Clear-sky closure studies of lower tropospheric aerosol and water vapor during ACE-2 using airborne sunphotometer, airborne in-situ, space-borne, and ground-based measurements

We report on clear-sky column closure experiments (CLEARCOLUMN) performed in the Canary Islands during the second Aerosol Characterization Experiment (ACE-2) in June/July 1997. We present CLEARCOLUMN results obtained by combining airborne sunphotometer and in-situ (optical particle counter, nephelometer, and absorption photometer) measurements taken aboard the Pelican aircraft, space-borne NOAA/AVHRR data and ground-based lidar and sunphotometer measurements. During both days discussed here, vertical profiles flown in cloud-free air masses revealed 3 distinctly different layers: a marine boundary layer (MBL) with varying pollution levels, an elevated dust layer, and a very clean layer between the MBL and the dust layer. A key result of this study is the achievement of closure between extinction or layer aerosol optical depth (AOD) computed from continuous in-situ aerosol size-distributions and composition and those measured with the airborne sunphotometer. In the dust, the agreement in layer AOD (λ=380–1060 nm) is 3–8%. In the MBL there is a tendency for the in-situ results to be slightly lower than the sunphotometer measurements (10–17% at λ=525 nm), but these differences are within the combined error bars of the measurements and computations

Sustainable drainage system site assessment method using urban ecosystem services

The United Kingdom's recently updated approach to sustainable drainage enhanced biodiversity and amenity objectives by incorporating the ecosystem approach and the ecosystem services concept. However, cost-effective and reliable methods to appraise the biodiversity and amenity values of potential sustainable drainage system (SuDS)sites and their surrounding areas are still lacking, as is a method to enable designers to distinguish and link the amenity and biodiversity benefits that SuDS schemes can offer. In this paper, therefore, the authors propose two ecosystem services- and disservices-based methods (i.e. vegetation structure cover-abundance examination and cultural ecosystem services and disservices variables appraisal) to aid SuDS designers to distinguish and link amenity and biodiversity benefits, and allow initial site assessments to be performed in a cost-effective and reliable fashion. Forty-nine representative sites within Greater Manchester were selected to test the two methods. Amenity and biodiversity were successfully assessed and habitat for species, carbon sequestration, recreation and education ecosystem services scores were produced,which will support SuDS retrofit design decision-making. Large vegetated SuDS sites with permanent aquatic features were found to be most capable of enhancing biodiversity- and amenity-related ecosystem services. Habitat for species and recreation ecosystem services were also found to be positively linked to each other. Finally, waste bins on site were found to help reduce dog faeces and litter coverage. Overall, the findings presented here enable future SuDS retrofit designs to be more wildlife friendly and socially inclusive

Developing an Integrated Ocean Observing System for New Zealand

New Zealand (NZ) is an island nation with stewardship of an ocean twenty times larger than its land area. While the challenges facing NZ’s ocean are similar to other maritime countries, no coherent national plan exists that meets the needs of scientists, stakeholders or kaitiakitanga (guardianship) of NZ’s ocean in a changing climate. The NZ marine science community used the OceanObs’19 white paper to establish a framework and implementation plan for a collaborative NZ ocean observing system (NZ-OOS). Co-production of ocean knowledge with Māori will be embedded in this national strategy for growing a sustainable, blue economy for NZ. The strengths of an observing system for a relatively small nation come from direct connections between the science impetus through to users and stakeholders of an NZ-OOS. The community will leverage off existing ocean observations to optimize effort and resources in a system that has historically made limited investment in ocean observing. The goal of the community paper will be achieved by bringing together oceanographers, data scientists and marine stakeholders to develop an NZ-OOS that provides best knowledge and tools to the sectors of society that use or are influenced by the ocean

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

A high-throughput <em>O</em>-glycopeptide discovery platform for seromic profiling

Biomarker microarrays are becoming valuable tools for serological screening of disease-associated autoantibodies. Post-translational modifications (PTMs) such as glycosylation extend the range of protein function, and a variety of glycosylated proteins are known to be altered in disease progression. Here, we have developed a synthetic screening microarray platform for facile display of O-glycosylated peptides (O-PTMs). By introducing a capping step during chemical solid-phase glycopeptide synthesis, selective enrichment of N-terminal glycopeptide end products were achieved on an amine-reactive hydrogel coated microarray glass surface, allowing high-throughput display of large numbers of glycopeptides. Utilizing a repertoire of recombinant glycosyltransferases enabled further diversification of the array libraries in-situ and display of a new level of potential biomarker candidates for serological screening. As proof-of-concept we have demonstrated that MUC1 glycopeptides could be assembled and used to detect autoantibodies in vaccine induced disease free breast cancer patients and in patients, with confirmed disease at time of diagnosis