1,720,986 research outputs found
Systems Biology Analysis of the Endocannabinoid System Reveals a Scale-free Network with Distinct Roles for Anandamide and 2-Arachidonoylglycerol
No full textAbstract We represented the endocannabinoid system (ECS) as a biological network, where ECS molecules are the nodes (123) and their interactions the links (189). ECS network follows a scale-free topology, which confers robustness against random damage, easy navigability, and controllability. Network topological parameters, such as clustering coefficient (i.e., how the nodes form clusters) of 0.0009, network diameter (the longest shortest path among all pairs of nodes) of 12, averaged number of neighbors (the mean number of connections per node) of 3.073, and characteristic path length (the expected distance between two connected nodes) of 4.715, suggested that molecular messages are transferred through the ECS network quickly and specifically. Interestingly, 75% of nodes are located on, or are active at the level of, the cell membrane. The hubs of ECS network are anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which have also the highest value of betweeness centrality, and their removal causes network collapse into multiple disconnected components. Importantly, AEA is a ubiquitous player while 2-AG plays more restricted actions. Instead, the product of their degradation, arachidonic acid, and their hydrolyzing enzyme, fatty acid amide hydrolase, FAAH, have a marginal impact on ECS network, indeed their removal did not significantly affect its topology
Retrospective and observational investigation of canine microcytosis in relationship to sex, breed, diseases, and other complete blood count parameters
No full textThe prevalence of canine microcytosis, detected as reduced mean corpuscolar volume (MCV) by impedance cell counter was investigated retrospectively in relationship to sex, breed, diseases, and other blood count parameters. One thousand and twelve (1,012) canine medical records with complete blood count (CBC) were evaluated for MCV results. CBCs were performed using impedance cell counter and stained blood smears for leukocyte differential count, erythrocyte morphology, and platelet estimation. Statistical analysis included both comparative and descriptive inves- tigations in dogs showing microcytosis (MICRO) versus dogs with normal MCV (control, CTR). MCV was lower than the reference range in 8.5% of medical records (86/1,012). Only 47.7% of MICRO dogs were affected by different degrees of anemia. In MICRO dogs, thrombocy- tosis was present in 19.8%, while 16.3% showed thrombo- cytopenia, and mild leukocytosis was found in 30.2%. Statistical analysis showed significant difference about sex and breeds in MICRO vs. CTR dogs while different disorders did not affect the MICRO vs. CTR dogs; few CBC parameters such as erythrocyte count, hematocrit, and red cell dimension width were both significantly related to MCV of MICRO dogs and between CTR and MICRO dogs. Multivariate hierarchical cluster analysis showed significant difference among clusters considering platelets and displayed a subgroup of patients in MICRO dogs. Microcytosis detected at low rate in CBC of clinical records is not always related to anemia. The comparison in MICRO and CTR dogs showed a significant difference for most blood count parameters dealing with erythrocytes and leukocytes but not for platelets
La biologia computazionale a servizio del linfoma canino: nuovi orizzonti?
No full textScopo del lavoro - Il linfoma è uno dei tumori più frequenti nel cane, rappresentando circa il 7-24% di tutte le neoplasie e oltre l’80% delle neoplasie ematologiche. Origina dal tessuto linfoide (linfonodi, milza, midollo) e può estendersi a tutti gli organi e tessuti dell’organismo ed in genere colpisce cani di mezza età o di età avanzata. Attualmente sono descritti almeno cinque diver- si tipi più frequenti di linfoma canino (LC): multicentrico, mediastinico, gastrointestinale, extra-nodale e del sistema nervoso centrale1. La sua eziologia non è nota ed è ritenuta essere una patologia multifattoriale. In particolare sono state riscontrate aber- razioni cromosomiche, il coinvolgimento di retrovirus e cause ambientali (erbicidi, solventi, inquinamento industriale). La pato- genesi rimane in gran parte ignota2.
In questo contesto, abbiamo utilizzato innovative metodiche di biomedical text mining (o Biomedical Informatics Natural Lan- guage Processing, BioNLP) e di modellistica computazionale per identificare le proteine coinvolte nel LC, sia per chiarirne i meccanismi patogenetici che, potenzialmente, per proporre possibili targets terapeutici e/o markers diagnostici. In particolare:
1) mediante l’uso del BioNLP è stata ottenuta una lista di proteine coinvolte nell’eziopatogenesi del LC accedendo alle
conoscenze contenute nel testo nascosto e non strutturato (hidden and unstructured text) presente negli articoli indiciz- zati su PubMed (http://www.ncbi.nlm.nih.gov/pubmed)3. In tal modo è stato possibile implementare le conoscenze ad oggi disponibili;
2) è stato costruito un modello computazionale basato sulla teoria delle reti biologiche (biological networks) con le molecole coinvolte (nodi della rete) e le loro interazioni (links tra i nodi)3;
3) l’analisi della topologia della rete ha consentito di identificare le molecole caratterizzate da un più elevato grado di control- lo sulla rete stessa, ovvero quelle che verosimilmente possono essere ottimi candidati come markers diagnostici e/o target terapeutici4,5.
Materiali e metodi - Per il BioNLP è stato usato il software Agilent Literature Search 3.1.1 (LitSearch version 2.6.9). L’ac- cesso ai dati è stato realizzato tra il 2 ed il 4 febbraio 2015. Una volta ottenuta la lista di proteine coinvolte, è stata condotta un’analisi per definirne le interazioni mediante il software STRING (Search Tool for the Retrieval of Interacting Genes/Proteins, http://string-db.org/). La rete formata dalle proteine (nodi) e dalle loro interazioni (links) è stata realizzata e visualizzata mediante Cytoscape 3.2.1, la topologia è stata analizzata con plug-in Network Analyzer (http://med.bioinf. mpi-inf. mpg.de/netanalyzer/index.php)6,7.
Risultati - La ricerca mediante BioNLP ha consentito di identificare una lista di 79 proteine coinvolte nell’eziopatogenesi del linfoma canino. L’analisi su STRING ha permesso di definire le loro interazioni per creare, con Cytoscape, una rete composta da 31 connected components, 554 nodi e 1614 links. L’analisi della rete (trattata come non diretta) ha permesso di classificarla come rete ad invarianza di scala (node degree distribution: y=370.18 x-1.629, r=0.663, R2=0.762) di tipo gerarchico (clustering coefficient =0.621, Averaged Clustering Coefficent vs. Number of Neighbors: y=1.932 x-0.629, r=0.915, R2=0.908). Proprio grazie a tale topologia è stato possibile identificare i nodi col maggior numero di links, gli hubs del sistema, che dimostrano anche un elevato grado di centralità nella rete (node degree vs. betweenness centrality r=0.676 e vs. closeness centrality r=0.677). Tali proteine sono elencate, in ordine decrescente di controllo, qui di seguito:
c-jun: insieme a c-fos coinvolto nel controllo del ciclo cellulare e nella regolazione dell’apoptosi.
p53: un fattore di trascrizione che regola il ciclo cellulare e ricopre la funzione di soppressore tumorale.
Grb2: un adaptor protein coinvolto nella trasduzione del segnale e nella comunicazione fra cellule; in particolare lega il recet- tore per EGF.
PIK3CB: fosfoinositide 3-chinasi, subunità catalitica beta, coinvolta in varie vie di trasduzione del segnale che regolano la cre- scita cellulare in risposta a vari stimoli mitotici.
LYN: appartiene alla famiglia delle proteinchinasi Src ed espresso principalmente da cellule ematopoietiche, tessuto nervoso, fegato e tessuto adiposo; in particolare nelle cellule emopoietiche è uno degli enzimi chiave coinvolti nella regolazione dell’at- tivazione cellulare.
PIK3R1: fosfatidilinositolo-3-chinasi, ha un importante ruolo nell’azione dell’insulina.
AKT1: attivata dalla fosfatidilinositolo-3-chinasi, i ratti KO per il gene Akt1 sono resistenti ai tumori.
PTPN6: coinvolta nella differenziazione cellulare, ciclo mitotico e trasformazione oncogena.
c-fos: vedi c-jun.
Conclusioni - Grazie all’uso di sofisticate metodiche computazionali è possibile individuare nuove proteine coinvolte nell’e- ziopatogenesi del LC, che potrebbero rappresentare futuri markers diagnostici e/o targets terapeutici
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
DNA uptake in swine sperm: Effect of plasmid topology and methyl-beta-cyclodextrin-mediated cholesterol depletion
No full textSperm-mediated gene transfer (SMGT), the ability of sperm cells to spontaneously incorporate exogenous DNA and to deliver it to oocytes during fertilization, has been proposed as an easy and efficient method for producing transgenic animals. SMGT is still undergoing development and optimization to improve the uptake efficiency of foreign DNA by sperm cells, which is a preliminary, yet critical, step for successful SMGT. Towards this aim, we developed a quantitative, real-time PCR-based assay to assess the absolute number of exogenous plasmids internalized into the spermatozoon. Using this technique, we found that the circular form of the DNA is more efficiently taken up than the linearized form. We also found that DNA internalization into the nucleus of porcine sperm cells is better under specific methyl-beta-cyclodextrin (MCD)-treated conditions, where the plasma membrane properties were altered without significantly compromising sperm physiology. These results provide the first evidence that membrane cholesterol depletion by MCD might represent a novel strategy for enhancing the ability of sperm to take up heterologous DNA. Mol. Reprod. Dev. 79: 853860, 2012. (C) 2012 Wiley Periodicals, Inc
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Endocannabinoid-binding CB1 and TRPV1 receptors as modulators of sperm capacitation
No full textMammalian spermatozoa reach the ability to fertilize only after they complete a complex series of physical-chemical modification, the capacitation. Recently, the endocannabinoid-binding type-1cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 (TRPV1) channel have been proposed to play a key role in the control of capacitation. In particular CB1, acting via a Gi protein/cAMP/PKA pathway, maintains low cAMP levels in early stages of post ejaculatory life of male gametes. By this way it promotes the maintenance of membrane stability, thus avoiding the premature fusion of plasma membrane (PM) and outer acrosome membrane (OAM), which is mandatory for the exocytosis of acrosome content. TRPV1, on the contrary, becomes active during the latest stages of capacitation, and allows the rapid increase in intracellular calcium concentration that leads to the removal of the F-actin network interposed between PM and OAM, leading to their fusion and, ultimately, to the acrosome reaction
- …
