San Sebastián University

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

This study uses a causal modelling methodology to examine competing methodological and theoretical hypotheses concerning the effects of product quality on direct costs and business unit return on i...

The phytohormone abscisic acid (ABA) mediates many complex aspects of plant development including seed maturation, dormancy, and germination as well as root growth. The B3-domain transcription factor abscisic acid-insensitive 3 (ABI3) is a central regulator in ABA signaling, but little is known of how this factor is regulated. Here, we show that ABI3 is an unstable protein and that an ABI3-interacting protein (AIP2), which contains a RING motif, can polyubiquitinate ABI3 in vitro. The AIP2 E3 ligase activity is abolished by mutations (C230S; C231S) in the RING motif and the AIP2 (C/S) mutant functions in a dominant-negative manner. AIP2 has a stronger binding affinity for the B2 + B3 domain of ABI3 than the A1 + B1 domain, but only ubiquitinates the latter. In double-transgenic plants, induced AIP2 expression leads to a decrease in ABI3 protein levels. In contrast, ABI3 levels are elevated upon induced expression of the AIP2 RING mutant, which interferes with the endogenous AIP2 E3 activity. An aip2-1-null mutant shows higher ABI3 protein levels compared with wild type after seed stratification, and is hypersensitive to ABA, mimicking the ABI3-overexpression phenotype, whereas AIP2-overexpression plants contain lower levels of ABI3 protein than wild type and are more resistant to ABA, phenocopying abi3. Our results indicate that AIP2 negatively regulates ABA signaling by targeting ABI3 for post-translational destruction.

tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.

The Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis vaccine that has the ability to induce non-specific cross-protection against pathogens that might be unrelated to the target disease. Vaccination with BCG reduces mortality in newborns and induces an improved innate immune response against microorganisms other than Mycobacterium tuberculosis, such as Candida albicans and Staphylococcus aureus. Innate immune cells, including monocytes and natural killer (NK) cells contribute to this unspecific immune protection in a way that is independent of memory T or B cells. This phenomenon associated to a memory-like response in innate immune cells is known as “trained immunity”. Epigenetic reprogramming through histone modification in the regulatory elements of particular genes has been reported as one of the mechanisms associated to the induction of trained immunity in both, humans and mice. Indeed, it has been shown that BCG vaccination induces changes in the methylation pattern of histones associated to specific genes in circulating monocytes leading to a "trained" state. Importantly, these modifications can lead to the expression and/or repression of genes that are related to increased protection against secondary infections after vaccination, with improved pathogen recognition and faster inflammatory responses. In this review, we will discuss the BCG-induced cross-protection and acquisition of trained immunity and potential heterologous effects of recombinant BCG vaccines.

The objective of this work is to review the literature of the main concepts that lead to determining the strategic approach, creation of strategies, organizational structures, strategy formulation, and strategic evaluation as a guide for the organizational management, taking into account the effects produced by the different types of strategies on the performance of organizations. In this article, the systemic literature review method was used to synthesize the result of multiple investigations and scientific literature. The process of reading and analysis of the literature was carried out through digital search engines with keywords in areas related to the strategic management. This research reveals the lack of scientific literature containing important theoretical concepts that serve the strategists as a guide in the creation, formulation, and evaluation of strategies. This review contributes to the existing literature by examining the impact of the strategic management on the organizational performance.

BACKGROUND: Although more than two thirds of the world's incarcerated individuals are based in low-income and middle-income countries (LMICs), the burden of psychiatric disorders in this population is not known. This review provides estimates for the prevalence of severe mental illness and substance use disorders in incarcerated individuals in LMICs. METHODS: For this systematic review and meta-analysis, we searched 17 electronic databases to identify prevalence studies of psychiatric disorders in prison populations in LMICs, published between January, 1987, and May, 2018. We included representative studies from general prison samples, providing information about four major psychiatric diagnoses: psychosis, major depression, alcohol use disorders, and drug use disorders. We pooled data from studies using random-effects meta-analyses and assessed the sources of heterogeneity by meta-regression. We extracted general population estimates from the Global Burden of Diseases 2016 database to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42015020905. FINDINGS: We identified 23 publications reporting prevalence estimates of severe mental illness and substance use disorders for 14 527 prisoners from 13 LMICs. In this population, the estimated pooled 1 year prevalence rates for psychosis were 6·2% (95% CI 4·0-8·6), 16·0% (11·7-20·8) for major depression, 3·8% (1·2-7·6) for alcohol use disorders, and 5·1% (2·9-7·8) for drug use disorders. We noted increased prevalence at prison intake and geographic variations for substance use disorders. For alcohol use disorders, prevalence was higher in the southeast Asian region than in the eastern Mediterranean region; and drug use disorders were more prevalent in the eastern Mediterranean region than in Europe. Prevalence ratios indicated substantially higher rates of severe mental illness and substance use disorders among prisoners than in the general population (the prevalence of non-affective psychosis was on average 16 times higher, major depression and illicit drug use disorder prevalence were both six times higher, and prevalence of alcohol use disorders was double that of the general population). INTERPRETATION: The prevalence of major psychiatric disorders is high in prisoners in LMIC compared with general populations. As these findings are likely to reflect unmet needs, the development of scalable interventions should be a public health priority in resource-poor settings. FUNDING: CONICYT of the Chilean government and the Wellcome Trust.

This study uses a causal modelling methodology to examine competing methodological and theoretical hypotheses concerning the effects of product quality on direct costs and business unit return on investment (ROI). Results show that the PIMS’ measures under study exhibit high reliability across all samples. The findings fail to support the widely held view that a high relative quality position is incompatible with achieving a low relative cost position in an industry.

Grid integration of renewable energy (REN) requires efficient and reliable power conversion stages, particularly with an increasing demand for high controllability and flexibility seen from the grid side. Underpinned by advanced control and information technologies, power electronics converters play an essential role in large-scale REN generation. However, the use of power converters has also exposed several challenges in conventional power grids, e.g., reducing the system inertia. In this article, grid integration using power electronics is presented for large-scale REN generation. Technical issues and requirements are discussed with a special focus on grid-connected wind, solar photovoltaic, and energy storage systems. In addition, the core of the energy generation and conversion—control for individual power converters (e.g., general current control) and for the system level (e.g., coordinated operation of large-scale energy systems)—is briefly discussed. Future research perspectives are then presented, which further advance large-scale REN generation technologies by incorporating more power electronics systems.

Long-term stable 3 nm gold nanoparticles are prepared by a simple reaction between HAuCl4 and sodium borohydride in water under ambient conditions which very efficiently catalyze 4-nitrophenol reduction to 4-nitroaniline.

Abstract Tissue-resident memory CD8 + T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8 + T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. This work unveils the ability of Trm cells to amplify the breath of cytotoxic CD8 + T cell responses through DCs, thereby strengthening anti-tumor immunity.

People involved with criminal justice frequently are exposed to violence and traumatic experiences. This may lead to posttraumatic stress disorder (PTSD); however, no review, to our knowledge, has synthetized findings in this setting. We conducted a systematic review and meta-analysis to estimate prevalence rates of PTSD in prison populations. Original studies in which prevalence rates of PTSD in unselected samples of incarcerated people were reported were systematically searched between 1980 and June 2017. Data were pooled using random-effects meta-analysis, and sources of heterogeneity for prespecified characteristics were assessed by meta-regression. We identified 56 samples comprising 21,099 imprisoned men and women from 20 countries. Point prevalence of PTSD ranged from 0.1% to 27% for male, and from 12% to 38% for female prisoner populations. The random-effects pooled point prevalence was 6.2% (95% confidence interval: 3.9, 9.0) in male prisoners and 21.1% (95% confidence interval: 16.9, 25.6) in female prisoners. The heterogeneity between the included studies was very high. Higher prevalence was reported in samples of female prisoners, smaller studies (n ≤ 200), and for investigations based in high-income countries. Existing evidence shows high levels of PTSD among imprisoned people, especially women. Psychosocial interventions to prevent violence, especially against children and women, and to mitigate its consequences in marginalized communities must be improved. Trauma-informed approaches for correctional programs and scalable PTSD treatments in prisons require further consideration.

Evidence on what people eat globally is limited in scope and rigour, especially as it relates to children and adolescents. This impairs target setting and investment in evidence-based actions to support healthy sustainable diets. Here we quantified global, regional and national dietary patterns among children and adults, by age group, sex, education and urbanicity, across 185 countries between 1990 and 2018, on the basis of data from the Global Dietary Database project. Our primary measure was the Alternative Healthy Eating Index, a validated score of diet quality; Dietary Approaches to Stop Hypertension and Mediterranean Diet Score patterns were secondarily assessed. Dietary quality is generally modest worldwide. In 2018, the mean global Alternative Healthy Eating Index score was 40.3, ranging from 0 (least healthy) to 100 (most healthy), with regional means ranging from 30.3 in Latin America and the Caribbean to 45.7 in South Asia. Scores among children versus adults were generally similar across regions, except in Central/Eastern Europe and Central Asia, high-income countries, and the Middle East and Northern Africa, where children had lower diet quality. Globally, diet quality scores were higher among women versus men, and more versus less educated individuals. Diet quality increased modestly between 1990 and 2018 globally and in all world regions except in South Asia and Sub-Saharan Africa, where it did not improve.

Model-predictive control (MPC) has emerged as a promising control method in power electronics, particularly for multiobjective control problems such as multilevel inverter (MLI) applications. Over the past two decades, improving the performance of MPC and tackling its technical challenges, such as computational load, modeling accuracy, cost function design, and weighting factor selection, have attracted great interest in power electronics. This article aims to discuss the current state of MPC strategies for MLI applications, describing the significance of each challenge with the reported effective solutions. Through this review, the MPC methods are categorized into two groups: direct MPC (without modulator) and indirect MPC (with modulator). The recent advances of each category are presented and analyzed, focusing on direct MPC as the most applied method for MLI topologies. In addition, some of the important concepts are experimentally validated through a case study and compared under the same operating conditions to evaluate the performance and highlight their features. Finally, the future trends of MPC for MLI applications are discussed based on the current state and reported developments.

selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis.

PURPOSE: The objective of this study was to evaluate the psychometric properties of the Constant-Murley Score (CMS) in various shoulder pathologies, based on a systematic review and expert standardized evaluations. METHODS: A systematic review was performed in MEDLINE and EMBASE databases. Titles and abstracts were reviewed and finally the included articles were grouped according to patients' pathologies. Two expert evaluators independently assessed the CMS properties of reliability, validity, responsiveness to change, interpretability and burden score in each group, using the EMPRO (Evaluating Measures of Patient Reported Outcomes) tool. The CMS properties were assessed per attribute and overall for each considered group. Only the concept and measurement model was assessed globally. RESULTS: Five individual pathologies (i.e. subacromial, fractures, arthritis, instability and frozen shoulder) and two additional groups (i.e. various pathologies and healthy subjects) were considered. Overall EMPRO scores ranged from 58.6 for subacromial to 30.6 points for instability. Responsiveness to change was the only quality to obtain at least 50 points across all groups, but for frozen shoulder. Insufficient information was obtained in relation to the concept and measurement model and great variability was seen in the other evaluated attributes. CONCLUSIONS: The current evidence does not support the CMS as a gold standard in shoulder evaluation. Its use is advisable for subacromial pathology; but data are inconclusive for other shoulder conditions. Prospective studies exploring the psychometric properties of the scale, particularly for fractures, arthritis, instability and frozen shoulder are needed. LEVEL OF EVIDENCE: Systematic review.

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8-14.4 million) incident T2D cases, representing 70.3% (68.8-71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0-27.1%)), excess refined rice and wheat intake (24.6% (22.3-27.2%)) and excess processed meat intake (20.3% (18.3-23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4-87.7%)) and Latin America and the Caribbean (81.8% (80.1-83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1-60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.

In order to evaluate the present distribution patterns of salmonids and their potential effects on native fish, we sampled 11 large lakes and 105 streams, encompassing a total of 13 main hydrographic watersheds of southern Chile (39 o to 52 o S). Overall, trout (Salmo trutta and Oncorhynchus mykiss) accounted for more than 60 % of total fish abundance and more than 80 % of total biomass, while 40 % of the streams sampled did not have native fish. Salmon, introduced for aquaculture, such as O. kisutch, Salmo salar, and O. tshawytscha, were only present in lakes with salmon farming and did not seem to be reproducing naturally in affluent streams. We tested the effect of river geographic origin (Andes mountains, central valley, or Coastal range) on fish abundance and found that rainbow trout was more restricted to the Andean streams with higher water discharge, while brown trout was widely distributed and did not relate to any of several catchment attributes measured. The abundance of native fish was greater in lakes than in streams and the highest native fish biodiversity occurred in streams of the central valley. The most common native species were Galaxias maculatus, G. platei, Brachygalaxias bullocki, Aplochiton zebra and Basilichthys australis. Streams with higher conductivity, larger pool areas, more fine sediments, and low brown trout densities were more suitable for native fish. Thus, catchments with higher anthropogenic disturbance appeared as refuges for native species. Given the descriptive nature of our study we can only presume the negative impacts of trout and salmon on native fish; an effect which should be superimposed on biogeographical conditioning of present distribution. Yet based on the present abundance and distribution patterns of salmonids and native fish, negative effects are very likely. Conservation of native fish biodiversity in central valley streams, far from protected areas or national parks and fully exposed to human perturbations represents a great challenge. We propose to enhance conservation by exerting a stronger sport fishing pressure on trout in those streams.

Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.

This paper proposes a conceptual theory of resilience in urbanism and demonstrates its application through a case study. The theory's underpinnings are the attributes of resilience that have been developed in ecological sciences, but have clear parallels in urbanism. They suggest that it may be possible to enhance the resilience of a city through the design of its urban morphology. The paper explores these ideas by examining the relationship between the community's adaptive behaviour and the spaces of the city of Concepción after its 2010 earthquake. This empirical evidence suggests that the role of the urban designer in earthquake-prone cities is perhaps more critical before an earthquake happens and that the more the idea of a resilient urban morphology is embedded as part of daily life, the more effective it is likely to be in the aftermath of a major earthquake.