Multivariate sequence analysis reveals additional function impacting residues in the SDR superfamily

The “extended” type of short chain dehydrogenases/reductases (SDR), share a remarkable similarity in their tertiary structures inspite of being highly divergent in their functions and sequences. We have carried out principal component analysis (PCA) on structurally equivalent residue positions of 10 SDR families using information theoretic measures like Jensen–Shannon divergence and average shannon entropy as variables. The results classify residue positions in the SDR fold into six groups, one of which is characterized by low Shannon entropies but high Jensen–Shannon divergence against the reference family SDR1E, suggesting that these positions are responsible for the specific functional identities of individual SDR families, distinguishing them from the reference family SDR1E. Site directed mutagenesis of three residues from this group in the enzyme UDP‐Galactose 4‐epimerase belonging to SDR1E shows that the mutants promote the formation of NADH containing abortive complexes. Finally, molecular dynamics simulations have been used to suggest a mechanism by which the mutants interfere with the re‐oxidation of NADH leading to the formation of abortive complexes. Proteins 2014; 82:2842–2856. © 2014 Wiley Periodicals, Inc.     

Immunochip Identifies Novel,and Replicates Known,Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single nucleotide polymorphisms (SNPs) in the intergenic regions LOC389203|RBPJ, LOC100131131|IL1R1, KIAA1919|REV3L, LOC643749|TRAF3IP2, and SNPs in the intron and untranslated regions (UTR) of IRF1 and the intronic region of ICOS and KIAA1542 showed association with RA (p < 5 × 10⁻⁵). Of the SNPs previously associated with RA in Caucasians, one SNP, rs874040, locating to the intergenic region LOC389203|RBPJ was replicated in this study. None of the variants in the PTPN22 gene was significantly associated. The seropositive subgroups showed similar results to the overall cohort. The effects observed across the HLA region are most likely due to HLA-DRB1, and secondary effects in the extended MHC cannot be detected. Seven non-HLA loci are associated with RA in black South Africans. Similar to Caucasians, the intergenic region between LOC38920 and RBPJ is associated with RA in this population. The strong association of the R620W variant of the PTPN22 gene with RA in Caucasians was not replicated since this variant was monomorphic in our study, but other SNP variants of the PTPN22 gene were also not associated with RA in black South Africans, suggesting that this locus does not play a major role in RA in this population.     

Reversine ameliorates hallmarks of cellular senescence in human skeletal myoblasts via reactivation of autophagy

Cellular senescence leads to the depletion of myogenic progenitors and decreased regenerative capacity. We show that the small molecule 2,6-disubstituted purine, reversine, can improve some well-known hallmarks of cellular aging in senescent myoblast cells. Reversine reactivated autophagy and insulin signaling pathway via upregulation of Adenosine Monophosphate-activated protein kinase (AMPK) and Akt2, restoring insulin sensitivity and glucose uptake in senescent cells. Reversine also restored the loss of connectivity of glycolysis to the TCA cycle, thus restoring dysfunctional mitochondria and the impaired myogenic differentiation potential of senescent myoblasts. Altogether, our data suggest that cellular senescence can be reversed by treatment with a single small molecule without employing genetic reprogramming technologies.     

Seed failure following hybridisation between 4nCorchorus capsularis L. (strain D. 154) and 3nC. olitorius L. (strain C.G.) and its reciprocal and some cytogenetical observations

In both types of crosses (3n C.G.×4n D 154 and 4n D 154×3n C.G.) pods were found to set. In the first case pods shed within 4 days. In the second case pods were found to persist till maturity. Only a few uppermost ovules were found to be fertilized. Pollen tubes were seen to reach the ovules within 24 hours. In 4n D 154×3n C.G. fusion of sperm with the egg was not noted to be complete till 3 days but the secondary nucleus is fertilized by other sperm. In 3n C.G.×D 154 fusion of sperm with egg or with polars was not complete within 3 days. Signs of degeneration of ovules were noted on the 5th day in both cases.     

Status and conservation of the Asian Elephant Elephas maximus in north-eastern India

A status survey of Asian Elephants Elephas maximus was conducted in the 9 north-eastern states of India. The habitat is contiguous with that in Bhutan, Myanmar and Bangladesh. Although the estimated population of 11 000 elephants is higher than in other regions of the Indian Sub-continent, it is fragmented and a number of small inviable isolated populations have formed. About 35% of the population is partly protected, but protection is inadequate. More areas and migration routes need to be protected. Man–elephant conflict is serious in many areas. A comprehensive Action Plan with a more pragmatic protected-area network has been proposed.     

Engineered Metasurface of Gold Funnels for Terahertz Wave Filtering

Surface plasmon polariton (SPP) excitation of the coupled light at small contact area of chromium pillars as the interface of metastructured gold funnel layer and silica medium can be enhanced locally in the gold meta-funnel-structured filter. In the present investigation, the filter is comprised of three layers, namely gold meta-funnels, nano-sized chromium pillars, and silica as the substrate. The incoming infrared (IR) waves, coupled with the excited plasmons at the first and second layers, form an excitation, known as deformed plasmon polariton. Asymmetric distribution of localized SPPs takes place owing to the inherent converging plasmonic feature of the gold funnel structure. The formation of reflection peaks with different magnitudes at different incidence angles of the polarized wave in the spectral characteristics makes the structure prominent for filtering the IR waves. Moreover, the gold meta-funnel-structured filter possesses the additional feature of distinguishing the type of polarized incidence wave. It was found that the transmission remains maximum corresponding to the normal incidence of the TE-polarized waves, whereas the TM-polarized waves over the same wavelength range are almost blocked for any value of incidence angle. The existence of transmission peaks corresponding to the TE waves demonstrates another application of this device as metastructured polarizer filter.     

Regulation of sugar metabolism in rice (Oryza sativa L.) seedlings under arsenate toxicity and its improvement by phosphate

The effect of arsenate with or without phosphate on the growth and sugar metabolism in rice seedlings cv. MTU 1010 was studied. Arsenate was found to be more toxic for root growth than shoot growth and water content of the seedlings gradually decreased with increasing concentrations. Arsenate exposure at 20 μM and 100 μM resulted in an increase in reducing sugar content and decrease in non-reducing sugar content. There was a small increase in starch content, the activity of starch phosphorylase was increased but α-amylase activity was found to be decreased. Arsenate toxicity also affected the activities of different carbohydrate metabolizing enzymes. The activities of sucrose degrading enzymes viz., acid invertase and sucrose synthase were increased whereas, the activity of sucrose synthesizing enzyme, viz. sucrose phosphate synthase declined. The combined application of arsenate with phosphate exhibited significant alterations of all the parameters tested under the purview of arsenate treatment alone which was congenial to better growth and efficient sugar metabolism in rice seedlings. Thus, the use of phosphorus enriched fertilizers may serve to ensure the production of healthy rice plants in arsenic contaminated soils.     

Histone methyltransferase SUV39H1 participates in host defense by methylating mycobacterial histone‐like protein HupB

Host cell defense against an invading pathogen depends upon various multifactorial mechanisms, several of which remain undiscovered. Here, we report a novel defense mechanism against mycobacterial infection that utilizes the histone methyltransferase, SUV39H1. Normally, a part of the host chromatin, SUV39H1, was also found to be associated with the mycobacterial bacilli during infection. Its binding to bacilli was accompanied by trimethylation of the mycobacterial histone‐like protein, HupB, which in turn reduced the cell adhesion capability of the bacilli. Importantly, SUV39H1‐mediated methylation of HupB reduced the mycobacterial survival inside the host cell. This was also true in mice infection experiments. In addition, the ability of mycobacteria to form biofilms, a survival strategy of the bacteria dependent upon cell–cell adhesion, was dramatically reduced in the presence of SUV39H1. Thus, this novel defense mechanism against mycobacteria represents a surrogate function of the epigenetic modulator, SUV39H1, and operates by interfering with their cell–cell adhesion ability.