Disrupted organ growth leads to disease development. Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely ...unknown. Here we show that cardiac activation of p38γ and p38δ increases during postnatal development and by hypertrophy-inducing stimuli. p38γ/δ promote cardiac hypertrophy by phosphorylating the mTORC1 and mTORC2 inhibitor DEPTOR, which leads to its degradation and mTOR activation. Hearts from mice lacking one or both kinases are below normal size, have high levels of DEPTOR, low activity of the mTOR pathway and reduced protein synthesis. The phenotype of p38γ/δ(-/-) mice is reverted by overactivation of mTOR with amino acids, shRNA-mediated knockdown of Deptor, or cardiomyocyte overexpression of active p38γ and p38δ. Moreover, in WT mice, heart weight is reduced by cardiac overexpression of DEPTOR. Our results demonstrate that p38γ/δ control heart growth by modulating mTOR pathway through DEPTOR phosphorylation and subsequent degradation.
The deposition and manipulation of human remains in natural caves are well known for the Neolithic of Southern Iberia. The cultural meaning of these practices is however still largely unclear. Cueva ...de los Marmoles (CM, Priego-Córdoba) is one of the most important cave contexts from Southern Spain, which returned a large number of commingled skeletal remains suggesting its funerary use from the Neolithic to the Late Bronze Age. Here we discuss CM from a chronological and cultural perspective based on new radiocarbon, anthropological, and taphonomic analyses. These include the estimation of the minimum number of individuals, the exploration of fragmentation patterns characterizing different skeletal regions, and the macroscopic and microscopic analysis of modifications to the remains of possible anthropic origin. Radiocarbon data point to a funerary use of CM between the 5
th
-2
nd
millennium cal. BCE. MNI estimates reveal the presence of at least 12 individuals (seven adults and five nonadults). The low representation of elements from hands and feet suggests that individuals were placed in the cave while partially decomposed. Anthropic traces on the remains (e.g. fresh fractures, marrow canal modifications, and scraping marks) hint at their intentional fragmentation, cleaning from residual soft tissues, and in some cases reutilization. These practices are well-exemplified by the recovery of one "skull cup" and of two long bones used as tools. These data align with those from other cave contexts from the same geographic region, suggesting the presence, especially during the Neolithic period, of shared ideologies centered on the human body.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer’s disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and ...central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.
Abstract
Background
Advanced age is a well-known risk factor for poor prognosis in COVID-19. However, few studies have specifically focused on very old inpatients with COVID-19. This study aims to ...describe the clinical characteristics of very old inpatients with COVID-19 and identify risk factors for in-hospital mortality at admission.
Methods
We conducted a nationwide, multicenter, retrospective, observational study in patients ≥ 80 years hospitalized with COVID-19 in 150 Spanish hospitals (SEMI-COVID-19) Registry (March 1–May 29, 2020). The primary outcome was in-hospital mortality. A uni- and multivariate logistic regression was performed to assess predictors of mortality at admission.
Results
A total of 2772 consecutive patients (49.4% men, median age 86.3 years) were analyzed. Rates of atherosclerotic cardiovascular disease, diabetes mellitus, dementia, and Barthel Index < 60 were 30.8%, 25.6%, 30.5%, and 21.0%, respectively. The overall case-fatality rate was 46.9% (n: 1301) and increased with age (80–84 years: 41.6%; 85–90 years: 47.3%; 90–94 years: 52.7%; ≥95 years: 54.2%). After analysis, male sex and moderate-to-severe dependence were independently associated with in-hospital mortality; comorbidities were not predictive. At admission, independent risk factors for death were: oxygen saturation < 90%; temperature ≥ 37.8°C; quick sequential organ failure assessment (qSOFA) score ≥ 2; and unilateral–bilateral infiltrates on chest x-rays. Some analytical findings were independent risk factors for death, including estimated glomerular filtration rate < 45 mL/min/1.73 m2; lactate dehydrogenase ≥ 500 U/L; C-reactive protein ≥ 80 mg/L; neutrophils ≥ 7.5 × 103/μL; lymphocytes < 0.8 × 103/μL; and monocytes < 0.5 × 103/μL.
Conclusions
This first large, multicenter cohort of very old inpatients with COVID-19 shows that age, male sex, and poor preadmission functional status—not comorbidities—are independently associated with in-hospital mortality. Severe COVID-19 at admission is related to poor prognosis.
Here we present an improved, rapid method for filling quasi-nulls in symmetrical radiation patterns synthesized by equispaced linear arrays, leading to the generation of multiple solutions. ...Considering the polynomial representation of the pattern, this null-filling is achieved by displacing the roots radially off the unit circle, keeping a constant displacement. This allows analyzing how the potential solutions vary with the quasi-uniform filling and the associated directivity loss. This method is based on the Cardano-Vieta relations, which link the coefficients of a complex Schelkunoff polynomial with its roots. As examples of application, we have considered a 20/100 element Dolph-Chebyshev pattern, with a spacing between the elements Formula: see text, side lobe level of - 20/- 28 dB and three inner sidelobes at - 40/- 50 dB.
Thermal inversions, typical in the winter season, consist of cold air at the Earth's surface being trapped under a layer of warmer air. Such an effect keeps normal convective overturning of the ...atmosphere from penetrating through. This phenomenon highly increases the toxicity of the atmosphere, while modifying its dielectric constant, resulting in major implications in terms of public health and wireless communications. Indeed, air pollution in large cities (related, in most cases, to particulate matter that consists of different chemical components, which can have warming or cooling effects) is primarily caused by chemical and photochemical reactions in the atmosphere. Appropriate usage of array antennas allows the effective tracking of changes in humidity (e.g., coated Yagi-Uda antennas, which do not interfere with 5G) and in the dielectric constant (e.g., optimized quasi-Yagi-Uda antennas, yielding to accurate measurements of sulfides and black carbon concentration). Remarkably, important health effects come from the combined action of electromagnetic fields with fine and coarse black carbon particles. The appearance of ducts, which are caused by thermal inversions, provokes the creation of super-refractive regions in the troposphere as well, which result in the anomalous propagation of wireless communications.
Processed fish is known to have been systematically traded in Europe since the Early Middle Ages to meet increasing demand of incipient markets and religious precepts, yet specific details regarding ...the supply of different fish in Southern Europe is often missing. Here, we address this gap through an integrated approach involving bone metrics and stable isotopic analysis of archaeological European hake (Merluccius merluccius, Merluccidae) from the Iberian Peninsula. The results offer new insights regarding historical fisheries production systems, including the regions exploited and commercial routes, whilst also revealing biological differences between archaeological and present‐day hake populations in the North‐east Atlantic and the Mediterranean Sea. This research highlights the fruitful result of combining ichthyoarchaeological and historical data for tracking down the origin and development of historical fisheries in south‐western Europe and their bearing on modern fisheries.
During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We ...provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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