Results suggest that in adolescents with borderline personality features the loss of mentalization is more apparent in the emergence of unusual alternative strategies (hypermentalizing) than in the loss of the capacity per se (no mentalizing or undermentalizing). Moreover, for the first time, empirical evidence is provided to support the notion that mentalizing exerts its influence on borderline traits through the mediating role of emotion dysregulation.
SUMMARY
Epstein-Barr virus (EBV), an oncogenic herpesvirus that causes human
malignancies, infects and immortalizes primary human B cells in
vitro into indefinitely proliferating lymphoblastoid cell lines,
which represent a model for EBV-induced tumorigenesis. The immortalization
efficiency is very low suggesting that an innate tumor suppressor mechanism is
operative. We identify the DNA damage response (DDR) as a major component of the
underlying tumor suppressor mechanism. EBV-induced DDR activation was not due to
lytic viral replication nor did the DDR marks co-localize with latent episomes.
Rather, a transient period of EBV-induced hyper-proliferation correlated with
DDR activation. Inhibition of the DDR kinases ATM and Chk2 markedly increased
transformation efficiency of primary B cells. Further, the viral latent
oncoproteins EBNA3C was required to attenuate the EBV-induced DNA damage
response We propose that heightened oncogenic activity in early cell divisions
activates a growth-suppressive DDR which is attenuated by viral latency products
to induce cell immortalization.
NAFLD is frequently observed in HIV-monoinfected patients, and NASH is a common cause of unexplained abnormal liver function in patients selected for liver biopsy. Metabolic disorders are key risk factors independently of HIV parameters. Future trials on pharmacological interventions in NASH with fibrosis should include patients with HIV.
A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor- pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. (Blood. 2010;116(23):e118-e127)
The authors describe the development of a theory-driven assessment and research protocol at the Adolescent Treatment Program of The Menninger Clinic. First, the theoretical framework behind a mentalization-based model for assessment and treatment is described. Next, the process whereby measures were selected to operationalize key components of the mentalization-based model is discussed, including a brief discussion of each measure and assessment procedure. The next section describes the clinical and research use of the data collected. Here, the authors describe how outcomes assessment information is integrated into the clinical decision-making process, and they outline the research questions they aim to answer through the assessment protocol. The authors conclude with a section on the challenges, pitfalls, and future directions of the project.
Epstein-Barr virus (EBV) infection of primary B cellsleads to the outgrowth of indefinitely proliferating lymphoblastoid cell lines (LCLs). However, the efficiency of immortalization is less than 10% of infected cells. We hypothesize that a robust innate tumor suppressor response prevents long-term outgrowth of the majority of infected cells. In this study we identify the DNA damage response (DDR) as a major component of this response. EBV infection of primary B cells activated hallmarks of the DDR including phosphorylated ATM, Chk2, g-H2AX, and 53BP1 foci. DDR activation was not due to lytic viral DNA replication nor did its marks co-localize with latent viral episomes. Rather, EBV induced a period of hyper-proliferation early after infection responsible for DDR activation. Microarray data supported the transient activation and subsequent attenuation of proliferation and DDR-associated mRNAs during LCL outgrowth. Importantly, activation of this pathway suppressed transformation as small molecule antagonism of the DNA damage responsive kinases ATM and Chk2 increased EBV transformation efficiency. Thus, we propose a model whereby EBV infection initially drives aberrant cellular DNA replication activating an anti-proliferative DNA damage response. Long-term outgrowth depends on attenuation of this hyper-proliferative signal through full latency III gene expression.
AcknowledgementsThis article has been published as part of Infectious
The ITER Neutral Beam Test Facility (NBTF), called PRIMA (Padova Research on ITER Megavolt Accelerator), is hosted in Padova, Italy and includes two experiments: MITICA, the full-scale prototype of the ITER heating neutral beam injector, and SPIDER, the full-size radio frequency negative-ions source. The NBTF realization and the exploitation of SPIDER and MITICA have been recognized as necessary to make the future operation of the ITER heating neutral beam injectors efficient and reliable, fundamental to the achievement of thermonuclear-relevant plasma parameters in ITER. This paper reports on design and R&D carried out to construct PRIMA, SPIDER and MITICA, and highlights the huge progress made in just a few years, from the signature of the agreement for the NBTF realization in 2011, up to now-when the buildings and relevant infrastructures have been completed, SPIDER is entering the integrated commissioning phase and the procurements of several MITICA components are at a well advanced stage.
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