Video Transformers: A Survey.

Transformer models have shown great success handling long-range interactions, making them a promising tool for modeling video. However, they lack inductive biases and scale quadratically with input length. These limitations are further exacerbated when dealing with the high dimensionality introduced by the temporal dimension. While there are surveys analyzing the advances of Transformers for vision, none focus on an in-depth analysis of video-specific designs. In this survey, we analyze the main contributions and trends of works leveraging Transformers to model video. Specifically, we delve into how videos are handled at the input level first. Then, we study the architectural changes made to deal with video more efficiently, reduce redundancy, re-introduce useful inductive biases, and capture long-term temporal dynamics. In addition, we provide an overview of different training regimes and explore effective self-supervised learning strategies for video. Finally, we conduct a performance comparison on the most common benchmark for Video Transformers (i.e., action classification), finding them to outperform 3D ConvNets even with less computational complexity.

Applying the retro-enantio approach to obtain a peptide capable of overcoming the blood-brain barrier.

The blood-brain barrier (BBB) is a formidable physical and enzymatic barrier that tightly controls the passage of molecules from the blood to the brain. In fact, less than 2 % of all potential neurotherapeutics are able to cross it. Here, by applying the retro-enantio approach to a peptide that targets the transferrin receptor, a full protease-resistant peptide with the capacity to act as a BBB shuttle was obtained and thus enabled the transport of a variety of cargos into the central nervous system.

Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome.

OBJECTIVE: Marfan's syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-ß signaling. TGF-ß is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-ß signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan's syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level. APPROACH AND RESULTS: Immunohistochemical and Western blotting analyses of dilated aortas from Marfan patients showed overexpression of contractile protein markers (α-smooth muscle actin, smoothelin, smooth muscle protein 22 alpha, and calponin-1) and collagen I in comparison with healthy aortas. VSMC explanted from Marfan aortic aneurysms showed increased in vitro expression of these phenotypic markers and also of myocardin, a transcription factor essential for VSMC-specific differentiation. These alterations were generally reduced after pharmacological inhibition of the TGF-ß pathway. Marfan VSMC in culture showed more robust actin stress fibers and enhanced RhoA-GTP levels, which was accompanied by increased focal adhesion components and higher nuclear localization of myosin-related transcription factor A. Marfan VSMC and extracellular matrix measured by atomic force microscopy were both stiffer than their respective controls. CONCLUSIONS: In Marfan VSMC, both in tissue and in culture, there are variable TGF-ß-dependent phenotypic changes affecting contractile proteins and collagen I, leading to greater cellular and extracellular matrix stiffness. Altogether, these alterations may contribute to the known aortic rigidity that precedes or accompanies Marfan's syndrome aneurysm formation.

Possible roles of amyloids in malaria pathophysiology.

The main therapeutic and prophylactic tools against malaria have been locked for more than a century in the classical approaches of using drugs targeting metabolic processes of the causing agent, the protist Plasmodium spp., and of designing vaccines against chosen antigens found on the parasite's surface. Given the extraordinary resources exhibited by Plasmodium to escape these traditional strategies, which have not been able to free humankind from the scourge of malaria despite much effort invested in them, new concepts have to be explored in order to advance toward eradication of the disease. In this context, amyloid-forming proteins and peptides found in the proteome of the pathogen should perhaps cease being regarded as mere anomalous molecules. Their likely functionality in the pathophysiology of Plasmodium calls for attention being paid to them as a possible Achilles' heel of malaria. Here we will give an overview of Plasmodium-encoded amyloid-forming polypeptides as potential therapeutic targets and toxic elements, particularly in relation to cerebral malaria and the blood-brain barrier function. We will also discuss the recent finding that the genome of the parasite contains an astonishingly high proportion of prionogenic domains.

Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor.

The treatment of Alzheimer's disease and many other brain-related disorders is limited because of the presence of the blood-brain barrier, which highly regulate the crossing of drugs. Metal nanoparticles have unique features that could contribute to the development of new therapies for these diseases. Nanoparticles have the capacity to carry several molecules of a drug; furthermore, their unique physico-chemical properties allow, for example, photothermal therapy to produce molecular surgery to destroy tumor cells and toxic structures. Recently, we demonstrated that gold nanoparticles conjugated to the peptide CLPFFD are useful to destroy the toxic aggregates of ß-amyloid, similar to the ones found in the brains of patients with Alzheimer's disease. However, nanoparticles, like many other compounds, have null or very low capacity to cross the blood-brain barrier. In order to devise a strategy to improve drug delivery to the brain, here we introduced the peptide sequence THRPPMWSPVWP into the gold nanoparticle-CLPFFD conjugate. This peptide sequence interacts with the transferrin receptor present in the microvascular endothelial cells of the blood-brain barrier, thus causing an increase in the permeability of the conjugate in brain, as shown by experiments in vitro and in vivo. Our results are highly relevant for the therapeutic applications of gold nanoparticles for molecular surgery in the treatment of neurodegenerative diseases such as Alzheimer's disease.

Ethanol increases p190RhoGAP activity, leading to actin cytoskeleton rearrangements.

We previously reported that cells chronically exposed to ethanol show alterations in actin cytoskeleton organization and dynamics in primary cultures of newborn rat astrocytes, a well-established in vitro model for foetal alcohol spectrum disorders. These alterations were attributed to a decrease in the cellular levels of active RhoA (RhoA-GTP), which in turn was produced by an increase in the total RhoGAP activity. We here provide evidence that p190RhoGAPs are the main factors responsible for such increase. Thus, in astrocytes chronically exposed to ethanol we observe: (i) an increase in p190A- and p190B-associated RhoGAP activity; (ii) a higher binding of p190A and p190B to RhoA-GTP; (iii) a higher p120RasGAP-p190A RhoGAP complex formation; and (iv) the recruitment of both p190RhoGAPs to the plasma membrane. The simultaneous silencing of both p190 isoforms prevents the actin rearrangements and the total RhoGAP activity increase triggered both by ethanol. Therefore, our data directly points p190RhoGAPs as ethanol-exposure molecular targets on glial cells of the CNS.

Silver sub-nanoclusters electrocatalyze ethanol oxidation and provide protection against ethanol toxicity in cultured mammalian cells.

Silver atomic quantum clusters (AgAQCs), with two or three silver atoms, show electrocatalytic activities that are not found in nanoparticles or in bulk silver. AgAQCs supported on glassy carbon electrodes oxidize ethanol and other alcohols in macroscopic electrochemical cells in acidic and basic media. This electrocatalysis occurs at very low potentials (from approximately +200 mV vs RHE), at physiological pH, and at ethanol concentrations that are found in alcoholic patients. When mammalian cells are co-exposed to ethanol and AgAQCs, alcohol-induced alterations such as rounded cell morphology, disorganization of the actin cytoskeleton, and activation of caspase-3 are all prevented. This cytoprotective effect of AgAQCs is also observed in primary cultures of newborn rat astrocytes exposed to ethanol, which is a cellular model of fetal alcohol syndrome. AgAQCs oxidize ethanol from the culture medium only when ethanol and AgAQCs are added to cells simultaneously, which suggests that cytoprotection by AgAQCs is provided by the ethanol electro-oxidation mediated by the combined action of AgAQCs and cells. Overall, these findings not only show that AgAQCs are efficient electrocatalysts at physiological pH and prevent ethanol toxicity in cultured mammalian cells, but also suggest that AgAQCs could be used to modify redox reactions and in this way promote or inhibit biological reactions.

[Studies conducted in Spain on concentrations in humans of persistent toxic compounds]. / Estudios realizados en España sobre concentraciones en humanos de compuestos tóxicos persistentes.

No systematic review is available on studies conducted in Spain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrations of DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individuals may be over 200-fold higher than those of others. The actual magnitude of human contamination by PTS and their trends across Spain -as well as the geographic and social heterogeneity- remain largely unknown.

Estudios realizados en España sobre concentraciones en humanos de compuestos tóxicos persistentes / Studies conducted in Spain on concentrations in humans of persistent toxic compounds

Aunque en España se han realizado estudios sobre concentraciones en medios biológicos humanos de compuestos tóxicos persistentes (CTP) desde hace varias décadas, no se ha llevado a cabo una revisión sistemática. Los objetivos fueron: a) identificar los estudios realizados en España en los últimos30 años que hubiesen determinado concentraciones en humanos de diclorodifeniltricloroetano (DDT), diclorodifenildicloroeteno (DDE), hexaclorobenceno (HCB), hexaclorociclohexanos (HCH) y policlorobifenilos (PCB), y b) sintetizar las principales característicasy resultados de cada estudio. Los estudios son sumamenteheterogéneos y la mayoría carece de representatividad poblacional. Las concentraciones de DDT y DDE parecenhaber decrecido moderadamente en los últimos 20 años. Haynumerosas fluctuaciones en los valores de HCB, HCH y PCB,en algún caso compatibles con un estancamiento. Se observan grandes diferencias en los valores detectados en los distintos estudios y dentro de un mismo grupo: las concentraciones de CTP de algunos individuos pueden llegar a ser más de 200 veces superiores a los de otros. La magnitud real de la contaminación humana por CTP y sus tendencias a lo largo del territorio español, así como su diversidad geográfica y social, siguen siendo ampliamente desconocidas

No systematic review is available on studies conducted inSpain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene(HCB), hexachlorocyclohexane (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrationsof DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individualsmay be over 200-fold higher than those of others. Theactual magnitude of human contamination by PTS and theirtrends across Spain –as well as the geographic and social heterogeneity– remain largely unknown

Monitoring concentrations of persistent organic pollutants in the general population: the international experience.

Assessing the adverse effects on human health of persistent organic pollutants (POPs) and the impact of policies aiming to reduce human exposure to POPs warrants monitoring body concentrations of POPs in representative samples of subjects. While numerous ad hoc studies are being conducted to understand POPs effects, only a few countries are conducting nationwide surveillance programs of human concentrations of POPs, and even less countries do so in representative samples of the general population. We tried to identify all studies worldwide that analyzed the distribution of concentrations of POPs in a representative sample of the general population, and we synthesized the studies' main characteristics, as design, population, and chemicals analyzed. The most comprehensive studies are the National Reports on Human Exposure to Environmental Chemicals (USA), the German Environmental Survey, and the Arctic Monitoring and Assessment Programme. Population-wide studies exist as well in New Zealand, Australia, Japan, Flanders (Belgium) and the Canary Islands (Spain). Most such studies are linked with health surveys, which is a highly-relevant additional strength. Only the German and Flemish studies analyzed POPs by educational level, while studies in the USA offer results by ethnic group. The full distribution of POPs concentrations is unknown in many countries. Knowledge gaps include also the interplay of age, gender, period and cohort effects on the prevalence of exposures observed by cross-sectional surveys. Local and global efforts to minimize POPs contamination, like the Stockholm convention, warrant nationwide monitoring of concentrations of POPs in representative samples of the general population. Results of this review show how such studies may be developed and used.

Lysophosphatidic acid rescues RhoA activation and phosphoinositides levels in astrocytes exposed to ethanol.

Long-term ethanol treatment substantially impairs glycosylation and membrane trafficking in primary cultures of rat astrocytes. Our previous studies indicated that these effects were attributable to a primary alteration in the dynamics and organization of the actin cytoskeleton, although the molecular mechanism(s) remains to be elucidated. As small Rho GTPases and phosphoinositides are involved in the actin cytoskeleton organization, we now explore the effects of chronic ethanol treatment on these pathways. We show that chronic ethanol treatment of rat astrocytes specifically reduced endogenous levels of active RhoA as a result of the increase of in the RhoGAP activity. Furthermore, ethanol-treated astrocytes showed reduced phosphoinositides levels. When lysophosphatidic acid was added to ethanol-treated astrocytes, it rapidly reverted actin cytoskeleton reorganization and raised active RhoA levels and phosphoinositides content to those observed in untreated astrocytes. Overall, our results indicate that the harmful effects of chronic exposure to ethanol on a variety of actin dynamics-associated cellular events are primarily because of alterations of activated RhoA and phosphoinositides pools.

Concentraciones de compuestos tóxicos persistentes en la población general española. Criterios para un diagnóstico de la situación actual / concentrations of persistent toxic compounds in the Spanish general population. Criteria for a diagnosis of the present situation

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