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Biology subjects

Mane, V.

Publications and source records attributed to Mane, V..

4 recordsLinked to original sources

Interlayer Communication Integrates Genetic and Mechanical Signals for Robust Leaf Morphogenesis

Leaf development requires coordinated growth across distinct tissue layers, integrating genetic regulation with mechanical coupling to achieve proper organ shaping. However, the mechanisms coordinating differentiation and growth across layers to ensure coherent leaf morphogenesis remain poorly understood. Therefore, we investigated the role of TCP4 as a potential central regulator of interlayer communication coupling genetic and mechanical signals during Arabidopsis leaf development. Three-dimensional analyses revealed pronounced asymmetry in the expression of TCP4 and its negative regulator, MIR319C, across developing primordia, establishing spatially patterned differentiation cues. Tissue-specific perturbations demonstrated that TCP4 activity in either epidermis or subepidermis modulates cell proliferation and expansion across layers through both protein mobility and mobility-independent signalling mechanisms. Strong epidermal TCP4 induction arrested leaf development by prematurely suppressing proliferation and preventing symmetry breaking, thereby locking primordia in cylindrical states. Live imaging revealed fundamental reprogramming of growth anisotropy, with TCP4 driving cortical microtubule alignment, increasing cell wall stiffness, and establishing layer-specific pectin patterns. Together, these findings establish TCP4 as an integrator of genetic and mechanical signals across leaf tissue layers, coupling transcriptional programmes to cytoskeletal organisation, cell wall remodelling, and cross-layer mechanical feedback.

plant biology↗

CUP-SHAPED COTYLEDON2 activates MIR319C transcription and promotes cell proliferation in Arabidopsis leaf primordia

The microRNA miR319 regulates leaf size in diverse plant species by reducing the level of the target transcripts that encode JAW-TCPs, the transcription factors (TF) that restrict leaf size by committing the proliferating pavement cells to differentiation. MIR319C, one of the three miR319-producing genes in Arabidopsis, is expressed throughout the incipient leaf primordia, and its expression domain gets restricted to the base at later stages, partly due to its transcriptional repression by JAW-TCPs. However, the factors that activate and maintain MIR319C expression in leaf primordia are yet unknown. Here, we identify the CUP-SHAPED COTYLEDON2 (CUC2) TF as a direct activator of MIR319C transcription. Using a yeast one-hybrid (Y1H) screen, we identified several NAC domain TFs as potential regulators of MIR319C. Subsequent ex vivo binding and transactivation assays suggested that CUC2 binds to a distal promoter region of the MIR319C locus and activates its transcription. Mutants with compromised CUC2 and MIR319C activities resulted in smaller leaves with fewer cells. Detailed morphometric analysis of higher order CUC2 and MIR319 loss-of-function mutants highlighted the crucial role of the CUC2-MIR319 module in maintaining the duration of cell proliferation in leaf primordia. Additionally, the phenotype of mutants with altered CUC2 and MIR319/JAW-TCP activities demonstrated that CUC2 enhances leaf size through the MIR319C-JAW-TCP pathway. Overall, our findings uncovered a novel role for CUC2 in sustaining cell division by activating MIR319C transcription in the leaf primordia.

plant biology↗

Mass lysis of bacterial predators drives the enrichment of antibiotic resistance in soil microbial communities

While studies on anthropogenic activities and antibiotic resistance are numerous, the impact of microbial interactions on resistance in complex communities remains uncertain. Here we demonstrate a correlation between the presence of Myxococcus xanthus in natural soil communities and the abundance of antibiotic-resistant bacteria. Further, introducing M. xanthus isolates also enriches antibiotic resistance. This is due to the mass lysis of M. xanthus cells, which results in a toxic environment that fosters the proliferation of pre-existing resistant bacteria rather than de novo resistance evolution. Metagenomic analysis revealed that this enrichment is not limited to the tested antibiotics in culture-based methods, indicating its broader relevance. Crucially, these findings go beyond laboratory settings, showing M. xanthus introduction enriches resistant isolates in natural soil communities. Finally, we demonstrate that the mass lysis of M. xanthus cells during starvation-induced development--key aspect of the lifecycle of M. xanthus--also results in the enrichment of antibiotic resistance in soil communities. Together, we demonstrate how life-history traits in bacterial predators, like M. xanthus, significantly impact antibiotic resistomes in nature. This study also highlights the complex dynamics at play in the evolution and maintenance of antibiotic resistance, emphasizing the role of interspecies interactions in shaping antibiotic resistance profiles.

evolutionary biology↗

In Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA product, Against SARS-CoV-2 in a Murine Model of COVID-19

Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosal compartments including the respiratory tract, with the secretory form of IgA (sIgA) being dominant and uniquely stable in these environments. sIgA is naturally found in human milk, which could be considered a global resource for this biologic, justifying the development of human milk sIgA as a dedicated airway therapeutic for respiratory infections such as SARS-CoV-2. In the present study, methods were therefore developed to efficiently extract human milk sIgA from donors who were either immunologically naive to SARS-CoV-2 (pooled as a control IgA) or had recovered from a PCR-confirmed SARS-CoV-2 infection that elicited high-titer anti-SARS-CoV-2 Spike sIgA Abs in their milk (pooled together to make LCTG-002). Mass spectrometry determined that proteins with a relative abundance of 1.0% or greater were all associated with sIgA. None of the proteins exhibited statistically significant differences between batches. Western blot demonstrated all batches consisted predominantly of sIgA. Compared to control IgA, LCTG-002 demonstrated significantly higher binding to Spike, and was also capable of blocking the Spike - ACE2 interaction in vitro with 6.3x greater potency compared to control IgA (58% inhibition at [~]240ug/mL). LCTG-002 was then tested in vivo for its capacity to reduce viral burden in the lungs of K18+hACE2 transgenic mice inoculated with SARS-CoV-2. LCTG-002 was demonstrated to significantly reduce SARS-CoV-2 titers in the lungs compared to control IgA when administered at either 250ug/day or 1 mg/day, as measured by TCID50, plaque forming units (PFU), and qRT-PCR, with a maximum reduction of 4.9 logs. This innovative study demonstrates that LCTG-002 is highly pure, efficacious, and well tolerated in vivo, supporting further development of milk-derived, polyclonal sIgA therapeutics against SARS-CoV-2 and other mucosal infections.

immunology↗