Transient receptor potential (TRP) channels belong to a large family of cation channels and are the "border guards" predominantly localized to the plasma membrane. Research over the years has considerably and highly developed the knowledge of expression and functional aspects of the TRPM channels. A closer look at the channel dynamics has dismantled undeniable substantiation for multifaceted roles for TRPM channel-mediated extracellular Ca(2+) influx in several physiological and pathophysiological functions. Given the wealth of literature unfolding the multiple roles of TRP channels in physiology in a very extensive range of different mammalian tissues, this review confines itself to the literature describing the multiple roles of TRPM channels in diabetes, smooth muscle cell regulation, immunological responses, and emerging aspects of cancer. We also focus on differential activities of TRPM channels after post-transcriptional and post-translational processing and their exquisite roles at various cellular and molecular levels.
To investigate the uniparental genetic structure of the Punjabi population from mtDNA aspect and to set up an appropriate mtDNA forensic database, we studied maternally unrelated Punjabi (N = 100) subjects from two caste groups (i.e. Arain and Gujar) belonging to territory of Punjab. The complete control region was elucidated by Sanger sequencing and the subsequent 58 different haplotypes were designated into appropriate haplogroups according to the most recently updated mtDNA phylogeny. We found a homogenous dispersal of Eurasian haplogroup uniformity among the Punjab Province and exhibited a strong connotation with the European populations. Punjabi castes are primarily a composite of substantial South Asian, East Asian and West Eurasian lineages. Moreover, for the first time we have defined the newly sub-haplogroup M52b1 characterized by 16223 T, 16275 G and 16438 A in Gujar caste. The vast array of mtDNA variants displayed in this study suggested that the haplogroup composition radiates signals of extensive genetic conglomeration, population admixture and demographic expansion that was equipped with diverse origin, whereas matrilineal gene pool was phylogeographically homogenous across the Punjab. This context was further fully acquainted with the facts supported by PCA scatterplot that Punjabi population clustered with South Asian populations. Finally, the high power of discrimination (0.8819) and low random match probability (0.0085%) proposed a worthy contribution of mtDNA control region dataset as a forensic database that considered a gold standard of today to get deeper insight into the genetic ancestry of contemporary matrilineal phylogeny.
Due to its geo strategic position at the crossroad of Asia, Pakistan has gained crucial importance of playing its pivotal role in subsequent human migratory events, both prehistoric and historic. This human movement became possible through an ancient overland network of trails called "The Silk Route" linking Asia Minor, Middle East China, Central Asia and Southeast Asia. This study was conducted to analyze complete mitochondrial control region samples of 100 individuals of four major Pashtun tribes namely, Bangash, Khattak, Mahsuds and Orakzai in the province of Khyber Pakhtunkhwa, Pakistan. All Pashtun tribes revealed high genetic diversity which is comparable to the other Central Asian, Southeast Asian and European populations. The configuration of genetic variation and heterogeneity further unveiled through Multidimensional Scaling, Principal Component Analysis and phylogenetic analysis. The results revealed that Pashtun are the composite mosaic of West Eurasian ancestry of numerous geographic origin. They received substantial gene flow during different invasive movements and have a high element of the Western provenance. The most common haplogroups reported in this study are: South Asian haplogroups M (28%) and R (8%); whereas, West Asians haplogroups are present, albeit in high frequencies (67%) and widespread over all; HV (15%), U (17%), H (9%), J (8%), K (8%), W (4%), N (3%) and T (3%). Moreover, we linked the unexplored genetic connection between Ashkenazi Jews and Pashtun. The presence of specific haplotypes J1b (4%) and K1a1b1a (5%) pointed to a genetic connection of Jewish conglomeration in Khattak tribe. This was a result of an ancient genetic influx in the early Neolithic period that led to the formation of a diverse genetic substratum in present day Pashtun.
The insight heterodox genetics of mtDNA infer new perspectives at the level of human mitochondrial control region heteroplasmy, which is substantial in evolutionary as well as forensic interpretation. The main goal of this study is to interrogate the recurrence and resolve the ambiguity of blurry spectrum of heteroplasmy in the human mtDNA control region of 50 Baluchi and 116 Sindhi unrelated individuals. Sanger sequencing was employed classically, that was further investigated by minisequencing. Only 20% Baluchi and 25.8% Sindhi were homoplasmic, whereas rest of 80% Baluchi and 74.1% Sindhi exhibited at least one heteroplasmy within the specimen. In total, 166 individuals have length heteroplasmy (LH) found at positions 16189, 303-315, 568-573, and 514-524, whilst point mutation heteroplasmy (PMH) was detected at positions 73, 16093, 16189, and 16234, respectively. Overall LH was observed albeit high frequency in Sindhi ethnic group (82%) rather than Baluchi's (37%), whereas PMH accumulation was relatively extensive (24%) in Baluchi's than Sindhi's (11.2%). The obtained results ascertained that growing knowledge of heteroplasmy assisted to develop consciences in the forensic community that heteroplasmy plays a pivotal role in the legal interpretation on a regular basis and knowledge of its biological underpinnings has a vital niche in the forensic science. Limited studies have focused on heteroplasmy, yet scientific attention should be given, in order to determine its magnitude in different ethnic boundaries.
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