A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase

Nup133 links CENP-F, NudE/EL, and the dynein/dynactin complex to anchor centrosomes to the nuclear membrane

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems

Involvement of the Nup107-160 nuclear pore subcomplex in entry, progression and exit from mitosis

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Pml39, a Novel Protein of the Nuclear Periphery Required for Nuclear Retention of Improper Messenger Ribonucleoparticles

Using a genetic screen, we have identified a previously uncharacterized Saccharomyces cerevisiae open reading frame (renamed PML39) that displays a specific interaction with nucleoporins of the Nup84 complex. Localization of a Pml39-green fluorescent protein (GFP) fusion and two-hybrid studies revealed that Pml39 is mainly docked to a subset of nuclear pore complexes opposite to the nucleolus through interactions with Mlp1 and Mlp2. The absence of Pml39 leads to a specific leakage of unspliced mRNAs that is not enhanced upon MLP1 deletion. In addition, overexpression of PML39-GFP induces a specific trapping of mRNAs transcribed from an intron-containing reporter and of the heterogenous nuclear ribonucleoprotein Nab2 within discrete nuclear domains. In a nup60Δ mutant, Pml39 is mislocalized together with Mlp1 and Mlp2 in intranuclear foci that also recruit Nab2. Moreover, pml39Δ partially rescues the thermosensitive phenotypes of messenger ribonucleoparticles (mRNPs) assembly mutants, indicating that PML39 deletion also bypasses the requirement for normally assembled mRNPs. Together, these data indicate that Pml39 is an upstream effector of the Mlps, involved in the retention of improper mRNPs in the nucleus before their export

National, longitudinal NASCITA birth cohort study: prevalence of overweight at 12 months of age in children born healthy

Objective To estimate the prevalence of overweight at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight.Methods The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (<5th), normal weight (5–84th) and overweight (≥85th centile) at 12 months of age according to the WHO percentiles of body mass index (BMI) and the prevalence of overweight was estimated. To test the association between the chance of being overweight and parental and newborn characteristics, and infant feeding, healthy newborns (no preterm/low birth weight and with no malformations), with appropriate-for-gestational-age birth weight were selected, and univariate and multivariate analyses were performed.Results The prevalence of overweight was 23.5% (95% CI 22.2% to 24.8%) in all cohort members with 12-month data (N=4270), and 23.1% in the appropriate-for-gestational age subsample (N=2835).A big infant appetite (OR 3.92, 95% CI 2.40 to 6.40) and living in southern Italy (OR 1.58, 95% CI 1.29 to 1.94) were the main variables associated with a greater likelihood of being overweight. Breastfeeding practice did not influence the chance of being overweight, but was associated with an increase (exclusive breast feeding for at least 6 months) or a decrease (breast feeding for at least 12 months) in BMI z score at 12 months.Conclusions The sociodemographic factors (eg, area of residence, maternal employment status) seem to be the most relevant determinants influencing the chance of being overweight at 12 months. Early interventions, with particular attention to vulnerable families, may be helpful in preventing childhood and adult obesity