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1.
Cell ; 174(1): 88-101.e16, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29909986

RESUMO

In colorectal cancer patients, a high density of cytotoxic CD8+ T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/ß-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8+ T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Subsequent release of proteases into the cytoplasm augments MHC class I presentation and activation of CD8+ T cells via cross-dressing of dendritic cells. Thus, our findings highlight a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs and suggest that therapies triggering mitophagy or inducing LMP in IECs may prove successful in shifting the balance toward anti-tumor immunity in colorectal cancer.


Assuntos
Imunidade Adaptativa , Mitofagia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Azoximetano/toxicidade , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Permeabilidade da Membrana Celular , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Compostos Ferrosos/metabolismo , Humanos , Interferon gama/metabolismo , Interferon gama/farmacologia , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Mitofagia/efeitos dos fármacos , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Taxa de Sobrevida
2.
J Headache Pain ; 25(1): 73, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714920

RESUMO

BACKGROUND: Management of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop- concept. Here, we aimed to evaluate effects of this concept on sick leave, presenteeism, and health care utilization. METHODS: In a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding economic outcome parameters assessed over 6 months. Multivariate binary logistic regression models were used to adjust for confounders. RESULTS: Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, the IC group showed significantly fewer days with sick leave or presenteeism (-5 days/month), fewer unscheduled contacts for IIH-specific problems (-2.3/month), and fewer physician or hospital contacts in general (-4.1 contacts/month). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of the IC concept in these groups. CONCLUSIONS: Interdisciplinary integrated management significantly improves the burden of IIH in terms of sick leave, presenteeism and healthcare consultations - particularly in socioeconomically underprivileged patient groups.


Assuntos
Instituições de Assistência Ambulatorial , Aceitação pelo Paciente de Cuidados de Saúde , Presenteísmo , Pseudotumor Cerebral , Licença Médica , Humanos , Feminino , Masculino , Adulto , Estudos Retrospectivos , Licença Médica/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Presenteísmo/estatística & dados numéricos , Pseudotumor Cerebral/terapia , Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade
3.
J Headache Pain ; 25(1): 92, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834953

RESUMO

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a debilitating condition characterized by increased intracranial pressure often presenting with chronic migraine-like headache. Calcitonin gene-related peptide (CGRP) plays an important pathophysiological role in primary headaches such as migraine, whilst its role in IIH has not yet been established. METHODS: This longitudinal exploratory study included patients with IIH, episodic migraine (EM) in a headache-free interval and healthy controls (HC). Blood samples were collected from a cubital vein and plasma CGRP (pCGRP) levels were measured by standardized ELISA. RESULTS: A total of 26 patients with IIH (mean age 33.2 years [SD 9.2], 88.5% female, median BMI 34.8 kg/m2 [IQR 30.0-41.4]), 30 patients with EM (mean age 27.6 years [7.5], 66.7% female) and 57 HC (mean age 25.3 years [5.2], 56.1% female) were included. pCGRP levels displayed a wide variation in IIH as well as in EM and HC on a group-level. Within IIH, those with migraine-like headache had significantly higher pCGRP levels than those with non-migraine-like headache (F(2,524) = 84.79; p < 0.001) and headache absence (F(2,524) = 84.79; p < 0.001) throughout the observation period, explaining 14.7% of the variance in pCGRP levels. CGRP measurements showed strong intraindividual agreement in IIH (ICC 0.993, 95% CI 0.987-0.996, p < 0.001). No association was found between pCGRP levels and ophthalmological parameters. CONCLUSIONS: Although interindividual heterogeneity of pCGRP levels is generally high, migraine-like headache seems to be associated with higher pCGRP levels. CGRP may play a role in the headache pathophysiology at least in a subgroup of IIH.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Pseudotumor Cerebral , Humanos , Feminino , Masculino , Adulto , Peptídeo Relacionado com Gene de Calcitonina/sangue , Pseudotumor Cerebral/sangue , Transtornos de Enxaqueca/sangue , Estudos Longitudinais , Adulto Jovem , Biomarcadores/sangue
4.
Int J Mol Sci ; 24(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240031

RESUMO

Spinal cord injury (SCI) results in the production of proinflammatory cytokines due to inflammasome activation. Lipocalin 2 (LCN2) is a small secretory glycoprotein upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 secretion is induced by infection, injury, and metabolic disorders. In contrast, LCN2 has been implicated as an anti-inflammatory regulator. However, the role of LCN2 in inflammasome activation during SCI remains unknown. This study examined the role of Lcn2 deficiency in the NLRP3 inflammasome-dependent neuroinflammation in SCI. Lcn2-/- and wild-type (WT) mice were subjected to SCI, and locomotor function, formation of the inflammasome complex, and neuroinflammation were assessed. Our findings demonstrated that significant activation of the HMGB1/PYCARD/caspase-1 inflammatory axis was accompanied by the overexpression of LCN2 7 days after SCI in WT mice. This signal transduction results in the cleaving of the pyroptosis-inducing protein gasdermin D (GSDMD) and the maturation of the proinflammatory cytokine IL-1ß. Furthermore, Lcn2-/- mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1ß production, pore formation, and improved locomotor function compared with WT. Our data suggest that LCN2 may play a role as a putative molecule for the induction of inflammasome-related neuroinflammation in SCI.


Assuntos
Proteína HMGB1 , Traumatismos da Medula Espinal , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipocalina-2/genética , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal/metabolismo , Citocinas/metabolismo , Caspases/metabolismo , Piroptose/fisiologia
5.
Laryngorhinootologie ; 102(6): 440-445, 2023 06.
Artigo em Alemão | MEDLINE | ID: mdl-37023779

RESUMO

Aspiration pneumonia is a common cause of death in dysphagia patients. In this review, we investigate whether a structured oral care approach can help to reduce pneumonia risk in dysphagic patients. In addition, guidelines for the implementation of oral care on the basis of the analyzed studies are presented. Oral care has positive effects on the risk of pneumonia in dysphagia patients. Oral care should be based on the principles of simplicity, safety, efficiency and effectiveness, universality and economy and it should include all parts of the oral cavity. Effective oral care takes less than five minutes a day. The tactile stimulation prepares the patient for dysphagia therapy and can be considered wisely-invested time.


Assuntos
Transtornos de Deglutição , Pneumonia Aspirativa , Pneumonia , Humanos , Transtornos de Deglutição/terapia , Transtornos de Deglutição/etiologia , Pneumonia Aspirativa/prevenção & controle , Pneumonia Aspirativa/complicações , Boca
6.
Chimia (Aarau) ; 74(10): 755-757, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115553

RESUMO

Switzerland Innovation, the Swiss innovation park with its five branches, is facilitating collaborations for companies, startups, and universities to find solutions to some of the world's most pressing challenges in the fields of health and the life sciences, in particular in the areas of chemistry, biochemistry, biomedicine, biotech, medtech and digital health. Together with its numerous and diverse partners, Switzerland Innovation creates an ecosystem for universities and research-based companies, accelerating the transformation of research results into marketable products and services.

7.
Cytotherapy ; 20(4): 532-542, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29500069

RESUMO

BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution. We developed and tested the performance of a CD45RA depletion module for the automatic cell-processing device CliniMACS Prodigy and investigated quality attributes of the generated products. METHODS: Unstimulated apheresis products from random volunteer donors were depleted of CD45RA+ cells on CliniMACS Prodigy, using Good Manufacturing Practice (GMP)-compliant reagents and methods throughout. Using phenotypic and functional in vitro assays, we assessed the cellular constitution of CD45RA-depleted products, including T-cell subset analyses, immunological memory function and allo-reactivity. RESULTS: Selections were technically uneventful and proceeded automatically with minimal hands-on time beyond tubing set installation. Products were near-qualitatively CD45RA+ depleted, that is, largely devoid of CD45RA+ T cells but also of almost all B and natural killer cells. Naive and effector as well as γ/δ T cells were greatly reduced. The CD4:CD8 ratio was fivefold increased. Mixed lymphocyte reaction assays of the product against third-party leukocytes revealed reduced allo-reactivity compared to starting material. Anti-pathogen responses were retained. DISCUSSION: The novel, closed, fully GMP-compatible process on Prodigy generates highly CD45RA-depleted cellular products predicted to be clinically meaningfully depleted of GvH reactivity.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Memória Imunológica/fisiologia , Imunoterapia Adotiva , Antígenos Comuns de Leucócito/metabolismo , Depleção Linfocítica , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/transplante , Adulto , Automação Laboratorial , Células Cultivadas , Feminino , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Humanos , Separação Imunomagnética/instrumentação , Separação Imunomagnética/métodos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Leucaférese/instrumentação , Leucaférese/métodos , Teste de Cultura Mista de Linfócitos , Depleção Linfocítica/instrumentação , Depleção Linfocítica/métodos , Masculino , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Doadores de Tecidos , Transplante Homólogo , Adulto Jovem
8.
Sensors (Basel) ; 16(8)2016 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-27529255

RESUMO

Hyperspectral imaging (HSI) is increasingly gaining acceptance in the medical field. Up until now, HSI has been used in conjunction with rigid endoscopy to detect cancer in vivo. The logical next step is to pair HSI with flexible endoscopy, since it improves access to hard-to-reach areas. While the flexible endoscope's fiber optic cables provide the advantage of flexibility, they also introduce an interfering honeycomb-like pattern onto images. Due to the substantial impact this pattern has on locating cancerous tissue, it must be removed before the HS data can be further processed. Thereby, the loss of information is to minimize avoiding the suppression of small-area variations of pixel values. We have developed a system that uses flexible endoscopy to record HS cubes of the larynx and designed a special filtering technique to remove the honeycomb-like pattern with minimal loss of information. We have confirmed its feasibility by comparing it to conventional filtering techniques using an objective metric and by applying unsupervised and supervised classifications to raw and pre-processed HS cubes. Compared to conventional techniques, our method successfully removes the honeycomb-like pattern and considerably improves classification performance, while preserving image details.


Assuntos
Endoscopia/métodos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/diagnóstico , Endoscopia/instrumentação , Humanos , Neoplasias Laríngeas/patologia
9.
J Sci Food Agric ; 96(1): 271-9, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25641020

RESUMO

BACKGROUND: Baseline research on the toughness of Egyptian goose meat is required. This study therefore investigates the post mortem pH and temperature decline (15 min-4 h 15 min post mortem) in the pectoralis muscle (breast portion) of this gamebird species. It also explores the enzyme activity of the Ca(2+)-dependent protease (calpain system) and the lysosomal cathepsins during the rigor mortis period. RESULTS: No differences were found for any of the variables between genders. The pH decline in the pectoralis muscle occurs quite rapidly (c = -0.806; ultimate pH ∼ 5.86) compared with other species and it is speculated that the high rigor temperature (>20 °C) may contribute to the increased toughness. No calpain I was found in Egyptian goose meat and the µ/m-calpain activity remained constant during the rigor period, while a decrease in calpastatin activity was observed. The cathepsin B, B & L and H activity increased over the rigor period. CONCLUSION: Further research into the connective tissue content and myofibrillar breakdown during aging is required in order to know if the proteolytic enzymes do in actual fact contribute to tenderisation.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Calpaína/metabolismo , Catepsinas/metabolismo , Carne/análise , Músculos Peitorais/metabolismo , Rigor Mortis , Temperatura , Animais , Egito , Feminino , Gansos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Estresse Mecânico
10.
J Sci Food Agric ; 96(5): 1828-35, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-26183427

RESUMO

BACKGROUND: Egyptian goose breast meat has been found to be very tough compared to the meat of other well-known fowl species. In attempting to clarify the toughness of the meat, the physical and biochemical changes during post-mortem conditioning (14 days) was investigated. RESULTS: Although there was increased cathepsin (B, B & L and H) activity, together with a decrease (P ≤ 0.05) in myofibrillar fragmentation lengths (32-25 µm) with conditioning, no change (decline) in shear force values was observed. The higher (P ≤ 0.05) shear force of the male breast portions may be linked to the higher (P ≤ 0.05) concentrations of total and insoluble collagen. CONCLUSIONS: No significant change (decline) in shear force values was observed. Conditioning of Egyptian goose meat as a means of improving the overall toughness cannot therefore not be proposed. The higher shear force and lower sensory tenderness of the male breast portions, as previously observed, may be linked to higher concentrations of total and insoluble collagen.


Assuntos
Análise de Alimentos , Manipulação de Alimentos/métodos , Carne/análise , Animais , Anseriformes , Catepsinas/metabolismo , Feminino , Masculino , Músculos Peitorais/química , Músculos Peitorais/metabolismo , Sensação
11.
Poult Sci ; 94(5): 1075-87, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25810407

RESUMO

With the current absence of scientific information on the nutritive aspects it is essential to investigate the fatty acid, mineral, and amino acid composition of Egyptian geese as well as the factors of influence. The forage vs. grain based diets of Egyptian geese during certain periods of the yr leads to variation in the content of the key fatty acids such as oleic acid, linoleic acid, and α-linolenic acid. The differences in these fatty acids results in variation between the n-6/n-3 ratios of the seasons; the portions from winter (July) are within the recommendations (ratio <5) and those from summer (November) not. This study indicates that Egyptian goose meat does not only vary in nutritional composition but season may also have a substantial effect on the flavor profile and ultimate uniformity of the meat. The season and portion effects were, however, interlinked but the general tendency shows that the portions, especially the breast and thigh do differ concerning the major fatty acids. No substantial differences were found in the mineral composition of the breast portion on account of season and gender; however there were some variation in certain amino acids such as lysine and arginine due to season/diet. This research provides essential information that should be considered not only regarding the everyday consumption of Egyptian goose meat but the potential utilization and ultimate consistency of this meat product.


Assuntos
Aminoácidos/química , Ácidos Graxos/química , Carne/análise , Minerais/química , Animais , Anseriformes , Feminino , Masculino , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/química , Estações do Ano , Fatores Sexuais
12.
Int J Cancer ; 134(11): 2547-59, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24243620

RESUMO

Epidermal growth factor receptor (EGFR) plays an important role in essential cellular processes such as proliferation, survival and migration. Aberrant activation of EGFR is frequently found in human cancers of various origins and has been implicated in cancer pathogenesis. The therapeutic antibody cetuximab (Erbitux) inhibits tumor growth by binding to the extracellular domain of EGFR, thereby preventing ligand binding and receptor activation. This activity is shared by the single chain antibody fragment scFv(225) that contains the same antigen binding domain. The unrelated EGFR-specific antibody fragment scFv(30) binds to the intracellular domain of the receptor and retains antigen binding upon expression as an intrabody in the reducing environment of the cytosol. Here, we used scFv(225) and scFv(30) domains to generate a novel type of bispecific transmembrane antibody termed 225.TM.30, that simultaneously targets intra- and extracellular EGFR epitopes. Bispecific 225.TM.30 and related membrane-anchored monospecific 225.TM and TM.30 proteins carrying extracellular scFv(225) or intracellular scFv(30) antibody fragments linked to a transmembrane domain were expressed in EGFR-overexpressing tumor cells using a doxycycline-inducible retroviral system. Induced expression of 225.TM.30 and 225.TM, but not TM.30 reduced EGFR surface levels and ligand-induced EGFR activation, while all three molecules markedly inhibited tumor cell growth. Co-localization of 225.TM with EGFR was predominantly found on the cell surface, while interaction with 225.TM.30 and TM.30 proteins resulted in the redistribution of EGFR to perinuclear compartments. Our data demonstrate functionality of this novel type of membrane-anchored intrabodies in tumor cells and suggest distinct modes of action of mono- and bispecific variants.


Assuntos
Anticorpos Biespecíficos/farmacologia , Neoplasias da Mama/terapia , Epitopos/imunologia , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/terapia , Anticorpos de Cadeia Única/farmacologia , Anticorpos Biespecíficos/imunologia , Western Blotting , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Membrana Celular/imunologia , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Feminino , Humanos , Imunoprecipitação , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Fosforilação , Transdução de Sinais , Anticorpos de Cadeia Única/imunologia , Células Tumorais Cultivadas
13.
J Cell Sci ; 125(Pt 21): 5196-207, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22899711

RESUMO

Chaperone-assisted sorting of post-translationally imported proteins is a general mechanism among all eukaryotic organisms. Interaction of some preproteins with the organellar membranes is mediated by chaperones, which are recognised by membrane-bound tetratricopeptide repeat (TPR) domain containing proteins. We have characterised AtTPR7 as an endoplasmic reticulum protein in plants and propose a potential function for AtTPR7 in post-translational protein import. Our data demonstrate that AtTPR7 interacts with the heat shock proteins HSP90 and HSP70 via a cytosol-exposed TPR domain. We further show by in vitro and in vivo experiments that AtTPR7 is associated with the Arabidopsis Sec63 homologue, AtERdj2. Interestingly, AtTPR7 can functionally complement a Δsec71 yeast mutant that is impaired in post-translational protein transport. These data strongly suggest that AtTPR7 not only has a role in chaperone binding but also in post-translational protein import into the endoplasmic reticulum, pointing to a general mechanism of chaperone-mediated post-translational sorting between the endoplasmic reticulum, mitochondria and chloroplasts in plant cells.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Chaperonas Moleculares/metabolismo , Sequência de Aminoácidos , Arabidopsis/citologia , Proteínas de Arabidopsis/química , Células Cultivadas , Retículo Endoplasmático/metabolismo , Técnicas de Inativação de Genes , Teste de Complementação Genética , Proteínas de Choque Térmico/metabolismo , Membranas Intracelulares/metabolismo , Chaperonas Moleculares/química , Anotação de Sequência Molecular , Dados de Sequência Molecular , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Transporte Proteico , Saccharomyces cerevisiae , Homologia de Sequência de Aminoácidos , Nicotiana
14.
Poult Sci ; 92(11): 3050-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24135611

RESUMO

There is no scientific research regarding Egyptian goose (Alopochen aegyptiacus) meat; therefore, a chemical analysis to establish the nutritional characteristics of the breast portion is described. Meat from guinea fowl, Pekin duck, ostrich, and broiler chicken were used as a reference. The high intramuscular fat content of Egyptian goose meat (5.6 g/100 g) may be linked to the fact that this species relies on fat for heat insulation and buoyancy. Egyptian goose meat is very high in polyunsaturated fatty acids (39.7%). The polyunsaturated fatty acid/saturated fatty acid ratio is within the recommendations (>0.4), although the n-6/n-3 ratio is higher than the suggested value of 5. The high Fe content of 7.5 mg/100 g is the differentiating factor within the mineral compositions and is related to the physical activity endured by the breast muscle of Egyptian geese. This study provides new insight into the nutritional characteristics of a meat species providing crucial information that is, as of yet, not available in the literature.


Assuntos
Anseriformes/fisiologia , Galliformes/fisiologia , Carne/análise , Valor Nutritivo , Struthioniformes/fisiologia , Animais , Composição Corporal
15.
Poult Sci ; 92(12): 3283-91, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24235240

RESUMO

The carcass yield, physical characteristics, and proximate composition of Egyptian geese (Alopochen aegyptiacus), a southern African gamebird species, have been studied. A total of 69 geese were harvested during 2 seasons: summer (n = 36) and winter (n = 33). This total group of geese consisted of 27 female birds and 42 male birds. Sex alone affected (P ≤ 0.05) the live and carcass weights, and the average muscle weight (g) of each portion was higher for the male fowl. The data does not indicate differences between the meat's physical characteristics on account of sex; however, the meat from the female birds did have a higher intramuscular fat content. Season (winter vs. summer) did not influence the average muscle weights (g) of the breast, thigh, and drumstick portions, but the intramuscular fat content content of the birds hunted in winter was higher. Muscle color and pH differed as a result of season with the summer meat having a higher pH and more vivid red color compared with winter. The physical characteristics and the proximate composition of the breast, thigh, and drumstick portions varied considerably. This is essentially connected to a difference in physical activity of the muscles in the portions. Overall, this study revealed that to ensure a consistent eating quality the harvesting periods of Egyptian geese should be considered.


Assuntos
Gansos/fisiologia , Carne/análise , Criação de Animais Domésticos , Animais , Composição Corporal , Cor , Dieta/veterinária , Feminino , Concentração de Íons de Hidrogênio , Masculino , Estações do Ano , Caracteres Sexuais , África do Sul
16.
Nat Genet ; 36(12): 1319-25, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15565110

RESUMO

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.


Assuntos
Antidepressivos/uso terapêutico , Depressão/genética , Proteínas de Choque Térmico HSP90/genética , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Receptores de Glucocorticoides/genética , Adulto , Análise de Variância , Antidepressivos/administração & dosagem , Western Blotting , Hormônio Liberador da Corticotropina/genética , Depressão/tratamento farmacológico , Fluorescência , Frequência do Gene , Genótipo , Alemanha , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Linfócitos/metabolismo , Neurofisinas/genética , Precursores de Proteínas/genética , Receptores de Glucocorticoides/metabolismo , Análise de Regressão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vasopressinas/genética
17.
J Sci Food Agric ; 93(11): 2829-40, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23427009

RESUMO

BACKGROUND: Malolactic fermentation (MLF) mediated by lactic acid bacteria (LAB) has been shown to modulate chemical and sensory attributes of wine. This study investigated the relation between consumer liking, chemical and sensory attributes of Vitis vinifera L. cv. Pinotage wines that were made over two vintages by four different lactic acid Oenococcus oeni starter cultures as well as a control treatment where MLF was prevented. RESULTS: Descriptive analysis showed that the sensory attributes buttery, caramel, vegetative flavour, fruity and nutty aroma differed significantly between the wines. These effects on the wines were not the same for the two vintages tested. Preference mapping results showed that the sensory attributes influenced the average consumer liking. The main chemical and sensory correlations found for MLF-treated wines were related to 2,3-butanedione (diacetyl) with the buttery character and various esters with fruity aromas. CONCLUSION: Although the direct effect of the bacterial starter cultures on wine sensory attributes is difficult to establish, and subject to variation over vintage, the present work suggests that the contribution of LAB starter cultures to wine sensory attributes can influence consumer liking. Selection of an MLF starter culture can thus potentially be used to develop specific wine styles.


Assuntos
Oenococcus/classificação , Oenococcus/metabolismo , Vitis/classificação , Vinho/normas , Comportamento do Consumidor , Fermentação , Humanos , Paladar
18.
J Sci Food Agric ; 93(7): 1610-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23132727

RESUMO

BACKGROUND: As eating quality is important for adoption of new varieties, nine orange-fleshed and three cream-fleshed sweet potato varieties were assessed for sensory characteristics, dry mass and free sugar content, instrumental texture and colour and consumer acceptability (n = 216) in a peri-urban South African setting. RESULTS: Cream-fleshed varieties were higher in yellow-green colour and sweet potato-like flavour and lower in graininess. Orange-fleshed varieties were higher in pumpkin-like flavour, orange colour, discolouration and sucrose content. Partial least squares regression analysis showed that the most accepted varieties (Impilo, Excel, Resisto, 2001_5_2, Serolane, W-119 and Monate) were associated with sweet flavour, dry mass and maltose content, while the least accepted varieties (Beauregard, Khano and 1999_1_7) were associated with wateriness. Pearson correlation analysis highlighted correlations of sensory attributes yellow and orange with instrumental colour measurements (colour a* and colour b*), instrumental firmness with sensory firmness, dry mass with sensory wateriness, and maltose content with sensory sweet and sweet potato-like flavour. The varieties were clustered into three groups. Consumer acceptability for eating quality correlated with maltose content, dry mass and sweet flavour. CONCLUSION: Chemical and instrumental measurements were identified to evaluate key attributes and will be useful in the intermediate phases of sweet potato varietal development.


Assuntos
Comportamento do Consumidor , Preferências Alimentares , Qualidade dos Alimentos , Ipomoea batatas/química , Maltose/análise , Paladar , Água/análise , Cor , Dieta , Sacarose Alimentar/análise , Dureza , Humanos , Ipomoea batatas/classificação , Análise dos Mínimos Quadrados , Tubérculos/química , África do Sul , Especificidade da Espécie
19.
Cancer Res ; 83(15): 2471-2479, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37289018

RESUMO

The emergence of resistance to targeted therapies restrains their efficacy. The development of rationally guided drug combinations could overcome this currently insurmountable clinical challenge. However, our limited understanding of the trajectories that drive the outgrowth of resistant clones in cancer cell populations precludes design of drug combinations to forestall resistance. Here, we propose an iterative treatment strategy coupled with genomic profiling and genome-wide CRISPR activation screening to systematically extract and define preexisting resistant subpopulations in an EGFR-driven lung cancer cell line. Integrating these modalities identifies several resistance mechanisms, including activation of YAP/TAZ signaling by WWTR1 amplification, and estimates the associated cellular fitness for mathematical population modeling. These observations led to the development of a combination therapy that eradicated resistant clones in large cancer cell line populations by exhausting the spectrum of genomic resistance mechanisms. However, a small fraction of cancer cells was able to enter a reversible nonproliferative state of drug tolerance. This subpopulation exhibited mesenchymal properties, NRF2 target gene expression, and sensitivity to ferroptotic cell death. Exploiting this induced collateral sensitivity by GPX4 inhibition clears drug-tolerant populations and leads to tumor cell eradication. Overall, this experimental in vitro data and theoretical modeling demonstrate why targeted mono- and dual therapies will likely fail in sufficiently large cancer cell populations to limit long-term efficacy. Our approach is not tied to a particular driver mechanism and can be used to systematically assess and ideally exhaust the resistance landscape for different cancer types to rationally design combination therapies. SIGNIFICANCE: Unraveling the trajectories of preexisting resistant and drug-tolerant persister cells facilitates the rational design of multidrug combination or sequential therapies, presenting an approach to explore for treating EGFR-mutant lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Transdução de Sinais , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Mutação
20.
J Sci Food Agric ; 92(13): 2741-50, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22522565

RESUMO

BACKGROUND: Plum skins are a waste product generated during production of plum juice or pulp. Polyphenols, shown to have various health-promoting properties, can be recovered from this waste product. Red-fleshed plum nectar formulations containing plum skin extract in varying amounts were characterised in terms of intensity of sensory attributes, consumer acceptability, colour, polyphenol content and antioxidant activity. Commercial beverages containing red fruits were used as benchmarks. RESULTS: The polyphenolic profile of the plum skin extract was similar to that of the pulp, including anthocyanins, flavonols, flavan-3-ols and a phenolic acid. Addition of the extract to plum nectar, which enhanced the colour, polyphenol content and antioxidant capacity, was limited by its negative sensory impact. The formulations were deemed acceptable by consumers, although a decrease in positive sensory attributes (plum flavour, plum aroma and sweetness) and an increase in negative sensory attributes (plant-like flavour, plant-like aroma, acidity and astringency) were observed with increasing skin extract content. The formulations compared favourably with commercial beverages in terms of colour total polyphenol content and antioxidant activity. CONCLUSION: Plum skins were successfully used to enhance the functional status of plum nectar. Use of a functional ingredient from plum skins is, therefore, a feasible value-addition strategy.


Assuntos
Antioxidantes/análise , Comportamento do Consumidor , Frutas/química , Extratos Vegetais/química , Preparações de Plantas , Polifenóis/análise , Prunus/química , Ácidos , Antioxidantes/farmacologia , Adstringentes , Bebidas , Cor , Alimento Funcional , Odorantes , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Paladar
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