The unfolding dark side:Age trends in dark personality features

Age and gender differences across the lifespan in dark personality features could provide hints regarding these features’ functions. We measured manipulation, callous affect, and egocentricity using the Dirty Dozen and their links with agreeableness in a pooled cross-sectional dataset (N = 4292) and a longitudinal dataset (N = 325). Age trends for all dark personality features were progressive through adolescence, but negative through adulthood. Men scored higher than women, but the gender gap varied with age. Trends for agreeableness partly mirrored these trends and changes in dark personality features and agreeableness were correlated. Results are discussed in light of the maturity principle of personality, gender role socialization processes, and issues regarding incremental validity of dark personality over traditional antagonism measures

Personality maturation around the world:A cross-cultural examination of Social-Investment Theory

During early adulthood, individuals from different cultures across the world tend to become more agreeable, more conscientious, and less neurotic. Two leading theories offer different explanations for these pervasive age trends: Five-factor theory proposes that personality maturation is largely determined by genetic factors, whereas social-investment theory proposes that personality maturation in early adulthood is largely the result of normative life transitions to adult roles. In the research reported here, we conducted the first systematic cross-cultural test of these theories using data from a large Internet-based sample of young adults from 62 nations (N = 884,328). We found strong evidence for universal personality maturation from early to middle adulthood, yet there were significant cultural differences in age effects on personality traits. Consistent with social-investment theory, results showed that cultures with an earlier onset of adult-role responsibilities were marked by earlier personality maturation. Keywords: personality development, Big Five, social investment, culture, adult development, cross-cultural differences, personalit

К анализу производственных затрат при столбовой системе отработки тонких пологих пластов угля комплексами нового поколения

У статті проаналізовано основні виробничі витрати при стовбовій системі відпрацювання тонких положистих пластів вугілля комплексами нового покоління. Розглянуто залежність собівартості видобутку вугілля при різних параметрах відпрацювання тонких положистих пластів вугілля.The article discusses the basic production spending for system development Pole thin flat layers of coal complexes of new generation. We consider the dependence of the cost of coal at different parameters development thin shallow coal seams

Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target

Cholangiocarcinoma is the second most common primary liver cancer and responds poorly to existing therapies. Intrahepatic cholangiocarcinoma (ICC) likely originates from the biliary tree and develops within the hepatic parenchyma. We have generated a flexible orthotopic allograft mouse model of ICC that incorporates common genetic alterations identified in human ICC and histologically resembles the human disease. We examined the utility of this model to validate driver alterations in ICC and tested their suitability as therapeutic targets. Specifically, we showed that the fused-in-glioblastoma-c- ros-oncogene1 (FIG-ROS1(S); FIG- ROS) fusion gene dramatically accelerates ICC development and that its inactivation in established tumors has a potent antitumor effect. Our studies establish a versatile model of ICC that will be a useful preclinical tool and validate ROS1 fusions as potent oncoproteins and therapeutic targets in ICC and potentially other tumor types

mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

MicroRNAs of the mir-17~92 cluster regulate multiple aspects of pancreatic tumor development and progression

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue. In a PDAC model driven by concomitant KRASG12D expression and Trp53 heterozygosity, mir-17~92 deficiency extended the survival of mice that lacked distant metastasis. Moreover, mir-17~92-deficient PDAC cell lines display reduced invasion activity in transwell assays, form fewer invadopodia rosettes than mir-17~92-competent cell lines and are less able to degrade extracellular matrix. Specific inhibition of miR-19 family miRNAs with antagomirs recapitulates these phenotypes, suggesting that miR-19 family miRNAs are important mediators of PDAC cell invasion. Together these data demonstrate an oncogenic role for mir-17~92 at multiple stages of pancreatic tumorigenesis and progression; specifically, they link this miRNA cluster to ERK pathway activation and precursor lesion maintenance in vivo and identify a novel role for miR-19 family miRNAs in promoting cancer cell invasion

Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer.

To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%) patients displaying p53-positive phenotype, defined as > or = 25% of positive cells. Patients with two or more first-degree relatives with cancer had an odds ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with those without a family history of cancer (trend test, P = 0.11). A possible association between body weight and p53 overexpression was observed. The ORs were 1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest quartile in comparison with the lowest quartile (trend test, P = 0.06). No association between occupational physical activity, smoking, drinking, parity and p53 overexpression was identified. The results suggest that p53 overexpression may be related to genetic predisposition to colorectal cancer, and p53-positive and p53-negative colorectal cancers may be controlled by different aetiological pathways

THE RELATIONSHIP BETWEEN HORIZONTAL FORCE-VELOCITY PROFILE AND VERTICAL STRENGTH IN FEMALE ICE HOCKEY PLAYERS

The primary purpose of this study was to evaluate the horizontal force-velocity (HFV) profiles of female collegiate ice hockey players and compare these to metrics of muscular strength. The secondary purpose of this study was to categorize strength metrics using reduction analyses to improve the interpretation and application of these results and that of future studies. Thirteen female ice hockey players (body mass = 66.7±18.0 kg; height = 171.6±6.2 cm) completed three 50-meter on-ice sprints. Instantaneous velocity was measured using a radar gun in which participant HFV profile metrics (maximal velocity, tau, force-velocity slope, maximum theoretical force, ratio decrease force) were derived. Forty-eight hours later, participants completed four strength tests (drop jump, countermovement jump, loaded countermovement jump, and isometric squat) measured using a dual force plate resulting in 64 metrics of strength. A stepwise regression was employed to assess the associations between strength and HFV profile metrics. All strength metrics were entered into a principal component analysis (PCA) to support the interpretation of the results. There were no significant associations between strength and HFV profile metrics. The PCA identified four clusters of strength metrics that were considered distinct strength properties in this population. This study presents a robust method for evaluating skating HFV profiles and strength metrics in ice hockey players and should be used in future studies to contribute to this body of literature

Cryo-EM structures of alphavirus conformational intermediates in low pH-triggered prefusion states

Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus-host membrane fusion for delivery of the capsid core and RNA genome into the cytosol to initiate virus translation and replication. However, mechanisms by which E1 and E2 glycoproteins rearrange in this process remain unknown. Here, we investigate prefusion cryoelectron microscopy (cryo-EM) structures of eastern equine encephalitis virus (EEEV) under acidic conditions. With models fitted into the low-pH cryo-EM maps, we suggest that E2 dissociates from E1, accompanied by a rotation (∼60°) of the E2-B domain (E2-B) to expose E1 fusion loops. Cryo-EM reconstructions of EEEV bound to a protective antibody at acidic and neutral pH suggest that stabilization of E2-B prevents dissociation of E2 from E1. These findings reveal conformational changes of the glycoprotein spikes in the acidified host endosome. Stabilization of E2-B may provide a strategy for antiviral agent development