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1.
Plant Dis ; 108(7): 1993-1999, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38213117

RESUMO

The root-lesion nematode, Pratylenchus penetrans, is a ubiquitous parasite of roots of temperate fruit trees. It affects early growth of trees replanted into former orchard sites where populations have built up and may contribute to decline complexes of older trees. Most British Columbia, Canada, apple acreage is planted with M.9 rootstock, but growers are increasingly considering Geneva-series rootstocks such as G.41 and G.935. Among these rootstocks, responses to P. penetrans, specifically, are poorly known. To compare the resistance and tolerance to P. penetrans of G.41, G.935, and M.9 rootstocks ('Ambrosia' scion), a field microplot experiment was established in spring of 2020 at the Summerland Research and Development Centre. The experimental design was a two by three factorial combination of: P. penetrans inoculation (+/-) and rootstock (G.41, G.935, and M.9), with 20 replicate microplots of each of the six treatment combinations arranged in a randomized complete block design. The P. penetrans inoculum was 5,400 nematodes per microplot (54 P. penetrans liter-1 soil), which is below commonly accepted damage thresholds. Though P. penetrans population densities were lower for the G.41 rootstock by the end of the 2021 growing season, the effects of P. penetrans were similar among rootstocks. In the establishment year (2020), P. penetrans caused significant reductions in aboveground growth. In 2021, shoot growth and root weight were reduced by P. penetrans. The nematode also reduced rates of leaf gas exchange and stem water potential. These data suggest that while G.41 and G.935 may have other horticultural benefits over M.9, they are equally susceptible to P. penetrans at the early stages of tree growth.


Assuntos
Malus , Doenças das Plantas , Raízes de Plantas , Animais , Malus/parasitologia , Raízes de Plantas/parasitologia , Doenças das Plantas/parasitologia , Tylenchoidea/fisiologia
2.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000244

RESUMO

Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6-mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.


Assuntos
Canabidiol , Pele , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Humanos , Pele/metabolismo , Pele/efeitos dos fármacos , Camundongos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico
3.
Genes Chromosomes Cancer ; 62(10): 589-596, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37222498

RESUMO

BACKGROUND: Approximately half of ovarian tumors have defects within the homologous recombination repair pathway. Tumors carrying pathogenic variants (PVs) in BRCA1/BRCA2 are more likely to respond to poly-ADP ribose polymerase (PARP) inhibitor treatment. Large rearrangements (LRs) are a challenging class of variants to identify and characterize in tumor specimens and may therefore be underreported. This study describes the prevalence of pathogenic BRCA1/BRCA2 LRs in ovarian tumors and discusses the importance of their identification using a comprehensive testing strategy. METHODS: Sequencing and LR analyses of BRCA1/BRCA2 were conducted in 20 692 ovarian tumors received between March 18, 2016 and February 14, 2023 for MyChoice CDx testing. MyChoice CDx uses NGS dosage analysis to detect LRs in BRCA1/BRCA2 genes using dense tiling throughout the coding regions and limited flanking regions. RESULTS: Of the 2217 PVs detected, 6.3% (N = 140) were LRs. Overall, 0.67% of tumors analyzed carried a pathogenic LR. The majority of detected LRs were deletions (89.3%), followed by complex LRs (5.7%), duplications (4.3%), and retroelement insertions (0.7%). Notably, 25% of detected LRs encompassed a single or partial single exon. This study identified 84 unique LRs, 2 samples each carried 2 unique LRs in the same gene. We identified 17 LRs that occurred in multiple samples, some of which were specific to certain ancestries. Several cases presented here illustrate the intricacies involved in characterizing LRs, particularly when multiple events occur within the same gene. CONCLUSIONS: Over 6% of PVs detected in the ovarian tumors analyzed were LRs. It is imperative for laboratories to utilize testing methodologies that will accurately detect LRs at a single exon resolution to optimize the identification of patients who may benefit from PARP inhibitor treatment.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Proteína BRCA1/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteína BRCA2/genética , Genes BRCA2 , Rearranjo Gênico , Reparo do DNA , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias da Mama/genética , Mutação em Linhagem Germinativa
4.
J Cell Biochem ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33876852

RESUMO

The American Cancer Society predicted more than 52 000 new cases of thyroid cancer in 2020, making it the most prevalent endocrine malignancy. Due to the approximately threefold higher incidence of thyroid cancer in women, we hypothesize that androgens and/or androgen receptors play a protective role and that thyroid cancer in men represents an escape from androgen-mediated cell regulation. The analysis of androgen receptor (AR) expression in patient tissue samples identified a 2.7-fold reduction in AR expression (p < 0.005) in papillary thyroid cancer compared with matched, normal tissue. An in vitro cell model was developed by stably transfecting AR into 8505C undifferentiated thyroid cancer cells (resulting in clone 84E7). The addition of DHT to the clone 84E7 resulted in AR translocation into the nucleus and a 70% reduction in proliferation, with a shift in the cell cycle toward G1 arrest. RNASeq analysis revealed significant changes in mRNA levels associated with proliferation, cell cycle, and cell cycle regulation. Furthermore, androgen significantly decreased the levels of the G1-associated cell cycle progression proteins cdc25a CDK6 CDK4 and CDK2 as well as increased the levels of the cell cycle inhibitors, p27 and p21. The data strongly suggest that DHT induces a G1 arrest in androgen-responsive thyroid cancer cells. Together, these data support our hypothesis that AR/androgen may play a protective, antiproliferative role and are consistent with younger men having a lower incidence of thyroid cancer than women.

5.
Glob Chang Biol ; 27(16): 3898-3910, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33993596

RESUMO

Over the last 200 years, conversion of non-cultivated land for agriculture has substantially reduced global soil organic carbon (SOC) stocks in upper soil layers. Nevertheless, practices such as no- or reduced tillage, application of organic soil amendments, and maintenance of continuous cover can increase SOC in agricultural fields. While these management practices have been well studied, the effects on SOC of cropping systems that incorporate irrigation are poorly understood. Given the large, and expanding, agricultural landbase under irrigation across the globe, this is a critical knowledge gap for climate change mitigation. We undertook a systematic literature review and subsequent meta-analysis of data from studies that examined changes in SOC on irrigated agricultural sites through time. We investigated changes in SOC by climate (aridity), soil texture, and irrigation method with the following objectives: (i) to examine the impact of irrigated agriculture on SOC storage; and (ii) to identify the conditions under which irrigated agriculture is most likely to enhance SOC. Overall, irrigated agriculture increased SOC stocks by 5.9%, with little effect of study length (2-47 years). However, changes in SOC varied by climate and soil depth, with the greatest increase in SOC observed on irrigated semi-arid sites at the 0-10 cm depth (14.8%). Additionally, SOC increased in irrigated fine- and medium-textured soils but not coarse-textured soils. Furthermore, while there was no overall change to SOC in flood/furrow irrigated sites, SOC tended to increase in sprinkler irrigated sites, and decrease in drip irrigated sites, especially at depths below 10 cm. This work sheds light on the nuances of SOC change across irrigated agricultural systems, highlights the importance of studying SOC storage in deeper soils, and will help guide future research on the impacts of irrigated agriculture on SOC.


Assuntos
Carbono , Solo , Agricultura , Sequestro de Carbono , Mudança Climática
6.
New Phytol ; 225(5): 1835-1851, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31514244

RESUMO

Dual-mycorrhizal plants are capable of associating with fungi that form characteristic arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) structures. Here, we address the following questions: (1) How many dual-mycorrhizal plant species are there? (2) What are the advantages for a plant to host two, rather than one, mycorrhizal types? (3) Which factors can provoke shifts in mycorrhizal dominance (i.e. mycorrhizal switching)? We identify a large number (89 genera within 32 families) of confirmed dual-mycorrhizal plants based on observing arbuscules or coils for AM status and Hartig net or similar structures for EM status within the same plant species. We then review the possible nutritional benefits and discuss the possible mechanisms leading to net costs and benefits. Cost and benefits of dual-mycorrhizal status appear to be context dependent, particularly with respect to the life stage of the host plant. Mycorrhizal switching occurs under a wide range of abiotic and biotic factors, including soil moisture and nutrient status. The relevance of dual-mycorrhizal plants in the ecological restoration of adverse sites where plants are not carbon limited is discussed. We conclude that dual-mycorrhizal plants are underutilized in ecophysiological-based experiments, yet are powerful model plant-fungal systems to better understand mycorrhizal symbioses without confounding host effects.


Assuntos
Micorrizas , Nitrogênio , Plantas , Solo , Simbiose
7.
Mycorrhiza ; 30(4): 407-417, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32363468

RESUMO

Ectomycorrhizal fungi supply their plant partners with nitrogen but can also retain substantial amounts. The concentration of nitrogen in the soil and the amount of carbon supplied from the host seem to influence the proportion of N retained by the fungus. In an experiment designed to determine whether differential supply of nitrogen to two plants influenced nitrogen transfer from fungus to plant within a mycorrhizal network, we observed rapid, substantial loss of nitrogen from pine seedlings. The loss occurred when the mycorrhizal fungus experienced a sudden increase in nitrogen supply. We grew Pinus contorta seedlings in association with Suillus tomentosus in low-nitrogen microcosms where some nitrogen was accessible only by hyphae. After 70 days, foliage of some seedlings was treated with nitrogen. Three days later, hyphal nutrient media were replaced with water or a solution containing nitrogen. Foliar treatment did not affect nitrogen transfer by the fungus to shoots, but by day 75, seedling nitrogen contents had dropped by 60% in microcosms where nitrogen had been added to the hyphal compartments. Those seedlings retained only 55% of the nitrogen originally present in the seed. Loss of nitrogen did not occur if water was added or the hyphae were severed. Because of the severing effect, we concluded that S. tomentosus triggered the loss of seedling nitrogen. Nitrogen may have been lost through increased root exudation or transfer to the fungus. Access to nitrogen from nutrient-rich germinants would benefit rhizosphere microorganisms, including ectomycorrhizal fungi colonizing pine from spores after wildfire.


Assuntos
Micorrizas , Pinus , Nitrogênio , Raízes de Plantas , Plântula , Solo
8.
Mycorrhiza ; 27(3): 247-260, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27900594

RESUMO

After stand-replacing disturbance, regenerating conifer seedlings become colonized by different ectomycorrhizal fungi (EMF) than the locally adapted EMF communities present on seedlings in mature forests. We studied whether EMF species that colonized subalpine fir (Abies lasiocarpa) seedlings in clearcuts differed from those that colonized seedlings in adjacent mature forests with respect to mycorrhizoplane extracellular enzyme activities (EEAs) and N status of the seedlings. We tested two alternate hypotheses: (1) that EEAs would differ between the two EMF communities, with higher activities associated with forest-origin communities, and (2) that acclimation to soil environment was considerable enough that EEAs would be determined primarily by the soil type in which the ectomycorrhizas were growing. Naturally colonized fir seedlings were reciprocally transplanted between clearcuts and forests, carrying different EMF communities with them. EEAs were influenced more by destination environment than by EMF community. EEAs were as high in early-successional as in late-successional communities in both destination environments. Buds of clearcut-origin seedlings had the same or higher N contents as forest seedlings after a growing season in either environment. These results indicate that (i) symbiotic EMF and/or their associated microbial communities demonstrate substantial ability to acclimate to new field environments; (ii) the ability to produce organic matter-degrading enzymes is not a trait that necessarily distinguishes early- and late-successional EMF communities in symbiosis; (iii) early-successional EMF are as capable of supporting seedling N accumulation in forest soils as late-successional EMF; and (iv) disturbed ecosystems where early-successional EMF are present should have high resilience for organic matter degradation.


Assuntos
Abies/microbiologia , Micorrizas/enzimologia , Nitrogênio/metabolismo , Plântula/microbiologia , Abies/metabolismo , Adaptação Fisiológica , Biodiversidade , Florestas , Micorrizas/classificação , Micorrizas/crescimento & desenvolvimento , Filogenia , Raízes de Plantas/microbiologia , Estações do Ano , Microbiologia do Solo , Simbiose
9.
Clin Chem ; 62(1): 208-17, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26430078

RESUMO

BACKGROUND: Primary deficiencies in mannosylation of N-glycans are seen in a majority of patients with congenital disorders of glycosylation (CDG). We report the discovery of a series of novel N-glycans in sera, plasma, and cultured skin fibroblasts from patients with CDG having deficient mannosylation. METHOD: We used LC-MS/MS and MALDI-TOF-MS analysis to identify and quantify a novel N-linked tetrasaccharide linked to the protein core, an N-tetrasaccharide (Neu5Acα2,6Galß1,4-GlcNAcß1,4GlcNAc) in plasma, serum glycoproteins, and a fibroblast lysate from patients with CDG caused by ALG1 [ALG1 (asparagine-linked glycosylation protein 1), chitobiosyldiphosphodolichol ß-mannosyltransferase], PMM2 (phosphomannomutase 2), and MPI (mannose phosphate isomerase). RESULTS: Glycoproteins in sera, plasma, or cell lysate from ALG1-CDG, PMM2-CDG, and MPI-CDG patients had substantially more N-tetrasaccharide than unaffected controls. We observed a >80% decline in relative concentrations of the N-tetrasaccharide in MPI-CDG plasma after mannose therapy in 1 patient and in ALG1-CDG fibroblasts in vitro supplemented with mannose. CONCLUSIONS: This novel N-tetrasaccharide could serve as a diagnostic marker of ALG1-, PMM2-, or MPI-CDG for screening of these 3 common CDG subtypes that comprise >70% of CDG type I patients. Its quantification by LC-MS/MS may be useful for monitoring therapeutic efficacy of mannose. The discovery of these small N-glycans also indicates the presence of an alternative pathway in N-glycosylation not recognized previously, but its biological significance remains to be studied.


Assuntos
Defeitos Congênitos da Glicosilação/diagnóstico , Manose-6-Fosfato Isomerase/análise , Manose-6-Fosfato Isomerase/deficiência , Manosiltransferases/análise , Manosiltransferases/deficiência , Oligossacarídeos/análise , Fosfotransferases (Fosfomutases)/análise , Fosfotransferases (Fosfomutases)/deficiência , Cromatografia Líquida de Alta Pressão , Defeitos Congênitos da Glicosilação/metabolismo , Humanos , Manose-6-Fosfato Isomerase/metabolismo , Manosiltransferases/metabolismo , Oligossacarídeos/metabolismo , Fosfotransferases (Fosfomutases)/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
10.
Mycorrhiza ; 26(4): 275-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26547440

RESUMO

Forest ecosystems of the Pacific Northwest of the USA are changing as a result of climate change. Specifically, rise of global temperatures, decline of winter precipitation, earlier loss of snowpack, and increased summer drought are altering the range of Pinus contorta. Simultaneously, flux in environmental conditions within the historic P. contorta range may facilitate the encroachment of P. ponderosa into P. contorta territory. Furthermore, successful pine species migration may be constrained by the distribution or co-migration of ectomycorrhizal fungi (EMF). Knowledge of the linkages among soil fungal diversity, community structure, and environmental factors is critical to understanding the organization and stability of pine ecosystems. The objectives of this study were to establish a foundational knowledge of the EMF communities of P. ponderosa and P. contorta in the Deschutes National Forest, OR, USA, and to examine soil characteristics associated with community composition. We examined EMF root tips of P. ponderosa and P. contorta in soil cores and conducted soil chemistry analysis for P. ponderosa cores. Results indicate that Cenococcum geophilum, Rhizopogon salebrosus, and Inocybe flocculosa were dominant in both P. contorta and P. ponderosa soil cores. Rhizopogon spp. were ubiquitous in P. ponderosa cores. There was no significant difference in the species composition of EMF communities of P. ponderosa and P. contorta. Ordination analysis of P. ponderosa soils suggested that soil pH, plant-available phosphorus (Bray), total phosphorus (P), carbon (C), mineralizable nitrogen (N), ammonium (NH4), and nitrate (NO3) are driving EMF community composition in P. ponderosa stands. We found a significant linear relationship between EMF species richness and mineralizable N. In conclusion, P. ponderosa and P. contorta, within the Deschutes National Forest, share the same dominant EMF species, which implies that P. ponderosa may be able to successfully establish within the historic P. contorta range and dominant EMF assemblages may be conserved.


Assuntos
Fungos/isolamento & purificação , Micorrizas/isolamento & purificação , Pinus ponderosa/microbiologia , Pinus/microbiologia , Mudança Climática , Ecossistema , Fungos/classificação , Fungos/genética , Micorrizas/classificação , Micorrizas/genética , Oregon , Estações do Ano
11.
Adm Policy Ment Health ; 43(3): 297-301, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25234345

RESUMO

This paper outlines the experience of the Child Outcomes Research Consortium-formerly known as the CAMHS Outcomes Research Consortium; the named changed in 2014 in recognition of the widening scope of the work of the collaboration; a learning collaboration of service providers, funders, service user groups and researchers across the UK and beyond, jointly committed to collecting and using routinely collected outcome data to improve and enhance service provision and improve understanding of how best to help young people with mental health issues and their families.


Assuntos
Serviços de Saúde da Criança , Pesquisa sobre Serviços de Saúde , Serviços de Saúde Mental , Medidas de Resultados Relatados pelo Paciente , Criança , Comportamento Cooperativo , Humanos , Aprendizagem , Avaliação de Resultados em Cuidados de Saúde
12.
J Biol Chem ; 289(45): 30950-61, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25231977

RESUMO

Three of the four kynurenine aminotransferases (KAT I, II, and IV) that synthesize kynurenic acid, a neuromodulator, are identical to glutamine transaminase K (GTK), α-aminoadipate aminotransferase, and mitochondrial aspartate aminotransferase, respectively. GTK/KAT I and aspartate aminotransferase/KAT IV possess cysteine S-conjugate ß-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome data banks as CCBL1 (cysteine conjugate beta-lyase 1). Also listed, despite the fact that no ß-lyase activity has been assigned to the encoded protein in the genome data bank, is a CCBL2 (synonym KAT III). We show that human KAT III/CCBL2 possesses cysteine S-conjugate ß-lyase activity, as does mouse KAT II. Thus, depending on the nature of the substrate, all four KATs possess cysteine S-conjugate ß-lyase activity. These present studies show that KAT III and glutamine transaminase L are identical enzymes. This report also shows that KAT I, II, and III differ in their ability to transaminate methyl-L-selenocysteine (MSC) and L-selenomethionine (SM) to ß-methylselenopyruvate (MSP) and α-ketomethylselenobutyrate, respectively. Previous studies have identified these seleno-α-keto acids as potent histone deacetylase inhibitors. Methylselenol (CH3SeH), also purported to have chemopreventive properties, is the γ-elimination product of SM and the ß-elimination product of MSC catalyzed by cystathionine γ-lyase (γ-cystathionase). KAT I, II, and III, in part, can catalyze ß-elimination reactions with MSC generating CH3SeH. Thus, the anticancer efficacy of MSC and SM will depend, in part, on the endogenous expression of various KAT enzymes and cystathionine γ-lyase present in target tissue coupled with the ability of cells to synthesize in situ either CH3SeH and/or seleno-keto acid metabolites.


Assuntos
Liases de Carbono-Enxofre/metabolismo , Selenometionina/química , Transaminases/metabolismo , Alcenos/química , Animais , Cisteína/química , Inibidores de Histona Desacetilases/química , Humanos , Cinética , Fígado/metabolismo , Camundongos , Neoplasias/metabolismo , Proteínas Recombinantes/química , Selenocisteína/química , Especificidade por Substrato , Espectrometria de Massas em Tandem
13.
Am J Hum Genet ; 90(2): 363-8, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22305527

RESUMO

Congenital disorders of glycosylation (CDG) are inherited autosomal-recessive diseases that impair N-glycosylation. Approximately 20% of patients do not survive beyond the age of 5 years old as a result of widespread organ dysfunction. Although most patients receive a CDG diagnosis based on abnormal glycosylation of transferrin, this test cannot provide a genetic diagnosis; indeed, many patients with abnormal transferrin do not have mutations in any known CDG genes. Here, we combined biochemical analysis with whole-exome sequencing (WES) to identify the genetic defect in an untyped CDG patient, and we found a 22 bp deletion and a missense mutation in DDOST, whose product is a component of the oligosaccharyltransferase complex that transfers the glycan chain from a lipid carrier to nascent proteins in the endoplasmic reticulum lumen. Biochemical analysis with three biomarkers revealed that N-glycosylation was decreased in the patient's fibroblasts. Complementation with wild-type-DDOST cDNA in patient fibroblasts restored glycosylation, indicating that the mutations were pathological. Our results highlight the power of combining WES and biochemical studies, including a glyco-complementation system, for identifying and confirming the defective gene in an untyped CDG patient. This approach will be very useful for uncovering other types of CDG as well.


Assuntos
Defeitos Congênitos da Glicosilação/genética , Exoma , Hexosiltransferases/genética , Proteínas de Membrana/genética , Mutação , Anormalidades Múltiplas/enzimologia , Anormalidades Múltiplas/genética , Sequência de Bases , Biomarcadores/metabolismo , Criança , Defeitos Congênitos da Glicosilação/enzimologia , Fibroblastos/metabolismo , Glicosilação , Hexosiltransferases/metabolismo , Humanos , Masculino , Proteínas de Membrana/metabolismo , Dados de Sequência Molecular , Linhagem , Transferrina/metabolismo
14.
Am J Hum Genet ; 90(4): 685-8, 2012 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-22444671

RESUMO

CHIME syndrome is characterized by colobomas, heart defects, ichthyosiform dermatosis, mental retardation (intellectual disability), and ear anomalies, including conductive hearing loss. Whole-exome sequencing on five previously reported cases identified PIGL, the de-N-acetylase required for glycosylphosphatidylinositol (GPI) anchor formation, as a strong candidate. Furthermore, cell lines derived from these cases had significantly reduced levels of the two GPI anchor markers, CD59 and a GPI-binding toxin, aerolysin (FLAER), confirming the pathogenicity of the mutations.


Assuntos
Amidoidrolases/genética , Coloboma/genética , Perda Auditiva Condutiva/genética , Cardiopatias Congênitas/genética , Ictiose/genética , Deficiência Intelectual/genética , Mutação , Toxinas Bacterianas/biossíntese , Sequência de Bases , Antígenos CD59/biossíntese , Células Cultivadas , Exoma/genética , Glicosilfosfatidilinositóis/metabolismo , Humanos , Dados de Sequência Molecular , Síndromes Neurocutâneas , Proteínas Citotóxicas Formadoras de Poros/biossíntese
15.
Genet Med ; 16(10): 751-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24651605

RESUMO

PURPOSE: The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1. METHODS: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. RESULTS: All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. CONCLUSION: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.


Assuntos
Anormalidades Múltiplas/genética , Degradação Associada com o Retículo Endoplasmático/genética , Mutação , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/genética , Transdução de Sinais/genética , Anormalidades Múltiplas/enzimologia , Anormalidades Múltiplas/patologia , Adolescente , Pré-Escolar , Deficiências do Desenvolvimento/patologia , Exoma/genética , Saúde da Família , Evolução Fatal , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Lactente , Masculino , Microcefalia/patologia , Transtornos dos Movimentos/patologia , Hipotonia Muscular/patologia , Linhagem , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/deficiência , Estudos Retrospectivos , Convulsões/patologia , Análise de Sequência de DNA/métodos , Adulto Jovem
16.
Animals (Basel) ; 14(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473090

RESUMO

As interest in animal-assisted therapy (AAT) and canine-assisted psychotherapy (CAP) grows, there are increasing calls for the management of related health, safety, and welfare concerns for canines, providers, and clients. Existing health and safety guidelines lack empirical support and are, at times, contradictory. Welfare is increasingly prioritized; however, tools to monitor and manage welfare are underutilized and under-reported. The aim of this study was to provide expert consensus on the minimum health, safety, and welfare standards required to develop and deliver a CAP group program to adolescents experiencing common mental health disorders. Diverse AAT experts were recruited globally. Using Delphi methodology, over two rounds, 40 panelists reached a consensus agreement to include 32 items from a possible 49 into the minimum standards. Health and safety measures included risk assessment, veterinary screening, preventative medicine, training in infection control, and first aid. Welfare measures included training in welfare assessment, documentation of welfare, and flexible, individualized responses to promote wellbeing. Intestinal screening for parasites and the prohibition of raw food were not supported. Flexible and individualized assessment and management of canine welfare were supported over fixed and time-limited work schedules. Clinical practice implications are discussed, and recommendations are made.

17.
Am Surg ; 90(8): 2075-2077, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38547538

RESUMO

Representing 68% of firearm-related injuries, nonfatal firearm injuries cause substantial morbidity and are associated with high costs to patients and the health care system. A retrospective analysis was performed to evaluate 359 adults in the Southeastern United States from 2019 to 2021. IBM SPSS was used for descriptive and parametric statistical analysis. The mean total cost of stay (TCOS) was $36,639.12, length of stay (LOS) was 8.61 days, number of times to the operating room was 1.88, and number of follow-ups was 3.21. Vascular and traumatic brain injuries were associated with higher TCOS and LOS. Vascular injuries were associated with more operating room visits. Bony injuries and non-TBI neurological injuries were associated with more follow-up appointments. In this brief report, we aim to understand the effect injury types have on these factors to help inform trauma protocol development with the goal of decreasing financial burdens.


Assuntos
Tempo de Internação , Ferimentos por Arma de Fogo , Humanos , Ferimentos por Arma de Fogo/economia , Ferimentos por Arma de Fogo/epidemiologia , Estudos Retrospectivos , Adulto , Masculino , Feminino , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Sudeste dos Estados Unidos/epidemiologia , Adulto Jovem , Custos de Cuidados de Saúde/estatística & dados numéricos
18.
BJPsych Bull ; : 1-13, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38174424

RESUMO

AIMS AND METHOD: Serious incident management and organisational learning are international patient safety priorities. Little is known about the quality of suicide investigations and, in turn, the potential for organisational learning. Suicide risk assessment is acknowledged as a complex phenomenon, particularly in the context of adult community mental health services. Root cause analysis (RCA) is the dominant investigative approach, although the evidence base underpinning RCA is contested, with little attention paid to the patient in context and their cumulative risk over time. RESULTS: Recent literature proposes a safety-II approach in response to the limitations of RCA. The importance of applying these approaches within a mental healthcare system that advocates a zero suicide framework, grounded in a restorative just culture, is highlighted. CLINICAL IMPLICATIONS: Although integrative reviews and syntheses have clear methodological limitations, this approach facilitates the management of a disparate body of work to advance a critical understanding of patient safety in adult community mental healthcare.

19.
Mol Genet Metab ; 110(1-2): 78-85, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23806237

RESUMO

Congenital disorders of glycosylation (CDG) are comprised of over 60 disorders with the majority of defects residing within the N-glycosylation pathway. Approximately 20% of patients do not survive beyond five years of age due to widespread organ dysfunction. A diagnosis of CDG is based on abnormal glycosylation of transferrin but this method cannot identify the specific gene defect. For many individuals diagnosed with CDG the gene defect remains unknown. To improve the molecular diagnosis of CDG we developed molecular testing for 25 CDG genes including single gene testing and next generation sequencing (NGS) panel testing. From March 2010 through November 2012, a total of 94 samples were referred for single gene testing and 68 samples were referred for NGS panel testing. Disease causing mutations were identified in 24 patients resulting in a molecular diagnosis rate of 14.8%. Coverage of the 24 CDG genes using panel testing and whole exome sequencing (WES) was compared and it was determined that many exons of these genes were not adequately covered using a WES approach and a panel approach may be the preferred first option for CDG patients. A collaborative effort between physicians, researchers and diagnostic laboratories will be very important as NGS testing using panels and exome becomes more widespread. This technology will ultimately improve the molecular diagnosis of patients with CDG in hard to solve cases.


Assuntos
Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Sequenciamento de Nucleotídeos em Larga Escala , Patologia Molecular , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Defeitos Congênitos da Glicosilação/patologia , Feminino , Glicosilação , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação
20.
Oecologia ; 173(4): 1499-1511, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23797413

RESUMO

Ectomycorrhizal fungal (EMF) communities vary among microhabitats, supporting a dominant role for deterministic processes in EMF community assemblage. EMF communities also differ between forest and clearcut environments, responding to this disturbance in a directional manner over time by returning to the species composition of the original forest. Accordingly, we examined EMF community composition on roots of spruce seedlings planted in three different microhabitats in forest and clearcut plots: decayed wood, mineral soil adjacent to downed wood, or control mineral soil, to determine the effect of retained downed wood on EMF communities over the medium and long term. If downed and decayed wood provide refuge habitat distinct from that of mineral soil, we would expect EMF communities on seedlings in woody habitats in clearcuts to be similar to those on seedlings planted in the adjacent forest. As expected, we found EMF species richness to be higher in forests than clearcuts (P ≤ 0.01), even though soil nutrient status did not differ greatly between the two plot types (P ≥ 0.05). Communities on forest seedlings were dominated by Tylospora spp., whereas those in clearcuts were dominated by Amphinema byssoides and Thelephora terrestris. Surprisingly, while substrate conditions varied among microsites (P ≤ 0.03), especially between decayed wood and mineral soil, EMF communities were not distinctly different among microhabitats. Our data suggest that niche partitioning by substrate does not occur among EMF species on very young seedlings in high elevation spruce-fir forests. Further, dispersal limitations shape EMF community assembly in clearcuts in these forests.


Assuntos
Ecossistema , Micorrizas/fisiologia , Picea/microbiologia , Solo/química , Madeira/química , DNA Fúngico/genética , Consórcios Microbianos , Minerais/análise , Micorrizas/classificação , Raízes de Plantas/microbiologia , Plântula/microbiologia , Microbiologia do Solo , Árvores/microbiologia
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