Search Results (20)

Visual object tracking is one of the core techniques in human-centered artificial intelligence, which is very useful for human–machine interaction. State-of-the-art tracking methods have shown their robustness and accuracy on many challenges. However, a large amount of videos with precisely dense annotations are required for fully supervised training of their models. Considering that annotating videos frame-by-frame is a labor- and time-consuming workload, reducing the reliance on manual annotations during the tracking models’ training is an important problem to be resolved. To make a trade-off between the annotating costs and the tracking performance, we propose a weakly supervised tracking method based on co-saliency learning, which can be flexibly integrated into various tracking frameworks to reduce annotation costs and further enhance the target representation in current search images. Since our method enables the model to explore valuable visual information from unlabeled frames, and calculate co-salient attention maps based on multiple frames, our weakly supervised methods can obtain competitive performance compared to fully supervised baseline trackers, using only 3.33% of manual annotations. We integrate our method into two CNN-based trackers and a Transformer-based tracker; extensive experiments on four general tracking benchmarks demonstrate the effectiveness of our method. Furthermore, we also demonstrate the advantages of our method on egocentric tracking task; our weakly supervised method obtains 0.538 success on TREK-150, which is superior to prior state-of-the-art fully supervised tracker by 7.7%. Full article

Articular chondrocytes are the primary cells responsible for maintaining the integrity and functionality of articular cartilage, which is essential for smooth joint movement. A key aspect of their role involves mechanosensitive ion channels, which allow chondrocytes to detect and respond to mechanical forces encountered during joint activity; nonetheless, the variety of mechanosensitive ion channels involved in this process has not been fully resolved so far. Because some members of the two-pore domain potassium (K2P) channel family have been described as mechanosensors in other cell types, in this study, we investigate whether articular chondrocytes express such channels. RT-PCR analysis reveals the presence of TREK-1 and TREK-2 channels in these cells. Subsequent protein expression assessments, including Western blotting and immunohistochemistry, confirm the presence of TREK-1 in articular cartilage samples. Furthermore, whole-cell patch clamp assays demonstrate that freshly isolated chondrocytes exhibit currents attributable to TREK-1 channels, as evidenced by activation by arachidonic acid (AA) and ml335 and further inhibition by spadin. Additionally, exposure to hypo-osmolar shock activates currents, which can be attributed to the presence of TREK-1 channels, as indicated by their inhibition with spadin. Therefore, these findings highlight the expression of TREK channels in rat articular chondrocytes and suggest their potential involvement in regulating the integrity of cartilage extracellular matrix. Full article

Botanical areas under international protection are important for preserving plant and animal ecosystems. Forest ecosystems within Important Plant Areas (IPAs) are essential for preserving biological and species diversity. In AP Vojvodina (Northern Serbia), there are 27 IPAs, totaling 328,208 ha. Fruška Gora National Park (FGNP) territory is under international protection as an IPA. A large part of this park is covered by a forest ecosystem comprising various deciduous and evergreen trees, shrubs, and grasses. The forest ecosystem in FGNP is rich with natural attractions that are important for hiking, mountaineering, trekking, scientific tourism, wildlife, bird and animal watching, and community tourism. In this article, the authors used a quantitative method of collecting and processing data obtained through survey research. For this research, 610 respondents (325 residents and 285 visitors) were surveyed. Using questionnaires, the respondents expressed their opinions about the tourism potential of FGNP, as well as the satisfaction of tourists with current tourism development. The research results indicate that the forest ecosystem within the FGNP and IPA area has an important potential for the development of nature-based tourism (NbT) and that this tourism form significantly affects not only the satisfaction of the respondents but also increased awareness of the preservation and protection of these areas. Full article

Over a third of patients with temporal lobe epilepsy (TLE) are not effectively treated with current anti-seizure drugs, spurring the development of gene therapies. The injection of adeno-associated viral vectors (AAV) into the brain has been shown to be a safe and viable approach. However, to date, AAV expression of therapeutic genes has not been regulated. Moreover, a common property of antiepileptic drugs is a narrow therapeutic window between seizure control and side effects. Therefore, a long-term goal is to develop drug-inducible gene therapies that can be regulated by clinically relevant drugs. In this study, a first-generation doxycycline-regulated gene therapy that delivered an engineered version of the leak potassium channel Kcnk2 (TREK-M) was injected into the hippocampus of male rats. Rats were electrically stimulated until kindled. EEG was monitored 24/7. Electrical kindling revealed an important side effect, as even low expression of TREK M in the absence of doxycycline was sufficient to cause rats to develop spontaneous recurring seizures. Treating the epileptic rats with doxycycline successfully reduced spontaneous seizures. Localization studies of infected neurons suggest seizures were caused by expression in GABAergic inhibitory neurons. In contrast, doxycycline increased the expression of TREK-M in excitatory neurons, thereby reducing seizures through net inhibition of firing. These studies demonstrate that drug-inducible gene therapies are effective in reducing spontaneous seizures and highlight the importance of testing for side effects with pro-epileptic stressors such as electrical kindling. These studies also show the importance of evaluating the location and spread of AAV-based gene therapies in preclinical studies. Full article

Problems such as global environmental pollution and climate change have made the public’s desire for nature and closeness to greenery increasingly strong amid rapid urbanization. Improving the ability of experiential environmental interpretation products and services is the basis for national parks to meet the public’s needs, and the evaluation of their effectiveness is a necessary basis for optimizing the quality of environmental interpretation services in response to the current problems of unsynchronized environmental interpretation facilities and service levels. Using Pudacuo National Park as a case study, 365 visitors’ spatio-temporal trajectories with GPS devices and questionnaire data were collected, and the interaction changes of visitors’ external spatiotemporal behaviors and internal emotional experiences were analyzed using cluster analysis, GPS geoprocessing model construction, and emotional mean calculation methods, and the results showed that (1) Pudacuo National Park visitors mainly comprise four types of visitor clusters, which are the sightseeing type, trekking + sightseeing type, cruise type, and hiking + cruise type, as well as four types of spatio-temporal behavior patterns; the differences of visitors’ spatiotemporal behavior patterns are reflected in spatial movement, time allocation, and stopping behavior, and correspond to different emotional experience intensity. (2) Emotional experience value is positively correlated with location stay time, and emotional experience intensity is higher, corresponding to spatio-temporal behavior patterns with longer trajectory distance, longer dwell time, and more stopping behaviors, indicating that environmental services promote longer visitor stopping time and generate high-quality recreation experiences. (3) Finally, we proposed the optimization of environmental interpretation mode according to the spatiotemporal emotional differences of different types of visitor clusters. This study provides a basis for improving the quality of visitor experience and optimizing the quality of environmental interpretation services and provides a useful reference for guiding the construction of high-quality and diverse ecological experiences in national parks. Full article

Western notions of pilgrimage produce images of religious adherence to known beliefs and their ritual expressions. Definitions of pilgrimage have expanded in recent decades to embrace treks to sites unattached to the sacred landscapes of traditional faith groups. Along with this expansion of meanings and practices has come a wider acceptance of travel for psychological transformation. Tourism can be argued as a modulated form of pilgrimage and traditional journeys of faith overlapping with instances of entirely secular tourism. Another purpose of pilgrimage can be as a therapeutic practice for those suffering from depressive disorders and related conditions. Its efficacy as therapy, along with its limits, are discussed in clinical and personal contexts with a view to including religious as well as secular perspectives. The pragmatics of such therapy are mapped against current trends in treatment. Full article

Echinochrome A (Ech A), a naphthoquinoid pigment from sea urchins, is known to have anti-inflammatory and analgesic effects that have been suggested to be mediated by antioxidant activity and intracellular signaling modulation. In addition to these mechanisms, the ion channels in keratinocytes, immune cells, and nociceptive neurons may be the target for the pharmacological effects. Here, using the patch clamp technique, we investigated the effects of Ech A on the Ca²⁺-permeable TRPV3, TRPV1 and Orai1 channels and the two-pore domain K⁺ (K2P) channels (TREK/TRAAK, TASK-1, and TRESK) overexpressed in HEK 293 cells. Ech A inhibited both the TRPV3 and Orai1 currents, with IC₅₀ levels of 2.1 and 2.4 μM, respectively. The capsaicin-activated TRPV1 current was slightly augmented by Ech A. Ech A alone did not change the amplitude of the TREK-2 current (I_TREK2), but pretreatments with Ech A markedly facilitated I_TREK2 activation by 2-APB, arachidonic acid (AA), and acidic extracellular pH (pH_e). Similar facilitation effects of Ech A on TREK-1 and TRAAK were observed when they were stimulated with 2-APB and AA, respectively. On the contrary, Ech A did not affect the TRESK and TASK-1 currents. Interestingly, the I_TREK2 maximally activated by the combined application of 2-APB and Ech A was not inhibited by norfluoxetine but was still completely inhibited by ruthenium red. The selective loss of sensitivity to norfluoxetine suggested an altered molecular conformation of TREK-2 by Ech A. We conclude that the Ech A-induced inhibition of the Ca²⁺-permeable cation channels and the facilitation of the TREK/TRAAK K2P channels may underlie the analgesic and anti-inflammatory effects of Ech A. Full article

Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake mechanisms. Astrocytes modulate calcium-mediated excitability and release several neurotransmitters and neuromodulators, including glutamate, and significantly modulate neurotransmission. Accumulating evidence supports the concept of excitotoxicity caused by astrocytic glutamatergic release in pathological conditions. Thus, the current review highlights different vesicular and non-vesicular mechanisms of astrocytic glutamate release and their implication in neurodegenerative diseases. As in presynaptic neurons, the vesicular release of astrocytic glutamate is also primarily meditated by calcium-mediated exocytosis. V-ATPase is crucial in the acidification and maintenance of the gradient that facilitates the vesicular storage of glutamate. Along with these, several other components, such as cystine/glutamate antiporter, hemichannels, BEST-1, TREK-1, purinergic receptors and so forth, also contribute to glutamate release under physiological and pathological conditions. Events of hampered glutamate uptake could promote inflamed astrocytes to trigger repetitive release of glutamate. This could be favorable towards the development and worsening of neurodegenerative diseases. Therefore, across neurodegenerative diseases, we review the relations between defective glutamatergic signaling and astrocytic vesicular and non-vesicular events in glutamate homeostasis. The optimum regulation of astrocytic glutamatergic transmission could pave the way for the management of these diseases and add to their therapeutic value. Full article

In this paper, we report the design, synthesis and biological evaluation of a novel S-allyl-l-cysteine (SAC) and gallic acid conjugate S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-l-cysteinate (MTC). We evaluate the effects on ischemia-reperfusion-induced PC12 cells, primary neurons in neonatal rats, and cerebral ischemic neuronal damage in rats, and the results showed that MTC increased SOD, CAT, GPx activity and decreased LDH release. PI3K and p-AKT protein levels were significantly increased by activating PI3K/AKT pathway. Mitochondrial pro-apoptotic proteins Bax and Bim levels were reduced while anti-apoptotic protein Bcl-2 levels were increased. The levels of cleaved caspase-9 and cleaved caspase-3 were also reduced in the plasma. The endoplasmic reticulum stress (ERS) was decreased, which in turns the survival rate of nerve cells was increased, so that the ischemic injury of neurons was protected accordingly. MTC activated the MEK-ERK signaling pathway and promoted axonal regeneration in primary neurons of the neonatal rat. The pretreatment of MEK-ERK pathway inhibitor PD98059 and PI3K/AKT pathway inhibitor LY294002 partially attenuated the protective effect of MTC. Using a MCAO rat model indicated that MTC could reduce cerebral ischemia-reperfusion injury and decrease the expression of proinflammatory factors. The neuroprotective effect of MTC may be due to inhibition of the over-activation of the TREK-1 channel and reduction of the current density of the TREK1 channel. These results suggested that MTC has a protective effect on neuronal injury induced by ischemia reperfusion, so it may have the potential to become a new type of neuro-ischemic drug candidate. Full article

Although research from a positive psychology perspective is conducted among different populations, few studies have examined the predictors of life satisfaction among young backpackers. The current study focused on young adults (ages 21–30), an age group for whom backpacking treks are a growing phenomenon, during their treks in the Far East and South America. Direct and indirect models were used to identify personal factors and environmental resources contributing to life satisfaction. After at least one month abroad, 318 young adults (M = 23.76) answered a self-report quantitative questionnaire. The findings show that personal resources, social support, and community participation were positively associated with life satisfaction, and risk-taking behaviors were negatively associated with life satisfaction. Social support and community participation partially mediated the association between risk-taking behaviors and life satisfaction and between personal resources and life satisfaction. The implications of the findings for the subjective well-being of young backpackers during their transition to adulthood include, among others, the need to help young backpackers maintain their personal and social resources as valuable assets for coping with challenges during their trips. It is also important to increase awareness of the possible wide-ranging negative effects of risk-taking behaviors during backpacking trips. Full article

Two-pore-domain potassium (K_2P-) channels conduct outward K⁺ currents that maintain the resting membrane potential and modulate action potential repolarization. Members of the K_2P channel family are widely expressed among different human cell types and organs where they were shown to regulate important physiological processes. Their functional activity is controlled by a broad variety of different stimuli, like pH level, temperature, and mechanical stress but also by the presence of lipids or pharmacological agents. In patients suffering from cardiovascular diseases, alterations in K_2P-channel expression and function have been observed, suggesting functional significance and a potential therapeutic role of these ion channels. For example, upregulation of atrial specific K_2P3.1 (TASK-1) currents in atrial fibrillation (AF) patients was shown to contribute to atrial action potential duration shortening, a key feature of AF-associated atrial electrical remodelling. Therefore, targeting K_2P3.1 (TASK-1) channels might constitute an intriguing strategy for AF treatment. Further, mechanoactive K_2P2.1 (TREK-1) currents have been implicated in the development of cardiac hypertrophy, cardiac fibrosis and heart failure. Cardiovascular expression of other K_2P channels has been described, functional evidence in cardiac tissue however remains sparse. In the present review, expression, function, and regulation of cardiovascular K_2P channels are summarized and compared among different species. Remodelling patterns, observed in disease models are discussed and compared to findings from clinical patients to assess the therapeutic potential of K_2P channels. Full article

The two-pore domain K_2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K_2P subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K⁺ current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions. In the past decade, great advances have been made in the investigation of the molecular determinants of mechanosensation, and members of the TREK subfamily have emerged among the best-understood examples of mammalian ion channels directly influenced by the tension of the phospholipid bilayer. In parallel, the crucial contribution of mechano-gated TREK channels to the regulation of membrane potential in several cell types has been reported. In this review, we summarize the general principles underlying the mechanical activation of K_2P channels, and focus on the physiological roles of mechanically induced hyperpolarization. Full article

Cardiac fibroblasts (CF) play a pivotal role in preserving myocardial function and integrity of the heart tissue after injury, but also contribute to future susceptibility to heart failure. CF sense changes to the cardiac environment through chemical and mechanical cues that trigger changes in cellular function. In recent years, mechanosensitive ion channels have been implicated as key modulators of a range of CF functions that are important to fibrotic cardiac remodelling, including cell proliferation, myofibroblast differentiation, extracellular matrix turnover and paracrine signalling. To date, seven mechanosensitive ion channels are known to be functional in CF: the cation non-selective channels TRPC6, TRPM7, TRPV1, TRPV4 and Piezo1, and the potassium-selective channels TREK-1 and K_ATP. This review will outline current knowledge of these mechanosensitive ion channels in CF, discuss evidence of the mechanosensitivity of each channel, and detail the role that each channel plays in cardiac remodelling. By better understanding the role of mechanosensitive ion channels in CF, it is hoped that therapies may be developed for reducing pathological cardiac remodelling. Full article

Currently, there is a lack of bioinformatics approaches to identify highly divergent tandem repeats (TRs) in eukaryotic genomes. Here, we developed a new mathematical method to search for TRs, which uses a novel algorithm for constructing multiple alignments based on the generation of random position weight matrices (RPWMs), and applied it to detect TRs of 2 to 50 nucleotides long in the rice genome. The RPWM method could find highly divergent TRs in the presence of insertions or deletions. Comparison of the RPWM algorithm with the other methods of TR identification showed that RPWM could detect TRs in which the average number of base substitutions per nucleotide (x) was between 1.5 and 3.2, whereas T-REKS and TRF methods could not detect divergent TRs with x > 1.5. Applied to the search of TRs in the rice genome, the RPWM method revealed that TRs occupied 5% of the genome and that most of them were 2 and 3 bases long. Using RPWM, we also revealed the correlation of TRs with dispersed repeats and transposons, suggesting that some transposons originated from TRs. Thus, the novel RPWM algorithm is an effective tool to search for highly divergent TRs in the genomes. Full article

Astrocytes, the most abundant cell type in the brain, are non-excitable cells and play critical roles in brain function. Mature astrocytes typically exhibit a linear current–voltage relationship termed passive conductance, which is believed to enable astrocytes to maintain potassium homeostasis in the brain. We previously demonstrated that TWIK-1/TREK-1 heterodimeric channels mainly contribute to astrocytic passive conductance. However, the molecular identity of astrocytic passive conductance is still controversial and needs to be elucidated. Here, we report that spadin, an inhibitor of TREK-1, can dramatically reduce astrocytic passive conductance in brain slices. A series of gene silencing experiments demonstrated that spadin-sensitive currents are mediated by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Our study clearly showed that TWIK-1/TREK-1-heterodimeric channels can act as the main molecular machinery of astrocytic passive conductance, and suggested that spadin can be used as a specific inhibitor to control astrocytic passive conductance. Full article