Isachne edamalayarensis sp. nov. (Poaceae: Micrairoideae) from southern Western Ghats,India

Isachne edamalayarensis, a new species from southern Western Ghats in Kerala, India, is described and illustrated. This species is similar to Isachne oreades (Domin) Bor but can be distinguished by its large and glabrous leaves, unequal glumes, and shape and size of lower and upper glumes.     

Mitochondrial E3 ligase MARCH5 regulates FUNDC1 to fine‐tune hypoxic mitophagy

Mitophagy is an essential process for mitochondrial quality control and turnover. It is activated by two distinct pathways, one dependent on ubiquitin and the other dependent on receptors including FUNDC1. It is not clear whether these pathways coordinate to mediate mitophagy in response to stresses, or how mitophagy receptors sense stress signals to activate mitophagy. We find that the mitochondrial E3 ligase MARCH5, but not Parkin, plays a role in regulating hypoxia‐induced mitophagy by ubiquitylating and degrading FUNDC1. MARCH5 directly interacts with FUNDC1 to mediate its ubiquitylation at lysine 119 for subsequent degradation. Degradation of FUNDC1 by MARCH5 expression desensitizes mitochondria to hypoxia‐induced mitophagy, whereas knockdown of endogenous MARCH5 significantly inhibits FUNDC1 degradation and enhances mitochondrial sensitivity toward mitophagy‐inducing stresses. Our findings reveal a feedback regulatory mechanism to control the protein levels of a mitochondrial receptor to fine‐tune mitochondrial quality.     

Pstl repeat: a family of short interspersed nucleotide element (SINE)-like sequences in the genomes of cattle, goat, and buffalo.

The PstI family of elements are short, highly repetitive DNA sequences interspersed throughout the genome of the Bovidae. We have cloned and sequenced some members of the PstI family from cattle, goat, and buffalo. These elements are approximately 500 bp, have a copy number of 2 x 10(5) - 4 x 10(5), and comprise about 4% of the haploid genome. Studies of nucleotide sequence homology indicate that the buffalo and goat PstI repeats (type II) are similar types of short interspersed nucleotide element (SINE) sequences, but the cattle PstI repeat (type I) is considerably more divergent. Additionally, the goat PstI sequence showed significant sequence homology with bovine serine tRNA, and is therefore likely derived from serine tRNA. Interestingly, Southern hybridization suggests that both types of SINEs (I and II) are present in all the species of Bovidae. Dendrogram analysis indicates that cattle PstI SINE is similar to bovine Alu-like SINEs. Goat and buffalo SINEs formed a separate cluster, suggesting that these two types of SINEs evolved separately in the genome of the Bovidae.     

Novel functional polymorphism on PADI-4 gene and its association with arthritis onset

BackgroundCitrullinated proteins formed by peptidyl arginine deiminases (PADIs) deimination of arginine residues in proteins are of particular interest in arthritis pathogenesis. Polymorphisms on the PADI-4 gene lead to the malfunctioning of PADIs leading to the onset of arthritis.ObjectiveThe present study was conducted to determine the polymorphisms on the PADI-4 gene and their association with rheumatoid arthritis (RA) as well as Osteoarthritis (OA).MethodologyTo achieve the above-mentioned objective a case-control study was conducted. Blood samples were collected from RA, OA, and control subjects. DNA was extracted from each blood sample by modified organic method and was quantified as well as qualified by DNA gel electrophoresis and Nanodrop. Patients were tested for rs874881, rs11203366, rs11203367, rs2240336, rs2240337, rs2240339, rs1748033 and rs2240340 polymorphic sites by amplifying targeted regions through PCR with site-specific primers. Genotyping was performed by Restriction Fragment Length Polymorphism and direct sequencing method. Mutations were identified by analyzing sequences on BioEdit software. Allelic, genetic, and multiple site analysis were performed by SHEsis and PLINK software. Change in the amino acid sequence was identified by MEGA 6.0 software.ResultsPolymorphisms were identified on all targeted polymorphic sites except rs2240337 in both RA and OA individuals. In addition, two novel mutations were also identified in exon 4 identified i-e SCV000804840: c.218T > C and SCV000807675: c.241G > T. All the SNPs except rs11203366 were found to be significantly associated with RA at an allelic level whereas all SNP’s have been significant risk factors in the onset of OA. At genotypic level rs874881, rs11203366, rs2240339, SCV000804840 and SCV000807675 were significantly associated to RA development whereas rs874881, rs11203366, rs11203367, rs2240339, SCV000804840 and SCV000807675 were genetic risk factors in OA onset. Haplotype analysis indicated that GACCACGCC and GACCACGCT were highly significant in disease development. Polymorphisms identified altered the functioning of PADIs by altering their amino acid sequence.ConclusionIn conclusion, it was found that PADI-4 gene polymorphism was not only involved in the onset of RA but was also found to be a significant risk factor in OA onset.     

ERK1/2 mediates lung adenocarcinoma cell proliferation and autophagy induced by apelin-13

The aim of this study was to investigate the role of apelin in the cell proliferation and autophagy of lung adenocarcin- oma. The over-expression of APJ in lung adenocarcinoma was detected by immunohistochemistry, while plasma apelin level in lung cancer patients was measured by enzyme-linked immunosorbent assay. Our findings revealed that apelin-13 significantly increased the phosphorylation of ERK1/2, the expression of cyclin D1, microtubule-associated protein 1 light chain 3A/B （LC3A/B）, and beclinl, and con- fwmed that apelin-13 promoted A549 cell proliferation and induced A549 cell autophagy via ERK1/2 signaling. More- over, there are pores on the surface of human lung adeno- carcinoma cell line A549 and apelin-13 causes cell surface smooth and glossy as observed under atomic force micros- copy. These results suggested that ERK1/2 signaling pathway mediates apelin-13-induced lung adenocarcinoma cell proliferation and autophagy. Under our experimental condition, autophagy associated with 3-methyladenine was not involved in cell proliferation.     

Nanoemulsions as vehicles for transdermal delivery of aceclofenac

The aim of the present study was to investigate the potential of a nanoemulsion formulation for transdermal delivery of aceclofenac. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudoternary phase diagrams. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for viscosity, droplet size, transmission electron microscopy, and refractive index. Transdermal permeation of aceclofenac through rat abdominal skin was determined by Franz diffusion cell. The in vitro skin permeation profile of optimized formulations was compared with that of aceclofenac conventional gel and nanoemulsion gel. A significant increase in permeability parameters such as steady-state flux (J(ss)), permeability coefficient (K(p)), and enhancement ratio (E(r)) was observed in optimized nanoemulsion formulation F1, which consisted of 2% wt/wt of aceclofenac, 10% wt/wt of Labrafil, 5% wt/wt of Triacetin, 35.33% wt/wt of Tween 80, 17.66% wt/wt of Transcutol P, and 32% wt/wt of distilled water. The anti-inflammatory effects of formulation F1 showed a significant increase (P < .05) in percent inhibition value after 24 hours when compared with aceclofenac conventional gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of aceclofenac.     

Purification and degradation of purified neurofilament proteins by the brain calcium-activated neutral proteases

The effect of the three forms (CANP1, CANP2 & CANP3) of calf brain calcium activated neutral protease (CANP) on the hydrolysis of purified neurofilament triplet proteins was investigated. It was observed that: each of the purified neurofilament proteins, was hydrolyzed slowly by CANP2 whereas the hydrolysis of 150 KDa and 68 kDa proteins by CANP1 & CANP3 was rapid; when assembled neurofilaments were used as a substrate, again differences in the rate and extent of degradation of the triplet proteins by the three proteases were observed. For example, little cleavage of the 68 kDa protein by CANP2 and CANP3 was noted whereas 210 kDa and 150 kDa proteins remained largely intact. CANP1 degraded the 150 kDa and 68 kDa proteins more rapidly than 210 kDa protein, where only a slight effect was noted. These data provide further proof of the existence of three different forms of CANP in the brain, and indications of the resistance of 210 kDa protein to proteolysis which may be compatible with its proposed special role in crossbridge formation.