Regulation of Male Fertility by the Renin-Angiotensin System

The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility.This study was supported by grants from the Basque Government (GIC12/173) and University of the Basque Country (UPV/EHU) (EHUA14/17)

La verdad como fundamento en Lev Tolstói y Mohandas K. Gandhi. Una interpretación para la ética de la noviolencia.

Nuestra pretensión es dilucidar qué papel ocupaba la búsqueda de la verdad en las fundamentaciones de la noviolencia expuestas por Lev Nikoláevich Tolstói y Mohandas K. Gandhi. Una vez propuesta y analizada la diferencia entre verdad relativa y verdad ontológica, se proponen algunas manifestaciones que podrían servir para hacer tangible dicha verdad ontológica. Como concepto inefable y escurridizo que es, reflexionamos sobre si su expresión cotidiana puede encontrarse –así lo proponemos- en la práctica virtuosa del amor, la justicia o la humildad, entre otros valores. En la primera parte del trabajo se ofrece una recopilación comparativa de las reflexiones legadas por estos dos referentes de la noviolencia; mientras que en la segunda parte se proponen algunas claves para interpretar la expresión de esta verdad ontológica. Dichas claves se harán concordar con las ideas y palabras de los propios autores, y se ofrecerán como expresión de la ética que puede cultivarse desde la noviolencia.Our work is an attempt to elucidate the role of truth and how it is considered in the foundations of nonviolence expressed by Lev Nikolaevich Tolstoy and Mohandas K. Gandhi.Once the difference between relative truth and ontological truth has been proposed and analyzed, this review reflects on some daily manifestations which could express this ontological truth. Accepting that we are dealing with an ineffable and elusive concept, we reflect on whether its daily expression can be found -as we propose- in the virtuous practice of love, justice, or humility, among other values.In the first part, we will compile the reflections bequeathed by these two mentors of nonviolence; in the second part, we will offer some keys to interpret those expressions of this ontological truth. These keys will be matched with the ideas spread by the authors themselves, and will be offered as the ethical values that may be cultivated by nonviolence thinking

Integrable Chiral Theories in 2+1 Dimensions

Following a recent proposal for integrable theories in higher dimensions based on zero curvature, new Lorentz invariant submodels of the principal chiral model in 2+1 dimensions are found. They have infinite local conserved currents, which are explicitly given for the su(2) case. The construction works for any Lie algebra and in any dimension, and it is given explicitly also for su(3). We comment on the application to supersymmetric chiral models.Comment: 13 page

"La ley de la violencia y la ley del amor", un manifiesto noviolento de Lev Tolstói

Reseña sobre dicha obra, inédita en español hasta el año 2018. Publicada por Hermida Editores

Integrable theories in any dimension and homogenous spaces

We construct local zero curvature representations for non-linear sigma models on homogeneous spaces, defined on a space-time of any dimension, following a recently proposed approach to integrable theories in dimensions higher than two. We present some sufficient conditions for the existence of integrable submodels possessing an infinite number of local conservation laws. Examples involving symmetric spaces and group manifolds are given. The $CP^N$ models are discussed in detail.Comment: LaTeX, 35 page

(Pro)renin Receptor Is Present in Human Sperm and It Adversely Affects Sperm Fertility Ability

Sperm fertility ability may be modulated by different molecular systems, such as the renin-angiotensin system (RAS). Although renin is one of its most relevant peptides, the presence and role of the (pro)renin receptor (PRR) is completely unknown. We have proved for the first time the existence of PRR and its transcript in human sperm by western blot and RT-PCR. Immunofluorescence studies showed that this receptor is mainly located in the apical region over the acrosome and in the postacrosomal region of the sperm head and along the sperm tail. In addition, this prospective cohort study also proves that semen samples with higher percentages of PRR-positive spermatozoa are associated with poor sperm motility, worse blastocyst development and no-viable blastocysts. Our results provide insight into how PRR play a negative role in sperm physiology that it may condition human embryo quality and development. An in-depth understanding of the role of PRR in sperm fertility can help elucidate its role in male infertility, as well as establish biomarkers for the diagnosis or selection of sperm to use during assisted reproductive techniques.This research was funded by grants from the Basque Government (GIC12/173; to M.G. and I.M.-H.) and University of the Basque Country (UPV/EHU; to M.G. and I.U.-A.) (EHUA14/17)

Infinite symmetries in the Skyrme model

We show that the Skyrme theory possesses a submodel with an infinite number of local conserved currents. The constraints leading to the submodel explore a decomposition of SU(2) with a complex field parametrizing the symmetric space SU(2)/U(1) and a real field in the direction of U(1). We demonstrate that the Skyrmions of topological charges $\pm 1$ belong to such integrable sector of the theory. Our results open ways to the development of exact methods, compensating for the non-existence of a BPS type sector in the Skyrme theory.Comment: 9 pages, LaTeX, version to appear in Phys. Lett.

SPANX-A/D protein subfamily plays a key role in nuclear organisation, metabolism and flagellar motility of human spermatozoa

Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes encode a protein family (SPANX-A, -B, -C and -D), whose expression is limited to the testis and spermatozoa in normal tissues and to a wide variety of tumour cells. Present only in hominids, SPANX-A/D is exclusively expressed in post-meiotic spermatids and mature spermatozoa. However, the biological role of the protein family in human spermatozoa is largely unknown. Combining proteomics and molecular approaches, the present work describes the presence of all isoforms of SPANX-A/D in human spermatozoa and novel phosphorylation sites of this protein family. In addition, we identify 307 potential SPANX-A/D interactors related to nuclear envelop, chromatin organisation, metabolism and cilia movement. Specifically, SPANX-A/D interacts with fumarate hydratase and colocalises with both fumarate hydratase and Tektin 1 proteins, involved in meeting energy demands for sperm motility, and with nuclear pore complex nucleoporins. We provide insights into the molecular features of sperm physiology describing for the first time a multifunctional role of SPANX-A/D protein family in nuclear envelope, sperm movement and metabolism, considered key functions for human spermatozoa. SPANX-A/D family members, therefore, might be promising targets for sperm fertility management.Spanish Health Department ISCIII-DT, Basque Government and Danish Medical Research Council. IU-A was supported by a fellowship from the University of the Basque Country (UPV/EHU). IM-H was supported by a fellowship from the Basque Government. I.K. was supported by a grant from the Danish Medical Research Counci

Morphine leads to global genome changes in H3K27me3 levels via a Polycomb Repressive Complex 2 (PRC2) self-regulatory mechanism in mESCs

Background: Environmentally induced epigenetic changes can lead to health problems or disease, but the mechanisms involved remain unclear. Morphine can pass through the placental barrier leading to abnormal embryo development. However, the mechanism by which morphine causes these effects and how they sometimes persist into adulthood is not well known. To unravel the morphine-induced chromatin alterations involved in aberrant embryo development, we explored the role of the H3K27me3/PRC2 repressive complex in gene expression and its transmission across cellular generations in response to morphine. Results: Using mouse embryonic stem cells as a model system, we found that chronic morphine treatment induces a global downregulation of the histone modification H3K27me3. Conversely, ChIP-Seq showed a remarkable increase in H3K27me3 levels at specific genomic sites, particularly promoters, disrupting selective target genes related to embryo development, cell cycle and metabolism. Through a self-regulatory mechanism, morphine downregulated the transcription of PRC2 components responsible for H3K27me3 by enriching high H3K27me3 levels at the promoter region. Downregulation of PRC2 components persisted for at least 48 h (4 cell cycles) following morphine removal, though promoter H3K27me3 levels returned to control levels. Conclusions: Morphine induces targeting of the PRC2 complex to selected promoters, including those of PRC2 components, leading to characteristic changes in gene expression and a global reduction in H3K27me3. Following morphine removal, enhanced promoter H3K27me3 levels revert to normal sooner than global H3K27me3 or PRC2 component transcript levels. We suggest that H3K27me3 is involved in initiating morphine-induced changes in gene expression, but not in their maintenance.This study was supported by grants from the Spanish Health Department ISCIII (DTS 18/00142) and University of the Basque Country. IM was supported by fellowship from Basque Government, and MA and IU were supported by fellowship from the University of the Basque Country (UPV/EHU)

Antibody persistence and booster responses 24-36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial.

This phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2-10-year-olds) in parent study NCT01339923. Children aged 35 months to 12 years (N = 851) were enrolled. Follow-on participants (N = 646) were randomised 2:1 to vaccination and non-vaccination subsets; vaccination subsets received an additional 4CMenB dose. Newly enrolled vaccine-naïve participants (N = 205) received 2 catch-up doses, 1 month apart (accelerated schedule). Antibody levels were determined using human serum bactericidal assay (hSBA) against MenB indicator strains for fHbp, NadA, PorA and NHBA. Safety was also evaluated. Antibody levels declined across follow-on groups at 24-36 months versus 1 month post-vaccination. Antibody persistence and booster responses were similar between infants receiving the reduced or licensed 4CMenB-schedule. An additional dose in follow-on participants induced higher hSBA titres than a first dose in vaccine-naïve children. Two catch-up doses in vaccine-naïve participants induced robust antibody responses. No safety concerns were identified. Antibody persistence, booster responses, and safety profiles were similar with either 2 + 1 or 3 + 1 vaccination schedules. The accelerated schedule in vaccine-naïve children induced robust antibody responses.Novartis Vaccines DivisionGlaxoSmithKline Biologicals S