Background There are only three cases of unbalanced translocation (X;1) reported in childhood in the literature, while no such phenotypic information is available in adults. Materials and methods To delineate the phenotype-genotype relationship of unbalanced translocation (X;1) in adulthood, we reported here a 20-year-old female with an unbalanced translocation (X;1) which was determined by spectral karyotyping, array-comparative genomic hybridization and subtelomeric fluorescence in situ hybridization (FISH). Results The phenotype of partial trisomy 1 and partial monosomy X of the present case was much attenuated, including premature ovarian failure, mental retardation, class I obesity, mild dysmorphism and delayed secondary sexual characteristics. The breakpoints of the unbalanced translocation were accurately located at Xq28 and 1q32AE1. The large amplification on Chromosome 1 q arm was found to involve 312 genes and the deletion on Chromosome X q arm also involved 141 genes. Overall, genes associated with physiological process (47 genes), cellular process (33), development (23), response to stimulus (1) and reproduction (1) were observed in the amplification on Chromosome 1 q arm. In addition, genes related to physiological process (23 genes), cellular process (13), development (6) and response to stimulus (2) were observed in the large deletion on chromosome X q arm. Late-replication studies revealed the existence of skewed X inactivation in the derivative X chromosome. Conclusions The phenotype of partial monosomy X and partial trisomy 1q is much attenuated in case of unbalanced translocation (X;1) in adulthood probably owing to skewed X inactivation in derivative X chromosome.

Purple sweet potato color (PSPC), a naturally occurring anthocyanin, has a powerful antioxidant activity in vitro and in vivo. This study explores whether PSPC has the neuroprotective effect on the aging mouse brain induced by D-galactose (D-gal). The mice administrated with PSPC (100 mg/kg.day, 4 weeks, from 9th week) via oral gavage showed significantly improved behavior performance in the open field and passive avoidance test compared with D-gal-treated mice (500 mg/kg.day, 8 weeks). We further investigate the mechanism involved in neuroprotective effects of PSPC on mouse brain. Interestingly, we found, PSPC decreased the expression level of glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), inhibited nuclear translocation of nuclear factor-kappaB (NF-κB), increased the activity of copper/zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA), respectively. Our data sugg...

Structural studies of polytopic membrane proteins are often hampered by the vagaries of these proteins in membrane mimetic environments and by the difficulties in handling them with conventional techniques. Designing and creating water-soluble analogues with preserved native structures offer an attractive alternative. We report here solution NMR studies of WSK3, a water-soluble analogue of the potassium channel KcsA. The WSK3 NMR structure (PDB ID code 2K1E ) resembles the KcsA crystal structures, validating the approach. By more stringent comparison criteria, however, the introduction of several charged residues aimed at improving water solubility seems to have led to the possible formations of a few salt bridges and hydrogen bonds not present in the native structure, resulting in slight differences in the structure of WSK3 relative to KcsA. NMR dynamics measurements show that WSK3 is highly flexible in the absence of a lipid environment. Reduced spectral density mapping and model-...

Monodispersed bimetallic PdAg nanoparticles can be fabricated through the emulsion-assisted ethylene glycol (EG) ternary system. Different compositions of bimetallic PdAg nanoparticles, Pd₈₀Ag₂₀, Pd₆₅Ag₃₅ and Pd₄₆Ag₅₄ can be obtained via adjusting the reaction parameters. For the formation process of the bimetallic PdAg nanoparticles, there have two-stage growth processes: firstly, nucleation and growth of the primary nanoclusters; secondly, formation of the secondary nanoparticles with the size-selection and relax process via the coalescence or aggregation of the primary nanoclusters. The as-prepared PdAg can be supported on the carbon black without any post-treatment, which exhibited high electro-oxidation activity towards methanol oxidation under alkaline media. More importantly, carbon-supported Pd₈₀Ag₂₀ nanoparticles reveal distinctly superior activities for the methanol oxidation, even if compared with commercial Pt/C electro-catalyst. It is concluded that the enhanced activit...

Nonoxidative activation of methane was carried out over Ag/ZSM-5 catalysts, prepared by the wetness impregnation method, and the catalysts were characterized by various techniques. Theoretical calculation was further employed to clarify the reaction mechanism of methane coupling over the catalysts. Ag + ions were found to be the main Ag species at low loading (1-5 wt %) whereas higher loading (10 wt %) resulted in metal clusters. Combined with experimental evidence and computer modeling, it is concluded that isolated Ag + ions play a crucial role in the catalytic coupling of methane under nonoxidative conditions.

Background. Neonatal asphyxia causes long-term neurological and behavioural impairment in the developing brain. Concurrent administration of xenon and hypothermia synergistically reduces long-term damage in a rat model of neonatal asphyxia. This study sought to investigate whether asynchronous administration of xenon and hypothermia is capable of combining synergistically to provide neuroprotection. Methods. Seven-day-old rats were subjected to right common carotid artery occlusion followed by 90 min hypoxia with 8% oxygen. After a 1 h recovery period, rats received asynchronous administration of mild hypothermia (358C) and xenon (20%) with a 1 or 5 h gap between interventions, xenon (20%) alone, or mild hypothermia (358C) alone. Infarct volume in the brain was measured 4 days after injury. Results. Administration of hypothermia or xenon alone, 1 and 6 h after the hypoxic ischaemic insult, respectively, provided no neuroprotection. Asynchronous administration of xenon and hypothermia at a 1 h interval produced a significant reduction in infarct volume [93 (7) vs 74 (8); P,0.05]. Reduction in infarct volume was also present when hypothermia and xenon were asynchronously administered with an intervening gap of 5 h [97 (5) vs 83 (3); P,0.05]. Conclusions. This finding provides a rationale for investigating the combined use of hypothermia and xenon in a progressive manner for the management of neonatal asphyxia. Thus, hypothermia can be administrated at the site of delivery and xenon can be administered later.

Objective: To summarize the experience in the diagnosis and treatment of carotid body tumor (CBT). Materials and Methods: CBT in 18 cases was confi rmed by digital subtraction angiography (DSA). Resection of the tumor under the carotid adventitial plane was performed in 10 cases, the tumor with the external carotid artery in fi ve cases, and the tumor with the internal and external arteries at the same time in three cases. Results: Neither death nor any major complications occurred in all the 18 cases. Our follow-up of the 18 patients revealed neither recurrence nor metastasis. Conclusion: DSA is the gold standard for the diagnosis of CBT. After confi rmation, thorough preoperative examination, suffi cient preoperative preparation, and correct surgical approaches can result in satisfactory surgical effects.

Human transcription factor IIA (TFIIA) is composed of three subunits (alpha, beta, and gamma). TFIIA interacts with the TATA-box binding protein and can overcome repression of transcription. TFIIA was found to be necessary for VP16-mediated transcriptional activation through a coactivator function. We have separated the coactivator and antirepression activities of TFIIA. A TFIIA lacking the alpha subunit was isolated from HeLa cells. This "mini-TFIIA" interacts with the TATA-box binding protein and can overcome repression of transcription, but it is defective in transcriptional coactivator function.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD. We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set. One SNP, rs17321050, in the transducin β-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 × 10-6) and joint analysis (P value = 4.53 × 10-6) in males. The SNP was also close to the replication t...

In this paper, we propose a new hard problem, called bilateral inhomogeneous small integer solution (Bi-ISIS), which can be seen as an extension of the small integer solution problem on lattices. The main idea is that, instead of choosing a rectangle matrix, we choose a square matrix with small rank to generate Bi-ISIS problem without affecting the hardness of the underlying SIS problem. Based on this new problem, we present two new hardness problems: computational Bi-ISIS and decisional problems. As a direct application of these problems, we construct a new lattice-based key exchange (KE) protocol, which is analogous to the classic Diffie-Hellman KE protocol. We prove the security of this protocol and show that it provides better security in case of worst-case hardness of lattice problems, relatively efficient implementations, and great simplicity.

Autism spectrum disorders (ASDs) are highly heritable, yet relatively few associated genetic loci have been replicated. Copy number variations (CNVs) have been implicated in autism; however, the majority of loci contribute to <1% of the disease population. Therefore, independent studies are important to refine associated CNV regions and discover novel susceptibility genes. In this study, a genome-wide SNP array was utilized for CNV detection by two distinct algorithms in a European ancestry case-control data set. We identify a significantly higher burden in the number and size of deletions, and disrupting more genes in ASD cases. Moreover, 18 deletions larger than 1 Mb were detected exclusively in cases, implicating novel regions at 2q22.1, 3p26.3, 4q12 and 14q23. Casespecific CNVs provided further evidence for pathways previously implicated in ASDs, revealing new candidate genes within the GABAergic signaling and neural development pathways. These include DBI, an allosteric binder of GABA receptors, GABARAPL1, the GABA receptor-associated protein, and SLC6A11, a postsynaptic GABA transporter. We also identified CNVs in COBL, deletions of which cause defects in neuronal cytoskeleton morphogenesis in model vertebrates, and DNER, a neuron-specific Notch ligand required for cerebellar development. Moreover, we found evidence of genetic overlap between ASDs and other neurodevelopmental and neuropsychiatric diseases. These genes include glutamate receptors (GRID1, GRIK2 and GRIK4), synaptic regulators (NRXN3, SLC6A8 and SYN3), transcription factor (ZNF804A) and RNA-binding protein FMR1. Taken together, these CNVs may be a few of the missing pieces of ASD heritability and lead to discovering novel etiological mechanisms.

Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P &lt; .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respe...

A novel ␣-particle emitting monoclonal antibody construct targeting the external domain of prostate-specific membrane antigen (PSMA) was prepared and evaluated in vitro and in vivo. The chelating agent, N-[2-amino-3-(p-isothiocyanatophen-yl)propyl]-trans-cyclohexane-1,2-diamine-N,N,N,N,N-pentaacetic acid, was appended to J591 monoclonal antibody to stably bind the 213 Bi radiometal ion. Bismuth-213 is a shortlived (t 1/2 ‫؍‬ 46 min) radionuclide that emits high energy ␣-particles with an effective range of 0.07-0.10 mm that are ideally suited to treating single-celled neoplasms and micrometastatic carcinomas. The LNCaP prostate cancer cell line had an estimated 180,000 molecules of PSMA per cell; J591 bound to PSMA with a 3-nM affinity. After binding, the radiolabeled construct-antigen complex was rapidly internalized into the cell, carrying the radiometal inside. [ 213 Bi]J591 was specifically cytotoxic to LNCaP. The LD 50 value of [ 213 Bi]J591 was 220 nCi/ml at a specific activity of 6.4 Ci/g. The potency and specificity of [ 213 Bi]J591 directed against LNCaP spheroids, an in vitro model for micrometastatic cancer, also was investigated. [ 213 Bi]J591 effectively stopped growth of LNCaP spheroids relative to an equivalent dose of the irrelevant control [ 213 Bi]HuM195 or unlabeled J591. Cytotoxicity experiments in vivo were carried out in an athymic nude mouse model with an i.m. xenograft of LNCaP cells. [ 213 Bi]J591 was able to significantly improve (P < 0.0031) median tumorfree survival (54 days) in these experiments relative to treatment with irrelevant control [ 213 Bi]HuM195 (33 days), or no treatment (31 days). Prostate-specific antigen (PSA) was also specifically reduced in treated animals. At day 51, mean PSA values were 104 ng/ml ؉/؊ 54 ng/ml (n ‫؍‬ 4, untreated animals), 66 ng/ml ؉/؊ 16 ng/ml (n ‫؍‬ 6, animals treated with [ 213 Bi]HuM195), and 28 ng/ml ؉/؊ 22 ng/ml (n ‫؍‬ 6, animals treated with [ 213 Bi]J591). The reduction of PSA levels in mice treated with [ 213 Bi]J591 relative to mice treated with [ 213 Bi]HuM195 and untreated control animals was significant with P < 0.007 and P < 0.0136, respectively. In conclusion, a novel [ 213 Bi]-radiolabeled J591 has been constructed that selectively delivers ␣-particles to prostate cancer cells for potent and specific killing in vitro and in vivo.

Hasselmo, Michael E., Christiane Linster, Madhvi Patil, Daveena Ma, and Milos Cekic. Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio. J. Neurophysiol. 77: 3326–3339, 1997. Norepinephrine has been proposed to influence signal-to-noise ratio within cortical structures, but the exact cellular mechanisms underlying this influence have not been described in detail. Here we present data on a cellular effect of norepinephrine that could contribute to the influence on signal-to-noise ratio. In brain slice preparations of the rat piriform (olfactory) cortex, perfusion of norepinephrine causes a dose-dependent suppression of excitatory synaptic potentials in the layer containing synapses among pyramidal cells in the cortex (layer Ib), while having a weaker effect on synaptic potentials in the afferent fiber layer (layer Ia). Effects of norepinephrine were similar in dose-response characteristics and laminar selectivity to the effects of the chol...

Thioethers Q 0580 CuI-Catalyzed Coupling Reactions of Aryl Iodides and Bromides with Thiols Promoted by Amino Acid Ligands.-Under optimized coupling conditions, good to excellent yields of the corresponding aryl sulfides are obtained. In the case of (IIb) both the bromo and the iodo group participate in the C-S coupling under conditions B), whereas the chloro group in thiol (If) is not affected.

Rates of admission for invasive Streptococcus pneumoniae infection in children vary considerably between institutions. We performed a retrospective study to investigate factors used in the decision to admit patients with invasive S. pneumoniae infection to Alberta Children's Hospital. Of 254 patients who were initially assessed in the emergency department, 38.2% were admitted to the hospital. Significant risk factors for admission as determined by a logistic regression model included murmur (odds ratio [OR], 18.98; 95% confidence interval [CI], 4.08-88.23), focal infection (OR, 11.41; 95% CI, 5.07-25.67), and older age (OR, 2.72; 95% CI, 1.03-7.17). Higher hemoglobin level (OR, 0.96; 95% CI, 0.93-0.99) and temperature of ú38.5ЊC (OR, 0.39; 95% CI, 0.18-0.85) were associated with a lower risk of admission. Two patients died (case-fatality rate, 0.7%). Despite the low rate of admission for invasive S. pneumoniae infections at our hospital, the mortality rate was comparable with those at institutions with higher rates of admission, thus suggesting that the factors we identified may be useful in deciding whether to admit patients with (or who are at high risk for) invasive S. pneumoniae infections.

Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m 2 and rHUG-CSF 150 mg/m 2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 × 10 6 /kg CD34 þ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score у1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P ¼ 0. 006 and 0. 02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poorprognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.

Directed by the temperature-induced phase transformation in the alkane (from heptane to dodecane)-P123-water-TEOS quadru-component system, i.e., from a swollen inverse hexagonal phase (H 2) to a swollen lamellar phase (L α) and then to a swollen normal micelles phase (L 1), complex silica materials, such as mesoporous nanofibres, multilamellar vesicles (MLVs) and mesocellular foams (MCFs), are constructed.