monitoring and control of fed batch processes.