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https://www.readbyqxmd.com/read/29031088/probing-the-correlation-of-neuronal-loss-neurofibrillary-tangles-and-cell-death-markers-across-the-alzheimer-s-disease-braak-stages-a-quantitative-study-in-humans
#1
Panos Theofilas, Alexander J Ehrenberg, Austin Nguy, Julia M Thackrey, Sara Dunlop, Maria B Mejia, Ana T Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Claudia K Suemoto, Camila F Nascimento, Marcus Chin, Daniel Medina-Cleghorn, Ana Maria Cuervo, Michelle Arkin, William W Seeley, Bruce L Miller, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29031067/new-pyridine-derivatives-as-inhibitors-of-acetylcholinesterase-and-amyloid-aggregation
#2
Fabiana Pandolfi, Daniela De Vita, Martina Bortolami, Antonio Coluccia, Roberto Di Santo, Roberta Costi, Vincenza Andrisano, Francesco Alabiso, Christian Bergamini, Romana Fato, Manuela Bartolini, Luigi Scipione
A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor (IC50 = 0.153 ± 0.016 μM) while the carbamate 11 was the most potent inhibitor of hBChE (IC50 = 0.828 ± 0.067 μM). A molecular docking study indicated that the carbamate 8 was able to bind AChE by interacting with both CAS and PAS, in agreement with the mixed inhibition mechanism...
September 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29028528/inhibitors-of-yellow-fever-virus-replication-based-on-1-3-5-triphenyl-4-5-dihydropyrazole-scaffold-design-synthesis-and-antiviral-evaluation
#3
Rossella Fioravanti, Nicoletta Desideri, Antonio Carta, Elena Maria Atzori, Ilenia Delogu, Gabriella Collu, Roberta Loddo
By the antiviral screening of an in house library of pyrazoline compounds, 4-(3-(4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide (5a) was identified as a promising hit compound for the development of anti- Yellow Fever Virus (YFV) agents. Structural optimization studies were focused on the development of 5a analogues which retain the potency as YFV inhibitors and show a reduced cytotoxicity. The synthesized 1-3,5-triphenyl-pyrazolines (4a-j, 5a-j, 6a-j) were evaluated in cell based assays for cytotoxicity and antiviral activity against representative viruses of two of the three genera of the Flaviviridae family, i...
September 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29027991/n6-isopentenyladenosine-dual-targeting-of-ampk-and-rab7-prenylation-inhibits-melanoma-growth-through-the-impairment-of-autophagic-flux
#4
Roberta Ranieri, Elena Ciaglia, Giuseppina Amodio, Paola Picardi, Maria Chiara Proto, Patrizia Gazzerro, Chiara Laezza, Paolo Remondelli, Maurizio Bifulco, Simona Pisanti
Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29027931/discovering-the-biological-target-of-5-epi-sinuleptolide-using-a-combination-of-proteomic-approaches
#5
Elva Morretta, Roberta Esposito, Carmen Festa, Raffaele Riccio, Agostino Casapullo, Maria Chiara Monti
Sinuleptolide and its congeners are diterpenes with a norcembranoid skeleton isolated from the soft coral genus Sinularia. These marine metabolites are endowed with relevant biological activities, mainly associated with cancer development. 5-epi-sinuleptolide has been selected as a candidate for target discovery studies through the application of complementary proteomic approaches. Specifically, a combination of conventional chemical proteomics based on affinity chromatography, coupled with high-resolution mass spectrometry and bioinformatics, as well as drug affinity responsive target stability (DARTS), led to a clear identification of actins as main targets for 5-epi-sinuleptolide...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29026157/bortezomib-promotes-khsv-and-ebv-lytic-cycle-by-activating-jnk-and-autophagy
#6
Marisa Granato, Maria Anele Romeo, Mariangela Sara Tiano, Roberta Santarelli, Roberta Gonnella, Maria Saveria Gilardini Montani, Alberto Faggioni, Mara Cirone
KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the majority of cancer cells harbor a latent infection, the few cells that undergo viral replication may contribute to the pathogenesis and maintenance of the virus-associated malignancies. Cytotoxic drugs used for the therapies of cancers harboring virus-infection often have, as side effect, the activation of viral lytic cycle. Therefore it is important to investigate whether they affect viral reactivation and understand the underlying mechanisms involved...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025908/a-germ-line-deletion-of-apobec3b-does-not-contribute-to-subtype-specific-childhood-acute-lymphoblastic-leukemia-etiology
#7
Amelia D Wallace, Stephen S Francis, Xiaorong Shao, Adam J de Smith, Kyle M Walsh, Roberta Mckean-Cowdin, Xiaomei Ma, Gary Dahl, Lisa F Barcellos, Joseph L Wiemels, Catherine Metayer
No abstract text is available yet for this article.
October 12, 2017: Haematologica
https://www.readbyqxmd.com/read/29024722/cellular-immune-activation-in-sardinian-middle-aged-older-adults-and-centenarians
#8
Salvatore Sotgia, Angelo Zinellu, Arduino A Mangoni, Roberta Serra, Gianfranco Pintus, Calogero Caruso, Luca Deiana, Ciriaco Carru
In addition to viral infections, malignant disorders, autoimmune diseases, and allograft rejection episodes, neopterin increases in older people where it is found to be predictive of overall mortality. Thus, the serum concentrations of this biomarker of systemic immune and inflammation activation, were measured in a small cohort of Sardinian middle-aged, older adults and centenarians. There was a significant positive correlation between neopterin concentrations and age with the subjects in the 95-year-old group with the highest values...
October 9, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29023728/application-of-3d-mass-spectrometry-imaging-to-tkis
#9
Lavinia Morosi, Silvia Giordano, Francesca Falcetta, Roberta Frapolli, Simonetta A Licandro, Cristina Matteo, Massimo Zucchetti, Paolo Ubezio, Eugenio Erba, Sonja Visentin, Maurizio D'Incalci, Enrico Davoli
Mass spectrometry imaging (MSI) allows visualization of endogenous and exogenous compound in tissue sections based on its molecular mass. The 3D reconstruction by MSI provides a more informative description of the tumor drug distribution compared to the high-performance liquid chromatography method, highlighting the heterogeneity of intratumor drug concentration. This additional information can be important in understanding chemoresistance to target agents. Here, we present the 3D visualization of the tyrosine kinase inhibitor (TKI), imatinib, in a xenograft model of resistant malignant pleural mesothelioma...
November 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29023598/the-greenland-shark-somniosus-microcephalus-hemoglobins-and-ligand-binding-properties
#10
Roberta Russo, Daniela Giordano, Gianluca Paredi, Francesco Marchesani, Lisa Milazzo, Giovanna Altomonte, Pietro Del Canale, Stefania Abbruzzetti, Paolo Ascenzi, Guido di Prisco, Cristiano Viappiani, Angela Fago, Stefano Bruno, Giulietta Smulevich, Cinzia Verde
A large amount of data is currently available on the adaptive mechanisms of polar bony fish hemoglobins, but structural information on those of cartilaginous species is scarce. This study presents the first characterisation of the hemoglobin system of one of the longest-living vertebrate species (392 ± 120 years), the Arctic shark Somniosus microcephalus. Three major hemoglobins are found in its red blood cells and are made of two copies of the same α globin combined with two copies of three very similar β subunits...
2017: PloS One
https://www.readbyqxmd.com/read/29022512/schistosoma-mansoni-purine-and-pyrimidine-biosynthesis-structures-and-kinetic-experiments-in-the-search-for-the-best-therapeutic-target
#11
Vitor Hugo Balasco Serrão, Humberto D'Muniz Pereira, Juliana Roberta Torini de Souza, Larissa Romanello
BACKGROUND: Schistosoma mansoni is the etiological agent of schistosomiasis, a debilitating treatment neglected tropical disease that affects approximately 218 million people worldwide. Despite its importance, the treatment of schistosomiasis relies on a single drug, praziquantel. Some reports on the resistance of S. mansoni to this drug have stimulated efforts to develop new drugs to treat this disease. S. mansoni possesses all the same pyrimidine pathways (de novo, salvage and thymidylate cycles) as those of its host...
October 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29020892/are-evidence-based-guidelines-reflected-in-clinical-practice-an-analysis-of-prospectively-collected-data-of-the-italian-thyroid-cancer-observatory-itco-1
#12
Livia Lamartina, Cosimo Durante, Giuseppe Lucisano, Giorgio Grani, Rocco Alfonso Bellantone, Celestino Pio Lombardi, Alfredo Pontecorvi, Emanuela Arvat, Francesco Felicetti, Maria Chiara Zatelli, Roberta Rossi, Efisio Puxeddu, Silvia Morelli, Massimo Torlontano, Umberto Crocetti, Teresa Montesano, Raffaele Giubbini, Fabio Orlandi, Gianluca Aimaretti, Fabio Monzani, Marco Attard, Cecilia Francese, Alessandro Antonelli, Paolo P Limone, Ruth Rossetto, Laura Fugazzola, Domenico Meringolo, Rocco Bruno, Salvatore Tumino, Graziano Ceresini, Marco Centanni, Salvatore Monti, Domenico Salvatore, Caterina Mian, Giovanna Spiazzi, Luca Persani, Daniele Barbaro, Antonio Nicolucci, Sebastiano Filetti
OBJECTIVES: The goal of evidence-based practice guidelines is to optimize the management of emerging diseases, such as differentiated thyroid cancer (DTC). The aim of this study was to assess therapeutic approaches for DTC in Italy and to see how closely these practices conformed to those recommended in the 2009 American Thyroid Association (ATA) guidelines. METHODS: The Italian Thyroid Cancer Observatory (ITCO) was established to prospectively collect data on thyroid cancers consecutively diagnosed in participating centers (uniformly distributed across the nation)...
October 12, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29020125/construction-and-validation-of-educational-materials-for-the-prevention-of-metabolic-syndrome-in-adolescents
#13
Ionara Holanda de Moura, Antônia Fabiana Rodrigues da Silva, Aparecida do Espírito Santo de Holanda Rocha, Luisa Helena de Oliveira Lima, Thereza Maria Magalhães Moreira, Ana Roberta Vilarouca da Silva
OBJECTIVE: To develop and validate an educational technology focused on prevention of metabolic syndrome among adolescents. METHODS: This was methodological research. Using an integrative review, the available publications on the subject were analyzed. Then, this knowledge was used to describe the theoretical content and, with the help of a graphic designer, the art and layout of the pages were developed. In the third phase, the booklet was evaluated and validated by 21 specialists and 39 adolescents...
October 5, 2017: Revista Latino-americana de Enfermagem
https://www.readbyqxmd.com/read/29019910/determination-of-salmonella-spp-e-coli-vtec-vibrio-spp-and-norovirus-gi-gii-in-bivalve-molluscs-collected-from-growing-natural-beds-in-sardinia-italy
#14
Marta Marceddu, Sonia Lamon, Simonetta G Consolati, Sara Ciulli, Roberta Mazza, Anna Mureddu, Domenico Meloni
The aim of the present study was to evaluate the presence of Salmonella spp., verotoxigenic E. coli (VTEC), Vibrio spp., and Norovirus GI-GII in bivalve molluscs, cockles, and European grooved carpet shells (Cerastoderma spp. and Ruditapes decussatus) collected from a class B growing natural bed in Sardinia (Italy). All of the samples were analysed for Salmonella spp. detection according to European Commission Regulation (EC) 2285/2015. Detection and enumeration of Vibrio spp. were performed according to previously published methods...
October 11, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/29019317/precept-an-evidence-assessment-framework-for-infectious-disease-epidemiology-prevention-and-control
#15
Thomas Harder, Anja Takla, Tim Eckmanns, Simon Ellis, Frode Forland, Roberta James, Joerg J Meerpohl, Antony Morgan, Eva Rehfuess, Holger Schünemann, Teun Zuiderent-Jerak, Helena de Carvalho Gomes, Ole Wichmann
Decisions in public health should be based on the best available evidence, reviewed and appraised using a rigorous and transparent methodology. The Project on a Framework for Rating Evidence in Public Health (PRECEPT) defined a methodology for evaluating and grading evidence in infectious disease epidemiology, prevention and control that takes different domains and question types into consideration. The methodology rates evidence in four domains: disease burden, risk factors, diagnostics and intervention. The framework guiding it has four steps going from overarching questions to an evidence statement...
October 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29018180/association-between-neuroendocrine-tumor-of-the-ileum-and-two-colonic-primary-malignancies-a-case-report-and-review-of-literature
#16
Luca Napolitano, Valentina D'Alessandro, Domenico Risio, Camilla Marinelli, Roberta Cianci, Paolo Innocenti
BACKGROUND: A high rate of association between neuroendocrine tumors (NETs) and secondary primary malignancy (SPM) has been described in literature and this association can occur either in a synchronous or a metachronous presentation. A wide range of hypothesis has been postulated to explain the high rate of association between NETs and SPM, without definitive conclusions. CASE PRESENTATION: We report a case of an ileal neuroendocrine tumor found incidentally at the histologic examination of the surgical specimen in a 72 years old male underwent to right hemi colectomy for two colic adenomatous polips with high grade dysplasia...
October 4, 2017: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/29018097/leaf-and-plant-age-affects-photosynthetic-performance-and-photoprotective-capacity
#17
Ludwik Wiktor Bielczynski, Mateusz Krzysztof Łącki, Iris Hoefnagels, Anna Gambin, Roberta Croce
In this work, we studied the changes in high light tolerance and photosynthetic activity in leaves of the Arabidopsis thaliana rosette throughout the vegetative stage of growth. We implemented an image analysis workflow to analyze the capacity of both the whole plant and individual leaves to cope with excess excitation energy by following the changes in the absorbed light energy partitioning. The data show that leaf and plant age are both important factors influencing the fate of excitation energy. During the dark-to-light transition, the age of the plant affects mostly steady state levels of photochemical and non-photochemical quenching (NPQ), leading to an increased photosynthetic performance of its leaves...
October 10, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29017520/the-nuclear-receptor-er%C3%AE-engages-ago2-in-regulation-of-gene-transcription-rna-splicing-and-risc-loading
#18
Roberta Tarallo, Giorgio Giurato, Giuseppina Bruno, Maria Ravo, Francesca Rizzo, Annamaria Salvati, Luca Ricciardi, Giovanna Marchese, Angela Cordella, Teresa Rocco, Valerio Gigantino, Biancamaria Pierri, Giovanni Cimmino, Luciano Milanesi, Concetta Ambrosino, Tuula A Nyman, Giovanni Nassa, Alessandro Weisz
BACKGROUND: The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease...
October 6, 2017: Genome Biology
https://www.readbyqxmd.com/read/29017104/shift-of-monocyte-subsets-along-their-continuum-predicts-cardiovascular-outcomes
#19
Roberta Cappellari, Marianna D'Anna, Benedetta Maria Bonora, Mauro Rigato, Andrea Cignarella, Angelo Avogaro, Gian Paolo Fadini
BACKGROUND AND AIMS: Distribution of monocyte subsets has been shown to predict cardiovascular outcomes. However, monocytes form a continuum and categorization into discrete subsets may be an oversimplification. We herein aimed at establishing whether distribution of monocytes based on CD14 and CD16 fluorescence intensity provides incremental and complementary information on cardiovascular outcomes beyond enumeration of traditional subsets. METHODS: A cohort of 227 patients at high cardiovascular risk was characterized at baseline and followed for a median of 4 years...
September 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29016679/perimenopause-and-emergence-of-an-alzheimer-s-bioenergetic-phenotype-in-brain-and-periphery
#20
Lisa Mosconi, Valentina Berti, Crystal Guyara-Quinn, Pauline McHugh, Gabriella Petrongolo, Ricardo S Osorio, Christopher Connaughty, Alberto Pupi, Shankar Vallabhajosula, Richard S Isaacson, Mony J de Leon, Russell H Swerdlow, Roberta Diaz Brinton
After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter...
2017: PloS One
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