Туризм как ресурс формирования социального благополучия

Социально-философское осмысления взаимосвязи и взаимовлияния туризма и благополучия актуально, поскольку туризм стал сферой жизни обществ, а социальное благополучие является фундаментальным залогом развития социума, его стабильности и процветания. По мнения автора, туризм становится одной из основ социального благополучия в объективных и субъективных его проявлениях. Благополучие, как основа личностной и социальной самореализации и успешности в достижении целей, в свою очередь, позволяет формировать жизненные стратегии глобального общества.Socio-philosophical understanding of the relationship and mutual influence of tourism and well-being is important, because tourism has become a sphere of life of societies, and social well-being is a fundamental guarantee of the development of society, its stability and prosperity. According to the author, tourism becomes one of the foundations of social well-being in its objective and subjective manifestations. Well-being, as the basis of personal and social self-realization and success in achieving the goals, in turn, allows to form the life strategies of the global society

Theory and numerical modeling of electrical self-potential signatures of unsaturated flow in melting snow

We have developed a new theory and numerical model of electrical self-potential (SP) signals associated with unsaturated flow in melting snow. The model is applicable to continuous natural-melt and transient-flow phenomena such as melt-water pulses, and is tested using laboratory column experiments. SP signals fundamentally depend on the temporal evolution of snow porosity and melt-water flux, electrical conductivity (EC) and pH. We infer a reversal of the sign of the zeta potential (a fundamental electrical property of grain surfaces in porous media), consistent with well-known elution sequences of ions that cause progressive increases and decreases in melt-water pH and EC respectively. Injection of fully-melted snow samples, containing the entire natural range of ions, into melting snow columns caused additional temporary reversals of the sign of the zeta potential. Widely-used empirical relationships between effective saturation, melt-water fraction, EC and pH, as well as snow porosity, grain size and permeability are found to be robust for modelling purposes. Thus, non-intrusive SP measurements can serve as proxies for snow melt-water fluxes and the temporal evolution of fundamental snow textural, hydraulic or water-quality parameters. Adaptation of automated multi-sensor SP acquisition technology from other environmental applications thus promises to bridge the widely acknowledged gap in spatial scale between satellite remote sensing and point measurements of snow properties. SP measurements and modelling may therefore contribute to solving a wide range of problems related to the assessment of water resource availability, avalanche or flood risk, or amplification of climatic forcing of ice-shelf, ice-sheet or glacier dynamics

An in vitro system to silence mitochondrial gene expression

The human mitochondrial genome encodes thirteen core subunits of the oxidative phosphorylation system, and defects in mitochondrial gene expression lead to severe neuromuscular disorders. However, the mech- anisms of mitochondrial gene expression remain poorly understood due to a lack of experimental ap- proaches to analyze these processes. Here, we present an in vitro system to silence translation in purified mitochondria. In vitro import of chemically synthesized precursor-morpholino hybrids allows us to target translation of individual mitochondrial mRNAs. By applying this approach, we conclude that the bicistronic, overlapping ATP8/ATP6 transcript is translated through a single ribosome/mRNA engagement. We show that recruitment of COX1 assembly factors to translating ribosomes depends on nascent chain formation. By defining mRNA-specific interactomes for COX1 and COX2, we reveal an unexpected function of the cytosolic oncofetal IGF2BP1, an RNA-binding protein, in mitochondrial translation. Our data provide insight into mitochondrial translation and innovative strategies to investigate mitochondrial gene expression

X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma

<p>Abstract</p> <p>Background</p> <p>It's well recognized that X-linked inhibitor of apoptosis (XIAP) was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac) was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC) were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI), clinicopathologic parameters and prognosis in IDC.</p> <p>Methods</p> <p>Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot.</p> <p>Results</p> <p>Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (<it>P </it>< 0.0001). It was noteworthy that 44 cases of IDC were positive in nuclear for XIAP, but none was for Smac. Expression status of Smac was more prevalent in HER2 positive group than negative group (<it>P </it>< 0.0001) and AI was positively correlated with HER2 protein expression (r_s= 0.265, <it>P </it>= 0.017). The present study first revealed that XIAP positive nuclear labeling (XIAP-N), but not cytoplasmic staining (XIAP-C), was the apoptotic marker correlated significantly with patients' shortened overall survival (<it>P </it>= 0.039). Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status.</p> <p>Conclusion</p> <p>Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.</p

LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies

Loss-of-function variants in the low-density lipoprotein receptor-related protein 10 (LRP10) gene have been associated with autosomal-dominant Parkinson's disease (PD), PD dementia, and dementia with Lewy bodies (DLB). Moreover, LRP10 variants have been found in individuals diagnosed with progressive supranuclear palsy and amyotrophic lateral sclerosis. Despite this genetic evidence, little is known about the expression and function of LRP10 protein in the human brain under physiological or pathological conditions. To better understand how LRP10 variants lead to neurodegeneration, we first performed an in-depth characterisation of LRP10 expression in post-mortem brains and human-induced pluripotent stem cell (iPSC)-derived astrocytes and neurons from control subjects. In adult human brain, LRP10 is mainly expressed in astrocytes and neurovasculature but undetectable in neurons. Similarly, LRP10 is highly expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived neurons. In astrocytes, LRP10 is present at trans-Golgi network, plasma membrane, retromer, and early endosomes. Interestingly, LRP10 also partially co-localises and interacts with sortilin-related receptor 1 (SORL1). Furthermore, although LRP10 expression and localisation in the substantia nigra of most idiopathic PD and DLB patients and LRP10 variant carriers diagnosed with PD or DLB appeared unchanged compared to control subjects, significantly enlarged LRP10-positive vesicles were detected in a patient carrying the LRP10 p.Arg235Cys variant. Last, LRP10 was detected in Lewy bodies (LB) at late maturation stages in brains from idiopathic PD and DLB patients and in LRP10 variant carriers. In conclusion, high LRP10 expression in non-neuronal cells and undetectable levels in neurons of control subjects indicate that LRP10-mediated pathogenicity is initiated via cell non-autonomous mechanisms, potentially involving the interaction of LRP10 with SORL1 in vesicle trafficking pathways. Together with the specific pattern of LRP10 incorporation into mature LBs, these data support an important mechanistic role for disturbed vesicle trafficking and loss of LRP10 function in neurodegenerative diseases

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes