Hexavalents in spermatocytes of Robertsonian heterozygotes between Mus m. domesticus 2n 26 from the Vulcano and Lipari Islands (Aeolian Archipelago, Italy)

The size and shape of the chromosomes, as well as the chromosomal domains that compose them, are determinants in the distribution and interaction between the bivalents within the nucleus of spermatocytes in prophase I of meiosis. Thus the nuclear architecture characteristic of the karyotype of a species can be modified by chromosomal changes such as Robertsonian (RB) chromosomes. In this study we analysed the meiotic prophase nuclear organization of the heterozygous spermatocytes from Mus musculus domesticus 2n=26, and the synaptic configuration of the hexavalent formed by the dependent Rb chromosomes Rbs 6.16, 16.10, 10.15, 15.17 and the telocentric chromosomes 6 and 17. Spreads of 88 pachytene spermatocytes from two males were studied and in all of them five metacentric bivalents, four telocentric bivalents, one hexavalent and the XY bivalent were observed. About 48% of the hexavalents formed a chain or a ring of synapsed chromosomes, the latter closed by synapsis between the short arms of telocentric chromosomes 6 and 17. About 52% of hexavalents formed an open chain of 10 synapsed chromosomal arms belonging to 6 chromosomes. In about half of the unsynapsed hexavalents one of the telocentric chromosome short arms appears associated with the X chromosome single axis, which was otherwise normally paired with the Y chromosome. The cluster of pericentromeric heterochromatin mostly determines the hexavalent’s nuclear configuration, dragging the centromeric regions and all the chromosomes towards the nuclear envelope similar to an association of five telocentric bivalents. These reiterated encounters between these chromosomes restrict the interactions with other chromosomal domains and might favour eventual rearrangements within the metacentric, telocentric or hexavalent chromosome subsets. The unsynapsed short arms of telocentric chromosomes frequently bound to the single axis of the X chromosome could further complicate the already complex segregation of hexavalent chromosomes

Robertsonian chromosomes and the nuclear architecture of mouse meiotic prophase spermatocytes

BACKGROUND: The nuclear architecture of meiotic prophase spermatocytes is based on higher-order patterns of spatial associations among chromosomal domains from different bivalents. The meiotic nuclear architecture depends on the chromosome characteristics and consequently is prone to modification by chromosomal rearrangements. In this work, we consider Mus domesticus spermatocytes with diploid chromosome number 2n = 40, all telocentric, and investigate a possible modification of the ancestral nuclear architecture due to the emergence of derived Rb chromosomes, which may be present in the homozygous or heterozygous condition. RESULTS: In the 2n = 40 spermatocyte nuclei random associations mediated by pericentromeric heterochromatin among the 19 telocentric bivalents ocurr at the nuclear periphery. The observed frequency of associations among them, made distinguishable by specific probes and FISH, seems to be the same for pairs that may or may not form Rb chromosomes. In the homozygote Rb 2n = 24 spermatocytes, associations also mediated by pericentromeric heterochromatin occur mainly between the three telocentric or the eight metacentric bivalents themselves. In heterozygote Rb 2n = 32 spermatocytes all heterochromatin is localized at the nuclear periphery, yet associations are mainly observed among the three telocentric bivalents and between the asynaptic axes of the trivalents. CONCLUSIONS: The Rb chromosomes pose sharp restrictions for interactions in the 2n = 24 and 2n = 32 spermatocytes, as compared to the ample possibilities for interactions between bivalents in the 2n = 40 spermatocytes. Undoubtedly the emergence of Rb chromosomes changes the ancestral nuclear architecture of 2n = 40 spermatocytes since they establish new types of interactions among chromosomal domains, particularly through centromeric and heterochromatic regions at the nuclear periphery among telocentric and at the nuclear center among Rb metacentric ones

The male mouse meiotic cilium emanates from the mother centriole at zygotene prior to centrosome duplication

Cilia are hair-like projections of the plasma membrane with an inner microtubule skeleton known as axoneme. Motile cilia and flagella beat to displace extracellular fluids, playing important roles in the airways and reproductive system. On the contrary, primary cilia function as cell-type-dependent sensory organelles, detecting chemical, mechanical, or optical signals from the extracellular environment. Cilia dysfunction is associated with genetic diseases called ciliopathies and with some types of cancer. Cilia have been recently identified in zebrafish gametogenesis as an important regulator of bouquet conformation and recombination. However, there is little information about the structure and functions of cilia in mammalian meiosis. Here we describe the presence of cilia in male mouse meiotic cells. These solitary cilia formed transiently in 20% of zygotene spermatocytes and reached considerable lengths (up to 15–23 µm). CEP164 and CETN3 localization studies indicated that these cilia emanate from the mother centriole prior to centrosome duplication. In addition, the study of telomeric TFR2 suggested that cilia are not directly related to the bouquet conformation during early male mouse meiosis. Instead, based on TEX14 labeling of intercellular bridges in spermatocyte cysts, we suggest that mouse meiotic cilia may have sensory roles affecting cyst function during prophase IThis work was funded by BIOUAM02-2020 to J.P. and R.G. and grants PID2019-104941RB-I00 from MCIN/AEI/10.13039/501100011033 and ACCI-2020 from CIBERER to F.G.

A perikinetochoric ring defined by MCAK and Aurora-B as a novel centromere domain

Mitotic Centromere-Associated Kinesin (MCAK) is a member of the kinesin-13 subfamily of kinesin-related proteins. In mitosis, this microtubule-depolymerising kinesin seems to be implicated in chromosome segregation and in the correction of improper kinetochore-microtubule interactions, and its activity is regulated by the Aurora-B kinase. However, there are no published data on its behaviour and function during mammalian meiosis. We have analysed by immunofluorescence in squashed mouse spermatocytes, the distribution and possible function of MCAK, together with Aurora-B, during both meiotic divisions. Our results demonstrate that MCAK and Aurora-B colocalise at the inner domain of metaphase I centromeres. Thus, MCAK shows a “cone”-like three-dimensional distribution beneath and surrounding the closely associated sister kinetochores. During the second meiotic division, MCAK and Aurora-B also colocalise at the inner centromere domain as a band that joins sister kinetochores, but only during prometaphase II in unattached chromosomes. During chromosome congression to the metaphase II plate, MCAK relocalises and appears as a ring below each sister kinetochore. Aurora-B also relocalises to appear as a ring surrounding and beneath kinetochores but during late metaphase II. Our results demonstrate that the redistribution of MCAK at prometaphase II/metaphase II centromeres depends on tension across the centromere and/or on the interaction of microtubules with kinetochores. We propose that the perikinetochoric rings of MCAK and Aurora-B define a novel transient centromere domain at least in mouse chromosomes during meiosis. We discuss the possible functions of MCAK at the inner centromere domain and at the perikinetochoric ring during both meiotic divisions

X chromosome inactivation during grasshopper spermatogenesis

Regulation of transcriptional activity during meiosis depends on the interrelated processes of recombination and synapsis. In eutherian mammal spermatocytes, transcription levels change during prophase-I, being low at the onset of meiosis but highly increased from pachytene up to the end of diplotene. However, X and Y chromosomes, which usually present unsynapsed regions throughout prophase-I in male meiosis, undergo a specific pattern of transcriptional inactivation. The interdependence of synapsis and transcription has mainly been studied in mammals, basically in mouse, but our knowledge in other unrelated phylogenetically species is more limited. To gain new insights on this issue, here we analyzed the relationship between synapsis and transcription in spermatocytes of the grasshopper Eyprepocnemis plorans. Autosomal chromosomes of this species achieve complete synapsis; however, the single X sex chromosome remains always unsynapsed and behaves as a univalent. We studied transcription in meiosis by immunolabeling with RNA polymerase II phosphorylated at serine 2 and found that whereas autosomes are active from leptotene up to diakinesis, the X chromosome is inactive throughout meiosis. This inactivation is accompanied by the accumulation of, at least, two repressive epigenetic modifications: H3 methylated at lysine 9 and H2AX phosphorylated at serine 139. Furthermore, we identified that X chromosome inactivation occurs in premeiotic spermatogonia. Overall, our results indicate: (i) transcription regulation in E. plorans spermatogenesis differs from the canonical pattern found in mammals and (ii) X chromosome inactivation is likely preceded by a process of heterochromatinization before the initiation of meiosi

To what extent do fiscal regimes equalize opportunities for income acquisition among citizens?.

This paper employs the theory of equality of opportunity, described in Roemer’s book (Equality of Opportunity, Harvard University Press, 1998), to compute the extent to which tax-and-transfer regimes in 11 countries equalize opportunities among citizens for income acquisition. Roughly speaking, equality of opportunity for incomes has been achieved in a country when it is the case that the distributions of post-fisc income are the same for different types of citizen, where a citizen’s type is defined by the socio-economic status of his parents. Intuitively, a country will have equalized opportunity if the chances of earning high (or low) income are equal for citizens from all family backgrounds. Of course, pre-fisc income distributions, by type, will not be identical, as long as the educational system does not entirely make up for the disadvantage that children, who come from poor families face, but the tax-and-transfer system can play a role in rectifying that inequality. We include, in our computation, two numbers that summarize the extent to which each country’s current fiscal regime achieves equalization of opportunities for income, and the deadweight loss that would be incurred by moving to the regime that does.Fiscal regimes; Equal opportunities; Income acquisition;

An excess of star-forming galaxies in the fields of high-redshift QSOs

We present submillimetre (submm) and mid-infrared (MIR) imaging observations of five fields centred on quasi-stellar objects (QSOs) at 1.7 <z< 2.8. All five QSOs were detected previously at submm wavelengths. At 850 (450) μm, we detect 17 (11) submillimetre galaxies (SMGs) in addition to the QSOs. The total area mapped at 850 μm is ∼28 arcmin2 down to rms noise levels of 1–2 mJy beam−1, depending on the field. Integral number counts are computed from the 850-μm data using the same analytical techniques adopted by ‘blank-field’ submm surveys. We find that the ‘QSO-field’ counts show a clear excess over the blank-field counts at deboosted flux densities of ∼2–4 mJy; at higher flux densities, the counts are consistent with the blank-field counts. Robust MIR counterparts are identified for all four submm detected QSOs and ∼60 per cent of the SMGs. The MIR colours of the QSOs are similar to those of the local ultraluminous infrared galaxy (ULIRG)/active galactic nuclei (AGN) Mrk 231 if placed at 1 <z< 3 whilst most of the SMGs have colours very similar to those of the local ULIRG Arp 220 at 1 <z< 3. MIR diagnostics therefore find no strong evidence that the SMGs host buried AGN although we cannot rule out such a possibility. Taken together our results suggest that the QSOs sit in regions of the early universe which are undergoing an enhanced level of major star formation activity, and should evolve to become similarly dense regions containing massive galaxies at the present epoch. Finally, we find evidence that the level of star formation activity in individual galaxies appears to be lower around the QSOs than it is around more powerful radio-loud AGN at higher redshifts.We thank Ian Smail for extensive comments on the draft manuscript and Mark Thompson for useful discussions. The JCMT is operated by The Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the United Kingdom, the Netherlands Organisation for Scientific Research and the National Research Council of Canada. JCMT data were taken under project IDs M03AU46, M03BU32 and M04BU14. This work is based (in part) on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under a contract with NASA. Support for this work was provided by NASA through an award issued by JPL/Caltech. JAS, MJP and FJC acknowledge support from the Royal Society. FJC acknowledges further support from the Spanish Ministerio de Educación y Ciencia under project ESP2006-13608

Diseño y aplicaciones de catalizadores de rodio e iridio moleculares y soportados en materiales nanoestructurados de carbono.

El trabajo desarrollado en esta Memoria se ha centrado en el diseño, síntesis, caracterizacióny estudios de estabilidad de compuestos moleculares de rodio e iridio soportados en materiales nanoestructurados de carbono. La actividad catalítica de los nuevos materiales híbridos y la de los complejos moleculares relacionados de rodio e iridio se ha evaluado en la hidrosililación de alquinos y en la oxidación química y electroquímica de agua, respectivamente.Los complejos de rodio(I) y (III) soportados en un óxido de grafeno reducido térmicamente a400 ºC por enlace covalente carbono-nitrógeno entre un ligando NHC mesoiónico (4-fenil-3-metil-1,2,3-triazol-5-ilideno) y la pared del grafeno, Rh(I)/Rh(III)-NHC@TRGO, y los complejos moleculares relacionados muestran alta actividad en la hidrosililación de alquinos y una excelente regio- y estereoselectividad al isómero cinético β-(Z)-vinilsilano. Concretamente, el catalizador ciclometalado [Cp*RhI(C,C')-Triaz] (Triaz = 1,4-difenil-3-metil-1,2,3-triazol-5-ilideno) es un catalizador sobresaliente en la hidrosililación de alquinos terminales, alifáticos y aromáticos, a temperatura ambiente con completa regio- y estereoselectividad al isómero β(Z)-vinilsilano. Por otro lado, aunque el catalizador híbrido relacionado de rodio(III)-triazolilideno no es activo a temperatura ambiente, muestra la misma actividad y selectividad que el catalizador homogéneo a 60 °C. Adicionalmente, los catalizadores híbridos basados en grafeno modificado Rh-NHC@TRGO son completamente reciclables en la hidrosililación de alquinos con excelente control de la selectividad -(Z). Los estudios por DFT del mecanismo de hidrosililación para el catalizador molecular de Rh(III) evidencian la posible participación de un mecanismo bifuncional metal-ligando basado en una ciclometalación reversible.Los materiales híbridos basados en complejos Ir(I)-NHC anclados a nanotubos de carbono a través de grupos éster, Ir(I)-NHC@CNT, son catalizadores eficientes en la oxidación química y electroquímica de agua. El estudio ha revelado que tanto los catalizadores moleculares homogéneos como los heterogéneos que poseen un ligando NHC funcionalizado con un grupo sulfonato son mucho más activos que los catalizadores moleculares relacionados con ligandos NHC no hidrosolubles, tanto en la oxidación química de agua, con CAN como oxidante de sacrificio, como en la oxidación electroquímica en la que se alcanzan valores de TOF de hasta 22000 h-1 a 1.4 V para el catalizador híbrido NHC-sulfonato. Por otro lado, se ha observado que la estructura grafítica del soporte juega un papel importante en el rendimiento electrocatalítico de oxidación de agua con complejos de iridio(I)-NHC soportados por enlace carbonato a dos óxidos de grafeno de diferente estructura grafítica. Se ha comprobado que el desplazamiento del ligando cloruro en los centros metálicos de iridio por grupos oxigenados de la pared nanoestructurada del grafeno tiene un impacto negativo en la actividad electrocatalítica del catalizador híbrido resultante.<br /

CYLD regulates keratinocyte differentiation and skin cancer progression in humans

CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapiesThis work was funded by grants from the Ministerio de Ciencia e Innovación PI06/1233 and PI10/01480 to MLC, and SAF2010-22156 to ARS

Meiotic Pairing and Segregation of Achiasmate Sex Chromosomes in Eutherian Mammals: The Role of SYCP3 Protein

In most eutherian mammals, sex chromosomes synapse and recombine during male meiosis in a small region called pseudoautosomal region. However in some species sex chromosomes do not synapse, and how these chromosomes manage to ensure their proper segregation is under discussion. Here we present a study of the meiotic structure and behavior of sex chromosomes in one of these species, the Mongolian gerbil (Meriones unguiculatus). We have analyzed the location of synaptonemal complex (SC) proteins SYCP1 and SYCP3, as well as three proteins involved in the process of meiotic recombination (RAD51, MLH1, and γ-H2AX). Our results show that although X and Y chromosomes are associated at pachytene and form a sex body, their axial elements (AEs) do not contact, and they never assemble a SC central element. Furthermore, MLH1 is not detected on the AEs of the sex chromosomes, indicating the absence of reciprocal recombination. At diplotene the organization of sex chromosomes changes strikingly, their AEs associate end to end, and SYCP3 forms an intricate network that occupies the Y chromosome and the distal region of the X chromosome long arm. Both the association of sex chromosomes and the SYCP3 structure are maintained until metaphase I. In anaphase I sex chromosomes migrate to opposite poles, but SYCP3 filaments connecting both chromosomes are observed. Hence, one can assume that SYCP3 modifications detected from diplotene onwards are correlated with the maintenance of sex chromosome association. These results demonstrate that some components of the SC may participate in the segregation of achiasmate sex chromosomes in eutherian mammals