Caenorhabditis elegans RAC1/ced-10 mutants as a new animal model to study very early stages of Parkinson's disease.

Patients with Parkinson's disease (PD) display non-motor symptoms arising prior to the appearance of motor signs and before a clear diagnosis. Motor and non-motor symptoms correlate with progressive deposition of the protein alpha-synuclein (Asyn) both within and outside of the central nervous system, and its accumulation parallels neurodegeneration. The genome of Caenorhabditis elegans does not encode a homolog of Asyn, thus rendering this nematode an invaluable system with which to investigate PD-related mechanisms in the absence of interference from endogenous Asyn aggregation. CED-10 is the nematode homolog of human RAC1, a small GTPase needed to maintain the function and survival of dopaminergic neurons against human Asyn-induced toxicity in C. elegans. Here, we introduce C. elegans RAC1/ced-10 mutants as a predictive tool to investigate early PD symptoms before neurodegeneration occurs. Deep phenotyping of these animals reveals that, early in development, they displayed altered defecation cycles, GABAergic abnormalities and an increased oxidation index. Moreover, they exhibited altered lipid metabolism evidenced by the accumulation of lipid droplets. Lipidomic fingerprinting indicates that phosphatidylcholine and sphingomyelin, but not phosphatidylethanolamine or phosphatidylserine, were elevated in RAC1/ced-10 mutant nematodes. These collective characteristics reflect the non-motor dysfunction, GABAergic neurotransmission defects, upregulation of stress response mechanisms, and metabolic changes associated with early-onset PD. Thus, we put forward an easy-to-manipulate preclinical animal model to deepen our understanding of early-stage PD and accelerate the translational path for therapeutic target discovery.

Seismotectonic studies of the coastal areas of India, Pakistan, Bangladesh, and Burma

Major geotectonic elements that are seismically active in the bear-shore areas of the Indian subcontinent are the Mekran fault off the coast of Pakistan, the western part of the Narmada-Son lineament, the West Coast Fault off the west coast of India - a southward extension of the Cambay Rift, the Palghat Gap, the Godavari and Mahanadi grabens, transecting rather at an angle to the eastern coast of India and the Arakan-Yoma arcuate belt of Burma, which is a part of the global Alpine-Himalayan orogenic belt, continuing southwards into the Andaman-Nicobar island complex and the Java-Sumatra trench on the ocean floor of the advancing Indo-Australian Plate. Observations along the coastal areas during historic and recent times, however, confirm the absence of significant tsunamis, though very mild tsunami surges have occasionally been observed along the coastal areas of the Bay of Bengal. No active volcanoes are known to exist in the coastal areas. Water reservois situiated near the marginal areas of the Peninsular Shield exhibit moderate to intense seismic activities, viz. Ukai, Bhasta, Koyna, Parambikulam, Sholayar, Idduki, and Kinnersani.(AU)