A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS

Vertical distribution and diet of Stenobrachius nannochir (Myctophidae) in the southern Bering Sea, summer, 1987

The vertical distribution and diet of the myctophid species Stenobrachius nannochir were examined on samples collected at various mesopelagic depths (>600m) day and night in the southern Bering Sea, in June and July 1987. This species exhibited no diel variation in vertical distribution, remaining at a depth of about 600m. Stomachs were examined from 226 specimens. The diet was dominated by copepoda, mostly Calanus plumchrus, Calanus cristatus, Eucalanus bungii bungii and Metridia pacifica. The stomach fullness and prey digestive stage indicated little evidence of feeding periodicity, suggesting that S. nannochir is an acyclic predator among the family Myctophidae. The acyclic feeding by this non-migrating myctophid appears to adapt it to exploit efficiently the broad vertical distribution and abundance of prey in the subarctic Pacific Ocean

Contrast-enhanced magnetic resonance pancreatography with gadoteridol by heavily T2-weighted three-dimensional fluid-attenuated inversion recovery: preliminary results in healthy subjects

The purpose of this study was to investigate the feasibility of contrast-enhanced magnetic resonance (MR) pancreatography with intravenously administered gadolinium-based contrast material (GBCM) in healthy subjects. Eight healthy male subjects (age: 29–53 years old, median: 37 years old) were enrolled. Contrast-enhanced MR pancreatography was scanned with heavily T2-weighted three-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) before and after intravenous GBCM administration. Two radiologists evaluated the images, referring to three-dimensional MR pancreatography by consensus. Scanning was performed five times at 1.5-h intervals (at 0.5, 2, 3.5, 5, and 6.5 h) after GBCM administration. In all subjects, pre-contrast-enhanced hT2W-3D-FLAIR images demonstrated no visualization of the main pancreatic duct. After GBCM administration, the main pancreatic duct was visualized in all subjects at 0.5 h (n=4, 50%) and/or 2 h (n=7, 88%). The mean signal intensity of the main pancreatic duct was 3.17 ± 0.78 at pre-contrast enhancement, 7.96 ± 4.60 at 0.5 h, and 8.08 ± 4.64 at 2 h. The signal intensity ratio of the main pancreatic duct against the pancreatic parenchyma was statistically higher (P < 0.01) at the 0.5-h and 2-h scans than that of pre-contrast-enhanced scan. Intravenously administered GBCM seeped into the pancreatic duct in sufficient concentration to alter the appearance of the main pancreatic duct by hT2W-3D-FLAIR in healthy subjects

Macrophage mannose receptor, CD206, predict prognosis in patients with pulmonary tuberculosis

Abstract Tuberculosis (TB) remains a leading cause of fatal infectious disease. Accumulations of macrophages are found in infected sites; thus, we hypothesized that a marker of activated macrophages may be related to prognosis of pulmonary TB (PTB). This study investigated serum soluble macrophage mannose receptor, sCD206, in PTB and examined its clinical significance. First, the concentration of sCD206 was measured in the sera of 96 patients with PTB (Tenryu cohort), and in pleural effusions from 29 patients with TB pleurisy. These were verified in another independent cohort (Shizuoka cohort). We found increased concentrations of sCD206 in sera, but not in pleural effusions of PTB patients. Notably, PTB patients with poor prognosis showed significantly higher levels of serum sCD206. At a cut-off value of 1,600 ng/mL in the Tenryu cohort, sCD206 predicted prognosis of PTB with area under the curve 0.847, sensitivity 77.3%, and specificity 86.5%. These results were validated in the Shizuoka cohort. Pathological analyses showed concordance of enhanced CD206 expression in lung and pleural tissues with caseating granuloma in TB. Serum sCD206 increased in PTB and was associated with prognosis. sCD206 is a potential biomarker for PTB