Being adaptive to pain enhances sham acupuncture analgesia:A crossover healthy human study

We have reported a model that distinguishes pain adaptive individuals (PA) from those who are pain non-adaptive (PNA). The present randomised, cross-over, participant-assessor blinded study aimed to determine the impact of pain adaptability on individuals’ response to real and sham acupuncture. Healthy volunteers (nine PA and 13 PNA) were randomly allocated to receive real and sham acupuncture on the left hand and forearm in two separate acupuncture sessions. Pressure pain thresholds (PPTs) were measured at bilateral forearms and right leg before, immediately after and 20 minutes after the end of acupuncture. Ratings to pinprick and suprathreshold PPT were also recorded. The two groups were comparable in their demographic and baseline data. Analgesia induced by real or sham acupuncture did not differ on any outcome measures. PA responded to acupuncture needling better than PNA, and to sham needling (20% increase in PPT) better than to real acupuncture (7.9%). Those differences were at 20 min after end of acupuncture in the areas distant to the needling sites. PNA reported little changes in PPT. Being adaptive to pain was associated with enhanced distant analgesia in response to sham acupuncture. Our finding might partly explain varied acupuncture analgesia in clinical practice and trials

Development and Evaluation of a Positive Youth Development Course for University Students in Hong Kong

With higher education, university graduates are important elements of the labor force in knowledge-based economies. With reference to the mental health and developmental problems in university students, there is a need to review university's role in nurturing holistic development of students. Based on the positive youth development approach, it is argued that promoting intrapersonal competencies is an important strategy to facilitate holistic development of young people in Hong Kong. In The Hong Kong Polytechnic University, a course entitled Tomorrow's Leader focusing on positive youth development constructs to promote student well-being will be offered on a compulsory basis starting from 2012/13 academic year under the new undergraduate curriculum structure. The proposed course was piloted in 2010/11 school year. Different evaluation strategies, including objective outcome evaluation, subjective outcome evaluation, process evaluation, and qualitative evaluation, are being carried out to evaluate the developed course. Preliminary evaluation findings based on the piloting experience in 2010/11 academic year are presented in this paper

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool

© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex

On-surface synthesis of graphene nanoribbons with zigzag edge topology

Graphene-based nanostructures exhibit a vast range of exciting electronic properties that are absent in extended graphene. For example, quantum confinement in carbon nanotubes and armchair graphene nanoribbons (AGNRs) leads to the opening of substantial electronic band gaps that are directly linked to their structural boundary conditions. Even more intriguing are nanostructures with zigzag edges, which are expected to host spin-polarized electronic edge states and can thus serve as key elements for graphene-based spintronics. The most prominent example is zigzag graphene nanoribbons (ZGNRs) for which the edge states are predicted to couple ferromagnetically along the edge and antiferromagnetically between them. So far, a direct observation of the spin-polarized edge states for specifically designed and controlled zigzag edge topologies has not been achieved. This is mainly due to the limited precision of current top-down approaches, which results in poorly defined edge structures. Bottom-up fabrication approaches, on the other hand, were so far only successfully applied to the growth of AGNRs and related structures. Here, we describe the successful bottom-up synthesis of ZGNRs, which are fabricated by the surface-assisted colligation and cyclodehydrogenation of specifically designed precursor monomers including carbon groups that yield atomically precise zigzag edges. Using scanning tunnelling spectroscopy we prove the existence of edge-localized states with large energy splittings. We expect that the availability of ZGNRs will finally allow the characterization of their predicted spin-related properties such as spin confinement and filtering, and ultimately add the spin degree of freedom to graphene-based circuitry.Comment: 15 pages, 4 figure

LMTK3 confers chemo-resistance in breast cancer

Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment. In a mouse model we showed that ectopic overexpression of LMTK3 decreases the efficacy of doxorubicin in reducing tumor growth. Interestingly, breast cancer cells overexpressing LMTK3 delayed the generation of double strand breaks (DSBs) after exposure to doxorubicin, as measured by the formation of γH2AX foci. This effect was at least partly mediated by decreased activity of ataxia-telangiectasia mutated kinase (ATM) as indicated by its reduced phosphorylation levels. In addition, our RNA-seq analyses showed that doxorubicin differentially regulated the expression of over 700 genes depending on LMTK3 protein expression levels. Furthermore, these genes were found to promote DNA repair, cell viability and tumorigenesis processes / pathways in LMTK3-overexpressing MCF7 cells. In human cancers, immunohistochemistry staining of LMTK3 in pre- and postchemotherapy breast tumor pairs from four separate clinical cohorts revealed a significant increase of LMTK3 following both doxorubicin and docetaxel based chemotherapy. In aggregate, our findings show for the first time a contribution of LMTK3 in cytotoxic drug resistance in breast cancer

Polymorphism in the Tyrosine Hydroxylase (TH) Gene Is Associated with Activity-Impulsivity in German Shepherd Dogs

We investigated the association between repeat polymorphism in intron 4 of the tyrosine hydroxylase (TH) gene and two personality traits, activity-impulsivity and inattention, in German Shepherd Dogs. The behaviour of 104 dogs was characterized by two instruments: (1) the previously validated Dog-Attention Deficit Hyperactivity Disorder Rating Scale (Dog-ADHD RS) filled in by the dog owners and (2) the newly developed Activity-impulsivity Behavioural Scale (AIBS) containing four subtests, scored by the experimenters. Internal consistency, inter-observer reliability, test-retest reliability and convergent validity were demonstrated for AIBS

Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay

BACKGROUND: In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD) plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate. RESULTS: In order to achieve a greater understanding of NMD regulated gene expression we used 2D-DiGE proteomics technology to examine the changes in protein expression induced in HeLa cells by UPF1 knockdown. QPCR based validation of the corresponding mRNAs, in response to both UPF1 knockdown and cycloheximide treatment, identified 17 bona fide NMD targets. Most of these were associated with bioinformatically predicted NMD activating features, predominantly upstream open reading frames (uORFs). Strikingly, however, the majority of transcripts up-regulated by UPF1 knockdown were either insensitive to, or even down-regulated by, cycloheximide treatment. Furthermore, the mRNA abundance of several down-regulated proteins failed to change upon UPF1 knockdown, indicating that UPF1`s role in regulating mRNA and protein abundance is more complex than previously appreciated. Among the bona fide NMD targets, we identified a highly conserved AS-NMD event within the 3` UTR of the HNRNPA2B1 gene. Overexpression of GFP tagged hnRNP A2 resulted in a decrease in endogenous hnRNP A2 and B1 mRNA with a concurrent increase in the NMD sensitive isoforms. CONCLUSIONS: Despite the large number of changes in protein expression upon UPF1 knockdown, a relatively small fraction of them can be directly attributed to the action of NMD on the corresponding mRNA. From amongst these we have identified a conserved AS-NMD event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels