Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Search for Daily Modulation of MeV Dark Matter Signals with DAMIC-M

Dark Matter (DM) particles with sufficiently large cross sections may scatter as they travel through Earth's bulk. The corresponding changes in the DM flux give rise to a characteristic daily modulation signal in detectors sensitive to DM-electron interactions. Here, we report results obtained from the first underground operation of the DAMIC-M prototype detector searching for such a signal from DM with MeV-scale mass. A model-independent analysis finds no modulation in the rate of 1$e^-$ events with periods in the range 1-48 h. We then use these data to place exclusion limits on DM in the mass range [0.53, 2.7] MeV/c$^2$ interacting with electrons via a dark photon mediator. Taking advantage of the time-dependent signal we improve by $\sim$2 orders of magnitude on our previous limit obtained from the total rate of 1$e^-$ events, using the same data set. This daily modulation search represents the current strongest limit on DM-electron scattering via ultralight mediators for DM masses around 1 MeV/c$^2$

Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer

In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT–PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types

Development of methods for the preparation of radiopure ⁸²Se sources for the SuperNEMO neutrinoless double-beta decay experiment

A radiochemical method for producing 82Se sources with an ultra-low level of contamination of natural radionuclides (40K, decay products of 232Th and 238U) has been developed based on cation-exchange chromatographic purification with reverse removal of impurities. It includes chromatographic separation (purification), reduction, conditioning (which includes decantation, centrifugation, washing, grinding, and drying), and 82Se foil production. The conditioning stage, during which highly dispersed elemental selenium is obtained by the reduction of purified selenious acid (H2SeO3) with sulfur dioxide (SO2) represents the crucial step in the preparation of radiopure 82Se samples. The natural selenium (600 g) was first produced in this procedure in order to refine the method. The technique developed was then used to produce 2.5 kg of radiopure enriched selenium (82Se). The produced 82Se samples were wrapped in polyethylene (12 μm thick) and radionuclides present in the sample were analyzed with the BiPo-3 detector. The radiopurity of the plastic materials (chromatographic column material and polypropylene chemical vessels), which were used at all stages, was determined by instrumental neutron activation analysis. The radiopurity of the 82Se foils was checked by measurements with the BiPo-3 spectrometer, which confirmed the high purity of the final product. The measured contamination level for 208Tl was 8-54 μBq/kg, and for 214Bi the detection limit of 600 μBq/kg has been reached.</p

The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina) – phenotypic manifestations and genetic approaches

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome

Regulation of number and size of digits by posterior Hox genes: a dose-dependent mechanism with potential evolutionary implications

The proper development of digits, in tetrapods, requires the activity of several genes of the HoxA and HoxD homeobox gene complexes. By using a variety of loss-of-function alleles involving the five Hox genes that have been described to affect digit patterning, we report here that the group 11, 12, and 13 genes control both the size and number of murine digits in a dose-dependent fashion, rather than through a Hox code involving differential qualitative functions. A similar dose-response is observed in the morphogenesis of the penian bone, the baculum, which further suggests that digits and external genitalia share this genetic control mechanism. A progressive reduction in the dose of Hox gene products led first to ectrodactyly, then to olygodactyly and adactyly. Interestingly, this transition between the pentadactyl to the adactyl formula went through a step of polydactyly. We propose that in the distal appendage of polydactylous short-digited ancestral tetrapods, such as Acanthostega, the HoxA complex was predominantly active. Subsequent recruitment of the HoxD complex contributed to both reductions in digit number and increase in digit length. Thus, transition through a polydactylous limb before reaching and stabilizing the pentadactyl pattern may have relied, at least in part, on asynchronous and independent changes in the regulation of HoxA and HoxD gene complexes

Electron energy-loss magnetic chiral dichroism of magnetic iron film affected by an underlayer in a double-layer structure

International audienceThe electron energy-loss magnetic chiral dichroism (EMCD) technique has been generally applied to single-phase magnetic crystals while rarely used for composite structures. It is mainly due to the lack of in-depth understanding of EMCD in the latter case where an additional phase may present under or above the investigated magnetic phase in the electron beam path. Here, we report EMCD signals acquired on a 15-nm-thick magnetic iron film with different thicknesses of the MgO substrate underlayer. By comparison, for areas with total thicknesses of t ¼ 0:59k and t ¼ 1:02k expressed with the mean free inelastic path of electron k, the relative dichroic signals at the Fe-L 3 edge are 3:8%61:0% and 3:5%61:6%, respectively, demonstrating no significant difference within the error range. However, the dichroic signal intensity at the Fe-L 2 edge peak is 77.6% larger in the thinner area of t ¼ 0:59k. Accordingly, the extracted m L =m s ratio of Fe 3d moments is 63% smaller in the thinner area even after the plural scattering is removed. Then, we confirm that the presence of an additional nonmagnetic phase under a magnetic iron crystal can noticeably affect the quantified value of the m L =m s ratio of iron moment determined from the EMCD measurements. Furthermore, the larger thickness of the underlayer may result in relatively higher valuation of the m L =m s ratio of the upper layer. A correction method, considering the different influence of the underlayer on the Fe-L 3 and L 2 edges, is in demand for developing potential applications of the EMCD technique to such composite nanomaterial systems. Published under license by AIP Publishing. https://doi.org/10.1063/1.5100245 Electron energy-loss magnetic chiral dichroism (EMCD) is an electron energy-loss spectroscopy (EELS)-based technique to locally characterize element-specific spin and orbital magnetic moments in crystalline materials. 1-3 The magnetic information is obtained from the EELS spectra recorded at two different positions on the diffraction plane, where different combinations of electron scattering vectors give rise to left-and right-handed polarized virtual photons in analogy with circular polarized X-rays in the synchrotron-based X-ray magnetic circular dichroism (XMCD) technique. 1 Since EMCD was first demonstrated by Schattschneider et al., 1 much effort has been made to develop it into a routine magnetic characterization technique in the transmission electron microscope (TEM). 4-14 Various EMCD experimental setups, for instance the energy spectrum imaging, 4,5 double aperture q À E mode, 6 spatially resolved EELS mode, 7 and scanning TEM, 8,9 have been proposed to improve the signal to noise ratio and the spatial resolution. In addition, the signal interpretation regarding the magnetic moment quantification has been widely concerned. The EMCD signal is not only simply affected by the intrinsic magnetism but also modulated by the dynamic electron diffraction condition which is related to the crystal structure, crystal orientation, and specimen thickness. 3,10,11 With a deep understanding of the dynamic diffraction, the quantification of element-specific and even site-specific orbital and spin moments has been experimentally realized. 11,12 Moreover, the theoretical simulation of the relative EMCD signal in various diffraction conditions has been widely applied for optimizing the experimental conditions 13,14 of EMCD or broadening its applications. 15 For the moment, the interpretation of quantitative results extracted from the EMCD signal is essentially based on an assumption that only one single-phase crystal is present in the electron beam path for each acquisition. Some EMCD experiments in the literature are actually in accordance with the assumed condition. For instance, experiments were performed on a single crystal in polycrystalline materials of Fe, 9 Co, 16 Ni, 16 or their oxides 7,17 or on epitaxially grown thin layers of single-crystalline Fe, Mn, and their compounds observed fro