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1.
RSC Adv ; 14(43): 31498-31501, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39372046

RESUMEN

Phosphodiester-linked cholane-pyrene-cholane trimers self-assemble into sheet-, tube- and worm-like nanostructures in aqueous conditions. The nanotubes and worm-like assemblies exist as single- or multi-walled objects.

2.
Environ Pollut ; : 125081, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39374762

RESUMEN

Cyanobacterial blooms are increasingly common in aquatic environments, raising concerns about the health impacts associated with the toxins they produce. One of these toxins is ß-Methylamino-L-alanine (BMAA), a neurotoxin linked to neurodegenerative diseases. Monitoring BMAA levels in the environment is challenging due to trace concentrations and complex matrices, and new approaches are needed for assessing exposure risk. In this laboratory study, Australian freshwater mussels, Velesunio ambiguus, were exposed to a BMAA-producing cyanobacterium, Microcystis aeruginosa, to assess its accumulation of the toxin over time. A sample preparation and analysis method was developed to allow accurate quantification of BMAA in the mussels at concentrations as low as 0.4 ng/g. Mussels exposed to M. aeruginosa accumulated BMAA, with concentrations increasing over the exposure period. Rapid depuration occurred after exposure to the cyanobacterium ended, with concentrations of BMAA quickly returning to pre-exposure levels. These results demonstrate the potential for mussels to be used as bioindicators in the field for monitoring BMAA levels over time, where rapid depuration is unlikely.

3.
Front Vet Sci ; 11: 1459293, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376926

RESUMEN

Lumpy skin disease (LSD) is an infectious disease currently spreading worldwide and poses a serious global threat. However, there is limited evidence and understanding to support the use of models to inform decision-making in LSD outbreak responses. This review aimed to identify modelling approaches that can be used before and during an outbreak of LSD, examining their characteristics and priorities, and proposing a structured workflow. We conducted a systematic review and identified 60 relevant publications on LSD outbreak modelling. The review identified six categories of question to be addressed following outbreak detection (origin, entry pathway, outbreak severity, risk factors, spread, and effectiveness of control measures), and five analytical techniques used to address them (descriptive epidemiology, risk factor analysis, spatiotemporal analysis, dynamic transmission modelling, and simulation modelling). We evaluated the questions each analytical technique can address, along with their data requirements and limitations, and accordingly assigned priorities to the modelling. Based on this, we propose a structured workflow for modelling during an LSD outbreak. Additionally, we emphasise the importance of pre-outbreak preparation and continuous updating of modelling post-outbreak for effective decision-making. This study also discusses the inherent limitations and uncertainties in the identified modelling approaches. To support this workflow, high-quality data must be collected in standardised formats, and efforts should be made to reduce inherent uncertainties of the models. The suggested modelling workflow can be used as a process to support rapid response for countries facing their first LSD occurrence and can be adapted to other transboundary diseases.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39353864

RESUMEN

Epigenome-wide association studies (EWAS) are susceptible to widespread confounding caused by population structure and genetic relatedness. Nevertheless, kinship estimation is challenging in EWAS without genotyping data. Here, we proposed MethylGenotyper, a method that for the first time enables accurate genotyping at thousands of single nucleotide polymorphisms (SNPs) directly from commercial DNA methylation microarrays. We modeled the intensities of methylation probes near SNPs with a mixture of three beta distributions corresponding to different genotypes and estimated parameters with an expectation-maximization algorithm. We conducted extensive simulations to demonstrate the performance of the method. When applying MethylGenotyper to the Infinium EPIC array data of 4662 Chinese samples, we obtained genotypes at 4319 SNPs with a concordance rate of 98.26%, enabling the identification of 255 pairs of close relatedness. Furthermore, we showed that MethylGenotyper allows for the estimation of both population structure and cryptic relatedness among 702 Australians of diverse ancestry. We also implemented MethylGenotyper in a publicly available R package (https://github.com/Yi-Jiang/MethylGenotyper) to facilitate future large-scale EWAS.


Asunto(s)
Metilación de ADN , Genotipo , Polimorfismo de Nucleótido Simple , Polimorfismo de Nucleótido Simple/genética , Metilación de ADN/genética , Humanos , Programas Informáticos , Estudio de Asociación del Genoma Completo/métodos , Algoritmos , Pueblo Asiatico/genética
5.
Food Res Int ; 195: 114944, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39277222

RESUMEN

The gelation of milk proteins can be achieved by various means, enabling the development of diverse products. In this study, heat-set milk protein gels (15 % protein) of diverse textures were made by pH modulation and two gels were selected for dynamic in vitro gastric digestion: a spoonable soft gel (SG, pH 6.55' G' of ∼100 Pa) and a sliceable firm gel (FG, pH 5.65; G' of ∼7000 Pa). The two gels displayed markedly different structural changes and digestion kinetics during gastric digestion. The SG underwent substantial structural compaction during the first 120 min of gastric digestion into a denser and firmer gastric chyme (26.3 % crude protein, G* of ∼8500 Pa) than the chyme of the FG (15.7 % crude protein, G* of ∼3000 Pa). These contrasting intragastric structural changes of the gels reversed their original textural differences, which led to slower digestion and gastric emptying of proteins from the SG compared with the FG. The different intragastric pH profiles during the digestion of the two gels likely played a key role by modulating the proteolytic activity and specificity (to κ-casein) of pepsin. Preferential early cleavage of κ-casein in SG stimulated coagulation and compaction of solid chyme, whereas rapid hydrolysis of αS- and ß-caseins in the FG weakened coagulation. This study provided new insights into controlling the structural development of dairy-based foods during gastric digestion and modulating digestion kinetics.


Asunto(s)
Digestión , Geles , Calor , Proteínas de la Leche , Geles/química , Digestión/fisiología , Concentración de Iones de Hidrógeno , Cinética , Proteínas de la Leche/química , Proteínas de la Leche/metabolismo , Vaciamiento Gástrico , Caseínas/química , Caseínas/metabolismo , Pepsina A/metabolismo , Animales , Manipulación de Alimentos/métodos , Proteolisis
6.
J Exp Med ; 221(10)2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39347789

RESUMEN

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional program, including Ednrb expression. Heme is a known inhibitor of Bach1, and, correspondingly, heme exposure induced Ednrb and iTAM signature genes in macrophages. Thus, iTAMs are a distinct macrophage subset regulated by the transcription factor Bach1 and characterized by Ednrb-mediated immunosuppressive and angiogenic functions.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Hemo , Hierro , Microambiente Tumoral , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Animales , Hierro/metabolismo , Ratones , Humanos , Hemo/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
7.
Brain Commun ; 6(5): fcae276, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39229494

RESUMEN

Reduced brain volumes and more prominent white matter hyperintensities on MRI scans are commonly observed among older adults without cognitive impairment. However, it remains unclear whether rates of change in these measures among cognitively normal adults differ as a function of genetic risk for late-onset Alzheimer's disease, including APOE-ɛ4, APOE-ɛ2 and Alzheimer's disease polygenic risk scores (AD-PRS), and whether these relationships are influenced by other variables. This longitudinal study examined the trajectories of regional brain volumes and white matter hyperintensities in relationship to APOE genotypes (N = 1541) and AD-PRS (N = 1093) in a harmonized dataset of middle-aged and older individuals with normal cognition at baseline (mean baseline age = 66 years, SD = 9.6) and an average of 5.3 years of MRI follow-up (max = 24 years). Atrophy on volumetric MRI scans was quantified in three ways: (i) a composite score of regions vulnerable to Alzheimer's disease (SPARE-AD); (ii) hippocampal volume; and (iii) a composite score of regions indexing advanced non-Alzheimer's disease-related brain aging (SPARE-BA). Global white matter hyperintensity volumes were derived from fluid attenuated inversion recovery (FLAIR) MRI. Using linear mixed effects models, there was an APOE-ɛ4 gene-dose effect on atrophy in the SPARE-AD composite and hippocampus, with greatest atrophy among ɛ4/ɛ4 carriers, followed by ɛ4 heterozygouts, and lowest among ɛ3 homozygouts and ɛ2/ɛ2 and ɛ2/ɛ3 carriers, who did not differ from one another. The negative associations of APOE-ɛ4 with atrophy were reduced among those with higher education (P < 0.04) and younger baseline ages (P < 0.03). Higher AD-PRS were also associated with greater atrophy in SPARE-AD (P = 0.035) and the hippocampus (P = 0.014), independent of APOE-ɛ4 status. APOE-ɛ2 status (ɛ2/ɛ2 and ɛ2/ɛ3 combined) was not related to baseline levels or atrophy in SPARE-AD, SPARE-BA or the hippocampus, but was related to greater increases in white matter hyperintensities (P = 0.014). Additionally, there was an APOE-ɛ4 × AD-PRS interaction in relation to white matter hyperintensities (P = 0.038), with greater increases in white matter hyperintensities among APOE-ɛ4 carriers with higher AD-PRS. APOE and AD-PRS associations with MRI measures did not differ by sex. These results suggest that APOE-ɛ4 and AD-PRS independently and additively influence longitudinal declines in brain volumes sensitive to Alzheimer's disease and synergistically increase white matter hyperintensity accumulation among cognitively normal individuals. Conversely, APOE-ɛ2 primarily influences white matter hyperintensity accumulation, not brain atrophy. Results are consistent with the view that genetic factors for Alzheimer's disease influence atrophy in a regionally specific manner, likely reflecting preclinical neurodegeneration, and that Alzheimer's disease risk genes contribute to white matter hyperintensity formation.

8.
BMC Prim Care ; 25(1): 324, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232645

RESUMEN

BACKGROUND: Telemedicine allows delivery of healthcare to occur between parties that are not in the same location. As telemedicine users are not co-present, effective communication methods are crucial to the delivery and reception of information. The aim of this study was to explore perspectives of general practitioners (GPs) and patients on the interactional components of telemedicine consultations. METHODS: Semi-structured qualitative interviews were held with telemedicine users; 15 GPs and nine patients self-selected from a larger telemedicine study. Participants were asked about their preparation for telemedicine consultations, conducting telemedicine consultations and post-consultation activities. Deidentified transcripts from the interviews were analysed thematically. RESULTS: GPs and patients discussed factors they used to decide whether a consultation would be best conducted by telemedicine or in-person; the condition to be discussed, the existing doctor-patient relationship and whether physical examination was required. Participants also described how they prepared for their telemedicine consultations, gathering relevant documents, and reading previous notes. Participants described strategies they employed to optimise the telemedicine interaction; improving conversational flow and building rapport, as well as difficulties they experienced when trying to provide and receive care via telemedicine. CONCLUSIONS: Patient factors including health literacy and familiarity with technology affect the transfer of information shared during telemedicine consultations and consideration of these factors when choosing patients for telemedicine is required. Many GPs and patients have innate communication skills to effectively deliver and receive care through telemedicine. However, they may not be aware of these subconscious techniques to use to optimise telemedicine consultations. Communication training could be delivered to increase conversational flow, build rapport, and establish safety netting.


Asunto(s)
Comunicación , Medicina General , Médicos Generales , Relaciones Médico-Paciente , Telemedicina , Humanos , Femenino , Masculino , Persona de Mediana Edad , Medicina General/organización & administración , Medicina General/métodos , Adulto , Investigación Cualitativa , Anciano , Entrevistas como Asunto , Consulta Remota , Actitud del Personal de Salud
9.
Front Endocrinol (Lausanne) ; 15: 1449326, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286269

RESUMEN

Background: The part played by oxytocin and oxytocin neurons in the regulation of food intake is controversial. There is much pharmacological data to support a role for oxytocin notably in regulating sugar consumption, however, several recent experiments have questioned the importance of oxytocin neurons themselves. Methods: Here we use a combination of histological and chemogenetic techniques to investigate the selective activation or inhibition of oxytocin neurons in the hypothalamic paraventricular nucleus (OxtPVH). We then identify a pathway from OxtPVH neurons to the bed nucleus of the stria terminalis using the cell-selective expression of channel rhodopsin. Results: OxtPVH neurons increase their expression of cFos after both physiological (fast-induced re-feeding or oral lipid) and pharmacological (systemic administration of cholecystokinin or lithium chloride) anorectic signals. Chemogenetic activation of OxtPVH neurons is sufficient to decrease free-feeding in Oxt Cre:hM3Dq mice, while inhibition in Oxt Cre:hM4Di mice attenuates the response to administration of cholecystokinin. Activation of OxtPVH neurons also increases energy expenditure and core-body temperature, without a significant effect on locomotor activity. Finally, the selective, optogenetic stimulation of a pathway from OxtPVH neurons to the bed nucleus of the stria terminalis reduces the consumption of sucrose. Conclusion: Our results support a role for oxytocin neurons in the regulation of whole-body metabolism, including a modulatory action on food intake and energy expenditure. Furthermore, we demonstrate that the pathway from OxtPVH neurons to the bed nucleus of the stria terminalis can regulate sugar consumption.


Asunto(s)
Ingestión de Energía , Metabolismo Energético , Neuronas , Oxitocina , Núcleo Hipotalámico Paraventricular , Núcleos Septales , Animales , Oxitocina/farmacología , Oxitocina/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleos Septales/metabolismo , Núcleos Septales/fisiología , Ratones , Neuronas/metabolismo , Masculino , Sacarosa/farmacología , Ratones Transgénicos , Ratones Endogámicos C57BL , Ingestión de Alimentos/fisiología
10.
New J Chem ; 48(36): 15731-15734, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39234596

RESUMEN

The self-assembly of highly functionalized phenanthrene-DNA conjugates into supramolecular nanostructures is presented. DNA oligomers modified with phenanthrene residues at the 3'-end and internal positions self-assemble into spherical nanostructures. The nanospheres exhibit light-harvesting properties. Upon irradiation of phenanthrene, the excitation energy is transferred along phenanthrene units, resulting in phenanthrene-pyrene exciplex formation.

11.
Z Rheumatol ; 2024 Sep 13.
Artículo en Alemán | MEDLINE | ID: mdl-39271483

RESUMEN

Large vessel vasculitis, including giant cell arteritis (GCA) and Takayasu arteritis (TAK), are autoimmune diseases primarily affecting the aorta and its branches. GCA is the most common primary vasculitis. Inflammatory changes in the vessel walls can cause serious complications such as amaurosis, stroke, and aortic dissection and rupture. Imaging techniques have become an integral part for the diagnosis and monitoring of large vessel vasculitis, allowing for effective disease monitoring. GCA and TAK exhibit similar patterns of vascular distribution. However, the temporal arteries are never involved in TAK, and axillary arteritis occurs more frequently in GCA. In most centers, ultrasound of the temporal and axillary arteries has replaced temporal artery biopsy as the primary diagnostic tool for GCA. In addition to ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and [18F]-FDG (fluorodeoxyglucose) positron emission tomography-computed tomography (PET) are important, particularly for visualizing the aorta. Moreover, PET-CT is now also capable of assessing the temporal arteries, although it is not yet widely available. In polymyalgia rheumatica (PMR), ultrasound of the shoulder and hip regions is part of the ACR/EULAR classification criteria. MRI allows detailed visualization of additional inflammatory extraarticular manifestations, showing characteristic inflammatory lesions in entheses, tendons, and ligaments. [18F]-FDG-PET-CT also enables the visualization of musculoskeletal inflammation, especially in the shoulder and hip regions, as well as paravertebral areas. Ultrasound can detect subclinical GCA in up to 23% of patients with PMR, which should be treated like GCA. Technological innovations such as new radiotracers and improved MRI imaging could further enhance the diagnosis and monitoring of large vessel vasculitis and PMR, thus playing a crucial role in improving the prognosis through faster initiation of therapy.

12.
Mol Psychiatry ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271753

RESUMEN

Abnormalities in cellular metabolism are seen early in Alzheimer's disease (AD). Astrocyte support for neuronal function has a high metabolic demand, and astrocyte glucose metabolism plays a key role in encoding memory. This indicates that astrocyte metabolic dysfunction might be an early event in the development of AD. In this paper we interrogate glycolytic and mitochondrial functional changes and mitochondrial structural alterations in patients' astrocytes derived with a highly efficient direct conversion protocol. In astrocytes derived from patients with sporadic (sAD) and familial AD (fAD) we identified reductions in extracellular lactate, total cellular ATP and an increase in mitochondrial reactive oxygen species. sAD and fAD astrocytes displayed significant reductions in mitochondrial spare respiratory capacity, have altered mitochondrial membrane potential and a stressed mitochondrial network. A reduction in glycolytic reserve and glycolytic capacity is seen. Interestingly, glycolytic reserve, mitochondrial spare respiratory capacity and extracellular lactate levels correlated positively with neuropsychological tests of episodic memory affected early in AD. We identified a deficit in the glycolytic enzyme hexokinase 1 (HK1), and correcting this deficit improved the metabolic phenotype in sAD not fAD astrocytes. Importantly, the amount of HK1 at the mitochondria was shown to be reduced in sAD astrocytes, and not in fAD astrocytes. Overexpression of HK1 in sAD astrocytes increases mitochondrial HK1 levels. In fAD astrocytes HK1 levels were unaltered at the mitochondria after overexpression. This study highlights a clear metabolic deficit in AD patient-derived astrocytes and indicates how HK1, with its roles in both oxidative phosphorylation and glycolysis, contributes to this.

13.
Chimia (Aarau) ; 78(7-8): 499-512, 2024 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-39221845

RESUMEN

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples.


Asunto(s)
Química Farmacéutica , Descubrimiento de Drogas , Endocannabinoides , Endocannabinoides/metabolismo , Endocannabinoides/química , Humanos , Industria Farmacéutica , Monoacilglicerol Lipasas/metabolismo , Monoacilglicerol Lipasas/antagonistas & inhibidores , Desarrollo de Medicamentos , Academia
14.
Vet Parasitol ; 332: 110306, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39265207

RESUMEN

Toxoplasma gondii is a globally distributed zoonotic protist, capable of infecting all warm-blooded animals. In Australia, cats (Felis catus) are the only definitive host capable of spreading T. gondii infection via oocysts. Free-roaming cats are widespread in Australia and can play a central role in the ecology of T. gondii. Therefore, understanding the epidemiology of this parasite in stray and feral cats is essential to understanding the potential risk of infection in animals and humans. Due to a lack of easily accessible commercial kits, an in-house modified agglutination test (MAT) was established to test for IgG antibodies against T. gondii, using cell culture-derived T. gondii tachyzoites, and compared with a commercial MAT. A total of 552 serum samples collected during 2018 - 2021 from stray (n = 456) and feral cats (n = 90) (samples with missing data n = 6) from four Australian states, representing different age groups of both sexes, were screened for antibodies against T. gondii. Risk factors for T. gondii infection were assessed using multivariable logistic regression analysis. The in-house MAT had excellent agreement with the commercial MAT and provided a reliable and economical serological tool for T. gondii screening in animals. The overall observed seroprevalence for T. gondii in cats was 40.4 % (223/552). Bodyweight (as a proxy for age), geographical location, season and whether cats were feral or stray, were factors associated with T. gondii seropositivity in cats. Sex was not found to be a risk factor for T. gondii infection in feral and stray cats. This study shows that Australian stray and feral cats have a high T. gondii seroprevalence, which may translate to significant health impacts for wildlife species, livestock and the public.

15.
Ann Am Thorac Soc ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255452

RESUMEN

RATIONALE: The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data. OBJECTIVES: To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI). METHODS: 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr. MRI was assessed using a validated MRI scoring system. MEASUREMENTS AND MAIN RESULTS: The MRI global score continuously increased from 5.5±4.6 at infancy (0yr) to 17.9±8.4 at adolescence (range 12-18yr), and the MRI morphology score from 5.0±3.9 to 12.4±6.0 (P<0.001). Bronchiectasis/wall thickening prevalence increased from 89.1% at infancy to approx. 100% from preschool age (1-5yr), and the subscore increased from 3.1±1.9 at infancy to 6.6±2.1 at adolescence (P<0.001). Mucus plugging prevalence increased from 55.4% at infancy to 83.5% at adolescence, and the subscore increased from 1.2±1.6 to 3.7±2.5 in the same period (P<0.001). Perfusion abnormalities were found in 44.4% at infancy, and increased to approx. 90% from preschool age (P<0.001). The MRI perfusion score increased from 1.1±1.6 at infancy to 5.6±3.0 at adolescence (P<0.001). Chronic Pseudomonas aeruginosa infection was associated with higher MRI scores from school age (6-11yr, P<0.05-0.001). CONCLUSIONS: This is the first study assessing longitudinal changes in lung morphology and perfusion in CF throughout the pediatric age range, providing percentiles as age-specific reference for lung disease severity. Our data may facilitate the use of MRI as an endpoint in clinical trials in children with CF.

16.
Genome Res ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255977

RESUMEN

Pleiotropy, measured as expression breadth across tissues, is one of the best predictors for protein sequence and expression conservation. In this study, we investigated its effect on the evolution of cis-regulatory elements (CREs). To this end, we carefully reanalyzed the Epigenomics Roadmap data for nine fetal tissues, assigning a measure of pleiotropic degree to nearly half a million CREs. To assess the functional conservation of CREs, we generated ATAC-seq and RNA-seq data from humans and macaques. We found that more pleiotropic CREs exhibit greater conservation in accessibility, and the mRNA expression levels of the associated genes are more conserved. This trend of higher conservation for higher degrees of pleiotropy persists when analyzing the transcription factor binding repertoire. In contrast, simple DNA sequence conservation of orthologous sites between species tends to be even lower for pleiotropic CREs than for species-specific CREs. Combining various lines of evidence, we propose that the lack of sequence conservation in functionally conserved pleiotropic CREs is due to within-element compensatory evolution. In summary, our findings suggest that pleiotropy is also a good predictor for the functional conservation of CREs, even though this is not reflected in the sequence conservation of pleiotropic CREs.

18.
Front Psychol ; 15: 1443707, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39295769

RESUMEN

Introduction: Resolution of a child's diagnosis, the process of accepting and adjusting to the reality of a child's significant diagnosis, has been often associated with decreased parental stress. Hope, a potential buffer against psychological distress, has been suggested as a potential explanation for this relationship. However, the mediating role of hope in the relationship between resolution of diagnosis and parental stress has not been explored. Methods: This study aimed to examine whether four types of hope (child, parental, societal, denial of diagnosis) mediated the relationship between resolution to an autism diagnosis and reduced parental stress. Participants included 73 parents (Mage = 43.22, SD = 7.69, female 97.3%) of autistic children (Mage = 11.15, SD = 4.56, male = 67.1%). Results: Resolution to diagnosis was negatively and significantly correlated with resolution to diagnosis, as well as child, parental and societal hope. These three hopes were also significantly and negatively correlated with parental stress. Importantly, when controlling for level of support and autism awareness, parental hope mediated the relationship between resolution to diagnosis and parental stress. Denial of diagnosis was not correlated with resolution or parental stress but did have significant but weak associate with the other hopes. Discussion: These findings suggest that hope based on parent's abilities to support their child and be supported themselves play an important role in parental stress once parents are more resolved to their child's diagnosis. Supporting parents to manage factors associated with supporting their child's needs, may benefit parents of autistic children.

19.
Cult Health Sex ; : 1-18, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285810

RESUMEN

Emotional intimacy is key to intimate partner relationship quality and satisfaction. For sexual minority men, queer and feminist theorists consistently link emotional intimacy to diverse sexual practices and partnership dynamics formulated within the relationship. This Photovoice study adds to those insights by drawing on individual photovoice interviews with 16 sexual minority men to describe participant's experiences of, and strategies for emotional intimacy in their intimate relationships. Analysis revealed three distinct yet entwined themes: (i) embracing vulnerabilities to drive self-acceptance; (ii) building relationality with partners; and (iii) securing connections with family, friends and community. By embracing vulnerabilities to drive self-acceptance, participants spoke to embodied courage and autonomy as key components for addressing wide-ranging emotional intimacy challenges in their relationships. In theme two, building relationality with partners, participants described how empathy, trust and reciprocity underpinned collaborative work to foster emotional intimacy. Lastly, in securing connections with family, friends and community, acceptance and inclusion were key to participants' sense of belonging and legitimacy which aided their emotional intimacy with partners. The findings provide guidance for tailored programmatic efforts to assist sexual minority men build intimate relationships.

20.
ACS Nano ; 18(39): 26655-26665, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39305260

RESUMEN

Despite the interest in improving the sensitivity of optical sensors using plasmonic nanoparticles (NPs) (rods, wires, and stars), the full structural characterization of complex shape nanostructures is challenging. Here, we derive from a single scanning transmission electron microscope diffraction map (4D-STEM) a detailed determination of both the 3D shape and atomic arrangement of an individual 6-branched AuAg nanostar (NS) with high-aspect-ratio legs. The NS core displays an icosahedral structure, and legs are decahedral rods attached along the 5-fold axes at the core apexes. The NS legs show an anomalous anisotropic spatial distribution (all close to a plane) due to an interplay between the icosahedral symmetry and the unzipping of the surfactant layer on the core. The results significantly improve our understanding of the star growth mechanism. This low dose diffraction mapping is promising for the atomic structure study of individual multidomain, multibranched, or multiphase NPs, even when constituted of beam-sensitive materials.

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