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1.
Glob Chang Biol ; 28(7): 2425-2441, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34908205

RESUMO

Depolymerization of high-molecular weight organic nitrogen (N) represents the major bottleneck of soil N cycling and yet is poorly understood compared to the subsequent inorganic N processes. Given the importance of organic N cycling and the rise of global change, we investigated the responses of soil protein depolymerization and microbial amino acid consumption to increased temperature, elevated atmospheric CO2 , and drought. The study was conducted in a global change facility in a managed montane grassland in Austria, where elevated CO2 (eCO2 ) and elevated temperature (eT) were stimulated for 4 years, and were combined with a drought event. Gross protein depolymerization and microbial amino acid consumption rates (alongside with gross organic N mineralization and nitrification) were measured using 15 N isotope pool dilution techniques. Whereas eCO2  showed no individual effect, eT had distinct effects which were modulated by season, with a negative effect of eT on soil organic N process rates in spring, neutral effects in summer, and positive effects in fall. We attribute this to a combination of changes in substrate availability and seasonal temperature changes. Drought led to a doubling of organic N process rates, which returned to rates found under ambient conditions within 3 months after rewetting. Notably, we observed a shift in the control of soil protein depolymerization, from plant substrate controls under continuous environmental change drivers (eT and eCO2 ) to controls via microbial turnover and soil organic N availability under the pulse disturbance (drought). To the best of our knowledge, this is the first study which analyzed the individual versus combined effects of multiple global change factors and of seasonality on soil organic N processes and thereby strongly contributes to our understanding of terrestrial N cycling in a future world.


Assuntos
Secas , Pradaria , Aminoácidos , Dióxido de Carbono/análise , Ecossistema , Nitrogênio/análise , Solo/química , Microbiologia do Solo
2.
Soil Biol Biochem ; 169: 108604, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35712047

RESUMO

Network analysis has been used for many years in ecological research to analyze organismal associations, for example in food webs, plant-plant or plant-animal interactions. Although network analysis is widely applied in microbial ecology, only recently has it entered the realms of soil microbial ecology, shown by a rapid rise in studies applying co-occurrence analysis to soil microbial communities. While this application offers great potential for deeper insights into the ecological structure of soil microbial ecosystems, it also brings new challenges related to the specific characteristics of soil datasets and the type of ecological questions that can be addressed. In this Perspectives Paper we assess the challenges of applying network analysis to soil microbial ecology due to the small-scale heterogeneity of the soil environment and the nature of soil microbial datasets. We review the different approaches of network construction that are commonly applied to soil microbial datasets and discuss their features and limitations. Using a test dataset of microbial communities from two depths of a forest soil, we demonstrate how different experimental designs and network constructing algorithms affect the structure of the resulting networks, and how this in turn may influence ecological conclusions. We will also reveal how assumptions of the construction method, methods of preparing the dataset, and definitions of thresholds affect the network structure. Finally, we discuss the particular questions in soil microbial ecology that can be approached by analyzing and interpreting specific network properties. Targeting these network properties in a meaningful way will allow applying this technique not in merely descriptive, but in hypothesis-driven research. Analysing microbial networks in soils opens a window to a better understanding of the complexity of microbial communities. However, this approach is unfortunately often used to draw conclusions which are far beyond the scientific evidence it can provide, which has damaged its reputation for soil microbial analysis. In this Perspectives Paper, we would like to sharpen the view for the real potential of microbial co-occurrence analysis in soils, and at the same time raise awareness regarding its limitations and the many ways how it can be misused or misinterpreted.

3.
New Phytol ; 232(6): 2457-2474, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34196001

RESUMO

Ectomycorrhizal plants trade plant-assimilated carbon for soil nutrients with their fungal partners. The underlying mechanisms, however, are not fully understood. Here we investigate the exchange of carbon for nitrogen in the ectomycorrhizal symbiosis of Fagus sylvatica across different spatial scales from the root system to the cellular level. We provided 15 N-labelled nitrogen to mycorrhizal hyphae associated with one half of the root system of young beech trees, while exposing plants to a 13 CO2 atmosphere. We analysed the short-term distribution of 13 C and 15 N in the root system with isotope-ratio mass spectrometry, and at the cellular scale within a mycorrhizal root tip with nanoscale secondary ion mass spectrometry (NanoSIMS). At the root system scale, plants did not allocate more 13 C to root parts that received more 15 N. Nanoscale secondary ion mass spectrometry imaging, however, revealed a highly heterogenous, and spatially significantly correlated distribution of 13 C and 15 N at the cellular scale. Our results indicate that, on a coarse scale, plants do not allocate a larger proportion of photoassimilated C to root parts associated with N-delivering ectomycorrhizal fungi. Within the ectomycorrhizal tissue, however, recently plant-assimilated C and fungus-delivered N were spatially strongly coupled. Here, NanoSIMS visualisation provides an initial insight into the regulation of ectomycorrhizal C and N exchange at the microscale.


Assuntos
Fagus , Micorrizas , Carbono , Nitrogênio , Raízes de Plantas
4.
Laryngorhinootologie ; 100(6): 443-452, 2021 06.
Artigo em Alemão | MEDLINE | ID: mdl-33761571

RESUMO

OBJECTIVE: Patients with hereditary hemorrhagic Telangiectasia (HHT) suffer from a rare and systemic disease which is characterized by vascular malformations leading to a variety of different symptoms. MATERIAL AND METHODS: A retrospective review of patients who were referred to our new HHT Center of Excellence (HHT COE) for evaluation and treatment between April 2014 and August 2019 was performed. RESULTS: 235 patients were treated at the West German HHT Center. 83 % of these were diagnosed with definite HHT (235/282, 83 %) and 9 % with possible HHT (26/282). The average latency between first manifestation and definite diagnosis of HHT was 18 years. Several initial symptoms were direct or indirect signs of bleeding (224/241, 93 %). In 83 % of the patients HHT was reported having caused their degree of disability. Older, female patients and those with severe epistaxis suffered from chronic iron deficiency anemia, took iron preparations (148/261, 57 %) and received 9 blood transfusions on average (± standard deviation: 41, minimum - maximum: 0-400, number of patients: 218). 10 % of all patients tolerated anticoagulant or antiplatelet agents. 74 % of patients with HHT used nasal creams/sprays/oils (177/238) and reported fewer bleedings compared to patients without nasal care (ESS: T-Test: 3.193; p = 0.003; anemia: Chi-square: 5.173; p = 0.023). CONCLUSIONS: The diagnostic latency of HHT was almost two decades. Patients with HHT particularly suffered from recurrent epistaxis, which was mostly treated with nasal care and coagulative therapies. Antiplatelet or anticoagulant agents can be used in patients with HHT with caution if indicated.


Assuntos
Telangiectasia Hemorrágica Hereditária , Anticoagulantes , Epistaxe/etiologia , Feminino , Humanos , Inibidores da Agregação Plaquetária , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/epidemiologia , Telangiectasia Hemorrágica Hereditária/terapia
5.
Laryngorhinootologie ; 100(5): 372-381, 2021 05.
Artigo em Alemão | MEDLINE | ID: mdl-33723832

RESUMO

OBJECTIVE: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare and systemic disorder which is characterized by recurrent epistaxis, mucocutaneous telangiectases, and visceral arteriovenous malformations (AVM). An interdisciplinary concept is recommended. MATERIAL AND METHODS: We performed a retrospective review of consecutive patients who were referred to our newly established HHT Center of Excellence (HHT COE) for evaluation and treatment between April 2014 and August 2019. RESULTS: A network of over 20 departments was established at the University Hospital Essen. In 261 of the 282 patients (93 %), who were referred to the hospital's COE, the HHT diagnosis was at least possible. Most patients suffered from several symptoms (epistaxis and / or telangiectasia: > 80 %, visceral involvement: 65 %) and received a variety of treatments, often in a multidisciplinary setting. Alongside this direct treatment, the COE leader manages the coordination of the center and its public relations, which involves more than 900 e-mails per year. International collaboration and exchanges of expertise within the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) can improve the treatment of patients with HHT particularly where these cases are complex. CONCLUSIONS: An HHT COE provides an interdisciplinary network where highly specialized diagnostic and therapeutic processes can be updated and optimized continuously.


Assuntos
Telangiectasia Hemorrágica Hereditária , Epistaxe/etiologia , Epistaxe/terapia , Humanos , Doenças Raras , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/terapia
6.
Breast Cancer Res Treat ; 169(3): 447-455, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29455299

RESUMO

PURPOSE: Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized. METHODS: This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA). RESULTS: Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail. CONCLUSIONS: This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.


Assuntos
Antígenos de Superfície/metabolismo , Neoplasias da Mama/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/genética , Biomarcadores , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Expressão Gênica , Glutamato Carboxipeptidase II/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
7.
Int J Gynecol Cancer ; 26(5): 873-83, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27101586

RESUMO

OBJECTIVES: Extensive surgical efforts to achieve an optimal debulking (no residual tumor) in primary surgery of ovarian cancer are today's criterion standard in gyneco-oncologic surgery. However, it is controversial whether extensive surgery, including resections of metastases in the upper abdomen and bowel resections, is justifiable in patients with not completely operable lesions. METHODS: All patients who had undergone surgery for ovarian cancer in the years 2002 to 2013 at our institution were viewed (n = 472). We retrospectively identified 278 operations for primary ovarian cancer. Ninety-six (35%) of the 278 patients showed postoperative tumor residuals and were included in this study. RESULTS: Fifty-five (57%) of 96 patients underwent bowel resection, showing significantly higher complication rates (64% vs 39% minor complications, P = 0.017; 31% vs 9.8% severe complications, P = 0.013) compared with patients without bowel resections as well as no improvement in progression-free or overall survival (median overall survival, 19.5 vs 32.9; P = 0.382). Multiple anastomoses (≥2) were associated with higher rates for anastomotic leakage (16.7% vs 2.6%, P = 0.02) and a higher mortality (16.7% vs 0%, P = 0.04) compared with patients with only 1 anastomosis. Extensive surgery of the upper abdomen was not associated with a significant increase in complication rates. CONCLUSIONS: Because of the increased morbidity of bowel resections without any evidence for improvement of survival, we suggest to restrain from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumor bulk.


Assuntos
Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Breast Cancer Res Treat ; 153(3): 531-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26323190

RESUMO

Several authors question the potential benefit of preoperative magnetic resonance imaging (MRI) against the background of possible overdiagnosis, false-positive findings, and unnecessary resections in patients with newly diagnosed breast cancer. In order to reveal a better selection of patients who should undergo preoperative MRI after histological confirmed breast cancer, the present analysis was implemented. We aimed to evaluate the influence of preoperative breast MRI in patients with newly diagnosed breast cancer to find subgroups of patients that are most likely to benefit from preoperative MRI by the detection of occult malignant foci. A total of 1102 consecutive patients who underwent treatment for primary breast cancer between 2002 and 2013 were retrospectively analyzed. All patients underwent triple assessment by breast ultrasound, mammography, and bilateral breast MRI. MRI findings not seen on conventional imaging that suggested additional malignant disease was found in 344 cases (31.2 %). Histological confirmed malignant foci were found in 223 patients (20.2 %) within the index breast and in 28 patients (2.5 %) in the contralateral breast. The rate of false-negative biopsies was 31 (2.8 %) and 62 (5.6 %), respectively. Premenopausal women (p = 0.024), lobular invasive breast cancer (p = 0.02) as well as patients with high breast density [American College of Radiology (ACR) 3 + 4; p = 0.01] were significantly associated with additional malignant foci in the index breast. Multivariate analysis confirmed lobular histology (p = 0.041) as well as the co-factors "premenopausal stage" and "high breast density (ACR 3+4)" (p = 0.044) to be independently significant. Previous studies revealed that breast MRI is a reliable tool for predicting tumor extension as well as for the detection of additional ipsilateral and contralateral tumor foci in histological confirmed breast cancer. In the present study, we demonstrate that especially premenopausal patients with high breast density as well as patients with lobular histology seem to profit from preoperative MRI.


Assuntos
Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética , Cuidados Pré-Operatórios , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Mamografia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fatores de Risco , Ultrassonografia Mamária
9.
New Phytol ; 205(4): 1537-1551, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25382456

RESUMO

Plants rapidly release photoassimilated carbon (C) to the soil via direct root exudation and associated mycorrhizal fungi, with both pathways promoting plant nutrient availability. This study aimed to explore these pathways from the root's vascular bundle to soil microbial communities. Using nanoscale secondary ion mass spectrometry (NanoSIMS) imaging and (13) C-phospho- and neutral lipid fatty acids, we traced in-situ flows of recently photoassimilated C of (13) CO2 -exposed wheat (Triticum aestivum) through arbuscular mycorrhiza (AM) into root- and hyphae-associated soil microbial communities. Intraradical hyphae of AM fungi were significantly (13) C-enriched compared to other root-cortex areas after 8 h of labelling. Immature fine root areas close to the root tip, where AM features were absent, showed signs of passive C loss and co-location of photoassimilates with nitrogen taken up from the soil solution. A significant and exclusively fresh proportion of (13) C-photosynthates was delivered through the AM pathway and was utilised by different microbial groups compared to C directly released by roots. Our results indicate that a major release of recent photosynthates into soil leave plant roots via AM intraradical hyphae already upstream of passive root exudations. AM fungi may act as a rapid hub for translocating fresh plant C to soil microbes.


Assuntos
Micorrizas/fisiologia , Fotossíntese , Exsudatos de Plantas/metabolismo , Microbiologia do Solo , Biomarcadores/metabolismo , Carbono/metabolismo , Isótopos de Carbono , Contagem de Colônia Microbiana , Ácidos Graxos/análise , Hifas/fisiologia , Hifas/efeitos da radiação , Luz , Micorrizas/crescimento & desenvolvimento , Micorrizas/efeitos da radiação , Nanotecnologia , Nitrogênio/metabolismo , Isótopos de Nitrogênio , Fosfolipídeos/análise , Fotossíntese/efeitos da radiação , Raízes de Plantas/citologia , Raízes de Plantas/microbiologia , Espectrometria de Massa de Íon Secundário , Frações Subcelulares/metabolismo , Fatores de Tempo , Triticum/microbiologia
10.
Ecol Lett ; 17(6): 680-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24628731

RESUMO

Under the current paradigm, organic matter decomposition and nutrient cycling rates are a function of the imbalance between substrate and microbial biomass stoichiometry. Challenging this view, we demonstrate that in an individual-based model, microbial community dynamics alter relative C and N limitation during litter decomposition, leading to a system behaviour not predictable from stoichiometric theory alone. Rather, the dynamics of interacting functional groups lead to an adaptation at the community level, which accelerates nitrogen recycling in litter with high initial C : N ratios and thus alleviates microbial N limitation. This mechanism allows microbial decomposers to overcome large imbalances between resource and biomass stoichiometry without the need to decrease carbon use efficiency (CUE), which is in contrast to predictions of traditional stoichiometric mass balance equations. We conclude that identifying and implementing microbial community-driven mechanisms in biogeochemical models are necessary for accurately predicting terrestrial C fluxes in response to changing environmental conditions.


Assuntos
Ecossistema , Modelos Biológicos , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Carbono/metabolismo , Nitrogênio/metabolismo
11.
Gynecol Oncol ; 135(2): 176-83, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25173585

RESUMO

OBJECTIVE: Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. METHODS: To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. RESULTS: A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. CONCLUSIONS: Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma.


Assuntos
Adenocarcinoma/imunologia , Neoplasias do Endométrio/imunologia , Macrófagos/imunologia , Linfócitos T Reguladores/imunologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfonodos/patologia , Metástase Linfática , Vasos Linfáticos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptores de Superfície Celular/imunologia , Estudos Retrospectivos
12.
Oncol Res Treat ; 47(4): 145-148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38382477

RESUMO

INTRODUCTION: Phyllodes tumors belong to uncommon fibroepithelial breast tumors with a range of biological behaviors. Phyllodes tumors are responsible for less than 1 percent of all neoplasms of the breast. CASE PRESENTATION: A 66-year-old woman presented to our Breastcancer Unit in March 2021 because of a huge mass of her left breast with bleeding out of a tumor necrosis. Five years ago in 2016, a benign phyllodes tumor was diagnosed externally. When we started the treatment, the tumor had a weight of 18.6 kg. CONCLUSION: We describe the surgical management and the systemic treatment of metastatic disease.


Assuntos
Neoplasias da Mama , Tumor Filoide , Feminino , Humanos , Idoso , Tumor Filoide/cirurgia , Tumor Filoide/diagnóstico , Tumor Filoide/patologia , Mastectomia , Neoplasias da Mama/cirurgia
13.
bioRxiv ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38464243

RESUMO

Hyperinflammatory disease is associated with an aberrant immune response resulting in cytokine storm. One such instance of hyperinflammatory disease is known as macrophage activation syndrome (MAS). The pathology of MAS can be characterised by significantly elevated serum levels of interleukin (IL)-18 and interferon (IFN)-γ. Given the role for IL-18 in MAS, we sought to establish the role of inflammasomes in the disease process. Using a murine model of CpG-DNA induced MAS, we discovered that the expression of the NLRP3 inflammasome was increased and correlated with IL-18 production. Inhibition of the NLRP3 inflammasome, or downstream caspase-1, prevented MAS-mediated upregulation of plasma IL-18 but interestingly did not alleviate key features of hyperinflammatory disease including hyperferritinaemia and splenomegaly. Furthermore IL-1 receptor blockade with IL-1Ra did not prevent the development of CpG-induced MAS, despite being clinically effective in the treatment of MAS. These data demonstrate that in the development of MAS, the NLRP3 inflammasome was essential for the elevation in plasma IL-18, a key cytokine in clinical cases of MAS, but was not a driving factor in the pathogenesis of CpG-induced MAS.

14.
Dis Model Mech ; 17(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38775430

RESUMO

Hyperinflammatory disease is associated with an aberrant immune response resulting in cytokine storm. One such instance of hyperinflammatory disease is known as macrophage activation syndrome (MAS). The pathology of MAS can be characterised by significantly elevated serum levels of interleukin-18 (IL-18) and interferon gamma (IFNγ). Given the role for IL-18 in MAS, we sought to establish the role of inflammasomes in the disease process. Using a murine model of CpG-oligonucleotide-induced MAS, we discovered that the expression of the NLRP3 inflammasome was increased and correlated with IL-18 production. Inhibition of the NLRP3 inflammasome or the downstream caspase-1 prevented MAS-mediated upregulation of IL-18 in the plasma but, interestingly, did not alleviate key features of hyperinflammatory disease including hyperferritinaemia and splenomegaly. Furthermore blockade of IL-1 receptor with its antagonist IL-1Ra did not prevent the development of CpG-induced MAS, despite being clinically effective in the treatment of MAS. These data demonstrate that, during the development of MAS, the NLRP3 inflammasome was essential for the elevation in plasma IL-18 - a key cytokine in clinical cases of MAS - but was not a driving factor in the pathogenesis of CpG-induced MAS.


Assuntos
Modelos Animais de Doenças , Inflamassomos , Interleucina-18 , Síndrome de Ativação Macrofágica , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Interleucina-18/sangue , Inflamassomos/metabolismo , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/patologia , Síndrome de Ativação Macrofágica/complicações , Caspase 1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Transporte/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/sangue , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Receptores de Interleucina-1/metabolismo
15.
ACS Appl Mater Interfaces ; 16(24): 31407-31418, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38841759

RESUMO

Intermolecular charge-transfer (CT) states are extended excitons with a charge separation on the nanometer scale. Through absorption and emission processes, they couple to the ground state. This property is employed both in light-emitting and light-absorbing devices. Their conception often relies on donor-acceptor (D-A) interfaces, so-called type-II heterojunctions, which usually generate significant electric fields. Several recent studies claim that these fields alter the energetic configuration of the CT states at the interface, an idea holding prospects like multicolor emission from a single emissive interface or shifting the absorption characteristics of a photodetector. Here, we test this hypothesis and contribute to the discussion by presenting a new model system. Through the fabrication of planar organic p-(i-)n junctions, we generate an ensemble of oriented CT states that allows the systematic assessment of electric field impacts. By increasing the thickness of the intrinsic layer at the D-A interface from 0 to 20 nm and by applying external voltages up to 6 V, we realize two different scenarios that controllably tune the intrinsic and extrinsic electric interface fields. By this, we obtain significant shifts of the CT-state peak emission of about 0.5 eV (170 nm from red to green color) from the same D-A material combination. This effect can be explained in a classical electrostatic picture, as the interface electric field alters the potential energy of the electric CT-state dipole. This study illustrates that CT-state energies can be tuned significantly if their electric dipoles are aligned to the interface electric field.

16.
Sci Adv ; 10(8): eadk6295, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394199

RESUMO

Soil microorganisms control the fate of soil organic carbon. Warming may accelerate their activities putting large carbon stocks at risk of decomposition. Existing knowledge about microbial responses to warming is based on community-level measurements, leaving the underlying mechanisms unexplored and hindering predictions. In a long-term soil warming experiment in a Subarctic grassland, we investigated how active populations of bacteria and archaea responded to elevated soil temperatures (+6°C) and the influence of plant roots, by measuring taxon-specific growth rates using quantitative stable isotope probing and 18O water vapor equilibration. Contrary to prior assumptions, increased community growth was associated with a greater number of active bacterial taxa rather than generally faster-growing populations. We also found that root presence enhanced bacterial growth at ambient temperatures but not at elevated temperatures, indicating a shift in plant-microbe interactions. Our results, thus, reveal a mechanism of how soil bacteria respond to warming that cannot be inferred from community-level measurements.


Assuntos
Carbono , Solo , Microbiologia do Solo , Bactérias , Archaea
17.
Cancers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893184

RESUMO

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

18.
Soil Biol Biochem ; 60(100): 95-104, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23645937

RESUMO

Substrate quality and the availability of nutrients are major factors controlling microbial decomposition processes in soils. Seasonal alteration in resource availability, which is driven by plants via belowground C allocation, nutrient uptake and litter fall, also exerts effects on soil microbial community composition. Here we investigate if seasonal and experimentally induced changes in microbial community composition lead to alterations in functional properties of microbial communities and thus microbial processes. Beech forest soils characterized by three distinct microbial communities (winter and summer community, and summer community from a tree girdling plot, in which belowground carbon allocation was interrupted) were incubated with different 13C-labeled substrates with or without inorganic N supply and analyzed for substrate use and various microbial processes. Our results clearly demonstrate that the three investigated microbial communities differed in their functional response to addition of various substrates. The winter communities revealed a higher capacity for degradation of complex C substrates (cellulose, plant cell walls) than the summer communities, indicated by enhanced cellulase activities and reduced mineralization of soil organic matter. In contrast, utilization of labile C sources (glucose) was lower in winter than in summer, demonstrating that summer and winter community were adapted to the availability of different substrates. The saprotrophic community established in girdled plots exhibited a significantly higher utilization of complex C substrates than the more plant root associated community in control plots if additional nitrogen was provided. In this study we were able to demonstrate experimentally that variation in resource availability as well as seasonality in temperate forest soils cause a seasonal variation in functional properties of soil microorganisms, which is due to shifts in community structure and physiological adaptations of microbial communities to altered resource supply.

19.
Soil Biol Biochem ; 67(100): 85-93, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24302785

RESUMO

Turbic Cryosols (permafrost soils characterized by cryoturbation, i.e., by mixing of soil layers due to freezing and thawing) are widespread across the Arctic, and contain large amounts of poorly decomposed organic material buried in the subsoil. This cryoturbated organic matter exhibits retarded decomposition compared to organic material in the topsoil. Since soil organic matter (SOM) decomposition is known to be tightly linked to N availability, we investigated N transformation rates in different soil horizons of three tundra sites in north-eastern Siberia and Greenland. We measured gross rates of protein depolymerization, N mineralization (ammonification) and nitrification, as well as microbial uptake of amino acids and NH4+ using an array of 15N pool dilution approaches. We found that all sites and horizons were characterized by low N availability, as indicated by low N mineralization compared to protein depolymerization rates (with gross N mineralization accounting on average for 14% of gross protein depolymerization). The proportion of organic N mineralized was significantly higher at the Greenland than at the Siberian sites, suggesting differences in N limitation. The proportion of organic N mineralized, however, did not differ significantly between soil horizons, pointing to a similar N demand of the microbial community of each horizon. In contrast, absolute N transformation rates were significantly lower in cryoturbated than in organic horizons, with cryoturbated horizons reaching not more than 32% of the transformation rates in organic horizons. Our results thus indicate a deceleration of the entire N cycle in cryoturbated soil horizons, especially strongly reduced rates of protein depolymerization (16% of organic horizons) which is considered the rate-limiting step in soil N cycling.

20.
Breast ; 71: 31-41, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37473629

RESUMO

PURPOSE: Radiation dermatitis (RD) is the most common side effect of adjuvant whole-breast or chest wall irradiation, majorly impacting quality of life in numerous patients. The use of barrier films (polyurethane dressings such as Hydrofilm® and Mepitel® film remaining on the skin for the duration of the radiation treatment) has been investigated as a prophylactic measure in several prospective trials. Here, we critically appraise the available evidence behind preventive barrier film application in the context of breast cancer treatment. METHODS: International literature was reviewed and high-quality randomised controlled trials (RCTs) were included in this meta-analysis. RESULTS: The results of 5 RCTs (663 patients; >90% Caucasian) were analysed. Overall, barrier films lead to improved clinician- and patient-reported outcomes: fewer grade ≥2 RD (11% vs. 42%; OR = 0.16; p < 0.001) and moist desquamation (2% vs. 16%; OR = 0.12; p = 0.006), as well as less patient-reported pain (standardised mean difference [SMD] -0.51; p < 0.001), itching (SMD -0.52; p = 0.001), burning (SMD -0.41; p = 0.011), and limitations in daily activities (SMD -0.20; p = 0.007). Furthermore, barrier films have a high acceptance rate among patients, as well as a favourable cost-benefit ratio. Possible side effects due to its application are mild and mostly self-limiting. Overall, there was a lack of information on the radiation treatment techniques used. CONCLUSION: The evidence presented in this meta-analysis suggests that barrier films are an excellent tool in the prevention of RD among Caucasian patients receiving whole-breast or chest wall irradiation. Its use should therefore be considered routinely in these patients.


Assuntos
Neoplasias da Mama , Radiodermite , Humanos , Feminino , Neoplasias da Mama/radioterapia , Radiodermite/etiologia , Radiodermite/prevenção & controle , Pele , Ensaios Clínicos Controlados Aleatórios como Assunto
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