Comparative Genomic Characterization of the Multimammate Mouse Mastomys coucha.

Mastomys are the most widespread African rodent and carriers of various diseases such as the plague or Lassa virus. In addition, mastomys have rapidly gained a large number of mammary glands. Here, we generated a genome, variome, and transcriptomes for Mastomys coucha. As mastomys diverged at similar times from mouse and rat, we demonstrate their utility as a comparative genomic tool for these commonly used animal models. Furthermore, we identified over 500 mastomys accelerated regions, often residing near important mammary developmental genes or within their exons leading to protein sequence changes. Functional characterization of a noncoding mastomys accelerated region, located in the HoxD locus, showed enhancer activity in mouse developing mammary glands. Combined, our results provide genomic resources for mastomys and highlight their potential both as a comparative genomic tool and for the identification of mammary gland number determining factors

Validating the Eating Disorder Inventory-3 (EDI-3): A Comparison Between 561 Female Eating Disorders Patients and 878 Females from the General Population

The Eating Disorder Inventory (EDI) is used worldwide in research and clinical work. The 3rd version (EDI-3) has been used in recent research, yet without any independent testing of its psychometric properties. The aim of the present study was twofold: 1) to establish national norms and to compare them with the US and international norms, and 2) to examine the factor structure, the internal consistency, the sensitivity and the specificity of subscale scores. Participants were Danish adult female patients (N = 561) from a specialist treatment centre and a control group (N = 878) was women selected from the Danish Civil Registration system. Small but significant differences were found between Danish and international, as well as US norms. Overall, the factor structure was confirmed, the internal consistency of the subscales was satisfactory, the discriminative validity was good, and sensitivity and specificity were excellent. The implications from these results are discussed

Somatic retrotransposition in the developing rhesus macaque brain.

The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic diversity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the divergence of apes and Old World monkeys, successive L1 subfamilies have emerged in each descendant primate germline. As revealed by case studies, the presently active human L1 subfamily can also mobilize during embryonic and brain development in vivo. It is unknown whether nonhuman primate L1s can similarly generate somatic insertions in the brain. Here we applied approximately 40× single-cell whole-genome sequencing (scWGS), as well as retrotransposon capture sequencing (RC-seq), to 20 hippocampal neurons from two rhesus macaques (Macaca mulatta). In one animal, we detected and PCR-validated a somatic L1 insertion that generated target site duplications, carried a short 5 transduction, and was present in ∼7% of hippocampal neurons but absent from cerebellum and nonbrain tissues. The corresponding donor L1 allele was exceptionally mobile in vitro and was embedded in PRDM4, a gene expressed throughout development and in neural stem cells. Nanopore long-read methylome and RNA-seq transcriptome analyses indicated young retrotransposon subfamily activation in the early embryo, followed by repression in adult tissues. These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a nonhuman primate, and allude to L1 mobility in the brain over the past 30 million years of human evolution.We thank John V. Moran for sharing L1.3 plasmids and the HeLa-JVM cell line, Margaret Z. Zdzienicka for sharing the V79B cell line, Jeffrey A. Jeddeloh for assistance with RC-seq probe design, and the QBI, TRI, and IGC flow cytometry facilities for technical advice. This study was funded by the following: Australian National Health and Medical Research Council (NHMRC) Investigator grants (GNT1161832 to S.W.C., GNT1176574 tN.J., GNT1173476 to S.R.R., GNT1173711 to G.J.F.), an NHMRCARC Dementia Research Development fellowship (GNT1108258 to G.O.B.), an Australian Government Research Training Program Scholarship awarded to P.G., the Australian Department of Health Medical Frontiers Future Fund (MRFF; MRF1175457 to A.D.E.), the Australian Research Council (DP200102919 to S.R.R. and G.J.F.), MINECO-FEDER (SAF2017-89745-R) and European Research Council (ERC-STG-2012-309433) funding and a private donation from Ms. Francisca Serrano (Trading y Bolsa para Torpes, Granada, Spain) to J.L.G-P., a National Institutes of Health (NIH) Office of Directors P51 grant (OD011092) to the Oregon National Primate Research Center to support L.C., an Andalusian Government EMERGIA grant (20_00225) to F.J.S-L., a CSL centenary fellowship to G.J.F., and the Mater Foundation. Rhesus macaque tissues were obtained from the Monkey Alcohol Tissue Research Resource (MATRR) biobank, supported by NIH grant 2R24 AA019431

Comparative Genomic Characterization of the Multimammate Mouse Mastomys coucha.

Mastomys are the most widespread African rodent and carriers of various diseases such as the plague or Lassa virus. In addition, mastomys have rapidly gained a large number of mammary glands. Here, we generated a genome, variome, and transcriptomes for Mastomys coucha. As mastomys diverged at similar times from mouse and rat, we demonstrate their utility as a comparative genomic tool for these commonly used animal models. Furthermore, we identified over 500 mastomys accelerated regions, often residing near important mammary developmental genes or within their exons leading to protein sequence changes. Functional characterization of a noncoding mastomys accelerated region, located in the HoxD locus, showed enhancer activity in mouse developing mammary glands. Combined, our results provide genomic resources for mastomys and highlight their potential both as a comparative genomic tool and for the identification of mammary gland number determining factors

Evaluation of a Guided Internet Self-Treatment Programme for Bulimia Nervosa in Several European Countries

OBJECTIVE: The purposes of this study were to evaluate the use of an online guided self-treatment programme for bulimia nervosa (BN) and to determine predictors of outcome. Data were collected in four European countries where the programme was simultaneously used. METHOD: One hundred and twenty-seven BN or subthreshold BN female patients (mean age of 24.7 years) participated in a 4-month intervention using a CBT based online-guided self-help programme. Contact during the treatment period included weekly e-mails with a coach. ASSESSMENT: Measures included the Eating Disorders Inventory-2 (EDI-2) and the Symptom Check List-Revised (SCL-90R). RESULTS: Severity of eating disorders symptoms and general psychopathology improved significantly. Twenty-three per cent of patients were symptom free at the end of treatment. The dropout rate was 25.2%. A better score of general psychological health was a predictor of a better outcome. CONCLUSIONS: This study encourages further developments and research on innovative therapy approaches, particularly for those disorders such as BN, with difficult therapy and unclear prognosis. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association

Somatic retrotransposition in the developing rhesus macaque brain.

The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic diversity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the divergence of apes and Old World monkeys, successive L1 subfamilies have emerged in each descendant primate germline. As revealed by case studies, the presently active human L1 subfamily can also mobilize during embryonic and brain development in vivo. It is unknown whether nonhuman primate L1s can similarly generate somatic insertions in the brain. Here we applied approximately 40× single-cell whole-genome sequencing (scWGS), as well as retrotransposon capture sequencing (RC-seq), to 20 hippocampal neurons from two rhesus macaques (Macaca mulatta). In one animal, we detected and PCR-validated a somatic L1 insertion that generated target site duplications, carried a short 5' transduction, and was present in ∼7% of hippocampal neurons but absent from cerebellum and nonbrain tissues. The corresponding donor L1 allele was exceptionally mobile in vitro and was embedded in PRDM4, a gene expressed throughout development and in neural stem cells. Nanopore long-read methylome and RNA-seq transcriptome analyses indicated young retrotransposon subfamily activation in the early embryo, followed by repression in adult tissues. These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a nonhuman primate, and allude to L1 mobility in the brain over the past 30 million years of human evolution