Sub-stellar companions of intermediate-mass stars with CoRoT: CoRoT–34b, CoRoT–35b, and CoRoT–36b

Theories of planet formation give contradicting results of how frequent close-in giant planets of intermediate mass stars (IMSs; 1.3≤M⋆≤3.2M⊙⁠) are. Some theories predict a high rate of IMSs with close-in gas giants, while others predict a very low rate. Thus, determining the frequency of close-in giant planets of IMSs is an important test for theories of planet formation. We use the CoRoT survey to determine the absolute frequency of IMSs that harbour at least one close-in giant planet and compare it to that of solar-like stars. The CoRoT transit survey is ideal for this purpose, because of its completeness for gas-giant planets with orbital periods of less than 10 d and its large sample of main-sequence IMSs. We present a high precision radial velocity follow-up programme and conclude on 17 promising transit candidates of IMSs, observed with CoRoT. We report the detection of CoRoT–34b, a brown dwarf close to the hydrogen burning limit, orbiting a 1.1 Gyr A-type main-sequence star. We also confirm two inflated giant planets, CoRoT–35b, part of a possible planetary system around a metal-poor star, and CoRoT–36b on a misaligned orbit. We find that 0.12±0.10 per cent of IMSs between 1.3≤M⋆≤1.6M⊙ observed by CoRoT do harbour at least one close-in giant planet. This is significantly lower than the frequency (⁠0.70±0.16 per cent⁠) for solar-mass stars, as well as the frequency of IMSs harbouring long-period planets (⁠∼8 per cent⁠)

Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer’s disease: a voxel-based lesion mapping study

Introduction: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer’s disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD. Methods: WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network. Results: WM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance. Conclusion: The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk

The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

BACKGROUND: Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA) axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS) as 1. adrenocorticotropic hormone (ACTH) is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR) agonists 3. angiotensin II (ATII) releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM)-nonREM cycle. METHODS: Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD) 53.3 ± 14.4 yr.) and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.). After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC) for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h) were used for statistical analysis, with analysis of co variance being performed with age as a covariate. RESULTS: No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p < 0.06). Aldosterone was largely increased in the first (p < 0.05) and second (p < 0.01) half of the night. Cross correlations between hormone concentrations revealed that in contrast to earlier findings, which included only male subjects, in our primarily female sample, renin and aldosterone secretion were not coupled and no difference between patients and controls could be found, suggesting a gender difference in RAAS regulation. No difference in conventional sleep EEG parameters were found in our sample. CONCLUSION: Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

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

Heike Heuser, Fotografien und Collagen : [eine Ausstellung in der Universitätsbibliothek Marburg vom 8. Juni bis 20. Juli 1994]

Layoutgetreues Digitalisat der Ausg.: Marburg : [s.n.], 1994 Standort: Universität Marburg, Zentralbibliothek Signatur: 4 A 73/505, 71 Bemerkungen: Schriften der Universitätsbibliothek Marburg ; 7

Heike Heuser, Fotografien und Collagen : [eine Ausstellung in der Universitätsbibliothek Marburg vom 8. Juni bis 20. Juli 1994]

Layoutgetreues Digitalisat der Ausg.: Marburg : [s.n.], 1994 Standort: Universität Marburg, Zentralbibliothek <4> Signatur: 4 A 73/505, 71 Bemerkungen: Schriften der Universitätsbibliothek Marburg ; 7

Arbeitsplatz Universität : [die Ausstellung findet vom 16.04.2002 bis 16.06.2002 in der Universitätsbibliothek statt] ; ein Projekt der Philipps-Universität Marburg ...

Layoutgetreues Digitalisat der Ausg.: Marburg : Univ.-Bibl., 2002 Standort: Universität Marburg, Zentralbibliothek (4) Signatur: 4 A 73/505, 112 Bemerkungen: Schriften der Universitätsbibliothek Marburg ; 11

Influence of SORL1 gene variants: association with CSF amyloid-β products in probable Alzheimer\u27s disease

SORL1 gene variants were described as risk factors of Alzheimer\u27s disease (AD). We investigated the association of four SORL1 variants with CSF levels of Aβ42 and Aβ40 in 153 AD patients recruited from a multicenter study of the German Competence Net Dementias. Only one SORL1 SNP was associated with altered Aβ42 levels in the single marker analysis (SNP21: p = 0.011), the other SNPs did not show an association with Aβ42 or Aβ40 CSF levels. Haplotype analysis identified a three marker SORL1 haplotype consisting of SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) which was associated with reduced Aβ42 CSF levels in AD patients (p = 0.003). Aβ40 levels were also lower in carriers of this haplotype; however, this did not reach statistical significance (p = 0.15). We found a SORL1 haplotype which was associated with CSF levels of amyloid-β cleavage products, measured as altered levels of Aβ42. Thus our data suggest that SORL1 gene variants might influence AD pathology