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The interactions of electrons with molecular systems under various conditions are essential to interdisciplinary research fields extending over the fundamental and applied sciences. In particular, investigating electron-induced ionization and dissociation of molecules may shed light on the radiation damage to living cells, the physicochemical processes in interstellar environments, and reaction mechanisms occurring in combustion or plasma. We have, therefore, studied electron-induced ionization and dissociation of the gas phase 3,4-dihydro-2H-pyran (DHP), a cyclic ether appearing to be a viable moiety for developing efficient clinical pharmacokinetics and revealing the mechanisms of biofuel combustion. The mass spectra in the m/z = 10-90 mass range were measured at several different energies of the ionizing electron beam using mass spectrometry. The mass spectra of DHP at the same energies were simulated using on-the-fly semi-classical molecular dynamics (MD) within the framework of the QCxMS formalism. The MD settings were suitably adjusted until a good agreement with the experimental mass spectra intensities was achieved, thus enabling a reliable assignment of cations and unraveling the plausible fragmentation channels. Based on the measurement of the absolute total ionization cross section of DHP (18.1 ± 0.9) × 10-16 cm2 at 100 eV energy, the absolute total and partial ionization cross sections of DHP were determined in the 5-140 eV electron energy. Moreover, a machine learning algorithm that was trained with measured cross sections from 25 different molecules was used to predict the total ionization cross section for DHP. Comparison of the machine learning simulation with the measured data showed acceptable agreement, similar to that achieved in past predictions of the algorithm.
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Most essential cellular functions are performed by proteins assembled into larger complexes. Fluorescence Polarization Microscopy (FPM) is a powerful technique that goes beyond traditional imaging methods by allowing researchers to measure not only the localization of proteins within cells, but also their orientation or alignment within complexes or cellular structures. FPM can be easily integrated into standard widefield microscopes with the addition of a polarization modulator. However, the extensive image processing and analysis required to interpret the data have limited its widespread adoption. To overcome these challenges and enhance accessibility, we introduce OOPS (Object-Oriented Polarization Software), a MATLAB package for object-based analysis of FPM data. By combining flexible image segmentation and novel object-based analyses with a high-throughput FPM processing pipeline, OOPS empowers researchers to simultaneously study molecular order and orientation in individual biological structures; conduct population assessments based on morphological features, intensity statistics, and FPM measurements; and create publication-quality visualizations, all within a user-friendly graphical interface. Here, we demonstrate the power and versatility of our approach by applying OOPS to punctate and filamentous structures.
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Polarización de Fluorescencia , Procesamiento de Imagen Asistido por Computador , Microscopía Fluorescente , Programas Informáticos , Microscopía Fluorescente/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Polarización de Fluorescencia/métodos , Biología Computacional/métodos , Humanos , AlgoritmosRESUMEN
Autism spectrum disorder (ASD) commonly co-occurs with congenital heart disease (CHD), but the molecular mechanisms underlying this comorbidity remain unknown. Given that children with CHD come to clinical attention by the newborn period, understanding which CHD variants carry ASD risk could provide an opportunity to identify and treat individuals at high risk for developing ASD far before the typical age of diagnosis. Therefore, it is critical to delineate the subset of CHD genes most likely to increase the risk of ASD. However, to date there is relatively limited overlap between high confidence ASD and CHD genes, suggesting that alternative strategies for prioritizing CHD genes are necessary. Recent studies have shown that ASD gene perturbations commonly dysregulate neural progenitor cell (NPC) biology. Thus, we hypothesized that CHD genes that disrupt neurogenesis are more likely to carry risk for ASD. Hence, we performed an in vitro pooled CRISPR interference (CRISPRi) screen to identify CHD genes that disrupt NPC biology similarly to ASD genes. Overall, we identified 45 CHD genes that strongly impact proliferation and/or survival of NPCs. Moreover, we observed that a cluster of physically interacting ASD and CHD genes are enriched for ciliary biology. Studying seven of these genes with evidence of shared risk (CEP290, CHD4, KMT2E, NSD1, OFD1, RFX3, TAOK1), we observe that perturbation significantly impacts primary cilia formation in vitro. While in vivo investigation of TAOK1 reveals a previously unappreciated role for the gene in motile cilia formation and heart development, supporting its prediction as a CHD risk gene. Together, our findings highlight a set of CHD risk genes that may carry risk for ASD and underscore the role of cilia in shared ASD and CHD biology.
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A new type of UV-curable pressure-sensitive adhesive containing Si atoms (Si-PSAs) was prepared by a solution-free UV-initiated telomerization process of n-butyl acrylate, acrylic acid, methyl methacrylate, and 4-acrylooxybenzophenone using triethylsilane (TES) as a telogen and an acylphosphine oxide (APO) as a radical photoinitiator. Selected commercial adhesion promoters were tested as additives in the formulation of adhesive compositions, i.e., (i) an organic copolymer with polar groups (carboxyl and hydroxyl); (ii) a hydroxymetal-organic compound; and (iii) a quaternary ammonium salt and (iv) a chlorinated polyolefin. No fillers, crosslinking agents, or photoinitiators were used in the adhesive compositions. NMR techniques confirmed the incorporation of silicon atoms into the polyacrylate structure. The influence of adhesion promoters on the kinetics of the UV-crosslinking process of Si-PSAs was investigated by a photo-DSC technique. The obtained Si-PSAs were characterized by adhesion (to steel, glass, PMMA, and PE), tack, and cohesion at 20 °C. Finally, the wetting angle of Si-PSAs with water was checked and their thermal stability was proved (TGA). Unexpectedly, the quaternary ammonium salt had the most favorable effect on improving the thermal stability of Si-PSAs (302 °C) and adhesion to glass and PMMA. In contrast, Si-PSAs containing the hydroxymetal-organic compound showed excellent adhesion to steel.
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The risk of HIV-1 infection and the rate of disease progression vary considerably among individuals and the genetic makeup of the host may be one of the possible reasons for this. We aimed to determine association of functional single nucleotide polymorphism (SNPs), -1082A/G (rs1800896), -819C/T (rs1800871), and -592C/A (rs1800872) in IL-10 gene, with the susceptibility to HIV-1 infection and clinical parameters expressed as a baseline CD4+ T cell count, CD8+ T cell count, and viral load. Therapy naïve HIV-1 infected individuals and HIV-1 seronegative controls from Poland were recruited for this study. Genotyping results revealed significantly higher frequency of -1082G/G genotype (28.1 % vs 16.1 %; p = 0.0019, OR=0.49) and -1082G allele (47.6 % vs 38.8 %; p = 0.0028, OR = 0.70) as well as lower frequency of -592 and -819 heterozygosity (45.0 % vs 34.4 %; p = 0.0266, OR = 1.47) in controls compared to seropositive subjects. High producing haplotype GCC was associated with increased risk of HIV-1 infection (p = 0.0018, OR = 1.52). Individuals possessing -592 and -819 minor allele had significantly higher CD8+ T cell count compared to the wild type allele carriers (p = 0.0303). Moreover, presence of -1082G allele was related with lower viral load as well as CD4+ and CD8+ T cells counts among patients infected with R5 HIV-1 variant. Thus, IL-10 gene promoter variants may be a risk factor for HIV-1 transmission and may modulate disease progression in the Polish population.
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Progresión de la Enfermedad , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH , VIH-1 , Interleucina-10 , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Carga Viral , Humanos , Interleucina-10/genética , VIH-1/fisiología , Polonia/epidemiología , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Masculino , Femenino , Adulto , Regiones Promotoras Genéticas/genética , Persona de Mediana Edad , Recuento de Linfocito CD4 , Alelos , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Adulto Joven , Estudios de Asociación GenéticaRESUMEN
BACKGROUND: The gene cAMP-Responsive Element Binding protein 3-like-1 (CREB3L1) has been implicated in bone development in mice, with CREB3L1 knock-out mice exhibiting fragile bones, and in humans, with CREB3L1 mutations linked to osteogenesis imperfecta. However, the mechanism through which Creb3l1 regulates bone development is not fully understood. RESULTS: To probe the role of Creb3l1 in organismal physiology, we used CRISPR-Cas9 genome editing to generate a Danio rerio (zebrafish) model of Creb3l1 deficiency. In contrast to mammalian phenotypes, the Creb3l1 deficient fish do not display abnormalities in osteogenesis, except for a decrease in the bifurcation pattern of caudal fin. Both, skeletal morphology and overall bone density appear normal in the mutant fish. However, the regeneration of caudal fin postamputation is significantly affected, with decreased overall regenerate and mineralized bone area. Moreover, the mutant fish exhibit a severe patterning defect during regeneration, with a significant decrease in bifurcation complexity of the fin rays and distalization of the bifurcation sites. Analysis of genes implicated in bone development showed aberrant patterning of shha and ptch2 in Creb3l1 deficient fish, linking Creb3l1 with Sonic Hedgehog signaling during fin regeneration. CONCLUSIONS: Our results uncover a novel role for Creb3l1 in regulating tissue growth and patterning during regeneration.
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INTRODUCTION: The formation of normal bone and bone healing requires the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after a fracture. Creb3l1 undergoes regulated intramembrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes. METHODS: To expand our understanding of Creb3l1's role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish Danio rerio caused a frameshift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ does not regulate transcription, and the creb3l1TA+/TA+ fish do not mediate creb3l1-dependent transcription. RESULTS: We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased regeneration and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates. CONCLUSION: Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway and document a novel role of Creb3l1 in tissue patterning.
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Endothelial cells (ECs) experience a variety of highly dynamic mechanical stresses. Among others, cyclic stretch and increased plasma membrane tension inhibit clathrin-mediated endocytosis (CME) in non-ECs. It remains elusive how ECs maintain CME in these biophysically unfavorable conditions. Previously, we have used simultaneous two-wavelength axial ratiometry (STAR) microscopy to show that endocytic dynamics are similar between statically cultured human umbilical vein endothelial cells (HUVECs) and fibroblast-like Cos-7 cells. Here, we asked whether biophysical stresses generated by blood flow influence CME. We used our data processing platform-DrSTAR-to examine if clathrin dynamics are altered in HUVECs after experiencing fluidic shear stress (FSS). We found that HUVECs cultivated under a physiological level of FSS had increased clathrin dynamics compared with static controls. FSS increased both clathrin-coated vesicle formation and nonproductive flat clathrin lattices by 2.3-fold and 1.9-fold, respectively. The curvature-positive events had significantly delayed curvature initiation relative to clathrin recruitment in flow-stimulated cells, highlighting a shift toward flat-to-curved clathrin transitions in vesicle formation. Overall, our findings indicate that clathrin dynamics and clathrin-coated vesicle formation can be modulated by the local physiological environment and represent an important regulatory mechanism.
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Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.
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Encéfalo , Neurofisiología , Neurociencias , Análisis de la Célula Individual , Humanos , Encéfalo/citología , Encéfalo/fisiología , Neuropatología/métodos , Neuropatología/tendencias , Neurofisiología/métodos , Neurofisiología/tendencias , Neurociencias/métodos , Neurociencias/tendencias , Análisis de la Célula Individual/métodos , Análisis de la Célula Individual/tendencias , Análisis de Expresión Génica de una Sola Célula , Transcriptoma , Flujo de Trabajo , AnimalesRESUMEN
Optimal vascular structure and function are essential for maintaining the physiological functions of the cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular and molecular composition. These changes result from multiple risk factors and may be compensatory adaptations to sustain blood vessel function. They occur in diverse cardiovascular pathologies, from hypertension to heart failure and atherosclerosis. Dynamic changes in the endothelium, fibroblasts, smooth muscle cells, pericytes or other vascular wall cells underlie remodelling. In addition, immune cells, including macrophages and lymphocytes, may infiltrate vessels and initiate inflammatory signalling. They contribute to a dynamic interplay between cell proliferation, apoptosis, migration, inflammation, and extracellular matrix reorganisation, all critical mechanisms of vascular remodelling. Molecular pathways underlying these processes include growth factors (e.g., vascular endothelial growth factor and platelet-derived growth factor), inflammatory cytokines (e.g., interleukin-1ß and tumour necrosis factor-α), reactive oxygen species, and signalling pathways, such as Rho/ROCK, MAPK, and TGF-ß/Smad, related to nitric oxide and superoxide biology. MicroRNAs and long noncoding RNAs are crucial epigenetic regulators of gene expression in vascular remodelling. We evaluate these pathways for potential therapeutic targeting from a clinical translational perspective. In summary, vascular remodelling, a coordinated modification of vascular structure and function, is crucial in cardiovascular disease pathology.
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Enfermedades Cardiovasculares , Hipertensión , Inflamación , Remodelación Vascular , Humanos , Inflamación/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/metabolismo , Hipertensión/fisiopatología , Hipertensión/metabolismo , Animales , Estrés Oxidativo , Transducción de Señal , Oxidación-ReducciónRESUMEN
Strong coupling between metal nanoparticles and molecules mixes their excitations, creating new eigenstates with modified properties such as altered chemical reactivity, different relaxation pathways or modified phase transitions. Here, we explore excited state plasmon-molecule coupling and discuss how strong coupling together with a changed orientation and number of an asymmetric molecule affects the generation of hot carriers in the system. We used a promising plasmonic material, magnesium, for the nanoparticle and coupled it with CPDT molecules, which are used in organic optoelectronic materials for organic electronic applications due to their facile modification, electron-rich structure, low band gap, high electrical conductivity and good charge transport properties. By employing computational quantum electronic tools we demonstrate the existence of a strong coupling mediated charge transfer plasmon whose direction, magnitude, and spectral position can be tuned. We find that the orientation of CPDT changes the nanoparticle-molecule gap for which maximum charge separation occurs, while larger gaps result in trapping hot carriers within the moieties due to weaker interactions. This research highlights the potential for tuning hot carrier generation in strongly coupled plasmon-molecule systems for enhanced energy generation or excited state chemistry.
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Emerging evidence indicates an association between blood pressure and inflammation, yet this relationship remains unclear in older adults, despite the elevated prevalence of hypertension. We investigated the association between blood pressure, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and white blood cell (WBC) count in a cohort of 3571 older adults aged 65 and above, and 587 middle-aged participants (55-59 years old). In women aged 65 and above, the relationship between inflammatory markers and blood pressure was consistent, with hs-CRP and WBC emerging as predictors of high blood pressure. For hs-CRP, the adjusted odds ratio (OR) was 1.5 (95% CI, 1.07 to 2.10, P = 0.02), and for WBC, the adjusted OR was 1.41 (95% CI, 1.02 to 1.94, P = 0.04), comparing the highest to the lowest quartiles. In men, only the WBC count was significantly associated with an increased OR for high BP (adjusted OR 1.49, 95% CI, 1.09 to 2.02, P = 0.01) across quartiles. Across the entire study population, in a fully adjusted model, all inflammatory markers were modestly associated with blood pressure levels, while the effect of being over 65 years was the most significant predictor of high blood pressure (OR 1.84, 95% CI, 1.50 to 2.25, P < 0.001). The link between key inflammation markers and blood pressure in older adults varies by sex and biomarker type and may differ from the relationship observed in younger individuals. These relationships are likely to be affected by factors linked to age.
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Biomarcadores , Presión Sanguínea , Proteína C-Reactiva , Hipertensión , Inflamación , Interleucina-6 , Humanos , Femenino , Masculino , Anciano , Biomarcadores/sangre , Persona de Mediana Edad , Proteína C-Reactiva/metabolismo , Hipertensión/sangre , Hipertensión/fisiopatología , Interleucina-6/sangre , Recuento de Leucocitos , Factores Sexuales , Inflamación/sangre , Presión Sanguínea/fisiologíaRESUMEN
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.
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Corteza Cerebral , Neurogénesis , Organoides , Humanos , Corteza Cerebral/embriología , Corteza Cerebral/metabolismo , Cromatina/metabolismo , Cromatina/genética , Aprendizaje Profundo , Elementos de Facilitación Genéticos , Regulación del Desarrollo de la Expresión Génica , Neurogénesis/genética , Neuronas/metabolismo , Organoides/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Regiones Promotoras Genéticas , Elementos Reguladores de la TranscripciónRESUMEN
Desmosomes are intercellular junctions that regulate mechanical integrity in epithelia and cardiac muscle. Dynamic desmosome remodeling is essential for wound healing and development, yet the mechanisms governing junction assembly remain elusive. While we and others have shown that cadherin ectodomains are highly organized, how this ordered architecture emerges during assembly is unknown. Using fluorescence polarization microscopy, we show that desmoglein 2 (Dsg2) ectodomain order gradually increases during 8 h of assembly, coinciding with increasing adhesive strength. In a scratch wound assay, we observed a similar increase in order in desmosomes assembling at the leading edge of migratory cells. Together, our findings indicate that cadherin organization is a hallmark of desmosome maturity and may play a role in conferring adhesive strength.
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Desmogleína 2 , Desmosomas , Cadherinas , Uniones Intercelulares , Adhesión CelularRESUMEN
BACKGROUND: Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. METHODS: The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186â 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. P-gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D. RESULTS: The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.226 [95% CI, 1.160-1.296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio (P-gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 [95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively). CONCLUSIONS: The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.
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Aminoácidos de Cadena Ramificada , Enfermedad Coronaria , Estudio de Asociación del Genoma Completo , Glicina , Hipertensión , Humanos , Glicina/sangre , Aminoácidos de Cadena Ramificada/sangre , Masculino , Femenino , Persona de Mediana Edad , Enfermedad Coronaria/sangre , Enfermedad Coronaria/genética , Enfermedad Coronaria/epidemiología , Hipertensión/sangre , Hipertensión/epidemiología , Hipertensión/genética , Análisis de la Aleatorización Mendeliana , Anciano , Reino Unido/epidemiología , Estudios ProspectivosRESUMEN
Neuromuscular junctions transmit signals from the nervous system to skeletal muscles, triggering their contraction, and their proper organization is essential for breathing and voluntary movements. αDystrobrevin-1 is a cytoplasmic component of the dystrophin-glycoprotein complex and has pivotal functions in regulating the integrity of muscle fibers and neuromuscular junctions. Previous studies identified that αDystrobrevin-1 functions in the organization of the neuromuscular junction and that its phosphorylation in the C-terminus is required in this process. Our proteomic screen identified several putative αDystrobrevin-1 interactors recruited to the Y730 site in phosphorylated and unphosphorylated states. Amongst various actin-modulating proteins, we identified the Arp2/3 complex regulator cortactin. We showed that similarly to αDystrobrevin-1, cortactin is strongly enriched at the neuromuscular postsynaptic machinery and obtained results suggesting that these two proteins interact in cell homogenates and at the neuromuscular junctions. Analysis of synaptic morphology in cortactin knockout mice showed abnormalities in the slow-twitching soleus muscle and not in the fast-twitching tibialis anterior. However, muscle strength examination did not reveal apparent deficits in knockout animals.
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Cortactina , Proteínas Asociadas a la Distrofina , Ratones Noqueados , Unión Neuromuscular , Animales , Unión Neuromuscular/metabolismo , Cortactina/metabolismo , Cortactina/genética , Ratones , Proteínas Asociadas a la Distrofina/metabolismo , Proteínas Asociadas a la Distrofina/genética , Músculo Esquelético/metabolismo , Humanos , FosforilaciónRESUMEN
Long-term exposures to environmental factors including airborne as well as noise pollutants, are associated with cardiovascular risk. However, the influence of environmental pollution on the young population is controversial. Accordingly, we aimed to investigate the relationships between long-term exposures to different environmental factors and major cardiovascular and inflammatory parameters and biomarkers in young, healthy subjects. Representative sample of permanent residents of two cities differing in air and noise pollution levels, aged 15-21 years, were recruited. Krakow and Lublin, both located in southern Poland, were chosen in relation to their similarities in demographic and geopolitical characteristics, but differences in air pollution (higher in Krakow) and noise parameters (higher in Lublin). A total of 576 subjects were studied: 292 in Krakow and 284 in Lublin. All subjects underwent health questionnaire, blood pressure measurements and biomarker determinations. Inflammatory biomarkers, such as CRP, hs-CRP, fibrinogen as well as homocysteine were all significantly higher in subjects living in Krakow as opposed to subjects living in Lublin (for hsCRP: 0.52 (0.32-0.98) mg/l vs. 0.35 (0.22-0.67) mg/l; p < 0.001). Increased inflammatory biomarker levels were observed in Krakow in both male and female young adults. Interestingly, significant differences were observed in blood pressure between male and female subjects. Males from Krakow had significantly higher mean systolic blood pressure (127.7 ± 10.4 mm/Hg vs. 122.4 ± 13.0 mm/Hg; p = 0.001), pulse pressure (58.7 ± 8.9 mm/Hg vs. 51.4 ± 12.3 mm/Hg; p < 0.001) and lower heart rate (p < 0.001) as compared to males living in Lublin. This was not observed in young adult females. Long-term exposure to environmental factors related to the place of residence can significantly influence inflammatory and cardiovascular parameters, even in young individuals. Interestingly, among otherwise healthy young adults, blood pressure differences exhibited significant variations based on biological sex.
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Biomarcadores , Presión Sanguínea , Exposición a Riesgos Ambientales , Inflamación , Humanos , Masculino , Femenino , Adulto Joven , Exposición a Riesgos Ambientales/efectos adversos , Adolescente , Inflamación/sangre , Biomarcadores/sangre , Polonia/epidemiología , Factores Sexuales , Adulto , Voluntarios Sanos , Hipertensión/etiología , Hipertensión/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisisRESUMEN
Malignant hypertension (MHT) is a hypertensive emergency with excessive blood pressure (BP) elevation and accelerated disease progression. MHT is characterized by acute microvascular damage and autoregulation failure affecting the retina, brain, heart, kidney, and vascular tree. BP must be lowered within hours to mitigate patient risk. Both absolute BP levels and the pace of BP rise determine risk of target-organ damage. Nonadherence to the antihypertensive regimen remains the most common cause for MHT, although antiangiogenic and immunosuppressant therapy can also trigger hypertensive emergencies. Depending on the clinical presentation, parenteral or oral therapy can be used to initiate BP lowering. Evidence-based outcome data are spotty or lacking in MHT. With effective treatment, the prognosis for MHT has improved; however, patients remain at high risk of adverse cardiovascular and kidney outcomes. In this review, we summarize current viewpoints on the epidemiology, pathogenesis, and management of MHT; highlight research gaps; and propose strategies to improve outcomes.
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Hipertensión Maligna , Humanos , Hipertensión Maligna/epidemiología , Hipertensión Maligna/fisiopatología , Hipertensión Maligna/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiologíaRESUMEN
Casimir torque, a rotational motion driven by zero-point energy minimization, is a problem that attracts notable research interest. Recently, it has been realized using liquid crystal phases and natural anisotropic substrates. However, for natural materials, substantial torque occurs only at van der Waals distances of ~10 nm. Here, we use Casimir self-assembly with triangular gold nanostructures for rotational self-alignment at truly Casimir distances (100 to 200 nm separation). The interplay of repulsive electrostatic and attractive Casimir potentials forms a stable quantum trap, giving rise to a tunable Fabry-Pérot microcavity. This cavity self-aligns both laterally and rotationally to maximize area overlap between templated and floating flakes. The rotational self-alignment is sensitive to the equilibrium distance between the two triangles and their area, offering possibilities for active control via electrostatic screening manipulation. Our self-assembled Casimir microcavities present a versatile and tunable platform for nanophotonic, polaritonic, and optomechanical applications.