Applications of Microarray Technology to Acute Myelogenous Leukemia

Microarray technology is a powerful tool, which has been applied to further the understanding of gene expression changes in disease. Array technology has been applied to the diagnosis and prognosis of Acute Myelogenous Leukemia (AML). Arrays have also been used extensively in elucidating the mechanism of and predicting therapeutic response in AML, as well as to further define the mechanism of AML pathogenesis. In this review, we discuss the major paradigms of gene expression array analysis, and provide insights into the use of software tools to annotate the array dataset and elucidate deregulated pathways and gene interaction networks. We present the application of gene expression array technology to questions in acute myelogenous leukemia; specifically, disease diagnosis, treatment and prognosis, and disease pathogenesis. Finally, we discuss several new and emerging array technologies, and how they can be further utilized to improve our understanding of AML

Numerical simulation of the open-pool reactor coolant system using a multi-domain approach

The computational simulation of large-scale reactors is currently limited by the high computational cost. The system codes allow addressing these problems, although with the well-known loss of local information. The use of coupling domains to reduce the problems looks like a proper alternative to settle this issue. In the present paper, a multi-domain coupling 3-dimensional/0-dimensional method to solve the thermal hydraulics of the TRIGA Mark I IPR-R1 reactor was implemented into a Finite Volume suite. Despite of the broadly literature about coupling methods, even in the nuclear engineering community, most of them manage with different codes in a fully explicit way. In the other hand, the benefit of solve different domain approaches inside the same software is in the use of monolithic algorithms. The proposed method consists on using 3-dimensional full CFD to simulate the reactor pool and 0-dimensional modelling for the external cooling loop. This is made by implementing a set of ad hoc dynamics boundary conditions to model the momentum and energy balances along the pipeline. This strategy was used to perform long-time steady state simulations of the reactor at the design power of 100 kW as well as for the repowering up to 265 kW. The results demonstrated that the core is efficiently cooled at the higher power without need to increase the coolant mass flow rate of the external system. Moreover, two accidental events were simulated: the first case was the Station Black Out at full power of 265 kW. The results indicated that the loss of the external heat sink led to a slow pool heating, but the core remains being cooled by the natural circulation in the pool. In fact, the mass flow rate through the core is only reduced in 15% by the loss of the external loop circulation. Finally, a large-Loss of Coolant Accident for the operational power of 100 kW and keeping the pump running is performed. In this case, the pool is quickly empty if safety systems do not take action and the core is uncovered after 450 s completely losing the core cooling capacity.Fil: Corzo, Santiago Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; ArgentinaFil: Godino, Dario Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; ArgentinaFil: Costa, Antonella Lombardi. Universidade Federal de Minas Gerais; Brasil. Conselho Nacional de Desenvolvimiento Científico e Tecnológico; BrasilFil: Reis, Patricia A. L.. Universidade Federal de Minas Gerais; Brasil. Conselho Nacional de Desenvolvimiento Científico e Tecnológico; BrasilFil: Pereira, Claubia. Universidade Federal de Minas Gerais; Brasil. Conselho Nacional de Desenvolvimiento Científico e Tecnológico; BrasilFil: Ramajo, Damian Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; Argentin

Pathogens in ornamental waters: a follow up study

Ornamental waters of easy access and populated with animals are quite attractive and can hide threats to human health. Here we evaluated the microbiota of ornamental waters in a Lisbon park. Water and biofilm samples where collected, in 2 lakes (L1-L2) and ornamental fountains (L3-L4) in February/2015. In May/2015 and monthly during a year (starting March/2016) samples from L4 where collected. Microbiota identification was performed as described previouslya. Biofilm assembly was monitored by crystal violet assay and SEMb and antibiotic susceptibility was performed by conventional methods. The results of the first water sampling (Feb/2015) revealed the presence of Enterobactereaceae and non-fermentative oxidase-positive bacteria. Fountains and lakes presented different microbota being the highest diversity found in L1 hosting a duck population. This result suggested the existence of an interplay between animal inhabitants and microbiota which was confirmed by the second sampling of L4 (May/2015). Between the 2 sampling events a fish population was introduced and the microbiota was completely altered with the appearance of a typical fish pathogen (Aeromonas spp). This tendency was also confirmed over 2016. K. pneumoniae and Aeromonas spp., present as planktonic and biofilm organized bacteria in 2015 showed an enhanced ability to assemble biofilms in vitro at 25 °C than at 37 °C. Bacteria recovered from biofilm showed an increased antibiotic resistance compared to planktonic counterparts. The pilot study conducted during 2015 and the follow up study (still in progress) support a periodic control of ornamental water microbiota as simple preventive measure to avoid potential health issues.Fundação para a Ciência e Tecnologia for the grant PEst-OE/CTM/UI0084/2011N/

Towards a New Science of a Clinical Data Intelligence

In this paper we define Clinical Data Intelligence as the analysis of data generated in the clinical routine with the goal of improving patient care. We define a science of a Clinical Data Intelligence as a data analysis that permits the derivation of scientific, i.e., generalizable and reliable results. We argue that a science of a Clinical Data Intelligence is sensible in the context of a Big Data analysis, i.e., with data from many patients and with complete patient information. We discuss that Clinical Data Intelligence requires the joint efforts of knowledge engineering, information extraction (from textual and other unstructured data), and statistics and statistical machine learning. We describe some of our main results as conjectures and relate them to a recently funded research project involving two major German university hospitals.Comment: NIPS 2013 Workshop: Machine Learning for Clinical Data Analysis and Healthcare, 201

Ana1/CEP295 is an essential player in the centrosome maintenance program regulated by Polo kinase and the PCM

Centrioles are part of centrosomes and cilia, which are microtubule organising centres (MTOC) with diverse functions. Despite their stability, centrioles can disappear during differentiation, such as in oocytes, but little is known about the regulation of their structural integrity. Our previous research revealed that the pericentriolar material (PCM) that surrounds centrioles and its recruiter, Polo kinase, are downregulated in oogenesis and sufficient for maintaining both centrosome structural integrity and MTOC activity. We now show that the expression of specific components of the centriole cartwheel and wall, including ANA1/CEP295, is essential for maintaining centrosome integrity. We find that Polo kinase requires ANA1 to promote centriole stability in cultured cells and eggs. In addition, ANA1 expression prevents the loss of centrioles observed upon PCM-downregulation. However, the centrioles maintained by overexpressing and tethering ANA1 are inactive, unlike the MTOCs observed upon tethering Polo kinase. These findings demonstrate that several centriole components are needed to maintain centrosome structure. Our study also highlights that centrioles are more dynamic than previously believed, with their structural stability relying on the continuous expression of multiple components.publishersversionpublishe

Unveiling the mechanism of action of 7α-acetoxy-6β-hydroxyroyleanone on an mrsa/visa strain: Membrane and cell wall interactions

UIDB/00100/2020 PTDC/MED-QUI/29036/2017 CEECIND/03414/2018 UIDB/04378/2020 PTDC/BIA-MIC/31645/2017 UID/DTP/04138/2019 UID/DTP/04567/2019 CBIOS/PRUID/BI1/2017 UIDB/04567/2020 UID/AMB/50017 UIDP/50017/2020 UIDB/50017/2020The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7α-Acetoxy-6β-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant Staphylococcus aureus (MRSA) strains. The high antibacterial activity and low cytotoxicity render this natural compound an interesting alternative against resistant bacteria. The aim of this study is to understand the mechanism of action of AHR on MRSA, using the MRSA/Vancomycin-intermediate S. aureus (VISA) strain CIP 106760, and to study the AHR effect on lipid bilayers and on the cell wall. Although AHR interacted with lipid bilayers, it did not have a significant effect on membrane passive permeability. Alternatively, bacteria treated with this royleanone displayed cell wall disruption, without revealing cell lysis. In conclusion, the results gathered so far point to a yet undescribed mode of action that needs further investigation.publishersversionpublishe

Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression

Adipose tissue-derived stem cells (ASCs) are an attractive source of stem cells with regenerative properties that are similar to those of bone marrow stem cells. Here, we analyze the role of ASCs in reducing the progression of kidney fibrosis. Progressive renal fibrosis was achieved by unilateral clamping of the renal pedicle in mice for 1 h; after that, the kidney was reperfused immediately. Four hours after the surgery, 2 x 10(5) ASCs were intraperitoneally administered, and mice were followed for 24 h posttreatment and then at some other time interval for the next 6 weeks. Also, animals were treated with 2 x 10(5) ASCs at 6 weeks after reperfusion and sacrificed 4 weeks later to study their effect when interstitial fibrosis is already present. At 24 h after reperfusion, ASC-treated animals showed reduced renal dysfunction and enhanced regenerative tubular processes. Renal mRNA expression of IL-6 and TNF was decreased in ASC-treated animals, whereas IL-4. IL-10, and HO-1 expression increased despite a lack of ASCs in the kidneys as determined by SRY analysis. As expected, untreated kidneys shrank at 6 weeks, whereas the kidneys of ASC-treated animals remained normal in size, showed less collagen deposition, and decreased staining for FSP-1, type I collagen, and Hypoxyprobe. the renal protection seen in ASC-treated animals was followed by reduced serum levels of TNF-alpha, KC, RANTES, and IL-1 alpha. Surprisingly, treatment with ASCs at 6 weeks, when animals already showed installed fibrosis, demonstrated amelioration of functional parameters, with less tissue fibrosis observed and reduced mRNA expression of type I collagen and vimentin. ASC therapy can improve functional parameters and reduce progression of renal fibrosis at early and later times after injury, mostly due to early modulation of the inflammatory response and to less hypoxia, thereby reducing the epithelial-mesenchymal transition.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)DECIT/Ministerio do SaudeComplex Fluids INCTUniversidade Federal de São Paulo, Div Nephrol, Escola Paulista Med, Expt & Clin Immunol Lab, BR-04023900 São Paulo, BrazilUniv São Paulo, Dept Pathol, São Paulo, BrazilUniv Fed Triangulo Mineiro, Div Pathol, Uberaba, MG, BrazilUniv São Paulo, Dept Immunol, Lab Transplantat Immunobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Escola Paulista Med, Expt & Clin Immunol Lab, BR-04023900 São Paulo, BrazilFAPESP: 09/13251-6FAPESP: 07/07139-3CNPq: 473844/2009-5Web of Scienc

Evaluation of the antibacterial activity and colouring capacity of two Hylocereus spp. Epicarps

Betalains are a group of secondary metabolites named chromoalkaloids that are synthesized from tyrosine. These compounds have gained some attention in the last few years mainly due to their interesting bioactive potential, namely antioxidant, antimicrobial, and other bioactive properties [1]. Their strong and vibrant colours are also one of the characteristics by which these compounds have gained visibility in the food and pharmaceutical industries [2]. Betalains can be divided in two groups regarding the colour range: betaxanthins in the orange to yellow range, and betacyanins in the purple to pink range. Thereby, these compounds can be used as natural colouring agents, providing alternatives to the massively used artificial counterparts [3]. Although there are already some natural options in the market, these are not enough to meet the needs of the food industry, due to the growing concern of consumers regarding what they eat.To FCT and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019); C. Lobo Roriz (SFRH/BD/117995/2016) and T.C.S. Pires (SFRH/BD/129551/2017) grants and National funding by FCT- Foundation for Science and Technology, P.I., through the institutional scientific employment program-contract for L. Barros contract. This work is funded by the European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project Mobilizador Norte-01-0247-FEDER-024479:ValorNatural®.info:eu-repo/semantics/publishedVersio

Roots and rhizomes of wild Asparagus: Nutritional composition, bioactivity and nanoencapsulation of the most potent extract

The nutritional composition and bioactive properties of roots and rhizomes of Asparagus stipularis were evaluated. Antioxidant activity of extracts obtained by infusion was evaluated using free radicals scavenging and reducing power methods. Porcine liver primary cell was used to check the hepatotoxicity of infusions. Results revealed that Asparagus samples are likely a source of nutrients, such as dietary fibre and essential fatty acids. HPLC-DAD-ESI/MS characterization of infusions allowed the identification and quantitation of 7 phenolic compounds, all hydroxycinnamoyl derivatives, with caffeic acid as the most abundant. Roots infusion contained the highest amounts of these compounds. It also exhibited the highest antioxidant activity in all assays, with EC50 values of 0.44 ± 0.01, 0.98 ± 0.03 and 0.64 ± 0.01 mg/mL for DPPH, ABTS and FRAP assays, respectively, with no toxicity towards PLP2 primary cell cultures (GI50 > 400 μg/mL). PLGA nanoparticles loaded with root extract were prepared using solvent-evaporation double emulsion method. Nanoparticles size was about 260 nm and a polydispersity index around 0.1, with a zeta potential of about -36 mV, as well as a good encapsulation efficiency of approximately 83%. Their morphology was analysed by SEM and spherical polymeric nanoparticles with a smooth surface were observed. FTIR and DSC were also performed, which allowed corroborating the efficacy of the encapsulation and to confirm the production of a stable and robust system to load Asparagus extracts. The developed nanoparticles are expected to be used as delivery systems for bioactive compounds of A. stipularis and they could be used as an innovative dietary supplement.The UCM authors would like to thank to ALIMNOVA Research Group (UCM GR105/18) and Spanish Government through the project PID2019-109365RA-I00. Authors are also grateful to Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020), LAQV (UIDB/50006/2020), CCMar (UIDB/04326/2020), CBIOS (UIDB/ 04567/2020) and iBB-IST (UIDB/04565/2020). A. Fernandes contract was provided by National funding by FCT, P. I., through the institutional scientific employment program-contract. The authors are also grateful to FEDER-Interreg España-Portugal programme for financial support through the project 0377_Iberphenol_6_E. The GIP-USAL is financially supported by the Spanish Government through the project AGL2015- 64522-C2-2-R.info:eu-repo/semantics/publishedVersio

Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma

Metabolomics based on untargeted flow infusion electrospray ionization high-resolution mass spectrometry (FIE-HRMS) can provide a snap-shot of metabolism in living cells. Lung Squamous Cell Carcinoma (SCC) is one of the predominant subtypes of Non-Small Cell Lung Cancers (NSCLCs), which usually shows a poor prognosis. We analysed lung SCC samples and matched histologically normal lung tissues from eight patients. Metabolites were profiled by FIE-HRMS and assessed using t-test and principal component analysis (PCA). Differentially accumulating metabolites were mapped to pathways using the mummichog algorithm in R, and biologically meaningful patterns were indicated by Metabolite Set Enrichment Analysis (MSEA). We identified metabolic rewiring networks, including the suppression of the oxidative pentose pathway and found that the normal tricarboxylic acid (TCA) cycle were decoupled from increases in glycolysis and glutamine reductive carboxylation. Well-established associated effects on nucleotide, amino acid and thiol metabolism were also seen. Novel aspects in SCC tissue were increased in Vitamin B complex cofactors, serotonin and a reduction of γ-aminobutyric acid (GABA). Our results show the value of FIE-HRMS as a high throughput screening method that could be exploited in clinical contexts