Hox Proteins Display a Common and Ancestral Ability to Diversify Their Interaction Mode with the PBC Class Cofactors

Hox protein function during development and evolution relies on conserved multiple interaction modes with cofactors of the PBC and Meis families

A Retinoic Acid Responsive Hoxa3 Transgene Expressed in Embryonic Pharyngeal Endoderm, Cardiac Neural Crest and a Subdomain of the Second Heart Field

A transgenic mouse line harbouring a β-galacdosidase reporter gene controlled by the proximal 2 kb promoter of Hoxa3 was previously generated to investigate the regulatory cues governing Hoxa3 expression in the mouse. Examination of transgenic embryos from embryonic day (E) 8.0 to E15.5 revealed regionally restricted reporter activity in the developing heart. Indeed, transgene expression specifically delineated cells from three distinct lineages: a subpopulation of the second heart field contributing to outflow tract myocardium, the cardiac neural crest cells and the pharyngeal endoderm. Manipulation of the Retinoic Acid (RA) signaling pathway showed that RA is required for correct expression of the transgene. Therefore, this transgenic line may serve as a cardiosensor line of particular interest for further analysis of outflow tract development

An ultraconserved Hox–Pbx responsive element resides in the coding sequence of Hoxa2 and is active in rhombomere 4

The Hoxa2 gene has a fundamental role in vertebrate craniofacial and hindbrain patterning. Segmental control of Hoxa2 expression is crucial to its function and several studies have highlighted transcriptional regulatory elements governing its activity in distinct rhombomeres. Here, we identify a putative Hox–Pbx responsive cis-regulatory sequence, which resides in the coding sequence of Hoxa2 and is an important component of Hoxa2 regulation in rhombomere (r) 4. By using cell transfection and chromatin immunoprecipitation (ChIP) assays, we show that this regulatory sequence is responsive to paralogue group 1 and 2 Hox proteins and to their Pbx co-factors. Importantly, we also show that the Hox–Pbx element cooperates with a previously reported Hoxa2 r4 intronic enhancer and that its integrity is required to drive specific reporter gene expression in r4 upon electroporation in the chick embryo hindbrain. Thus, both intronic as well as exonic regulatory sequences are involved in Hoxa2 segmental regulation in the developing r4. Finally, we found that the Hox–Pbx exonic element is embedded in a larger 205-bp long ultraconserved genomic element (UCE) shared by all vertebrate genomes. In this respect, our data further support the idea that extreme conservation of UCE sequences may be the result of multiple superposed functional and evolutionary constraints

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Subjective Evaluation of the Voice by the V.H.I. and Estimation of the Prevalence of Vocal Disorders among 723 Teachers

The literature shows that 20% of the teachers suffer from a vocal disorder. The researchers find frequent symptoms such as roughness, vocal fatigue and aggravation of the mean F0, peri-laryngeal pain and physical discomfort. Dysphonia is more frequent in female teachers. Age, years of experience, type of subject taught and environmental factors, vocal abuse, and stress have an impact on voice. They diminish the vocal performances of these professionals which has negative financial consequences. In our study, the voice of 723 teachers were evaluated by means of the VHI (F: 634, M: 89), teaching in ordinary schools or in positive discrimination schools. Fifteen municipality in the Brussel area participated in the study. We obtain a good test retest reliability for the whole group (F: 0,774 ; E: 0.749 ; P: 0.806 ; G : 0.836 – p>0.001). The scores at the retest are significantly lower for the global scores and the three subscales (G p<0.001, F p<0.001 ; E p=0.003 et P p<0.001). Intra-scale correlation is high (F versus E : 0.434 ; F vs P :0.455 ; E vs P : 0.527). The prevalence of vocal disorders was computed with regard to past ENT and speech pathology history and actual treatments, it was evaluated to 10,5%. Teachers who had been consulting an ENT or a speech language pathologist had higher scores at the global VHI. The elder the subjects are and the more teaching experience they have, the lesser they report vocal disorders (p=0.026 et p=0.013). The variables sex (p≥ 0.063), subject taught (p≥ 0.468), smoking (p=0.757), type of school (p≥ 0.867) and class grade (p≥ 0.212) do not have a significant impact on the VHI scores

Structural and morphological Control of TiO2 nanoparticles by selective adsorption of organic molecules

Semiconducting nanocrystals with tailored shapes have been widely investigated in the past decades because of their many shape-dependant properties. Anatase, a metastable phase of the titanium dioxyde (TiO2), is one of the most interesting material in many applications, such as photocatalysis, photovoltaics, photo/electrochromics or sensors. [1] In addition to an influence of the nanoparticles size, recent works on the anatase phase demonstrated the effect of the expressed surfaces nature on the nanoparticles photoreactivity. [2] Sol-gel method has been used to obtain a wide range of anatase nanoparticles sizes and morphologies by the control of concentrations, ions in solution, solution acidity and aging parameters. [3] In order to avoid the brookite phase often obtained with the anatase phase, microwave heating was efficiently used. Furthermore, conventional heating method has been compared with hydrothermal and microwave activated synthesis. The precise morphological control has been achieved by selective adsorption of organic molecules during synthesis: different shapes of anatase nanoparticles have been synthesized. [4,5]. The influences of synthesis parameters and the organic molecules nature on the nanoparticles structure and morphology have been analysed with various techniques, such as XRD and HRTEM

Evaluation subjective de la voix (VHI) chez 723 enseignants en région Bruxelloise.

Les études montrent qu’en moyenne 20% des enseignants présentent des troubles vocaux. Les auteurs relèvent des symptômes fréquents comme la raucité, la fatigue vocale, l’aggravation de la voix, les douleurs péri-laryngées et la sensation d’inconfort physique. Ils rapportent que la dysphonie est plus fréquente chez les femmes. L’âge, le nombre d’années d’expérience, le type de cours enseigné les facteurs environnementaux, l’abus, le malmenage vocal et le stress ont un impact sur la voix. Ces facteurs amenuisent les performances vocales professionnelles des enseignants et ont des conséquences non négligeables en terme d’économie. Dans notre étude, nous avons évalué la voix de 723 enseignants (F :634/ H :89), exerçant en écoles ordinaires ou en écoles à discrimination positive, à l’aide du VHI. Nous avons établi un premier état des lieux dans 15 communes de la région bruxelloise. Des mesures de fiabilité, de pertinence et de cohérence ont été réalisées. Nous obtenons une bonne fiabilité test-retest (F : 0,774 ; E : 0.749 ; P : 0.806 ; G : 0.836 – p>0.001 pour tous). Les scores du re-test sont significativement inférieurs pour les 3 sous-échelles (F p<0.001 ; E p=0.003 et P p<0.001) et le score global (p<0.001). La corrélation entre les 3 sous échelles est élevée (FvsE : 0.434 ; FvsP :0.455 ; EvsP : 0.527). La prévalence des troubles vocaux a été calculée en tenant compte des variables antécédents ORL, logopédiques et des traitements logopédiques en cours. Elle s’élève à 10,5%. Les enseignants ayant été confronté à une difficulté vocale (vu par un ORL ou/et un logopède) présentent donc des scores plus élevés au VHI global. Par contre, nous observons que plus les sujets sont âgés et ont de l’expérience moins ils ont de troubles vocaux (p=0.026 et p=0.013). De même, les variables telles que le genre (p≥ 0.063), la matière enseignée (p≥ 0.468), le fait de fumer (p=0.757), le type (p≥ 0.867) et le degré d’enseignement (p≥ 0.212) n’influent pas de manière significative les scores aux V.H.I

Steering the Mechanism of the Furan-Maleimide Retro-Diels-Alder Reaction to a Sequential Pathway with an External Mechanical Force

Mechanical forces are known to control rates of chemical reactions and govern reaction pathways, possibly inducing a change of mechanism with respect to the zero force one. We report on a switching of mechanism of the retro Diels-Alder bond breaking from concerted at zero force to sequential under tension for four furan–maleimide adducts, mechanophores widely used in polymer mechanochemistry because they can undergo reversible breakage under tension. The four different adducts differ by their regio- and stereochemistry. The reaction paths on the force modified potential energy surfaces were characterized by isometric and isotensional approaches and determining stationary points (equilibrium geometries and transition states) as a function of the applied force, as well as by analyzing the redistribution of strain energy over the internal degrees of freedom. We evidence different bond breaking pathways and rate constants for the four isomers, the proximal configurations being favored over the distal ones. The switch from a concerted pathway at zero force to a sequential one occurs for a threshold force that is significantly higher (≈ 2.4 nN) for the distal-exo adduct than for the other three (≈ 1 nN), explaining its larger resistance to breaking and its almost inert character under tension. The switch is accompanied by the rupture of one of the two scissile bonds which leads to a twice smaller imaginary frequency of the transition state and an increase of the activation barrier, which then decreases for higher force strengths (> 3nN) to become barrierless at a critical force value

Bond breaking of furan-maleimide adducts via a diradical sequential mechanism under an external mechanical force

Substituted furan-maleimide Diels-Alder adducts are bound by dynamical covalent bonds that make them particularly attractive mechanophores. Thermally activated [4+2] retro Diels-Alder (DA) reactions predominantly proceed via a concerted mechanism on the ground electronic state. We show that an asymmetric stretching direction along the anchoring bonds in both the endo and exo isomers of proximal dimethyl furan-maleimide adducts favors a sequential pathway. The switching from a concerted to a sequential mechanism occurs at external forces ≈ 1nN. The first bond rupture occurs for a projection of the pulling force on the scissile bond ≈ 4 nN for the exo adduct and ≈ 4.5 nN for the endo one. The reaction is inhibited for external forces up to ≈3.1 nN for the endo adduct and 3.6 nN the exo one after which it is activated. In the activated region, at 4 nN, the rupture rate of the first bond for the endo adduct is computed to be ≈ 2 orders of magnitude larger than for exo one in qualitative agreement with recent sonication experiments [ Z. Wang, S. L. Craig, Chemical Communications 2019, 55, 12263-12266.] In the intermediate region of the path between the rupture of the first and the second bond the lowest singlet state exhibits a diradical character for both adducts and is close in energy to a diradical triplet state. The computed values of spin-orbit coupling along the path are too small for inducing intersystem crossings. These findings open the way for the rational design of DA mechanophores