Parkinson's disease plasma biomarkers: An automated literature analysis followed by experimental validation

Diagnosis of Parkinson's disease (PD) is currently assessed by the clinical evaluation of extrapyramidal signs. The identification of specific biomarkers would be advisable, however most studies stop at the discovery phase, with no biomarkers reaching clinical exploitation. To this purpose, we developed an automated literature analysis procedure to retrieve all the background knowledge available in public databases. The bioinformatic platform allowed us to analyze more than 51,000 scientific papers dealing with PD, containing information on 4121 proteins. Out of these, we could track back 35 PD-related proteins as present in at least two published 2-DE maps of human plasma. Then, 9 different proteins (haptoglobin, transthyretin, apolipoprotein A-1, serum amyloid P component, apolipoprotein E, complement factor H, fibrinogen γ, thrombin, complement C3) split into 32 spots were identified as a potential diagnostic pattern. Eventually, we compared the collected literature data to experimental gels from 90 subjects (45 PD patients, 45 non-neurodegenerative control subjects) to experimentally verify their potential as plasma biomarkers of PD

Aislamiento, cultivo y caracterización de líneas celulares embrionarias bovinas

Isolation, culture, and characterization of embryonic cell lines from bovine blastocysts This study was aimed to develop methods for isolation, culture and characterization of embryonic cell lines from in vitro produced bovine blastocysts. Inner cell masses arising from blastocysts were isolated by immunosurgery onto mitomocin-C-inactivated mouse embryonic fibroblast (MEF). After 10 to 15 days of culture the primary cell colonies were disaggregated, seeded in a new MEF, and cultured for 3 to 6 days up to form new colonies. The primary cell colonies, passage 2, passage 3 and post-thawed colonies expressed pluripotency markers such us SSEA-4, TRA-1-60 and Oct4 and were alkaline phosphatase positive. More research is needed to confirm pluripotency and selfrenew stage within the obtained embryonic stem-like cells (ES-like).El objetivo principal de este trabajo es el aislamiento, cultivo y caracterización de líneas embrionarias producidas a partir del aislamiento de masa celular interna (MCI) de blastocisto bovino. Las MCI se aislaron mediante inmunocirugía y se cultivaron en monocapas de fibroblastos embrionarios de ratón (MEF) mitóticamente inactivados. Tras 10-15 días de cultivo primario, las colonias surgidas se disgregaron, resembraron en una nueva MEF, y cultivaron por tiempo variable para tratar de obtener nuevas colonias. Tanto los cultivos primarios como los pases 2 y 3, así como las colonias supervivientes a la congelación, expresaron los marcadores de pluripotencia SSEA-4, TRA-1-60 y Oct4, y fueron positivos al test de la fosfatasa alcalina. A falta de pruebas para el diagnóstico de la pluripotencia y capacidad de autorrenovación, las células obtenidas presentan parte de las características de las células troncales embrionarias (ES-like)

Dabigatran accumulation in acute kidney injury: is more better than less to prevent bleeding? A case report.

Dabigatran is an oral anticoagulant that is mainly renally excreted. Despite its efficacy in preventing thromboembolic events, concerns arise regarding bleeding complications in patients with acute kidney injury. Idarucizumab is its specific antidote and reverses quickly and effectively dabigatran anticoagulation effects in situations of severe bleeding or pending surgical procedures, but its benefit beyond these two indications remains uncertain. We present a case of a woman with atrial fibrillation anticoagulated by dabigatran and admitted with Streptococcus agalactiae meningitis, acute kidney injury and dabigatran accumulation. Idarucizumab was not administered initially as she did not meet its current strict indications. However, subsequently, significant bleeding necessitated its use. A rebound increase in dabigatran concentration was associated with an intracranial hemorrhage, but the combination of additional doses of idarucizumab with hemodialysis lowered the dabigatran concentration and prevented significant rebound increases. Further investigation into the optimal management of dabigatran accumulation and acute kidney injury-associated bleeding is needed to enhance patient outcomes and safety. Early initiation of hemodialysis together with idarucizumab administration may be crucial in preventing life-threatening bleeding events in these patients

Principles of early human development and germ cell program from conserved model systems

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during week 2-3 of early postimplantation development(1). Using in vitro models of hPGC induction(2-4), recent studies suggest striking mechanistic differences in specification of human and mouse PGCs(5). This may partly be due to the divergence in their pluripotency networks, and early postimplantation development(6-8). Since early human embryos are inaccessible for direct studies, we considered alternatives, including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs (pPGCs) originate from the posterior pre-primitive streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. Together with human and monkey in vitro models simulating peri-gastrulation development, we show conserved principles for epiblast development for competency for PGC fate, followed by initiation of the epigenetic program(9-11), regulated by a balanced SOX17–BLIMP1 gene dosage. Our combinatorial approach using human, porcine and monkey in vivo and in vitro models, provides synthetic insights on early human development

Rapid malignant progression of an intraparenchymal choroid plexus papillomas

Background: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only 0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health Organization (WHO) classification describes three histological grades: grade I is choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial localization. Case Description: Here we report a very rare case of an intraparenchymal parietal CPP with a rapid histological transition from grade I to grade III WHO in a 67-year-old man, in <7 months. Conclusion: Because of the rarity of these oncotypes, descriptions of each new case are useful, mostly to consider this diagnostic entity in extraventricular brain tumors of adults, despite an unusual location

Peripheral facial palsy following ventriculoperitoneal shunt. The lesson we have learned

The most frequent complications after shunt surgery are infective and obstructive. Other types are less common, and eventually occur due to technical errors during brain ventricular puncture, opening the intraperitoneal cavity or the tunnelling of the catheter between the two points. Although rare, there are well-reported complications related to the poor positioning of the distal catheter, with perforation of organs and tissues. We report a very rare case of a male patient with normal pressure hydrocephalus submitted to ventriculoperitoneal shunt. During tunnelling of the shunt stylet, a peripheral facial palsy due to injury to the extra cranial segment of the facial nerve occurred. To the best of our knowledge this is the second case described in Literature. The patient and the surgeon should be aware of this very rare but possible complication in shunt surgery being careful to the course of the facial nerve in the mastoid region

Efecto de la adición atrasada de suero fetal bovino al medio de cultivo sobre la producción in vitro de embriones de novillas criollas criadas a gran altura en el Ecuador

El estudio tuvo como objetivo evaluar el efecto del suero fetal bovino (FCS) agregado al medio de cultivo los días 5 a 7 después de la fertilización in vitro sobre la producción y posterior criotolerancia de blastocistos de vaquillonas criollas ecuatorianas. Se recolectaron complejos cúmulo-ovocitos (COCs) inmaduros mediante aspiración intravaginal guiada por ultrasonido (OPU) de 10 vaquillonas criollas y de ovarios de matadero en ocho sesiones. Los COCs se sometieron a maduración in vitro (MIV), fecundación (FIV) y cultivo (IVC). El día 1 después de la FIV, los presuntos embriones de cada fuente de ovocitos (OPU [O] y Matadero [A]) se asignaron aleatoriamente en dos grupos según si se añadió FCS al 2.5% (v/v) al medio de cultivo el día 5 después de la FIV: 1) O-FCS+, 2) O-FCS-, 3) A-FCS+ y 4) A-FCS-. El día 7 después de la FIV se vitrificaron embriones de alta calidad. La criotolerancia de los embriones vitrificados-calentados se evaluó según la reexpansión del blastocele a las 2 h y la posterior reexpansión y eclosión a las 24 y 48 h de incubación. La tasa de blastocistos el día 7 no difirió entre la fuente de ovocitos y el grupo FCS. Después del proceso de vitrificación/calentamiento, la adición de FCS solo afectó la tasa de reexpansión a las 2 h, independientemente de la fuente de ovocitos (p<0.05). Asimismo, la tasa de eclosión de los blastocistos a las 48 h de incubación se vio drásticamente afectada únicamente en los ovocitos derivados de OPU (p<0.01). En conclusión, la suplementación de FCS el día 5 después de la FIV no mejoró la producción de blastocistos y afectó negativamente la criotolerancia de embriones bovinos in vitro derivados de vaquillonas criollas criadas en los Andes ecuatorianos.This experiment aimed to assess the effect of fetal calf serum (FCS) added to culture medium on day 5 to 7 after in vitro fertilization on production and subsequent cryotolerance of blastocysts from Ecuadorian Creole heifers. Immature cumulus-oocyte complexes (COCs) were collected by ovum pick-up (OPU) from 10 Creole heifers and from ovaries collected at abattoir in eight collection sessions. COCs were subjected to in vitro maturation (IVM), fertilization (IVF), and culture (IVC). On day 1 after IVF, presumptive embryos from each oocyte source (OPU [O] and Abattoir [A]) were allocated randomly in two groups according to whether 2.5% (v/v) FCS was added to culture medium on day 5 after IVF: 1) O-FCS+, 2) O-FCS-, 3) A-FCS+, and 4) A-FCS-. On day 7 after IVF, high quality embryos were vitrified. Cryotolerance of vitrified-warmed embryos was assessed according to blastocele re-expansion at 2 h and subsequent re-expansion and hatching at 24 and 48 h of re-incubation. Blastocysts rate on day 7 did not differ between oocyte source and FCS group. After vitrification/warming process, addition of FCS affected the re-expansion rate only at 2 h, irrespective of the oocyte source (p<0.05). Likewise, blastocysts hatching rate at 48 h of incubation was drastically affected only in OPU-derived oocyte (p<0.01). Supplementation of FCS on day 5 after IVF did not improve blastocyst production and adversely affected the cryotolerance of in vitro bovine embryos derived from creole heifers raised on Ecuadorian Andean highlands

A gene expression atlas of the domestic pig

<p>Abstract</p> <p>Background</p> <p>This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering.</p> <p>Results</p> <p>The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development.</p> <p>Conclusions</p> <p>As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites <url>http://biogps.org and http://www.macrophages.com/pig-atlas</url>.</p

Axolotl Nanog activity in mouse embryonic stem cells demonstrates that ground state pluripotency is conserved from urodele amphibians to mammals

Cells in the pluripotent ground state can give rise to somatic cells and germ cells, and the acquisition of pluripotency is dependent on the expression of Nanog. Pluripotency is conserved in the primitive ectoderm of embryos from mammals and urodele amphibians, and here we report the isolation of a Nanog ortholog from axolotls (axNanog). axNanog does not contain a tryptophan repeat domain and is expressed as a monomer in the axolotl animal cap. The monomeric form is sufficient to regulate pluripotency in mouse embryonic stem cells, but axNanog dimers are required to rescue LIF-independent self-renewal. Our results show that protein interactions mediated by Nanog dimerization promote proliferation. More importantly, they demonstrate that the mechanisms governing pluripotency are conserved from urodele amphibians to mammals. © 2010. Published by The Company of Biologists Ltd