Wnt signaling establishes the microtubule polarity in neurons through regulation of Kinesin-13

Neuronal polarization is facilitated by the formation of axons with parallel arrays of plus-end-out and dendrites with the nonuniform orientation of microtubules. In C. elegans, the posterior lateral microtubule (PLM) neuron is bipolar with its two processes growing along the anterior–posterior axis under the guidance of Wnt signaling. Here we found that loss of the Kinesin-13 family microtubule-depolymerizing enzyme KLP-7 led to the ectopic extension of axon-like processes from the PLM cell body. Live imaging of the microtubules and axonal transport revealed mixed polarity of the microtubules in the short posterior process, which is dependent on both KLP-7 and the minus-end binding protein PTRN-1. KLP-7 is positively regulated in the posterior process by planar cell polarity components of Wnt involving rho-1/rock to induce mixed polarity of microtubules, whereas it is negatively regulated in the anterior process by the unc-73/ced-10 cascade to establish a uniform microtubule polarity. Our work elucidates how evolutionarily conserved Wnt signaling establishes the microtubule polarity in neurons through Kinesin-13.     

New Computational Approach for Peptide Vaccine Design Against SARS-COV-2

International Journal of Peptide Research and Therapeutics - The design for vaccines using in silico analysis of genomic data of different viruses has taken many different paths, but lack of any...     

Therapeutic applications of lysostaphin against Staphylococcus aureus

Staphylococcus aureus, an opportunistic pathogen, causes diverse community and nosocomial-acquired human infections, including folliculitis, impetigo, sepsis, septic arthritis, endocarditis, osteomyelitis, implant-associated biofilm infections and contagious mastitis in cattle. In recent days, both methicillin-sensitive and methicillin-resistant S. aureus infections have increased. Highly effective anti-staphylococcal agents are urgently required. Lysostaphin is a 27 kDa zinc metallo antimicrobial lytic enzyme that is produced by Staphylococcus simulans biovar staphylolyticus and was first discovered in the 1960s. Lysostaphin is highly active against S. aureus strains irrespective of their drug-resistant patterns with a minimum inhibitory concentration of ranges between 0·001 and 0·064 μg ml⁻¹. Lysostaphin has activity against both dividing and non-dividing S. aureus cells; and can seep through the extracellular matrix to kill the biofilm embedded S. aureus. In spite of having excellent anti-staphylococcal activity, its clinical application is hindered because of its immunogenicity and reduced bio-availability. Extensive research with lysostaphin lead to the development of several engineered lysostaphin derivatives with reduced immunogenicity and increased serum half-life. Therapeutic efficacy of both native and engineered lysostaphin derivatives was studied by several research groups. This review provides an overview of the therapeutic applications of native and engineered lysostaphin derivatives developed to eradicate S. aureus infections.     

Antixenosis,tolerance and genetic analysis of some rice landraces for resistance to Nilaparvata lugens (Stål.)

Twenty-six rice landraces from West Bengal, India were evaluated for antixenosis and tolerance against brown planthopper (BPH) biotype 4 at the Bidhan Chandra Krishi Viswavidyalaya (BCKV), West Bengal. High levels of resistance were observed in six landraces, namely Badshabhog, Gamra, Haldichuri, Janglijata, Kalabhat and Khara. These phenotypically resistant rice landraces including Ptb33 exhibited lowest feeding rate, fecundity, nymphal and adult preference, survival, plant dry weight loss per mg of BPH dry weight produced (PDWL), and higher functional plant loss index (FPLI), more days to wilt and unhatched eggs compared with the susceptible check Swarna. All the landraces were classified into four major clusters at 10 unit distance by the scale of similarity during genetic diversity analysis through 21 gene-linked SSR markers of BPH resistance. Some phenotypically resistant landraces were gathered under the major cluster I indicating their analogous genetic history, while some were grouped with susceptible landraces exhibiting their genetic variation. The resistant landraces can be used as potential donors in the breeding programme for the development of rice varieties with resistance to BPH.     

HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India

Background

Several studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes.

Results

Single nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ² tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM.

Conclusions

This study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM.     

Combination of Ascorbate and α-Tocopherol as a Preventive Therapy against Structural and Functional Defects of Erythrocytes in Visceral Leishmaniasis

The redox unbalance in erythrocytes has been found to contribute significantly in the development of anemia in visceral leishmaniasis (VL). The present study revealed enhanced production of reactive oxygen species (ROS) and gradual depletion of α-tocopherol and ascorbate in the erythrocytes of infected animals. The response of erythrocytes to chronic treatment with antioxidants was studied in hamsters during leishmanial infection. Treatment with a combination of α-tocopherol and ascorbate proved to be the most effective preventive for the proteolytic degradation of erythrocyte membrane. Erythrocytes from infected animals were thermally more sensitive compared to the control ones. Combination of both antioxidants was most successful in resisting heat induced structural defects in the cells. Cross-linking of membrane proteins subsequent to oxidative damage in the red cells was accompanied by the formation of high molecular weight protein band at the top of the resolving gel in the presence of the cross-linking agent dimethyladepimidate (DMA). Marked inhibition of cross-linking was observed with combination of both antioxidants. Treatment with α-tocopherol and ascorbate together could withstand osmotic lysis of erythrocytes in the infected animals very efficiently. Decreased hemoglobin (Hb) level was successfully replenished and was coupled with significant increase in the life span of red cells after treating the animals with both antioxidants. Results indicate better efficacy of the combination therapy with α-tocopherol and ascorbate in protecting the erythrocytes from structural and functional damages during leishmanial infection.     

Which comes first: Renal inflammation or oxidative stress in spontaneously hypertensive rats?

The present study was undertaken to identify whether inflammation or oxidative stress is the primary abnormality in the kidney in spontaneously hypertensive rats (SHR). Renal inflammation and oxidative stress were evaluated in 2- and 3-week-old prehypertensive SHR and age-matched genetically normotensive control Wistar-Kyoto (WKY) rats. Blood pressure was similar in WKY and SHR rats at 2 and 3 weeks, of age. Renal inflammation (macrophage and nuclear factor-κB) was elevated in SHR at 3 weeks, but not at 2 weeks, of age compared with age-matched WKY rats. Renal oxidative stress (nitrotyrosine, 8-hydroxy-2′-deoxyguanosine and p47phox) was also clearly elevated in 3-week-old SHR compared with age-matched WKY rats. Additionally, NADPH oxidase subunit p47phox was found elevated in 2-week-old SHR compared to age-matched WKY rats. Moreover, antioxidant (N-acetyl-l-cysteine and Tempol) treatment reduced renal inflammation in prehypertensive SHR. We therefore conclude that the oxidative stress appears before inflammation as a primary abnormality in the kidney in prehypertensive SHR.     

Cryptic species,taxonomic inflation,or a bit of both? New species phenomenon in Sri Lanka as suggested by a phylogeny of dwarf geckos (Reptilia,Squamata, Gekkonidae,Cnemaspis)

We evaluated the status of 16 of 22 recognized Sri Lankan Cnemaspis Strauch species, and flagged overlooked diversity with two mitochondrial (cyt b & ND2) and two nuclear markers (RAG1 & PDC) totalling 2829 base pairs. A fossil-calibrated timetree and sampling of other South Asian Cnemaspis provide insights into the diversification of the genus in peninsular India and Sri Lanka. Phylogenetic analyses consistently inferred two broad clades within South Asian Cnemaspis, with Sri Lankan species in two clades, which we call the podihuna and kandiana clades. Each Sri Lankan clade as a whole is sister to Indian taxa and nested within Indian lineages. Cnemaspis modigliani Das from Indonesia is a member of the kandiana clade. This suggests a minimum of two dispersal events between India and Sri Lanka and one between Sri Lanka/India and South-east Asia. South Asian Cnemaspis date back to at least the Eocene, in Sri Lanka to the early Miocene, with late Miocene diversification in the kandiana clade. All but one of the named species we sampled is likely to be valid, and 10 divergent unnamed lineages may warrant specific recognition. A resolution of Sri Lankan Cnemaspis taxonomy will require thorough sampling and the use of both morphological and molecular data.