TraPS-VarI: Identifying genetic variants altering phosphotyrosine based signalling motifs

Patient stratification and individualized therapeutic strategies rely on the established knowledge of genotype-specific molecular and cellular alterations of biological and therapeutic significance. Whilst almost all approved drugs have been developed based on the Reference Sequence protein database (RefSeq), the latest genome sequencing studies establish the substantial prevalence of non-synonymous genetic mutations in the general population, including stop-insertion and frame shift mutations within the coding regions of membrane proteins. While the availability of individual genotypes are becoming increasingly common, the biological and clinical interpretations of mutations among individual genomes is largely lagging behind. Lately, transmembrane proteins of haematopoietic (myeloid and lymphoid) derived immune cells have attracted much attention as important targets for cancer immunotherapies. As such, the signalling properties of haematological transmembrane receptors rely on the membrane-proximal phosphotyrosine based sequence motifs (TBSMs) such as ITAM (immunoreceptor tyrosine-based activation motif), ITIM (immunoreceptor tyrosine-based inhibition motif) and signal transducer and activator of transcription 3 (STAT3)-recruiting YxxQ motifs. However, mutations that alter the coding regions of transmembrane proteins, resulting in either insertion or deletion of crucial signal modulating TBSMs, remains unknown. To conveniently identify individual cell line-specific or patient-specific membrane protein altering mutations, we present the Transmembrane Protein Sequence Variant Identifier (TraPS-VarI). TraPS-VarI is an annotation tool for accurate mapping of the effect of an individual's mutation in the transmembrane protein sequence, and to identify the prevalence of TBSMs. TraPS-VarI is a biologist and clinician-friendly algorithm with a web interface and an associated database browser (https://www.traps-vari.org/)

(2E,4E)-Ethyl 5-(phenyl­sulfon­yl)penta-2,4-dienoate

In the title compound, C13H14O4S, both C=C double bonds adopt an E conformation. In the crystal, mol­ecules are linked into centrosymmetric R 2 2(14) dimers via pairs of C—H⋯O hydrogen bonds

Low cost high throughput image based root phenotyping pipeline for evaluation of sugarcane root system architecture under drought stress

Root System Architecture (RSA) plays an important role in the agronomic performance of a crop. Incorporation of these root traits in breeding program is hampered by the complexity in accessing the roots and its phenotyping. Lack of high throughput root phenotyping platforms for sugarcane is one of the major constraints in sugarcane root studies. In the present study an attempt was made to develop high throughput sugarcane root phenotyping pipeline comprising of a low cost plant cultivation platform and customized root image acquisition platform and image analyses using already available automated software. PVC tube system of specified dimension were used for plant growth and customized optical correction tank were used for imaging RSA. The acquired root images were fed into automated software GIAroots and about twenty quantitative root phenotype data were extracted and analysed. The working of the whole pipeline from plant growth to image analyses is demonstrated through comparative root phenotyping under drought using five genotypes of sugarcane wild relative Erianthus arundinaceus and three commercial sugarcane varieties.The relationships between the different root variables and genotypes in PCA biplots indicated high correlation among the different root traits. The study shows the low cost high throughput image based root phenotyping pipeline can be used to extract quantifiable root traits and analysed within a short span of time

Ssr-based molecular profiling of selected donors of wide compatibility, elongated uppermost internode, stigma exsertion and submergence tolerance traits and parental lines of commercial rice (o. Sativa l.) Hybrids

Molecular breeding plays an important role in sustainable agriculture development. Hybrid rice technology aims to increase the yield potential of rice beyond the level of inbred high-yielding varieties (HYVs) by exploiting the phenomenon of hybrid vigour or heterosis. Improvement of hybrid rice parental line is necessary to meet the food security problem. Parental polymorphism was carried with 215 SSR markers between five recurrents and ten donors. During the foreground selection, both reported markers (S5-Indel and BF-S5) were validated for wide compatibility, 2 out of 14 (ART5 and SC3) validates for submergence tolerance, one out of two (RM5) validate for stigma exsertion, whereas 2 of 3 markers (RM5970, RM3476) validated for elongated uppermost internode traits between recurrents and donors. For background selection, maximum polymorphic markers (112) between IR58025eB i.e improved maintainer line with elongated uppermost internode and Oryza meridionalis and minimum polymorphic markers (42) between IR79156B and IR91-1591-3 were found. Marker-assisted backcrossing accelerate, the transfer of gene of interest in desirable genetic background. Genotypes IR58025B and IR58025eB emerged as genetically most similar with a value of 97%. The genotypes IR64 Sub1 and Oryza meridionalis were found most divergent showing 33% genetic similarity. Dissimilarity coefficient of the generated information obtained on genetic relatedness would be supportive in further rice breeding program

Genetic variability in trait-specific rice germplasm groups based on coefficient of parentage, SSR markers and fertility restoration

To maximize heterosis, it is important to understand the genetic diversity of germplasm and associate useful phenotypic traits such as fertility restoration for hybrid rice breeding. The objectives of the present study were to characterize genetic diversity within a set of rice germplasm groups using coefficient of parentage (COP) values and 58 simple sequence repeat (SSR) markers for 124 genotypes having different attributes such as resistance/tolerance to various biotic and abiotic stresses. These lines were also used for identifying prospective restorers and maintainers for wild abortive-cytoplasmic male sterile (CMS) line. The mean COP value for all the lines was 0.11, indicating that the genotypes do not share common ancestry. The SSR analysis generated a total of 268 alleles with an average of 4.62 alleles per locus. The mean polymorphism information content value was 0.53, indicating that the markers selected were highly polymorphic. Grouping based on COP analysis revealed three major clusters pertaining to the indica, tropical japonica and japonica lines. A similar grouping pattern with some variation was also observed for the SSR markers. Fertility restoration phenotype based on the test cross of the 124 genotypes with a CMS line helped identify 23 maintainers, 58 restorers and 43 genotypes as either partial maintainers or partial restorers. This study demonstrates that COP analysis along with molecular marker analysis might encourage better organization of germplasm diversity and its use in hybrid rice breeding. Potential restorers identified in the study can be used for breeding high-yielding stress-tolerant medium-duration rice hybrids, while maintainers would prove useful for developing new rice CMS lines

Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T cells regulates autoimmunity of the central nervous system

Nicotinic acid adenine dinucleotide phosphate represents a newly identified second messenger in T cells involved in antigen receptor-mediated calcium signalling. Its function in vivo is, however, unknown due to the lack of biocompatible inhibitors. Using a recently developed inhibitor, we explored the role of nicotinic acid adenine dinucleotide phosphate in autoreactive effector T cells during experimental autoimmune encephalomyelitis, the animal model for multiple sclerosis. We provide in vitro and in vivo evidence that calcium signalling controlled by nicotinic acid adenine dinucleotide phosphate is relevant for the pathogenic potential of autoimmune effector T cells. Live two photon imaging and molecular analyses revealed that nicotinic acid adenine dinucleotide phosphate signalling regulates T cell motility and re-activation upon arrival in the nervous tissues. Treatment with the nicotinic acid adenine dinucleotide phosphate inhibitor significantly reduced both the number of stable arrests of effector T cells and their invasive capacity. The levels of pro-inflammatory cytokines interferon-gamma and interleukin-17 were strongly diminished. Consecutively, the clinical symptoms of experimental autoimmune encephalomyelitis were ameliorated. In vitro, antigen-triggered T cell proliferation and cytokine production were evenly suppressed. These inhibitory effects were reversible: after wash-out of the nicotinic acid adenine dinucleotide phosphate antagonist, the effector T cells fully regained their functions. The nicotinic acid derivative BZ194 induced this transient state of non-responsiveness specifically in post-activated effector T cells. Naïve and long-lived memory T cells, which express lower levels of the putative nicotinic acid adenine dinucleotide phosphate receptor, type 1 ryanodine receptor, were not targeted. T cell priming and recall responses in vivo were not reduced. These data indicate that the nicotinic acid adenine dinucleotide phosphate/calcium signalling pathway is essential for the recruitment and the activation of autoaggressive effector T cells within their target organ. Interference with this signalling pathway suppresses the formation of autoimmune inflammatory lesions and thus might qualify as a novel strategy for the treatment of T cell mediated autoimmune diseases

Removal of chromium from aqueous solutions using Derris indica wood based activated carbon. Adsorption batch studies

Adsorption efficiency in removal of chromium from waste water has been studied using Derris indica based activated carbon by conducting batch adsorption tests. Adsorption kinetics of chromium removal by Derris indica was examined by varying factors such as pH and concentration of synthetic solution and dosage of activated carbon. It has been found that the Derris indica based activated carbon is able to remove 80 mg/dm3 of chromium from aqueous solution by dosage of 0.8 g/150 cm3 with optimum contact time of 15 min. The isotherm data confirms with both Langmuir and Freundlich isotherm forms

Membrane-proximal binding of STAT3 revealed by cancer-associated receptor variants

In cancer biology, somatic mutations in the extracellular (ligand binding) and cytosolic (functional/catalytic) domains are pursued with great interest. However, in our recent publication we report that germline mutations in the membrane-proximal region of type I receptors are able to modulate the amplitude of signal transducer and activator of transcription 3 (STAT3) signaling in cells. This unexpected finding has implications for the prognosis of heritable cancer