Uncoupled Embryonic and Extra-Embryonic Tissues Compromise Blastocyst Development after Somatic Cell Nuclear Transfer

Somatic cell nuclear transfer (SCNT) is the most efficient cell reprogramming technique available, especially when working with bovine species. Although SCNT blastocysts performed equally well or better than controls in the weeks following embryo transfer at Day 7, elongation and gastrulation defects were observed prior to implantation. To understand the developmental implications of embryonic/extra-embryonic interactions, the morphological and molecular features of elongating and gastrulating tissues were analysed. At Day 18, 30 SCNT conceptuses were compared to 20 controls (AI and IVP: 10 conceptuses each); one-half of the SCNT conceptuses appeared normal while the other half showed signs of atypical elongation and gastrulation. SCNT was also associated with a high incidence of discordance in embryonic and extra-embryonic patterns, as evidenced by morphological and molecular “uncoupling”. Elongation appeared to be secondarily affected; only 3 of 30 conceptuses had abnormally elongated shapes and there were very few differences in gene expression when they were compared to the controls. However, some of these differences could be linked to defects in microvilli formation or extracellular matrix composition and could thus impact extra-embryonic functions. In contrast to elongation, gastrulation stages included embryonic defects that likely affected the hypoblast, the epiblast, or the early stages of their differentiation. When taking into account SCNT conceptus somatic origin, i.e. the reprogramming efficiency of each bovine ear fibroblast (Low: 0029, Med: 7711, High: 5538), we found that embryonic abnormalities or severe embryonic/extra-embryonic uncoupling were more tightly correlated to embryo loss at implantation than were elongation defects. Alternatively, extra-embryonic differences between SCNT and control conceptuses at Day 18 were related to molecular plasticity (high efficiency/high plasticity) and subsequent pregnancy loss. Finally, because it alters re-differentiation processes in vivo, SCNT reprogramming highlights temporally and spatially restricted interactions among cells and tissues in a unique way

Systematic review of care needs for older patients treated with anticancer drugs

Objective: When treated with anticancer therapies, a number of issues are raised for older patients such as physical needs (coping with symptoms and side-effects) or psychological needs. Geriatric tailored interventions addressing these needs may be effective in terms of improving quality of life of our patients. Methods: A systematic review was performed in September 2017 in MEDLINE. All reports assessing older patients with cancer care needs in the context of anticancer systemic therapy were reviewed. Results: A total of 357 articles were analyzed. From these, 35 studies were included in the analysis. Compared to younger patients, the elderly had less supportive care needs. While older patients asked for less information than their younger counterparts, they still requested information on diagnosis, seriousness of the disease, chances of cure, spread of the disease, recovery, courses of illness, possible consequences, treatment procedures, treatment options, possible side effects and how to deal with them, and what they could do in daily life. When taking into consideration the various needs as assessed by the "Supportive Care Needs Survey", physical and daily living were the most frequently reported needs with emphasis on nutrition, coping with physical symptoms, dealing with side effects of treatment, and performing usual physical tasks and activities. Conclusion: Information demand seemed moderate but a great deal of attention was paid to nutrition and well-being. (C) 2018 Elsevier Ltd. All rights reserved

Associations between Plasmatic Polyunsaturated Fatty Acids Concentrations and Cognitive Status and Decline in Neurocognitive Disorders

International audienceTo examine the association of plasmatic and erythrocyte concentrations polyunsaturated fatty acids (PUFA) with both cognitive status and decline. Longitudinal observational cohort study. Setting: Memory Clinic of Lyon Sud university hospital. 140 patients, aged 60 and older, were referred to the memory clinic, and successively included in the cohort, between March 2010 and February 2014. Concentration of omega-3 PUFA (eicosapentaenoic: EPA and docosahexaenoic: DHA) and omega-6 PUFA (arachidonic: AA), were measured at baseline in plasma and in the erythrocytes membrane. Cognitive status was assessed using the mini mental state examination (MMSE), at baseline and every six months during follow-up. The median follow-up period was of 11,5 months. Compared to participants with minor neurocognitive disorders (MMSEae24), participants with major neurocognitive disorders (NCD) had lower plasmatic concentrations of EPA and DHA (p \textless 0.05) at baseline. Erythrocyte AA and DHA concentrations were significantly lower in patients with cognitive decline (defined as a ae2 points loss of MMSE per year), while no difference in plasmatic concentrations was observed. Our study suggests that omega-3 PUFA plasma concentrations (mainly EPA and DHA) could be associated with cognitive status in older people. Moreover, in this exploratory study, lower erythrocyte PUFA concentrations (AA and DHA) were associated with accelerated decline and could be proposed as a surrogate marker for prediction of cognitive decline

Deciphering the genetic regulation of peripheral blood transcriptome in pigs through expression genome-wide association study and allele-specific expression analysis

Background: Efforts to improve sustainability in livestock production systems have focused on two objectives: investigating the genetic control of immune function as it pertains to robustness and disease resistance, and finding predictive markers for use in breeding programs. In this context, the peripheral blood transcriptome represents an important source of biological information about an individual ’ s health and immunological status, and has been proposed for use as an intermediate phenotype to measure immune capacity. The objective of this work was to study the genetic architecture of variation in gene expression in the blood of healthy young pigs using two approaches: an expression genome-wide association study (eGWAS) and allele-specific expression (ASE) analysis. [br/] Results: The blood transcriptomes of 60-day-old Large White pigs were analyzed by expression microarrays for eGWAS (242 animals) and by RNA-Seq for ASE analysis (38 animals). Using eGWAS, the expression levels of 1901 genes were found to be associated with expression quantitative trait loci (eQTLs). We recovered 2839 local and 1752 distant associations (Single Nucleotide Polymorphism or SNP located less or more than 1 Mb from expression probe, respectively). ASE analyses confirmed the extensive cis -regulation of gene transcription in blood, and revealed allelic imbalance in 2286 SNPs, which affected 763 gene s. eQTLs and ASE-genes were widely distributed on all chromosomes. By analyzing mutually overlapping eGWAS results, we were able to describe putative regulatory networks, which were further refined using ASE data. At the functional level, genes with genetically controlled expression that were detected by eGWAS and/or ASE analys es were significantly enriched in biological processes related to RNA processing and immune function. Indeed, numerous distant and local regulatory relationships were detected within the major histocompatibility complex region on chromosome 7, revealing ASE for most class I and II genes. Conclusions : This study represents, to the best of our knowledge, the first genome-wide map of the genetic control of gene expression in porcine peripheral blood. T hese results represent an interesting resource for the identification of genetic markers and blood biomarkers associated with variations in immunity traits in pigs, as well as any other complex traits for which blood is an appropriate surrogate tissue

Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing

The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens

Additional file 4: Table S3. of Deciphering the genetic regulation of peripheral blood transcriptome in pigs through expression genome-wide association study and allele-specific expression analysis

ASE analysis results. (XLSX 126 kb

Additional file 11: Figure S4. of Deciphering the genetic regulation of peripheral blood transcriptome in pigs through expression genome-wide association study and allele-specific expression analysis

Gene association network centered on eQTL-SNP H3GA0029721. A: Circo plot produced by R package RCirco which maps eQTL-SNP H3GA0029721 and its associated genes according to their genomic position. The blue links represent associations between this eQTL-SNP on SSC10 and 47 genes that map onto other chromosomes. B: The distribution of all (grey) and significant (red) correlation coefficients calculated from pairwise comparisons of expression variation in probes associated with H3GA0029721, performed by the PCIT algorithm. (PDF 131 kb

Football (association) / par N. G. Tunmer,... et Eugène Fraysse,... ; [avant-propos par G. de Saint-Clair]

Collection : Petite bibliothèque athlétiqueContient une table des matièresAvec mode text

Molecular uncoupling of E and EE tissues in SCNT conceptuses.

<p>The gene set used to classify each conceptus includes six genes from the extra-embryonic tissues and has been described as an accurate predictor of embryonic stages in controls. A) Patterns resulting from AI: examples of a filamentous conceptus with a disc at stage 3 (Fil-N2) and a trophoblastic vesicle (TV) with an ablated disc since Day 15. B) Patterns resulting from SCNT: examples of tubular conceptuses with a delayed embryonic disc (stage 2) or no disc (Ab2).</p

New biological outcomes of validated DEGs.

<p>A) <i>FN1</i> is restricted to the endoderm. <i>In situ</i> hybridisation in AI (a), IVP (b), and SCNT D18 EE tissues: Med (c), Low (d), High (e), using an anti-sense FN1 DIG-labelled riboprobe. (t) trophoblast, (e) endoderm. In the AI panel, f) shows c93/<i>SOLD1</i>, a trophoblast-specific control from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038309#pone.0038309-Degrelle1" target="_blank">[23]</a>. The sense probe gave a negative signal in all tissues (not shown). Despite differential expression levels in array and QPCR data, this gene is expressed in the same cells, regardless of conceptus origin. Only a small part of each conceptus is shown. Scale bar is 150 µm. B) Microvilli abnormalities in SCNT EE tissues at D18. In the SCNT groups where <i>MYO6</i> and <i>LHFPL2</i> were underexpressed (b, c), epithelial microvilli appeared shorter and/or fused. SEM images of the external face (extra-embryonic ectoderm or trophoblast) of D18 EE tissues from SCNT Low and Med conceptuses as compared to controls (AI in a). Magnifications: a) x 30000, b) x 35000, c) x 30000. C) <i>PLIN2</i> is expressed in the trophoblast of D18 EE tissues and absent from the yolk sac at D25 [the yolk sac is composed of endoderm (e) and mesoderm (m)]. It is also expressed in binucleated cells (BNC) from D63 bovine placentas. BNC are differentiated trophoblast cells, often considered as the anatomical equivalent of mouse giant cells. <i>In situ</i> hybridisations with an anti-sense PLIN2 DIG-labelled riboprobe on tissue cross-sections from D18 EET (a), D25 Yolk sac (b) and D63 placentas (c) developed after AI. The sense probe gave a negative signal in all tissues; data are not shown. Only a small part of each tissue is shown. Scale bar is 100 µm.</p