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  • 1
    In: Journal of Neurochemistry, Wiley, Vol. 103, No. 3 ( 2007-11), p. 1228-1236
    Abstract: Tau is a microtubule‐associated protein that is important for establishing and maintaining neuronal morphology. In addition to its role in normal cells, tau protein is involved in many neurodegenerative diseases, e.g. Alzheimer’s disease (AD) and frontotemporal dementia, as the main component of intraneuronal aggregates. Alternative splicing of tau gene in the brain can give rise to at least six protein variants. A causative role of skewed tau exon 10 inclusion has been defined in frontotemporal dementia; however, no link was established between the aberrant splicing of tau and AD. Here, we applied a single‐molecule‐based technology, polymerase colony or polony , to simultaneously monitor tau splicing variant and haplotype profile in sporadic AD and normal brains. We found that the coordinated expression of tau exons 2 and 10 is altered in AD. Additional investigations of cis and trans mechanisms of this observation revealed a decreased protein expression of a known tau splicing factor, htra2‐beta‐1 in AD, thereby implicating a trans mechanism. Our results demonstrate that dysregulation of combinatorial splicing might serve as a signature for aging‐related diseases, and the polony assay could be widely adapted for the study of other tauopathies. Furthermore, splicing‐based therapeutics is an emerging area of drug development, and a well‐defined and quantitative assay for monitoring single‐gene transcriptome will be relevant for such development.
    Type of Medium: Online Resource
    ISSN: 0022-3042 , 1471-4159
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2007
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  • 2
    In: Journal of Surgical Oncology, Wiley, Vol. 117, No. 5 ( 2018-04), p. 1020-1028
    Abstract: Age and frailty have been correlated with poor clinical outcomes in cancer. Core muscle index (CMI) and nutritional status are integral in assessing frailty. We explored the effect of pre‐operative serum albumin and body composition on clinical outcomes in patients with epithelial ovarian cancer (EOC). Methods We identified stage III‐IV EOC patients undergoing primary cytoreductive surgery from 2007 to 2015. Data were abstracted from medical records. Body composition measurements were obtained from pre‐operative imaging. Psoas muscle cross‐sectional area was normalized to height 2 to determine CMI. Sarcopenia was defined as CMI below the population mean. The influence of sarcopenia on short‐term morbidity was evaluated. Relationships among body composition measurements and albumin were assessed with Spearman correlations. Patient characteristics and body composition measurements between patients with and without sarcopenia were compared with parametric and non‐parametric statistical methods. Kaplan‐Meier survival curves were compared using log‐rank. Results 102 women met inclusion criteria. Sarcopenia correlated with albumin ( P  = 0.0002). Sarcopenia was not associated with short‐term morbidity or time to recurrence. Sarcopenia was associated with nearly a fourfold increased risk of death when hypoalbuminemia was present ( P  = 0.02). Conclusions Pre‐operative sarcopenia in combination with hypoalbuminemia was associated with significantly worse survival.
    Type of Medium: Online Resource
    ISSN: 0022-4790 , 1096-9098
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1475314-5
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  • 3
    In: Global Ecology and Biogeography, Wiley, Vol. 31, No. 10 ( 2022-10), p. 2085-2104
    Abstract: After environmental disasters, species with large population losses may need urgent protection to prevent extinction and support recovery. Following the 2019–2020 Australian megafires, we estimated population losses and recovery in fire‐affected fauna, to inform conservation status assessments and management. Location Temperate and subtropical Australia. Time period 2019–2030 and beyond. Major taxa Australian terrestrial and freshwater vertebrates; one invertebrate group. Methods From 〉  1,050 fire‐affected taxa, we selected 173 whose distributions substantially overlapped the fire extent. We estimated the proportion of each taxon’s distribution affected by fires, using fire severity and aquatic impact mapping, and new distribution mapping. Using expert elicitation informed by evidence of responses to previous wildfires, we estimated local population responses to fires of varying severity. We combined the spatial and elicitation data to estimate overall population loss and recovery trajectories, and thus indicate potential eligibility for listing as threatened, or uplisting, under Australian legislation. Results We estimate that the 2019–2020 Australian megafires caused, or contributed to, population declines that make 70–82 taxa eligible for listing as threatened; and another 21–27 taxa eligible for uplisting. If so‐listed, this represents a 22–26% increase in Australian statutory lists of threatened terrestrial and freshwater vertebrates and spiny crayfish, and uplisting for 8–10% of threatened taxa. Such changes would cause an abrupt worsening of underlying trajectories in vertebrates, as measured by Red List Indices. We predict that 54–88% of 173 assessed taxa will not recover to pre‐fire population size within 10 years/three generations. Main conclusions We suggest the 2019–2020 Australian megafires have worsened the conservation prospects for many species. Of the 91 taxa recommended for listing/uplisting consideration, 84 are now under formal review through national processes. Improving predictions about taxon vulnerability with empirical data on population responses, reducing the likelihood of future catastrophic events and mitigating their impacts on biodiversity, are critical.
    Type of Medium: Online Resource
    ISSN: 1466-822X , 1466-8238
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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    detail.hit.zdb_id: 2021283-5
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  • 4
    In: Global Change Biology, Wiley, Vol. 27, No. 15 ( 2021-08), p. 3432-3447
    Abstract: Marine reserves are a key tool for the conservation of marine biodiversity, yet only ~2.5% of the world's oceans are protected. The integration of marine reserves into connected networks representing all habitats has been encouraged by international agreements, yet the benefits of this design has not been tested empirically. Australia has one of the largest systems of marine reserves, providing a rare opportunity to assess how connectivity influences conservation success. An Australia‐wide dataset was collected using baited remote underwater video systems deployed across a depth range from 0 to 100 m to assess the effectiveness of marine reserves for protecting teleosts subject to commercial and recreational fishing. A meta‐analytical comparison of 73 fished species within 91 marine reserves found that, on average, marine reserves had 28% greater abundance and 53% greater biomass of fished species compared to adjacent areas open to fishing. However, benefits of protection were not observed across all reserves (heterogeneity), so full subsets generalized additive modelling was used to consider factors that influence marine reserve effectiveness, including distance‐based and ecological metrics of connectivity among reserves. Our results suggest that increased connectivity and depth improve the aforementioned marine reserve benefits and that these factors should be considered to optimize such benefits over time. We provide important guidance on factors to consider when implementing marine reserves for the purpose of increasing the abundance and size of fished species, given the expected increase in coverage globally. We show that marine reserves that are highly protected (no‐take) and designed to optimize connectivity, size and depth range can provide an effective conservation strategy for fished species in temperate and tropical waters within an overarching marine biodiversity conservation framework.
    Type of Medium: Online Resource
    ISSN: 1354-1013 , 1365-2486
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 5
    In: International Journal of Cancer, Wiley, Vol. 135, No. 5 ( 2014-09), p. 1110-1118
    Abstract: What's new? Based on a large genome‐wide scan of DNA methylation, this study reports that global DNA methylation patterns can robustly segregate tumor and non‐malignant pancreata. Cancer methylation also affects key pathways in pancreatic carcinogenesis, including TGF‐β, WNT, and axon guidance signaling. This study confirms that methylation plays an important role in the development and progression of pancreatic cancer, with implications for both ongoing research and therapeutic development.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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    detail.hit.zdb_id: 1474822-8
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  • 6
    In: Molecular Oncology, Wiley, Vol. 16, No. 1 ( 2022-01), p. 104-115
    Abstract: This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi‐omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA‐Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP‐selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow‐up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11–22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan‐based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan‐based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2322586-5
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  • 7
    In: Journal of Bone and Mineral Research, Wiley, Vol. 33, No. 8 ( 2018-08), p. 1435-1443
    Abstract: Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low‐trauma non‐VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non‐VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z ‐score predicted both VF and non‐VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2] , p  = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0] , p  = 0.01). VF and low LS BMD Z ‐score at baseline as well as glucocorticoid exposure predicted incident VF and non‐VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 8
    In: Conservation Biology, Wiley, Vol. 36, No. 2 ( 2022-04)
    Abstract: Las pesquerías marinas de los ecosistemas costeros en muchas áreas del mundo históricamente han removido a individuos de gran tamaño, potencialmente perjudicando el funcionamiento ambiental y la sostenibilidad a largo plazo de las poblaciones de peces. Los reportes sobre los indicadores basados en el tamaño que se vinculan con la estructura de la red alimenticia pueden contribuir al manejo basado en el ecosistema, aunque la aplicación de estos indicadores a grandes (inter‐ecosistemas) escalas geográficas ha estado limitada a datos de captura dependientes de las pesquerías o métodos basados en el buceo restringidos a aguas someras ( 〈 20 m), lo cual puede representar erróneamente la abundancia de peces de gran tamaño capturados para la pesca. Obtuvimos los datos de la estructura del tamaño corporal de 82 teleósteos marinos demersales focalizados por razones recreativas o comerciales tomados de 2,904 despliegues de video estéreo subacuático remoto con cebo (stereo‐BRUV, en inglés). El muestreo se realizó hasta los 50 metros de profundidad y abarcó aproximadamente 10,000 km del talud continental de Australia. El relieve marino, la profundidad del agua y la gravedad humana (es decir, un indicador de los impactos humanos) fueron los pronosticadores más sólidos de la probabilidad de incidencia de los peces de gran tamaño y de la abundancia de peces por encima del tamaño legal mínimo de captura. Las reservas marinas de protección total tienen un efecto positivo sobre la abundancia de los peces que están por encima del tamaño legal, aunque el efecto varió según el grupo de especies. Como contraste, los peces de tamaño sublegal fueron pronosticados de mejor manera usando gradientes de la temperatura de la superficie marina (media y varianza). En las áreas con un impacto humano reducido, los peces de gran tamaño corporal tenían hasta tres veces mayor probabilidad de aparecer y los peces de tamaño legal eran aproximadamente cinco veces más abundantes. Para los grupos de especies conspicuas con afinidades contrastantes de hábitat, ambiente y biogeografía, la abundancia de peces de tamaño legal normalmente declinó conforme aumentó el impacto humano. Nuestros análisis cuantitativos a gran escala resaltan la importancia conjunta que tienen la complejidad marina, las regiones con una huella humana reducida y las reservas marinas de protección total para la protección de los peces de gran tamaño corporal en una extensa gama de especies y configuraciones ecosistémicas. Efectos de la Huella Humana y los Factores Biofísicos sobre la Estructura del Tamaño Corporal de Especies Marinas Capturadas para la Pesca
    Type of Medium: Online Resource
    ISSN: 0888-8892 , 1523-1739
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2020041-9
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  • 9
    In: Journal of Bone and Mineral Research, Wiley, Vol. 38, No. 8 ( 2023-08), p. 1104-1115
    Abstract: Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one‐time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty‐six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z ‐scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (−1.09 ± 1.53 versus −1.27 ± 1.25, p  = 0.549). LS BMD Z ‐scores declined from baseline to 12 months in children with ON (−0.31 ± 1.02) but not in those without (0.13 ± 0.82, p  = 0.035); the hip BMD Z ‐scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (−1.77 ± 1.22) compared to those without (−1.03 ± 1.07, p  = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z ‐scores were lower in children with ON (hip −0.98 ± 0.95 versus −0.28 ± 1.06, p  = 0.010; TB −1.36 ± 1.10 versus −0.48 ± 1.50, p  = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p  = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI] , 1.15–2.13; p  = 0.004), and hip BMD Z ‐score at MRI (OR 2.23; 95% CI, 1.02–4.87; p  = 0.046) were independently associated with ON. Overall, one‐third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z ‐scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z ‐scores at MRI were significantly associated with prevalent, off‐therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2008867-X
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  • 10
    In: American Journal of Botany, Wiley, Vol. 91, No. 10 ( 2004-10), p. 1446-1480
    Abstract: Based on an overview of progress in molecular systematics of the true fungi (Fungi/Eumycota) since 1990, little overlap was found among single‐locus data matrices, which explains why no large‐scale multilocus phylogenetic analysis had been undertaken to reveal deep relationships among fungi. As part of the project “Assembling the Fungal Tree of Life” (AFTOL), results of four Bayesian analyses are reported with complementary bootstrap assessment of phylogenetic confidence based on (1) a combined two‐locus data set (nucSSU and nucLSU rDNA) with 558 species representing all traditionally recognized fungal phyla (Ascomycota, Basidiomycota, Chytridiomycota, Zygomycota) and the Glomeromycota, (2) a combined three‐locus data set (nucSSU, nucLSU, and mitSSU rDNA) with 236 species, (3) a combined three‐locus data set (nucSSU, nucLSU rDNA, and RPB2 ) with 157 species, and (4) a combined four‐locus data set (nucSSU, nucLSU, mitSSU rDNA, and RPB2 ) with 103 species. Because of the lack of complementarity among single‐locus data sets, the last three analyses included only members of the Ascomycota and Basidiomycota. The four‐locus analysis resolved multiple deep relationships within the Ascomycota and Basidiomycota that were not revealed previously or that received only weak support in previous studies. The impact of this newly discovered phylogenetic structure on supraordinal classifications is discussed. Based on these results and reanalysis of subcellular data, current knowledge of the evolution of septal features of fungal hyphae is synthesized, and a preliminary reassessment of ascomal evolution is presented. Based on previously unpublished data and sequences from GenBank, this study provides a phylogenetic synthesis for the Fungi and a framework for future phylogenetic studies on fungi.
    Type of Medium: Online Resource
    ISSN: 0002-9122 , 1537-2197
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 2053581-8
    SSG: 12
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