Caffeic Acid Derivatives Inhibit the Growth of Colon Cancer: Involvement of the PI3-K/Akt and AMPK Signaling Pathways

The aberrant regulation of phosphatidylinositide 3-kinases (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) signaling pathways in cancer has prompted significant interest in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been reported to possess important anti-inflammatory actions. However, the molecular mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the proliferation of human colorectal cancer (CRC) cells have yet to be elucidated

Ruptured Intracranial Mycotic Aneurysm in Infective Endocarditis: A Natural History

Mycotic aneurysms are a rare cause of intracranial aneurysms that develop in the presence of infections such as infective endocarditis. They account for a small percentage of all intracranial aneurysms and carry a high-mortality rate when ruptured. The authors report a case of a 54-year-old man who presented with infective endocarditis of the mitral valve and acute stroke. He subsequently developed subarachnoid hemorrhage during antibiotic treatment, and a large intracranial aneurysm was discovered on CT Angiography. His lesion quickly progressed into an intraparenchymal hemorrhage, requiring emergent craniotomy and aneurysm clipping. Current recommendations on the management of intracranial Mycotic Aneurysms are based on few retrospective case studies. The natural history of the patient's ruptured aneurysm is presented, as well as a literature review on the management and available treatment modalities

Explaining primary health care pharmacy expenditure using classification of medications for chronic conditions

Background The Valencian Autonomous Community (Spain) has implemented a scheme of purchasing services with the participation of public and private providers. Five districts are managed using public¿private partnership. The financing model is capitation and inter-center invoice. The pharmaceutical benefits are not included in the per capita assignment. Objectives Modeling and explaining pharmacy expenditure using electronic prescriptions drug data. Methods A database of electronic prescription corresponding to 625,246 patients between November 2008 and October 2009 was used to run four linear models that explain the pharmaceutical expenditures. We take as dependent variable the neperian log of total pharmacy annual cost per patient in the primary health setting. The independent variables used combined demographics with revised classification in 18 chronic conditions obtained from the anatomical therapeutic chemical classification index (ATC). Results The retrospective model selected included: gender, pharmaceutical co-payment status and 8 dummy variables for the number of chronic conditions of each patient from 1 to 8 or more. The goodness-of-fit achieved is measured in R2 of 57%. Conclusions These models must be considered in the current capitation system for pharmaceutical budgeting in a primary care setting established at regional level, as is the case in the Valencian Autonomous Community. The use of diagnostics and information regarding hospital encounters appears to be a complementary option for refining models of capitation of pharmaceutical and total health expenditure.The authors thank the General Direction of Pharmacy of the Valencian Department of Health for financial support and the working group for providing the data set. The opinions expressed in this paper are those of the authors and do not necessarily reflect those of the afore-named. Any errors are the authors' responsibility. We would also like to thank the two anonymous reviewers for their comments, which helped greatly to improve this paper.Vivas Consuelo, DJJ.; Guadalajara Olmeda, MN.; Barrachina Martínez, I.; Trillo-Mata, J.; Usó-Talamantes, R.; De La Poza, E. (2011). Explaining primary health care pharmacy expenditure using classification of medications for chronic conditions. Health Policy. 103(1):9-15. https://doi.org/10.1016/j.healthpol.2011.08.014S915103

The Vehicle, Fall 1984

Vol. 26, No. 1 Table of Contents Thoughts on I-57Jim Caldwellpage 3 A Night Between Lonely and BlindJennifer K. Soulepage 4 What is Unnatural is Sometimes MagicAngelique Jenningspage 4 Cutting ClosenessBecky Lawsonpage 5 PhotoBrian Ormistonpage 6 The Sensuality of Corn One Week in AugustMichelle Mitchellpage 7 American MusicJim Caldwellpage 7 Water is WaitingMichael Kuopage 8 WhereJennifer K. Soulepage 8 The Fishing HoleJan Kowalskipage 9 Miller\u27s PondSue Gradypage 9 PhotoCathy Stonerpage 11 Young Man Reading To His LoverMaggie Kennedypage 11 ShellsChristopher R. Albinpage 12 In The ShadeJohn Fehrmannpage 12 FallLynanne Feilenpage 13 IndecisionDave L. Brydenpage 13 Dark Falls SoftlyAngelique Jenningspage 14 Not a Parked \u2757 Chevy in the Summer in the CountryMichelle Mitchellpage 20 BirdAnnie Heisepage 20 Clouds Created Only For Poets And Certain WomenJennifer K. Soulepage 21 SandGraham Lewispage 22 PhotoFred Zwickypage 23 Judgment CallCathy Moepage 23 I was hip that night Dan Hintzpage 24 A Sight Of WindDan Von Holtenpage 25 Tillard Isabel M. Parrottpage 26 The WidowMaggie Kennedypage 27 The SeparationMichelle Mitchellpage 27 The Garden Hose TrialMaggie Kennedypage 28 InterruptionsJennifer K. Soulepage 28 On Happening Across Jesus While Cleaning the BasementMaggie Kennedypage 29 GileonMichelle Mitchellpage 30 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 36 A Visit to Grandpa Gib\u27s HouseTammy Veachpage 37 For Having SeenAngelique Jenningspage 38 PhotoJudy Klancicpage 39 The Earth in BlueSusan J. Bielskypage 39 Things I Could Have SaidAngelique Jenningspage 40 AcrosticsAnnie Heisepage 40https://thekeep.eiu.edu/vehicle/1044/thumbnail.jp

The Vehicle, Fall 1984

Vol. 26, No. 1 Table of Contents Thoughts on I-57Jim Caldwellpage 3 A Night Between Lonely and BlindJennifer K. Soulepage 4 What is Unnatural is Sometimes MagicAngelique Jenningspage 4 Cutting ClosenessBecky Lawsonpage 5 PhotoBrian Ormistonpage 6 The Sensuality of Corn One Week in AugustMichelle Mitchellpage 7 American MusicJim Caldwellpage 7 Water is WaitingMichael Kuopage 8 WhereJennifer K. Soulepage 8 The Fishing HoleJan Kowalskipage 9 Miller\u27s PondSue Gradypage 9 PhotoCathy Stonerpage 11 Young Man Reading To His LoverMaggie Kennedypage 11 ShellsChristopher R. Albinpage 12 In The ShadeJohn Fehrmannpage 12 FallLynanne Feilenpage 13 IndecisionDave L. Brydenpage 13 Dark Falls SoftlyAngelique Jenningspage 14 Not a Parked \u2757 Chevy in the Summer in the CountryMichelle Mitchellpage 20 BirdAnnie Heisepage 20 Clouds Created Only For Poets And Certain WomenJennifer K. Soulepage 21 SandGraham Lewispage 22 PhotoFred Zwickypage 23 Judgment CallCathy Moepage 23 I was hip that night Dan Hintzpage 24 A Sight Of WindDan Von Holtenpage 25 Tillard Isabel M. Parrottpage 26 The WidowMaggie Kennedypage 27 The SeparationMichelle Mitchellpage 27 The Garden Hose TrialMaggie Kennedypage 28 InterruptionsJennifer K. Soulepage 28 On Happening Across Jesus While Cleaning the BasementMaggie Kennedypage 29 GileonMichelle Mitchellpage 30 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 36 A Visit to Grandpa Gib\u27s HouseTammy Veachpage 37 For Having SeenAngelique Jenningspage 38 PhotoJudy Klancicpage 39 The Earth in BlueSusan J. Bielskypage 39 Things I Could Have SaidAngelique Jenningspage 40 AcrosticsAnnie Heisepage 40https://thekeep.eiu.edu/vehicle/1044/thumbnail.jp

Natural Genome Diversity of AI-2 Quorum Sensing in Escherichia coli: Conserved Signal Production but Labile Signal Reception

Quorum sensing (QS) regulates the onset of bacterial social responses in function to cell density having an important impact in virulence. Autoinducer-2 (AI-2) is a signal that has the peculiarity of mediating both intra- and interspecies bacterial QS. We analyzed the diversity of all components of AI-2 QS across 44 complete genomes of Escherichia coli and Shigella strains. We used phylogenetic tools to study its evolution and determined the phenotypes of single-deletion mutants to predict phenotypes of natural strains. Our analysis revealed many likely adaptive polymorphisms both in gene content and in nucleotide sequence. We show that all natural strains possess the signal emitter (the luxS gene), but many lack a functional signal receptor (complete lsr operon) and the ability to regulate extracellular signal concentrations. This result is in striking contrast with the canonical species-specific QS systems where one often finds orphan receptors, without a cognate synthase, but not orphan emitters. Our analysis indicates that selection actively maintains a balanced polymorphism for the presence/absence of a functional lsr operon suggesting diversifying selection on the regulation of signal accumulation and recognition. These results can be explained either by niche-specific adaptation or by selection for a coercive behavior where signal-blind emitters benefit from forcing other individuals in the population to haste in cooperative behaviors.International Early Career Scientist grant from the Howard Hughes Medical Institute: (HHMI 55007436), Institut Pasteur, the CNRS, FCT award: (SFRH/BPD/26852/2006), salary support of LAO/ITQB & FCT

Discovery of a Small-Molecule Probe for V-ATPase Function

Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been implicated in a number of diseases. Recent studies have elucidated roles for the lysosome in the regulation of protein synthesis, metabolism, membrane integrity, and other processes involved in homeostasis. Complex small-molecule natural products have greatly contributed to the investigation of lysosomal function in cellular physiology. Here we report the discovery of a novel, small-molecule modulator of lysosomal acidification derived from diversity-oriented synthesis through high-content screening

Nodavirus colonizes and replicates in the testis of gilthead seabream and European sea bass modulating its immune and reproductive functions

Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to assess local responses. Our in vitro results show that the changes observed on the expression of immune and reproductive genes in the testis of both species are different to those observed upon in vivo infections in most of the casesMINECO and FEDER (AGL2010-20801-C02-01; AGL2010-20801-C02-02; AGL2013-43588-P); Fundación Séneca (04538/GERM/06)Versión del editor4,411

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

International audienceno abstrac