Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics.

Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case-control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10(-9) to 0.004) and NHWs (p values of 2.2 × 10(-6) to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53-1.99 and 1.37-1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21-3.22 and 1.67-2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10(-5)), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors

How to Create Suitable Augmented Reality Application to Teach Social Skills for Children with ASD

Autism spectrum disorders (ASDs) are characterized by a reduced ability to appropriately express social greetings. Studies have indicated that individuals with ASD might not recognize the crucial nonverbal cues that usually aid social interaction. This study applied augmented reality (AR) with tabletop role-playing game (AR-RPG) to focus on the standard nonverbal social cues to teach children with ASD, how to appropriately reciprocate when they socially interact with others. The results showed that intervention system provides an AR combined with physical manipulatives and presents corresponding specific elements in an AR 3D animation with dialogue; thus, it can be used to help them increase their social interaction skills and drive their attention toward the meaning and social value of greeting behavior in specific social situations. We conclude that AR-RPG of social situations helped children with ASD recognize and better understand these situations and moderately effective in teaching the target greeting responses

Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent JNK activation regulates caspase-3 and mitochondria pathways

Our previous report demonstrated that bovine ephemeral fever virus (BEFV)-infected cultured cells could induce caspase-dependent apoptosis. This study aims to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK) cells, and a kinetic study showed a higher efficiency of replication and a greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N-terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis. In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418 phosphorylation and JNK phosphorylation and kinase activity, which was inhibited specifically by SU6656 and SP600125, respectively. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also activated simultaneously upon BEFV infection. In addition, cytochrome c, but not Smac/DIABLO, was released gradually from mitochondria after BEFV infection. SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage. Taken together, these results strongly support the hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV-induced apoptosis. The molecular mechanism identified in our study may provide useful information for the treatment of BEFV

Spawning rings of exceptional points out of Dirac cones

The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformations of the Dirac cone often reveal intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. These two fields of research are in fact connected: here we discover the ability of a Dirac cone to evolve into a ring of exceptional points, which we call an "exceptional ring." We experimentally demonstrate this concept in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation that exists in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain

GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure

<p>Abstract</p> <p>Background</p> <p>Arsenic is a strong stimulus of heme oxygenase (HO)-1 expression in experimental studies in response to oxidative stress caused by a stimulus. A functional GT-repeat polymorphism in the HO-1 gene promoter was inversely correlated to the development of coronary artery disease in diabetics and development of restenosis following angioplasty in patients. The role of this potential vascular protective factor in carotid atherosclerosis remains unclear. We previously reported a graded association of arsenic exposure in drinking water with an increased risk of carotid atherosclerosis. In this study, we investigated the relationship between HO-1 genetic polymorphism and the risk of atherosclerosis related to arsenic.</p> <p>Methods</p> <p>Three-hundred and sixty-seven participants with an indication of carotid atherosclerosis and an additional 420 participants without the indication, which served as the controls, from two arsenic exposure areas in Taiwan, a low arsenic-exposed Lanyang cohort and a high arsenic-exposed LMN cohort, were studied. Carotid atherosclerosis was evaluated using a duplex ultrasonographic assessment of the extracranial carotid arteries. Allelic variants of (GT)n repeats in the 5'-flanking region of the HO-1 gene were identified and grouped into a short (S) allele (< 27 repeats) and long (L) allele (≥ 27 repeats). The association of atherosclerosis and the HO-1 genetic variants was assessed by a logistic regression analysis, adjusted for cardiovascular risk factors.</p> <p>Results</p> <p>Analysis results showed that arsenic's effect on carotid atherosclerosis differed between carriers of the class S allele (OR 1.39; 95% CI 0.86-2.25; <it>p </it>= 0.181) and non-carriers (OR 2.65; 95% CI 1.03-6.82; <it>p </it>= 0.044) in the high-exposure LMN cohort. At arsenic exposure levels exceeding 750 μg/L, difference in OR estimates between class S allele carriers and non-carriers was borderline significant (<it>p </it>= 0.051). In contrast, no such results were found in the low-exposure Lanyang cohort.</p> <p>Conclusions</p> <p>This exploratory study suggests that at a relatively high level of arsenic exposure, carriers of the short (GT)n allele (< 27 repeats) in the HO-1 gene promoter had a lower probability of developing carotid atherosclerosis than non-carriers of the allele after long-term arsenic exposure via ground water. The short (GT)n repeat in the HO-1 gene promoter may provide protective effects against carotid atherosclerosis in individuals with a high level of arsenic exposure.</p

Effects of a Chinese Herbal Medicine, Guan-Jen-Huang (Aeginetia indica Linn.), on Renal Cancer Cell Growth and Metastasis

Aeginetia indica Linn. (Guan-Jen-Huang, GJH), a traditional Chinese herb, has the potential to be an immunomodulatory agent. The purpose of this study was to explore the effect of GJH in the treatment of renal cancer. Concentration-effect curves for the influence of GJH on cellular proliferation showed a biphasic shape. Besides, GJH had a synergistic effect on cytotoxicity when combined with 5-fluorouracil (5-FU)which may be due to the alternation of the chemotherapeutic agent resistance-related genes and due to the synergistic effects on apoptosis. In addition, treatment with GJH extract markedly reduced 786-O cell adherence to human umbilical vein endothelial cells (HUVECs) and decreased 786-O cell migration and invasion. In a xenograft animal model, GJH extract had an inhibitory effect on tumor cell-induced metastasis. Moreover, western blot analysis showed that the expression of intercellular adhesion molecule-1 (ICAM-1) in 786-O cells was significantly decreased by treatment with GJH extract through inactivation of nuclear factor-κB (NF–κB). These results suggest that GJH extract has a synergistic effect on apoptosis induced by chemotherapeutic agents and an inhibitory effect on cell adhesion, migration, and invasion, providing evidence for the use of water-based extracts of GJH as novel alternative therapeutic agents in the treatment of human renal cancer

Antiinflammatory and Antioxidant Flavonoids and Phenols from Cardiospermum halicacabum (倒地鈴 Dào Dì Líng)

ABSTRACTSeventeen compounds, quercetin-3-O-α-l-rhamnoside (1), kaempferol-3-O-α-l-rhamnoside (2), apigenin-7-O-β-d-glucuronide (3), apigenin 7-O-β-d-glucuronide methyl ester (4), apigenin 7-O-β-d-glucuronide ethyl ester (5), chrysoeriol (6), apigenin (7), kaempferol (8), luteolin (9), quercetin (10), methyl 3,4-dihydroxybenzoate (11), p-coumaric acid (12), 4-hydroxybenzoic acid (13), hydroquinone (14), protocathehuic acid (15), gallic acid (16), and indole-3-carboxylic acid (17), were isolated from the ethanol extract of Taiwanese Cardiospermum halicabum. All chemical structures were determined by physical and extensive spectroscopic analyses such as 1H Nuclear Magnetic Resonance spectroscopy (NMR), 13C NMR, 1H-1H Correlation spectroscopy (1H-1H COSY), Heteronuclear Multiple Quantum Coherence spectroscopy (HMQC), Heteronuclear Multiple-bond Correlation spectroscopy (HMBC), and Nuclear Overhauser Effect spectroscopy (NOESY), as well as comparison with literature values. Furthermore, the High-Performance Liquid Chromatography-Photodiode Array Detector (HPLC-DAD) fingerprint profile was established for the determination of major constituents in the EtOAc extract and retention times of the isolated compounds. All isolated compounds were also evaluated for antiinflammatory and antioxidant activities

Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+ cells remain unclear. Initially, HNSCC-ALDH1+ cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+ cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression property ALDH1− cells to that of ALDH1+ cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+ cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1− cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+ cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+ cells

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan

<p>Abstract</p> <p>Background</p> <p>Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers.</p> <p>Methods</p> <p>To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped.</p> <p>Results</p> <p>The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, <it>p </it>= 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.</p> <p>Conclusions</p> <p>The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.</p

Dioscorea Phytocompounds Enhance Murine Splenocyte Proliferation Ex Vivo and Improve Regeneration of Bone Marrow Cells In Vivo

Specific cytokines have been tested clinically for immunotherapy of cancers; however, cytotoxicity has often impaired their usefulness. Consequently, alternative approaches are increasingly desirable. Dioscorea spp. tuber is a widely used traditional Chinese medicinal herb claimed to confer immunostimulatory activity. In this study, we evaluated Dioscorea as an adjuvant therapy for use alongside chemotherapy for cancer. Phytocompounds from Dioscorea tubers were ethanol fractioned and used for ex vivo splenocyte proliferation assay or in vivo force-feeding of mice pre-treated with the chemotherapy agent 5-fluorouracil. Co-treatment with a 50–75% ethanol-partitioned fraction of the tuber extract of D. batatas (DsCE-II) and interleukin (IL)-2 resulted in a significantly higher rate of murine splenocyte cell proliferation ex vivo than treatment with DsCE-II or IL-2 alone. This DsCE-II fraction, which contains a polysaccharide with a high proportion of β-1,4-linkage mannose (≥64%), also promoted the regeneration of specific progenitor cell populations in damaged bone marrow tissues of 5-fluorouracil-treated mice. Colony-forming unit (CFU) analyses demonstrated that the population of CFU-GM cells, but not CFU-GEMM or BFU-E cells, preferentially recovered to ~67% in the bone marrow of immune-suppressed mice fed with DsCE-II. DsCE-II efficacy level was ~85% of that obtained by subcutaneous administration of recombinant G-CSF proteins (5 μg kg−1) in mice tested in parallel. This study suggests that the DsCE-II fraction of D. batatas extract may be considered for further development as a dietary supplement for use alongside chemotherapy during cancer treatment