Epstein-barr virus-encoded latent membrane protein 1 impairs G2 checkpoint in human nasopharyngeal epithelial cells through defective Chk1 activation

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development. © 2012 Deng et al.published_or_final_versio

Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.published_or_final_versio

Skyrmions in a ferromagnetic Bose-Einstein condensate

The recently realized multicomponent Bose-Einstein condensates provide opportunities to explore the rich physics brought about by the spin degrees of freedom. For instance, we can study spin waves and phase separation, macroscopic quantum tunneling, Rabi oscillations, the coupling between spin gradients and superfluid flow, squeezed spin states, vortices and other topological excitations. Theoretically, there have been already some studies of the ground-state properties of these systems and their line-like vortex excitations. In analogy with nuclear physics or the quantum Hall effect, we explore here the possibility of observing point-like topological excitations or skyrmions. These are nontrivial spin textures that in principle can exist in a spinor Bose-Einstein condensate. In particular, we investigate the stability of skyrmions in a fictitious spin-1/2 condensate of Rb87 atoms. We find that skyrmions can exist in this case only as a metastable state, but with a lifetime of the order of, or even longer than, the typical lifetime of the condensate itself. In addition to determining the size and the lifetime of the skyrmion, we also present its spin texture and finally briefly consider its dynamical properties.Comment: 4 pages (REVtex), 3 PDF figures. See also cond-mat/000237

The association between internet addiction and psychiatric co-morbidity: A meta-analysis

Background: This study evaluates the association between Internal Addiction (IA) and psychiatric co-morbidity in the literature.Methods: Meta-analyses were conducted on cross-sectional, case-control and cohort studies which examined the relationship between IA and psychiatric co-morbidity. Selected studies were extracted from major online databases. The inclusion criteria are as follows: 1) studies conducted on human subjects; 2) IA and psychiatric co-morbidity were assessed by standardised questionnaires; and 3) availability of adequate information to calculate the effect size. Random-effects models were used to calculate the aggregate prevalence and the pooled odds ratios (OR).Results: Eight studies comprising 1641 patients suffering from IA and 11210 controls were included. Our analyses demonstrated a significant and positive association between IA and alcohol abuse (OR = 3.05, 95% CI = 2.14-4.37, z = 6.12, P < 0.001), attention deficit and hyperactivity (OR = 2.85, 95% CI = 2.15-3.77, z = 7.27, P < 0.001), depression (OR = 2.77, 95% CI = 2.04-3.75, z = 6.55, P < 0.001) and anxiety (OR = 2.70, 95% CI = 1.46-4.97, z = 3.18, P = 0.001).Conclusions: IA is significantly associated with alcohol abuse, attention deficit and hyperactivity, depression and anxiety. © 2014 Ho et al.; licensee BioMed Central Ltd

Linkage and association of myocilin (MYOC) polymorphisms with high myopia in a Chinese population

Author name used in this publication: Maurice K.H. Yap2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study

Author name used in this publication: Cornelia Man2013-2014 > Academic research: refereed > Publication in refereed journalpublished_fina

Suicide with psychiatric diagnosis and without utilization of psychiatric service

<p>Abstract</p> <p>Background</p> <p>Considerable attention has been focused on the study of suicides among those who have received help from healthcare providers. However, little is known about the profiles of suicide deceased who had psychiatric illnesses but made no contact with psychiatric services prior to their death. Behavioural model of health service use is applied to identify factors associated with the utilization of psychiatric service among the suicide deceased.</p> <p>Methods</p> <p>With respect to completed suicide cases, who were diagnosed with a mental disorder, a comparison study was made between those who had (contact group; n = 52; 43.7%) and those who had not made any contact (non-contact group; n = 67; 56.3%) with a psychiatrist during the final six months prior to death. A <it>sample </it>of 119 deceased cases aged between 15 and 59 with at least one psychiatric diagnosis assessed by the Structured Clinical Interview for DSM-IV-TR (SCID I) were selected from a psychological autopsy study in Hong Kong.</p> <p>Results</p> <p>The contact and non-contact group could be well distinguished from each other by "<it>predisposing</it>" variables: age group & gender, and most of the "<it>enabling"</it>, and "<it>need" </it>variables tested in this study. Multiple logistic regression analysis has found four factors are statistically significantly associated with non-contact suicide deceased: (i) having non-psychotic disorders (OR = 13.5, 95% CI:2.9-62.9), (ii) unmanageable debts (OR = 10.5, CI:2.4-45.3), (iii) being full/partially/self employed at the time of death (OR = 10.0, CI:1.6-64.1) and (iv) having higher levels of social problem-solving ability (SPSI) (OR = 2.0, CI:1.1-3.6).</p> <p>Conclusion</p> <p>The non-contact group was clearly different from the contact group and actually comprised a larger proportion of the suicide population that they could hardly be reached by usual individual-based suicide prevention efforts. For this reason, both universal and strategic suicide prevention measures need to be developed specifically in non-medical settings to reach out to this non-contact group in order to achieve better suicide prevention results.</p

Suicide among adults aged 30–49: A psychological autopsy study in Hong Kong

<p>Abstract</p> <p>Background</p> <p>A surge in suicide rates in middle age people in Hong Kong and many Asian countries was recently observed. However, there is a paucity of suicide research on this subgroup of people in Asia.</p> <p>Methods</p> <p>The next-of-kin of 85 suicide cases and 85 community subjects aged 30–49 years were interviewed by a psychological autopsy approach. Information was triangulated by interview notes, coroner's court files, and police investigation reports.</p> <p>Results</p> <p>A multiple logistic regression analysis identified the following risk factors for suicide among the middle age people in Hong Kong: the presence of at least one psychiatric disorder (OR = 37.5, 95% CI 11.5–121.9, p < 0.001), indebtedness (OR = 9.4, 95% CI 2.2–40.8, p < 0.01), unemployment (OR = 4.8, 95% CI 1.3–17.5, p < 0.05), never married (OR = 4.2, 95% CI 1.1–16.3, p < 0.05), and lived alone (OR = 3.9, 95% CI 1.2–13.4, p < 0.05).</p> <p>Conclusion</p> <p>The data show that socio-economical factors had a strong impact on suicide in the target group. Further research is needed to explore any positive qualities that protect the middle-aged from suicide. The prevention of suicide in the middle-aged requires multiple strategies.</p

The driver landscape of sporadic chordoma

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma

The Evolution of the Epidemic of Charcoal-Burning Suicide in Taiwan: A Spatial and Temporal Analysis

Shu-Sen Chang and colleagues describe the epidemiology of an epidemic of suicide by charcoal burning in Taiwan and discuss possible reasons for its spread