Hormon wzrostu a proces starzenia się

Studies in mutant, gene knock-out and transgenic mice have demonstrated that growth hormone (GH) signalling has a major impact on ageing and longevity. Growth hormone-resistant and GH-deficient animals live much longer than their normal siblings, while transgenic mice overexpressing GH are short lived. Actions of GH in juvenile animals appear to be particularly important for life extension and responsible for various phenotypic characteristics of long-lived hypopituitary mutants. Available evidence indicates that reduced GH signalling is linked to extended longevity by multiple interacting mechanisms including increased stress resistance, reduced growth, altered profiles of cytokines produced by the adipose tissue, and various metabolic adjustments such as enhanced insulin sensitivity, increased oxygen consumption (VO2/g) and reduced respiratory quotient. The effects of removing visceral fat indicate that increased levels of adiponectin and reduced levels of pro-inflammatory cytokines in GH-resistant mice are responsible for their increased insulin sensitivity. Increased VO2 apparently represents increased energy expenditure for thermogenesis, because VO2 of mutant and normal mice does not differ at thermoneutral temperature. Recent studies identified GH- and IGF-1-dependent maintenance of bone marrow populations of very small embryonic-like stem cells (VSELs) as another likely mechanism of delayed ageing and increased longevity of GH-deficient and GH-resistant animals. Many of the physiological characteristics of long-lived, GH-related mouse mutants are shared by exceptionally long-lived people and by individuals genetically predisposed to longevity.W badaniach na zmutowanych i transgenicznych myszach wykazano, że przekazywanie sygnałów przez hormon wzrostu (GH) wywiera istotny wpływ na procesy starzenia się organizmu i długowieczność. Zwierzęta, u których stwierdza się oporność na hormon wzrostu lub jego niedobór, żyją dłużej niż ich normalne rodzeństwo, podczas gdy myszy transgeniczne wykazujące nadekspresję GH żyją krótko. Działania, jakie wywiera GH u młodocianych zwierząt wydają się odgrywać szczególnie ważną rolę w wydłużaniu życia i są odpowiedzialne za różnorodne cechy fenotypowe długowiecznych mutantów z niedoczynnością przysadki. Z dostępnych dowodów naukowych wynika, że osłabione przekazywanie sygnałów przez GH wiąże się ze zwiększeniem długowieczności, u podstawy czego leży wiele współzależnych mechanizmów obejmujących zwiększoną odporność na stres, osłabione wzrastanie, zmieniony profil cytokin wytwarzanych przez tkankę tłuszczową, a także różne adaptacje metaboliczne, np. zwiększona insulinowrażliwość, zwiększone zużycie tlenu (VO2/g) i zmniejszony współczynnik oddechowy. Konsekwencje usunięcia trzewnej tkanki tłuszczowej wskazują, i że zwiększoną insulinowrażliwość u myszy opornych na GH odpowiedzialne jest zwiększone stężenie adyponektyny i zmniejszone stężenie cytokin prozapalnych. Zwiększone VO2 wydaje się wynikać ze zwiększenia wydatkowania energii na termogenezę, bowiem w temperaturze termoneutralnej VO2 u myszy zmutowanych i myszy niezmutowanych nie różni się. W najnowszych badaniach — jako kolejny prawdopodobny mechanizm opóźnionego starzenia się organizmu i zwiększonej długowieczności u zwierząt z niedoborem GH i opornością na GH — zidentyfikowano zależne od GH i IGF1 podtrzymywanie szpikowych populacji bardzo małych komórek macierzystych podobnych do zarodkowych (VSEL, very small embryonic-like stem cells). Wiele z cech fizjologicznych długowiecznych myszy z mutacjami związanymi z GH występuje też u bardzo długo żyjących ludzi i osób genetycznie predysponowanych do długowieczności

Microstructure And Residual Stress In Functionally Graded 316L Stainless Steel/Inconel 625 Alloys Fabricated By Direct Energy Deposition

Functionally graded materials (FGMs) provide a unique solution to combine distinct properties within a single component to enhance its overall performance. Understanding the microstructure and residual stress distribution is particularly important as the material dissimilarity in FGMs can result in high residual stress that affects the mechanical integrity of structural components. This work aims to study the microstructure and residual stress of additively manufactured FGMs and the effects of isothermal annealing. In this study, 316L stainless steel/Inconel 625 FGMs were built by direct energy deposition and characterized by optical and electron microscopy as well as synchrotron-based X-ray diffraction. Our study reveals that thermal annealing at 500°C for 3 h has minimal effects on the microstructure and chemistry of the graded materials, but effectively relieves the residual stress and leads to a uniform distribution of residual stress

Preparative Synthesis of dTDP-L-Rhamnose Through Combined Enzymatic Pathways

dTDP-L-rhamnose, an important precursor of O-antigen, was prepared on a large scale from dTMP by executing an one-pot reaction in which six enzymes are involved. Two enzymes, dTDP-4-keto-6-deoxy-D-glucose 3,5-epimerase and dTDP-4-keto-rhamnose reductase, responsible for the conversion of dTDP-4-keto-6-deoxy- D-glucose to dTDP-L-rhamnose, were isolated from their putative sequences in the genome of Mesorhizobium loti, functionally expressed in Escherichia coli, and their enzymatic activities were identified. The two enzymes were combined with an enzymatic process for dTDP-4- keto-6-deoxy-D-glucose involving TMP kinase, acetate kinase, dTDP-glucose synthase, and dTDP-glucose 4,6- dehydratase, which allowed us to achieve a preparative scale synthesis of dTDP-L-rhamnose using dTMP and glucose-1-phosphate as starting materials. About 82% yield of dTDP-L-rhamnose was obtained based on initial dTMP concentration at 20 mM dTMP, 1 mM ATP, 10 mM NADH, 60 mM acetyl phosphate, and 80 mM glucose-1- phosphate. From the reaction with 20 ml volume, approximately 180 mg of dTDP-L-rhamnose was obtained in an overall yield of 60% after two-step purification, that is, anion exchange chromatography and gel filtration for desalting. The purified product was identifiedbyHPLC, ESI-MS,andNMR,showingabout95%purity

Insulin-Like Growth Factor-I Stimulates Histone H3 and H4 Acetylation in the Brain in Vivo

IGF-I is essential to normal brain growth and exerts actions on neural stem cells and each major neural cell lineage. Whereas many studies show that IGF-I regulates gene expression, mechanisms by which it modulates transcription have not been explored. Chromatin modifications, such as histone phosphorylation, acetylation, and methylation, are known to be important initial steps in gene regulation, and acetylation of histone H3 and H4 is associated with gene activation. In this study, we show that IGF-I modulates the acetylation of H3 and H4 histones in the brain of two transgenic mouse lines and that these effects are associated with activation of the phosphoinositide 3-kinase/Akt signaling pathway. This provides evidence that the chromatin architecture modification contributes to the action of IGF-I on gene expression in the mammalian central nerve system

A HRNet-based Rehabilitation Monitoring System

The rehabilitation treatment helps to heal minor sports and occupational injuries. In a traditional rehabilitation process, a therapist will assign certain actions to a patient to perform in between hospital visits, and it will rely on the patient to remember actions correctly and the schedule to perform them. Unfortunately, many patients forget to perform actions or fail to recall actions in detail. As a consequence, the rehabilitation treatment is hampered or, in the worst case, the patient may suffer from additional injury caused by performing incorrect actions. To resolve these issues, we propose a HRNet-based rehabilitation monitoring system, which can remind a patient when to perform the actions and display the actions for the patient to follow via the patient's smartphone. In addition, it helps the therapist to monitor the progress of the rehabilitation for the patient. Our system consists of an iOS app and several components at the server side. The app is in charge of displaying and collecting action videos. The server computes the similarity score between the therapist's actions and the patient's in the videos to keep track of the number of repetitions of each action. Theses stats will be shown to both of the patient and therapist. The extensive experiments show that the F1-Score of the similarity calculation is as high as 0.9 and the soft accuracy of the number of repetitions is higher than 90%

Thyroxine modifies the effects of growth hormone in Ames dwarf mice

Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early-life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity

A Multi-Scale Approach to Study Biochemical and Biophysical Aspects of Resveratrol on Diesel Exhaust Particle-Human Primary Lung Cell Interaction

Diesel exhaust particles (DEPs) are major air pollutants that lead to numerous human disorders, especially pulmonary diseases, partly through the induction of oxidative stress. Resveratrol is a polyphenol that ameliorates the production of reactive oxygen species (ROS) and delays aging-related processes. Herein we studied the cytoprotective effect of resveratrol on DEP-exposed human lung cells in a factorial experimental design. This work investigates biophysical features including cellular compositions and biomechanical properties, which were measured at the single-cell level using confocal Raman microspectroscopy (RM) and atomic force microscopy (AFM), respectively. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least square regression (PLS) analysis were applied to analyze Raman spectra with and without resveratrol protection. The health status of individual cells could be effectively predicted using an index derived from characteristic Raman spectral peak (e.g., 1006 cm−1) based on PLS model. AFM measurements indicated that cellular adhesion force was greatly reduced, while Young’s modulus was highly elevated in resveratrol treated DEP-exposed cells. Anti-oxidant resveratrol reduced DEP-induced ROS production and suppressed releases of several cytokines and chemokines. These findings suggest resveratrol may enhance resistance of human lung cells (e.g., SAEC) to air pollutants (e.g. DEPs)

Solution structural analysis of the single-domain parvulin TbPin1

10.1371/journal.pone.0043017PLoS ONE78

Nitrogen-vacancy magnetometry of individual Fe-triazole spin crossover nanorods

[Fe(Htrz)2(trz)](BF4) (Fe-triazole) spin crossover molecules show thermal, electrical, and optical switching between high spin (HS) and low spin (LS) states, making them promising candidates for molecular spintronics. The LS and HS transitions originate from the electronic configurations of Fe(II) and are considered to be diamagnetic and paramagnetic respectively. The Fe(II) LS state has six paired electrons in the ground states with no interaction with the magnetic field and a diamagnetic behavior is usually observed. While the bulk magnetic properties of Fe-triazole compounds are widely studied by standard magnetometry techniques their magnetic properties at the individual level are missing. Here we use nitrogen vacancy (NV) based magnetometry to study the magnetic properties of the Fe-triazole LS state of nanoparticle clusters and individual nanorods of size varying from 20 to 1000 nm. Scanning electron microscopy (SEM) and Raman spectroscopy are performed to determine the size of the nanoparticles/nanorods and to confirm their respective spin states. The magnetic field patterns produced by the nanoparticles/nanorods are imaged by NV magnetic microscopy as a function of applied magnetic field (up to 350 mT) and correlated with SEM and Raman. We found that in most of the nanorods the LS state is slightly paramagnetic, possibly originating from the surface oxidation and/or the greater Fe(III) presence along the nanorods’ edges. NV measurements on the Fe-triazole LS state nanoparticle clusters revealed both diamagnetic and paramagnetic behavior. Our results highlight the potential of NV quantum sensors to study the magnetic properties of spin crossover molecules and molecular magnets

The microtubule-associated protein, EB1, links AIM2 inflammasomes with autophagy-dependent secretion

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. Finally, we found that the 5′-AMP activated protein kinase may regulate this EB1-mediated autophagy-based inflammasome-induced secretion of IL-1β. These findings reveal a novel EB1-mediated pathway for the secretion of IL-1β