Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

Background: Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result: The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion: Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

Spectral analysis of noise in the neonatal intensive care unit

Objective To perform spectral analysis of noise generated by equipments and activities in a level III neonatal intensive care unit (NICU) and measure the real time sequential hourly noise levels over a 15 day period. Methods Noise generated in the NICU by individual equipments and activities were recorded with a digital spectral sound analyzer to perform spectral analysis over 0.5–8 KHz. Sequential hourly noise level measurements in all the rooms of the NICU were done for 15 days using a digital sound pressure level meter. Independent sample t test and one way ANOVA were used to examine the statistical significance of the results. The study has a 90% power to detect at least 4 dB differences from the recommended maximum of 50 dB with 95 % confidence. Results The mean noise levels in the ventilator room and stable room were 19.99 dB (A) sound pressure level (SPL) and 11.81 dB (A) SPL higher than the maximum recommended of 50 dB (A) respectively (p < 0.001). The equipments generated 19.11 dB SPL higher than the recommended norms in 1–8 KHz spectrum. The activities generated 21.49 dB SPL higher than the recommended norms in 1–8 KHz spectrum (p< 0.001). The ventilator and nebulisers produced excess noise of 8.5 dB SPL at the 0.5 KHz spectrum.Conclusion Noise level in the NICU is unacceptably high. Spectral analysis of equipment and activity noise have shown noise predominantly in the 1–8 KHz spectrum. These levels warrant immediate implementation of noise reduction protocols as a standard of care in the NICU.

Voluntary Control of Multisaccade Gaze Shifts During Movement Preparation and Execution

Ramakrishnan A, Chokhandre S, Murthy A. Voluntary control of multisaccade gaze shifts during movement preparation and execution. J Neurophysiol 103: 2400-2416, 2010. First published February 17, 2010; doi: 10.1152/jn.00843.2009. Although the nature of gaze control regulating single saccades is relatively well documented, how such control is implemented to regulate multisaccade gaze shifts is not known. We used highly eccentric targets to elicit multisaccade gaze shifts and tested the ability of subjects to control the saccade sequence by presenting a second target on random trials. Their response allowed us to test the nature of control at many levels: before, during, and between saccades. Although the saccade sequence could be inhibited before it began, we observed clear signs of truncation of the first saccade, which confirmed that it could be inhibited in midflight as well. Using a race model that explains the control of single saccades, we estimated that it took about 100 ms to inhibit a planned saccade but took about 150 ms to inhibit a saccade during its execution. Although the time taken to inhibit was different, the high subject-wise correlation suggests a unitary inhibitory control acting at different levels in the oculomotor system. We also frequently observed responses that consisted of hypometric initial saccades, followed by secondary saccades to the initial target. Given the estimates of the inhibitory process provided by the model that also took into account the variances of the processes as well, the secondary saccades (average latency similar to 215 ms) should have been inhibited. Failure to inhibit the secondary saccade suggests that the intersaccadic interval in a multisaccade response is a ballistic stage. Collectively, these data indicate that the oculomotor system can control a response until a very late stage in its execution. However, if the response consists of multiple movements then the preparation of the second movement becomes refractory to new visual input, either because it is part of a preprogrammed sequence or as a consequence of being a corrective response to a motor error.

Voluntary Energy Harvesting Relays and Selection in Cooperative Wireless Networks

The use of energy harvesting (EH) nodes as cooperative relays is a promising and emerging solution in wireless systems such as wireless sensor networks. It harnesses the spatial diversity of a multi-relay network and addresses the vexing problem of a relay's batteries getting drained in forwarding information to the destination. We consider a cooperative system in which EH nodes volunteer to serve as amplify-and-forward relays whenever they have sufficient energy for transmission. For a general class of stationary and ergodic EH processes, we introduce the notion of energy constrained and energy unconstrained relays and analytically characterize the symbol error rate of the system. Further insight is gained by an asymptotic analysis that considers the cases where the signal-to-noise-ratio or the number of relays is large. Our analysis quantifies how the energy usage at an EH relay and, consequently, its availability for relaying, depends not only on the relay's energy harvesting process, but also on its transmit power setting and the other relays in the system. The optimal static transmit power setting at the EH relays is also determined. Altogether, our results demonstrate how a system that uses EH relays differs in significant ways from one that uses conventional cooperative relays.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-gamma and IL-17 production in blood from TB plus patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-gamma and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-gamma production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions: The pattern of immune target recognition is different in regard to IFN-gamma and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Mud-packing frog: A novel breeding behaviour and parental care in a stream dwelling new species of Nyctibatrachus (Amphibia, Anura, Nyctibatrachidae)

Reproductive modes are diverse and unique in anurans. Selective pressures of evolution, ecology and environment are attributed to such diverse reproductive modes. Globally forty different reproductive modes in anurans have been described to date. The genus Nyctibatrachus has been recently revised and belongs to an ancient lineage of frog families in the Western Ghats of India. Species of this genus are known to exhibit mountain associated clade endemism and novel breeding behaviours. The purpose of this study is to present unique reproductive behaviour, oviposition and parental care in a new species Nyctibatrachus kumbara sp. nov. which is described in the paper. Nyctibatrachus kumbara sp. nov. is a medium sized stream dwelling frog. It is distinct from the congeners based on a suite of morphological characters and substantially divergent in DNA sequences of the mitochondrial 16S rRNA gene. Males exhibit parental care by mud packing the egg clutch. Such parental care has so far not been described from any other frog species worldwide. Besides this, we emphasize that three co-occurring congeneric species of Nyctibatrachus, namely N. jog, N. kempholeyensis and Nyctibatrachus kumbara sp. nov. from the study site differ in breeding behaviour, which could represent a case of reproductive character displacement. These three species are distinct in their size, call pattern, reproductive behaviour, maximum number of eggs in a clutch, oviposition and parental care, which was evident from the statistical analysis. The study throws light on the reproductive behaviour of Nyctibatrachus kumbara sp. nov. and associated species to understand the evolution and adaptation of reproductive modes of anurans in general, and Nyctibatrachus in particular from the Western Ghats.