Ssp1 CaMKK: A Sensor of Actin Polarization That Controls Mitotic Commitment through Srk1 in Schizosaccharomyces pombe

Background

Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is required for diverse cellular functions. Mammalian CaMKK activates CaMKs and also the evolutionarily-conserved AMP-activated protein kinase (AMPK). The fission yeast Schizosaccharomyces pombe CaMKK, Ssp1, is required for tolerance to limited glucose through the AMPK, Ssp2, and for the integration of cell growth and division through the SAD kinase Cdr2.

Results

Here we report that Ssp1 controls the G2/M transition by regulating the activity of the CaMK Srk1. We show that inhibition of Cdc25 by Srk1 is regulated by Ssp1; and also that restoring growth polarity and actin localization of ssp1-deleted cells by removing the actin-monomer-binding protein, twinfilin, is sufficient to suppress the ssp1 phenotype.

Conclusions

These findings demonstrate that entry into mitosis is mediated by a network of proteins, including the Ssp1 and Srk1 kinases. Ssp1 connects the network of components that ensures proper polarity and cell size with the network of proteins that regulates Cdk1-cyclin B activity, in which Srk1 plays an inhibitory role.     

Indene-based frameworks targeting the 5-HT6 serotonin receptor: Ring constraint in indenylsulfonamides using cyclic amines and structurally abbreviated counterparts

Further studies in quest of 5-HT₆ serotonin receptor ligands led to the design and synthesis of a few selected examples of N-(inden-5-yl)sulfonamides with a ring-constrained aminoethyl side chain at the indene 3-position, some of which exhibited a high binding affinity, such as the pyrrolidine analogue 28 (K_i = 3 nM). Moreover, the structurally abbreviated N-(inden-5-yl)sulfonamides showed K_i values ?43 nM, which indicates that neither the N,N-aminoethyl nor the conformationally restricted aminoethyl side arm at the indene 3-position are required for binding. Selected compounds were then tested in a functional cAMP stimulation assay and found to act as 5-HT₆ antagonists, although with moderate potency at the micromolar level.     

Serum insulin-like growth factor levels do not predict functional recovery after hospitalization in nonagenarian patients

AIM: To analyze the insulin-like growth factor 1 (IGF-1) serum levels in nonagenarian patients and to investigate the predictive capacity of this measure to assess the functional recovery of this population following hospitalization. METHODS: We performed a prospective study in 60 consecutive nonagenarian patients admitted for medical or surgical diseases. We assessed IGF-1 serum levels and nutritional status. The functional status was assessed using the Barthel index. Thirty-four patients were reinvestigated 3 months after discharge from hospital. RESULTS: The mean levels of IGF-1 were lower in nonagenarians than in younger patients. No relationship was found between IGF-1 levels and nutritional status. The decline in Barthel index values 3 months after discharge from hospital did not correlate with serum levels of IGF-1 on admission. CONCLUSION: IGF-1 serum levels in nonagenarian patients do not predict functional recovery after hospitalization.     

Extremely reduced dispersal and gene flow in an island bird

The Réunion grey white-eye, Zosterops borbonicus, a passerine bird endemic to Réunion Island in the Mascarene archipelago, represents an extreme case of microgeographical plumage colour variation in birds, with four distinct colour forms occupying different parts of this small island (2512 km²). To understand whether such population differentiation may reflect low levels of dispersal and gene flow at a very small spatial scale, we examined population structure and gene flow by analysing variation at 11 microsatellite loci among four geographically close localities (<26 km apart) sampled within the distribution range of one of the colour forms, the brown-headed brown form. Our results revealed levels of genetic differentiation that are exceptionally high for birds at such a small spatial scale. This strong population structure appears to reflect low levels of historical and contemporary gene flow among populations, unless very close geographically (<10 km). Thus, we suggest that the Réunion grey white-eye shows an extremely reduced propensity to disperse, which is likely to be related to behavioural processes.