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1.
Prostate ; 84(7): 623-635, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38450798

RESUMO

BACKGROUND: There are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants. METHODS: In May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research. RESULTS: An increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups. CONCLUSIONS: There are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Reprodutibilidade dos Testes , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Próstata/patologia , Organoides/patologia , Xenoenxertos , Microambiente Tumoral
2.
Plant Physiol ; 175(1): 333-350, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28724622

RESUMO

Successful fertilization relies on the production and effective release of viable pollen. Failure of anther opening (dehiscence), results in male sterility, although the pollen may be fully functional. MYB26 regulates the formation of secondary thickening in the anther endothecium, which is critical for anther dehiscence and fertility. Here, we show that although the MYB26 transcript shows expression in multiple floral organs, the MYB26 protein is localized specifically to the anther endothecium nuclei and that it directly regulates two NAC domain genes, NST1 and NST2, which are critical for the induction of secondary thickening biosynthesis genes. However, there is a complex relationship of regulation between these genes and MYB26. Using DEX-inducible MYB26 lines and overexpression in the various mutant backgrounds, we have shown that MYB26 up-regulates both NST1 and NST2 expression. Surprisingly normal thickening and fertility rescue does not occur in the absence of MYB26, even with constitutively induced NST1 and NST2, suggesting an additional essential role for MYB26 in this regulation. Combined overexpression of NST1 and NST2 in myb26 facilitates limited ectopic thickening in the anther epidermis, but not in the endothecium, and thus fails to rescue dehiscence. Therefore, by a series of regulatory controls through MYB26, NST1, NST2, secondary thickening is formed specifically within the endothecium; this specificity is essential for anther opening.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo , Arabidopsis/citologia , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/citologia , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Epiderme Vegetal/citologia , Epiderme Vegetal/genética , Epiderme Vegetal/crescimento & desenvolvimento , Epiderme Vegetal/metabolismo , Pólen/citologia , Pólen/genética , Pólen/crescimento & desenvolvimento , Pólen/metabolismo , Fatores de Transcrição/genética
3.
Int J Lang Commun Disord ; 53(2): 218-227, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29159842

RESUMO

BACKGROUND: Clinical placements are crucial to the development of skills and competencies in speech-language pathology (SLP) education and, more generally, a requirement of all health professional training programmes. Literature from medical education provides a context for understanding how the environment can be vital to all students' learning. Given the increasing costs of education and demands on health services, students who struggle or fail on clinical placement place an additional burden on educators. Therefore, if more is known or understood about these students and their experience in relation to the clinical learning environment, appropriate strategies and support can be provided to reduce the burden. However, this literature does not specifically explore marginal or failing students and their experience. AIMS: To review existing research that has explored failing and struggling health professional students undertaking clinical placements and, in particular, SLP students. METHODS & PROCEDURES: A critical narrative review was undertaken. Three electronic databases, ProQuest, CINAHL and OVID (Medline 1948-), were searched for papers exploring marginal and failing students in clinical placement contexts across all health professions, published between 1988 and 2017. Data were extracted and examined to determine the breadth of the existing research, and publications were critically appraised and major research themes identified. MAIN CONTRIBUTION: Sixty-nine papers were included in the review. The majority came from medicine and nursing in the United States and United Kingdom, with other allied health disciplines less well represented. The review identified key themes with the majority of papers focused on identification of at risk students and support and remediation. The review also highlighted the absence of literature relating to the student voice and in the allied health professions. CONCLUSIONS & IMPLICATIONS: This review highlighted the limited research related to failing/struggling student learning in clinical contexts, and only a handful of papers have specifically addressed marginal or failing students in allied health professions. The complexity of interrelated factors in this field has been highlighted in this review. Further research needs to include the student's voice to develop greater understanding and insights of struggle and failure in clinical contexts.


Assuntos
Pessoal de Saúde/educação , Fracasso Acadêmico , Pessoal de Saúde/economia , Humanos , Patologia da Fala e Linguagem/educação
4.
New Phytol ; 213(2): 778-790, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27787905

RESUMO

Viable pollen is essential for plant reproduction and crop yield. Its production requires coordinated expression at specific stages during anther development, involving early meiosis-associated events and late pollen wall formation. The ABORTED MICROSPORES (AMS) transcription factor is a master regulator of sporopollenin biosynthesis, secretion and pollen wall formation in Arabidopsis. Here we show that it has complex regulation and additional essential roles earlier in pollen formation. An inducible-AMS reporter was created for functional rescue, protein expression pattern analysis, and to distinguish between direct and indirect targets. Mathematical modelling was used to create regulatory networks based on wild-type RNA and protein expression. Dual activity of AMS was defined by biphasic protein expression in anther tapetal cells, with an initial peak around pollen meiosis and then later during pollen wall development. Direct AMS-regulated targets exhibit temporal regulation, indicating that additional factors are associated with their regulation. We demonstrate that AMS biphasic expression is essential for pollen development, and defines distinct functional activities during early and late pollen development. Mathematical modelling suggests that AMS may competitively form a protein complex with other tapetum-expressed transcription factors, and that biphasic regulation is due to repression of upstream regulators and promotion of AMS protein degradation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Pólen/crescimento & desenvolvimento , Pólen/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Dexametasona/farmacologia , Fertilidade/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Modelos Biológicos , Mutação/genética , Pólen/efeitos dos fármacos , Pólen/genética , Ligação Proteica/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteínas Recombinantes de Fusão/metabolismo
5.
Plant Cell Rep ; 36(1): 81-87, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27662835

RESUMO

KEY MESSAGE: This study highlights the changes in umami-related nucleotide and glutamate levels when the AMP deaminase gene was elevated in transgenic tomato. Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour can be imparted by the presence of glutamate and is greatly enhanced by the addition of ribonucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP). The production of IMP is regulated by the enzyme adenosine monophosphate (AMP) deaminase which functions to convert AMP into IMP. We have generated transgenic tomato (Solanum lycopersicum) lines over expressing AMP deaminase under the control of a fruit-specific promoter. The transgenic lines showed substantially enhanced levels of AMP deaminase expression in comparison to the wild-type control. Elevated AMP deaminase levels resulted in the reduced accumulation of glutamate and increased levels of the umami nucleotide GMP. AMP concentrations were unchanged. The effects on the levels of glutamate and GMP were unexpected and are discussed in relation to the metabolite flux within this pathway.


Assuntos
AMP Desaminase/metabolismo , Metaboloma , Solanum lycopersicum/enzimologia , Paladar , Monofosfato de Adenosina/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Ácido Glutâmico/metabolismo , Guanosina Monofosfato/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Metaboloma/genética , Proteínas de Plantas , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Transgenes
6.
Brain Inj ; 31(13-14): 1889-1902, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28945465

RESUMO

BACKGROUND: There has been limited empirical speech-language pathology (SLP) study of language and cognitive communication during post-traumatic amnesia (PTA) and the early stages after TBI. The purpose of the current research was to explore the potential means and utility of assessing cognitive communication during PTA and the post-acute recovery period. METHOD: This research used a longitudinal mixed methods design to describe language and cognitive communication assessment and recovery profiles of three patients with TBI. Cognitive communication was assessed with repeated standardised and non-standardised methods during PTA (rated with Westmead PTA Scale) and at follow-up 3 months after PTA emergence. RESULTS: All participants demonstrated a profile of language and cognitive communication strengths and weaknesses during PTA and the post-acute period, also evident at follow-up. Improvement occurred gradually throughout PTA, although with individual fluctuation across test occasions. There was no marked change in communication function immediately before and after PTA emergence, indicating that cognitive communication ability and those functions measured on the Westmead PTA Scale (memory and orientation) did not recover at the same rate. CONCLUSION: It was feasible to assess language and cognitive communication throughout PTA and the post-acute period, and early assessment results were relevant to the patient's ongoing communicative function. It is suggested that early and repeated SLP assessment may contribute to the prediction of persisting cognitive communication issues.


Assuntos
Amnésia/complicações , Amnésia/etiologia , Lesões Encefálicas Traumáticas/complicações , Transtornos Cognitivos/etiologia , Transtornos da Comunicação/etiologia , Adulto , Feminino , Humanos , Testes de Linguagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índices de Gravidade do Trauma
7.
Brain Inj ; 31(10): 1320-1330, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28657359

RESUMO

BACKGROUND: Social communication impairment is a persisting and debilitating consequence of traumatic brain injury (TBI). However, there has been little empirical speech-language pathology (SLP) study focusing on the early stage of recovery after TBI, including during post-traumatic amnesia (PTA). This research reports on social communication presentation and recovery during late PTA and the post-acute period, assessed with standardized measures. METHOD: Using mixed-methods case study research, four participants with severe TBI were assessed with social communication assessment measures over the later stages of PTA and/or at PTA emergence, and at follow-up three months later. Assessment tools included the Measure of Cognitive Linguistic Abilities Family Questionnaire, the La Trobe Communication Questionnaire and The Profile of Pragmatic Impairment in Communication and included patient and friend/family perspectives. RESULTS: It was possible to identify a profile of social communication disorder on SLP measures for participants during PTA that persisted at follow-up, but with decreased severity. Self and friend/family member ratings of social communication indicated an increased awareness of social difficulty at three months after PTA emergence. CONCLUSION: Findings provided information about presentation and course of recovery of social communication ability for participants in the early stage of rehabilitation after TBI. These findings have implications for timing and methods of SLP assessment during PTA.


Assuntos
Amnésia/psicologia , Lesões Encefálicas Traumáticas/psicologia , Transtornos da Comunicação/diagnóstico , Comunicação , Comportamento Social , Adulto , Amnésia/etiologia , Lesões Encefálicas Traumáticas/complicações , Cognição/fisiologia , Transtornos da Comunicação/etiologia , Transtornos da Comunicação/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Patologia da Fala e Linguagem , Inquéritos e Questionários
8.
Plant Physiol ; 167(4): 1717-30, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25667314

RESUMO

Floral formation, in particular anther and pollen development, is a complex biological process with critical importance for seed set and for targeted plant breeding. Many key transcription factors regulating this process have been identified; however, their direct role remains largely unknown. Using publicly available gene expression data from Arabidopsis (Arabidopsis thaliana), focusing on those studies that analyze stamen-, pollen-, or flower-specific expression, we generated a network model of the global transcriptional interactions (FlowerNet). FlowerNet highlights clusters of genes that are transcriptionally coregulated and therefore likely to have interacting roles. Focusing on four clusters, and using a number of data sets not included in the generation of FlowerNet, we show that there is a close correlation in how the genes are expressed across a variety of conditions, including male-sterile mutants. This highlights the important role that FlowerNet can play in identifying new players in anther and pollen development. However, due to the use of general floral expression data in FlowerNet, it also has broad application in the characterization of genes associated with all aspects of floral development and reproduction. To aid the dissection of genes of interest, we have made FlowerNet available as a community resource (http://www.cpib.ac.uk/anther). For this resource, we also have generated plots showing anther/flower expression from a variety of experiments: These are normalized together where possible to allow further dissection of the resource.


Assuntos
Arabidopsis/genética , Bases de Dados Genéticas , Flores/genética , Regulação da Expressão Gênica de Plantas/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Análise por Conglomerados , Flores/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Análise de Sequência com Séries de Oligonucleotídeos , Pólen/genética , Pólen/crescimento & desenvolvimento , Reprodução , Fatores de Transcrição/genética
9.
Brain Inj ; 30(9): 1131-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27314438

RESUMO

PRIMARY OBJECTIVE: There have been few reports of the approaches taken by speech-language pathologists (SLPs) when assessing cognitive communication (CC) during post-traumatic amnesia (PTA) after TBI. This study sought to understand SLPs' rationales for CC assessment during PTA and to examine their perspectives on assessment methods during the early recovery period. METHODS AND PROCEDURES: In this qualitative study, 10 SLPs participated in semi-structured face-to-face or telephone interviews about their rationales and methods for CC assessment during PTA and early recovery. Content analysis was conducted using NVivo software to identify key categories. MAIN OUTCOME AND RESULTS: SLPs reported their reasons for CC assessment as including: (1) Documenting changes and monitoring progress, (2) Feedback to team, family and patient, (3) Diagnosis of communication disorder, (4) Planning and (5) Prognosis. They described conducting ongoing, informal assessment and monitoring of CC, using a combination of standardized and non-standardized measures during PTA, and commenced formal testing after PTA resolution to formulate a baseline level of communication function. CONCLUSIONS: The current study highlighted the importance that SLPs placed on an individualized approach in CC assessment. Findings provided insight into the process of assessment of CC during PTA and the early stage of recovery after TBI.


Assuntos
Amnésia Retrógrada/reabilitação , Atitude do Pessoal de Saúde , Lesões Encefálicas/reabilitação , Cognição , Comunicação , Patologia da Fala e Linguagem , Amnésia Retrógrada/etiologia , Lesões Encefálicas/complicações , Humanos , Pesquisa Qualitativa
10.
Clin Linguist Phon ; 30(7): 489-518, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27002416

RESUMO

This review examined previous research applications of linguistic discourse analysis to assess the language of adults with aphasia. A comprehensive literature search of seven databases identified 165 studies that applied linguistic measures to samples of discourse collected from people with aphasia. Analysis of methodological applications revealed an increase in published research using linguistic discourse analysis over the past 40 years, particularly to measure the generalisation of therapy outcomes to language in use. Narrative language samples were most frequently subject to analysis though all language genres were observed across included studies. A total of 536 different linguistic measures were applied to examine language behaviours. Growth in the research use of linguistic discourse analysis and suggestions that this growth may be reflected in clinical practice requires further investigation. Future research directions are discussed to investigate clinical use of discourse analysis and examine the differences that exist between research and clinical practice.


Assuntos
Afasia , Linguística , Projetos de Pesquisa , Humanos , Narração
11.
Plant Physiol ; 164(3): 1338-49, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24424320

RESUMO

The trans-Golgi network (TGN) plays a central role in cellular secretion and has been implicated in sorting cargo destined for the plasma membrane. Previously, the Arabidopsis (Arabidopsis thaliana) echidna (ech) mutant was shown to exhibit a dwarf phenotype due to impaired cell expansion. However, ech also has a previously uncharacterized phenotype of reduced male fertility. This semisterility is due to decreased anther size and reduced amounts of pollen but also to decreased pollen viability, impaired anther opening, and pollen tube growth. An ECH translational fusion (ECHPro:ECH-yellow fluorescent protein) revealed developmentally regulated tissue-specific expression, with expression in the tapetum during early anther development and microspore release and subsequent expression in the pollen, pollen tube, and stylar tissues. Pollen viability and production, along with germination and pollen tube growth, were all impaired. The ech anther endothecium secondary wall thickening also appeared reduced and disorganized, resulting in incomplete anther opening. This did not appear to be due to anther secondary thickening regulatory genes but perhaps to altered secretion of wall materials through the TGN as a consequence of the absence of the ECH protein. ECH expression is critical for a variety of aspects of male reproduction, including the production of functional pollen grains, their effective release, germination, and tube formation. These stages of pollen development are fundamentally influenced by TGN trafficking of hormones and wall components. Overall, this suggests that the fertility defect is multifaceted, with the TGN trafficking playing a significant role in the process of both pollen formation and subsequent fertilization.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Pólen/crescimento & desenvolvimento , Vesículas Secretórias/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Rede trans-Golgi/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclopentanos/farmacologia , Fertilidade/efeitos dos fármacos , Fertilidade/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Germinação/efeitos dos fármacos , Giberelinas/farmacologia , Ácidos Indolacéticos/farmacologia , Mutação/genética , Tamanho do Órgão/efeitos dos fármacos , Oxilipinas/farmacologia , Fenótipo , Pólen/anatomia & histologia , Pólen/citologia , Pólen/genética , Tubo Polínico/efeitos dos fármacos , Tubo Polínico/genética , Tubo Polínico/crescimento & desenvolvimento , Transporte Proteico/efeitos dos fármacos , Vesículas Secretórias/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Proteínas de Transporte Vesicular/genética , Rede trans-Golgi/efeitos dos fármacos
12.
Plant Cell ; 24(7): 2874-85, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22773749

RESUMO

Auxin transport, which is mediated by specialized influx and efflux carriers, plays a major role in many aspects of plant growth and development. AUXIN1 (AUX1) has been demonstrated to encode a high-affinity auxin influx carrier. In Arabidopsis thaliana, AUX1 belongs to a small multigene family comprising four highly conserved genes (i.e., AUX1 and LIKE AUX1 [LAX] genes LAX1, LAX2, and LAX3). We report that all four members of this AUX/LAX family display auxin uptake functions. Despite the conservation of their biochemical function, AUX1, LAX1, and LAX3 have been described to regulate distinct auxin-dependent developmental processes. Here, we report that LAX2 regulates vascular patterning in cotyledons. We also describe how regulatory and coding sequences of AUX/LAX genes have undergone subfunctionalization based on their distinct patterns of spatial expression and the inability of LAX sequences to rescue aux1 mutant phenotypes, respectively. Despite their high sequence similarity at the protein level, transgenic studies reveal that LAX proteins are not correctly targeted in the AUX1 expression domain. Domain swapping studies suggest that the N-terminal half of AUX1 is essential for correct LAX localization. We conclude that Arabidopsis AUX/LAX genes encode a family of auxin influx transporters that perform distinct developmental functions and have evolved distinct regulatory mechanisms.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Transporte Biológico , Padronização Corporal , Cotilédone/citologia , Cotilédone/genética , Cotilédone/crescimento & desenvolvimento , Cotilédone/metabolismo , Técnicas de Inativação de Genes , Proteínas de Membrana Transportadoras/genética , Família Multigênica , Mutagênese Insercional , Fenótipo , Raízes de Plantas/citologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Feixe Vascular de Plantas/citologia , Feixe Vascular de Plantas/genética , Feixe Vascular de Plantas/crescimento & desenvolvimento , Feixe Vascular de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plântula/citologia , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
13.
Clin Linguist Phon ; 29(2): 85-101, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25216374

RESUMO

Decline in linguistic function has been associated with decline in cognitive function in previous research. This research investigated the informativeness of written language samples of Australian men from the Health in Men's Study (HIMS) aged from 76 to 93 years using the Computerised Propositional Idea Density Rater (CPIDR 5.1). In total, 60,255 words in 1147 comments were analysed using a linear-mixed model for statistical analysis. Results indicated no relationship with education level (p = 0.79). Participants for whom English was not their first learnt language showed Propositional Idea Density (PD) scores slightly lower (0.018 per 1 word). Mean PD per 1 word for those for whom English was their first language for comments below 60 words was 0.494 and above 60 words 0.526. Text length was found to have an effect (p = <0.0001). The mean PD was higher than previously reported for men and lower than previously reported for a similar cohort for Australian women.


Assuntos
Diagnóstico por Computador , Transtornos da Linguagem/diagnóstico , Testes de Linguagem , Linguística , Redação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Escolaridade , Humanos , Masculino , Multilinguismo , Semântica , Fatores Sexuais , Software , Acidente Vascular Cerebral/diagnóstico , Austrália Ocidental
14.
New Phytol ; 201(3): 825-836, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24400898

RESUMO

Excessive gibberellin (GA) signalling, mediated through the DELLA proteins, has a negative impact on plant fertility. Loss of DELLA activity in the monocot rice (Oryza sativa) causes complete male sterility, but not in the dicot model Arabidopsis (Arabidopsis thaliana) ecotype Landsberg erecta (Ler), in which DELLA function has been studied most extensively, leading to the assumption that DELLA activity is not essential for Arabidopsis pollen development. A novel DELLA fertility phenotype was identified in the Columbia (Col-0) ecotype that necessitates re-evaluation of the general conclusions drawn from Ler. Fertility phenotypes were compared between the Col-0 and Ler ecotypes under conditions of chemical and genetic GA overdose, including mutants in both ecotypes lacking the DELLA paralogues REPRESSOR OF ga1-3 (RGA) and GA INSENSITIVE (GAI). Ler displays a less severe fertility phenotype than Col-0 under GA treatment. Col-0 rga gai mutants, in contrast with the equivalent Ler phenotype, were entirely male sterile, caused by post-meiotic defects in pollen development, which were rescued by the reintroduction of DELLA into either the tapetum or developing pollen. We conclude that DELLA activity is essential for Arabidopsis pollen development. Differences between the fertility responses of Col-0 and Ler might be caused by differences in downstream signalling pathways or altered DELLA expression.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Ecótipo , Pólen/crescimento & desenvolvimento , Pólen/metabolismo , Proteínas Repressoras/metabolismo , Arabidopsis/citologia , Proteínas de Arabidopsis/genética , Teste de Complementação Genética , Meiose , Mutação/genética , Infertilidade das Plantas , Pólen/citologia , Proteínas Repressoras/genética
15.
Brain Inj ; 28(13-14): 1657-66, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25158134

RESUMO

PRIMARY OBJECTIVE: This study's objective was to examine the current assessment practices of SLPs working with adults with acquired cognitive communication impairments following a TBI. METHODS AND PROCEDURES: Two hundred and sixty-five SLPs from the UK, the US, Canada, Australia and New Zealand responded to the online survey stating the areas of communication frequently assessed and the assessment tools they use. MAIN OUTCOMES AND RESULTS: SLPs reported that they routinely assessed functional communication (78.8%), whereas domains such as discourse were routinely assessed by less than half of the group (44.3%). Clinicians used aphasia and cognitive communication/high level language tools and tools assessing functional performance, discourse, pragmatic skills or informal assessments were used by less than 10% of the group. The country and setting of service delivery influenced choice of assessment tools used in clinical practice. CONCLUSIONS: These findings have implications for training of SLPs in a more diverse range of assessment tools for this clinical group. The findings raise questions regarding the statistical validity and reliability of assessments currently used in clinical practice. It highlights the need for further research into how SLPs can be supported in translating current evidence about the use of assessment tools into clinical practice.


Assuntos
Atividades Cotidianas , Afasia/reabilitação , Atitude do Pessoal de Saúde , Lesões Encefálicas/reabilitação , Cognição , Atividades Cotidianas/psicologia , Adulto , Afasia/etiologia , Afasia/fisiopatologia , Austrália , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Canadá , Protocolos Clínicos , Feminino , Pesquisas sobre Atenção à Saúde , Letramento em Saúde , Humanos , Masculino , Nova Zelândia , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes , Comportamento Social , Patologia da Fala e Linguagem , Reino Unido , Estados Unidos
16.
PLoS One ; 19(5): e0297675, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728263

RESUMO

BACKGROUND: Physical activity (PA) declines with age despite the knowledge that physical inactivity is a leading cause of disease, death, and disability worldwide. To better tailor PA interventions to older adults, researchers are turning to the collaborative principles of co-design. The purpose of this systematic review was to compare the effectiveness of co-designed PA interventions and standard care for increasing PA and other health outcomes (i.e., physical function, quality of life, mental health, functional independence, attendance and attrition rates) in older adults. METHODS: A search was conducted in MEDLINE, AgeLine, CINAHL, Embase, and SPORTDiscus. Records were screened by independent pairs of reviewers. Primary research studies conducted among community-dwelling older adults (age 60+) comparing co-designed PA interventions to standard care were considered for inclusion. Controls included wait-list control, usual care, sham interventions, PA interventions without the use of co-design, and no intervention. A random effects meta-analysis was conducted, and the standardized mean difference (SMD) was used to report effect estimates. Quality of evidence was rated using GRADE. RESULTS: Of 16,191 studies screened, eight (N = 16,733) were included in this review. Most studies reported results favouring the effect of co-design on physical activity; however, only two studies (N = 433) could be pooled for meta-analysis resulting in a SMD of 0.28, (95% CI = -0.13 to 0.69; p = 0.19; I2 = 56%) immediately post-intervention. The GRADE quality of evidence was very low. The quantitative analysis of three studies reported improved physical function. CONCLUSION: This review did not demonstrate that co-designed PA interventions are more effective than standard care for increasing PA in older adults; however, evidence was limited and of very low quality. Further well-designed trials are warranted to better understand the impacts of co-designed PA interventions and how to best implement them into practice. TRIAL REGISTRATION: PROSPERO registration number: CRD42022314217.


Assuntos
Exercício Físico , Qualidade de Vida , Humanos , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Saúde Mental
17.
Brain Inj ; 27(7-8): 819-30, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23758272

RESUMO

PRIMARY OBJECTIVE: To investigate speech pathologists' current practice with adults who are in post-traumatic amnesia (PTA). METHOD: Speech pathologists with experience of adults in PTA were invited to take part in an online survey through Australian professional email/internet-based interest groups. RESULTS: Forty-five speech pathologists responded to the online survey. The majority of respondents (78%) reported using informal, observational assessment methods commencing at initial contact with people in PTA or when patients' level of alertness allowed and initiating formal assessment on emergence from PTA. Seven respondents (19%) reported undertaking no assessment during PTA. Clinicians described using a range of techniques to monitor cognitive-communication during PTA, including static, dynamic, functional and impairment-based methods. CONCLUSIONS: The study confirmed that speech pathologists have a key role in the multidisciplinary team caring for the person in PTA, especially with family education and facilitating interactions with the rehabilitation team and family. Decision-making around timing and means of assessment of cognitive-communication during PTA appeared primarily reliant on speech pathologists' professional experience and the culture of their workplace. The findings support the need for further research into the nature of cognitive-communication disorder and resolution over this period.


Assuntos
Amnésia Retrógrada/terapia , Lesões Encefálicas/complicações , Transtornos de Deglutição/terapia , Disartria/terapia , Fonoterapia , Patologia da Fala e Linguagem , Amnésia Retrógrada/etiologia , Amnésia Retrógrada/fisiopatologia , Amnésia Retrógrada/reabilitação , Atitude do Pessoal de Saúde , Austrália/epidemiologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/psicologia , Lesões Encefálicas/reabilitação , Lesões Encefálicas/terapia , Comunicação , Transtornos da Comunicação/etiologia , Transtornos da Comunicação/terapia , Tomada de Decisões , Transtornos de Deglutição/etiologia , Progressão da Doença , Disartria/etiologia , Feminino , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Equipe de Assistência ao Paciente , Papel Profissional , Recuperação de Função Fisiológica , Patologia da Fala e Linguagem/métodos , Patologia da Fala e Linguagem/tendências
18.
Int J Lang Commun Disord ; 48(1): 102-14, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23317388

RESUMO

BACKGROUND: Aphasiologists often research, assess and treat linguistic impairment and its consequences for daily life separately. Studies that link the language used by people with aphasia to routine communicative activities may expand the linguistic forms treated as relevant for successful communication by people with aphasia. Previous research has suggested that initiating topics in conversation can be problematic for people with aphasia, but it has not been widely investigated. AIMS: This paper uses Conversation Analysis to examine how a person with aphasia initiated topics in everyday conversation. It describes the utility of and-prefacing for topic initiation. METHODS & PROCEDURES: A person with chronic aphasia ('Valerie') was recruited to participate and was video-recorded speaking with four conversation partners. Approximately 3.5 h of recordings were collected, and transcribed according to conversation analytic conventions. Topic initiations in this data set were identified and analysed using conversation analytic procedures. OUTCOMES & RESULTS: It was found that topic initiations often led to trouble, and that Valerie recurrently used and-prefaced turns when initiating topics (e.g. and how was your turkey?). This paper argues that and-prefacing was an advantageous method for initiating topics because it smoothed the conversational discontinuities that this action creates. CONCLUSIONS & IMPLICATIONS: These findings are consistent with previous observations about the hazardousness of topic initiation for people with aphasia. Valerie's use of and-prefacing suggests that conjunctions and other turn prefaces may be useful for promoting successful communication by people with aphasia during everyday conversation. Future investigation should identify if and how other people with aphasia use turn prefacing when initiating topics, and whether this changes over time.


Assuntos
Afasia/diagnóstico , Transtornos da Comunicação/diagnóstico , Relações Interpessoais , Comportamento Verbal , Idoso de 80 Anos ou mais , Afasia/terapia , Transtornos da Comunicação/terapia , Compreensão , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Testes Neuropsicológicos , Casas de Saúde , Semântica , Percepção da Fala , Medida da Produção da Fala , Gravação em Vídeo
19.
Clin Cancer Res ; 29(15): 2933-2943, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37223924

RESUMO

PURPOSE: Patients with neuroendocrine prostate cancer (NEPC) are often managed with immunotherapy regimens extrapolated from small-cell lung cancer (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared with other prostate cancer types and SCLC. EXPERIMENTAL DESIGN: In this retrospective study, a cohort of 170 patients with 230 RNA-sequencing and 104 matched whole-exome sequencing data were analyzed. Differences in immune and stromal constituents, frequency of genomic alterations, and associations with outcomes were evaluated. RESULTS: In our cohort, 36% of the prostate tumors were identified as CD8+ T-cell inflamed, whereas the remaining 64% were T-cell depleted. T-cell-inflamed tumors were enriched in anti-inflammatory M2 macrophages and exhausted T cells and associated with shorter overall survival relative to T-cell-depleted tumors (HR, 2.62; P < 0.05). Among all prostate cancer types in the cohort, NEPC was identified to be the most immune depleted, wherein only 9 out of the 36 total NEPC tumors were classified as T-cell inflamed. These inflamed NEPC cases were enriched in IFN gamma signaling and PD-1 signaling compared with other NEPC tumors. Comparison of NEPC with SCLC revealed that NEPC had poor immune content and less mutations compared with SCLC, but expression of checkpoint genes PD-L1 and CTLA-4 was comparable between NEPC and SCLC. CONCLUSIONS: NEPC is characterized by a relatively immune-depleted tumor immune microenvironment compared with other primary and metastatic prostate adenocarcinoma except in a minority of cases. These findings may inform development of immunotherapy strategies for patients with advanced prostate cancer.


Assuntos
Carcinoma Neuroendócrino , Tumores Neuroendócrinos , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/metabolismo , Carcinoma Neuroendócrino/patologia , Microambiente Tumoral/genética
20.
Int J Lang Commun Disord ; 47(5): 511-21, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22938062

RESUMO

BACKGROUND: Aphasia affects family members in addition to the individuals with the communication disorder. In order to develop appropriate services for the relatives of people with aphasia post-stroke, their rehabilitation goals need to be identified. AIM: The aim of the current investigation was to identify the rehabilitation goals that family members of individuals with aphasia have for themselves. METHODS & PROCEDURES: Forty-eight family members of adults with aphasia post-stroke participated in in-depth semi-structured interviews to identify the rehabilitation goals they had for themselves. All the interviews were transcribed verbatim and analysed using qualitative content analysis. OUTCOMES & RESULTS: Analysis revealed seven categories of goals that the family members had for themselves: to be included in rehabilitation, to be provided with hope and positivity, to be able to communicate and maintain their relationship with the person with aphasia, to be given information, to be given support, to look after their own well-being, and to be able to cope with new responsibilities. A few participants reported that, at certain times during the rehabilitation process, they did not have any goals for themselves. CONCLUSIONS & IMPLICATIONS: This study highlights that family members of individuals with aphasia have a number of aphasia-related rehabilitation goals for themselves. In order to provide a family-centred approach to rehabilitation, health professionals, including speech-language pathologists, need systematically to identify and address family members' goals in light of the categories revealed in this investigation.


Assuntos
Afasia/reabilitação , Cuidadores/psicologia , Família/psicologia , Avaliação das Necessidades , Reabilitação do Acidente Vascular Cerebral , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Narração , Relações Profissional-Família , Pesquisa Qualitativa , Apoio Social
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