In populations that have a high degree of admixture, such as in Brazil, the sole use of ethnicity self-declaration information is not a good method for classifying individuals regarding their ...ethnicity. Here, we evaluate the relationship of self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of the mitochondrial DNA (mtDNA), and the genomic ancestry was obtained using 48 autosomal insertion-deletion ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as White, 13.8% as Brown and 10.4% as Black. Classification of the mtDNA haplogroups showed that 46.3% had African mtDNA, and the genomic ancestry analysis showed that the main contribution was European (57.4%). When we looked at the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities from 367 individuals who self-declared as White, 37.6% showed African mtDNA, and they had a high contribution of European genomic ancestry (63.3%) but also a significant contribution of African ancestry (22.2%). Of the 68 individuals who self-declared as Brown, 25% showed Amerindian mtDNA and similar contribution of European and African genomic ancestries. Of the 51 subjects who self-declared as black, 80.4% had African mtDNA, and the main contribution of genomic ancestry was African (55.6%), but they also had a significant proportion of European ancestry (32.1%). The Brazilian population had a uniform degree of Amerindian genomic ancestry, and it was only with the use of genetic markers (autosomal or mitochondrial) that we were able to capture Amerindian ancestry information. Additionally, it was possible to observe a high degree of heterogeneity in the ancestry for both types of genetic markers, which shows the high genetic admixture that is present in the Brazilian population. We suggest that in epidemiological studies, the use of these methods could provide complementary information.
A double-phase argon Time Projection Chamber (TPC), with an active mass of 185 g, has been designed and constructed for the Recoil Directionality (ReD) experiment. The aim of the ReD project is to ...investigate the directional sensitivity of argon-based TPCs via columnar recombination to nuclear recoils in the energy range of interest (20–
200
keV
nr
) for direct dark matter searches. The key novel feature of the ReD TPC is a readout system based on cryogenic Silicon Photomultipliers (SiPMs), which are employed and operated continuously for the first time in an argon TPC. Over the course of 6 months, the ReD TPC was commissioned and characterised under various operating conditions using
γ
-ray and neutron sources, demonstrating remarkable stability of the optical sensors and reproducibility of the results. The scintillation gain and ionisation amplification of the TPC were measured to be
g
1
=
(
0.194
±
0.013
)
photoelectrons/photon and
g
2
=
(
20.0
±
0.9
)
photoelectrons/electron, respectively. The ratio of the ionisation to scintillation signals (S2/S1), instrumental for the positive identification of a candidate directional signal induced by WIMPs, has been investigated for both nuclear and electron recoils. At a drift field of 183 V/cm, an S2/S1 dispersion of 12% was measured for nuclear recoils of approximately 60–
90
keV
nr
, as compared to 18% for electron recoils depositing 60 keV of energy. The detector performance reported here meets the requirements needed to achieve the principal scientific goals of the ReD experiment in the search for a directional effect due to columnar recombination. A phenomenological parameterisation of the recombination probability in LAr is presented and employed for modeling the dependence of scintillation quenching and charge yield on the drift field for electron recoils between 50–500 keV and fields up to 1000 V/cm.
Landscape change alters the visual scale of agricultural landscapes, as production units get larger and strips of taller vegetation are removed between smaller units. Visual scale, defined as the ...perceptual units reflecting the experience of landscape rooms, visibility and openness, is considered a key factor shaping landscape preference. The visual expression of landscapes affects people in many ways; aesthetic appreciation, health and well being. In order to understand how landscape changes alter the visual scale of landscapes, and hence its effect on human beings, it is important to establish efficient and practical ways of measuring visual scale and its relation to landscape preferences. This paper presents an empirical test of the ability to predict landscape preference of two photo-based indicators of visual scale;
percentage open land in the view and
size of landscape rooms. A preference survey was conducted with two groups of respondents; a student group from the Norwegian University of Life Sciences (UMB) and a public group. The student group was chosen to represent future landscape professionals. Photos of landscapes varying in the expression of visual scale were shown to survey respondents, who were asked to give scores according to how much they liked the landscapes. Both indicators were found to be predictors of preference for the student group, but not for the public group. The results demonstrate that student preferences do not reflect the landscape preferences of the wider public. The different appreciation of visual scale in the landscape of future landscape professionals and the public implies that experts wanting to reflect preferences of the wider public should be cautious when evaluating the visual impact of landscape change.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex ...with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval CI, 42.7—151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5—61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8—6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5—2.2). In comparison with the period 2000—2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3—.9) in 1996—1999 and 0.9 (95% CI, .6—1.2) in 2004—2007. Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
Feline coronavirus (FCoV) exists as two different genotypes, FCoV type I and II, each including two biotypes, feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV), the ...latter being a virulent variant originating from the former virus. Recently, two amino acid substitutions, M1058L and S1060A, within the spike protein have been associated to the FECV/FIPV virulence change. In this study, we have analysed the frequency of detection of such mutations in FIPV and FECV strains circulating in Italian cats and obtained information about their evolutionary relationships with reference isolates. A total of 40 FCoV strains, including 19 strains from effusions or tissue samples of FIP cats and 21 strains from faecal samples of non-FIP cats, were analysed. Mutation M1058L was detected in 16/18 FCoV-I and 1/1 FCoV-II strains associated with FIP, while change S1060A was presented by two FIPV strains. By phylogenetic analysis, FCoV sequences clustered according to the genotype but not according to the biotype, with FECV/FIPV strains recovered from the same animal being closely related. Further studies are needed to better define the genetic signatures associated with the FECV/FIPV virulence shift.
•Spike protein sequences from FCoV strains circulating in Italian FIP (n = 19) and non-FIP (n = 21) cats were analysed.•Mutations M1058L and S1060A were detected in 17 and 2 FCoV strains associated with FIP, respectively.•By phylogenetic analysis, FCoV sequences clustered according to the genotype but not according to the pathotype.•FECV/FIPV strains recovered from the same animal were closely related at the phylogenetic level.•Further studies will better define the genetic signatures associated with the FCoV virulence shift.
Baker, Gordon et al. present the first international case series describing the neurodevelopmental disorder associated with Synaptotagmin 1 (SYT1) de novo missense mutations. Key features include ...movement abnormalities, severe intellectual disability, and hallmark EEG alterations. Expression of patients' SYT1 mutations in mouse neurons disturbs presynaptic vesicle dynamics in a mutation-specific manner.
Abstract
Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1I368T and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals' phenotypes, suggesting that the efficiency of SYT1-mediated neurotransmitter release is critical to cognitive development. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1.
The concept of naturalness is one of the more studied concepts in landscape preference research and describes how close a landscape is to a perceived natural state. In this study we explored the ...relationship between landscape preference and three landscape indicators of naturalness (level of succession, number of woodland patches and shape index of edges). We used computer-generated visualisations of a hypothetical landscape containing pasture and broadleaved woodland. In the landscape simulations we altered the values of the naturalness indicators between the levels of low, medium and high, creating 27 different visualisations. The survey was distributed as an on-line survey in seven different languages and obtained 703 respondents. The study showed a strong relationship with preference for both the level of succession and number of woodland patches, and a weaker relationship with shape index of edges. The two demographic factors which were shown to contribute most to the formation of preference were gender and having a landscape related profession. The results suggest that the selected indicators are more important drivers of preference than demographic factors.
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