PINTURA Y ABSTRACCIÓN REPRESENTACIÓN DEL ENEAGRAMA A TRAVÉS DE MANCHAS ORGÁNICAS

[ES] Trabajo de fin de grado teórico-plástico, en la que se ha trabajado la experimentación de manchas orgánicas desde una perspectiva abstracta, con el fin de representar las distintas personalidades del Eneagrama. Este trabajo cuenta con dos series que pertenecen a una misma obra, ambas construidas desde la pintura, compartiendo rasgos teóricos y prácticos.[EN] Theoretical-plastic final thesis, in which the experimentation of organic stains from an abstract perspective has been worked out, in order to represent the different personalities of the Enneagram. This project has two series that belong to the same work, both built from painting, sharing theoretical and practical features.Teixeira Deniz, M. (2020). PINTURA Y ABSTRACCIÓN REPRESENTACIÓN DEL ENEAGRAMA A TRAVÉS DE MANCHAS ORGÁNICAS. Universitat Politècnica de València. http://hdl.handle.net/10251/165498TFG

Impact of the interplay between stemness features, p53 and pol iota on replication pathway choices

Using human embryonic, adult and cancer stem cells/stem cell-like cells (SCs), we demonstrate that DNA replication speed differs in SCs and their differentiated counterparts. While SCs decelerate DNA replication, differentiated cells synthesize DNA faster and accumulate DNA damage. Notably, both replication phenotypes depend on p53 and polymerase iota (POL$_{ι}$). By exploring protein interactions and newly synthesized DNA, we show that SCs promote complex formation of p53 and POL$_{ι}$ at replication sites. Intriguingly, in SCs the translocase ZRANB3 is recruited to POL$_{ι}$ and required for slow-down of DNA replication. The known role of ZRANB3 in fork reversal suggests that the p53–POL$_{ι}$ complex mediates slow but safe bypass of replication barriers in SCs. In differentiated cells, POL$_{ι}$ localizes more transiently to sites of DNA synthesis and no longer interacts with p53 facilitating fast POL$_{ι}$-dependent DNA replication. In this alternative scenario, POL$_{ι}$ associates with the p53 target p21, which antagonizes PCNA poly-ubiquitination and, thereby potentially disfavors the recruitment of translocases. Altogether, we provide evidence for diametrically opposed DNA replication phenotypes in SCs and their differentiated counterparts putting DNA replication-based strategies in the spotlight for the creation of therapeutic opportunities targeting SCs

Investigation of the Pygmy Dipole Resonance in photon scattering experiments

The Pygmy Dipole Resonance (PDR) is the dominating electric dipole excitation below and around the particle separation threshold and exhausts only a few percent of the energy-weighted sum rule. Nevertheless, it may have some impact on reaction rates in nucleosynthesis processes. Therefore, investigations to get more insights in this excitation mode are crucial. A common approach to study the PDR of atomic nuclei is the Nuclear Resonance Fluorescence method (NRF) which bases on real-photon scattering. Absolute cross sections, spin and parity quantum numbers are determined in a model-independent way if suited experimental setups are used. In general, there are two complementary NRF experiments which are presented in this paper

Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD

Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice

ABSTRACT Mast cells are important tissue‐resident sensor and effector immune cells but also play a major role in osteoporosis development. Mast cells are increased in numbers in the bone marrow of postmenopausal osteoporotic patients, and mast cell–deficient mice are protected from ovariectomy (OVX)‐induced bone loss. In this study, we showed that mast cell–deficient Mcpt5‐Cre R‐DTA mice were protected from OVX‐induced disturbed fracture healing, indicating a critical role for mast cells in the pathomechanisms of impaired bone repair under estrogen‐deficient conditions. We revealed that mast cells trigger the fracture‐induced inflammatory response by releasing inflammatory mediators, including interleukin‐6, midkine (Mdk), and C‐X‐C motif chemokine ligand 10 (CXCL10), and promote neutrophil infiltration into the fracture site in OVX mice. Furthermore, mast cells were responsible for reduced osteoblast and increased osteoclast activities in OVX mice callus, as well as increased receptor activator of NF‐κB ligand serum levels in OVX mice. Additional in vitro studies with human cells showed that mast cells stimulate osteoclastogenesis by releasing the osteoclastogenic mediators Mdk and CXCL10 in an estrogen‐dependent manner, which was mediated via the estrogen receptor alpha on mast cells. In conclusion, mast cells negatively affect the healing of bone fractures under estrogen‐deficient conditions. Hence, targeting mast cells might provide a therapeutic strategy to improve disturbed bone repair in postmenopausal osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial

Introduction: Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. Methods: This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. Results: Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. Conclusions: Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. Trial registration: Clinicaltrials.gov NCT02181101. Registered September 200

Semen inhibits Zika virus infection of cells and tissues from the anogenital region

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid.Peer reviewe

The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial

Introduction Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. Methods This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. Results Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. Conclusions Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. Trial registration Clinicaltrials.gov NCT02181101. Registered September 2005