New structural forms of a mycobacterial adenylyl cyclase Rv1625c

Rv1625c is one of 16 adenylyl cyclases encoded in the genome of Mycobacterium tuberculosis. In solution Rv1625c exists predominantly as a monomer, with a small amount of dimer. It has been shown previously that the monomer is active and the dimeric fraction is inactive. Both fractions of wild-type Rv1625c crystallized as head-to-head inactive domain-swapped dimers as opposed to the head-to-tail dimer seen in other functional adenylyl cyclases. About half of the molecule is involved in extensive domain swapping. The strain created by a serine residue located on a hinge loop and the crystallization condition might have led to this unusual domain swapping. The inactivity of the dimeric form of Rv1625c could be explained by the absence of the required catalytic site in the swapped dimer. A single mutant of the enzyme was also generated by changing a phenylalanine predicted to occur at the functional dimer interface to an arginine. This single mutant exists as a dimer in solution but crystallized as a monomer. Analysis of the structure showed that a salt bridge formed between a glutamate residue in the N-terminal segment and the mutated arginine residue hinders dimer formation by pulling the N-terminal region towards the dimer interface. Both structures reported here show a change in the dimerization-arm region which is involved in formation of the functional dimer. It is concluded that the dimerization arm along with other structural elements such as the N-terminal region and certain loops are vital for determining the oligomeric nature of the enzyme, which in turn dictates its activity.

Wireless scheduling with partial channel state information: large deviations and optimality

We consider a server serving a time-slotted queued system of multiple packet-based flows, where not more than one flow can be serviced in a single time slot. The flows have exogenous packet arrivals and time-varying service rates. At each time, the server can observe instantaneous service rates for only a subset of flows ( selected from a fixed collection of observable subsets) before scheduling a flow in the subset for service. We are interested in queue length aware scheduling to keep the queues short. The limited availability of instantaneous service rate information requires the scheduler to make a careful choice of which subset of service rates to sample. We develop scheduling algorithms that use only partial service rate information from subsets of channels, and that minimize the likelihood of queue overflow in the system. Specifically, we present a new joint subset-sampling and scheduling algorithm called Max-Exp that uses only the current queue lengths to pick a subset of flows, and subsequently schedules a flow using the Exponential rule. When the collection of observable subsets is disjoint, we show that Max-Exp achieves the best exponential decay rate, among all scheduling algorithms that base their decision on the current ( or any finite past history of) system state, of the tail of the longest queue. To accomplish this, we employ novel analytical techniques for studying the performance of scheduling algorithms using partial state, which may be of independent interest. These include new sample-path large deviations results for processes obtained by non-random, predictable sampling of sequences of independent and identically distributed random variables. A consequence of these results is that scheduling with partial state information yields a rate function significantly different from scheduling with full channel information. In the special case when the observable subsets are singleton flows, i.e., when there is effectively no a priori channel state information, Max-Exp reduces to simply serving the flow with the longest queue; thus, our results show that to always serve the longest queue in the absence of any channel state information is large deviations optimal.

A new rock dwelling Hemidactylus (Squamata: Gekkonidae) from Chhattisgarh, India

A distinct new species of gecko of the genus Hemidactylus is described from the Kanker district of Chhattisgarh State, east-central India. This large-sized (SVL average 81.33 +/- 13.40 to at least 98.0 mm) Hemidactylus is characterized by a dorsum with small granules, intermixed with 10-12 rows of irregularly arranged, slightly larger, rounded, weakly-keeled tubercles at midbody; 10-12 and 13-15 subdigital lamellae on the first and fourth digits, respectively, of both manus and pes; a single enlarged postcloacal tubercle on either side of the tail; 10-12 femoral pores on each thigh separated by 5-8 poreless scales; 12-14 supralabials and 10-12 infralabials.

A new rock dwelling Hemidactylus (Squamata: Gekkonidae) from Chhattisgarh, India

A distinct new species of gecko of the genus Hemidactylus is described from the Kanker district of Chhattisgarh State, east-central India. This large-sized (SVL average 81.33 +/- 13.40 to at least 98.0 mm) Hemidactylus is characterized by a dorsum with small granules, intermixed with 10-12 rows of irregularly arranged, slightly larger, rounded, weakly-keeled tubercles at midbody; 10-12 and 13-15 subdigital lamellae on the first and fourth digits, respectively, of both manus and pes; a single enlarged postcloacal tubercle on either side of the tail; 10-12 femoral pores on each thigh separated by 5-8 poreless scales; 12-14 supralabials and 10-12 infralabials.

Evaluation of developmental toxicity and apoptotic induction of the aqueous extract of Millettia pachycarpa using zebrafish as model organism

Extensive and indiscriminate use of synthetic compounds and natural compounds obtained from plant sources have resulted in serious threats to the aquatic ecosystem and human health. Aqueous extract of the root of the plant, Milletia pachycarpa Benth, is currently used for killing fish in the state of Manipur, India. Moreover, this plant is also used as traditional medicine in this region. Although it is widely used in traditional medicine, there is limited information available regarding the adverse effects and mechanism underlying its toxicity. This study examined the effects of exposure to aqueous extract of M. pachycarpa (AEMP) on early embryonic development of zebrafish embryos and mechanisms underlying toxicity. Zebrafish embryos treated with different concentrations of the AEMP produced embryonic lethality and developmental defects. The 96-hr-LC50 of AEMP was found to be 4.276 mu g/mL. Further, multiple developmental abnormalities such as pericardial edema, yolk sac edema, spinal curvature, swim bladder deflation, decreased heart rate, and delayed hatching were also observed in a dose-dependent manner. Zebrafish embryo showing moderate-to-severe developmental defects following AEMP exposure cannot swim properly. Further, this study examined oxidative stress and apoptosis in embryos exposed to AEMP. Enhanced production of ROS and apoptosis was found in brain, trunk, and tail of zebrafish embryos treated with AEMP. Data suggest that oxidative stress and apoptosis are associated with AEMP-induced embryonic lethality and developmental toxicity in zebrafish embryos.