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Objectives: The action of stress hormones, mainly glucocorticoids, starts and coordinates the systemic response to stressful events. The HPA axis activity is predicated on information processing and modulation by upstream centres, such as the hippocampus where adult‐born neurons (hABN) have been reported to be an important component in the processing and integration of new information. Still, it remains unclear whether and how hABN regulates HPA axis activity and CORT production, particularly when considering sex differences. Materials and Methods: Using both sexes of a transgenic rat model of cytogenesis ablation (GFAP‐Tk rat model), we examined the endocrinological and behavioural effects of disrupting the generation of new astrocytes and neurons within the hippocampal dentate gyrus (DG). Results: Our results show that GFAP‐Tk male rats present a heightened acute stress response. In contrast, GFAP‐Tk female rats have increased corticosterone secretion at nadir, a heightened, yet delayed, response to an acute stress stimulus, accompanied by neuronal hypertrophy in the basal lateral amygdala and increased expression of the glucocorticoid receptors in the ventral DG. Conclusions: Our results reveal that hABN regulation of the HPA axis response is sex‐differentiated. [ABSTRACT FROM AUTHOR]

Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy‐prone mouse models uncovered an unanticipated link between CIN and aging. Using young to old‐aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we investigated mitotic mechanisms that contribute to age‐associated CIN. We found that elderly cells have an increased number of stable kinetochore–microtubule (k‐MT) attachments and decreased efficiency in the correction of improper k‐MT interactions. Chromosome mis‐segregation rates in old‐aged cells decreased upon both genetic and small‐molecule enhancement of MT‐depolymerizing kinesin‐13 activity. Notably, restored chromosome segregation accuracy inhibited the phenotypes of cellular senescence. Therefore, we provide mechanistic insight into age‐associated CIN and disclose a strategy for the use of a small‐molecule to inhibit age‐associated CIN and to delay the cellular hallmarks of aging. Synopsis: Disturbed kinetochore‐microtubule (k‐MT) dynamics is a major driver of chromosomal instability (CIN), which increases with aging and contributes to senescence. The number of k‐MT attachments is increased in elderly cells.Aged cells display defective MT‐depolymerizing kinesin‐13 activity and k‐MT error correction.Chromosome segregation fidelity can be restored by genetic and small molecule enhancement of kinesin‐13 activity in old cells.The destabilization of k‐MT attachments rescues the cellular aging phenotypes associated with CIN. [ABSTRACT FROM AUTHOR]

CD44 isoforms are often upregulated in gastric cancer and have been associated with increased metastatic potential and poor survival. To evaluate the functional impact of O‐glycan truncation on CD44 we have analysed glyco‐engineered cancer cell models displaying shortened O‐glycans. Here, we demonstrate that induction of aberrant O‐glycan termination through various molecular mechanisms affects CD44 molecular features. We show that CD44 is a major carrier of truncated O‐glycans and that this truncation is accompanied by an increased hyaluronan binding capacity and affects extracellular shedding. In addition, short O‐glycans promoted the colocalization of CD44v6 with the receptor tyrosine kinase RON and concomitantly increased activation. Our in vitro findings were validated in gastric cancer clinical samples. [ABSTRACT FROM AUTHOR]

ABSTRACT Amyloid fibers, implicated in a wide range of diseases, are formed when proteins misfold and stick together in long rope-like structures. As a natural mechanism, osmolytes can be used to modulate protein aggregation pathways with no interference with other cellular functions. The osmolyte sucrose delays fibrillation of the ribosomal protein S6 leading to softer and less shaped-defined fibrils. The molecular mechanism used by sucrose to delay S6 fibrillation was studied based on the two-state unfolding kinetics of the secondary and tertiary structures. It was concluded that the delay in S6 fibrillation results from stabilization and compaction of the slightly expanded tertiary native structure formed under fibrillation conditions. Interestingly, this compaction extends to almost all S6 tertiary structure but hardly affects its secondary structure. The part of the S6 tertiary structure that suffered more compaction by sucrose is known to be the first part to unfold, indicating that the native S6 has entered the unfolding pathway under fibrillation conditions. Proteins 2015; 83:2039-2051. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]