Form and Function of Proteins. Historical Background and the Indian Effort in Macromolecular Crystallography

Global efforts in macromolecular crystallography started in the thirties of the last century. However, definitive results began to emerge only in the late fifties and the early sixties. India has a long tradition in crystallography. The country had a head start in theoretical and computational structural biology, thanks to the efforts of G.N. Ramachandran and his colleagues in the fifties and the sixties. However, macromolecular crystallography got off the ground in India only in the eighties, particularly after the Bangalore group received adequate support from the Department of Science and Technology under their Thrust Area Programme. The Bangalore centre was also identified as a national nucleus for the development of the area in the country. Since then work in the area has spread widely and is being carried out by several groups, mainly led by scientists trained at Bangalore or their descendents, in about thirty institutions in India. In addition to the Department of Science and Technology, the effort is now supported by other agencies like the Department of Biotechnology and the Council of Scientific and Industrial Research. The problems addressed by macromolecular crystallographers in India encompass almost all aspects of modern biology. Indian efforts in macromolecular crystallography have also become an important component of the international efforts in the area.

Superconductivity in Ba(Pb,Bi,Sb)O3, Ba(Pb,Bi,Te)O3 and (Ba,La) (Pb,Bi,Tl)O3 systems

It is possible to substitute Bi in the superconducting BaPb0.75Bi0.25O3 by Sb or Te without destroying the superconductivity. With Sb, a continuous series of solid solutions BaPb0.75Bi0.25?ySbyO3 (0 less-than-or-equals, slant y less-than-or-equals, slant 0.25) exists, while with Te, perovskite BaPb0.75Bi0.25?yTeyO3 exists only upto y = 0.15. With increasing substitution by Sb or Te, Tc decreases continously in both the systems. Superconductivity with a maximum Tc of 8K is found in Ba0.9La0.1Pb0.9?yBiyTl0.1O3 for y = 0.25.

Interplay between NS3 protease and human La protein regulates translation-replication switch of Hepatitis C virus

HCV NS3 protein plays a central role in viral polyprotein processing and RNA replication. We demonstrate that the NS3 protease (NS3(pro)) domain alone can specifically bind to HCV-IRES RNA, predominantly in the SLIV region. The cleavage activity of the NS3 protease domain is reduced upon HCV-RNA binding. More importantly, NS3(pro) binding to the SLIV hinders the interaction of La protein, a cellular IRES-trans acting factor required for HCV IRES-mediated translation, resulting in inhibition of HCV-IRES activity. Although overexpression of both NS3(pro) as well as the full length NS3 protein decreased the level of HCV IRES mediated translation, replication of HCV replicon RNA was enhanced significantly. These observations suggest that the NS3(pro) binding to HCV IRES reduces translation in favor of RNA replication. The competition between the host factor (La) and the viral protein (NS3) for binding to HCV IRES might regulate the molecular switch from translation to replication of HCV.

Relook into the historical progress and philosophy of Indian space exploration

A study of the history and philosophy of the contribution of India towards the exploration of space since antiquity provides interesting insights. The contributions are described during the three periods namely: (1) the ten millenniums from 10,000 BC with a twilight period up to 900 AD; (2) the ten centuries from 900 AD to 1900 AD; and (3) the ten decades from 1900 AD to 2000 AD; called mythological, medieval, and modern respectively. Some important events during the above periods provide a reference view of the progress. The Vedas during the mythological period and the Siddhantas during the medieval periods, which are based on astronomical observations, indicate that the Indian contribution preceded other cultures. But most Western historians ignore this fact time and again in spite of many proofs provided to the contrary. This chapter also shows that Indians had the proper scientific attitude of developing any physical theory through the triplet of mind, model, and measurements. It is this same triplet that forms the basis of the present day well known Kalman filter technique. Up to about 1500 BC the Indian contribution was leading but during foreign invasion and occupation it lagged and has been improving only after independence.

The Asian elephants Elephas maximus of Cat Tien National Park, Vietnam: status and conservation of a vanishing population

This study updates the status and conservation of the Endangered Asian elephant Elephas maximus in Cat Tien National Park, Vietnam. Line transect indirect surveys, block surveys for elephant signs, village surveys of elephant-human conflict incidents, guard-post surveys for records of sightings, and surveys of elephant food plants were undertaken during the dry and wet seasons of 2001. A minimum of 11 elephants and a maximum of 15-17 elephants was estimated for c. 500 km2 of the Park and its vicinity. The elephants are largely confined to the southern boundary of the Park and make extensive use of the adjoining La Nga State Forest Enterprises. During the dry season the elephants depend on at least 26 species of wild and cultivated plants, chiefly the fruits of cashew. Most of the villages surveyed reported some elephant-human conflict. Two adult male elephants seem to cover a large area to raid crops, whereas the family groups restrict themselves to a few villages; overall, the conflict is not serious. Since 2001 there have been no reports of any deaths or births of elephants in the Park. We make recommendations for habitat protection and management, increasing the viability of the small population, reducing elephant-human conflicts, and improving the chances of survival of the declining elephants of this Park. The Government has now approved an Action Plan for Urgent Conservation Areas in Vietnam that calls for the establishment of three elephant conservation areas in the country, including Cat Tien National Park.

Reassessing the earthquake hazard in Kerala based on the historical and current seismicity

Given the lack of proper constraints in understanding earthquake mechanisms in the cratonic interiors and the general absence of good quality database, here we reassess the seismic hazard in the province of Kerala, a part of the aEuro cent stable continental interioraEuro cent, based on an improved historical and instrumental database. The temporal pattern of the current seismicity suggests that > 60% of the microtremors in Kerala occurs with a time lag after the peak rainfall, indicating that hydroseismicity may be a plausible model to explain the low-level seismicity in this region. Further, an increment in overall seismicity rate in the region in the recent years is explained as due to increased anthropogenic activities, which includes changes in hydrological pathways as a consequence of rapid landscape changes. Our analyses of the historical database eliminate a few events that are ascribed to this region; this exercise has also led to identification of a few events, not previously noted. The improved historical database essentially suggests that the central midland region is more prone to seismic activity compared to other parts of Kerala. This region appears to have generated larger number of significant earthquakes; the most prominent being the multiple events (doublets) of 1856 and 1953, whose magnitudes are comparable to that of the 2000/2001 (central Kerala) events. Occurrences of these historical events and the recent earthquakes, and the local geology indicative of pervasive faulting as shown by widely distributed pseudotachylite veins suggest that the NNW-SSE trending faults in central midland Kerala may host discrete potentially active sources that may be capable of generating light to moderate size earthquakes. The frequency of earthquakes in central Kerala evident from the historical database requires that the seismic codes stipulated for this region are made mandatory.

HuR Displaces Polypyrimidine Tract Binding Protein To Facilitate La Binding to the 3 ` Untranslated Region and Enhances Hepatitis C Virus Replication

HuR is a ubiquitous, RNA binding protein that influences the stability and translation of several cellular mRNAs. Here, we report a novel role for HuR, as a regulator of proteins assembling at the 3' untranslated region (UTR) of viral RNA in the context of hepatitis C virus (HCV) infection. HuR relocalizes from the nucleus to the cytoplasm upon HCV infection, interacts with the viral polymerase (NS5B), and gets redistributed into compartments of viral RNA synthesis. Depletion in HuR levels leads to a significant reduction in viral RNA synthesis. We further demonstrate that the interaction of HuR with the 3' UTR of the viral RNA affects the interaction of two host proteins, La and polypyrimidine tract binding protein (PTB), at this site. HuR interacts with La and facilitates La binding to the 3' UTR, enhancing La-mediated circularization of the HCV genome and thus viral replication. In addition, it competes with PTB for association with the 3' UTR, which might stimulate viral replication. Results suggest that HuR influences the formation of a cellular/viral ribonucleoprotein complex, which is important for efficient initiation of viral RNA replication. Our study unravels a novel strategy of regulation of HCV replication through an interplay of host and viral proteins, orchestrated by HuR. IMPORTANCE Hepatitis C virus (HCV) is highly dependent on various host factors for efficient replication of the viral RNA. Here, we have shown how a host factor (HuR) migrates from the nucleus to the cytoplasm and gets recruited in the protein complex assembling at the 3' untranslated region (UTR) of HCV RNA. At the 3' UTR, it facilitates circularization of the viral genome through interaction with another host factor, La, which is critical for replication. Also, it competes with the host protein PTB, which is a negative regulator of viral replication. Results demonstrate a unique strategy of regulation of HCV replication by a host protein through alteration of its subcellular localization and interacting partners. The study has advanced our knowledge of the molecular mechanism of HCV replication and unraveled the complex interplay between the host factors and viral RNA that could be targeted for therapeutic interventions.