Lundqvistbisgaard0849

78) and female welfare support workers (rate ratio 1.49, 95% CI 1.20 to 1.86) have higher suicide rate ratios compared with the reference group (excluding occupations from the comparison groups).

The age-standardised suicide rates of male welfare support workers are comparable to occupations which have been identified as high-risk occupations for suicide. Both female and male welfare support workers are at elevated risk of suicide compared with other occupations. Further research is required to understand the drivers of the elevated risk in this group.

The age-standardised suicide rates of male welfare support workers are comparable to occupations which have been identified as high-risk occupations for suicide. Both female and male welfare support workers are at elevated risk of suicide compared with other occupations. Further research is required to understand the drivers of the elevated risk in this group.To study the mechanisms controlling front-rear polarity in migrating cells, we used zebrafish primordial germ cells (PGCs) as an in vivo model. We find that polarity of bleb-driven migrating cells can be initiated at the cell front, as manifested by actin accumulation at the future leading edge and myosin-dependent retrograde actin flow toward the other side of the cell. In such cases, the definition of the cell front, from which bleb-inhibiting proteins such as Ezrin are depleted, precedes the establishment of the cell rear, where those proteins accumulate. Conversely, following cell division, the accumulation of Ezrin at the cleavage plane is the first sign for cell polarity and this aspect of the cell becomes the cell back. Together, the antagonistic interactions between the cell front and back lead to a robust polarization of the cell. Furthermore, we show that chemokine signaling can bias the establishment of the front-rear axis of the cell, thereby guiding the migrating cells toward sites of higher levels of the attractant. We compare these results to a theoretical model according to which a critical value of actin treadmilling flow can initiate a positive feedback loop that leads to the generation of the front-rear axis and to stable cell polarization. Together, our in vivo findings and the mathematical model, provide an explanation for the observed nonoriented migration of primordial germ cells in the absence of the guidance cue, as well as for the directed migration toward the region where the gonad develops.P27, a cell cycle inhibitor, is also able to drive repression of Sox2 This interaction plays a crucial role during development of p27 -/- pituitary tumors because loss of one copy of Sox2 impairs tumorigenesis [H. Li et al., Cell Stem Cell 11, 845-852 (2012)]. However, SOX2 is expressed in both endocrine and stem cells (SCs), and its contribution to tumorigenesis in either cell type is unknown. We have thus explored the cellular origin and mechanisms underlying endocrine tumorigenesis in p27 -/- pituitaries. We found that pituitary hyperplasia is associated with reduced cellular differentiation, in parallel with increased levels of SOX2 in stem and endocrine cells. Using conditional loss-of-function and lineage tracing approaches, we show that SOX2 is required cell autonomously in p27 -/- endocrine cells for these to give rise to tumors, and in SCs for promotion of tumorigenesis. This is supported by studies deleting the Sox2 regulatory region 2 (Srr2), the target of P27 repressive action. Single cell transcriptomic analysis further reveals that activation of a SOX2-dependent MAPK pathway in SCs is important for tumorigenesis. Altogether, our data highlight different aspects of the role of SOX2 following loss of p27, according to cellular context, and uncover an unexpected SOX2-dependent tumor-promoting role for SCs. Plinabulin datasheet Our results imply that targeting SCs, in addition to tumor cells, may represent an efficient antitumoral strategy in certain contexts.In mammals with frontal eyes, optic-nerve fibers from nasal retina project to the contralateral hemisphere of the brain, and fibers from temporal retina project ipsilaterally. The division between crossed and uncrossed projections occurs at or near the vertical meridian. If the division was precise, a problem would arise. Small objects near midline, but nearer or farther than current fixation, would produce signals that travel to opposite hemispheres, making the binocular disparity of those objects difficult to compute. However, in species that have been studied, the division is not precise. Rather, there are overlapping crossed and uncrossed projections such that some fibers from nasal retina project ipsilaterally as well as contralaterally and some from temporal retina project contralaterally as well as ipsilaterally. This increases the probability that signals from an object near vertical midline travel to the same hemisphere, thereby aiding disparity estimation. We investigated whether there is a deficit in binocular vision near the vertical meridian in humans and found no evidence for one. We also investigated the effectiveness of the observed decussation pattern, quantified from anatomical data in monkeys and humans. We used measurements of naturally occurring disparities in humans to determine disparity distributions across the visual field. We then used those distributions to calculate the probability of natural disparities transmitting to the same hemisphere, thereby aiding disparity computation. We found that the pattern of overlapping projections is quite effective. Thus, crossed and uncrossed projections from the retinas are well designed for aiding disparity estimation and stereopsis.Staphylococcus aureus causes invasive infections and easily acquires antibiotic resistance. Even antibiotic-susceptible S. aureus can survive antibiotic therapy and persist, requiring prolonged treatment and surgical interventions. These so-called persisters display an arrested-growth phenotype, tolerate high antibiotic concentrations, and are associated with chronic and recurrent infections. To characterize these persisters, we assessed S. aureus recovered directly from a patient suffering from a persistent infection. We show that host-mediated stress, including acidic pH, abscess environment, and antibiotic exposure promoted persister formation in vitro and in vivo. Multiomics analysis identified molecular changes in S. aureus in response to acid stress leading to an overall virulent population. However, further analysis of a persister-enriched population revealed major molecular reprogramming in persisters, including down-regulation of virulence and cell division and up-regulation of ribosomal proteins, nucleotide-, and amino acid-metabolic pathways, suggesting their requirement to fuel and maintain the persister phenotype and highlighting that persisters are not completely metabolically inactive.