C. elegans epigenetic regulation in development and aging

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.The precise developmentalmap of the Caenorhabditis elegans cell lineage, as well as a complete genome sequence and feasibility of genetic manipulation make this nematode species highly attractive to study the role of epigenetics during development. Genetic dissection of phenotypical traits, such as formation of egg-laying organs or starvation- resistant dauer larvae, has illustrated how chromatin modifiers may regulate specific cell-fate decisions and behavioral programs. Moreover, the transparent body of C. elegans facilitates non-invasive microscopy to study tissue-specific accumulation of heterochromatin at the nuclear periphery. We also review here recent findings on how small RNA molecules contribute to epigenetic control of gene expression that can be propagated for several generations and eventually determine longevity.This work was supported by the CNRS [to F.P.]; Fondation ARC [SFI20101201659 to F.P.]; Ligue Contre le Cancer [to F.P.]; the Spanish Ministry of Economy and Competitiveness [BFU2010-15478 to P.A.]; the Autonomous Government of Andalusia [P08-CVI-3920 to P.A.]; and the European Regional Development Fund.Peer Reviewe

A LysLysLys-tag as trigger in polynorepinephrine epitope imprinting: The case study of soluble PD-L1 detection in serum by optical-based sensing

Polycatecholamines (pCAs)-based molecularly imprinted polymers (MIPs) represent the new performing generation of biocompatible ligand/receptor mimetics. In this context, dealing with MIPs synthesis for bio-macromolecules detection/extraction, one of the critical steps in ensuring effective binding affinity for the parent molecule is the selection of suitable epitopes for pCAs imprinting. To address this challenge, here we investigated the ability of lysine (K) residues to trigger the epitope imprinting process into a polynorepinephrine (PNE) matrix. To this aim, we first designed a set of model epitopes composed of three K and six alanine (A) residues to investigate the influence of each 'KA' combination on the imprinting process and the resulting binding performance by Surface Plasmon Resonance (SPR). Only the case of three flanking K residues in N-terminus arose as an excellent trigger for epitope imprinting. The efficacy of the 3K-tag strategy was then evaluated on two peptide templates belonging to soluble programmed cell death protein 1 ligand (PD-L1), which is of great interest as a cancer biomarker in liquid biopsies. These templates were selected due to their negligible natural ability to be imprinted into the PNE matrix and were modified with 3K-tags, in N-, C-, and N/C- positions, respectively. The SPR sensor developed by exploiting the N-3K tag strategy allowed us to achieve excellent sensitivity (0.31 ± 0.04 ng mL-1) and repeatability (avCV% = 4.5) in human serum samples. This strategy opens new insights both for epitopes' design for pCAs-based mimetics and as triggering tags when native epitopes display negligible imprinting capabilities

The C. elegans HP1 homologue HPL-2 and the LIN-13 zinc finger protein form a complex implicated in vulval development.

International audienceHP1 proteins are essential components of heterochromatin and contribute to the transcriptional repression of euchromatic genes via the recruitment to specific promoters by corepressor proteins including TIF1 and Rb. The Caenorhabditis elegans HP1 homologue HPL-2 acts in the "synMuv" (synthetic multivulval) pathway, which defines redundant negative regulators of a Ras signaling cascade required for vulval induction. Several synMuv genes encode for chromatin-associated proteins involved in transcriptional regulation, including Rb and components of the Mi-2/NuRD and TIP60/NuA4 chromatin remodeling complexes. Here, we show that HPL-2 physically interacts in vitro and in vivo with the multiple zinc finger protein LIN-13, another member of the synMuv pathway. A variant of the conserved PXVXL motif found in many HP1-interacting proteins mediates LIN-13 binding to the CSD of HPL-2. We further show by in vivo localization studies that LIN-13 is required for HPL-2 recruitment in nuclear foci. Our data suggest that the LIN-13/HPL-2 complex may physically link a subset of the Rb related synMuv proteins to chromatin

Family Functioning, Identity Commitments, and School Value among Ethnic Minority and Ethnic Majority Adolescents

Ethnic minority youth show worse school adjustment than their ethnic majority peers. Yet, it remains unclear whether this gap can be explained by differences in family functioning and consequent identity commitments. This study examined (1) whether family functioning relates to identity commitments over time and (2) whether identity commitments impact later school value (3) among minority and majority adolescents. Minority (N = 205, Mage = 16.25 years, 31.1% girls) and majority adolescents (N = 480, Mage = 15.73 years, 47.9% girls) participated in this preregistered three-wave longitudinal study (T1: March-April 2012; T2: October 2012; T3: March-April 2013). Dynamic Panel Models revealed that most within-person cross-lagged associations were not significant in the total sample. Yet, multigroup analyses revealed differences between groups: Stronger identity commitments related to lower school value among minority adolescents, but were unrelated to school value among majority adolescents over time. Additionally, higher school value increased identity commitments among minority youth, yet it decreased identity commitments among majority youth over time. The findings highlight the differential interplay between identity commitments and school adjustment for minority and majority adolescents, with important implications for their future life chances

A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report

Background Mutations in RAB39B at Xq28 causes a rare form of X-linked intellectual disability (ID) and Parkinson’s disease. Neurofibromatosis type 1 (NF1) is caused by heterozygous mutations in NF1 occurring de novo in about 50% of cases, usually due to paternal gonadal mutations. This case report describes clinical and genetic findings in a boy with the occurrence of two distinct causative mutations in NF1 and RAB39B explaining the observed phenotype. Case presentation Here we report a 7-year-old boy with multiple café-au-lait macules (CALMs) and freckling, severe macrocephaly, peculiar facial gestalt, severe ID with absent speech, epilepsy, autistic traits, self-harming, and aggressiveness. Proband is an only child born to a father aged 47. Parents did not present signs of NF1, while a maternal uncle showed severe ID, epilepsy, and tremors.By RNA analysis of NF1, we identified a de novo splicing variant (NM_000267.3:c.6579+2T>C) in proband, which explained NF1 clinical features but not the severe ID, behavioral problems, and aggressiveness. Family history suggested an X-linked condition and massively parallel sequencing of X-exome identified a novel RAB39B mutation (NM_171998.2:c.436_447del) in proband, his mother, and affected maternal uncle, subsequently validated by Sanger sequencing in these and other family members. Conclusions The case presented here highlights how concurrent genetic defects should be considered in NF1 patients when NF1 mutations cannot reasonably explain all the observed clinical features

The development of parental monitoring during adolescence : A meta-analysis

As adolescents grow up, one of the important developmental tasks is to individuate themselves and to become more autonomous from parents. This requires a realignment of the parent-adolescent communication. The current meta-analytic study aims at identifying developmental changes in parent-adolescent communication, conceptualized within the parental monitoring framework, as entailing parental solicitation, control and knowledge, and adolescent’s disclosure and secrecy. Thirty-one longitudinal studies published between 2000 and 2015 were identified and included in the current meta-analysis. Informants, age at assessment and study duration were tested as moderators. Results showed a low to medium normative decline in parental control (Cohen’s d = −.395, 95% CI [−.541, −.249]), knowledge (d = −.245,95% CI [−.331, −.160] and adolescence disclosure (d = −.147, 95% CI [−.204, −.090]), and an increase in adolescent’s secrecy (d = .194, CI [031, .356]). Parental solicitation decreased based on parents’ (d = −.242, 95% CI[−.376, −.109]) but not on adolescents’ reports (d = .038, 95% CI[−.099, .175]). Another significant moderator was the duration of the study, with studies longer than 2 years being able to detect a more pronounced change in parental control than studies lasting less than 2 years (≤2 years, d = −.139 vs. duration > 2 years, d = −.581). Limitations of the current knowledge and new directions of studies are discussed.Peer reviewe

Shadow monochromatic backlighting: Large-field high resolution X-ray shadowgraphy with improved spectral tunability

The shadow monochromatic backlighting (SMB) scheme, a modification of the well-known soft X-ray monochromatic backlighting scheme, is proposed. It is based on a spherical crystal as the dispersive element and extends the traditional scheme by allowing one to work with a wide range of Bragg angles and thus in a wide spectral range. The advantages of the new scheme are demonstrated experimentally and supported numerically by ray-tracing simulations. In the experiments, the X-ray backlighter source is a laser-produced plasma, created by the interaction of an ultrashort pulse, Ti:Sapphire laser (120 fs, 3–5 mJ, 1016 W/cm2 on target) or a short wavelength XeCl laser (10 ns, 1–2 J, 1013 W/cm2 on target) with various solid targets (Dy, Ni + Cr, BaF2). In both experiments, the X-ray sources are well localized spatially (∼20 μm) and are spectrally tunable in a relatively wide wavelength range (λ = 8–15 Å). High quality monochromatic (δλ/λ ∼ 10−5–10−3) images with high spatial resolution (up to ∼4 μm) over a large field of view (a few square millimeters) were obtained. Utilization of spherically bent crystals to obtain high-resolution, large field, monochromatic images in a wide range of Bragg angles (35° < Θ < 90°) is demonstrated for the first time

Disability assessment using Google Maps

Objectives To evaluate the concordance between Google Maps  application (GM ) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). Materials and methods This is a cross-sectional multicenter study. AS and EDSS were calculated using GM  and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. Results Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM  and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1–7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01–1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04–1.17, p = 0.002) were associated with discrepancies between GM  and routine clinical scoring. Conclusion GM  could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM  should be considered for validation in further clinical studies

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans.

The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between Caenorhabditis elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex. Supporting a functional connection, we find that mutants of COMPASS and SIN3 complex components genetically interact and have similar phenotypic defects including misregulation of common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3S HDAC complex at promoters