Splicing Functions and Global Dependency on Fission Yeast Slu7 Reveal Diversity in Spliceosome Assembly

The multiple short introns in Schizosaccharomyces pombe genes with degenerate cis sequences and atypically positioned polypyrimidine tracts make an interesting model to investigate canonical and alternative roles for conserved splicing factors. Here we report functions and interactions of the S. pombe slu7(+) (spslu7(+)) gene product, known from Saccharomyces cerevisiae and human in vitro reactions to assemble into spliceosomes after the first catalytic reaction and to dictate 3' splice site choice during the second reaction. By using a missense mutant of this essential S. pombe factor, we detected a range of global splicing derangements that were validated in assays for the splicing status of diverse candidate introns. We ascribe widespread, intron-specific SpSlu7 functions and have deduced several features, including the branch nucleotide-to-3' splice site distance, intron length, and the impact of its A/U content at the 5' end on the intron's dependence on SpSlu7. The data imply dynamic substrate-splicing factor relationships in multiintron transcripts. Interestingly, the unexpected early splicing arrest in spslu7-2 revealed a role before catalysis. We detected a salt-stable association with U5 snRNP and observed genetic interactions with spprp1(+), a homolog of human U5-102k factor. These observations together point to an altered recruitment and dependence on SpSlu7, suggesting its role in facilitating transitions that promote catalysis, and highlight the diversity in spliceosome assembly.

Conformational Diversity in Contryphans from Conus Venom: cis-trans Isomerisation and Aromatic/Proline Interactions in the 23-Membered Ring of a 7-Residue Peptide Disulfide Loop

Conformational diversity or shapeshifting in cyclic peptide natural products can, in principle, confer a single molecular entity with the property of binding to multiple receptors. Conformational equilibria have been probed in the contryphans, which are peptides derived from Conus venom possessing a 23-membered cyclic disulfide moiety. The natural sequences derived from Conus inscriptus, GCV(D)LYPWC* (In936) and Conus loroisii, GCP(D)WDPWC* (Lo959) differ in the number of proline residues within the macrocyclic ring. Structural characterisation of distinct conformational states arising from cis-trans equilibria about Xxx-Pro bonds is reported. Isomerisation about the C2-P3 bond is observed in the case of Lo959 and about the Y5-P6 bond in In936. Evidence is presented for as many as four distinct species in the case of the synthetic analogue V3P In936. The Tyr-Pro-Trp segment in In936 is characterised by distinct sidechain orientations as a consequence of aromatic/proline interactions as evidenced by specific sidechain-sidechain nuclear Overhauser effects and ring current shifted proton chemical shifts. Molecular dynamics simulations suggest that Tyr5 and Trp7 sidechain conformations are correlated and depend on the geometry of the Xxx-Pro bond. Thermodynamic parameters are derived for the cis trans equilibrium for In936. Studies on synthetic analogues provide insights into the role of sequence effects in modulating isomerisation about Xxx-Pro bonds.

Full-rate full-diversity finite feedback space-time schemes with minimum feedback and transmission duration

A Finite Feedback Scheme (FFS) for a quasi-static MIMO block fading channel with finite N-ary delay-free noise-free feedback consists of N Space-Time Block Codes (STBCs) at the transmitter, one corresponding to each possible value of feedback, and a function at the receiver that generates N-ary feedback. A number of FFSs are available in the literature that provably attain full-diversity. However, there is no known full-diversity criterion that universally applies to all FFSs. In this paper a universal necessary condition for any FFS to achieve full-diversity is given, and based on this criterion the notion of Feedback-Transmission duration optimal (FT-optimal) FFSs is introduced, which are schemes that use minimum amount of feedback N for the given transmission duration T, and minimum T for the given N to achieve full-diversity. When there is no feedback (N = 1) an FT-optimal scheme consists of a single STBC, and the proposed condition reduces to the well known necessary and sufficient condition for an STBC to achieve full-diversity. Also, a sufficient criterion for full-diversity is given for FFSs in which the component STBC yielding the largest minimum Euclidean distance is chosen, using which full-rate (N-t complex symbols per channel use) full-diversity FT-optimal schemes are constructed for all N-t > 1. These are the first full-rate full-diversity FFSs reported in the literature for T < N-t. Simulation results show that the new schemes have the best error performance among all known FFSs.

Diversity order vs rate in an AWGN channel

We study the diversity order vs rate of an additive white Gaussian noise (AWGN) channel in the whole capacity region. We show that for discrete input as well as for continuous input, Gallager's upper bounds on error probability have exponential diversity in low and high rate region but only subexponential in the mid-rate region. For the best available lower bounds and for the practical codes one observes exponential diversity throughout the capacity region. However we also show that performance of practical codes is close to Gallager's upper bounds and the mid-rate subexponential diversity has a bearing on the performance of the practical codes. Finally we show that the upper bounds with Gaussian input provide good approximation throughout the capacity region even for finite constellation.

Non-Syndromic Hearing Impairment in India: High Allelic Heterogeneity among Mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE

Mutations in the autosomal genes TMPRSS3, TMC1, USHIC, CDH23 and TMIE are known to cause hereditary hearing loss. To study the contribution of these genes to autosomal recessive, non-syndromic hearing loss (ARNSHL) in India, we examined 374 families with the disorder to identify potential mutations. We found four mutations in TMPRSS3, eight in TMC1, ten in USHIC, eight in CDH23 and three in TMIE. Of the 33 potentially pathogenic variants identified in these genes, 23 were new and the remaining have been previously reported. Collectively, mutations in these five genes contribute to about one-tenth of ARNSHL among the families examined. New mutations detected in this study extend the allelic heterogeneity of the genes and provide several additional variants for structure-function correlation studies. These findings have implications for early DNA-based detection of deafness and genetic counseling of affected families in the Indian subcontinent.

Variation at Diabetes- and Obesity-Associated Loci May Mirror Neutral Patterns of Human Population Diversity and Diabetes Prevalence in India

South Asian populations harbor a high degree of genetic diversity, due in part to demographic history. Two studies on genome-wide variation in Indian populations have shown that most Indian populations show varying degrees of admixture between ancestral north Indian and ancestral south Indian components. As a result of this structure, genetic variation in India appears to follow a geographic cline. Similarly, Indian populations seem to show detectable differences in diabetes and obesity prevalence between different geographic regions of the country. We tested the hypothesis that genetic variation at diabetes-and obesity-associated loci may be potentially related to different genetic ancestries. We genotyped 2977 individuals from 61 populations across India for 18 SNPs in genes implicated in T2D and obesity. We examined patterns of variation in allele frequency across different geographical gradients and considered state of origin and language affiliation. Our results show that most of the 18 SNPs show no significant correlation with latitude, the geographic cline reported in previous studies, or by language family. Exceptions include KCNQ1 with latitude and THADA and JAK1 with language, which suggests that genetic variation at previously ascertained diabetes-associated loci may only partly mirror geographic patterns of genome-wide diversity in Indian populations.

Structural Diversity in Multinuclear PdII Assemblies that Show Low- Humidity Proton Conduction

Systematic investigation on synergetic effects of geometry, length, denticity, and asymmetry of donors was performed through the formation of a series of uncommon Pd-II aggregates by employing the donor in a multicomponent self-assembly of a cis-blocked 90 degrees Pd-II acceptor and a tetratopic donor. Some of these assemblies represent the first examples of these types of structures, and their formation is not anticipated by only taking the geometry of the donor and the acceptor building units into account. Analysis of the crystal packing of the X-ray structure revealed several H bonds between the counteranions (NO3-) and water molecules (OHON). Moreover, H-bonded 3D-networks of water are present in the molecular pockets, which show water-adsorption properties with some variation in water affinity. Interestingly, these complexes exhibit proton conductivity (1.87x10(-5)-6.52x10(-4)Scm(-1)) at 296K and low relative humidity (ca. 46%) with activation energies of 0.29-0.46eV. Moreover, the conductivities further increase with the enhancement of humidity. The ability of these assemblies to exhibit proton-conducting properties under low-humidity conditions makes these materials highly appealing as electrolytes in batteries and in fuel-cell applications.

Interference Alignment With Diversity for the 2 x 2 X-Network With Four Antennas

A transmission scheme based on the Alamouti code, which we call the Li-Jafarkhani-Jafar (LJJ) scheme, was recently proposed for the 2 x 2 X-network i.e., two-transmitter (Tx) two-receiver X-network] with two antennas at each node. This scheme was claimed to achieve a sum degrees of freedom (DoF) of 8/3 and also a diversity gain of two when fixed finite constellations are employed at each Tx. Furthermore, each Tx required the knowledge of only its own channel unlike the Jafar-Shamai scheme which required global CSIT to achieve the maximum possible sum DoF of 8/3. In this paper, we extend the LJJ scheme to the 2 x 2 X-network with four antennas at each node. The proposed scheme also assumes only local channel knowledge at each Tx. We prove that the proposed scheme achieves the maximum possible sum DoF of 16/3. In addition, we also prove that, using any fixed finite constellation with appropriate rotation at each Tx, the proposed scheme achieves a diversity gain of at least four.

Structural diversity and ligand specificity of lectins. The Bangalore effort

Structural studies in this laboratory encompass four of the five major classes of plant lectins, including the one discovered by us. In addition to addressing issues specific to individual lectins, the work provided insights into protein folding, quaternary association and generation of ligand specificity. Legume and beta-prism fold lectins constitute families of proteins in which small alterations in essentially the same tertiary structure lead to large variations in quaternary structure, including that involving an open structure. Strategies for generating ligand specificity include water bridges, variation in loop length, post translational modification and oligomerization. Three of the structural classes investigated have subunits with three-fold symmetry. The symmetry in the structure is reflected in the sequence to different extents in different subclasses. The evolutionary implications of this observation have been explored. The work on lectins has now been extended to those from mycobacteria.

Species and acoustic diversity of bats in a palaeotropical wet evergreen forest in southern India

The Western Ghats of India is among the top 25 biodiversity hotspots in the world. About 43% of the reported 117 bat species in India are found in this region, but few quantitative studies of bat echolocation calls and diversity have been carried out here thus far. A quantitative study of bat diversity was therefore conducted using standard techniques, including mist-netting, acoustical and roost surveys in the wet evergreen forests of Kudremukh National Park in the Western Ghats of Karnataka. A total of 106 bats were caught over 108 sampling nights, representing 17 species, 3 belonging to Megachiroptera and 14 to Microchiroptera. Acoustical and roost surveys added three more species, two from Microchiroptera and one from Megachiroptera. Of these 20 species, 4 belonged to the family Pteropodidae, 10 to Vespertilionidae, 3 to Rhinolophidae, 2 to Megadermatidae and 1 to Hipposideridae. We recorded the echolocation calls of 13 of the 16 microchiropteran species, of which the calls of 4 species (Pipistrellus coromandra, Pipistrellus affinis, Pipistrellus ceylonicus and Harpiocephalus harpia) have been recorded for the first time. Discriminant function analyses of the calls of 11 species provided 91.7% correct classification of individuals to their respective species, indicating that the echolocation calls could be used successfully for non-invasive acoustic surveys and monitoring of bat species in the future.

Splicing Functions and Global Dependency on Fission Yeast Slu7 Reveal Diversity in Spliceosome Assembly

The multiple short introns in Schizosaccharomyces pombe genes with degenerate cis sequences and atypically positioned polypyrimidine tracts make an interesting model to investigate canonical and alternative roles for conserved splicing factors. Here we report functions and interactions of the S. pombe slu7(+) (spslu7(+)) gene product, known from Saccharomyces cerevisiae and human in vitro reactions to assemble into spliceosomes after the first catalytic reaction and to dictate 3' splice site choice during the second reaction. By using a missense mutant of this essential S. pombe factor, we detected a range of global splicing derangements that were validated in assays for the splicing status of diverse candidate introns. We ascribe widespread, intron-specific SpSlu7 functions and have deduced several features, including the branch nucleotide-to-3' splice site distance, intron length, and the impact of its A/U content at the 5' end on the intron's dependence on SpSlu7. The data imply dynamic substrate-splicing factor relationships in multiintron transcripts. Interestingly, the unexpected early splicing arrest in spslu7-2 revealed a role before catalysis. We detected a salt-stable association with U5 snRNP and observed genetic interactions with spprp1(+), a homolog of human U5-102k factor. These observations together point to an altered recruitment and dependence on SpSlu7, suggesting its role in facilitating transitions that promote catalysis, and highlight the diversity in spliceosome assembly.

Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection

In India, the low prevalence of HIV-associated dementia (HAD) in the Human immunodeficiency virus type 1 (HIV-1) subtype C infection is quite paradoxical given the high-rate of macrophage infiltration into the brain. Whether the direct viral burden in individual brain compartments could be associated with the variability of the neurologic manifestations is controversial. To understand this paradox, we examined the proviral DNA load in nine different brain regions and three different peripheral tissues derived from ten human subjects at autopsy. Using a highly sensitive TaqMan probe-based real-time PCR, we determined the proviral load in multiple samples processed in parallel from each site. Unlike previously published reports, the present analysis identified uniform proviral distribution among the brain compartments examined without preferential accumulation of the DNA in any one of them. The overall viral DNA burden in the brain tissues was very low, approximately 1 viral integration per 1000 cells or less. In a subset of the tissue samples tested, the HIV DNA mostly existed in a free unintegrated form. The V3-V5 envelope sequences, demonstrated a brain-specific compartmentalization in four of the ten subjects and a phylogenetic overlap between the neural and non-neural compartments in three other subjects. The envelope sequences phylogenetically belonged to subtype C and the majority of them were R5 tropic. To the best of our knowledge, the present study represents the first analysis of the proviral burden in subtype C postmortem human brain tissues. Future studies should determine the presence of the viral antigens, the viral transcripts, and the proviral DNA, in parallel, in different brain compartments to shed more light on the significance of the viral burden on neurologic consequences of HIV infection.

Quantifying the Transmit Diversity Order of Euclidean Distance Based Antenna Selection in Spatial Modulation

In this letter, we quantify the transmit diversity order of the SM system operating in a closed-loop scenario. Specifically, the SM system relying on Euclidean distance based antenna subset selection (EDAS) is considered and the achievable diversity gain is evaluated. Furthermore, the resultant trade-off between the achievable diversity gain and switching gain is studied. Simulation results confirm our theoretical results. Specifically, at a symbol error rate of about 10(-4) the signal-to-noise ratio gain achieved by EDAS is about 7 dB in case of 16-QAM and about 5 dB in case of 64-QAM.