Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects.

Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the 1-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 183 aborted fetuses compared with 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI: 4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous/FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital gastric intrinsic factor (GIF) deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.

Foreign DNA acquisition by invertebrate genomes.

Recent studies have highlighted that the accidental acquisition of DNA from other species by invertebrate genomes is much more common than originally thought. The transferred DNAs are of bacterial or eukaryote origin and in both cases the receiver species may end up utilising the transferred genes for its own benefit. Frequent contact with prokaryotic DNA from symbiotic endocellular bacteria may predispose invertebrates to incorporate this genetic material into their genomes. Increasing evidence also points to viruses as major players in transferring genes and mobile elements between the species they infect. Unexpectedly a gene flux between Hymenoptera and Lepidoptera mediated by endogenous viruses of parasitic wasps has been recently unravelled, suggesting we are probably just seeing the tip of the iceberg concerning horizontal gene transfers in invertebrates. In the context of insect for feed and food, if the new technology of insect genome editing (such as Crisper/Cas9) were used to modify the genome of reared insects it is important to take into account the risk that an introduced gene can be transferred. More generally, although insects are traditionally consumed in Asia and Africa, knowledge on insect viruses is still limited rendering it difficult to predict the impact they might have in the context of insect rearing at an industrial scale.

A non-synonymous polymorphism in galectin-3 lectin domain is associated with allergic reactions to beta-lactam antibiotics.

Genetic predictors of beta-lactam (BL) allergy are mostly related to Immunoglobulin E (IgE) synthesis and atopy. Despite this context, little attention has been devoted to genes of IgE/FcɛRI pathway, such as galectin-3, a ß-galactoside-binding lectin, which binds to IgE. We evaluated the association of LGALS3 polymorphisms with BL allergy in 395 Spanish and 198 Italian cases, compared with 310- and 339-matched controls, respectively. The rs11125 predicted BL allergy with an odds ratio of 4.0 in Spanish population (P<0.0001). This association was replicated with an odds ratio of 5.1 in Italian population (P<0.0001); rs11125 predicted also increased serum level of total IgE in Spanish controls. These data are consistent with the predicted deleterious influence of Gln>His substitution produced by rs11125 on galactose-binding activity of galectin-3. In conclusion, LGALS3 is the strongest genetic predictor of BL allergy reported so far. This association reflects the influence of genes of IgE/FcɛRI pathway in this pathology.

Association of the interferon-ß gene with pericentromeric heterochromatin is dynamically regulated during virus infection through a YY1-dependent mechanism.

Nuclear architecture as well as gene nuclear positioning can modulate gene expression. In this work, we have analyzed the nuclear position of the interferon-ß (IFN-ß) locus, responsible for the establishment of the innate antiviral response, with respect to pericentromeric heterochromatin (PCH) in correlation with virus-induced IFN-ß gene expression. Experiments were carried out in two different cell types either non-infected (NI) or during the time course of three different viral infections. In NI cells, we showed a monoallelic IFN-ß promoter association with PCH that strongly decreased after viral infection. Dissociation of the IFN-ß locus away from these repressive regions preceded strong promoter transcriptional activation and was reversible within 12 h after infection. No dissociation was observed after infection with a virus that abnormally maintained the IFN-ß gene in a repressed state. Dissociation induced after virus infection specifically targeted the IFN-ß locus without affecting the general structure and nuclear distribution of PCH clusters. Using cell lines stably transfected with wild-type or mutated IFN-ß promoters, we identified the proximal region of the IFN-ß promoter containing YY1 DNA-binding sites as the region regulating IFN-ß promoter association with PCH before as well as during virus infection.

Nonstructural NSs protein of rift valley fever virus interacts with pericentromeric DNA sequences of the host cell, inducing chromosome cohesion and segregation defects.

Rift Valley fever virus (RVFV) is an emerging, highly pathogenic virus; RVFV infection can lead to encephalitis, retinitis, or fatal hepatitis associated with hemorrhagic fever in humans, as well as death, abortions, and fetal deformities in animals. RVFV nonstructural NSs protein, a major factor of the virulence, forms filamentous structures in the nuclei of infected cells. In order to further understand RVFV pathology, we investigated, by chromatin immunoprecipitation, immunofluorescence, fluorescence in situ hybridization, and confocal microscopy, the capacity of NSs to interact with the host genome. Our results demonstrate that even though cellular DNA is predominantly excluded from NSs filaments, NSs interacts with some specific DNA regions of the host genome such as clusters of pericentromeric gamma-satellite sequence. Targeting of these sequences by NSs was correlated with the induction of chromosome cohesion and segregation defects in RVFV-infected murine, as well as sheep cells. Using recombinant nonpathogenic virus rZHDeltaNSs210-230, expressing a NSs protein deleted of its region of interaction with cellular factor SAP30, we showed that the NSs-SAP30 interaction was essential for NSs to target pericentromeric sequences, as well as for induction of chromosome segregation defects. The effect of RVFV upon the inheritance of genetic information is discussed with respect to the pathology associated with fetal deformities and abortions, highlighting the main role played by cellular cofactor SAP30 on the establishment of NSs interactions with host DNA sequences and RVFV pathogenesis.

Correlation between the shape of the ion mobility signals and the stepwise folding process of polylactide ions.

In the field of polymer characterization, the use of ion mobility mass spectrometry (IMMS) remains mainly devoted to the temporal separation of cationized oligomers according to their charge states, molecular masses and macromolecular architectures in order to probe the presence of different structures. When analyzing multiply charged polymer ions by IMMS, the most striking feature is the observation of breaking points in the evolution of the average collision cross sections with the number of monomer units. Those breaking points are associated to the folding of the polymer chain around the cationizing agents. Here, we scrutinize the shape of the arrival time distribution (ATD) of polylactide ions and associate the broadening as well as the loss of symmetry of the ATD signals to the coexistence of different populations of ions attributed to the transition from opened to folded stable structures. The observation of distinct distributions reveals the absence of folded/extended structure interconversion on the ion mobility time scale (1-10 ms) and then on the lifetime of ions within the mass spectrometer at room temperature. In order to obtain information on the possible interconversion between the different observed populations upon ion activation, we performed IM-IM-MS experiments (tandem ion mobility measurements). To do so, mobility-selected ions were activated by collisions before a second mobility measurement. Interestingly, the conversion by collisional activation from a globular structure into a (partially) extended structure, i.e. the gas phase unfolding of the ions, was not observed in the energetic regime available with the used experimental setup. The absence of folded/extended interconversion, even upon collisional activation, points to the fact that the polylactide ions are 'frozen' in their specific 3D structure during the desolvation/ionization electrospray processes. Copyright © 2017 John Wiley & Sons, Ltd.

Quantification of mitral regurgitation by the automated cardiac output method: an in vitro and in vivo study.

BACKGROUND: Recently, the automated cardiac output method (ACM) was introduced for the calculation of blood flow at the left ventricular outflow tract (LVOT). This study was performed to examine the possibility of using ACM for flow calculation at the level of the mitral valve and for the quantification of mitral regurgitation (MR) in vitro and in vivo. METHODS AND RESULTS: In a computer-controlled in vitro model of the human heart, aortic and mitral normal bioprosthetic valves were inserted. ACM and electromagnetic probe flow measurements correlated well at the LVOT and at the mitral level (r2 = 0.79 and 0.77, respectively). For stroke volumes ranging from 30 to 100 ml/beat, there was no statistically significant bias between ACM and electromagnetic flow probe (-1.5 and 1.3 ml for LVOT and mitral level, respectively). Limits of agreement were [-14; +11] ml and [-18; +16] ml, respectively. We evaluated 68 patients in our in vivo study. They were divided into three groups according to the results of "standard" echocardiographic Doppler methods for the semiquantification of MR: echocardiographic color Doppler cartography, intensity of the continuous wave Doppler spectra, and in some patients, pulmonary venous flow, conventional Doppler, and proximal isovelocity surface area quantitative data. Group 1 consisted of 35 patients without MR or a physiologic one; the 17 patients in group 2 had a mild MR (1-2/4) and in group 3, 16 patients with MR 3-4/4 were included. Regurgitant volume (RV) was calculated as the difference between ACM mitral flow and ACM aortic flow, and regurgitant fraction (RF) was defined as the ratio between RV and ACM mitral flow. When mitral flow was measured only from the four-chamber view, we found in group 1, RV = -0.57 (0.67) L/min and RF = -16% (19%); in group 2, RV = -0.31 (1.06) L/min and RF = -8% (19%); and in group 3, RV = 1.53 (0.94) L/min and RF = 23% (13%). RV and RF were statistically higher in group 3 compared with group 2 or group 1 (p < 0.0005), but no significant difference was found between groups 1 and 2. When mitral flow was measured by the mean value of ACM four-chamber and two-chamber views, this resulted in group 1, RV = -0.26 (0.63) L/min and RF = -8% (15%); in group 2, RV = 0.01 (1.04) L/min and RF = -2% (18%); and in group 3, RV = 2.07 (1.21) L/min and RF = 34% (19%). RV and RF were again significantly higher in group 3 (p < 0.0001). There was no significant difference between group 1 and group 2, but in group 1 RF was no longer statistically different from 0%. CONCLUSIONS: (1) In our in vitro setting, ACM is reliable both at the LVOT and at the mitral valve. (2) In the in vivo situation, some overlapping does exist between the three groups of MR. However, ACM is a very easy, rapid, and objective method to differentiate hemodynamic nonsignificant (<3/4) from significant (> or =3/4) MR. Together with other well-known methods for the quantification of MR, it should facilitate the gradation of MR in the clinical setting. The absence of significant differences between group 1 and group 2 proves that the accuracy of ACM measurements at the mitral valve needs to be ameliorated before ACM can be used as a gold standard for the noninvasive measurement of RV and RF.

[Uncommon cause of mitral insufficiency: pacemaker lead malpositioning in the left ventricle. Case report]. / Cause inhabituelle d'insuffisance mitrale: implantation involontaire d'une sonde de stimulation endocavitaire dans le ventricule gauche. A propos d'un cas.

Cardiac pacemakers' insertions may be associated with different types of complications such as lead's malposition. The authors report the observation of lead's malposition in the left ventricular chamber through the interatrial septum. This malposition is potentially dangerous because of the potent risk factor for stroke and thromboembolism that the patient might run. The diagnosis of this malposition can be done by surface electrocardiogram and thorax X-ray. However, we do insist on the importance of echocardiography and furthermore of transesophageal echocardiography which can lead to a much better choice in the treatment.

aubergine mutations in Drosophila melanogaster impair P cytotype determination by telomeric P elements inserted in heterochromatin.

Transposable P elements inserted in the heterochromatic Telomeric Associated Sequences on the X chromosome (1A site) of Drosophila melanogaster have a very strong capacity to elicit the P cytotype, a maternally transmitted condition which represses P element transposition and P-induced hybrid dysgenesis. This repressive capacity has previously been shown to be sensitive to mutant alleles of the gene Su(var)205, which encodes HP1 (Heterochromatin Protein 1), thus suggesting a role for chromatin structure in repression. Since an interaction between heterochromatin formation and RNA interference has been reported in various organisms, we tested the effect of mutant alleles of aubergine, a gene that has been shown to play a role in RNA interference in Drosophila, on the repressive properties of telomeric P elements. Seven out of the eight mutant alleles tested clearly impaired the repressive capacities of the two independent telomeric P insertions at 1A analyzed. P repression by P strains whose repressive capacities are not linked to the presence of P copies at 1A were previously found to be insensitive to Su(var)205; here, we show that they are also insensitive to aubergine mutations. These results strongly suggest that both RNA interference and heterochromatin structure are involved in the establishment of the P cytotype elicited by telomeric P elements, and reinforce the hypothesis that different mechanisms for repression of P elements exist which depend on the chromosomal location of the regulatory copies of P.

P element-encoded regulatory products enhance Repeat-Induced Gene Silencing (RIGS) of P-lacZ-white clusters in Drosophila melanogaster.

In Drosophila melanogaster, some clusters of P transgenes ( P-lacZ-white) display a variegating phenotype for the white marker in the eye, a phenomenon termed "Repeat-Induced Gene Silencing" (RIGS). We have tested the influence of the P element repression state (P cytotype) on the eye phenotype of several P-lac-w clusters that differ in transgene copy number or genomic insertion site. P element-encoded regulatory products strongly enhance RIGS. The effect occurs in both sexes, is detectable with clusters having at least three copies and is observed at both genomic locations tested (cytogenetic regions 50C and 92E). Single variegating P-lac-w transgenes located in pericentromeric heterochromatin are not affected by P regulatory products. All P strain backgrounds tested enhance RIGS, including chromosomes bearing a single P element encoding a truncated P transposase or carrying a single internally deleted KP element. Therefore, clusters are highly sensitive to different types of P repressors. Finally, a chimeric gene in which the 5' portion of the P element is fused to the polyhomeotic coding sequence (ph(p1)) also strongly enhances silencing of P-lac-w clusters. These results have implications for the mechanism of action of the P repressors and show that P transgene clusters represent a new class of P-sensitive alleles, providing a simple assay for somatic P repression that can be completed in one generation.