| 1. |
- Pocas, Juliana, et al.
(författare)
-
Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
- 2023
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:20
-
Tidskriftsartikel (refereegranskat)abstract
- Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
|
|
| 2. |
- Ferreira, Catarina, et al.
(författare)
-
Polyphasic characterization of carbapenemresistant Klebsiella pneumoniae clinical isolates suggests vertical transmission of the bla KPC-3 gene
- 2021
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 16:2 Febuary
-
Tidskriftsartikel (refereegranskat)abstract
- Carbapenem-resistant Klebsiella pneumoniae are a major global threat in healthcare facilities. The propagation of carbapenem resistance determinants can occur through vertical transmission, with genetic elements being transmitted by the host bacterium, or by horizontal transmission, with the same genetic elements being transferred among distinct bacterial hosts. This work aimed to track carbapenem resistance transmission by K. pneumoniae in a healthcare facility. The study involved a polyphasic approach based on conjugation assays, resistance phenotype and genotype analyses, whole genome sequencing, and plasmid characterization by pulsed field gel electrophoresis and optical DNA mapping. Out of 40 K. pneumoniae clinical isolates recovered over two years, five were carbapenem- and multidrug- resistant and belonged to multilocus sequence type ST147. These isolates harboured the carbapenemase encoding blaKPC-3 gene, integrated in conjugative plasmids of 140 kbp or 55 kbp, belonging to replicon types incFIA/incFIIK or incN/incFIIK, respectively. The two distinct plasmids encoding the blaKPC-3 gene were associated with distinct genetic lineages, as confirmed by optical DNA mapping and whole genome sequence analyses. These results suggested vertical (bacterial strain-based) transmission of the carbapenem-resistance genetic elements. Determination of the mode of transmission of antibiotic resistance in healthcare facilities, only possible based on polyphasic approaches as described here, is essential to control resistance propagation.
|
|
| 3. |
- Garcia, Catarina, et al.
(författare)
-
Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors
- 2020
-
Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is among the leading causes of death worldwide. One of the most challenging obstacles in cancer treatment is multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp) is associated with MDR. The growing incidence of cancer and the development of MDR drive the search for novel and more effective anticancer drugs to overcome the MDR problem. Royleanones are natural bioactive compounds frequently found in Plectranthus spp. The cytotoxic diterpene 6,7-dehydroroyleanone (1) is the main component of the P. madagascariensis (Pers.) Benth. essential oil, while 7α-acetoxy-6β-hydroxyroyleanone (2) can be isolated from acetonic extracts of P. grandidentatus Gürke. The reactivity of the natural royleanones 1 and 2 was explored to obtain a small library of new P-gp inhibitors. Four new derivatives (6,7-dehydro-12-O-tert-butyl-carbonate-royleanone (20), 6,7-dehydro-12-O-methylroyleanone (21), 6,7-dehydro-12-O-benzoylroyleanone (22), and 7α-acetoxy-6β-hydroxy-12-O-benzoylroyleanone (23) were obtained as pure with overall modest to excellent yields (21–97%). P-gp inhibition potential of the derivatives 20–23 was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R with the P-gp overexpression, through MTT assay. Previously prepared diterpene 7α-acetoxy-6β-benzoyloxy-12-O-(4-chloro)benzoylroyleanone (4), has also been tested. The P-gp inhibiting effects of compounds 1–4 were also assessed through a Rhodamine 123 accumulation assay. Derivatives 4 and 23 have significant P-gp inhibitory potential. Regarding stability and P-gp inhibition potential, results suggest that the formation of benzoyl esters is a more convenient approach for future derivatives with enhanced effect on the cell viability decrease. Compound 4 presented higher anti-P-gp potential than the natural diterpenes 1, 2, and 3, with comparable inhibitory potential to Dexverapamil. Moreover, derivative 4 showed the ability to sensitize the resistant NCI-H460/R cells to doxorubicin.
|
|
| 4. |
- Kurz, Alexander, et al.
(författare)
-
RHAPSODY - Internet-based support for caregivers of people with young onset dementia : program design and methods of a pilot study
- 2016
-
Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 28:12, s. 2091-2099
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Young Onset Dementia (YOD), defined by first symptoms of cognitive or behavioral decline occurring before the age of 65 years, is relatively rare compared to dementia of later onset, but it is associated with diagnostic difficulty and heavy burden on affected individuals and their informal carers. Existing health and social care structures rarely meet the needs of YOD patients. Internet-based interventions are a novel format of delivering health-related education, counseling, and support to this vulnerable yet underserved group. Methods: The RHAPSODY (Research to Assess Policies and Strategies for Dementia in the Young) project is a European initiative to improve care for people with YOD by providing an internet-based information and skill-building program for family carers. The e-learning program focuses on managing problem behaviors, dealing with role change, obtaining support, and looking after oneself. It will be evaluated in a pilot study in three countries using a randomized unblinded design with a wait-list control group. Participants will be informal carers of people with dementia in Alzheimer's disease or behavioral-variant Frontotemporal degeneration with an onset before the age of 65 years. The primary outcome will be caregiving self-efficacy after 6 weeks of program use. As secondary outcomes, caregivers' stress and burden, carer health-related quality of life, caring-related knowledge, patient problem behaviors, and user satisfaction will be assessed. Program utilization will be monitored and a health-economic evaluation will also be performed. Conclusions: The RHAPSODY project will add to the evidence on the potential and limitations of a conveniently accessible, user-friendly, and comprehensive internet-based intervention as an alternative for traditional forms of counseling and support in healthcare, aiming to optimize care and support for people with YOD and their informal caregivers.
|
|
| 5. |
- Bolmsjö, Gunnar, 1955-, et al.
(författare)
-
Robotic Friction Stir Welding of complex geometry and mixed materials
- 2018
-
Ingår i: 50th International Symposium on Robotics, ISR 2018. - : VDE Verlag GmbH. - 9783800746996 - 9781510870314 ; , s. 35-41
-
Konferensbidrag (refereegranskat)abstract
- Friction stir welding (FSW) is a solid state process for joining materials which has demonstrated advantages compares with other methods which include joining of mixed materials, hard to weld alloys and consistent and high quality. This paper presents a study of robotic FSW initiated by Volvo Skövde plant to join an insert workpiece of extruded aluminium with a cylinder block of aluminium casting. A three-stage procedure was decided to determine the feasibility to apply robotic FSW. The stages included study of welding the mixed materials, weld along the complex joint line with holes and channels close to the joint, and finally welding the cylinder block. The results based on preliminary analysis indicate that the final tests were successful and the process is feasible for the challenging case study. However, further studies are recommended in order to identify the operating parameters window, tool design, and control of the process in order to optimize productivity and quality. © VDE VERLAG GMBH
|
|
| 6. |
- Farinha-Ferreira, Miguel, et al.
(författare)
-
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior
- 2022
-
Ingår i: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 214
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely & UDelta;9-tetrahydro-cannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct out-comes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious-or depressive-like behaviors. We then tested whether chronic adolescent HU -210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treat-ment simultaneously induced marked antidepressant-and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.
|
|
| 7. |
- Ferreira, Catarina, et al.
(författare)
-
Genetic variation in the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain
- 2019
-
Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 220, s. 748-759
-
Tidskriftsartikel (refereegranskat)abstract
- Bacteria harboring conjugative plasmids have the potential for spreading antibiotic resistance through horizontal gene transfer. It is described that the selection and dissemination of antibiotic resistance is enhanced by stressors, like metals or antibiotics, which can occur as environmental contaminants. This study aimed at unveiling the composition of the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain (H1FC54) under different mating conditions. To meet this objective, plasmid pulsed field gel electrophoresis, optical mapping analyses and DNA sequencing were used in combination with phenotype analysis. Strain H1FC54 was observed to harbor five plasmids, three of which were conjugative and two of these, pH1FC54_330 and pH1FC54_140, contained metal and antibiotic resistance genes. Transconjugants obtained in the absence or presence of tellurite (0.5 μM or 5 μM), arsenite (0.5 μM, 5 μM or 15 μM) or ceftazidime (10 mg/L) and selected in the presence of sodium azide (100 mg/L) and tetracycline (16 mg/L) presented distinct phenotypes, associated with the acquisition of different plasmid combinations, including two co-integrate plasmids, of 310 kbp and 517 kbp. The variable composition of the conjugative plasmidome, the formation of co-integrates during conjugation, as well as the transfer of non-transferable plasmids via co-integration, and the possible association between antibiotic, arsenite and tellurite tolerance was demonstrated. These evidences bring interesting insights into the comprehension of the molecular and physiological mechanisms that underlie antibiotic resistance propagation in the environment.
|
|
| 8. |
- Ferreira, Manuel A R, et al.
(författare)
-
Eleven loci with new reproducible genetic associations with allergic disease risk.
- 2019
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
|
|
| 9. |
- Ferreira Magalhães, Ana Catarina, 1986-, et al.
(författare)
-
Thermal dissipation effect on temperature-controlled friction stir welding : [Efeito da dissipação térmica inducida durante soldadura por friçcão linear sob controlo de temperatura]
- 2019
-
Ingår i: Soldagem & Inspeção. - 0104-9224 .- 1980-6973. ; 24
-
Tidskriftsartikel (refereegranskat)abstract
- During Friction Stir Welding (FSW) of complex geometries, the thermal dissipation, induced by geometric features or the surrounding environment, may strongly affect the final weld quality. In order to guarantee a consistent weld quality for different conditions, in-process welding parameter adaptation is needed. This paper studies the effect of thermal dissipation, induced by the backing bar thermal conductivity, on the weld temperature and the temperature controller response to it. A new temperature sensor solution, the Tool-Workpiece Thermocouple (TWT) method, was applied to acquire online temperature measurements during welding. An FSW-robot equipped with temperature control, achieved by rotation speed adaptation, was used. AA7075-T6 lap joints were performed with and without temperature control. The cooling rate during welding was register plus macrographs and tensile tests were assessed. The controller demonstrated a fast response promoting the heat input necessary to maintain the set welding temperature. The results demonstrated that temperature control using the TWT method is suitable to achieve higher joint performance and provides a fast setup of optimal parameters for different environments. © 2019, Universidade Federal de Uberlandia. All rights reserved.
|
|
| 10. |
- Ferreira Magalhães, Ana Catarina, 1986-
(författare)
-
Thermoelectric Measurements for Temperature Control of Robotic Friction Stir Welding
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Friction stir welding (FSW) has undergone a rapid expansion in several industrial sectors such as in the aerospace, marine, railway and automotive sectors. Current industrial applications are mainly simple long straight welds, but there is a growth of interest in components with higher geometric complexity. However, welding of geometrically complex components represents a challenging task due to the resulting uneven induced thermal dissipation along the weld, but especially due to the need for suitable equipment, able to accurately follow a complex 3D path under high mechanical loads, while managing the machine deflection. This is the case for robots, where the high process forces result in deflections, which affects robots' compliance, leading to weld failures and poor consistency in mechanical properties.In the presented approach, the rotational speed is controlled during welding in order to maintain the set temperature value along the weld. An innovative method to measure the process temperature, the tool-workpiece thermocouple (TWT), which offers a temperature estimation from the whole tool-workpiece interface (TWT-data), is set as the controlled variable. The overall aim of this thesis is then to demonstrate the industrial applicability of TWT temperature control for joining geometrically complex components using robotic friction stir welding.The TWT-data signal is demonstrated to be fast, repeatable and representative of the welding temperature. Moreover, TWT-data supplies online information during the whole weld procedure, especially during plunging. The shoulder contact with the workpiece is identified by TWT-data, providing for an improved plunging operation, which was demonstrated to significantly improve the use of robotic FSW, overcoming the lack of stiffness inherent to this equipment type at this welding stage.Improved joint performance, low tensile strength variation along the weld path and a reduced number of failed welds were achieved by welding under temperature control. As a result, such a welding approach simplifies the development of a welding procedure, allowing for a decrease in time and material. The concept was successfully validated by performing two welds consisting of two dissimilar materials in a two-dimensional weld path on a geometrically complex component by using robotic equipment. The temperature control approach is not limited to robotic equipment, but also suitable for standard FSW equipment, being of interest to a various range of applications where quality and/or time is an important factor.
|
|
