Search

OBJECTIVE: To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. METHOD: Participants included European ancestry (EA, n=4045) and African ancestry (AA, n=1550) individuals from the multigenerational COGA sample (56% female, M(age) ~ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score, and AUD comorbidities, including antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. RESULTS: Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HR] 0.70–0.83, ps < 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66–0.82, ps < 0.05) and those with MDD were more likely to marry (HR = 1.34, p < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (ORs 1.59–2.21, ps < 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. CONCLUSIONS: In a high-risk sample, alcohol use disorder was associated with reduced likelihood of marriage in European and African ancestry individuals, and increased risk of divorce in European ancestry individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce.

Aim This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). Methods The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. Results Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald’s ω = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. Conclusion The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.

Higher parental educational attainment is associated with higher offspring educational attainment. In this study, we incorporated genotypic and phenotypic information from fathers, mothers, and offspring to disentangle the genetic and socioenvironmental pathways underlying this association. Data were drawn from a sample of individuals of European ancestry from the collaborative study on the genetics of alcoholism (

Substance use disorders (SUDs) incur serious social and personal costs. Risk for SUDs is complex, ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2,475) ancestries. SUD outcomes included: 1) alcohol dependence, 2) nicotine dependence; 3) drug dependence, and 4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 1.37 – 1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11 – 1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09 – 1.18). The full model explained 6% - 13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86 - 8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

Background This study examined whether polygenic risk scores (PRS) for lifetime cannabis and alcohol use were associated with misusing opioids, and whether sex differences existed in these relations in an urban, African-American sample. Methods Data were drawn from three cohorts of participants (N = 1,103; 45% male) who were recruited in first grade as part of a series of elementary school-based, universal preventive intervention trials conducted in a Mid-Atlantic region of the U.S. In young adulthood, participants provided a DNA sample and reported on whether they had used heroin or misused prescription opioids in their lifetime. Three substance use PRS were computed based on prior GWAS: lifetime cannabis use from Pasman et al. (2018), heavy drinking indexed via maximum number of drinks from Gelernter et al. (2019), and alcohol consumption from Kranzler et al. (2019). Results Higher PRS for lifetime cannabis use, greater heavy drinking, and greater alcohol consumption were associated with heightened risk for misusing opioids among the whole sample. Significant sex by PRS interactions were also observed such that higher PRS for heavy drinking and alcohol consumption were associated with a greater likelihood of opioid misuse among males, but not females. Conclusion Our findings further elucidate the genetic contributions to misusing opioids by showing that the genetics of cannabis and alcohol consumption are associated with lifetime opioid misuse among young adults, though replication of our findings is needed.

Experiences of racial discrimination have been shown to increase risk for alcohol problems. Some individuals may be particularly vulnerable to the negative effects of racial discrimination. However, little research has examined interaction effects between racial discrimination and individual characteristics, such as genetic predispositions and personality, in relation to alcohol outcomes. This study examined whether genetic risk and dimensions of impulsivity moderate the association between racial discrimination and alcohol problems among African American young adults (n = 383, M

In Taiwan, the use of subtitle is common in TV programs and movies. However, studies on subtitles mostly focus on foreign language learning and film subtitle translation. Few studies address how subtitle types and emotion-laden films affect the viewers' eye movement patterns.We aim to examine how the emotion type of film (happy, sad, angry, fear, or neutral) and subtitle type (meaningful subtitle, no subtitle, or meaningless subtitle) affect the dwell times and fixation counts in the subtitle area.This study is a 5 (emotion type of film) × 3 (subtitle type) between-participants design. There were 15 participants per condition, resulting in a total of 225 participants. After watching a film, participants filled out a self-reported questionnaire regarding this film.The subtitled films have more fixation counts and dwell time for the meaningful subtitle compared to meaningless subtitle and no subtitle. The dwell time was longer on the subtitle area for the sad film than the neutral and happy films. Also, the dwell time was longer on the subtitle area for the fear film than the happy film. There were more fixation counts on the subtitle area for the sad film than the angry and happy films.The subtitle meaning is critical in directing overt attention. Also, overt attention directed to the subtitle area is affected by the different emotion types of films.

Objective Total laryngectomy (TL) is a life-saving procedure for individuals with advanced laryngeal cancer and those suffering from recurrence after initial treatment. The present study aimed to evaluate the differences between stapler closure (SC) and manual closure (MC) of the pharynx during TL for patients with laryngeal cancer. Design/setting A systematic literature search was performed using the PubMed, EMBASE and Cochrane Library databases. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). Dichotomous data were calculated as odds ratios (ORs), and continuous data were calculated as mean differences (MD) with 95% confidence intervals (CI). Main outcome/results A total of 7 studies (535 patients) were included in this meta-analysis. Pooled analysis showed that the operative time of TL was significantly reduced in the SC group (MD, -63.2; 95% CI, -106.0 to -20.4). Moreover, the SC group had a lower incidence of pharyngocutaneous fistula (OR = 0.38; 95% CI, 0.18 to 0.83; P = 0.016) and hospital stay (MD, -2.9; 95% CI, -5.6 to -0.1). The incidence of postoperative surgical site infection (OR = 0.41; 95% CI, 0.02 to 8.73; P = 0.565) was comparable between the two groups. Conclusion Based on these results, SC may be a useful option for patients who need TL.

A surgical response to upper airway (UA) surgery for obstructive sleep apnea (OSA) depends on adequate correction of collapsible sites in the UA. This pilot study aimed to examine the surgical response to UA surgery directed by drug-induced sleep computed tomography (DI-SCT) for OSA.Prospective case series.Tertiary referral center.This study recruited 29 OSA patients (median age, 41 years; median body mass index, 26.9 kg/mDI-SCT showed that 28 (97%) patients had collapses at multiple sites, all of whom underwent multilevel UA surgery accordingly. The apnea-hypopnea index decreased from 53.6 to 26.8 ( P.001). There were 18 (62%) nonresponders and 11 (38%) responders. Multiple-site collapses could not predict surgical response ( P.99). The nonresponders had significant improvements in velopharyngeal, oropharyngeal lateral wall, and tongue collapses (all P.05), whereas the responders had significant improvements in velopharyngeal and oropharyngeal lateral wall collapses (both P ≤ .05).Despite multilevel OSA surgery, residual UA obstruction in nonresponders likely occurs due to multiple mechanisms. DI-SCT may help to elucidate the reasons for a nonresponse.

Atrial fibrillation (AF) is the most common cardiovascular disease (CVD), and most existing algorithms are usually designed for the diagnosis (i.e., feature classification) or prediction of AF. Artificial intelligence (AI) algorithms integrate the diagnosis of AF electrocardiogram (ECG) and predict the possibility that AF will occur in the future. In this paper, we utilized the MIT-BIH AF Database (AFDB), which is composed of data from normal people and patients with AF and onset characteristics, and the AFPDB database (i.e., PAF Prediction Challenge Database), which consists of data from patients with Paroxysmal AF (PAF, the records contain the ECG preceding an episode of PAF), and subjects who do not have documented AF. We extracted the respective characteristics of the databases and used them in modeling diagnosis and prediction. In the aspect of model construction, we regarded diagnosis and prediction as two classification problems, adopted the traditional support vector machine (SVM) algorithm, and combined them. The improved quantum particle swarm optimization support vector machine (IQPSO-SVM) algorithm was used to speed the training time. During the verification process, the clinical FZU-FPH database created by Fuzhou University and Fujian Provincial Hospital was used for hybrid model testing. The data were obtained from the Holter monitor of the hospital and encrypted. We proposed an algorithm for transforming the PDF ECG waveform images of hospital examination reports into digital data. For the diagnosis model and prediction model trained using the training set of the AFDB and AFPDB databases, the sensitivity, specificity, and accuracy measures were 99.2% and 99.2%, 99.2% and 93.3%, and 91.7% and 92.5% for the test set of the AFDB and AFPDB databases, respectively. Moreover, the sensitivity, specificity, and accuracy were 94.2%, 79.7%, and 87.0%, respectively, when tested using the FZU-FPH database with 138 samples of the ECG composed of two labels. The composite classification and prediction model using a new water-fall ensemble method had a total accuracy of approximately 91% for the test set of the FZU-FPH database with 80 samples with 120 segments of ECG with three labels.

The Blomia tropicalis (Blo t) mite species is considered a storage mite in temperate climate zones and an important source of indoor allergens causing allergic asthma and rhinitis in tropical and subtropical regions. Here, we report the crystal structure of one of the allergens from Blo t, recombinant proBlo t 1 (rproBlo t 1), determined at 2.1 Å resolution. Overall, the fold of rproBlo t 1 is characteristic for the pro-form of cysteine proteases from the C1A class. Structural comparison of experimentally mapped Der f 1/Der p1 IgG epitopes to the same surface patch on Blo t 1, as well as of sequence identity of surface-exposed residues, suggests limited cross-reactivity between these allergens and Blo t 1. This is in agreement with ELISA inhibition results showing that, although cross-reactive human IgE epitopes exist, there are unique IgE epitopes for both Blo t 1 and Der p 1.

Parental alcohol use disorders (AUDs) and parental separation are associated with increased risk for early use of alcohol in offspring, but whether they increase risks for early use of other substances and for early sexual debut is under-studied. We focused on associations of parental AUDs and parental separation with substance initiation and sexual debut to (1) test the strength of the associations of parental AUDs and parental separation with time to initiation (age in years) of alcohol, tobacco and cannabis use and sexual debut and (2) compare the strength of association of parental AUD and parental separation with initiation.Prospective adolescent and young adult cohort of a high-risk family study, the Collaborative Study on the Genetics of Alcoholism (COGA).Six sites in the United States.A total of 3257 offspring (aged 14-33 years) first assessed in 2004 and sought for interview approximately every 2 years thereafter; 1945 (59.7%) offspring had a parent with an AUD.Diagnostic interview data on offspring substance use and sexual debut were based on first report of these experiences. Parental life-time AUD was based on their own self-report when parents were interviewed (1991-2005) for most parents, or on offspring and other family member reports for parents who were not interviewed. Parental separation was based on offspring reports of not living with both biological parents most of the time between ages 12 and 17 years.Parental AUDs were associated with increased hazards for all outcomes, with cumulative hazards ranging from 1.19 to 2.71. Parental separation was also an independent and consistent predictor of early substance use and sexual debut, with hazards ranging from 1.19 to 2.34. The strength of association of parental separation with substance initiation was equal to that of having two AUD-affected parents, and its association with sexual debut was stronger than the association of parental AUD in one or both parents.Parental alcohol use disorders (AUDs) and parental separation are independent and consistent predictors of increased risk for early alcohol, tobacco and cannabis use and sexual debut in offspring from families with a high risk of parental AUDs.

Background Few studies included information on components and sources when exploring the cardiovascular health effects from personal exposure to particulate matters (PM). We previously reported that exposure to PM between 1.0 and 2.5 μm (PM 2.5–1 ) was associated with increased cardio-ankle vascular index (CAVI, an arterial stiffness index), while exposure to PM smaller than 0.25 μm (PM 0.25 ) decreased the heart rate variability (HRV) indices. The purpose of this study was to investigate the association between PM elements and cardiovascular health effects and identify responsible sources. Methods In a panel study of seventeen mail carriers, the subjects were followed for 5–6 days while delivering mail outdoors. Personal filter samples of PM 2.5–1 and PM 0.25 were analyzed for their elemental concentrations. The source-specific exposures were further estimated by using absolute principal factor analysis. We analyzed the component- and source-specific health effects on HRV indices and CAVI using mixed models. Results Several elements in PM 2.5–1 (e.g., cadmium and strontium) were associated with the CAVI. Subsequent analyses showed that an interquartile range increase in exposure to PM from regional sources was significantly associated with a 3.28% increase in CAVI (95% confidence interval (CI), 1.47%–5.13%). This significant effect remained (3.35%, CI: 1.62%–5.11%) after controlling for the ozone exposures. For exposures to PM 0.25 , manganese, calcium, nickel, and chromium were associated with the CAVI and/or the HRV indices. Conclusions Our study suggests that PM 2.5–1 and PM 0.25 components may be associated with different cardiovascular effects. Health risks from exposure to PM from sources other than vehicle exhaust should not be underappreciated.

Fve is a fungal protein isolated from the golden needle mushroom Flammulina velutipes and has previously been reported to trigger immunological responses in both mouse and human lymphocytes. In this study, we evaluated the potential application of Fve as an adjuvant for tumour immunotherapy and examined the underlying mechanism(s). When the human papillomavirus (HPV)-16 E7 oncoprotein was used as a model antigen, mice coimmunized with HPV-16 E7 and Fve showed enhanced production of HPV-16 E7-specific antibodies as well as expansion of HPV-16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells as compared with mice immunized with HPV-16 E7 alone. Tumour protection assays showed that 60% of mice coimmunized with HPV-16 E7 plus Fve, as compared with 20% of those immunized only with HPV-16 E7, remained tumour-free for up to 167 days after challenge with the tumour cells. Tumour therapeutic assays showed that HPV-16 E7 plus Fve treatment significantly prolonged the survival of tumour-bearing mice as compared with those treated only with HPV-16 E7. In vivo cell depletion and adoptive T-cell transfer assays showed that CD4(+) and CD8(+) T cells and IFN-gamma played critical roles in conferring the antitumour effects. Interestingly, Fve could stimulate the maturation of splenic dendritic cells in vivo and induce antigen-specific CD8(+) T-cell immune responses. In summary, Fve has potent adjuvant properties that enhance T helper type 1 antigen-specific humoral and cellular immune responses which confer strong antitumour effects. The use of Fve as an adjuvant could be an attractive alternative to the current vaccination strategy for cancer immunotherapy.

Bifunctional apoptosis regulator (BAR) is an endoplasmic reticulum protein that interacts with both the extrinsic and intrinsic apoptosis pathways. We hypothesize that over-expression of BAR Delta RING prevents apoptosis and injury following ischaemia/reperfusion (I/R) and attenuates doxorubicin (DOX)-induced cardiotoxicity.We generated a line of transgenic mice that carried a human BAR Delta RING transgene under the control of the mouse alpha-myosin heavy chain promoter. The RING domain, which binds ubiquitin conjugating enzymes, was deleted to prevent auto-ubiquitination of BAR and allow accumulation of the BAR protein, which binds apoptosis-regulating proteins. High levels of human BAR Delta RING transcripts and 42 KDa BAR Delta RING protein were expressed in the hearts of transgenic mice. When excised hearts were reperfused ex vivo for 45 min as Langendorff preparations after 45 min of global ischaemia, the functional recovery of the hearts, expressed as left ventricular developed pressure x heart rate, was 23 +/- 1.7% in the non-transgenic hearts compared with 51.5 +/- 4.3% in the transgenic hearts (P0.05). For in vivo studies, mice were subjected to 50 min of ligation of the left descending anterior coronary artery followed by 4 h of reperfusion. The infarct sizes following I/R injury, expressed as the percentage of the area at risk, were significantly smaller in the transgenic mice than in the non-transgenic mice (29 +/- 4 vs. 55 +/- 4%, P0.05). In hearts of mice subjected to cardiac I/R injury, BAR transgenic hearts had significantly fewer in situ oligo-ligation-positive cardiac cells (5.0 +/- 0.4 vs. 13.4 +/- 0.5%, P0.05). Over-expression of BAR Delta RING also significantly attenuated DOX-induced cardiac dysfunction and apoptosis.Our results demonstrate that over-expression of BAR Delta RING renders the heart more resistant to I/R injury and DOX-induced cardiotoxicity, and this protection correlates with reduced cardiomyocyte apoptosis.

Single-stranded telomeric DNA tends to form a four-base-paired planar structure termed G-quadruplex. This structure was easily formed in vitro in the presence of monovalent cations. However, the existence of this structure in native human telomeres is unclear. Here we address this important question through the distinctive properties of 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) upon binding to various DNA structures. Although the fluorescence of BMVC increases significantly in the presence of DNA, BMVC has high sensitivity and binding preference to quadruplex d(T(2)AG(3))(4) over duplex DNA. In addition, the fluorescent emissions were characterized around 575 nm for quadruplex d(T(2)AG(3))(4) and 545 nm for most of duplex DNA. The 575-nm fluorescence emissions were detected in the mixtures of 2 nM BMVC with the chromosomal DNA that were extracted from human cells, suggesting the presence of quadruplex structure in human nucleus. Further analyzing the BMVC fluorescence at the ends of metaphase chromosomes and other regions of chromosomes, we detected the quadruplex-binding BMVC fluorescence at telomere-proximal regions. Together these results provide the first evidence for the presence of quadruplex structures in human telomeres.

Background: Eczema is a known risk factor for the development of wheeze in childhood. Cord blood T-cell cytokine responses have been shown to be associated with the development of both early childhood eczema and wheeze. Our objective is to study and compare the influence of intrinsic T-cell cytokine responses on the development of wheezing and eczema in the first 2 years of life in a birth cohort of at risk (first degree family with atopic disease) infants. Methods: Cord blood samples were collected from 195 eligible subjects of a birth cohort of 253 subjects. The subjects studied were those who developed either wheezing (n = 34) or eczema (n = 29) in the first 2 years of life, and 65 healthy infants served as control. Cytokines from phytohaemagglutinin stimulated mononuclear cells were analyzed using multiplex cytokine assays and the cytokine profiles in the 3 groups were compared. Results: Most of the subjects were non-atopic with only 3/34 (9%) wheeze and 9/29 (31%) eczema subjects sensitized to the common dietary or inhalant allergens. After adjustment for potential risk factors, wheeze, but not eczema subjects, presented with hyper-responsive cytokine profiles with increased production of T-cell cytokines IL-2 and IL-5. IL-5 was the strongest risk factor associated to the development of wheeze at 2 years of age (OR, 35; 95% CI, 5.0 – 246.7). Conclusion: Cord blood cytokine responses in early onset wheeze and eczema are distinctly different. This suggests that the tendency to develop early onset wheeze may be influenced by preexisting immune factors independent to those for eczema.

Der p 2, a major allergen of Dermatophagoides pteronyssinus mites, is one of the most clinically relevant allergens to allergic patients worldwide. FIP-fve protein (Fve) from the golden needle mushroom (Flammulina velutipes) is an immunomodulatory protein with potential Th1-skewed adjuvant properties. Here, we produced and immunologically evaluated a Der p 2-Fve fusion protein as a potential immunotherapeutic for allergic diseases. Using an inducible expression system in cultured rice suspension cells, the recombinant Der p 2-Fve fusion protein (designated as OsDp2Fve) was expressed in rice cells under the control of an α-amylase gene (αAmy8) promoter and secreted under sucrose starvation. OsDp2Fve was partially purified from the cultured medium. The conformation of Der p 2 in OsDp2Fve remains intact as reflected by its unaltered allergenicity, as assessed by human IgE ELISA and histamine release assays, compared to non-fusion Der p 2 protein. Furthermore, the Fve protein expressed in OsDp2Fve retains its in vitro lymphoproliferative activity but loses its hemagglutination and lymphoagglutination effects compared to the native protein. Notably, in vivo evaluation showed that mice administered with OsDp2Fve possessed an enhanced production of Der p 2-specific IgG antibodies without potentiating the production of Der p 2-specific IgE and Th2 effector cytokines in comparison with mice co-administered with native Fve and Der p 2 proteins. These results suggest that the recombinant Der p 2-Fve fusion protein produced in rice suspension cell cultures has a great potential for allergy immunotherapy.

The effects on heart rate variability (HRV) and arterial stiffness from exposure to ambient particulate matter and ozone have not been studied simultaneously. The aim of this study was to analyze these effects with refined exposure estimates from personal measurements of ozone and size-resolved particulate matter mass concentrations. The authors recruited 17 mail carriers in a panel study in Taipei County, Taiwan, during February-March, 2007, and each subject was followed for 5-6 days. Personal ozone and size-fractionated particulate matter exposures were monitored during working hours while carriers delivered mail outdoors. Cardiovascular effects were evaluated with heart rate variability (HRV) indices and an arterial stiffness index, the cardio-ankle vascular index (CAVI). The authors used linear mixed models to examine the association between personal exposure data and the HRV index and CAVI. They found that an interquartile range increase in personal exposure to ozone and particulate matter of between 1.0 and 2.5 microm was associated with a 4.8% and 2.5% increase in CAVI, respectively, in the single-pollutant models. In contrast, the personal exposure data showed no significant effects on HRV. In 2-pollutant models, personal ozone exposure remained significantly associated with the CAVI measurements. The study results indicate that vascular function may be more sensitive to air pollutants than the autonomic balance.

Purpose of review Antiallergy DNA vaccine is an attractive alternative for the prevention and treatment of allergic diseases. This review covers recent studies to enhance potency and safety of antiallergy DNA vaccines. Recent findings Dendritic cell-targeted allergen gene vaccination using fascin gene promoter inhibited IgE production and allergic inflammation but not airway hyperresponsiveness. Targeting allergen expression at immature dendritic cells or induction of tolerogenic dendritic cells could induce antiallergic T regulatory cells. Vaccination with DNA-encoded Ag85B and AIMP1 as adjuvants could downregulate established Th2-mediated allergic responses. Forced ubiquitation or targeting allergens to lysosomal/endosomal compartments could avoid risk of allergen sensitization. Gene gun delivery of conventional antiallergy DNA vaccine is a risk factor. Replicase-based allergy DNA vaccines showed enhanced immunogenecity and safety as compared to conventional DNA vaccines. TANK-binding kinase-1 (TBK1) is a novel key molecule in DNA vaccine-induced immunogenicity. Summary Dendritic cell-based approach has been actively explored to enhance immunogenicity of antiallergy DNA vaccines. Codelivery of hypoallergenic DNA vaccines with potent adjuvants via a desirable delivery mode will help to fulfill the requirements for clinical application of antiallergy DNA vaccines. Activation of TBK1 signaling pathway could be a novel strategy to enhance immunogenicity of DNA vaccines.

Blomia tropicalis allergens are the most important mite allergens in tropical regions. Most of them only have 30-40% sequence identity with their Dermatophagoides counterparts and they share low IgE cross reactivity and exhibit different immunobiology. Unlike the pyroglyphid counterparts, Blo t 5 is the major allergen whereas Blo t 1 only has modest allergenicity.

We have investigated a novel compound, 3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide (BMVC), for inhibiting telomerase activity and distinguishing human lung H1299 and oral Ca9-22 cancer cells from lung IMR90 and skin Detroit-551 normal fibroblast cells. The telomeric repeat amplification protocol (TRAP) assay shows that the concentration of BMVC that inhibits 50% of the telomerase activity (IC50) is ca. 0.05 microM. On the other hand, the cell-viability assay indicates that the cytotoxicity was less than 15% to the H1299 and Ca9-22 cancer cells, and almost negligible to the MRC-5 and Detroit-551 normal cells after incubation with 0.5 microM BMVC for 72 h. The low concentration of 0.05 microM of BMVC can inhibit telomerase activity but does not have general toxic effects to normal cells, implying that BMVC is a promising telomerase inhibitor. Moreover, wide-field fluorescence images of 0.1 microM BMVC-treated cells show bright fluorescence spots in the nuclei of the most H1299 and Ca9-22 cancer cells. Interestingly, similar fluorescence spots are hardly observed in the nuclei of the IMR90 and Detroit-551 normal cells, implying that BMVC might be a useful marker to distinguish tumor cells and normal cells.

Summary Background Sensitization to mite and cockroach allergens is common, and diagnosis and therapy of allergy can be further complicated by the presence of allergen isoforms and panallergens. Purified recombinant and native allergens are useful for studies to resolve such problems. Objective To assess the allergenicity of native and recombinant mite glutathione S-transferase (GST) (Der p 8) and study the IgE cross-reactivity between Der p 8 and cockroach GST. Methods Der p 8 cDNA encoding a new isoform was isolated and expressed in yeast. Native Der p 8 was affinity purified from mite extract. IgE reactivity to native and recombinant Der p 8 was assessed by ELISA using sera from allergic subjects from Taiwan, Singapore and Malaysia. IgE cross-reactivity between Der p 8 and cockroach GST was examined by IgE inhibition assays. Results Our Der p 8 cDNA encoded a basic isoform (pI=8.5) containing six polymorphic residues located at positions 46, 106, 149, 160, 167 and 184. At least 8 isoforms of native Der p 8 were detected by two-dimensionalgel and immunoblot analyses. Sera from Taiwanese asthmatics showed 96% and 84% IgE reactivity to native Der p 8 and recombinant Der p 8, respectively. Native Der p 8 showed 75% and 65% IgE reactivity with sera from Malaysia and Singapore, respectively. Conclusions A high frequency of sensitization to mite GST among allergic subjects was observed but the titres of IgE reactivity were low. The IgE cross-reactivity between mite and cockroach GST suggests that GST is a panallergen.

Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/β-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APC Min ) mouse cancer model, PPARγ expression in the colonic mucosa is markedly altered. In addition, PPARγ protein levels are elevated, possibly through sequestration by activated β-catenin in colon cancer cell lines. Induction of the Wnt/β-catenin pathway by LiCl also elevated PPARγ levels and induced PPARγ-dependent reporter and endogenous target genes. Mechanistically, PPARγ, through interactions with β-catenin and T cell transcription factor (Tcf)-4, may be a determinant of cell fate and is likely a target of the Wnt pathway in cancer cells.