Biology subjects

Raman, R.

Publications and source records attributed to Raman, R..

28 records · Page 2Linked to original sources

bioRxiv2021

Insights on the mutational landscape of the SARS-CoV-2 Omicron variant

The SARS-COV2 Omicron variant has sparked global concern due to the possibility of enhanced transmissibility and escape from vaccines and therapeutics. In this study, we describe the mutational landscape of the Omicron variant using amino acid interaction (AAI) networks. AAI network analysis is particularly well suited for interrogating the impact of constellations of mutations as occur on Omicron that may function in an epistatic manner. Our analyses suggest that as compared to previous variants of concern, the Omicron variant has increased antibody escape breadth due to mutations in class 3 and 4 antibody epitopes as well as increased escape depth due to accumulated mutations in class 1 antibody epitopes. We note certain RBD mutations that might further enhance Omicrons escape, and in particular advise careful surveillance of two subclades bearing R346S/K mutations with relevance for certain therapeutic antibodies. Further, AAI network analysis suggests that the function of certain therapeutic monoclonal antibodies may be disrupted by Omicron mutations as a result of the cumulative indirect perturbations to the epitope surface properties, despite point-mutation analyses suggesting these antibodies are tolerant of the set of Omicron mutations in isolation. Finally, for several Omicron mutations that do not appear to contribute meaningfully to antibody escape, we find evidence for a plausible role in enhanced transmissibility via disruption of RBD-down conformational stability at the RBD-RBD interface.

bioinformatics↗

bioRxiv2021

Multi-environment QTL analysis delineates a major locus associated with homoeologous exchanges for water-use efficiency and seed yield in allopolyploid Brassica napus

O_LICanola varieties exhibit discernible variation in drought avoidance and drought escape traits, suggesting its adaptation to water-deficit environments. However, the underlying mechanisms are poorly understood. C_LIO_LIA doubled haploid (DH) population was analysed to identify QTL associated with water use efficiency (WUE) related traits. Based on the resequenced parental genome data, we developed sequence-capture based markers for fine mapping. mRNA-Seq was performed to determine the expression of candidate genes underlying QTL for carbon isotope discrimination ({Delta}13C). C_LIO_LIQTL contributing to main and QTL x Environment interaction effects for {Delta}13C and for agronomic WUE were identified. One multi-trait QTL for {Delta}13C, days to flower, plant height and seed yield was identified on chromosome A09, in the vicinity of ERECTA. Interestingly, this QTL region was overlapped with a homoeologous exchange event (HE), suggesting its association with the major QTL. Transcriptome analysis revealed several differentially expressed genes between parental lines, including in HE regions. C_LIO_LIThis study provides insights into the complexity of WUE related genes in the context of canola adaptation to water-deficit conditions. Our results suggest that alleles for high {Delta}13C contribute positively to canola yield. Genetic and genomic resources developed herein could be utilised to make genetic gains for improving canola WUE. C_LI

plant biology↗

bioRxiv2021

Mapping Potential Antigenic Drift Sites (PADS) on SARS-CoV-2 Spike in Continuous Epitope-Paratope Space

SARS-CoV-2 mutations with antigenic effects pose a risk to immunity developed through vaccination and natural infection. While vaccine updates for current variants of concern (VOCs) are underway, it is likewise important to prepare for further antigenic mutations as the virus navigates the heterogeneous global landscape of host immunity. Toward this end, a wealth of data and tools exist that can augment existing genetic surveillance of VOC evolution. In this study, we integrate published datasets describing genetic, structural, and functional constraints on mutation along with computational analyses of antibody-spike co-crystal structures to identify a set of potential antigenic drift sites (PADS) within the receptor binding domain (RBD) and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Further, we project the PADS set into a continuous epitope-paratope space to facilitate interpretation of the degree to which newly observed mutations might be antigenically synergistic with existing VOC mutations, and this representation suggests that functionally convergent and synergistic antigenic mutations are accruing across VOC NTDs. The PADS set and synergy visualization serve as a reference as new mutations are detected on VOCs, enable proactive investigation of potentially synergistic mutations, and offer guidance to antibody and vaccine design efforts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/446560v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@13b884forg.highwire.dtl.DTLVardef@171fe3eorg.highwire.dtl.DTLVardef@eac445org.highwire.dtl.DTLVardef@fba613_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

A molecular mechanism by which amyloid-β induces transcriptional inactivation of CREB in Alzheimer's Disease

Synaptic dysfunction caused by soluble {beta}-Amyloid (A{beta}) is a hallmark of the early stage of Alzheimers disease (AD) and is tightly linked to cognitive decline. A{beta} induces by yet unknown mechanisms disruption of transcriptional activity of cAMP- responsive element-binding protein (CREB), a master regulator of cell survival and plasticity-related gene expression. Here, we report that A{beta} elicits cytonuclear trafficking of Jacob, a protein serves as a mobile signaling hub that docks a signalosome to CREB, which induces transcriptional inactivation and subsequent synapse impairment and eventually loss in AD. The small chemical compound Nitarsone selectively hinders assembly of this signalosome and thereby restores CREB transcriptional activity. Nitarsone prevents impairment of synaptic plasticity as well as cognitive decline in mouse models of AD. Collectively, the data suggest that targeting Jacob induced CREB shutoff is a therapeutic avenue against early synaptic dysfunction in AD.

neuroscience↗

bioRxiv2020

QTL mapping reveals genomic regions for yield based on incremental tolerance index to drought stress and related agronomic traits in canola

Drought stress especially at the reproductive stage is a major limiting factor that compromises the productivity and profitability of canola in many regions of the world. Improved genetics for drought tolerance would enable the identification and development of resilient varieties, resulting in increased canola production. The main objective of this study was to dissect the genetic basis of seed yield under water-limited conditions in canola. A doubled haploid population derived from a cross between two Australian parental lines, RP04 and Ag-Outback, was evaluated to identify the genetic variation in fractional normalised deviation vegetative index (NDVI), above ground shoot biomass accumulation, flowering time, and plasticity in seed yield under irrigated and rainfed field conditions in two consecutive years. An irrigation treatment was applied at the 50% flowering stage and an incremental drought tolerance index (DTI) was estimated for seed yield. By utilising a genetic linkage map based on 18,851 genome-wide DArTseq markers, we identified 25 genomic regions significantly associated with different traits (LOD [≥] 3), accounting for 5.5 to 22.3% of the genotypic variance. Three significant genomic regions on chromosome A06, A10 and C04 were associated with DTI for seed yield. Some of the QTL were localised in the close proximity of candidates genes involved in traits contributing to drought escape and drought avoidance mechanisms, including FLOWERING LOCUS T (FT) and FLOWERING LOCUS C (FLC). Trait-marker associations identified herein can be validated across diverse environments, and the sequence based markers may be used in a marker assisted selection breeding strategy to enhance drought tolerance in canola breeding germplasm.

plant biology↗

bioRxiv2019

An epigenetic LTR-retrotransposon insertion in the upstream region of BnSHP1.A9 controls quantitative pod shattering resistance in Brassica napus

Seed loss resulting from pod shattering is a major problem in oilseed rape (Brassica napus L.) production worldwide. However, the molecular mechanisms underlying pod shatter resistance are not well understood. Here we show that the pod shatter resistance at quantitative trait locus, qSRI.A9.1 is controlled by a SHATTERPROOF1 (SHP1) paralog in B. napus (BnSHP1.A9). Expression analysis by quantitative RT-PCR showed that BnSHP1.A9 was specifically expressed in flower buds, flowers and developing siliques in the oilseed rape line (R1) carrying the qSRI.A9.1 allele with negative effect, but not expressed in any tissue of the line (R2) carrying the positive effect qSRI.A9.1 allele. Transgenic plants constitutively expressing BnSHP1.A9 alleles from pod resistant and pod shattering parental lines showed that both alleles are responsible for pod shattering via promoting lignification of enb layer, which indicated allelic difference of BnSHP1.A9 gene per se is not the causal factor of the QTL. The upstream sequence of BnSHP1.A9 in the promotor region harboring highly methylated long terminal repeat retrotransposon insertion (LTR, 4803bp) in R2 repressed the expression of BnSHP.A9, and thus contributed to the positive effect on pod shatter resistance. Genetic and association analysis revealed that the copia LTR retrotransposon based marker BnSHP1.A9-R2 can be used for breeding for pod shatter resistant varieties and reducing the loss of seed yield in oilseed rape.

genetics↗

bioRxiv2019

CNN explains tuning properties of anterior, but not middle, face-processing areas in macaque IT

Recent computational studies have emphasized layer-wise quantitative similarity between convolutional neural networks (CNNs) and the primate visual ventral stream. However, whether such similarity holds for the face-selective areas, a subsystem of the higher visual cortex, is not clear. Here, we extensively investigate whether CNNs exhibit tuning properties as previously observed in different macaque face areas. While simulating four past experiments on a variety of CNN models, we sought for the model layer that quantitatively matches the multiple tuning properties of each face area. Our results show that higher model layers explain reasonably well the properties of anterior areas, while no layer simultaneously explains the properties of middle areas, consistently across the model variation. Thus, some similarity may exist between CNNs and the primate face-processing system in the near-goal representation, but much less clearly in the intermediate stages, thus giving motivation for a more comprehensive model for understanding the entire system.

neuroscience↗

bioRxiv2019

SIPA1L2 controls trafficking and signaling of TrkB-containing amphisomes at presynaptic terminals

Amphisomes are transient organelles that derive from fusion of autophagosomes with late endosomes. They rapidly transform into degradative autolysosomes, whereas non-degradative roles of the autophagic pathway have been barely described. Here we show that in neurons BDNF/TrkB receptor bearing Rab7 / Light chain 3 (LC3) - positive amphisomes signal at presynaptic boutons during retrograde trafficking to the soma. Local signaling and inward transport essentially require the Rap GTPase-activating (RapGAP) protein SIPA1L2, which directly binds to TrkB and Snapin to connect TrkB-containing amphisomes to dynein. Association with LC3 regulates the RapGAP activity of SIPA1L2 and thereby retrograde trafficking. Following induction of presynaptic plasticity amphisomes dissociate from dynein at boutons, and this enables local signaling and promotes transmitter release. Accordingly, sipa1l2 knockout mice show impaired BDNF-dependent presynaptic plasticity. Collectively, the data suggest that TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity.

neuroscience↗

bioRxiv2019

GWAS hints at pleiotropic roles for FLOWERING LOCUS T in flowering time and yield-related traits in canola

Transition to flowering at the right time is critical for local adaptation and to maximize seed yield in canola, which is an important oilseed crop. There is extensive variation among canola varieties in flowering time. However, our understanding of underlying genes and their role in canola productivity is still limited. We reveal natural variation in flowering time and response to photoperiod in a diverse GWAS panel (up to 368 accessions) of canola and identify associated SNPs across multiple experiments. Complementary QTL and eQTL mapping studies were also conducted in an Australian doubled haploid (DH) population for flowering time and other grain yield related traits. We show that several associations that were repeatedly detected across experiments map in the vicinity of FLOWERING LOCUS T (FT) paralogues and its known transcriptional regulators. QTL mapping study in a DH population detected consistent genomic regions close to FT paralogs. FT sequences vary between accessions and FT expression in field and controlled environment grown plants was correlated with flowering time. FT paralogs displayed association not only with flowering time, but also with plant emergence, shoot biomass and grain yield. Our findings suggest that FT paralogs not only modulate flowering time but also modulate yield-related productivity traits in canola. HighlightThe genetic association, eQTL and expression analyses suggest that FT paralogs have multifaceted roles in canola flowering time, plant development and productivity traits.

plant biology↗

bioRxiv2018

Sex Determination in the garden lizard, Calotes versicolor: Is Environment a Factor?

The Indian garden lizard, C. versicolor, is known to lack sex chromosomes (Singh, 1974, Ganesh et al 1997). A report from the tropical southern India (Inamdar et al., 2012), claims a TSD (FMFM) mechanism in this species in which the male/female ratio in embryos oscillates within a range of 3-4{degrees}C. The present study presents results of experiments done in 4 consecutive breeding seasons of C. versicolor belonging to the subtropical/temperate climate of northern region of India. Eggs were grown at different temperatures (at 24.5/28/31.5{degrees}C) or under seminatural conditions. Another set of eggs was exposed to fadrozol, an aromatase inhibitor (AI), or Lithium Chloride (inhibitor of GSK3 enzyme inducing Wnt4-dependent Beta-Catenin). Results confirm our earlier finding that in this subtropical population of C. versicolor, temperature does not regulate gonadal differentiation but AI-induces sex reversal to the male sex (Ganesh and Raman, 1995, Ganesh et al 1999). We also report lack of any effect of Sox9 inhibitor on sexual differentiation which may be due to inadequate quantity or mode of application. Importantly, we report the serendipitous observation that in each year almost all the embryos/hatchlings were of the same sex ( females in 2013, 15, 16 and males in 2014) regardless of the rearing condition and duration of incubation. Obviously, parthenogenesis is not the cause of it. In the absence of an obvious reason to explain this pattern, we surmise that in this north Indian population of C. versicolor, female is the default sex, and certain epigenetic regulators could modulate the sexual differentiation of the individual.

developmental biology↗