Search

The identification of genes that confer either extension of life span or accelerate age-related decline was a step forward in understanding the mechanisms of aging and revealed that it is partially controlled by genetics and transcriptional programs. Here, we discovered that the human DNA sequence C16ORF70 encodes a protein, named MYTHO (macroautophagy and youth optimizer), which controls life span and health span. MYTHO protein is conserved from Caenorhabditis elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the orthologous myt-1 gene in C. elegans dramatically shortened life span and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy likely because it acts as a scaffold that binds WIPI2 and BCAS3 to recruit and assemble the conjugation system at the phagophore, the nascent autophagosome. We conclude that MYTHO is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance and healthy aging., Introduction In nature, organisms are continuously exposed to environmental stresses that challenge their survival. The species that quickly and efficiently adapt to hostile conditions are positively selected. This response is [...]

El objetivo de esta contribución es divulgar una metodología que incluye una serie de técnicas y métodos, disponibles en diferentes instituciones académicas y de investigación de nuestro país, que posibilita el estudio y la caracterización de los Sistemas Petroleros. Dicha metodología incluye el análisis de inclusiones fluidas (IF) con hidrocarburos (HC), alojadas en fases minerales que han cristalizado en equilibrio junto con fluidos acuosos de diferente origen (sedimentario, ígneo, hidrotermal o metamórfico), combinado con Fluorescencia con luz incidente UV (ultravioleta) y Espectrometría Raman. Como caso de estudio, se presenta la implementación de la metodología propuesta en el análisis de IF con HC identificadas en cristales de baritina del área de Colipilli-Naunauco (Cuenca Neuquina, provincia del Neuquén), la que permitió determinar la composición de los HC, así como obtener datos térmicos que posibilitaron la interpretación de los procesos de entrampamiento, maduración y migración de los HC en este sistema hidrotermal-magmático. Los resultados presentados podrán ser de interés no sólo para el avance del conocimiento de la temática, sino también para la industria petrolera, en un contexto de transición energética que demanda la incorporación de nuevos recursos a menor costo y la optimización del desarrollo de los recursos ya disponibles.

The gilded bronze eagles that stand upon the summit of the Tabernacle by Michelozzo in the Abbey of San Miniato al Monte, Florence (Italy) are an exquisite example of Italian Renaissance sculpture. Commissioned by Piero di Cosimo de Medici, the two eagles, representing the ancient Arte di Calimala, were cast and decorated by Maso di Bartolomeo in the 1448–1449 period. A multi-analytical approach was set up to characterize the state of conservation, materials used, and artistic technique of the eagles. Non-invasive methods were used and integrated with micro-invasive analyses, such as X-ray fluorescence (XRF) and Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry on powders (XRPD), scanning electron microscopy coupled with EDS (SEM-EDS), and metallographic investigation. The results depict shiny-looking eagles, suggesting the use of oil gilding on almost all surfaces and revealing the presence of polychromies, which is almost unusual in XV-century bronze statuary and is initially hidden by deposits and corrosion products. Indeed, the paws were originally painted with azurite, while the use of cinnabar imparted a vivid red color to the tongue. A black paint containing mercury was found on the eyes and talons. The bales of cloth were decorated with silver, which is now almost completely lost and whose remains are not visible due to being tarnished, while fine details in gold were detected on the lanyard.

IntroductionGrowth Differentiation Factor 15 (GDF15) is a mitokine expressed in response to various stresses whose circulating levels increase with age and are associated with numerous pathological conditions, including muscle wasting and sarcopenia. However, the use of circulating GDF15 (c-GDF15) as a biomarker of sarcopenia is still debated. Moreover, the role of GDF15 intracellular precursor, pro-GDF15, in human skeletal muscle (SM-GDF15) is not totally understood. In order to clarify these points, the association of both forms of GDF15 with parameters of muscle strength, body composition, metabolism and inflammation was investigated.Methodsthe levels of c-GDF15 and SM-GDF15 were evaluated in plasma and muscle biopsies, respectively, of healthy subjects (HS) and patients with lower limb mobility impairment (LLMI), either young (70 years-old). Other parameters included in the analysis were Isometric Quadriceps Strength (IQS), BMI, lean and fat mass percentage, Vastus lateralis thickness, as well as circulating levels of Adiponectin, Leptin, Resistin, IGF-1, Insulin, IL6, IL15 and c-PLIN2. Principal Component Analysis (PCA), Canonical Discriminant Analysis (CDA) and Receiving Operating Characteristics (ROC) analysis were performed.Resultsc-GDF15 but not SM-GDF15 levels resulted associated with decreased IQS and IGF-1 levels in both HS and LLMI, while only in LLMI associated with increased levels of Resistin. Moreover, in LLMI both c-GDF15 and SM-GDF15 levels were associated with IL-6 levels, but interestingly SM-GDF15 is lower in LLMI with respect to HS. Furthermore, a discrimination of the four groups of subjects based on these parameters was possible with PCA and CDA. In particular HS, LLMI over 70 years or under 40 years of age were discriminated based on SM-GDF15, c-GDF15 and Insulin levels, respectively.Conclusionour data support the idea that c-GDF15 level could be used as a biomarker of decreased muscle mass and strength. Moreover, it is suggested that c-GDF15 has a different diagnostic significance with respect to SM-GDF15, which is likely linked to a healthy and active state.

Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5–10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients.

Abstract Background Arbuscular mycorrhizal (AM) symbiosis is the most widespread association between plant roots and fungi in natural and agricultural ecosystems. This work investigated the influence of mycorrhization on the economically relevant part of the tomato plant, by analyzing its impact on the physiology of the fruit. To this aim, a combination of phenological observations, transcriptomics (Microarrays and qRT-PCR) and biochemical analyses was used to unravel the changes that occur on fruits from Micro-Tom tomato plants colonized by the AM fungus Glomus mosseae. Results Mycorrhization accelerated the flowering and fruit development and increased the fruit yield. Eleven transcripts were differentially regulated in the fruit upon mycorrhization, and the mycorrhiza-responsive genes resulted to be involved in nitrogen and carbohydrate metabolism as well as in regulation and signal transduction. Mycorrhization has increased the amino acid abundance in the fruit from mycorrhizal plants, with glutamine and asparagine being the most responsive amino acids. Conclusions The obtained results offer novel data on the systemic changes that are induced by the establishment of AM symbiosis in the plant, and confirm the work hypothesis that AM fungi may extend their influence from the root to the fruit.

The prevention of cardiovascular diseases is a fundamental pillar for reducing morbidity and mortality caused by non-communicable diseases. Social determinants, such as socioeconomic status, education, neighborhood, physical environment, employment, social support networks, and access to health care, play a crucial role in influencing health outcomes and health inequities within populations. Social determinants and stress in women are interconnected factors that can significantly impact women’s health and well-being. Pregnancy is a good time to engage young women and introduce them to beneficial behaviors, such as adopting essential life skills, especially diet, and learning stress management techniques. Stress influences diet, and women are more likely to engage in unhealthy eating behaviors such as emotional eating or coping with stress with food. Strong action is needed to improve women’s lifestyle starting at a young age considering that this lays the foundation for a lower cardiovascular risk in adults and the elderly. The objective of this review is to examine cardiovascular primary prevention in young healthy women, focusing particularly on unresolved issues and the influence of social determinants, as well as the correlation with stressors and their influence on diet.

As members of the plant microbiota, arbuscular mycorrhizal fungi (AMF, Glomeromycotina) symbiotically colonize plant roots. AMF also possess their own microbiota, hosting some uncultivable endobacteria. Ongoing research has revealed the genetics underlying plant responses to colonization by AMF, but the fungal side of the relationship remains in the dark. Here, we sequenced the genome of Gigaspora margarita, a member of the Gigasporaceae in an early diverging group of the Glomeromycotina. In contrast to other AMF, G. margarita may host distinct endobacterial populations and possesses the largest fungal genome so far annotated (773.104 Mbp), with more than 64% transposable elements. Other unique traits of the G. margarita genome include the expansion of genes for inorganic phosphate metabolism, the presence of genes for production of secondary metabolites and a considerable number of potential horizontal gene transfer events. The sequencing of G. margarita genome reveals the importance of its immune system, shedding light on the evolutionary pathways that allowed early diverging fungi to interact with both plants and bacteria.

Prostate-specific antigen (PSA) is the most commonly used serum marker for prostate cancer. It plays a role in cancer detection, treatment monitoring, and more recently, in guiding adaptive therapy protocols, where treatment is alternated based on PSA levels. However, the relationship between PSA levels and tumor volume remains poorly understood. Empirical evidence suggests that different cancer cell types produce varying amounts of PSA. Despite this, current mathematical cancer models often assume either that all cell types contribute equally to PSA levels or that only certain subpopulations produce PSA at fixed rates. In this study, we compare Zhang et al.'s classical adaptive therapy protocol with the standard of care, which involves continuous maximum tolerable dose treatment, under different assumptions regarding PSA production. Specifically, we explore the possibility that testosterone-dependent, testosterone-producing, and testosterone-independent cells contribute to PSA production to varying degrees. We use the time to competitive release as a proxy for the time to disease progression. Our findings indicate that adaptive therapy consistently results in a longer time to competitive release compared to the standard of care, regardless of the assumptions about PSA production. However, when testosterone-independent cells are the sole PSA producers, Zhang et al.'s adaptive therapy protocol becomes inapplicable, as PSA levels never fall to half of their initial value, preventing therapy discontinuation. Additionally, we observe that the number and duration of treatment cycles in adaptive therapy are highly sensitive to assumptions about how much each cell type contributes to PSA production. Overall, our results emphasize the need for a deeper understanding of patient-specific PSA dynamics, which could enhance the effectiveness of adaptive therapy in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Chronic low back pain (cLBP) is one of the leading worldwide causes of disability. The smallest worthwhile effect (SWE) parameter has been proposed to find a threshold of clinical relevance. Specific values of the SWE have been calculated in patients with cLBP for pain intensity, physical functioning and time to recovery for physiotherapy compared with no intervention. Our objectives are 1) To evaluate how authors have interpreted the clinical relevance of the effect of physiotherapy compared to no-intervention on pain, physical functioning and time to recovery; 2) To reinterpret the clinical relevance of these between-group differences based on the available SWE estimates; 3) To evaluate, for descriptive purposes, whether the studies are adequately powered or underpowered considering the published SWE values and a power threshold of 80%. A systematic search in Medline, PEDro, Embase and Cochrane CENTRAL will be conducted. We will search for RCT investigating the effectiveness of physiotherapy as compared to no interventions in people with cLBP. We will compare the authors' interpretation of results for clinical relevance with their results to determine if they meet their a-priori definitions. Then, we will perform a re-interpretation of the between-group differences based on SWE values published for cLBP.

The soil is vital for life on Earth and its biodiversity. However, being a non-renewable and threatened resource, preserving soil quality is crucial to maintain a range of ecosystem services critical to ecological balances, food production and human health. In an agricultural context, soil quality is often perceived as the ability to support field production, and thus soil quality and fertility are strictly interconnected. The concept of, as well as the ways to assess, soil fertility has undergone big changes over the years. Crop performance has been historically used as an indicator for soil quality and fertility. Then, analysis of a range of physico-chemical parameters has been used to routinely assess soil quality. Today it is becoming evident that soil quality must be evaluated by combining parameters that refer both to the physico-chemical and the biological levels. However, it can be challenging to find adequate indexes for evaluating soil quality that are both predictive and easy to measure in situ. An ideal soil quality assessment method should be flexible, sensitive enough to detect changes in soil functions, management and climate, and should allow comparability among sites. In this review, we discuss the current status of soil quality indicators and existing databases of harmonized, open-access topsoil data. We also explore the connections between soil biotic and abiotic features and crop performance in an agricultural context. Finally, based on current knowledge and technical advancements, we argue that the use of plant health traits represents a powerful way to assess soil physico-chemical and biological properties. These plant health parameters can serve as proxies for different soil features that characterize soil quality both at the physico-chemical and at the microbiological level, including soil quality, fertility and composition of soil microbial communities.

IntroductionGrowth Differentiation Factor 15 (GDF15) is a mitochondrial-stress-responsive molecule whose expression strongly increases with aging and age-related diseases. However, its role in neurodegenerative diseases, including Alzheimer’s disease (AD), is still debated.MethodsWe have characterized the expression of GDF15 in brain samples from AD patients and non-demented subjects (controls) of different ages.ResultsAlthough no difference in CSF levels of GDF15 was found between AD patients and controls, GDF15 was expressed in different brain areas and seems to be predominantly localized in neurons. The ratio between its mature and precursor form was higher in the frontal cortex of AD patients compared to age-matched controls (p

El objetivo de este trabajo fue aplicar indicadores e índices ambientales en una zona costera localizada en el noreste de la provincia de Buenos Aires (Argentina). El área de estudio se ubica en el sector de la planicie costera del Río de la Plata, correspondiente al partido de Ensenada. La misma es un área con alto valor para la biodiversidad regional y brinda numerosos servicios ecosistémicos. Además, está expuesta de manera recurrente a inundaciones y anegamientos, los cuales, determinan fuertes condicionantes para el uso del suelo. Se identificaron y seleccionaron indicadores que aportan información sobre características estructurales y funcionales del medio natural, respecto de su fragilidad frente a intervenciones, a partir de los criterios: vulnerabilidad natural, valor patrimonial y condicionamientos naturales frente a intervenciones antrópicas; estos indicadores fueron integrados para obtener un Índice de Fragilidad Natural Territorial (IFNT). Se generaron mapas temáticos de índices parciales y un mapa final correspondiente al IFNT, mediante el uso de Sistemas de Información Geográfica (SIG). Los resultados obtenidos establecen que el 15,1 % de la superficie del partido presenta una fragilidad natural entre muy alta (2,1 %) y alta (13 %) y un 20,2 %, con valores medios, asociados a ambientes de escasa pendiente del centro, W y E-SE del territorio, así como al sector más próximo a la ribera rioplatense, donde se asientan áreas urbanas. Se observó tendencia de crecimiento urbano avanzando sobre sectores identificados con fragilidad entre muy alta y media. Este índice se considera una herramienta útil para la planificación territorial sostenible.

Abstract Introduction Implementation of clinical practice guidelines (CPGs) to manage musculoskeletal conditions among physiotherapists appears suboptimal. Osteoarthritis is one of the most disabling conditions worldwide and several studies showed a lack of knowledge of and adherence to osteoarthritis CPGs in physiotherapists’ clinical practice. However, those studies are not conclusive, as they examine the knowledge of and adherence to CPGs only in isolation, or only by focussing on a single treatment. Thus, analysis of the knowledge of and adherence to CPGs in the same sample would allow for a better understanding of the evidence-to-practice gap, which, if unaddressed, can lead to suboptimal care for these patients. This study aims at assessing Italian physiotherapists’ evidence-to-practice gap in osteoarthritis CPGs. Methods An online survey divided into two sections investigating knowledge of and adherence to CPGs was developed based on three high-quality, recent and relevant CPGs. In the first section, participants had to express their agreement with 24 CPG statements through a 1 (completely disagree) to 5 (completely agree) scale. We defined a ≥ 70% agreement with a statement as consensus. In the second section, participants were shown a clinical case, with different interventions to choose from. Participants were classified as ‘Delivering’ (all recommended interventions selected), ‘Partially Delivering’ (some recommended interventions missing) and ‘Non-Delivering’ (at least one non-recommended interventions selected) the recommended intervention, depending on chosen interventions. Results 822 physiotherapists (mean age (SD): 35.8 (13.3); female 47%) completed the survey between June and July 2020. In the first section, consensus was achieved for 13/24 statements. In the second section, 25% of the participants were classified as ‘Delivering’, 22% as ‘Partially Delivering’ and 53% as ‘Non-Delivering’. Conclusions Our findings revealed an adequate level of knowledge of osteoarthritis CPGs regarding the importance of exercise and education. However, an adequate level of adherence has yet to be reached, since many physiotherapists did not advise weight reduction, but rest from physical activity, and often included secondary treatments (e.g. manual therapy) supported by low-level evidence. These results identify an evidence-to-practice gap, which may lead to non-evidence based practice behaviours for the management of patients with osteoarthritis.

Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5–10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients. [ABSTRACT FROM AUTHOR]