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1.
Hum Mol Genet ; 31(5): 733-747, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-34568901

RESUMO

Congenital muscular dystrophy type 1A (MDC1A), the most common congenital muscular dystrophy in Western countries, is caused by recessive mutations in LAMA2, the gene encoding laminin alpha 2. Currently, no cure or disease modifying therapy has been successfully developed for MDC1A. Examination of patient muscle biopsies revealed altered distribution of lysosomes. We hypothesized that this redistribution was a novel and potentially druggable aspect of disease pathogenesis. We explored this hypothesis using candyfloss (caf), a zebrafish model of MDC1A. We found that lysosome distribution in caf zebrafish was also abnormal. This altered localization was significantly associated with fiber detachment and could be prevented by blocking myofiber detachment. Overexpression of transcription factor EB, a transcription factor that promotes lysosomal biogenesis, led to increased lysosome content and decreased fiber detachment. We conclude that genetic manipulation of the lysosomal compartment is able to alter the caf zebrafish disease process, suggesting that lysosome function may be a target for disease modification.


Assuntos
Distrofias Musculares , Peixe-Zebra , Animais , Humanos , Laminina/genética , Lisossomos/genética , Lisossomos/patologia , Músculo Esquelético/patologia , Distrofias Musculares/patologia , Fatores de Transcrição , Peixe-Zebra/genética
2.
EMBO Rep ; 23(2): e54396, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34910840

RESUMO

Embryonic development is a complex process in which cells divide, migrate, and differentiate in a precise spatiotemporal pattern. Cell-cell communication among neighboring cells plays a central role in specifying cell fate and in coordinating development. Embryonic development also relies on physical interaction between cells and coordinated changes in cell shape. A more recently investigated phenomenon is the coupling of development of adjacent tissues via inter-tissue adhesion. In this issue of EMBO Reports, Monnot and colleagues identify a role for inter-tissue adhesion in the development of adjacent sensory organs in the zebrafish. Specifically, eye morphogenesis influences the organ shape and retrograde axon growth in the adjacent olfactory placode via a shared extracellular matrix.


Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Ectoderma/metabolismo , Organogênese/genética , Aderências Teciduais , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
3.
Aggress Behav ; 49(4): 396-408, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36842143

RESUMO

Youth violence continues to be a major developmental and health concern. Preventative resources at individual, family, and community levels may reduce risk, yet the extent to which youth violence perpetration differs by patterns of risk and protective factors remains unknown. Using data from the Florida Youth Substance Abuse Survey (N = 4630; 49% female; Mage = 14.69), we conducted person-centered, latent profile analyses to identify four patterns for risk of violence perpetration among middle and high school youth. Youth in the Low Risk-High Protection profile (37%) had low likelihood of violence perpetration. Youth in the Low Risk-Low Protection profile (4%) were characterized by poor family functioning, low school belonging, and low community protection. These youth had similar odds of violence perpetration as youth in the Moderate Risk-Moderate Protection profile (44%), which were elevated compared to the Low Risk-High Protection profile. Youth in the High Risk-Low Protection profile (15%), which had the highest levels of risk factors and lowest levels of protective factors, had the highest likelihood of violence perpetration. The High Risk-Low Protection profile was expected based on past research, but the emergence of the Low Risk-Low Protection profile is a unique contribution to the research. Findings contribute to the literature by going beyond a cumulative risk model, identifying subgroups with various patterns of risk and protection in the population, and highlighting the importance of selected prevention for subgroups of youth with high risk or challenging family and community environments.


Assuntos
Comportamento do Adolescente , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Feminino , Masculino , Violência/prevenção & controle , Instituições Acadêmicas , Meio Social , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
4.
Plant J ; 106(5): 1387-1400, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33735457

RESUMO

ATP is secreted to the extracellular matrix, where it activates plasma membrane receptors for controlling plant growth and stress-adaptive processes. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), was the first plant ATP receptor to be identified but key downstream proteins remain sought after. Here, we identified 120 proteins secreted by Arabidopsis cell cultures and screened them for putative stress-responsive proteins using ATP-affinity purification. We report three Arabidopsis proteins isolated by ATP-affinity: PEROXIDASE 52, SUBTILASE-LIKE SERINE PROTEASE 1.7 and PHOSPHOLIPASE C-LIKE 1. In wild-type Arabidopsis, the expression of genes encoding all three proteins responded to fumonisin B1, a cell death-activating mycotoxin. The expression of PEROXIDASE 52 and PHOSPHOLIPASE C-LIKE 1 was altered in fumonisin B1-resistant salicylic acid induction-deficient (sid2) mutants. Exposure to fumonisin B1 suppressed PHOSPHOLIPASE C-LIKE 1 expression in sid2 mutants, suggesting that the inactivation of this gene might provide mycotoxin tolerance. Accordingly, gene knockout mutants of PHOSPHOLIPASE C-LIKE 1 were resistant to fumonisin B1-induced death. The activation of PHOSPHOLIPASE C-LIKE 1 gene expression by exogenous ATP was not blocked in dorn1 loss-of-function mutants, indicating that DORN1 is not required. Furthermore, exogenous ATP rescued both the wild type and the dorn1 mutants from fumonisin-B1 toxicity, suggesting that different ATP receptor(s) are operational in this process. Our results point to the existence of additional plant ATP receptor(s) and provide crucial downstream targets for use in designing screens to identify these receptors. Finally, PHOSPHOLIPASE C-LIKE 1 serves as a convergence point for fumonisin B1 and extracellular ATP signalling, and functions in the Arabidopsis stress response to fumonisin B1.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Fumonisinas/metabolismo , Fosfolipases/metabolismo , Transdução de Sinais , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Morte Celular , Membrana Celular/metabolismo , Matriz Extracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Peroxidases/genética , Peroxidases/metabolismo , Fosfolipases/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteômica , Estresse Fisiológico , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo
5.
Prev Sci ; 23(4): 523-537, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34714506

RESUMO

Past reviews of cyberbullying preventative interventions have critiqued the field regarding scientific rigor, and a meta-analysis found that randomized controlled trials (RCTs) of such interventions were more effective than non-RCTs. However, no review has examined the risk of bias, dosage, modality, and delivery context of such programs to date. The current study addresses this gap through a systematic review of the literature. Potential articles (N = 4,737) from 4 databases were identified and screened (Academic Search Premier including ERIC, PsychINFO, and the Psychology and Behavioral Collection; PubMed; Web of Science; Compendex); 72 articles were reviewed for eligibility. Final articles included (N = 30) were based on a rigorous search process guided by inclusion and exclusion criteria. The majority of studies were conducted in Europe; two were conducted in the USA, three in Australia, and two in the Middle East. Efforts to reduce risk of bias were evaluated using the Cochrane's Risk of Bias tool. Harvest plots were constructed to qualitatively illustrate the rigor, dosage, modality, and context of the interventions, and meta-analytic random effects models were conducted to examine effect sizes of the interventions on cyberbullying perpetration and victimization. Results suggest that cyberbullying interventions delivered through schools are effective, though expanded follow-up time is suggested, and additional evidence is needed for home settings and digital delivery.


Assuntos
Bullying , Vítimas de Crime , Cyberbullying , Austrália , Bullying/prevenção & controle , Cyberbullying/prevenção & controle , Humanos , Instituições Acadêmicas
6.
Qual Life Res ; 29(2): 463-472, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31646416

RESUMO

PURPOSE: There are many validated quality-of-life (QoL) measures designed for people living with dementia. However, the majority of these are completed via proxy-report, despite indications from community-based studies that consistency between proxy-reporting and self-reporting is limited. The aim of this study was to understand the relationship between self- and proxy-reporting of one generic and three disease-specific quality-of-life measures in people living with dementia in care home settings. METHODS: As part of a randomised controlled trial, four quality-of-life measures (DEMQOL, EQ-5D-5L, QOL-AD and QUALID) were completed by people living with dementia, their friends or relatives or care staff proxies. Data were collected from 726 people living with dementia living in 50 care homes within England. Analyses were conducted to establish the internal consistency of each measure, and inter-rater reliability and correlation between the measures. RESULTS: Residents rated their quality of life higher than both relatives and staff on the EQ-5D-5L. The magnitude of correlations varied greatly, with the strongest correlations between EQ-5D-5L relative proxy and staff proxy. Internal consistency varied greatly between measures, although they seemed to be stable across types of participants. There was poor-to-fair inter-rater reliability on all measures between the different raters. DISCUSSION: There are large differences in how QoL is rated by people living with dementia, their relatives and care staff. These inconsistencies need to be considered when selecting measures and reporters within dementia research.


Assuntos
Demência/psicologia , Procurador , Qualidade de Vida/psicologia , Autorrelato , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários
7.
BMC Health Serv Res ; 20(1): 512, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503536

RESUMO

BACKGROUND: The health and social care workforce requires access to appropriate education and training to provide quality care for people with dementia. Success of a training programme depends on staff ability to put their learning into practice through behaviour change. This study aimed to investigate the barriers and facilitators to implementation of dementia education and training in health and social care services using the Theoretical Domains Framework (TDF) and COM-B model of behaviour change. METHODS: A mixed-methods design. Participants were dementia training leads, training facilitators, managers and staff who had attended training who worked in UK care homes, acute hospitals, mental health services and primary care settings. Methods were an online audit of care and training providers, online survey of trained staff and individual/group interviews with organisational training leads, training facilitators, staff who had attended dementia training and managers. Data were analysed using descriptive statistics and thematic template analysis. RESULTS: Barriers and facilitators were analysed according the COM-B domains. "Capability" factors were not perceived as a significant barrier to training implementation. Factors which supported staff capability included the use of interactive face-to-face training, and training that was relevant to their role. Factors that increased staff "motivation" included skilled facilitation of training, trainees' desire to learn and the provision of incentives (e.g. attendance during paid working hours, badges/certifications). "Opportunity" factors were most prevalent with lack of resources (time, financial, staffing and environmental) being the biggest perceived barrier to training implementation. The presence or not of external support from families and internal factors such as the organisational culture and its supportiveness of good dementia care and training implementation were also influential. CONCLUSIONS: A wide range of factors may present as barriers to or facilitators of dementia training implementation and behaviour change for staff. These should be considered by health and social care providers in the context of dementia training design and delivery in order to maximise potential for implementation.


Assuntos
Demência/terapia , Pessoal de Saúde/educação , Capacitação em Serviço/organização & administração , Serviço Social/organização & administração , Pessoal de Saúde/psicologia , Pesquisa sobre Serviços de Saúde , Humanos , Pesquisa Qualitativa , Inquéritos e Questionários , Reino Unido
8.
Aging Ment Health ; 24(3): 511-521, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30596270

RESUMO

Background and objectives: People with dementia occupy around one quarter of general hospital beds, with concerns consistently raised about care quality. Improving workforce knowledge, skills and attitudes is a mechanism for addressing this. However little is known about effective ways of training healthcare staff about dementia. This study aimed to understand models of dementia training most likely to lead to improved practice and better care experiences for people with dementia, and to understand barriers and facilitators to implementation.Method: A collective case study was conducted in three National Health Service Acute Hospital Trusts in England. Multiple data sources were used including interviews with training leads/facilitators, ward managers and staff who had attended training; satisfaction surveys with patients with dementia and/or carers; and observations of care using Dementia Care Mapping.Results: Interactive face-to-face training designed for general hospital staff was valued. Simulation and experiential learning methods were felt to be beneficial by some staff and stressful and distressing by others. Skilled delivery by an experienced and enthusiastic facilitator was identified as important. Staff identified learning and practice changes made following their training. However, observations revealed not all staff had the knowledge, attitudes and skills needed to deliver good care. Patient and carer satisfaction with care was mixed. A major barrier to training implementation was lack of resources. Supportive managers, organisational culture and strong leadership were key facilitators.Conclusion: Dementia training can lead to improved care practices. There are a range of key barriers and facilitators to implementation that must be considered.


Assuntos
Demência , Hospitais Gerais , Recursos Humanos em Hospital/educação , Demência/terapia , Inglaterra , Humanos , Medicina Estatal
9.
Anal Chem ; 91(4): 2847-2853, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30676721

RESUMO

The spread of antibiotic-resistant bacteria poses a global threat to public health. Conventional bacterial detection and identification methods often require pre-enrichment and/or sample preprocessing and purification steps that can prolong diagnosis by days. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most widespread antibiotic-resistant bacteria and is the leading cause of hospital-acquired infections. Here, we have developed a method to specifically capture and detect MRSA directly from patient nasal swabs with no prior culture and minimal processing steps using a microfluidic device and antibody-functionalized magnetic nanoparticles. Bacteria are captured based on antibody recognition of a membrane-bound protein marker that confers ß-lactam antibiotic resistance. MRSA identification is then achieved by the use of a strain-specific antibody functionalized with alkaline phosphatase for electrochemical detection. This approach ensures that only those bacteria of the target strain and resistance profile are measured. The method has a limit of detection of 845 CFU/mL and excellent discrimination against high concentrations of common nontarget nasal flora with a turnaround time of under 4.5 h. This detection method was successfully validated using clinical nasal swab specimens ( n = 30) and has the potential to be tailored to various bacterial targets.


Assuntos
Técnicas Eletroquímicas/instrumentação , Dispositivos Lab-On-A-Chip , Nanopartículas de Magnetita/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Anticorpos Imobilizados/química , Desenho de Equipamento , Humanos , Limite de Detecção , Infecções Estafilocócicas/microbiologia
10.
New Phytol ; 224(4): 1518-1531, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31549420

RESUMO

Forward genetic screens play a key role in the identification of genes contributing to plant stress tolerance. Using a screen for freezing sensitivity, we have identified a novel freezing tolerance gene, SENSITIVE-TO-FREEZING8, in Arabidopsis thaliana. We identified SFR8 using recombination-based mapping and whole-genome sequencing. As SFR8 was predicted to have an effect on cell wall composition, we used GC-MS and polyacrylamide gel electrophoresis to measure cell-wall fucose and boron (B)-dependent dimerization of the cell-wall pectic domain rhamnogalacturonan II (RGII) in planta. After treatments to promote borate-bridging of RGII, we assessed freeze-induced damage in wild-type and sfr8 plants by measuring electrolyte leakage from freeze-thawed leaf discs. We mapped the sfr8 mutation to MUR1, a gene encoding the fucose biosynthetic enzyme GDP-d-mannose-4,6-dehydratase. sfr8 cell walls exhibited low cell-wall fucose levels and reduced RGII bridging. Freezing sensitivity of sfr8 mutants was ameliorated by B supplementation, which can restore RGII dimerization. B transport mutants with reduced RGII dimerization were also freezing-sensitive. Our research identifies a role for the structure and composition of the plant primary cell wall in determining basal plant freezing tolerance and highlights the specific importance of fucosylation, most likely through its effect on the ability of RGII pectin to dimerize.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Parede Celular/metabolismo , Arabidopsis/citologia , Proteínas de Arabidopsis/genética , Boro/metabolismo , Clonagem Molecular , Congelamento , Fucose/metabolismo , Mutação , Pectinas/química , Pectinas/metabolismo , Células Vegetais/metabolismo , Estresse Fisiológico/fisiologia
11.
J Am Chem Soc ; 139(3): 1020-1028, 2017 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-28002665

RESUMO

Methods that can rapidly and specifically analyze nucleic acid sequences will revolutionize the diagnosis and treatment of disease by allowing molecular-level information to be used during routine medicine. In this Perspective, we discuss chemistry-driven approaches that will make the detection of DNA and RNA sequences more routine in clinical settings. In addition, we discuss unmet needs and areas where future effort is necessary to enable nucleic acids analysis to become a mainstream tool in routine clinical medicine. Methods for next-generation sequencing of DNA are producing a wealth of information by allowing the study of how specific genetic mutations or single nucleotide polymorphisms influence the onset of disease, prognosis, or response to treatment. To give this information clinical utility, new methods of detecting nucleic acid sequences are being developed in order to rapidly obtain genetic information in more streamlined formats, and with the ability to obtain information outside of a laboratory setting. Challenges remain in this area, however, and new chemistries that will facilitate fast, simple nucleic acids analysis in a clinical setting are needed.


Assuntos
DNA/análise , Sequenciamento de Nucleotídeos em Larga Escala , RNA/análise , Sequência de Aminoácidos , DNA/genética , Humanos , RNA/genética
12.
Mol Cell Proteomics ; 14(6): 1556-68, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25862728

RESUMO

Programmed cell death is essential for plant development and stress adaptation. A detailed understanding of the signal transduction pathways that regulate plant programmed cell death requires identification of the underpinning protein networks. Here, we have used a protagonist and antagonist of programmed cell death triggered by fumonisin B1 as probes to identify key cell death regulatory proteins in Arabidopsis. Our hypothesis was that changes in the abundance of cell death-regulatory proteins induced by the protagonist should be blocked or attenuated by concurrent treatment with the antagonist. We focused on proteins present in the mobile phase of the extracellular matrix on the basis that they are important for cell-cell communications during growth and stress-adaptive responses. Salicylic acid, a plant hormone that promotes programmed cell death, and exogenous ATP, which can block fumonisin B1-induced cell death, were used to treat Arabidopsis cell suspension cultures prior to isobaric-tagged relative and absolute quantitation analysis of secreted proteins. A total of 33 proteins, whose response to salicylic acid was suppressed by ATP, were identified as putative cell death-regulatory proteins. Among these was CYCLASE1, which was selected for further analysis using reverse genetics. Plants in which CYCLASE1 gene expression was knocked out by insertion of a transfer-DNA sequence manifested dramatically increased cell death when exposed to fumonisin B1 or a bacterial pathogen that triggers the defensive hypersensitive cell death. Although pathogen inoculation altered CYCLASE1 gene expression, multiplication of bacterial pathogens was indistinguishable between wild type and CYCLASE1 knockout plants. However, remarkably severe chlorosis symptoms developed on gene knockout plants in response to inoculation with either a virulent bacterial pathogen or a disabled mutant that is incapable of causing disease in wild type plants. These results show that CYCLASE1, which had no known function hitherto, is a negative regulator of cell death and regulates pathogen-induced symptom development in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Morte Celular/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Trifosfato de Adenosina/farmacologia , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Morte Celular/efeitos dos fármacos , Fumonisinas/farmacologia , Proteômica , Pseudomonas syringae/fisiologia , Ácido Salicílico/farmacologia
13.
J Biol Chem ; 289(34): 23504-19, 2014 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-25006247

RESUMO

Inflammasomes are macromolecular complexes that mediate inflammatory and cell death responses to pathogens and cellular stress signals. Dysregulated inflammasome activation is associated with autoinflammatory syndromes and several common diseases. During inflammasome assembly, oligomerized cytosolic pattern recognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein ASC. Inflammasome assembly is mediated by pyrin domains (PYDs) and caspase recruitment domains, which are protein interaction domains of the death fold superfamily. However, the molecular details of their interactions are poorly understood. We have studied the interaction between ASC and pyrin PYDs that mediates ASC recruitment to the pyrin inflammasome, which is implicated in the pathogenesis of familial Mediterranean fever. We demonstrate that both the ASC and pyrin PYDs have multifaceted binding modes, involving three sites on pyrin PYD and two sites on ASC PYD. Molecular docking of pyrin-ASC PYD complexes showed that pyrin PYD can simultaneously interact with up to three ASC PYDs. Furthermore, ASC PYD can self-associate and interact with pyrin, consistent with previous reports that pyrin promotes ASC clustering to form a proinflammatory complex. Finally, the effects of familial Mediterranean fever-associated mutations, R42W and A89T, on structural and functional properties of pyrin PYD were investigated. The R42W mutation had a significant effect on structure and increased stability. Although the R42W mutant exhibited reduced interaction with ASC, it also bound less to the pyrin B-box domain responsible for autoinhibition and hence may be constitutively active. Our data give new insights into the binding modes of PYDs and inflammasome architecture.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Inflamassomos/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Proteínas Adaptadoras de Sinalização CARD , Proteínas do Citoesqueleto/genética , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Pirina , Homologia de Sequência de Aminoácidos
14.
Plant J ; 80(2): 255-68, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25065716

RESUMO

Meiosis is a specialized cell division essential for sexual reproduction. During meiosis the chromosomes are highly organized, and correct chromosome architecture is required for faithful segregation of chromosomes at anaphase I and II. Condensin is involved in chromosome organization during meiotic and mitotic cell divisions. Three condensin subunits, AtSMC4 and the condensin I and II specific subunits AtCAP-D2 and AtCAP-D3, respectively, have been studied for their role in meiosis. This has revealed that both the condensin I and condensin II complexes are required to maintain normal structural integrity of the meiotic chromosomes during the two nuclear divisions. Their roles appear functionally distinct in that condensin I is required to maintain normal compaction of the centromeric repeats and 45S rDNA, whereas loss of condensin II was associated with extensive interchromosome connections at metaphase I. Depletion of condensin is also associated with a slight reduction in crossover formation, suggesting a role during meiotic prophase I.


Assuntos
Adenosina Trifosfatases/fisiologia , Proteínas de Arabidopsis/fisiologia , Arabidopsis/citologia , Cromossomos de Plantas , Proteínas de Ligação a DNA/fisiologia , Meiose , Morfogênese , Complexos Multiproteicos/fisiologia , Arabidopsis/genética , Centrômero , DNA de Plantas , Heterozigoto
15.
J Am Chem Soc ; 137(33): 10468-71, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26256820

RESUMO

Due to their structural and mechanical properties, 1D helical protein assemblies represent highly attractive design targets for biomolecular engineering and protein design. Here we present a designed, tetrameric protein building block, Zn8R4, which assembles via Zn coordination interactions into a series of crystalline, helical nanotubes whose widths can be controlled by solution conditions. X-ray crystallography and transmission electron microscopy (TEM) measurements indicate that all classes of protein nanotubes are constructed through the same 2D arrangement of Zn8R4 tetramers held together by Zn coordination. The mechanical properties of these nanotubes are correlated with their widths. All Zn8R4 nanotubes are found to be highly flexible despite possessing crystalline order, owing to their minimal interbuilding-block interactions mediated solely by metal coordination.


Assuntos
Nanotecnologia/métodos , Nanotubos/química , Proteínas/química , Modelos Moleculares , Estrutura Secundária de Proteína , Zinco/química
17.
J Comp Pathol ; 205: 11-16, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37506667

RESUMO

We report the pathological and molecular findings in an adult male Himalayan red panda (Ailurus fulgens fulgens) whose death was attributed to parenchymal brain haemorrhage (PBH) of the thalamus. Post-mortem examination revealed severe, acute PBH and intraventricular haemorrhage with major involvement of the thalamus, as well as scattered chronic microinfarctions. Vascular disease in the brain and other organs was suggestive of systemic hypertension. Histological lesions included arteriolar hyalinosis and varying degrees of arteriosclerosis, arterial tunica media hypertrophy and hyperplasia and infiltration of arterial walls by lipid-laden macrophages. Other relevant findings included marked myocardial fibrosis, lymphoplasmacytic tubulointerstitial nephritis, lymphoplasmacytic meningoencephalitis and chronic mitral valve degeneration. The changes in the cerebral vasculature were consistent with hypertensive encephalopathy and a cerebrovascular accident, specifically PBH, which has not been previously reported in this species. Additionally, polymerase chain reaction analysis for red panda amdoparvovirus (RPAV) was positive in the brain and kidneys. Preceded by hypertensive vascular changes and brain microinfarctions, sudden death in this animal likely resulted from fatal PBH with intraventricular haemorrhage. The clinicopathological role of RPAV infection is unknown in this case, although its contribution to the chronic renal disease is considered possible in the context of our current understanding of RPAV-associated pathology.


Assuntos
Ailuridae , Acidente Vascular Cerebral , Masculino , Animais , Rim , Acidente Vascular Cerebral/veterinária , Hemorragia/veterinária
18.
Pediatr Infect Dis J ; 42(10): 862-866, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37625080

RESUMO

BACKGROUND: Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region. METHODS: We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined risk factors and performed a geospatial analysis, including a comparative analysis of human cases and locations of surrendered infected stray animals in the same region. RESULTS: Children diagnosed with toxocariasis were most commonly of Hispanic/Latino ethnicity (30/46; 65%), white race (41/45; 91%) and receiving Medicaid (34/44, 77%). Many infected children had contact with dogs or cats. Ocular toxocariasis was associated with a lack of peripheral eosinophilia ( P < 0.001). No other Toxocara syndromes were associated with defined absolute eosinophil count levels. Post-treatment resolution of eosinophilia was variable, ranging from 1 to 172 weeks. A Toxocara hotspot was identified in northeast Houston, comprising one of the lowest median household incomes in the region. CONCLUSIONS: Toxocariasis is a devastating zoonotic infection in children living in the US. As it is not a reportable disease, the true burden remains unknown. It is critical to increase awareness of toxocariasis to direct public health interventions and ultimately reduce Toxocara -induced morbidity in US children.


Assuntos
Doenças do Gato , Doenças do Cão , Toxocaríase , Estados Unidos , Humanos , Criança , Animais , Gatos , Cães , Saúde Pública , Toxocaríase/epidemiologia , Hospitais Pediátricos , Estudos Soroepidemiológicos , Zoonoses/epidemiologia
19.
Inorg Chem ; 51(4): 2065-78, 2012 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-22289382

RESUMO

A mixed-valence complex, [Fe(III)Fe(II)L1(µ-OAc)(2)]BF(4)·H(2)O, where the ligand H(2)L1 = 2-{[[3-[((bis(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy-5-methylbenzyl](pyridin-2-ylmethyl)amino]methyl]phenol}, has been studied with a range of techniques, and, where possible, its properties have been compared to those of the corresponding enzyme system purple acid phosphatase. The Fe(III)Fe(II) and Fe(III)(2) oxidized species were studied spectroelectrochemically. The temperature-dependent population of the S = 3/2 spin states of the heterovalent system, observed using magnetic circular dichroism, confirmed that the dinuclear center is weakly antiferromagnetically coupled (H = -2JS(1)·S(2), where J = -5.6 cm(-1)) in a frozen solution. The ligand-to-metal charge-transfer transitions are correlated with density functional theory calculations. The Fe(III)Fe(II) complex is electron paramagnetic resonance (EPR)-silent, except at very low temperatures (<2 K), because of the broadening caused by the exchange coupling and zero-field-splitting parameters being of comparable magnitude and rapid spin-lattice relaxation. However, a phosphate-bound Fe(III)(2) complex showed an EPR spectrum due to population of the S(tot) = 3 state (J= -3.5 cm(-1)). The phosphatase activity of the Fe(III)Fe(II) complex in hydrolysis of bis(2,4-dinitrophenyl)phosphate (k(cat.) = 1.88 × 10(-3) s(-1); K(m) = 4.63 × 10(-3) mol L(-1)) is similar to that of other bimetallic heterovalent complexes with the same ligand. Analysis of the kinetic data supports a mechanism where the initiating nucleophile in the phosphatase reaction is a hydroxide, terminally bound to Fe(III). It is interesting to note that aqueous solutions of [Fe(III)Fe(II)L1(µ-OAc)(2)](+) are also capable of protein cleavage, at mild temperature and pH conditions, thus further expanding the scope of this complex's catalytic promiscuity.


Assuntos
Fosfatase Ácida/química , Compostos Férricos/química , Compostos Ferrosos/química , Glicoproteínas/química , Fosfatase Ácida/metabolismo , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Domínio Catalítico , Bovinos , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Compostos Férricos/metabolismo , Compostos Ferrosos/metabolismo , Glicoproteínas/metabolismo , Hidrólise , Modelos Moleculares , Piridinas/química , Piridinas/metabolismo , Soroalbumina Bovina/metabolismo
20.
Patient Educ Couns ; 105(10): 3134-3142, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688719

RESUMO

OBJECTIVES: The COVID-19 pandemic has significantly impacted oncology. With pandemic restrictions limiting close contact between individuals, telehealth (the use of teleconferencing/videoconferencing to conduct real-time medical consultations) has been increasingly utilised. This qualitative study aimed to explore adult cancer patient, caregiver, and clinician (doctor, nurse, allied health) telehealth experiences during COVID-19 in urban and rural Australian settings and identify potential enablers and barriers to sustained telehealth implementation. METHODS: English-speaking participants completed semi-structured interviews regarding their telehealth experiences since March 2020. Interviews ceased when data saturation occurred. Iterative thematic analysis was conducted using NVivo 12 Pro. RESULTS: Thirty-four interviews (clinician=14, patient=13, caregiver=7) were conducted from April to August 2021. Analysis generated seven themes relating to telehealth use: 1) Acceptability as a form of consultation, 2) Impacts on healthcare provision, 3) Communication & relationships, 4) Efficient form of consultation, 5) Comfort of conducting telehealth in different environments, 6) Technological barriers and 7) Future preferences. CONCLUSIONS: The rapid uptake of telehealth during the pandemic has mostly been well-received, and telehealth can be appropriately used in oncology. PRACTICE IMPLICATIONS: Barriers including providing appropriate facilities, technology, and telehealth training; and selecting appropriate patients must be addressed to enable sustained telehealth use in future cancer care.


Assuntos
COVID-19 , Neoplasias , Telemedicina , Adulto , Austrália , COVID-19/epidemiologia , Cuidadores , Humanos , Neoplasias/terapia , Pandemias
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