Population differentiation of Southern Indian male lineages correlates with agricultural expansions predating the caste system

Christina J. Adler, Alan Cooper, Clio S.I. Der Sarkissian and Wolfgang Haak are contributors to the Genographic ConsortiumPrevious studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that both Y chromosome and caste designation are paternally inherited, and genotyped 1,680 Y chromosomes representing 12 tribal and 19 non-tribal (caste) endogamous populations from the predominantly Dravidian-speaking Tamil Nadu state in the southernmost part of India. Tribes and castes were both characterized by an overwhelming proportion of putatively Indian autochthonous Y-chromosomal haplogroups (H-M69, F-M89, R1a1-M17, L1-M27, R2-M124, and C5-M356; 81% combined) with a shared genetic heritage dating back to the late Pleistocene (10–30 Kya), suggesting that more recent Holocene migrations from western Eurasia contributed, <20% of the male lineages. We found strong evidence for genetic structure, associated primarily with the current mode of subsistence. Coalescence analysis suggested that the social stratification was established 4–6 Kya and there was little admixture during the last 3 Kya, implying a minimal genetic impact of the Varna(caste) system from the historically-documented Brahmin migrations into the area. In contrast, the overall Y-chromosomal patterns, the time depth of population diversifications and the period of differentiation were best explained by the emergence of agricultural technology in South Asia. These results highlight the utility of detailed local genetic studies within India, without prior assumptions about the importance of Varna rank status for population grouping, to obtain new insights into the relative influences of past demographic events for the population structure of the whole of modern India.GaneshPrasad ArunKumar, David F. Soria-Hernanz, Valampuri John Kavitha, Varatharajan Santhakumari Arun, Adhikarla Syama, Kumaran Samy Ashokan, Kavandanpatti Thangaraj Gandhirajan, Koothapuli Vijayakumar, Muthuswamy Narayanan, Mariakuttikan Jayalakshmi, Janet S. Ziegle, Ajay K. Royyuru, Laxmi Parida, R. Spencer Wells, Colin Renfrew, Theodore G. Schurr, Chris Tyler Smith, Daniel E. Platt, Ramasamy Pitchappan, The Genographic Consortiu

Biotechnological Perspective of Reactive Oxygen Species (ROS)-Mediated Stress Tolerance in Plants

All environmental cues lead to develop secondary stress conditions like osmotic and oxidative stress conditions that reduces average crop yields by more than 50% every year. The univalent reduction of molecular oxygen (O2) in metabolic reactions consequently produces superoxide anions (O2•−) and other reactive oxygen species (ROS) ubiquitously in all compartments of the cell that disturbs redox potential and causes threat to cellular organelles. The production of ROS further increases under stress conditions and especially in combination with high light intensity. Plants have evolved different strategies to minimize the accumulation of excess ROS like avoidance mechanisms such as physiological adaptation, efficient photosystems such as C4 or CAM metabolism and scavenging mechanisms through production of antioxidants and antioxidative enzymes. Ascorbate-glutathione pathway plays an important role in detoxifying excess ROS in plant cells, which includes superoxide dismutase (SOD) and ascorbate peroxidase (APX) in detoxifying O2•−radical and hydrogen peroxide (H2O2) respectively, monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) involved in recycling of reduced substrates such as ascorbate and glutathione. Efficient ROS management is one of the strategies used by tolerant plants to survive and perform cellular activities under stress conditions. The present chapter describes different sites of ROS generation and and their consequences under abiotic stress conditions and also described the approaches to overcome oxidative stress through genomics and genetic engineering

Treosulfan Exposure Predicts Thalassemia-free Survival In Patients With Beta Thalassemia Major (TM) Undergoing Allogeneic Hematopoietic Cell Transplantation

A toxicity-reduced conditioning regimen with Treosulfan, Fludarabine, and Thiotepa in patients with high-risk β- thalassemia major has significantly improved HCT outcomes. However, complications resulting from regimen-related toxicities (RRTs), mixed chimerism, and graft rejection remain a challenge. We evaluated the dose-exposure-response relationship of Treosulfan and its active metabolite S, S-EBDM, in a uniform cohort of patients with β-thalassemia major to identify whether therapeutic drug monitoring (TDM) and dose adjustment of Treosulfan is feasible. Plasma Treosulfan/S, S-EBDM levels were measured in seventy-seven patients using a validated LC-MS/MS method, and the PK parameters were estimated using nlmixr2. The influence of Treosulfan & S, S-EBDM exposure, and GSTA1/NQO1 polymorphisms on graft rejection, RRTs, chimerism status, and 1-year Overall Survival (OS), and Thalassemia Free Survival (TFS) were assessed. We observed that Treosulfan exposure was lower in patients with graft rejection than those without (1655 vs. 2037 mg*h/L, p=0.07). Pharmacodynamic modeling analysis to identify therapeutic cut-off revealed that Treosulfan exposure ≥1660 mg*hr/L was significantly associated with better 1-year TFS (97% vs. 81%, p=0.02) and a trend to better 1-year OS (90% vs. 69%, p=0.07). Further, multivariate analysis adjusting for known PreHCT risk factors also revealed Treosulfan exposure <1660mg*h/L (HR=3.23; 95% CI=1.12-9.34; p=0.03) and GSTA1*B variant genotype (HR=3.75; 95% CI=1.04-13.47; p=0.04) to be independent predictors for inferior 1-year TFS. We conclude that lower Treosulfan exposure increases the risk of graft rejection and early transplant-related mortality affecting TFS. As no RRTs were observed with increasing Treosulfan exposure, TDM-based dose adjustment could be feasible and beneficial