Cell polarization enables zygotes to acquire spatial asymmetry, which in turn patterns cellular and tissue axes during development. Local modification in the actomyosin cytoskeleton mediates spatial segregation of partitioning-defective (PAR) proteins at the cortex, but how mechanical changes in the cytoskeleton are transmitted to PAR proteins remains elusive. Here we uncover a role of actomyosin contractility in the remodelling of PAR proteins through cortical clustering. During embryonic polarization in Caenorhabditis elegans, actomyosin contractility and the resultant cortical tension stimulate clustering of PAR-3 at the cortex. Clustering of atypical protein kinase C (aPKC) is supported by PAR-3 clusters and is antagonized by activation of CDC-42. Cortical clustering is associated with retardation of PAR protein exchange at the cortex and with effective entrainment of advective cortical flows. Our findings delineate how cytoskeleton contractility couples the cortical clustering and long-range displacement of PAR proteins during polarization. The principles described here would apply to other pattern formation processes that rely on local modification of cortical actomyosin and PAR proteins.

Pontes et al. show that plasma membrane mechanics exerts an upstream control during cell motility. Variations in plasma membrane tension orchestrate the behavior of the cell leading edge, with increase–decrease cycles in tension promoting adhesion row positioning.

Concerns have been raised about whether preclinical models sufficiently mimic molecular disease processes observed in nonalcoholic steatohepatitis (NASH) patients, bringing into question their translational value in studies of therapeutic interventions in the process of NASH/fibrosis. We investigated the representation of molecular disease patterns characteristic for human NASH in high‐fat diet (HFD)‐fed Ldlr‐/‐.Leiden mice and studied the effects of obeticholic acid (OCA) on these disease profiles. Multiplatform serum metabolomic profiles and genome‐wide liver transcriptome from HFD‐fed Ldlr‐/‐.Leiden mice were compared with those of NASH patients. Mice were profiled at the stage of mild (24 weeks HFD) and severe (34 weeks HFD) fibrosis, and after OCA intervention (24‐34 weeks; 10 mg/kg/day). Effects of OCA were analyzed histologically, biochemically, by immunohistochemistry, using deuterated water technology (de novo collagen formation), and by its effect on the human‐based transcriptomics and metabolomics signatures. The transcriptomics and metabolomics profile of Ldlr‐/‐.Leiden mice largely reflected the molecular signature of NASH patients. OCA modulated the expression of these molecular profiles and quenched specific proinflammatory‐profibrotic pathways. OCA attenuated specific facets of cellular inflammation in liver (F4/80‐positive cells) and reduced crown‐like structures in adipose tissue. OCA reduced de novo collagen formation and attenuated further progression of liver fibrosis, but did not reduce fibrosis below the level before intervention. Conclusion: HFD‐fed Ldlr‐/‐.Leiden mice recapitulate molecular transcriptomic and metabolomic profiles of NASH patients, and these signatures are modulated by OCA. Intervention with OCA in developing fibrosis reduces collagen deposition and de novo synthesis but does not resolve already manifest fibrosis in the period studied. These data show that human molecular signatures can be used to evaluate the translational character of preclinical models for NASH.

Follicular lymphomas with plasmacytic differentiation were described more than two decades ago. However, the possibility that some of these reported cases are marginal zone lymphomas or composite lymphomas must be considered. In addition, it is also uncertain whether follicular lymphomas with plasmacytic differentiation have any unique cytogenetic or other features. Therefore, fluorescence immunophenotypic and interphase cytogenetic analysis of 14 well-characterized follicular lymphomas with plasmacytic differentiation was performed using a CD138 antibody to identify the plasma cells and with BCL2, BCL6, IGH@ and MALT1 breakapart probes and a chromosome 12 centromeric probe. CD10 was expressed in 12/14 cases, BCL6 in 12/12 cases and BCL2 in 12/14 cases. At least one cytogenetic abnormality was identified in 12/14 cases. The same abnormality was present in both the plasmacytic (CD138 þ ) and non-plasmacytic (CD138À) component in all 10 evaluable cases. BCL2 rearrangements were present in seven cases (5 IGH@ rearranged, 1 IGH@-not rearranged, 1 IGH@-not evaluable), BCL6 rearrangement in two (1 also with BCL2/IGH@ rearrangement), þ 12 in 1, þ MALT1 without þ 18 in 1, IGH@ rearrangement without other abnormalities in 1 and IGH@ rearranged or partially deleted in 1 case. No cases showed þ BCL6 (3q27) or a MALT1 rearrangement. All six cases with an isolated BCL2 rearrangement had predominantly interfollicular plasmacytic cells whereas, 6/7 cases without the translocation had concentrations of intrafollicular or perifollicular plasmacytic cells (Po0.005), as did the case with BCL2 and BCL6 translocations. These results support the existence of bona fide follicular lymphomas with plasmacytic differentiation and support the clonal relationship of the neoplastic lymphoid and plasma cells in at least most of these cases. The differential distribution of the plasma cells, specifically in relation to the presence or absence of an isolated BCL2 rearrangement suggests that the latter cases may be distinctive, sharing some features with marginal zone lymphomas.