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Biology subjects

Aggarwal, H.

Publications and source records attributed to Aggarwal, H..

3 recordsLinked to original sources

"Editing the conserved IPA1-TB1 regulatory module reshapes plant architecture and enhances tillering in wheat

Plant architecture is a major determinant of yield potential in cereal crops, where tiller number directly influences spike production and grain yield. The transcriptional regulators Ideal Plant Architecture 1 (IPA1) and Teosinte Branched1 (TB1) constitute a conserved genetic module controlling axillary bud activity and branching in grasses; however, their functional contribution to wheat architecture remains largely unexplored. Here, we employed CRISPR/Cas9-mediated genome editing to investigate the roles of TaIPA1 and TaTB1 in regulating tillering in hexaploid wheat (Triticum aestivum L.). Comparative genomic analysis identified conserved IPA1 orthologs across the wheat A, B, and D sub-genomes, with strong conservation of the SQUAMOSA-binding protein domain. Sequencing analysis confirmed targeted mutations, including nucleotide substitutions and insertions that generated frameshift mutations and premature stop codons. Genome-edited lines exhibited enhanced tillering compared with wild-type plants. Several TaIPA1 mutant lines produced up to two-fold higher tiller numbers, while TaTB1 knockout lines showed earlier tiller initiation and [~]50% increased tillering. Notably, enhanced tillering was associated with increased grain weight without affecting spikelet number per spike. Together, these results demonstrate that the conserved TaIPA1-TaTB1 regulatory module plays a pivotal role in shaping wheat plant architecture. Targeted manipulation of this pathway using CRISPR/Cas9 provides a promising strategy for optimizing tillering and developing high-yielding wheat ideotypes.

molecular biology↗

Oral glucose feeding enhances adherence of quiescent lymphocytes to fibronectin via non-canonical insulin signalling.

Impaired glucose metabolism is associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Conversely, infusion of functional immune cells restores glucose metabolism. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent circulating lymphocytes are missing. Here we find that oral glucose load in healthy men and mice enhance adherence of circulating peripheral blood mononuclear cells (PBMCs) to fibronectin. This led to increased homing of post-load PBMCs to injured blood vessels. Cell culture based experiments on Jurkat-T cells and PBMCs demonstrated that insulin elicits these adhesive effects through a non-canonical signalling involving insulin growth factor-1 receptor (IGF-1R) and phospholipase C gamma-1 (PLC{gamma}-1) mediated activation of integrin {beta}1. Our findings point to the relevance of post-prandial insulin spikes in regulating homing of circulating T-cells to various organs for tissue repair and immunity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/464163v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@11edce6org.highwire.dtl.DTLVardef@1389835org.highwire.dtl.DTLVardef@90c96eorg.highwire.dtl.DTLVardef@1988a63_HPS_FORMAT_FIGEXP M_FIG Insulin mediates fibronectin adherence of lymphocytes through non-canonical signalling. Insulin mediates auto-phosphorylation of IGF-1 receptor at Tyr1135 leading to activation of PLC-{gamma}1 through Tyr783 phosphorylation, which in turn leads to the activation of integrin 1 through intracellular calcium to ultimately enhance adhesion of quiescent lymphocytes to fibronectin. C_FIG

physiology↗

An HIV-1 broadly neutralizing antibody from a clade C infected pediatric elite neutralizer potently neutralizes the contemporaneous and autologous evolving viruses

Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite-neutralizers are potential candidates for isolation of HIV-1 bNAbs and coexistence of bNAbs such as BG18 with neutralization susceptible autologous viruses in an HIV-1 infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1 infected children than adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults. Therefore, we evaluated the specificity of plasma neutralizing antibodies of an antiretroviral naive HIV-1 clade C chronically infected pediatric elite neutralizer AIIMS_330. The plasma antibodies showed broad and potent HIV-1 neutralizing activity with >87% (29/33) breadth, median inhibitory dilution (ID50) value of 1246 and presence of N160 and N332-supersite dependent HIV-1 bNAbs. The sorting of BG505.SOSIP.664.C2 T332N gp140 HIV-1 antigen-specific single B cells of AIIMS_330 resulted in the isolation of an HIV-1 N332-supersite dependent bNAb AIIMS-P01. The AIIMS-P01 neutralized 67% of HIV-1 cross-clade viruses; exhibited substantial indels despite limited somatic hypermutations; interacted with native-like HIV-1 trimer as observed in negative stain electron microscopy and demonstrated high binding affinity. In addition, AIIMS-P01 potently neutralized the coexisting and evolving autologous viruses suggesting the coexistence of vulnerable autologous viruses and HIV-1 bNAbs in AIIMS_330 pediatric elite neutralizer. Further studies on such pediatric elite-neutralizers and isolation of novel HIV-1 pediatric bNAbs may provide newer insights to guide vaccine design.\n\nImportanceMore than 50% of the HIV-1 infections globally are caused by clade C viruses. Till date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are underway to design immunogens that can elicit correlates of protection upon vaccination. Here we report the isolation and characterization of an HIV-1 N332-supersite dependent bNAb AIIMS-P01 from a clade C chronically infected pediatric elite neutralizer. The N332-supersite is an important epitope and is one of the current HIV-1 vaccine targets. AIIMS-P01 potently neutralized the contemporaneous and autologous evolving viruses and exhibits substantial indels despite low somatic hypermutations. Taken together with the information on infant bNAbs, further isolation of bNAbs contributing to the plasma breadth in HIV-1 infected children may help to better understand their development and characteristics, which in turn may guide vaccine design.

immunology↗