Assessment of pollution prevention and control technology for plating operations

The National Center for Manufacturing Sciences (NCMS) is sponsoring an on-going project to assess pollution prevention and control technology available to the plating industry and to make this information available to those who can benefit from it. Completed project activities include extensive surveys of the plating industry and vendors of technologies and an indepth literature review. The plating industry survey was performed in cooperation with the National Association of Metal Finishers. The contractor that conducted the surveys and prepared the project products was CAI Engineering. The initial products of the project were made available in April, 1994. These products include an extensive report that presents the results of the surveys and literature review and an electronic database. The project results are useful for all those associated with pollution prevention and control in the plating industry. The results show which treatment, recovery and bath maintenance technologies have been most successful for different plating processes and the costs for purchasing and operating these technologies. The project results also cover trends in chemical substitution, the identification of compliance-problem pollutants, sludge generation rates, off-site sludge recovery and disposal options, and many other pertinent topics

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.</p

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Publisher Copyright: © 2023, The Author(s).Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.Peer reviewe

Cluster headache genome-wide association study and meta-analysis identifies eight loci and implicates smoking as causal risk factor.

OBJECTIVE: Aggregating data for the first genome-wide association study meta-analysis of cluster headache, to identify genetic risk variants and gain biological insights. METHODS: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from ten European and one East Asian cohorts. We first performed an inverse-variance genome-wide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by five complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis and Mendelian randomization were part of the downstream analyses. RESULTS: The estimated SNP-based heritability of cluster headache was 14.5%. We identified nine independent signals in seven genome-wide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, ADHD, depression and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. INTERPRETATION: This first genome-wide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. This article is protected by copyright. All rights reserved

Effect of Photoperiod on Developmental Morphology and Enolase Isoenzyme Immunohistochemistry in Rat and Djungarian Hamster Superficial Pineal Glands

The best understood functional activity of the pineal gland is its diurnal production of melatonin in response to environmental lighting cues. Several enzymes of the melatonin pathway respond to daily photoperiod changes, for example hydroxyindole-O-methyltransferase (HIOMT) and serotonin N-acetyltransferase (SNAT). Increased levels of the glycolytic enzyme neuron-specific enolase (NSE) are thought to reflect increased physiological demands placed on neurons and neuroendocrine tissues. Homodimer non-neuronal enolase isoenzyme (NNE) is immunolocalized to cells, and the hybrid enolase (consisting of subunits from NSE and NNE) has been seen in cerebellar stellate and basket cells. Although not rate limiting, concentrations of both NSE and NNE in the rat pineal gland rival that of the forebrain. The rat pinealocytes demonstrates a mosaic pattern of immunostaining for the NSE antigen. Furthermore, an increasing proximal to distal immunostaining gradient has been reported in the gland. In this study, it was hypothesized that structural and immunohistochemical differences represent pinealocyte heterogenous functional activity. This was tested in two rodent populations (rats and Djungarian hamsters) by means of evaluating the effect of photoperiod manipulation on morphological development and immunohistochemical localization of enolase isoenzymes. Djungarian hamsters respond well to photoperiod changes, while laboratory rats are thought to be insensitive to environmental lighting changes. The effect of photoperiod in the hamster was confirmed by significantly different (p \u3c 0.01) body and testes weights for animals housed under the two different photoperiods (long day, 16L:8D; short day 6L:18D). In addition, rats exposed to the long day photoperiod (12L:12D) had significantly greater body and testes weights (p \u3c 0.05) than animals raised under the short day photoperiod (6L:18D). Photoperiod also influenced pineal gland soluble protein, protein concentration, and NSE concentration in both species. Generally, the levels were greatest in extracts from the glands of animals subjected to the short day environment. Gel electrophoresis revealed a protein or group of proteins that were particularly responsive to changes in environmental lighting; the estimated molecular weight was 80 kD. In both species, NNE exhibited the same heterogenous immunostaining as NSE, and was localized to the same pinealocytes in adjacent sections. The preceding strongly suggests that the hybrid enolase is found in the rat and hamster pineal gland. If so, this may reflect a balance between simultaneous expression of the NSE and NNE genes. The NSE increasing proximal to distal immunostaining gradient was repeated by NNE in the rat gland, but it was in the opposite direction for the hamster. Morphological features, however, may have contributed to the gradient nature of enolase isoenzyme immunostaining, in that regional nuclear and blood vessel volume fractions were influenced by photoperiod