Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia.

BACKGROUND: Pulmonary hypertension (PH) in patients with bronchopulmonary dysplasia (BPD) results from vasoconstriction and/or vascular remodeling, which can be regulated by mitogen-activated protein kinases (MAPKs). MAPKs are deactivated by dual-specificity phosphatases (DUSPs). We hypothesized that single-nucleotide polymorphisms (SNPs) in DUSP genes could be used to predict PH in BPD. METHODS: Preterm infants diagnosed with BPD (n = 188) were studied. PH was defined by echocardiographic criteria. Genomic DNA isolated from patient blood samples was analyzed for 31 SNPs in DUSP genes. Clinical characteristics and minor allele frequencies were compared between BPD-PH (cases) and BPD-without PH (control) groups. Biomarker models to predict PH in BPD using clinical and SNP data were tested by calculations of area under the ROC curve. RESULTS: In our BPD cohort, 32% (n = 61) had PH. Of the DUSP SNPs evaluated, DUSP1 SNP rs322351 was less common, and DUSP5 SNPs rs1042606 and rs3793892 were more common in cases than in controls. The best fit biomarker model combines clinical and DUSP genetic data with an area under the ROC curve of 0.76. CONCLUSION: We identified three DUSP SNPs as potential BPD-PH biomarkers. Combining clinical and DUSP genetic data yields the most robust predictor for PH in BPD.

The h-Sbx WO3+2x Oxygen Excess Antimony Tungsten Bronze.

We describe the previously unreported oxygen excess hexagonal antimony tungsten bronze is reported, with a composition of Sb0.5 W3 O10 , in the following denoted as h-Sbx WO3+2x with x=0.167, to demonstrate its analogy to classical Ax WO3 tungsten bronzes. This compound forms in a relatively narrow temperature range between 580 °C

Single-Crystal Growth and Characterization of the Chalcopyrite Semiconductor CuInTe2 for Photoelectrochemical Solar Fuel Production.

Transition-metal chalcogenides are a promising family of materials for applications as photocathodes in photoelectrochemical (PEC) H2 generation. A long-standing challenge for chalcopyrite semiconductors is characterizing their electronic structure, both experimentally and theoretically, because of their relatively high-energy band gaps and spin-orbit coupling (SOC), respectively. In this work, we present single crystals of CuInTe2, whose relatively small optically measured band gap of 0.9 ± 0.03 eV enables electronic structure characterization by angle-resolved photoelectron spectroscopy (ARPES) in conjunction with first-principles calculations incorporating SOC. ARPES measurements reveal bands that are steeply dispersed in energy with a band velocity of 2.5-5.4 × 105 m/s, almost 50% of the extremely conductive material graphene. Additionally, CuInTe2 single crystals are fabricated into electrodes to experimentally determine the valence band edge energy and confirm the thermodynamic suitability of CuInTe2 for water redox chemistry. The electronic structure characterization and band edge position presented in this work provide kinetic and thermodynamic factors that support CuInTe2 as a strong candidate for water reduction.

A single nucleotide polymorphism in the dimethylarginine dimethylaminohydrolase gene is associated with lower risk of pulmonary hypertension in bronchopulmonary dysplasia.

AIM: Pulmonary hypertension (PH) develops in 25-40% of bronchopulmonary dysplasia (BPD) patients, substantially increasing mortality. We have previously found that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) production, is elevated in patients with BPD-associated PH. ADMA is metabolised by N(á´³) ,N(á´³) -dimethylarginine dimethylaminohydrolase (DDAH). Presently, we test the hypothesis that there are single nucleotide polymorphisms (SNPs) in DDAH1 and/or DDAH2 associated with the development of PH in BPD patients. METHODS: BPD patients were enrolled (n = 98) at Nationwide Children's Hospital. Clinical characteristics and 36 SNPs in DDAH1 and DDAH2 were compared between BPD-associated PH patients (cases) and BPD-alone patients (controls). RESULTS: In BPD patients, 25 (26%) had echocardiographic evidence of PH (cases). In this cohort, DDAH1 wild-type rs480414 was 92% sensitive and 53% specific for PH in BPD, and the DDAH1 SNP rs480414 decreased the risk of PH in an additive model of inheritance (OR = 0.39; 95% CI [0.18-0.88], p = 0.01). CONCLUSION: The rs480414 SNP in DDAH1 may be protective against the development of PH in patients with BPD. Furthermore, the DDAH1 rs480414 may be a useful biomarker in developing predictive models for PH in patients with BPD.

Controlling pharmaceutical crystallization with designed polymeric heteronuclei.

To investigate the hypothesis that molecules acting as crystallization inhibitors in solution could be transformed into crystallization promoters, additives were synthesized that mimic the pharmaceuticals acetaminophen and mefenamic acid and also possess polymerizable functionality. It was found that, in solution, these additives face-selectively inhibit crystal growth and lead to overall slower crystal appearance. In contrast, when the tailor-made additives were incorporated into an insoluble polymer, the induction time for the onset of crystal formation for both pharmaceuticals was substantially decreased. This approach now allows for the synthesis of tailor-made polymers that decrease the induction time for crystal appearance and may find application in compounds that are resistant to crystallization or in improving the fidelity of heteronucleation approaches to solid form discovery.

Apolipoprotein E4 as a predictor of outcomes in pediatric mild traumatic brain injury.

The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large children's hospitals. Outcomes were assessed acutely in the Emergency Department and at follow-ups at 2 weeks, 3 months, and 12 months post-injury. Among the 99 participants, 28 had at least one epsilon4 allele. Children with and without an epsilon4 allele did not differ demographically. Children with an epsilon4 allele were significantly more likely than those without an epsilon4 allele to have a Glasgow Coma Scale score of less than 15, but the groups did not differ on any other measures of injury severity. Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children.

O6-methylguanine-DNA methyltransferase activity and promoter methylation status in pediatric rhabdomyosarcoma.

OBJECTIVES: To determine the activity of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) and MGMT promoter methylation status of pediatric rhabdomyosarcoma (RMS) and examine MGMT in RMS tumors from different prognostic groups. METHODS: Fifteen samples each of the alveolar (ARMS) and embryonal (ERMS) subtypes were obtained for analysis of MGMT activity and promoter methylation status. MGMT activity was assayed by measuring the removal of O6-[3H] methylguanine from [3H]-methylated substrate by a tumor extract containing the enzyme. Promoter methylation status was examined using methylation-specific polymerase chain reaction (PCR). RESULTS: MGMT activity was successfully assayed from 25 samples, 10 ERMS and 15 ARMS. All ERMS and 11 of the 15 ARMS samples displayed high activity levels. There was significant intertumor variability among both subtypes but no significant difference in mean activity between the two histologic groups. There were trends toward increased activity in ERMS tumors and tumors from anatomically unfavorable locations. Only one tumor was hypermethylated at the MGMT promoter region. CONCLUSIONS: This analysis suggests that a low percentage of RMS samples are hypermethylated at the MGMT promoter and that most have significant MGMT activity, implying that clinical trials with MGMT-modulating agents may have a role in the treatment of these tumors. This analysis does not support MGMT activity as an explanation of the differential response to chemotherapy demonstrated by ARMS and ERMS, but does suggest that MGMT may be involved in RMS treatment failure regardless of subtype and in the poorer response shown by tumors from unfavorable locations.