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The propensity to develop neurodegenerative diseases is influenced by diverse factors including genetic background, sex, lifestyle, including dietary habits and being overweight, and age. Indeed, with aging, there is an increased incidence of obesity and neurodegenerative processes, both of which are associated with inflammatory responses, in a sex-specific manner. High fat diet (HFD) commonly leads to obesity and markedly affects metabolism, both peripherally and centrally. Here we analyzed the metabolic and inflammatory responses of middle-aged (11-12 months old) transgenic amyloid precursor protein (TgAPP) mice of both sexes to HFD for 18 weeks (starting at 7-8 months of age). We found clear sex differences with females gaining significantly more weight and fat mass than males, with a larger increase in circulating leptin levels and expression of inflammatory markers in visceral adipose tissue. Glycemia and insulin levels increased in HFD fed mice of both sexes, with TgAPP mice being more affected than wild type (WT) mice. In the hypothalamus, murine amyloid ß (Aß) levels were increased by HFD intake exclusively in males, reaching statistical significance in TgAPP males. On a low fat diet (LFD), TgAPP males had significantly lower mRNA levels of the anorexigenic neuropeptide proopiomelanocortin (POMC) than WT males, with HFD intake decreasing the expression of the orexigenic neuropeptides Agouti-related peptide (AgRP) and neuropeptide Y (NPY), especially in TgAPP mice. In females, HFD increased POMC mRNA levels but had no effect on AgRP or NPY mRNA levels, and with no effect on genotype. There was no effect of diet or genotype on the hypothalamic inflammatory markers analyzed or the astrogliosis marker glial acidic protein (GFAP); however, levels of the microglial marker Iba-1 increased selectively in male TgAPP mice. In summary, the response to HFD intake was significantly affected by sex, with fewer effects due to genotype. Hypothalamic inflammatory cytokine ex

For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain.

The Multi-Modal Ultrasound Breast Imaging platform (MUBI) is a joint development of the Spanish National Research Council (CSIC) and the Complutense University of Madrid (UCM). It is composed of a ring of 16 transducers with 128 elements each, with a diameter of 22 cm, and working with a central frequency of 3.2 MHz. The total number of elements is 2048, and the electronic system can operate in single-element emission-reception or phased-array modes. It is intended to be a flexible platform for multi-modal ultrasound imaging research, combining reflection, transmission, and elasticity imaging, mainly oriented to breast diagnosis. In this work, research advances on the system are presented: Development of a fully operational prototype to be used with patients, design and manufacturing of calibration and anthropomorphic phantoms and design of an elastography device based on a waveform generator controlled vibrator. The work describes the design and laboratory preliminary tests of the new system components.

The development of innovative engineered epoxy composites aiming to manufacture cost-efficient materials with reduced weight and enhanced physical properties remains as a current industrial challenge. In this work we report an original procedure for manufacturing glass-fiber epoxy reinforced nanocomposites (GFECs) by employing electrospun fiber-mats as a reinforcing phase. These fibers have been produced from polyacrylonitrile and multiwalled carbon nanotubes solutions. Optimal protocols are designed by combining Taguchi method with the morphological, structural and mechanical properties obtained by scanning electron microscopy, profilometry and tensile tests. It is demonstrated that GFECs fabricated using GF800 glass fiber show an improvement/enhancement of the mechanical properties with a fracture strain up to 500¿MPa (around 20% higher than the non-reinforced epoxy composite counterpart). It is also shown that GFECs fabricated using GF3M glass fiber exhibited a reduction of the roughness up to 56%, which corresponds with a roughness improvement from N8 to N7 following the guidelines provided by the ISO 1302. These results suggest that this type of nanocomposites would be suitable to be used in the aeronautics and automotive industries., This work was financially supported by the “Convocatoria de Ayudas a la Realización de Proyectos de Grupos de Investigación 2020-2021” of the Universidad Católica de Murcia (UCAM), Spain, Reference: PMFI-12/21. Pavel Ryzhakov, Jordi Pons-Prats, and Christian Narváez- Muñoz would also like to acknowledge the support of the Ministerio de Ciencia, Innovación y Universidades of Spain via the “Severo Ochoa Programme” for Centres of Excellence in R&D (reference: CEX2018-000797-S) given to the International Centre for Numerical Methods in Engineering (CIMNE). The work of Christian Narváez- Muñoz was financially supported by the “Severo Ochoa PhD Scholarship” Reference: PRE2020-096632. Pavel Ryzhakov and Jordi Pons-Prats are Serra Hunter fellows., Peer Reviewed, Postprint (author's final draft)

Estradiol and hypothalamic paraventricular nucleus (PVN) help coordinate reproduction with body physiology, growth and metabolism. PVN integrates hormonal and neural signals originating in the periphery, generating an output mediated both by its long-distance neuronal projections, and by a variety of neurohormones produced by its magnocellular and parvocellular neurosecretory cells. Here we review the cyto-and chemo-architecture, the connectivity and function of PVN and the sex-specific regulation exerted by estradiol on PVN neurons and on the expression of neurotransmitters, neuromodulators, neuropeptides and neurohormones in PVN. Classical and non-classical estrogen receptors (ERs) are expressed in neuronal afferents to PVN and in specific PVN interneurons, projecting neurons, neurosecretory neurons and glial cells that are involved in the input–output integration and coordination of neurohormonal signals. Indeed, PVN ERs are known to modulate body homeostatic processes such as autonomic functions, stress response, reproduction, and metabolic control. Finally, the functional implications of the estrogenic modulation of the PVN for body homeostasis are discussed.

The existence of sex differences in disease incidence is attributed, in part, to sex differences in metabolism. Uncovering the precise mechanism driving these differences is an extraordinarily complex process influenced by genetics, endogenous hormones, sex-specific lifetime events, individual differences and external environmental/social factors. In fact, such differences may be subtle, but across a life span, increase susceptibility to a pathology. Whilst research persists in the hope of discovering an elegant biological mechanism to underpin sex differences in disease, here, we show, for the first time, that such a mechanism may be subtle in nature but influenced by multiple sex-specific factors. A proteomic dataset was generated from a gonadectomized mouse model treated with Tibolone, a menopausal hormone therapy. Following functional enrichment analysis, we identified that Alzheimer's disease and the electron transport chain-associated pathways were regulated by sex-hormone interactions. Specifically, we identified that the expression of three respirasome proteins, NDUFA2, NDUFA7 and UQCR10, is significantly altered by compounding factors that contribute to sex differences. These proteins function in bioenergetics and produce reactive oxygen species, which are each dysregulated in many diseases with sex differences in incidence. We show sex-specific reprogrammed responses to Tibolone following gonadectomy, which primarily influence the expression of proteins contributing to metabolic pathways. This further infers that metabolic differences may underpin the observed sex differences in disease, but also that hormone therapy research now has potential in exploring sex-specific interventions to produce an effective method of prevention or treatment.

descripción no proporcionada por scopus

descripción no proporcionada por scopus