European Red List of Habitats Part 1. Marine habitats

The European Red List of Habitats provides an overview of the risk of collapse (degree of endangerment) of marine, terrestrial and freshwater habitats in the European Union (EU28) and adjacent regions (EU28+), based on a consistent set of categories and criteria, and detailed data and expert knowledge from involved countries1. A total of 257 benthic marine habitat types were assessed. In total, 19% (EU28) and 18% (EU28+) of the evaluated habitats were assessed as threatened in categories Critically Endangered, Endangered and Vulnerable. An additional 12% were Near Threatened in the EU28 and 11% in the EU28+. These figures are approximately doubled if Data Deficient habitats are excluded. The percentage of threatened habitat types differs across the regional seas. The highest proportion of threatened habitats in the EU28 was found in the Mediterranean Sea (32%), followed by the North-East Atlantic (23%), the Black Sea (13%) and then the Baltic Sea (8%). There was a similar pattern in the EU28+. The most frequently cited pressures and threats were similar across the four regional seas: pollution (eutrophication), biological resource use other than agriculture or forestry (mainly fishing but also aquaculture), natural system modifications (e.g. dredging and sea defence works), urbanisation and climate change. Even for habitats where the assessment outcome was Data Deficient, the Red List assessment process has resulted in the compilation of a substantial body of useful information to support the conservation of marine habitats

Euclid preparation. Spectroscopy of active galactic nuclei with NISP

The statistical distribution and evolution of key properties (e.g. accretion rate, mass, or spin) of active galactic nuclei (AGN), remain an open debate in astrophysics. The ESA Euclid space mission, launched on July 1st 2023, promises a breakthrough in this field. We create detailed mock catalogues of AGN spectra, from the rest-frame near-infrared down to the ultraviolet, including emission lines, to simulate what Euclid will observe for both obscured (type 2) and unobscured (type 1) AGN. We concentrate on the red grisms of the NISP instrument, which will be used for the wide-field survey, opening a new window for spectroscopic AGN studies in the near-infrared. We quantify the efficiency in the redshift determination as well as in retrieving the emission line flux of the H$\alpha$+[NII] complex as Euclid is mainly focused on this emission line as it is expected to be the brightest one in the probed redshift range. Spectroscopic redshifts are measured for 83% of the simulated AGN in the interval where the H$\alpha$+[NII] is visible (0.89<z<1.83 at a line flux $>2x10^{-16}$ erg s$^{-1}$ cm$^{-2}$, encompassing the peak of AGN activity at $z\simeq 1-1.5$) within the spectral coverage of the red grism. Outside this redshift range, the measurement efficiency decreases significantly. Overall, a spectroscopic redshift is correctly determined for ~90% of type 2 AGN down to an emission line flux of $3x10^{-16}$ erg s$^{-1}$ cm$^{-2}$, and for type 1 AGN down to $8.5x10^{-16}$ erg s$^{-1}$ cm$^{-2}$. Recovered black hole mass values show a small offset with respect to the input values ~10%, but the agreement is good overall. With such a high spectroscopic coverage at z<2, we will be able to measure AGN demography, scaling relations, and clustering from the epoch of the peak of AGN activity down to the present-day Universe for hundreds of thousand AGN with homogeneous spectroscopic information.Comment: 29 pages, 23 figures. Submitted to A&A, revised versio

An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD

Euclid preparation: XXXVIII. Spectroscopy of active galactic nuclei with NISP

The statistical distribution and evolution of key properties of active galactic nuclei (AGN), such as their accretion rate, mass, and spin, remains a subject of open debate in astrophysics. The ESA Euclid space mission, launched on July 1 2023, promises a breakthrough in this field. We create detailed mock catalogues of AGN spectra from the rest-frame near-infrared down to the ultraviolet -including emission lines -to simulate what Euclid will observe for both obscured (type 2) and unobscured (type 1) AGN. We concentrate on the red grisms of the NISP instrument, which will be used for the wide-field survey, opening a new window for spectroscopic AGN studies in the near-infrared. We quantify the efficiency in the redshift determination as well as in retrieving the emission line flux of the Hα+[N II] complex, as Euclid is mainly focused on this emission line, given that it is expected to be the brightest one in the probed redshift range. Spectroscopic redshifts are measured for 83% of the simulated AGN in the interval where the Hα is visible (i.e. 0.89 &lt; z &lt; 1.83 at a line flux of &gt; 2 × 10-16 erg s-1 cm-2, encompassing the peak of AGN activity at z ≃ 1 - 1.5) within the spectral coverage of the red grism. Outside this redshift range, the measurement efficiency decreases significantly. Overall, a spectroscopic redshift iscorrectly determined for about 90% of type 2 AGN down to an emission line flux of roughly 3 × 10-16 erg s-1 cm-2, and for type 1 AGN down to 8.5 × 10-16 erg s-1 cm-2. Recovered values for black hole mass show a small offset with respect to the input values by about 10%, but the agreement is good overall. With such a high spectroscopic coverage at z &lt; 2, we will be able to measure AGN demography, scaling relations, and clustering from the epoch of the peak of AGN activity down to the present-day Universe for hundreds of thousands of AGN with homogeneous spectroscopic information

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18–94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

A data-driven examination of apathy and depressive symptoms in dementia with independent replication

Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found in the Appendix and at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdfSupporting Information is available online at: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/dad2.12398#support-information-section .Copyright © 2023 The Authors. Apathy is one of the most common neuropsychiatric symptoms (NPS) and is associated with poor clinical outcomes. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies. We used latent class analysis (LCA) with two independent cohorts to understand how apathy and depression symptoms co-occur statistically. We further explored the relationship between latent class membership, demographics, and the presence of other NPS. The LCA identified a four-class solution (no symptoms, apathy, depression, and combined apathy/depression), reproducible over both cohorts, providing robust support for an apathy syndrome distinct from depression and confirming that an apathy/depression syndrome exists, supported by the model fit test with the four-class solution scores evidencing better fitting (Bayesian information criterion adjusted and entropy R2). Using a data-driven method, we show distinct and statistically meaningful co-occurrence of apathy and depressive symptoms. There was evidence that these classes have different clinical associations, which may help inform diagnostic categories for research studies and clinical practice. Highlights: * We found four classes: no symptoms, apathy, depression and apathy/depression. * Apathy conferred a higher probability for agitation. * Apathy diagnostic criteria should include accompanying neuropsychiatric symptoms.This paper represents independent research partly funded by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. This study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California