Evolution of protein domain repertoires of CALHM6.

Calcium (Ca2 +) homeostasis is essential in conducting various cellular processes including nerve transmission, muscular movement, and immune response. Changes in Ca2 + concentration in the cytoplasm are significant in bringing about various immune responses such as pathogen clearance and apoptosis. Various key players are involved in calcium homeostasis such as calcium binders, pumps, and channels. Sequence-based evolutionary information has recently been exploited to predict the biophysical behaviors of proteins, giving critical clues about their functionality. Ion channels are reportedly the first channels developed during evolution. Calcium homeostasis modulator protein 6 (CALHM6) is one such channel. Comprised of a single domain called Ca_hom_mod, CALHM6 is a stable protein interacting with various other proteins in calcium regulation. No previous attempt has been made to trace the exact evolutionary events in the domain of CALHM6, leaving plenty of room for exploring its evolution across a wide range of organisms. The current study aims to answer the questions by employing a computational-based strategy that used profile Hidden Markov Models (HMMs) to scan for the CALHM6 domain, integrated the data with a time-calibrated phylogenetic tree using BEAST and Mesquite, and visualized through iTOL. Around 4,000 domains were identified, and 14,000 domain gain, loss, and duplication events were observed at the end which also included various protein domains other than CALHM6. The data were analyzed concerning CALHM6 evolution as well as the domain gain, loss, and duplication of its interacting partners: Calpain, Vinculin, protein S100-A7, Thioredoxin, Peroxiredoxin, and Calmodulin-like protein 5. Duplication events of CALHM6 near higher eukaryotes showed its increasing complexity in structure and function. This in-silico phylogenetic approach applied to trace the evolution of CALHM6 was an effective approach to get a better understanding of the protein CALHM6.

Vaccinomics Approach for Multi-Epitope Vaccine Design against Group A Rotavirus Using VP4 and VP7 Proteins.

Rotavirus A is the most common cause of Acute Gastroenteritis globally among children <5 years of age. Due to a segmented genome, there is a high frequency of genetic reassortment and interspecies transmission which has resulted in the emergence of novel genotypes. There are concerns that monovalent (Rotarix: GlaxoSmithKline Biologicals, Rixensart, Belgium) and pentavalent (RotaTeq: MERCK & Co., Inc., Kenilworth, NJ, USA) vaccines may be less effective against non-vaccine strains, which clearly shows the demand for the design of a vaccine that is equally effective against all circulating genotypes. In the present study, a multivalent vaccine was designed from VP4 and VP7 proteins of RVA. Epitopes were screened for antigenicity, allergenicity, homology with humans and anti-inflammatory properties. The vaccine contains four B-cell, three CTL and three HTL epitopes joined via linkers and an N-terminal RGD motif adjuvant. The 3D structure was predicted and refined preceding its docking with integrin. Immune simulation displayed promising results both in Asia and worldwide. In the MD simulation, the RMSD value varied from 0.2 to 1.6 nm while the minimum integrin amino acid fluctuation (0.05-0.1 nm) was observed with its respective ligand. Codon optimization was performed with an adenovirus vector in a mammalian expression system. The population coverage analysis showed 99.0% and 98.47% in South Asia and worldwide, respectively. These computational findings show potential against all RVA genotypes; however, in-vitro/in-vivo screening is essential to devise a meticulous conclusion.

An update on stem cells applications in burn wound healing.

Burn wounds have proven to be capable of having a long lasting devastating effects on human body. Conventional therapeutic approaches are not up to the mark as they are unable to completely heal the burn wound easily and effectively. Major pitfalls of these treatments include hypertrophic scarring, contracture and necrosis. Presence of these limitations in the current therapies necessitate the search for a better and more efficient cure. Regenerative potency of stem cells in burn wound healing outweigh the traditional treatment procedures. The use of multiple kinds of stem cells are gaining interest due to their enhanced healing efficiency. Distinctions of stem cells include better and faster burn wound healing, decreased inflammation levels, less scar progression and fibrosis on site. In this review, we have discussed the wound-healing process, present methods used for stem cells administration, methods of enhancing stem cells potency and human studies. Pre-clinical and the clinical studies focused on the treatment of thermal and radiation burns using stem cells from 2003 till the present time have been enlisted. Studies shows that the use of stem cells on burn wounds, whether alone or by the help of a scaffold significantly improves healing. Homing of the stem cells at the wound site results in the re-epithelialization, angiogenesis, granulation, inhibition of apoptosis, and regeneration of skin appendages together with reduced infection rate in the human studies. Several studies on animals have shown that stem cells can effectively promote wound healing. Although more research is needed to find out the effectiveness of this treatment in patients with severe burn wounds.