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1.
Augment Altern Commun ; : 1-14, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967645

RESUMEN

A socio-neurocognitive approach to augmentative and alternative communication (AAC) shows several underlying domains of communicative competence: Attention, perception, cognition, memory, orientation, socio-emotional development, motor skills, and language. To determine developmental markers of these underlying core domains of communicative competence in children with communication support needs, we developed a new screening instrument. The present article consists of three consecutive studies. In study 1, we constructed the first version of the screening instrument based on a sample of both children without disabilities and children with Down syndrome. In study 2, we confirmed the reliability (i.e., internal consistency) of the screening instrument in a new group of young children with typical development and established concurrent validity with the Early Language Scale. In study 3, we established concurrent validity with the Communication Matrix in a clinical sample of children with communication support needs. The screening instrument can be used in clinical practice as part of AAC assessment to provide comprehensive insights into strengths and weaknesses in the underlying core domains of communicative competence of children with communication support needs.

2.
BMC Public Health ; 24(1): 1770, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961413

RESUMEN

In the UK people living in disadvantaged communities are less likely than those with higher socio-economic status to have a healthy diet. To address this inequality, it is crucial scientists, practitioners and policy makers understand the factors that hinder and assist healthy food choice in these individuals. In this scoping review, we aimed to identify barriers and facilitators to healthy eating among disadvantaged individuals living in the UK. Additionally, we used the Theoretical Domains Framework (TDF) to synthesise results and provide a guide for the development of theory-informed behaviour change interventions. Five databases were searched, (CINAHL, Embase, MEDLINE, PsycINFO, and Web of Science) for articles assessing healthy dietary intake of disadvantaged adults living in the UK. A total of 50 papers (34 quantitative; 16 qualitative) were included in this review. Across all studies we identified 78 barriers and 49 facilitators found to either impede and/or encourage healthy eating. Both barriers and facilitators were more commonly classified under the Environmental, Context and Resources TDF domain, with 74% of studies assessing at least one factor pertaining to this domain. Results thus indicate that context related factors such as high cost and accessibility of healthy food, rather than personal factors, such as lack of efficiency in healthy lifestyle drive unhealthy eating in disadvantaged individuals in the UK. We discuss how such factors are largely overlooked in current interventions and propose that more effort should be directed towards implementing interventions that specifically target infrastructures rather than individuals.


Asunto(s)
Dieta Saludable , Poblaciones Vulnerables , Humanos , Reino Unido , Poblaciones Vulnerables/psicología , Dieta Saludable/psicología , Adulto
3.
Pharmacol Ther ; 260: 108686, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38969307

RESUMEN

Exposure to adversities during early life stages (early life adversities - ELA), ranging from pregnancy to adolescence, represents a major risk factor for the vulnerability to mental disorders. Hence, it is important to understand the molecular and functional underpinning of such relationship, in order to develop strategies aimed at reducing the psychopathologic burden associated with ELA, which may eventually lead to a significant improvement in clinical practice. In this review, we will initially recapitulate clinical and preclinical evidence supporting the link between ELA and psychopathology and we will primarily discuss the main biological mechanisms that have been described as potential mediators of the effects of ELA on the psychopathologic risk, including the role for genetic factors as well as sex differences. The knowledge emerging from these studies may be instrumental for the development of novel therapeutic strategies aimed not only at correcting the deficits that emerge from ELA exposure, but also in preventing the manifestation of a full-blown psychopathologic condition. With this respect, we will specifically focus on adolescence as a key time frame for disease onset as well as for early therapeutic intervention. We believe that incorporating clinical and preclinical research data in the context of early life adversities can be instrumental to elucidate the mechanisms contributing to the risk for psychopathology or that may promote resilience. This will ultimately allow the identification of 'at risk' individuals who may benefit from specific forms of interventions that, by interfering with disease trajectories, could result in more benign clinical outcomes.

4.
Adv Mater ; : e2405294, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984494

RESUMEN

Adaptive networks can sense and adjust to dynamic environments to optimize their performance. Understanding their nanoscale responses to external stimuli is essential for applications in nanodevices and neuromorphic computing. However, it is challenging to image such responses on the nanoscale with crystallographic sensitivity. Here, the evolution of nanodomain networks in (PbTiO3)n/(SrTiO3)n superlattices (SLs) is directly visualized in real space as the system adapts to ultrafast repetitive optical excitations that emulate controlled neural inputs. The adaptive response allows the system to explore a wealth of metastable states that are previously inaccessible. Their reconfiguration and competition are quantitatively measured by scanning x-ray nanodiffraction as a function of the number of applied pulses, in which crystallographic characteristics are quantitatively assessed by assorted diffraction patterns using unsupervised machine-learning methods. The corresponding domain boundaries and their connectivity are drastically altered by light, holding promise for light-programable nanocircuits in analogy to neuroplasticity. Phase-field simulations elucidate that the reconfiguration of the domain networks is a result of the interplay between photocarriers and transient lattice temperature. The demonstrated optical control scheme and the uncovered nanoscopic insights open opportunities for the remote control of adaptive nanoscale domain networks.

5.
Ecol Evol ; 14(7): e11672, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38988351

RESUMEN

Environmental change exerts a profound effect on soil microbial domains-including bacteria, fungi, and protists-that each perform vital ecological processes. While these microbial domains are ubiquitous and extremely diverse, little is known about how they respond to environmental changes in urban soil ecosystems and what ecological processes shape them. Here we investigated the community assembly processes governing bacteria, fungi, and protists through the lens of four distinct subcommunities: abundant, conditionally rare, conditionally abundant, and rare taxa. We show that transient taxa, including the conditionally rare and conditionally rare or abundant taxa, were the predominant subcommunities. Deterministic processes (e.g., environmental filtering) had major roles in structuring all subcommunities of fungi, as well as conditionally rare and abundant protists. Stochastic processes had strong effects in structuring all subcommunities of bacteria (except rare taxa) and conditionally rare protists. Overall, our study underscores the importance of complementing the traditional taxonomy of microbial domains with the subcommunity approach when investigating microbial communities in urban soil ecosystems.

6.
J Evol Equ ; 24(3): 63, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989137

RESUMEN

In this paper, we consider a dynamic model of fracture for viscoelastic materials, in which the constitutive relation, involving the Cauchy stress and the strain tensors, is given in an implicit nonlinear form. We prove the existence of a solution to the associated viscoelastic dynamic system on a prescribed time-dependent cracked domain via a discretization-in-time argument. Moreover, we show that such a solution satisfies an energy-dissipation balance in which the energy used to increase the crack does not appear. As a consequence, in analogy to the linear case this nonlinear model exhibits the so-called viscoelastic paradox.

7.
Epilepsia ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949199

RESUMEN

OBJECTIVE: Numerous studies have examined epilepsy surgery outcomes, yet the variability in the level of detail reported hampers our ability to apply these findings broadly across patient groups. Established reporting standards in other clinical research fields enhance the quality and generalizability of results, ensuring that the insights gained from studying these surgeries can benefit future patients effectively. This study aims to assess current reporting standards for epilepsy surgery research and identify potential gaps and areas for enhancement. METHODS: The Enhancing the Quality and Transparency of Health Research (EQUATOR) repository was accessed from inception to April 27, 2023, yielding 561 available reporting standards. Reporting standards were manually reviewed in duplicate independently for applicability to epilepsy and/or neurosurgery research. The reporting standards had to cover the following aspects in human studies: (1) reporting standards for epilepsy/epilepsy surgery and (2) reporting standards for neurosurgery. Disagreements were resolved by a third author. The top five neurosurgery, neurology, and medicine journals were also identified through Google Scholar's citation index and examined to determine the relevant reporting standards they recommended and whether those were registered with EQUATOR. RESULTS: Of the 561 EQUATOR reporting standards, 181 were pertinent to epilepsy surgery. One was related to epilepsy, six were specific to surgical research, and nine were related to neurological/neurosurgical research. The remaining 165 reporting standards were applicable to research across various disciplines and included but were not limited to CONSORT (Consolidated Standards of Reporting Trails), STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). None of these required reporting factors associated with epilepsy surgery outcomes, such as duration of epilepsy or magnetic resonance imaging findings. SIGNIFICANCE: Reporting standards specific to epilepsy surgery are lacking, reflecting a gap in standards that may affect the quality of publications. Improving this gap with a set of specific reporting standards would ensure that epilepsy surgery studies are more transparent and rigorous in their design.

8.
Age Ageing ; 53(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38970302

RESUMEN

BACKGROUND: Discharging older adult patients from the hospital poses risks due to their vulnerable conditions, complex instructions and limited health literacy. Insufficient information about medication side effects adds to patient concerns. To address this, a post-discharge information summary system was developed. While it has shown positive impacts, concerns exist regarding implementation fidelity. OBJECTIVE: This study employed a theory-driven approach to understand health providers' perspectives on effective implementation. METHOD: Individual semi-structured interviews were conducted via telephone with nurses, doctors and pharmacists from local public hospitals. All interviews were audio-recorded and transcribed verbatim. Theoretical Domains Framework (TDF) was applied for direct content analysis. Belief statements were generated by thematic synthesis under each of the TDF domains. RESULTS: A total of 98 participants were interviewed. Out of the 49 belief statements covering eight TDF domains, 19 were determined to be highly relevant to the implementation of the post-discharge information summary system. These TDF domains include knowledge, skills, social/professional role and identity, beliefs about consequences, intentions, memory, attention and decision processes, environmental context and resources and social influences. CONCLUSION: Our study contributes to the understanding of determinants in implementing discharge interventions for older adult patients' self-care. Our findings can inform tailored strategies for frontline staff, including aligning programme rationale with stakeholders, promoting staff engagement through co-creation, reinforcing positive programme outcomes and creating default settings. Future research should employ rigorous quantitative designs to examine the actual impact and relationships among these determinants.


Asunto(s)
Alta del Paciente , Investigación Cualitativa , Automanejo , Humanos , Femenino , Masculino , Anciano , Conocimientos, Actitudes y Práctica en Salud , Entrevistas como Asunto , Actitud del Personal de Salud , Persona de Mediana Edad , Educación del Paciente como Asunto
9.
Methods Enzymol ; 700: 77-104, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38971613

RESUMEN

The biophysical drivers of membrane lateral heterogeneity, often termed lipid rafts, have been largely explored using synthetic liposomes or mammalian plasma membrane-derived giant vesicles. Yeast vacuoles, an organelle comparable to mammalian lysosomes, is the only in vivo system that shows stable micrometer scale phase separation in unperturbed cells. The ease of manipulating lipid metabolism in yeast makes this a powerful system for identifying lipids involved in the onset of vacuole membrane heterogeneity. Vacuole domains are induced by stationary stage growth and nutritional starvation, during which they serve as a docking and internalization site for lipid droplet energy stores. Here we describe methods for characterizing vacuole phase separation, its physiological function, and its lipidic drivers. First, we detail methodologies for robustly inducing vacuole domain formation and quantitatively characterizing during live cell imaging experiments. Second, we detail a new protocol for biochemical isolation of stationary stage vacuoles, which allows for lipidomic dissection of membrane phase separation. Third, we describe biochemical techniques for analyzing lipid droplet internalization in vacuole domains. When combined with genetic or chemical perturbations to lipid metabolism, these methods allow for systematic dissection of lipid composition in the structure and function of ordered membrane domains in living cells.


Asunto(s)
Metabolismo de los Lípidos , Saccharomyces cerevisiae , Vacuolas , Vacuolas/metabolismo , Saccharomyces cerevisiae/metabolismo , Microdominios de Membrana/metabolismo , Gotas Lipídicas/metabolismo , Membrana Celular/metabolismo , Lipidómica/métodos
10.
Methods Enzymol ; 700: 455-483, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38971610

RESUMEN

Over the years, it has become more and more obvious that lipid membranes show a very complex behavior. This behavior arises in part from the large number of different kinds of lipids and proteins and how they dynamically interact with each other. In vitro studies using artificial membrane systems have shed light on the heterogeneity based on lipid-lipid interactions in multicomponent bilayer mixtures. Inspired by the raft hypothesis, the coexistence of liquid-disordered (ld) and liquid-ordered (lo) phases has drawn much attention. It was shown that ternary lipid mixtures containing low- and high-melting temperature lipids and cholesterol can phase separate into a lo phase enriched in the high-melting lipids and cholesterol and a ld phase enriched in the low-melting lipids. Depending on the model membrane system under investigation, different domain sizes, shapes, and mobilities have been found. Here, we describe how to generate phase-separated lo/ld phases in model membrane systems termed pore-spanning membranes (PSMs). These PSMs are prepared on porous silicon substrates with pore sizes in the micrometer regime. A proper functionalization of the top surface of the substrates is required to achieve the spreading of giant unilamellar vesicles (GUVs) to obtain PSMs. Starting with lo/ld phase-separated GUVs lead to membrane heterogeneities in the PSMs. Depending on the functionalization strategy of the top surface of the silicon substrate, different membrane heterogeneities are observed in the PSMs employing fluorescence microscopy. A quantitative analysis of the heterogeneity as well as the dynamics of the lipid domains is described.


Asunto(s)
Membrana Dobles de Lípidos , Membrana Dobles de Lípidos/química , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Porosidad , Microdominios de Membrana/química , Microdominios de Membrana/metabolismo , Colesterol/química
11.
Int J Mol Sci ; 25(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39000402

RESUMEN

Von Willebrand factor (VWF) is a multimer with a variable number of protomers, each of which is a head-to-head dimer of two multi-domain monomers. VWF responds to shear through the unfolding and extension of distinct domains, thereby mediating platelet adhesion and aggregation to the injured blood vessel wall. VWF's C1-6 segment uncoils and then the A2 domain unfolds and extends in a hierarchical and sequential manner. However, it is unclear whether there is any reservoir of further extensibility. Here, we explored the presence of cryptic extensibility in VWF by nanodissecting individual, pre-stretched multimers with atomic force microscopy (AFM). The AFM cantilever tip was pressed into the surface and moved in a direction perpendicular to the VWF axis. It was possible to pull out protein loops from VWF, which resulted in a mean contour length gain of 217 nm. In some cases, the loop became cleaved, and a gap was present along the contour. Frequently, small nodules appeared in the loops, indicating that parts of the nanodissected VWF segment remained folded. After analyzing the nodal structure, we conclude that the cryptic extensibility lies within the C1-6 and A1-3 regions. Cryptic extensibility may play a role in maintaining VWF's functionality in extreme shear conditions.


Asunto(s)
Microscopía de Fuerza Atómica , Factor de von Willebrand , Factor de von Willebrand/química , Factor de von Willebrand/metabolismo , Humanos , Multimerización de Proteína , Dominios Proteicos
12.
IUCrJ ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38980142

RESUMEN

X-ray free-electron laser (XFEL) light sources have enabled the rapid growth of time-resolved structural experiments, which provide crucial information on the function of macromolecules and their mechanisms. Here, the aim was to commission the SwissMX fixed-target sample-delivery system at the SwissFEL Cristallina experimental station using the PSI-developed micro-structured polymer (MISP) chip for pump-probe time-resolved experiments. To characterize the system, crystals of the light-sensitive protein light-oxygen-voltage domain 1 (LOV1) from Chlamydomonas reinhardtii were used. Using different experimental settings, the accidental illumination, referred to as light contamination, of crystals mounted in wells adjacent to those illuminated by the pump laser was examined. It was crucial to control the light scattering from and through the solid supports otherwise significant contamination occurred. However, the results here show that the opaque MISP chips are suitable for defined pump-probe studies of a light-sensitive protein. The experiment also probed the sub-millisecond structural dynamics of LOV1 and indicated that at Δt = 10 µs a covalent thioether bond is established between reactive Cys57 and its flavin mononucleotide cofactor. This experiment validates the crystals to be suitable for in-depth follow-up studies of this still poorly understood signal-transduction mechanism. Importantly, the fixed-target delivery system also permitted a tenfold reduction in protein sample consumption compared with the more common high-viscosity extrusion-based delivery system. This development creates the prospect of an increase in XFEL project throughput for the field.

13.
Methods Mol Biol ; 2842: 79-101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39012591

RESUMEN

To achieve exquisite control over the epigenome, we need a better predictive understanding of how transcription factors, chromatin regulators, and their individual domain's function, both as modular parts and as full proteins. Transcriptional effector domains are one class of protein domains that regulate transcription and chromatin. These effector domains either repress or activate gene expression by interacting with chromatin-modifying enzymes, transcriptional cofactors, and/or general transcriptional machinery. Here, we discuss important design considerations for high-throughput investigations of effector domains, recent advances in discovering new domains in human cells and testing how domain function depends on amino acid sequence. For every effector domain, we would like to know the following: What role does the cell type, signaling state, and targeted context have on activation, silencing, and epigenetic memory? Large-scale measurements of transcriptional activities can help systematically answer these questions and identify general rules for how all these parameters affect effector domain activities. Last, we discuss what steps need to be taken to turn a newly discovered effector domain into a robust, precise epigenome editor. With more carefully considered high-throughput investigations, soon we will have better predictive control over the epigenome.


Asunto(s)
Epigénesis Genética , Humanos , Transcripción Genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación de la Expresión Génica , Cromatina/genética , Cromatina/metabolismo , Ensayos Analíticos de Alto Rendimiento/métodos , Dominios Proteicos , Epigenómica/métodos
14.
Res Q Exerc Sport ; : 1-13, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012628

RESUMEN

Japan faces significant challenges associated with its super-aged society. Exercise and physical activity are recommended strategies to promote healthy aging and quality of life in older age. However, what determines exercise behavior among Japanese older adults is relatively unknown. The principle aim of this study was to explore exercise determinants and their relation to exercise behavior among Japanese older adults. Completed self-report questionnaires were received from 1,000 Japanese older adults aged between 65 and 74 years who resided in the Kansai area. A cross-sectional maximum likelihood path analysis was used to test the relationships between variables, where it was hypothesized that affective experiences in childhood had an indirect association with the exercise behavior of Japanese older adults through the seven psychological determinants of exercise. Demographic factors were also included in the model as potential influences of all factors. Knowledge held the largest significant direct association with exercise behavior (ß = .539, p = <.001), particularly more intense forms of exercise such as resistance exercise (ß = .725, p = <.001) and moderate to strenuous exercise (ß = .420, p = <.001), whilst affective exercise experience in childhood (B = 3.749, p = <.001) and gender (B = 5.183, p = .003) held significant indirect associations. This paper emphasizes the importance of exercise-related knowledge among Japanese older adults and future research is warranted to further explore the role of positive affective exercise experiences in childhood and their influence on exercise behavior, especially amongst girls.

15.
Philos Trans A Math Phys Eng Sci ; 382(2277): 20230300, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39005018

RESUMEN

In this article, we study general properties of distributed shape derivatives admitting a volumetric tensor representation of order two. We obtain a general result providing a range of expressions for the shape derivative, with the distributed shape derivative at one end of the range and the standard Hadamard formula at the other end. We further apply this result to a cost functional depending on the solution of a fourth-order elliptic equation, and obtain the distributed shape derivative in the case of open sets, and the Hadamard formula for sets of class [Formula: see text]. We also consider the case of polygons, for which a description of the weak singularities of the solution appearing in the neighbourhood of the vertices is required to obtain the Hadamard formula. This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

16.
Genome Med ; 16(1): 88, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992748

RESUMEN

BACKGROUND: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as "genetic constraint". Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. METHODS: We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. RESULTS: We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. CONCLUSIONS: Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation.


Asunto(s)
Mutación Missense , Humanos , Dominios Proteicos , Predisposición Genética a la Enfermedad
17.
Clin Kidney J ; 17(7): sfae086, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39015838

RESUMEN

Background: Due to the high correlation of chronic kidney disease (CKD) with other comorbidities, the sole effect of CKD on deprived people is not clear. In addition, there is a paucity of evidence in the literature linking isolated domains of deprivation to outcomes. This study aimed to examine whether deprivation was associated with adverse outcomes in patients with CKD, independent of cardiometabolic morbidities. Individual domains of deprivation were also evaluated. Methods: A retrospective study of patients with non-dialysis-dependent CKD (ND-CKD) in the Salford Kidney Study to investigate the association of deprivation with outcomes. The English Indices of Deprivation was used for the comparative analysis of the five quintiles of deprivation. Two propensity score methods were used to attenuate the confounding effect of cardiometabolic morbidities between the least and the most deprived groups. Results: People living in the least deprived areas (n = 319) had a lower risk of combined outcomes (all-cause mortality and renal replacement therapy) when compared with the most deprived group (n = 813) [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71-0.98]. The negative association of deprivation remained after matching but with mixed statistical significance when using different propensity methods (HR 0.85; 95% CI 0.70-1.03 for propensity score matching and HR 0.77; 95% CI 0.61-0.98 for inverse probability weighting). The association of combined outcomes varied across component index of multiple deprivation domains with wide CIs. However, areas with lower scores for education, income and employment were significantly associated with a higher risk. Conclusions: This study has identified that in people with ND-CKD, unemployment, poor educational attainment and lower household income were associated with poor outcomes. The association of deprivation with adverse outcomes persists despite adjustment for cardiometabolic morbidities.

18.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38935071

RESUMEN

Advances in chromatin mapping have exposed the complex chromatin hierarchical organization in mammals, including topologically associating domains (TADs) and their substructures, yet the functional implications of this hierarchy in gene regulation and disease progression are not fully elucidated. Our study delves into the phenomenon of shared TAD boundaries, which are pivotal in maintaining the hierarchical chromatin structure and regulating gene activity. By integrating high-resolution Hi-C data, chromatin accessibility, and DNA double-strand breaks (DSBs) data from various cell lines, we systematically explore the complex regulatory landscape at high-level TAD boundaries. Our findings indicate that these boundaries are not only key architectural elements but also vibrant hubs, enriched with functionally crucial genes and complex transcription factor binding site-clustered regions. Moreover, they exhibit a pronounced enrichment of DSBs, suggesting a nuanced interplay between transcriptional regulation and genomic stability. Our research provides novel insights into the intricate relationship between the 3D genome structure, gene regulation, and DNA repair mechanisms, highlighting the role of shared TAD boundaries in maintaining genomic integrity and resilience against perturbations. The implications of our findings extend to understanding the complexities of genomic diseases and open new avenues for therapeutic interventions targeting the structural and functional integrity of TAD boundaries.


Asunto(s)
Cromatina , Roturas del ADN de Doble Cadena , Reparación del ADN , Regulación de la Expresión Génica , Humanos , Cromatina/metabolismo , Cromatina/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Animales , Genómica/métodos , Inestabilidad Genómica , Ensamble y Desensamble de Cromatina
19.
J Theor Biol ; 592: 111878, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901778

RESUMEN

Heaps' or Herdan-Heaps' law is a linguistic law describing the relationship between the vocabulary/dictionary size (type) and word counts (token) to be a power-law function. Its existence in genomes with certain definition of DNA words is unclear partly because the dictionary size in genome could be much smaller than that in a human language. We define a DNA word as a coding region in a genome that codes for a protein domain. Using human chromosomes and chromosome arms as individual samples, we establish the existence of Heaps' law in the human genome within limited range. Our definition of words in a genomic or proteomic context is different from other definitions such as over-represented k-mers which are much shorter in length. Although an approximate power-law distribution of protein domain sizes due to gene duplication and the related Zipf's law is well known, their translation to the Heaps' law in DNA words is not automatic. Several other animal genomes are shown herein also to exhibit range-limited Heaps' law with our definition of DNA words, though with various exponents. When tokens were randomly sampled and sample sizes reach to the maximum level, a deviation from the Heaps' law was observed, but a quadratic regression in log-log type-token plot fits the data perfectly. Investigation of type-token plot and its regression coefficients could provide an alternative narrative of reusage and redundancy of protein domains as well as creation of new protein domains from a linguistic perspective.

20.
Curr Oncol ; 31(6): 3278-3290, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38920732

RESUMEN

Primary care providers (PCPs) have been given the responsibility of managing the follow-up care of low-risk cancer survivors after they are discharged from the oncology center. Survivorship Care Plans (SCPs) were developed to facilitate this transition, but research indicates inconsistencies in how they are implemented. A detailed examination of enablers and barriers that influence their use by PCPs is needed to understand how to improve SCPs and ultimately facilitate cancer survivors' transition to primary care. An interview guide was developed based on the second version of the Theoretical Domains Framework (TDF-2). PCPs participated in semi-structured interviews. Qualitative content analysis was used to develop a codebook to code text into each of the 14 TDF-2 domains. Thematic analysis was also used to generate themes and subthemes. Thirteen PCPs completed the interview and identified the following barriers to SCP use: unfamiliarity with the side effects of cancer treatment (Knowledge), lack of clarity on the roles of different healthcare professionals (Social Professional Role and Identity), follow-up tasks being outside of scope of practice (Social Professional Role and Identity), increased workload, lack of options for psychosocial support for survivors, managing different electronic medical records systems, logistical issues with liaising with oncology (Environmental Context and Resources), and patient factors (Social Influences). PCPs value the information provided in SCPs and found the follow-up guidance provided to be most helpful. However, SCP use could be improved through streamlining methods of communication and collaboration between oncology centres and community-based primary care settings.


Asunto(s)
Supervivientes de Cáncer , Atención Primaria de Salud , Supervivencia , Humanos , Supervivientes de Cáncer/psicología , Planificación de Atención al Paciente , Ciencia de la Implementación , Femenino , Neoplasias/terapia , Neoplasias/psicología , Personal de Salud/psicología , Masculino
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