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1.
Cell ; 174(1): 88-101.e16, 2018 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-29909986

RESUMEN

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.


Asunto(s)
Inmunidad Adaptativa , Mitofagia , Inmunidad Adaptativa/efectos de los fármacos , Animales , Azoximetano/toxicidad , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Permeabilidad de la Membrana Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Citocinas/metabolismo , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Compuestos Ferrosos/metabolismo , Humanos , Interferón gamma/metabolismo , Interferón gamma/farmacología , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Lisosomas/metabolismo , Masculino , Ratones , Ratones Noqueados , Mitofagia/efectos de los fármacos , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Tasa de Supervivencia
2.
J Headache Pain ; 25(1): 73, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714920

RESUMEN

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.


Asunto(s)
Instituciones de Atención Ambulatoria , Aceptación de la Atención de Salud , Presentismo , Seudotumor Cerebral , Ausencia por Enfermedad , Humanos , Femenino , Masculino , Adulto , Estudios Retrospectivos , Ausencia por Enfermedad/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Presentismo/estadística & datos numéricos , Seudotumor Cerebral/terapia , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Persona de Mediana Edad
3.
J Headache Pain ; 25(1): 92, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834953

RESUMEN

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.


Asunto(s)
Péptido Relacionado con Gen de Calcitonina , Trastornos Migrañosos , Seudotumor Cerebral , Humanos , Femenino , Masculino , Adulto , Péptido Relacionado con Gen de Calcitonina/sangre , Seudotumor Cerebral/sangre , Trastornos Migrañosos/sangre , Estudios Longitudinales , Adulto Joven , Biomarcadores/sangre
4.
Int J Mol Sci ; 24(10)2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37240031

RESUMEN

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.


Asunto(s)
Proteína HMGB1 , Traumatismos de la Médula Espinal , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lipocalina 2/genética , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Enfermedades Neuroinflamatorias , Traumatismos de la Médula Espinal/metabolismo , Citocinas/metabolismo , Caspasas/metabolismo , Piroptosis/fisiología
5.
Laryngorhinootologie ; 102(6): 440-445, 2023 06.
Artículo en Alemán | MEDLINE | ID: mdl-37023779

RESUMEN

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.


Asunto(s)
Trastornos de Deglución , Neumonía por Aspiración , Neumonía , Humanos , Trastornos de Deglución/terapia , Trastornos de Deglución/etiología , Neumonía por Aspiración/prevención & control , Neumonía por Aspiración/complicaciones , Boca
6.
Chimia (Aarau) ; 74(10): 755-757, 2020 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-33115553

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-29500069

RESUMEN

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.


Asunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Memoria Inmunológica/fisiología , Inmunoterapia Adoptiva , Antígenos Comunes de Leucocito/metabolismo , Depleción Linfocítica , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/trasplante , Adulto , Automatización de Laboratorios , Células Cultivadas , Femenino , Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad , Humanos , Separación Inmunomagnética/instrumentación , Separación Inmunomagnética/métodos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Leucaféresis/instrumentación , Leucaféresis/métodos , Prueba de Cultivo Mixto de Linfocitos , Depleción Linfocítica/instrumentación , Depleción Linfocítica/métodos , Masculino , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/inmunología , Donantes de Tejidos , Trasplante Homólogo , Adulto Joven
8.
Sensors (Basel) ; 16(8)2016 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-27529255

RESUMEN

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.


Asunto(s)
Endoscopía/métodos , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/diagnóstico , Endoscopía/instrumentación , Humanos , Neoplasias Laríngeas/patología
9.
J Sci Food Agric ; 96(1): 271-9, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25641020

RESUMEN

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.


Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Calpaína/metabolismo , Catepsinas/metabolismo , Carne/análisis , Músculos Pectorales/metabolismo , Rigor Mortis , Temperatura , Animales , Egipto , Femenino , Gansos , Humanos , Concentración de Iones de Hidrógeno , Masculino , Estrés Mecánico
10.
J Sci Food Agric ; 96(5): 1828-35, 2016 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-26183427

RESUMEN

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.


Asunto(s)
Análisis de los Alimentos , Manipulación de Alimentos/métodos , Carne/análisis , Animales , Anseriformes , Catepsinas/metabolismo , Femenino , Masculino , Músculos Pectorales/química , Músculos Pectorales/metabolismo , Sensación
11.
Poult Sci ; 94(5): 1075-87, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25810407

RESUMEN

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.


Asunto(s)
Aminoácidos/química , Ácidos Grasos/química , Carne/análisis , Minerales/química , Animales , Anseriformes , Femenino , Masculino , Músculo Esquelético/anatomía & histología , Músculo Esquelético/química , Estaciones del Año , Factores Sexuales
12.
Int J Cancer ; 134(11): 2547-59, 2014 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-24243620

RESUMEN

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.


Asunto(s)
Anticuerpos Biespecíficos/farmacología , Neoplasias de la Mama/terapia , Epítopos/inmunología , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/terapia , Anticuerpos de Cadena Única/farmacología , Anticuerpos Biespecíficos/inmunología , Western Blotting , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Membrana Celular/inmunología , Proliferación Celular , Ensayo de Inmunoadsorción Enzimática , Receptores ErbB/inmunología , Receptores ErbB/metabolismo , Femenino , Humanos , Inmunoprecipitación , Inmunoterapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Fosforilación , Transducción de Señal , Anticuerpos de Cadena Única/inmunología , Células Tumorales Cultivadas
13.
J Cell Sci ; 125(Pt 21): 5196-207, 2012 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-22899711

RESUMEN

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.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Secuencia de Aminoácidos , Arabidopsis/citología , Proteínas de Arabidopsis/química , Células Cultivadas , Retículo Endoplásmico/metabolismo , Técnicas de Inactivación de Genes , Prueba de Complementación Genética , Proteínas de Choque Térmico/metabolismo , Membranas Intracelulares/metabolismo , Chaperonas Moleculares/química , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Mapeo de Interacción de Proteínas , Estructura Terciaria de Proteína , Transporte de Proteínas , Saccharomyces cerevisiae , Homología de Secuencia de Aminoácido , Nicotiana
14.
Poult Sci ; 92(11): 3050-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24135611

RESUMEN

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.


Asunto(s)
Anseriformes/fisiología , Galliformes/fisiología , Carne/análisis , Valor Nutritivo , Struthioniformes/fisiología , Animales , Composición Corporal
15.
Poult Sci ; 92(12): 3283-91, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24235240

RESUMEN

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.


Asunto(s)
Gansos/fisiología , Carne/análisis , Crianza de Animales Domésticos , Animales , Composición Corporal , Color , Dieta/veterinaria , Femenino , Concentración de Iones de Hidrógeno , Masculino , Estaciones del Año , Caracteres Sexuales , Sudáfrica
16.
Nat Genet ; 36(12): 1319-25, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15565110

RESUMEN

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.


Asunto(s)
Antidepresivos/uso terapéutico , Depresión/genética , Proteínas HSP90 de Choque Térmico/genética , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Polimorfismo de Nucleótido Simple/genética , Receptores de Glucocorticoides/genética , Adulto , Análisis de Varianza , Antidepresivos/administración & dosificación , Western Blotting , Hormona Liberadora de Corticotropina/genética , Depresión/tratamiento farmacológico , Fluorescencia , Frecuencia de los Genes , Genotipo , Alemania , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Linfocitos/metabolismo , Neurofisinas/genética , Precursores de Proteínas/genética , Receptores de Glucocorticoides/metabolismo , Análisis de Regresión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vasopresinas/genética
17.
J Sci Food Agric ; 93(11): 2829-40, 2013 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-23427009

RESUMEN

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.


Asunto(s)
Oenococcus/clasificación , Oenococcus/metabolismo , Vitis/clasificación , Vino/normas , Comportamiento del Consumidor , Fermentación , Humanos , Gusto
18.
J Sci Food Agric ; 93(7): 1610-9, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23132727

RESUMEN

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.


Asunto(s)
Comportamiento del Consumidor , Preferencias Alimentarias , Calidad de los Alimentos , Ipomoea batatas/química , Maltosa/análisis , Gusto , Agua/análisis , Color , Dieta , Sacarosa en la Dieta/análisis , Dureza , Humanos , Ipomoea batatas/clasificación , Análisis de los Mínimos Cuadrados , Tubérculos de la Planta/química , Sudáfrica , Especificidad de la Especie
19.
Cancer Res ; 83(15): 2471-2479, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37289018

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Transducción de Señal , Receptores ErbB/metabolismo , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Mutación
20.
J Sci Food Agric ; 92(13): 2741-50, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22522565

RESUMEN

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.


Asunto(s)
Antioxidantes/análisis , Comportamiento del Consumidor , Frutas/química , Extractos Vegetales/química , Preparaciones de Plantas , Polifenoles/análisis , Prunus/química , Ácidos , Antioxidantes/farmacología , Astringentes , Bebidas , Color , Alimentos Funcionales , Odorantes , Extractos Vegetales/farmacología , Polifenoles/farmacología , Gusto
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