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Martin C.J.,Harvard University | Booty M.G.,Harvard University | Rosebrock T.R.,Harvard University | Nunes-Alves C.,Harvard University | And 7 more authors.
Cell Host and Microbe | Year: 2012

Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism. © 2012 Elsevier Inc. Source


Silva A.,University of Minho | Oliveira T.,University of Minho | Novais P.,University of Minho | Neves J.,University of Minho | Leao P.,Bs PT Government Associate Laboratory
Advances in Intelligent Systems and Computing | Year: 2016

In this work a 5-year survival prediction model was developed for colon cancer using machine learning methods. The model was based on the SEER dataset which, after preprocessing, consisted of 38,592 records of colon cancer patients. Survival prediction models for colon cancer are not widely and easily available. Results showed that the performance of the model using fewer features is close to that of the model using a larger set of features recommended by an expert physician, which indicates that the first may be a good compromise between usability and performance. The purpose of such a model is to be used in Ambient Assisted Living applications, providing decision support to health care professionals. © Springer International Publishing Switzerland 2016. Source


Rios R.,University of Granada | Lupianez C.B.,University of Granada | Campa D.,German Cancer Research Center | Campa D.,University of Pisa | And 31 more authors.
Endocrine-Related Cancer | Year: 2015

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420MMpatients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM(odds ratio (OR)=1.32-2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05× 10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models. © 2015 Society for Endocrinology. Source


Costa A.M.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Costa A.M.S.,Bs PT Government Associate Laboratory | Mano J.F.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Mano J.F.,Bs PT Government Associate Laboratory
European Polymer Journal | Year: 2015

Ideal candidates for the repair of robust biological tissues should exhibit diverse features such as biocompatibility, strength, toughness, self-healing ability and a well-defined structure. Among the available biomaterials, hydrogels, as highly hydrated 3D-crosslinked polymeric networks, are promising for Tissue Engineering purposes as result of their high resemblance with native extracellular matrix. However, these polymeric structures often exhibit a poor mechanical behavior, hampering their use in load-bearing applications. During the last years, several efforts have been made to create new strategies and concepts to fabricate strong and tough hydrogels. Although it is already possible to shape the mechanical properties of artificial hydrogels to mimic biotissues, critical issues regarding, for instance, their biocompatibility and hierarchical structure are often neglected. Therefore, this review covers the structural and mechanical characteristics of the developed methodologies to toughen hydrogels, highlighting some pioneering efforts employed to combine the aforementioned properties in natural-based hydrogels. © 2015 Elsevier Ltd. Source


Thorvaldsson A.,Swerea IVF | Thorvaldsson A.,Chalmers University of Technology | Silva-Correia J.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Silva-Correia J.,Bs PT Government Associate Laboratory | And 6 more authors.
Journal of Applied Polymer Science | Year: 2013

In this work a new method is presented to efficiently produce hydrogel scaffolds reinforced with nanofibers to show enhanced mechanical properties and improved structural integrity. The method is based on a combination of air brush spraying of a hydrogel and electrospinning of nanofibers. With air brush spraying the controllability is enhanced and the potential for scale-up increased. The developed method was used to successfully reinforce gellan gum hydrogels with electrospun polycaprolactone nanofibers. Optical and rheological evaluations were performed and showed that parameters such as the amount of incorporated nanofibers, gellan gum concentration and calcium chloride (crosslinker) concentrations could be used to modulate material properties. Incorporation of a small amount of nanofibers had a reinforcing effect and resulted in a hydrogel with rheological properties similar to the human nucleus pulposus (NP). The method is flexible and carries potential for designing scaffolds for e.g. NP tissue regeneration. © 2012 Wiley Periodicals, Inc. Source

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