Sex Differences in the Chronology of Deciduous Tooth Emergence in White and Black Children

Tooth emergence in 376 black and white children between the ages of 4 and 33 months was studied in southeastern Michigan. The results indicate a trend in both groups for boys to show earlier tooth emergence in early stages and for girls to show earlier tooth emergence in later stages of deciduous tooth emergence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66947/2/10.1177_00220345740530024001.pd

Dental Caries Experience in the Deciduous Dentition of Rural Guatemalan Children Ages 6 Months to 7 Years

A study of 528 Guatemalan children indicated that caries prevalence in the deciduous dentition was twice as great as but in the permanent dentition was similar to that for US white children. This is a repeated observation for children of some preindustrial societies. Caries experience was significantly greater in boys. Until 4 years of age, caries attack was greater in the anterior segment of the oral cavity; linear enamel hypoplasia was a predisposing factor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68238/2/10.1177_00220345760550064501.pd

Multiaperture UBVRIzJHKUBVRIzJHK Photometry of Galaxies in the Coma Cluster

We present a set of $UBVRIzJHK_s$ photometry for 745 $J+H$ band selected objects in a $22.5' \times 29.2'$ region centered on the core of the Coma cluster. This includes 516 galaxies and is at least 80% complete to H=16, with a spectroscopically complete sample of 111 cluster members (nearly all with morphological classification) for $H < 14.5$. For each object we present total \cite{kron80} magnitudes and aperture photometry. As an example, we use these data to derive color-magnitude relations for Coma early-type galaxies, measure the intrinsic scatter of these relations and its dependence on galaxy mass, and address the issue of color gradients. We find that the color gradients are mild and that the intrinsic scatter about the color-magnitude relation is small ($\sim 0.05$ mag in $U-V$ and less than $\sim 0.03$ in $B-R$, $V-I$ or $J-K$). There is no evidence that the intrinsic scatter varies with galaxy luminosity, suggesting that the cluster red sequence is established at early epochs over a range of $\sim 100$ in stellar mass.Comment: 41 pages, 5 figures, 18 data tables attached to source files or available on request from R. De propris. Accepted for publication in Astrophysical Journal Supplement Serie

An Epidemiologic Study of Dental Caries in Preschool Children in the United States by Race and Socioeconomic Level

The prevalence of dental caries in 1,155 white and black preschool children was studied in the United States in 1969 and 1970. The results demonstrated that white children of the lower socioeconomic level had a significantly greater prevalence of dental caries than middle class white children, but a significantly lower prevalence than black children, most of whom represented the lower social class.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67244/2/10.1177_00220345740530023501.pd

Characterization of Lifestyle inSpinocerebellar Ataxia Type 3 andAssociation with Disease Severity

Background: Lifestyle could influence the course of hereditary ataxias, but representative data are missing. Objective: The objective of this study was to characterize lifestyle in spinocerebellar ataxia type 3 (SCA3) and investigate possible associations with disease parameters. Methods: In a prospective cohort study, data on smoking, alcohol consumption, physical activity, physiotherapy, and body mass index (BMI) were collected from 243 patients with SCA3 and 119 controls and tested for associations with age of onset, disease severity, and progression. Results: Compared with controls, patients with SCA3 were less active and consumed less alcohol. Less physical activity and alcohol abstinence were associated with more severe disease, but not with progression rates or age of onset. Smoking, BMI, or physiotherapy did not correlate with disease parameters. Conclusion: Differences in lifestyle factors of patients with SCA3 and controls as well as associations of lifestyle factors with disease severity are likely driven by the influence of symptoms on behavior. No association between lifestyle and disease progression was detected. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder SocietyFunding agencies: This publication is an outcome of the European Spinocerebellar ataxia type 3/Machado-Joseph disease initiative (ESMI), an EU Joint Programme–Neurodegenerative Disease Research (JPND) project (see www.jpnd.eu). The project is supported through the following funding organizations under the aegis of JPND: Germany, Federal Ministry of Education and Research (funding codes 01ED1602A/B); The Netherlands, The Netherlands Organisation for Health Research and Development; Portugal, Foundation for Science and Technology (FCT); United Kingdom, Medical Research Council. This project has received funding from the European Union’s Horizon 2020 research and innovation program under Grant 643417. At the US sites, this work was in part supported by the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke Grant R01 NS080816. P.G. is supported by the National Institute for Health Research University College London Hospitals (UCLH) Biomedical Research Centre. P.G. receives also support from the North Thames Clinical Research Network (CRN). P.G. and H.G.M. work at University College London Hospitals/University College London, which receives a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. P.G. received funding from CureSCA3 in support of H.G.M.’s work. This work was moreover supported, in part, by the Deutsche Forschungsgemeinschaft (German Research Foundation) No. 441409627, as part of the Progression chart of Spastic ataxias (PROSPAX) consortium under the frame of the European Joint Programme on Rare Diseases (EJP RD), under the EJP RD COFUND-EJP N 825575 (to M.S., B.v.W,) and Grant 779257 “Solve-RD” from the Horizon 2020 research and innovation program to M.S

Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1

We used mouse hepatic chromatin enriched with an FXR antibody and chromatin immunoprecipitation-sequencing (ChIP-seq) to evaluate FXR binding on a genome-wide scale. This identified 1656 FXR-binding sites and 10% were located within 2 kb of a transcription start site which is much higher than predicted by random occurrence. A motif search uncovered a canonical nuclear receptor IR-1 site, consistent with in vitro DNA-binding studies reported previously. A separate nuclear receptor half-site for monomeric receptors such as LRH-1 was co-enriched and FXR activation of four newly identified promoters was significantly augmented by an LRH-1 expression vector in a co-transfection assay. There were 1038 genes located within 20 kb of a peak and a gene set enrichment analysis showed that genes identified by our ChIP-seq analysis are highly correlated with genes activated by an FXR-VP16 adenovirus in primary mouse hepatocytes providing functional relevance to the genome-wide binding study. Gene Ontology analysis showed FXR-binding sites close to many genes in lipid, fatty acid and steroid metabolism. Other broad gene clusters related to metabolism, transport, signaling and glycolysis were also significantly enriched. Thus, FXR may have a much wider role in cellular metabolism than previously appreciated

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants

[Background]: Disrupted pre-mRNA splicing is a frequent deleterious mechanism in hereditary cancer. We aimed to functionally analyze candidate spliceogenic variants of the breast cancer susceptibility gene CHEK2 by splicing reporter minigenes.[Methods]: A total of 128 CHEK2 splice-site variants identified in the Breast Cancer After Diagnostic Gene Sequencing (BRIDGES) project (https://cordis.europa.eu/project/id/634935) were analyzed with MaxEntScan and subsetted to 52 variants predicted to impact splicing. Three CHEK2 minigenes, which span all 15 exons, were constructed and validated. The 52 selected variants were then genetically engineered into the minigenes and assayed in MCF-7 (human breast adenocarcinoma) cells.[Results]. Of 52 variants, 46 (88.5%) impaired splicing. Some of them led to complex splicing patterns with up to 11 different transcripts. Thirty-four variants induced splicing anomalies without any trace or negligible amounts of the full-length transcript. A total of 89 different transcripts were annotated, which derived from different events: single- or multi-exon skipping, alternative site-usage, mutually exclusive exon inclusion, intron retention or combinations of the abovementioned events. Fifty-nine transcripts were predicted to introduce premature termination codons, 7 kept the original open-reading frame, 5 removed the translation start codon, 6 affected the 5′UTR (Untranslated Region), and 2 included missense variations. Analysis of variant c.684-2A > G revealed the activation of a non-canonical TG-acceptor site and exon 6 sequences critical for its recognition.[Conclusions]: Incorporation of minigene read-outs into an ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based classification scheme allowed us to classify 32 CHEK2 variants (27 pathogenic/likely pathogenic and 5 likely benign). However, 20 variants (38%) remained of uncertain significance, reflecting in part the complex splicing patterns of this gene.P. Devilee, M.P.G. Vreeswijk, D.F. Easton, M. de la Hoya, and E.A. Velasco-Sampedro have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 634935. E.A. Velasco-Sampedro’s lab is supported by grants from the Spanish Ministry of Science and Innovation, Plan Nacional de I + D + I 2013–2016, ISCIII (PI20/00225) co-funded by FEDER from Regional Development European Funds (European Union) and from the Consejería de Educación, Junta de Castilla y León, ref. CSI242P18 (actuación cofinanciada P.O. FEDER 2014–2020 de Castilla y León), Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Escalera de Excelencia, Junta de Castilla y Leon (Ref. CLU-2019–2002). M. de la Hoya lab is supported by a grant from the Spanish Ministry of Science and Innovation, Plan Nacional de I + D + I 2013–2016, ISCIII (PI20/00110) co-funded by FEDER from Regional Development European Funds (European Union). D.F. Easton is supported by Government of Canada through Genome Canada and the Canadian Institutes of Health Research, The Ministère de l’Économie et de l’Innovation du Québec through Genome Québec, and by the Wellcome Trust [grant no: v203477/Z/16/Z]; E. Bueno-Martínez is a postdoctoral researcher funded by the University of Valladolid (POSTDOC-UVA05, 2022–2025). L. Sanoguera-Miralles is supported by a predoctoral fellowship from the AECC-Scientific Foundation, Sede Provincial de Valladolid (2019–2023). I. Llinares-Burguet is supported by predoctoral fellowships from the Consejería de Educación, Junta de Castilla y León (2022–2025). A. Esteban-Sánchez is supported through the Operational Program for Youth Employment and Youth Employment Initiative (YEI) of the Community of Madrid in 2020, and co-financed by the European Social Fund.Peer reviewe