Description: We conducted blinded psychiatric assessments of 26 Amish subjects (52 ± 11 years) from four families with prevalent bipolar spectrum disorder, identified 10 potentially pathogenic alleles by exome sequencing, tested association of these alleles with clinical diagnoses in the larger Amish Study of Major Affective Disorder (ASMAD) cohort, and studied mutant potassium channels in neurons. Fourteen of 26 Amish had bipolar spectrum disorder. The only candidate allele shared among them was rs78247304, a non-synonymous variant of KCNH7 (c.1181G〉A, p.Arg394His). KCNH7 c.1181G〉A and nine other potentially pathogenic variants were subsequently tested within the ASMAD cohort, which consisted of 340 subjects grouped into controls subjects and affected subjects from overlapping clinical categories (bipolar 1 disorder, bipolar spectrum disorder and any major affective disorder). KCNH7 c.1181G〉A had the highest enrichment among individuals with bipolar spectrum disorder ( 2 = 7.3) and the strongest family-based association with bipolar 1 ( P = 0.021), bipolar spectrum ( P = 0.031) and any major affective disorder ( P = 0.016). In vitro, the p.Arg394His substitution allowed normal expression, trafficking, assembly and localization of HERG3/Kv11.3 channels, but altered the steady-state voltage dependence and kinetics of activation in neuronal cells. Although our genome-wide statistical results do not alone prove association, cumulative evidence from multiple independent sources (parallel genome-wide study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data) implicates neuronal HERG3/Kv11.3 potassium channels in the pathophysiology of bipolar spectrum disorder. Such a finding, if corroborated by future studies, has implications for mental health services among the Amish, as well as development of drugs that specifically target HERG3/Kv11.3.

Description: Prospective qualitative and quantitative non-invasive evaluation of intestinal acute GVHD by contrast-enhanced ultrasound sonography Bone Marrow Transplantation 48, 1421 (November 2013). doi:10.1038/bmt.2013.65 Authors: E Benedetti, B Bruno, G B McDonald, A Paolicchi, F Caracciolo, F Papineschi, M Pelosini, D Campani, S Galimberti & M Petrini

Description: Increasingly researchers are looking to bring together perspectives across multiple scales, or to combine insights from different techniques, for the same region of interest. To this end, correlative microscopy has already yielded substantial new insights in two dimensions (2D). Here we develop correlative tomography where the correlative task is somewhat more challenging because the volume of interest is typically hidden beneath the sample surface. We have threaded together x-ray computed tomography, serial section FIB-SEM tomography, electron backscatter diffraction and finally TEM elemental analysis all for the same 3D region. This has allowed observation of the competition between pitting corrosion and intergranular corrosion at multiple scales revealing the structural hierarchy, crystallography and chemistry of veiled corrosion pits in stainless steel. With automated correlative workflows and co-visualization of the multi-scale or multi-modal datasets the technique promises to provide insights across biological, geological and materials science that are impossible using either individual or multiple uncorrelated techniques. Scientific Reports 4 doi: 10.1038/srep04711

Description: Background Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. Methods Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. Results Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid ( 2 1 =0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression ( 2 1 = 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively ( 2 1 = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group ( 2 1 = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald 2 = 9.16; P = .003) but not 5-fluorouracil–treated (Wald 2 = 1.22; P = .27) patients. Conclusions Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Description: The new mineral whelanite, Cu 2 Ca 6 [Si 6 O 17 (OH)](CO 3 )(OH) 3 (H 2 O) 2 , was approved by the Commission on New Minerals and Mineral Names (IMA) in 1977, but until now a description has not been published. The mineral is orthorhombic with space group Pn 2 n and cell parameters a = 5.6551(4), b = 3.683(3), c = 27.1372(7) Å, V = 565.3(5) Å 3 , and Z = 1. The mineral occurs with thaumasite, stringhamite, and kinoite in a copper-rich, diopside–garnet–magnetite skarn at the Bawana mine, Beaver County, Utah, and has also been confirmed to occur at other localities. At the Bawana mine, it is found as irregular clusters and radial aggregates of platy to lath-like crystals up to 1 mm in length, flattened on {001} and elongated on [100]. The color and streak are pale blue and the luster is vitreous. The laths are flexible, but not elastic. Cleavage is perfect on {001} and good on {010}, producing splintery fracture. The Mohs’ hardness is about 21/2. The measured density is 2.74(3) g/cm 3 and the calculated density is 2.737 g/cm 3 based upon the empirical formula. The mineral is biaxial (–), α = 1.612(2), β = 1.622(calc), and = 1.626(2), and 2 V meas = 64(1)°. The pleochroism is weak: X = Y (pale blue) 〈 Z (light blue). The optical orientation is X = a , Y = c , Z = b . A combination of electron microprobe analyses and thermogravimetric analyses (for CO 2 and H 2 O) yielded: CaO 34.46, CuO 12.09, FeO 1.52, SiO 2 37.96, CO 2 5.93, H 2 O 8.86, total 100.82 wt%, providing the empirical formula (based on O = 26): Cu 1.41 Fe 0.20 Ca 5.68 Si 5.84 C 1.25 O 26 H 9.09 . Raman spectroscopy shows evidence of (CO 3 ) 2– , (OH) – , and H 2 O. The strongest powder X-ray diffraction lines are [ d ( hkl ) I ]: 6.79(004)52, 3.072(111)43, 3.013(112)100, 2.921(113)39, 2.802(114)45, 2.522(116,205)44, and 1.839(020,1.1.12)37. The crystal structure ( R 1 = 3.89% for 567 F o 〉 4 F ) contains two different types of polyhedral layers parallel to {001}, which alternate along [001] and are linked to one another by sharing corners with wollastonite-like silicate chains running parallel [010]. One polyhedral layer, consisting of edge-sharing CaO 7 polyhedra, is identical to that in the structures of the tobermorites (tobermorite 9Å, tobermorite 11Å, tobermorite 14Å, and clinotobermorite). The other layer is brucite-like, with alternating ribbons of edge-sharing Cu 2+ O 6 and CaO 6 octahedra. Disordered CO 3 and H 2 O groups are also located in the interlayer region. The crystal structure of whelanite exhibits OD character.