Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD

Fabrication of super-hydrophobic nickel film on copper substrate with improved corrosion inhibition by electrodeposition process

Inspired by the famous “lotus effect”, we have fabricated the super-hydrophobic surfaces with nickel film on copper substrates using a one-step electrodeposition method. By adjusting processing time, water contact angle of as-prepared surfaces can reach as high as 160.3 ± 1.5° with small rolling angle of 3.0 ± 0.5°, showing excellent super-hydrophobicity. After the deposition of nickel coating, the pristine copper surfaces became much rough with packed cauliflower-/thorn-like clusters. This unique surface texture contributed to trapping large amount of air and forming the air cushion underneath the water droplet, which can prevent the liquids contacting the copper substrate. The examination of surface chemical compositions implied that the deposited super-hydrophobic coating consisted of nickel crystals and nickel myristate. In this research, the formation mechanism of the electrodeposited super-hydrophobicity was extensively explained based on the analyses of surface texture and surface chemistry. Moreover, the corrosion resistance of the as-fabricated super-hydrophobic surface was estimated by the potentiodynamic polarization tests as well as the electrochemical impedance spectroscopy (EIS) measurements. The results demonstrate that the super-hydrophobic nickel coating showed excellent corrosion inhibition in simulated seawater solution. The existence of the super-hydrophobic coating could be regarded as a barrier and thus provide a perfect air-liquid interface that inhibits the penetration of the corrosive ions. This facile and effective method of electrodeposition process offers a promising approach for mass production of super-hydrophobic surfaces on various metals

Few-body resonances in light nuclei

We have localized several few-body resonances in light nuclei, using methods which can properly handle two- or three-body resonant states. Among other results, we predict the existence of a three-neutron resonance, small spin-orbit splittings between the low-lying states in He-5 and Li-5, the nonexistence of the soft dipole resonance in He-6, new 1+ states in Li-8 and B-8, and the presence of a nonlinear amplification phenomenon in the 0+_2 state of C-12

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries