Biology subjects

Bhalla, N.

Publications and source records attributed to Bhalla, N..

3 recordsLinked to original sources

bioRxiv2018

PCH-2TRIP13 regulates spindle checkpoint strength

Spindle checkpoint strength is dictated by three criteria: the number of unattached kinetochores, cell volume and cell fate. We show that the conserved AAA-ATPase, PCH-2/TRIP13, which remodels the checkpoint effector Mad2 from an active conformation to an inactive one, controls checkpoint strength in C. elegans. When we manipulate embryos to decrease cell volume, PCH-2 is no longer required for the spindle checkpoint or recruitment of Mad2 at unattached kinetochores. This role in checkpoint strength is not limited to large cells: the stronger checkpoint in germline precursor cells also depends on PCH-2. PCH-2 is enriched in germline precursor cells and this enrichment relies on conserved factors that induce asymmetry in the early embryo. Finally, the stronger checkpoint in germline precursor cells is regulated by CMT-1, the ortholog of p31comet, which is required for both PCH-2s localization to unattached kinetochores and its enrichment in germline precursor cells. Thus, PCH-2, likely by regulating the availability of inactive Mad2 at and near unattached kinetochores, governs checkpoint strength. This role may be specifically relevant in scenarios where maintaining genomic stability is particularly challenging, such as in oocytes and early embryos enlarged for developmental competence and germline cells that maintain immortality.

cell biology↗

bioRxiv2018

The action of a cosmetic hair treatment on follicle function

OBJECTIVEHuman hair changes with age: fibre diameter and density decrease, hair growth slows and shedding increases. This series of controlled studies examined the effect on hair growth parameters of a new leave-on hair treatment (LOT) formulated with DynagenTM (containing hydrolysed yeast protein) and zinc salts.\n\nMETHODSHair growth data were collected from healthy women aged 18-65 years. The LOTs effect on hair growth was measured in a randomized double-blind study and in hair samples; its effect on follicle-cell proliferation was assessed by quantifying Ki67 expression in scalp biopsies. The LOTs effect on plucking force was determined in an ex vivo model. Dynagens effect on the expression of the tight-junction marker claudin-1 was analysed in cultured follicles. The effect on protease activity of zinc salts used in the LOT was examined in vitro.\n\nRESULTSHair growth rate decreased with increasing subject age. The LOT significantly increased hair growth rate, fibre diameter, bundle cross-sectional area, Ki67 expression and the plucking force required to remove hair. Dynagen significantly increased claudin-1 expression in cultured follicles. Protease activity was reduced by zinc salts.\n\nCONCLUSIONThe Dynagen-based LOT increases hair-fibre diameter, strengthens the follicular root structure and increases hair growth rate.

physiology↗

bioRxiv2018

Shugoshin is essential for meiotic prophase checkpoints in C. elegans

The conserved factor Shugoshin is dispensable in C. elegans for the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of the meiotic chromosomal protein, HTP-3. Null sgo-1 mutants exhibit additional phenotypes similar to that of a partial loss of function allele of HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei, when HTP-3 is present but not yet loaded onto chromosome axes, suggesting an early role in regulating meiotic chromosome metabolism. We propose that SGO-1 acts during pre-meiotic replication to ensure fully functional meiotic chromosome architecture, rendering these chromosomes competent for checkpoint activity and normal progression of meiotic recombination. Given that most research on Shugoshin has been focused on its regulation of sister chromatid cohesion in meiosis, this novel role may be conserved but previously uncharacterized in other organisms. Further, our findings expand the repertoire of Shugoshins functions beyond coordinating regulatory activities at the centromere.

cell biology↗