Expanding EMC foldopathies: Topogenesis deficits alter the neural crest

The endoplasmic reticulum (ER) membrane protein complex (EMC) is essential for the insertion of a wide variety of transmembrane proteins into the plasma membrane across cell types. Each EMC is composed of Emc1-7, Emc10, and either Emc8 or Emc9. Recent human genetics studies have implicated variants in EMC genes as the basis for a group of human congenital diseases. The patient phenotypes are varied but appear to affect a subset of tissues more prominently than others. Namely, craniofacial development seems to be commonly affected. We previously developed an array of assays in Xenopus tropicalis to assess the effects of emc1 depletion on the neural crest, craniofacial cartilage, and neuromuscular function. We sought to extend this approach to additional EMC components identified in patients with congenital malformations. Through this approach, we determine that EMC9 and EMC10 are important for neural crest development and the development of craniofacial structures. The phenotypes observed in patients and our Xenopus model phenotypes similar to EMC1 loss of function likely due to a similar mechanism of dysfunction in transmembrane protein topogenesis.     

SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study

Archives of Microbiology - Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four...     

Quantification of biochemical compounds in Bauhinia Variegata Linn flower extract and its hepatoprotective effect

Liver disorders may occur as a result of exposure to chemical compounds capable of inducing the oxidative stress and hepatic injuries. The aim of present study was to investigate the effects of flower extracts of B. Variegata for the treatment of liver injury induced by the CCl₄. About 1 ml/kg body weight (b.w) of CCl4 was induced to experimental mice by intraperitoneal way for 14 days. The methanol and chloroform extracts (100, 200 and 300 mg/kg b.w) were administered to experimental animals for 14 days along with standard drug Silymarine (100 mg/kg b.w). The extracts alone showed no evidence of hepatic toxicity but animals exposed to CCl₄ without the treatment with B. Variegata presented variations in levels of liver enzymes, antioxidant enzymes, proteins and blood cells as well as injuries in liver cells were also observed during histopathological study. However, after the treatments especially with 300 mg/kg b.w of methanol flower extracts levels of liver markers (ALT, AST and ALP), antioxidant enzymes and blood cells decreases and turned towards normal levels. Whereas level of total proteins and bilirubin was improved and damaged liver cells were repaired. The curative activity of flower extracts can be correlated to the higher potential of antioxidants and occurrence of Quercetin and some other organic compounds those were investigated from flower extracts of B. Variegata during HPLC and GC-MS analysis. The finding of this study supports the use of B. Variegata flower formulation in folk medicines.     

Observations on the floristic,life-form,leaf-size spectra and habitat diversity of vegetation in the Bhimber hills of Kashmir Himalayas

Vegetation analysis provides the prerequisites to understand the overall community structure and function of any ecosystem and is a fundamental requirement for the precise evaluation of biodiversity. Although many studies have assessed floristic attributes of specific areas, there are still unexplored regions, as is the case of the mountain region in the Kashmir Himalayas. Current research highlighted the recent findings of the scientific characterization of floristic and ecological aspects on the forest flora found in the Bhimber hills, Pakistan. Floristically, a total of 93 species belonging to 80 genera in 41 families were recorded. The species distribution patterns across the families were disproportionate with half of the species contributed by 8 families and 25 families were monotypic. Based on the floristic analysis, Asteraceae was the largest family with 12% of species followed by Poaceae with (11%) species. PAST software, a multivariate ecological community analysis was used to classify the species similarities and differences among the different habitat types. According to the habitat wise distribution, 21% of species were growing in the natural forest habitat, while 15% of species were dispersed in highly distributed habitats along roadsides and 8% on pedestrians. In terms of functional diversity, the herbaceous growth form was dominant (58%). The biological spectrum revealed therophytes as the dominant life form as it indicates the disturbed habitat vegetation. The phytogeographical analysis revealed that the maximum (69%) species were native, while the minimum (31%) species were exotic. Thus, the study of these functional and habitat diversity patterns can significantly improve our understanding of the ecological aspects of the flora in the geographical location. This information may additionally be useful in devising management plans to ensure sustainable utilization and better management of forest landscapes in this Himalayan region.     

Antibacterial,anti-biofilm and anticancer potentials of green synthesized silver nanoparticles using benzoin gum (<Emphasis Type="Italic">Styrax benzoin</Emphasis>) extract

This study described a simple and green approach for the synthesis of silver nanoparticles (AgNPs) employing benzoin gum water extract as a reducing and capping agent and their applications. The AgNPs were characterized by ultraviolet–visible spectrophotometer, X-ray diffraction pattern, field emission transmission electron microscopy, dynamic light scattering, zeta potential and fourier transform infrared spectroscopy. The AgNPs showed promising antimicrobial activity against various pathogens (Gram-negative, Gram-positive and fungus) and possessed high free radical scavenging activity (104.5 ± 7.21 % at 1 mg/ml). In addition, the AgNPs exhibited strong cytotoxicity towards human cervical cancer and human lung cancer cells as compared to the normal mouse macrophage cells. Moreover, the AgNPs possessed anti-biofilm activity against Escherichia coli, and compatibility to human keratinocyte HaCaT cells, which suggests the use of dressing with the AgNPs in chronic wound treatment. Therefore, AgNPs synthesized by benzoin gum extract are comparatively green and may have broad spectrum potential application in biomedicine.     

Ultrasonic synthesis of tyramine derivatives as novel inhibitors of α-glucosidase in vitro

Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC₅₀?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC₅₀?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC₅₀ values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.     

Tomato bushy stunt virus (TBSV) infecting Lycopersicon esculentum

Tomato bushy stunt virus (TBSV) was detected in tomato crop (Lycopersicon esculentum) in Egypt with characteristic mosaic leaf deformation, stunting, and bushy growth symptoms. TBSV infection was confirmed serologically by ELISA and calculated incidence was 25.5%. Basic physicochemical properties of a purified TBSV Egh isolate were identical to known properties of tombusviruses of isometric 30-nm diameter particles, 41-kDa coat protein and the genome of approximately 4800 nt. This is the first TBSV isolate reported in Egypt. Cloning and partial sequencing of the isolate showed that it is more closely related to TBSV-P and TBSV-Ch than TBSV-Nf and TBSV-S strains of the virus. However, it is distinct from the above strains and could be a new strain of the virus which further confirms the genetic diversity of tombusviruses.