Skill obsolescence, vintage effects and changing tasks

Human capital is no doubt one of the most important factors for future economic growth and well-being. However, human capital is also prone to becoming obsolete over time. Skills that have been acquired at one point in time may perfectly match the skill requirements at that time but may become obsolete as time goes by. Thus, in the following paper, we study the depreciation processes of the human capital of workers performing different types of tasks with different skill requirements over a period of more than twenty years. We argue that two types of tasks must be distinguished: knowledge-based tasks and experience-based tasks. Knowledge-based tasks demand skills depending on the actual stock of technological knowledge in a society whereas experience-based tasks demand skills depending on personal factors and individual experience values. We show, by applying Mincer regressions on four different cross sections, that the human capital of people performing knowledge-based tasks suffers more from depreciation than the human capital of individuals performing experience-based tasks

Telomerase Maintains Telomere Structure in Normal Human Cells

AbstractIn normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in cycling primary presenescent human fibroblasts, previously believed to lack hTERT expression and telomerase activity. Disruption of telomerase activity in normal human cells slows cell proliferation, restricts cell lifespan, and alters the maintenance of the 3′ single-stranded telomeric overhang without changing the rate of overall telomere shortening. Together, these observations support the view that telomerase and telomere structure are dynamically regulated in normal human cells and that telomere length alone is unlikely to trigger entry into replicative senescence

EZH2 promotes a bi-lineage identity in basal-like breast cancer cells

The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a ‘bi-lineage’ differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition

Are sedatives and hypnotics associated with increased suicide risk of suicide in the elderly?

<p>Abstract</p> <p>Background</p> <p>While antidepressant-induced suicidality is a concern in younger age groups, there is mounting evidence that these drugs may reduce suicidality in the elderly. Regarding a possible association between other types of psychoactive drugs and suicide, results are inconclusive. Sedatives and hypnotics are widely prescribed to elderly persons with symptoms of depression, anxiety, and sleep disturbance. The aim of this case-control study was to determine whether specific types of psychoactive drugs were associated with suicide risk in late life, after controlling for appropriate indications.</p> <p>Methods</p> <p>The study area included the city of Gothenburg and two adjacent counties (total 65+ population 210 703 at the start of the study). A case controlled study of elderly (65+) suicides was performed and close informants for 85 suicide cases (46 men, 39 women mean age 75 years) were interviewed by a psychiatrist. A population based comparison group (n = 153) was created and interviewed face-to-face. Primary care and psychiatric records were reviewed for both suicide cases and comparison subjects. All available information was used to determine past-month mental disorders in accordance with DSM-IV.</p> <p>Results</p> <p>Antidepressants, antipsychotics, sedatives and hypnotics were associated with increased suicide risk in the crude analysis. After adjustment for affective and anxiety disorders neither antidepressants in general nor SSRIs showed an association with suicide. Antipsychotics had no association with suicide after adjustment for psychotic disorders. Sedative treatment was associated with an almost fourteen-fold increase of suicide risk in the crude analyses and remained an independent risk factor for suicide even after adjustment for any DSM-IV disorder. Having a current prescription for a hypnotic was associated with a four-fold increase in suicide risk in the adjusted model.</p> <p>Conclusion</p> <p>Sedatives and hypnotics were both associated with increased risk for suicide after adjustment for appropriate indications. Given the extremely high prescription rates, a careful evaluation of the suicide risk should always precede prescribing a sedative or hypnotic to an elderly individual.</p

Evidence That SOX2 Overexpression Is Oncogenic in the Lung

BACKGROUND: SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung. METHODOLOGY/PRINCIPAL FINDINGS: We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63). CONCLUSIONS: These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer