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The pollution haven hypothesis (PHH) suggests that foreign direct investment (FDI) inflows contribute to rising carbon dioxide (CO 2 ) emissions in developing countries. This study aims to investigate the validity of the PHH in Cote d’Ivoire. For this purpose, FDI, real gross domestic product (GDP) per capita, energy consumption, and agriculture value added are included in the carbon dioxide emissions’ function. Based on time series data spanning from 1980 to 2014, the study utilized the autoregressive distributed lag (ARDL) approach. In addition to the introduction of structural breaks in the estimations techniques, this study contributes to the literature by focusing on a typical developing country that is currently experiencing increases both in FDI inflows and in CO 2 emissions. The findings indicated a cointegration relationship between the variables. Additionally, the ARDL results validate the PHH in Cote d’Ivoire as we find a positive relationship between FDI and CO 2 emissions. Likewise, the results showed that GDP per capita, energy consumption, and agriculture value added have a positive impact on CO 2 emissions. Based on the results, we advise Ivorian policymakers to strengthen the environmental regulations and focus on attracting clean FDI. Besides, the Ivorian government should implement energy-saving policies and promote the use of environment-friendly techniques in the agriculture sector.

While the relationship between carbon dioxide (CO 2 ) emission and its determinants has been widely examined in Asia, little attention has been paid to the role played by the participation in global value chains (GVCs). Thus, this study aims to fill this research gap by investigating the relationship between participation in GVCs and CO 2 emissions in eleven Asian countries along with economic growth, energy consumption, trade openness, and population density. The study covers the period 1995q1–2014q4 and employs both fully modified ordinary least square (FMOLS) and dynamic ordinary least square (DOLS) methods, as well as cointegration and causality tests to examine the dynamics between variables. The findings indicate a cointegration relationship between the variables. Moreover, both FMOLS and DOLS results show that higher participation in global value chains leads to a reduction of CO 2 emissions, while economic growth and energy consumption increase CO 2 emissions. The outcomes also indicate a negative relationship between trade openness and CO 2 emissions. Thus, the selected Asian countries should promote policies aimed at enhancing their participation in global value chains and expanding their openness to trade. Besides, the selected countries are expected to implement energy-saving policies and promote cleaner sources of energy.

Non-invasive prenatal diagnosis of single-gene disorders (SGD-NIPD) has been widely accepted, but is mostly limited to the exclusion of either paternal or de novo mutations. Indeed, it is still difficult to infer the inheritance of the maternal allele from cell-free DNA (cfDNA) analysis. Based on the study of maternal haplotype imbalance in cfDNA, relative haplotype dosage (RHDO) was developed to address this challenge. Although RHDO has been shown to be reliable, robust control of statistical error and explicit delineation of critical parameters for assessing the quality of the analysis have not been fully addressed. We present here a universal and adaptable enhanced-RHDO (eRHDO) procedure through an automated bioinformatics pipeline with a didactic visualization of the results, aiming to be applied for any SGD-NIPD in routine care. A training cohort of 43 families carrying CFTR , NF1 , DMD , or F8 mutations allowed the characterization and optimal setting of several adjustable data variables, such as minimum sequencing depth, type 1 and type 2 statistical errors, as well as the quality assessment of intermediate steps and final results by block score and concordance score. Validation was successfully performed on a test cohort of 56 pregnancies. Finally, computer simulations were used to estimate the effect of fetal-fraction, sequencing depth and number of informative SNPs on the quality of results. Our workflow proved to be robust, as we obtained conclusive and correctly inferred fetal genotypes in 94.9% of cases, with no false-negative or false-positive results. By standardizing data generation and analysis, we fully describe a turnkey protocol for laboratories wishing to offer eRHDO-based non-invasive prenatal diagnosis for single-gene disorders as an alternative to conventional prenatal diagnosis.

Purpose Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. Up to now, four genome-wide association studies of AN have been conducted to date and identified only few significant loci. However, both previous studies focused on common variation and on rare exonic variants. Currently, de novo variants are one of the most significant risk factors for neurodevelopmental disorders and psychiatric disorders. Methods We analyzed by whole exome sequencing a cohort of nine female AN individuals and their parents (mother and father), and focused our analysis on de novo variants. Results Here, we found seven de novo missense variants in potential genes in nine studied AN patients. Four of these genes ( CSMD1, CREB3, PTPRD and GAB1 ) belong to a same signaling pathway involving neuron differentiation and dopamine pathway. Conclusions This study provides a list of interesting genes such as CSDM1 and CREB3 that are candidates to be involved in the etiology of anorexia nervosa. Level of Evidence basic research.

BackgroundAnorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.The present study will aim to identify markers that can predict body mass index (BMI) stability 6 months after discharge. The secondary aim of this study will be focused on characterising the biological, genetic, epigenetic and neurocognitive markers of remission in AN.Methods and analysisOne hundred and twenty-five (n=125) female adult inpatients diagnosed with AN will be recruited and evaluated at three different times: at the beginning of hospitalisation, when discharged and 6 months later. Depending on the BMI at the third visit, patients will be split into two groups: stable remission (BMI≥18.5 kg/m²) or unstable remission (BMI<18.5 kg/m²). One hundred (n=100) volunteers will be included as healthy controls.Each visit will consist in self-reported inventories (measuring depression, anxiety, suicidal thoughts and feelings, eating disorders symptoms, exercise addiction and the presence of comorbidities), neurocognitive tasks (Delay Discounting Task, Trail-Making Test, Brixton Test and Slip-of-action Task), the collection of blood samples, the repeated collection of blood samples around a standard meal and MRI scans at rest and while resolving a delay discounting task.Analyses will mainly consist in comparing patients stabilised 6 months later and patients who relapsed during these 6 months.Ethics and disseminationInvestigators will ask all participants to give written informed consent prior to participation, and all data will be recorded anonymously. The study will be conducted according to ethics recommendations from the Helsinki declaration (World Medical Association, 2013). It was registered on clinicaltrials.gov on 25 August 2020 as ‘Remission Factors in Anorexia Nervosa (REMANO)’, with the identifier NCT04560517 (for more details, see https://clinicaltrials.gov/ct2/show/record/NCT04560517). The present article is based on the latest protocol version from 29 November 2019. The sponsor, Institut National de la Santé Et de la Recherche Médicale (INSERM, https://www.inserm.fr/), is an academic institution responsible for the monitoring of the study, with an audit planned on a yearly basis.The results will be published after final analysis in the form of scientific articles in peer-reviewed journals and may be presented at national and international conferences.Trial registration number clinicaltrials.govNCT04560517

Mental retardation (MR) is defined as an overall intelligence quotient lower than 70, associated with functional deficit in adaptive behavior, such as daily-living skills, social skills and communication. Affecting 1–3% of the population and resulting from extraordinary heterogeneous environmental, chromosomal and monogenic causes, MR represents one of the most difficult challenges faced today by clinician and geneticists. Detailed analysis of the Online Mendelian Inheritance in Man database and literature searches revealed more than a thousand entries for MR, and more than 290 genes involved in clinical phenotypes or syndromes, metabolic or neurological disorders characterized by MR. We estimate that many more MR genes remain to be identified. The purpose of this review is to provide an overview on the remarkable progress achieved over the last decade in delineating genetic causes of MR, and to highlight the emerging biological and cellular processes and pathways underlying pathogeneses of human cognitive disorders.

Globozoospermia is a rare but serious teratozoospermia, characterised by ejaculates consisting of entirely of round-headed spermatozoa without acrosomes or, in the case of partial globozoospermia, containing a variable proportion (20 to 90%) of spermatozoa without acrosomes. Men with total globozoospermia are infertile, and even the use of intracytoplasmic sperm injection (ICSI) has been associated with disappointing success rates. This study confirmed need to complement spermogram with genetic testing in order to confirm diagnosis and to advice on the appropriate management of patients, regardless of phenotype on spermogram.

Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear. We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations. During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5-48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1-81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1-113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4-37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10(-5)). DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.

The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.Genetic correlates of autism in natives of remote islandsA study of the genetic architecture of autism among people living on the remote Faroe Islands highlights the role of both common and rare gene variants to autism. Claire Leblond from the Institut Pasteur in Paris, France, and colleagues profiled the genetics of 357 Faroese individuals, including 36 with autism, 136 of their relatives and 185 non-autistic controls. Similar to the findings of genetic studies of autism from elsewhere, the researchers discovered rare structural variants in known autism-associated genes and a few new candidate genes linked to brain function. However, unlike studies from larger mainland populations, they also showed that inbreeding on these remote islands increased the likelihood of carrying two copies of the point mutations that contribute to autism.

We have recently reported a missense mutation in exon 4 of the tubulin alpha 1A (Tuba1a) gene in a hyperactive N-ethyl-N-nitrosourea (ENU) induced mouse mutant with abnormal lamination of the hippocampus. Neuroanatomical similarities between the Tuba1a mutant mouse and mice deficient for Doublecortin (Dcx) and Lis1 genes, and the well-established functional interaction between DCX and microtubules (MTs), led us to hypothesize that mutations in TUBA1A (TUBA3, previous symbol), the human homolog of Tuba1a, might give rise to cortical malformations. This hypothesis was subsequently confirmed by the identification of TUBA1A mutations in two patients with lissencephaly and pachygyria, respectively. Here we report additional TUBA1A mutations identified in six unrelated patients with a large spectrum of brain dysgeneses. The de novo occurrence was shown for all mutations, including one recurrent mutation (c.790C>T, p.R264C) detected in two patients, and two mutations that affect the same amino acid (c.1205G>A, p.R402H; c.1204C>T, p.R402C) detected in two other patients. Retrospective examination of MR images suggests that patients with TUBA1A mutations share not only cortical dysgenesis, but also cerebellar, hippocampal, corpus callosum, and brainstem abnormalities. Interestingly, the specific high level of Tuba1a expression throughout the period of central nervous system (CNS) development, shown by in situ hybridization using mouse embryos, is in accordance with the brain-restricted developmental phenotype caused by TUBA1A mutations. All together, these results, in combination with previously reported data, strengthen the relevance of the known interaction between MTs and DCX, and highlight the importance of the MTs/DCX complex in the neuronal migration process. Hum Mutat 28(11), 1055-1064, 2007. © 2007 Wiley-Liss, Inc.