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Multicellular lifestyle requires cell-cell connections. In multicellular cyanobacteria, septal junctions enable molecular exchange between sister cells and are required for cellular differentiation. The structure of septal junctions is poorly understood, and it is unknown whether they are capable of controlling intercellular communication. Here, we resolved the in situ architecture of septal junctions by electron cryotomography of cryo-focused ion beam-milled cyanobacterial filaments. Septal junctions consisted of a tube traversing the septal peptidoglycan. Each tube end comprised a FraD-containing plug, which was covered by a cytoplasmic cap. Fluorescence recovery after photobleaching showed that intercellular communication was blocked upon stress. Gating was accompanied by a reversible conformational change of the septal junction cap. We provide the mechanistic framework for a cell junction that predates eukaryotic gap junctions by a billion years. The conservation of a gated dynamic mechanism across different domains of life emphasizes the importance of controlling molecular exchange in multicellular organisms.
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Uniones Comunicantes/metabolismo , Anabaena/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbonil Cianuro m-Clorofenil Hidrazona/análogos & derivados , Carbonil Cianuro m-Clorofenil Hidrazona/farmacología , Comunicación Celular/efectos de los fármacos , Microscopía por Crioelectrón , Uniones Comunicantes/química , Uniones Comunicantes/ultraestructura , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , MutagénesisRESUMEN
Radial cell columns are a hallmark feature of cortical architecture in many mammalian species. It has long been held, based on the lack of orientation columns, that such functional units are absent in rodent primary visual cortex (V1). These observations led to the view that rodent visual cortex has a fundamentally different network architecture than that of carnivores and primates. While columns may be lacking in rodent V1, we describe in this review that modular clusters of inputs to layer 1 and projection neurons in the layers below are prominent features of the mouse visual cortex. We propose that modules organize thalamocortical inputs, intracortical processing streams, and transthalamic communications that underlie distinct sensory and sensorimotor functions.
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Corteza Visual , Ratones , Animales , Retroalimentación , Corteza Visual/fisiología , Interneuronas , Sensación , Vías Visuales/fisiología , MamíferosRESUMEN
It is known that the primate amygdala forms projections to many areas of the ipsilateral cortex, but the extent to which it forms connections with the contralateral visual cortex remains less understood. Based on retrograde tracer injections in marmoset monkeys, we report that the amygdala forms widespread projections to the ipsilateral extrastriate cortex, including V1 and areas in both the dorsal (MT, V4T, V3a, 19M, and PG/PFG) and the ventral (VLP and TEO) streams. In addition, contralateral projections were found to target each of the extrastriate areas, but not V1. In both hemispheres, the tracer-labeled neurons were exclusively located in the basolateral nuclear complex. The number of labeled neurons in the contralateral amygdala was small relative to the ipsilateral connection (1.2% to 5.8%). The percentage of contralateral connections increased progressively with hierarchical level. An injection in the corpus callosum demonstrated that at least some of the amygdalo-cortical connections cross through this fiber tract, in addition to the previously documented path through the anterior commissure. Our results expand knowledge of the amygdalofugal projections to the extrastriate cortex, while also revealing pathways through which visual stimuli conveying affective content can directly influence early stages of neural processing in the contralateral visual field.
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Amígdala del Cerebelo , Callithrix , Corteza Visual , Animales , Corteza Visual/fisiología , Amígdala del Cerebelo/fisiología , Masculino , Vías Nerviosas/fisiología , Lateralidad Funcional/fisiología , Femenino , Neuronas/fisiología , Cuerpo Calloso/fisiología , Técnicas de Trazados de Vías Neuroanatómicas , Vías Visuales/fisiologíaRESUMEN
We investigated the immediate and longer-term impact (over 4-6 months) of probable COVID-19 infection on mental health, wellbeing, financial hardship, and social interactions among older people living in England. Data were analysed from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the pandemic (2018-19) and at two COVID-19 assessments in 2020 (June-July and November-December). The associations of probable COVID-19 infection (first COVID-19 assessment) with depression, anxiety, poor quality of life (QoL), loneliness, financial hardship, and social contact with family/friends at the first and second COVID-19 assessments were tested using linear/logistic regression and were adjusted for pre-pandemic outcome measures. Participants with probable infection had higher levels of depression and anxiety, poorer QoL, and greater loneliness scores compared with those without probable infection at both the first (ORdepression = 1.62, P-value = 0.005; ORanxiety = 1.59, P-value = 0.049; bpoorQoL = 1.34, P < 0.001; bloneliness = 0.49, P < 0.001) and second (ORdepression = 1.56, P-value = 0.003; ORanxiety = 1.55, P-value = 0.041; bpoorQoL = 1.38, P-value < 0.001; bloneliness = 0.31, P-value = 0.024) COVID-19 assessments. Participants with probable infection also experienced greater financial difficulties than those without infection at the first assessment (OR = 1.50, P-value = 0.011). Probable COVID-19 infection is associated with longer-term deterioration of mental health and wellbeing and short-term increases in financial hardship among older adults. It is important to monitor the mental health of older people affected by COVID-19 and provide additional support to those in need.
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COVID-19 , Estrés Financiero , Salud Mental , Anciano , COVID-19/economía , COVID-19/psicología , Humanos , Soledad , Estudios Longitudinales , Calidad de VidaRESUMEN
A cardinal feature of the neocortex is the progressive increase of the spatial receptive fields along the cortical hierarchy. Recently, theoretical and experimental findings have shown that the temporal response windows also gradually enlarge, so that early sensory neural circuits operate on short timescales whereas higher-association areas are capable of integrating information over a long period of time. While an increased receptive field is accounted for by spatial summation of inputs from neurons in an upstream area, the emergence of timescale hierarchy cannot be readily explained, especially given the dense interareal cortical connectivity known in the modern connectome. To uncover the required neurobiological properties, we carried out a rigorous analysis of an anatomically based large-scale cortex model of macaque monkeys. Using a perturbation method, we show that the segregation of disparate timescales is defined in terms of the localization of eigenvectors of the connectivity matrix, which depends on three circuit properties: 1) a macroscopic gradient of synaptic excitation, 2) distinct electrophysiological properties between excitatory and inhibitory neuronal populations, and 3) a detailed balance between long-range excitatory inputs and local inhibitory inputs for each area-to-area pathway. Our work thus provides a quantitative understanding of the mechanism underlying the emergence of timescale hierarchy in large-scale primate cortical networks.
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Conectoma , Modelos Neurológicos , Neocórtex/fisiología , Red Nerviosa/fisiología , Animales , MacacaRESUMEN
One goal of systems neuroscience is a structure-function model of nervous system organization that would allow mechanistic linking of mind, brain, and behavior. A necessary but not sufficient foundation is a connectome, a complete matrix of structural connections between the nodes of a nervous system. Connections between two nodes can be described at four nested levels of analysis: macroconnections between gray matter regions, mesoconnections between neuron types, microconnections between individual neurons, and nanoconnections at synapses. A long history of attempts to understand how the brain operates as a system began at the macrolevel in the fifth century, was revolutionized at the meso- and microlevels by Cajal and others in the late nineteenth century, and reached the nanolevel in the mid-twentieth century with the advent of electron microscopy. The greatest challenge today is extracting knowledge and understanding of nervous system structure-function architecture from vast amounts of data.
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Encéfalo/fisiología , Conectoma , Vías Nerviosas/fisiología , Neuronas/fisiología , Sinapsis/fisiología , Animales , Conectoma/métodos , Humanos , Modelos NeurológicosRESUMEN
STUDY QUESTION: What are the experiences and outcomes of donor conceived adults who are actively searching for, open to contact with, or not searching for donor connections? SUMMARY ANSWER: Most participants were actively searching or open to contact, and 67% had found or been found by a connection; finding or not finding experiences were complex. WHAT IS KNOWN ALREADY: There is variation among donor conceived individuals in their interest in donor connections. Individual reasons for searching for connections, and which donor connections are searched for, also vary. Most research studies have focussed on individuals who are actively searching for their donor or donor siblings. Global increases in direct-to-consumer DNA testing and social media participation mean that connections may be made to individuals unaware of their (or their relatives') involvement with donor conception. These social and technological changes have also increased the chances of donor conceived individuals being contacted without expecting or desiring contact. STUDY DESIGN, SIZE, DURATION: This study included 88 donor conceived adults, in the UK, who participated in an online multi-method survey between January and August 2022. The survey was designed in consultation with staff and volunteers from the UK's largest community networks for donor conception families (Donor Conception Network, DCN) and donor conceived people (Donor Conceived Register Registrants' Panel, DCRRP). It was piloted by five donor conceived people before its launch. Participants were recruited with assistance from DCN and DCRRP, via social media, university mailing lists, and snowballing. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were mostly female (n = 65, 74%) and sperm donor conceived (n = 79, 90%). Of the 88 participants, 39 (44%) were actively searching for their donor connections, 44 (50%) were open to contact but not actively searching, and 5 (6%) were not searching. Questions were closed (yes/no, rating scale, or multiple choice) or open-ended, addressing experiences of donor conception, searching for connections, and finding or not finding connections. Data were analysed both quantitatively and qualitatively. MAIN RESULTS AND THE ROLE OF CHANCE: Quantitative results showed no differences between the groups on any demographic variables or in when or how they found out about being donor conceived, and no differences between active searchers and those open to contact in whether they had found their donor connections. Significant differences were found between groups in their interest in their genetic history and the perceived importance of genetics to their sense of identity, with active searchers being more interested and rating this as more important than those open to contact. Methods of searching significantly differed across groups, with active searchers using genetic testing and social media more than those open to contact. 59 participants across all groups (active searchers (n = 29, 74%), open to contact (n = 27, 61%), not open to contact (n = 3, 60%)) had found or been found by a donor connection. Experiences of finding or not finding donor connections among participants actively searching or open to contact were captured by the theme complexities, with six subthemes: uncertainties in searching and relating; searching as open-ended; different donor connections, different experiences; expectations and realities; searching and finding or not finding as catalysing change; and experiences of other donor conceived people. LIMITATIONS, REASONS FOR CAUTION: Most participants were members of relevant community organizations. As is common in research in this area, the sample was mostly female and conceived using donor sperm. Donor conceived people who are disinterested in donor connections may be unlikely to participate in research on this topic. WIDER IMPLICATIONS OF THE FINDINGS: The nature and impact of the search process itself should be considered when developing appropriate mechanisms of support for all donor conceived people, regardless of whether they are actively searching for connections or not. Further research should seek to better understand how donor conceived people with varying levels of interest in searching for donor connections differ from one another. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the UK Economic and Social Research Council [New Investigator Award ES/S015426/1]. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.
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BACKGROUND: The American Association of Medical Colleges trialed residency application initiatives including geographic preferences and preference signals in 2022. OBJECTIVE: To assess the impact of geographic preferences on application outcomes during the 2022 residency match year. DESIGN: Cross-sectional. PARTICIPANTS: Applicants to categorical and preliminary internal medicine during the 2022 application cycle who completed the Texas Seeking Transparency in Applications to Residency survey. MAIN MEASURES: The primary outcome was interview rate (interview offers/total applications) and whether an application resulted in a match. The key dependent variables were geographic preferences and program-specific preference signals. We also assessed differences in utilization of geographic preferences between specialties. KEY RESULTS: A total of 970 applicants into categorical (n = 884) and preliminary (n = 86) internal medicine were included in our study. A total of 704 (72.6%) applicants submitted at least one geographic preference and 424 (43.7%) submitted three preferences. On average, applicants who submitted a geographic preference had a higher interview rate than those who did not (46.0% vs. 41.8%). Applications submitted with both a preference signal and geographic preference were significantly more likely to receive an interview offer (OR: 3.2, p < 0.01) and match (OR: 6.4, p < 0.01) than applications with neither a preference signal nor a geographic preference. Geographic preferences were associated with an increase in the odds of an application receiving an interview offer, even in the setting of a preference signal (OR: 1.4, p < 0.01). CONCLUSIONS: Both preference signals and geographic preferences have significant associations with odds of an application receiving an interview and matching for both categorical and preliminary internal medicine applicants. This study can be used to inform applicants, advisors, and programs how novel application strategies can affect important application outcomes for US medical school graduates. As more specialties pilot alternative processes, it will be important to study all application outcomes among varying applicant populations.
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Internado y Residencia , Humanos , Estados Unidos , Estudios Transversales , Medicina Interna , Texas , Encuestas y CuestionariosRESUMEN
The emotional and cognitive cerebellum has been explored by several studies in the past years. Recent evidence suggested the possible contribution of the cerebellum in processing emotional prosody, namely the ability to comprehend the emotional content of a given vocal utterance, likely mediated by anatomical and functional cerebello-prefrontal connections. In the present study, the involvement of a functional cerebello-prefrontal network in recognising emotional prosody was assessed by combining non-invasive anodal transcranial direct current stimulation (tDCS) over the right or the left cerebellum and functional Near Infrared Spectroscopy of the prefrontal cortex, in a double-blind within-subject experimental design on healthy participants. The results showed that right and, to a less extent, left cerebellar tDCS (as compared to sham stimulation) reduced neural activation in the prefrontal cortex while accuracy and reaction times at the vocal recognition task remained unchanged. These findings highlight functional properties of the cerebello-frontal connections and the psychophysiological effects of cerebellar brain stimulation, with possible clinical applications in psychiatric and neurological conditions.
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RESEARCH QUESTION: What are the support needs of donor conceived individuals who are searching for or open to matching with genetic connections? DESIGN: A total of 88 donor conceived adults in the UK participated in an online survey open between January and August 2022. Participants were asked about their level of awareness of current resource provision, recommendations for resources to support the process of searching for genetic connections, and recommendations for resources to support with feelings about searching for or being found by genetic connections. RESULTS: Participants were found to have varying levels of awareness of the resources available to them, with 39% describing themselves as aware, 41% as partly aware and 20% as unaware. Their recommendations for practical and emotional resources also varied. The most recommended resources for practical support were DNA testing and changes to UK law. The most recommended resources for emotional support were counselling and peer and other support groups. CONCLUSIONS: The impact of legal and technological changes such as direct-to-consumer DNA testing and the legal transition to identifiable donation may be felt by donor conceived individuals irrespective of their year of birth. The wishes of donor conceived individuals for different support resources should be borne in mind by practitioners, regulatory bodies, and policy makers going forward.
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Donación de Oocito , Donantes de Tejidos , Adulto , Humanos , Donación de Oocito/psicología , Donantes de Tejidos/psicología , Consejo , ADN , Reino UnidoRESUMEN
Primary afferents originating from the mesencephalic trigeminal nucleus provide the main source of proprioceptive information guiding mastication, and thus represent an important component of this critical function. Unlike those of other primary afferents, their cell bodies lie within the central nervous system. It is believed that this unusual central location allows them to be regulated by synaptic input. In this study, we explored the ultrastructure of macaque mesencephalic trigeminal nucleus neurons to determine the presence and nature of this synaptic input in a primate. We first confirmed the location of macaque mesencephalic trigeminal neurons by retrograde labeling from the masticatory muscles. Since the labeled neurons were by far the largest cells located at the edge of the periaqueductal gray, we could undertake sampling for electron microscopy based on soma size. Ultrastructurally, mesencephalic trigeminal neurons had very large somata with euchromatic nuclei that sometimes displayed deeply indented nuclear membranes. Terminal profiles with varied vesicle characteristics and synaptic density thicknesses were found in contact with either their somatic plasma membranes or somatic spines. However, in contradistinction to other, much smaller, somata in the region, the plasma membranes of the mesencephalic trigeminal somata had only a few synaptic contacts. They did extend numerous somatic spines of various lengths into the neuropil, but most of these also lacked synaptic contact. The observed ultrastructural organization indicates that macaque trigeminal mesencephalic neurons do receive synaptic contacts, but despite their central location, they only avail themselves of very limited input.
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Macaca , Núcleos del Trigémino , Animales , Neuronas/fisiología , Mesencéfalo/fisiología , Tegmento MesencefálicoRESUMEN
Mechanical problems like break or crack in Luer connectors or hubs, clamps, and tubings are common non-infectious complications of tunneled dialysis catheters (TDC), which may lead to other TDC complications and the need to insert a new catheter. These can be tackled using TDC repair kits or spare parts, which are often not available, resulting in the insertion of a new TDC that increases morbidity, TDC-related procedures, and healthcare costs. We discuss two cases of broken Luer connections of TDC, which were managed by exchanging the broken Luer connector of TDC with the similar Luer connector of a temporary dialysis catheter. Both the repaired TDCs are thereafter functioning well. This improvised technique provides an easy, effective, long-lasting option that salvages the existing TDC and reduces the cost factor.
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Catéteres de Permanencia , Falla de Equipo , Diálisis Renal , Humanos , Diálisis Renal/economía , Diálisis Renal/instrumentación , Catéteres de Permanencia/efectos adversos , Catéteres de Permanencia/economía , Masculino , Fallo Renal Crónico/terapia , Persona de Mediana Edad , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/economía , Cateterismo Venoso Central/instrumentación , Análisis Costo-Beneficio , Femenino , Remoción de Dispositivos/métodos , Remoción de Dispositivos/economía , Diseño de EquipoRESUMEN
Synaptic tract-tracing studies in macaques have provided a wealth of data about cortico-cortical connections that have been used to identify regularities and propose models and theories to explain cortical connectivity. The two most relevant of these models are the distance rule model (DRM) and the structural model (SM). They relate the strength and laminar pattern of cortico-cortical connections to two different factors: Euclidean distance (according to the DRM) and cortical type distance (according to the SM). If both predictive factors were correlated, the DRM and the SM would be compatible, but quite often, two cortical areas of similar cortical type are far apart from each other. In the present article, we have performed a conceptual analysis of the DRM and the SM to obtain predictions from each of the two models about strength and laminar pattern of cortico-cortical connections. We then tested the predictive power of each model with analyses of several cortico-cortical connectivity databases to check which of them provide the most accurate predictions. We conclude that the DRM and the SM capture the decrease in connection strength with increasing Euclidean and cortical type distances, respectively; but, for laminar pattern, type distance is a better predictor than Euclidean distance.
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Corteza Cerebral , Primates , Animales , Macaca , Modelos EstructuralesRESUMEN
In trace fear conditioning, the prelimbic cortex exhibits persistent activity during the interval between the conditioned and unconditioned stimuli, which maintains a conditioned stimulus representation. Regions cooperating for this function or encoding the conditioned stimulus before the interval could send inputs to the prelimbic cortex, supporting learning. The basolateral amygdala has conditioned stimulus- and unconditioned stimulus-responsive neurons, convergently activated. The prelimbic cortex could directly project to the basolateral amygdala to associate the transient memory of the conditioned stimulus with the unconditioned stimulus. We investigated the neuronal circuit supporting temporal associations using contextual fear conditioning with a 5-s interval, in which 5 s separates the contextual conditioned stimulus from the unconditioned stimulus. Injecting retrobeads, we quantified c-Fos in prelimbic cortex- or basolateral amygdala-projecting neurons from 9 regions after contextual fear conditioning with a 5-s interval or contextual fear conditioning, in which the conditioned and unconditioned stimuli overlap. The contextual fear conditioning with a 5-s interval activated ventral CA1 and perirhinal cortex neurons projecting to the prelimbic cortex and prelimbic cortex neurons projecting to basolateral amygdala. Both fear conditioning activated ventral CA1 and lateral entorhinal cortex neurons projecting to basolateral amygdala and basolateral amygdala neurons projecting to prelimbic cortex. The perirhinal cortex â prelimbic cortex and ventral CA1 â prelimbic cortex connections are the first identified prelimbic cortex afferent projections participating in temporal associations. These results help to understand time-linked memories, a process required in episodic and working memories.
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Complejo Nuclear Basolateral , Corteza Perirrinal , Complejo Nuclear Basolateral/fisiología , Corteza Prefrontal/fisiología , Aprendizaje/fisiología , Condicionamiento Clásico/fisiologíaRESUMEN
It has been shown that the functional dependency of the brain exists in both direct and indirect regional relationships. Therefore, it is necessary to map higher-order coupling in brain structure and function to understand brain dynamic. However, how to quantify connections between not directly regions remains unknown to schizophrenia. The word2vec is a common algorithm through create embeddings of words to solve these problems. We apply the node2vec embedding representation to characterize features on each node, their pairwise relationship can give rise to correspondence relationships between brain regions. Then we adopt pearson correlation to quantify the higher-order coupling between structure and function in normal controls and schizophrenia. In addition, we construct direct and indirect connections to quantify the coupling between their respective functional connections. The results showed that higher-order coupling is significantly higher in schizophrenia. Importantly, the anomalous cause of coupling mainly focus on indirect structural connections. The indirect structural connections play an essential role in functional connectivity-structural connectivity (SC-FC) coupling. The similarity between embedded representations capture more subtle network underlying information, our research provides new perspectives for understanding SC-FC coupling. A strong indication that the structural backbone of the brain has an intimate influence on the resting-state functional.
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Conectoma , Esquizofrenia , Humanos , Conectoma/métodos , Imagen de Difusión Tensora/métodos , Encéfalo , Algoritmos , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodosRESUMEN
Predictions are constantly generated from diverse sources to optimize cognitive functions in the ever-changing environment. However, the neural origin and generation process of top-down induced prediction remain elusive. We hypothesized that motor-based and memory-based predictions are mediated by distinct descending networks from motor and memory systems to the sensory cortices. Using functional magnetic resonance imaging (fMRI) and a dual imagery paradigm, we found that motor and memory upstream systems activated the auditory cortex in a content-specific manner. Moreover, the inferior and posterior parts of the parietal lobe differentially relayed predictive signals in motor-to-sensory and memory-to-sensory networks. Dynamic causal modeling of directed connectivity revealed selective enabling and modulation of connections that mediate top-down sensory prediction and ground the distinctive neurocognitive basis of predictive processing.
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Corteza Auditiva , Mapeo Encefálico , Lóbulo Parietal/diagnóstico por imagen , Cognición , Imagen por Resonancia Magnética/métodos , Corteza Auditiva/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagenRESUMEN
BACKGROUND: Most people want to remain at home as they age. Ageing in place - remaining at home and connected to the community - is a national and international policy priority; however, to better understand how policy might be implemented, a more nuanced understanding is required about older adults' lived experiences of ageing in place, especially the experiences of those aged 80 and above. OBJECTIVE: To describe and explore the social processes which enable ageing in place from the perspective of community-dwelling older people (80+). METHODS: Forty-six respondents (80-100+ years) participated in the first wave of a longitudinal qualitative study set in North East England. Semi-structured interviews were conducted in participants' homes between June 2022 and January 2023. Interviews were analysed using reflexive thematic analysis. RESULTS: Participants positioned their homes as a place of freedom and as the antithesis of a 'care home'. Remaining in place was important for all participants; a key priority for them was to remain physically active to enable this. However, many participants faced significant hurdles to remaining in place. These were primarily related to health and mobility issues. Some participants were able to overcome such barriers by drawing on financial resources and available social networks. CONCLUSION: The home is central to understanding older peoples' (80+) experiences of ageing. In a socio-political context which promotes ageing in place, the social factors shaping experiences of ageing in place must be considered. This involves attending to the challenges of later life, particularly health and especially mobility and physical function. Currently, those with resources (social and economic) are better equipped to respond to such challenges, thus potentially exacerbating widening inequalities in ageing. By foregrounding the perspectives of those ageing in place alongside social factors shaping their experiences, our study has important implications for policy and health and social care. We show that a more equitable allocation of resources is vital to fulfil the ageing in place policy agenda. Furthermore, we highlight a need to recognise commitments to ageing in place displayed by people aged 80 and above, especially when remaining in place becomes difficult to achieve.
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Vida Independiente , Investigación Cualitativa , Humanos , Estudios Longitudinales , Anciano de 80 o más Años , Masculino , Femenino , Vida Independiente/psicología , Inglaterra/epidemiología , Envejecimiento/psicología , Envejecimiento/fisiologíaRESUMEN
Ras dimerization is critical for Raf activation. Here we show that the Ras binding domain of Raf (Raf-RBD) induces robust Ras dimerization at low surface densities on supported lipid bilayers and, to a lesser extent, in solution as observed by size exclusion chromatography and confirmed by SAXS. Community network analysis based on molecular dynamics simulations shows robust allosteric connections linking the two Raf-RBD D113 residues located in the Galectin scaffold protein binding site of each Raf-RBD molecule and 85 Å apart on opposite ends of the dimer complex. Our results suggest that Raf-RBD binding and Ras dimerization are concerted events that lead to a high-affinity signaling complex at the membrane that we propose is an essential unit in the macromolecular assembly of higher order Ras/Raf/Galectin complexes important for signaling through the Ras/Raf/MEK/ERK pathway.
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Simulación de Dinámica Molecular , Proteínas Proto-Oncogénicas p21(ras)/química , Quinasas raf/química , Galectinas/química , Galectinas/genética , Galectinas/metabolismo , Humanos , Dominios Proteicos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Quinasas raf/genética , Quinasas raf/metabolismoRESUMEN
INTRODUCTION: Although mindfulness-based interventions (MBIs) show promise for promoting positive youth development, little is known about student engagement in MBIs. Initial research presents mixed findings in MBI engagement related to participant characteristics, and there is a lack of research examining the influence of context on engagement, despite the critical role context plays in academic engagement. This study examines the contribution of student demographic characteristics and classroom context to MBI engagement. METHODS: Survey engagement data were collected at three time points from 106 ninth grade students (Mage = 14.17 years, 60.4% female, 44.2% Black, 24.8% Hispanic/Latino) who participated in the Be CALM program during the 2021-2022 school year. Latent growth curve modeling was used to examine trajectory of student engagement and assess student and classroom predictors of engagement. RESULTS: There was no overall change in the trajectory of student engagement, although variability was observed across classes. Identifying as Hispanic/Latino was associated with lower engagement (ß = -.25, p = .008), although this did not appear to be related to program experience. Peer connections predicted engagement at the end of the program (ß = .39, p < .001). Post hoc analyses suggested that student engagement may be related to teacher program delivery quality. CONCLUSIONS: Student engagement in MBIs appears related to classroom context more than student characteristics, although further research with larger samples is needed to assess the link between engagement and program outcomes. Findings have implications for designing school-based MBIs and training school staff to deliver them in culturally responsive ways.
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Atención Plena , Humanos , Femenino , Adolescente , Masculino , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Aprendizaje Social , Emociones , Encuestas y CuestionariosRESUMEN
Pulmonary atresia with an intact ventricular septum is characterised by heterogeneity in right ventricle morphology and coronary anatomy. In some cases, the presence of ventriculocoronary connections may promote coronary artery stenosis or interruption, and aortic diastolic pressure may not be sufficient to drive coronary blood flow. This requires a correct evaluation (currently done by angiography) which depends on whether the patient can be offered decompression of the right ventricle. To date, there is no objective method to do so, so we designed a percutaneous, transitory technique with the purpose of occluding the transtricuspid anterograde flow. The manoeuverer was performed in a 25-day-old female with pulmonary atresia with intact ventricular septum, right ventricle at suprasystemic level, and selective coronarography was not conclusive, the anterior descendant with stenosis in its middle third and from this point, thinner with to-fro flow. Occlusion was performed with a balloon catheter. We re-evaluated the coronary flow and the normalised anterior descendant flow. We hope that with this new method, we can give a more accurate diagnosis and determine the cases in which the coronary circulation is truly not right ventricle dependent to offer a greater number of patients biventricular or 1.5 ventricular repairs and thereby improve their quality of life and survival, the ones that turn out to be right ventricular dependant; offer them an early reference for cardiac transplant or in case it is not available to consider univentricular palliation knowing that this probably would not reduce the risk of ischaemia and/or death over time.