Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.     

Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies

Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.     

Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.     

Effect of inoculum size, relative humidity, storage temperature, and ripening stage on the attachment of Salmonella Montevideo to tomatoes and tomatillos

The influence of inoculum populations and environmental factors on attachment of Salmonella Montevideo to the surface of tomatoes and tomatillos was evaluated. To study the effect of inoculum size, red, ripe tomatoes were spot-inoculated with bacterial suspensions (10(5) and 10(8) CFU/fruit) and stored at 22 degrees C under 100% relative humidity. The effects of temperature (12, 22, and 30 degrees C) and relative humidity (75, 85, and 97%) on attachment of the pathogen (10(7) CFU/fruit) to tomatoes (red and green) and ripe tomatillos were also evaluated. Inoculated fruits were stored for 90 min at all combinations of temperature and relative humidity, and after rinsing with water, the number of cells attached to the surface was determined. Salmonella Montevideo attached to the surface of tomatoes within 90 min. A direct correlation between the number of attached cells and the population in the inoculum was observed. The percentage of cells that attached immediately after inoculation was approximately 0.3% for the three test products. After storage for 90 min at various temperature and relative humidity conditions, the number of adhering cells ranged from 4.0 to 5.4 log CFU/fruit (1.2% of inoculum). Both the type of product and the temperature/relative humidity combination had a significant (P < 0.05) effect on attachment of Salmonella Montevideo to the surfaces of tomatoes and tomatillos. Scanning electron micrographs of the cuticles of inoculated washed tomatoes and tomatillos revealed typical skin cell patterns, and only a few randomly dispersed Salmonella Montevideo were observed. Deposition of Salmonella Montevideo on the surface of tomatoes and tomatillos could result in attachment and subsequent colonization under suitable conditions.     

Increased sensitivity for the diagnosis of Taenia saginata cysticercus infection by additional heart examination compared to the EU-approved routine meat inspection

In spite of the statutory meat inspection at abattoirs, Taenia saginata cysticercus infection in cattle remains an economically important parasitic disease for the livestock industry by affecting food safety. The routinely performed standard meat inspection protocol has a low diagnostic sensitivity for the detection of T. saginata cysticerci infections. Therefore, an abattoir trial aiming to increase the detection level was undertaken. In three EU-approved abattoirs, several additional heart incisions were performed in a total of 1088 slaughtered cattle originating from 832 farms throughout Switzerland. Cysticerci as putative parasitic lesions were classified by visual examination during meat inspection and confirmed microscopically and/or by molecular analyses. With the EU-approved routine meat inspection, bovine cysticercosis was diagnosed in 1.8% (20/1088) of the slaughtered animals. Additional incisions into the heart muscle revealed a further 29 cases, indicating that the prevalence was at least 4.5%. All infected animals originated from individual farms. This straightforward technique had a significantly higher sensitivity and is feasible for routine practice. It also confirms that the prevalence of this zoonotic parasite in the cattle population is underestimated based on the routine abattoir reports.     

A survey on the sanitary condition of commercial foods of plant origin sold in Brazil

The objective of the study was to evaluate the hygienic conditions and practices of commercial foods of plant origin in establishments and street marketed by street vendors in cities in the State of Rio de Janeiro, Brazil. Forty different sales points were evaluated (establishments that prepared and sold fruit juices and street vendors that commercialized fresh coconut water, sugarcane juice and orange juice) using a questionnaire with 12 items, divided into three blocks (salesmen/handlers, operations, installations). The results indicated that the activities related to the commerce of fruit beverages in the cities of São Gonçalo and Rio de Janeiro required the elaboration of a set of actions by the Sanitary Vigilance Agency in order to improve the hygienic and sanitary level and minimize health risk to consumers. Important requirements in the legislation relevant to this type of food are still not followed; adequate packaging and storage of the raw material, obtaining the raw material from registered suppliers, hygiene of the handlers and adequate management of wastes produced during the activities in question are amongst the main items deserving attention.     

Reading in graduate school: A survey of doctoral students in clinical psychology.

To what extent do graduate students in clinical psychology complete assigned readings? A total of 744 graduate students in American Psychological Association-accredited doctoral programs completed an online survey regarding reading in graduate school (67% response rate, of those viewing the survey). The reported amount of assigned reading varied widely, with an average of 330 pages per week. Compliance ratings suggested that about half the assigned reading is completed thoroughly and that thorough reading is more common than skimming or not reading assigned material. Motivating and hindering factors for reading are reported, and implications for faculty are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrochemical AFM investigation of horseradish peroxidase enzyme electro-immobilization with polypyrrole conducting polymer

In this paper we investigate the nano-characterization of polypyrrole (Ppy) thin film electro-synthesized on highly oriented pyrolitic graphite (HOPG) with and without horseradish peroxidase enzyme (HRP) using Atomic force microscopy (AFM) performed in contact mode and fluid cell with electrolyte and potential control (ECAFM). In situ electro-synthesis of thin polypyrrole film was made by cyclic volt–amperommetry achieving structured Ppy nanoparticles with two types of particle sizes and the same ellipsoidal shape. Furthermore, the electro-immobilization of HRP, onto this film, was made at a fixed potential, achieving different morphology characterized by highly rough, non-homogeneous structure, and partial maintaining of the ellipsoidal particle in specific sites. The effect of polarization time on morphological parameters was studied and two mechanisms of electro-immobilization of HRP with Ppy conducting polymers were proposed.     

A case-based approach for coordinated action selection in robot soccer

Designing coordinated robot behaviors in uncertain, dynamic, real-time, adversarial environments, such as in robot soccer, is very challenging. In this work we present a case-based reasoning approach for cooperative action selection, which relies on the storage, retrieval, and adaptation of example cases. We focus on cases of coordinated attacking passes between robots in the presence of the defending opponent robots. We present the case representation explicitly distinguishing between controllable and uncontrollable indexing features, corresponding to the positions of the team members and opponent robots, respectively. We use the symmetric properties of the domain to automatically augment the case library. We introduce a retrieval technique that weights the similarity of a situation in terms of the continuous ball positional features, the uncontrollable features, and the cost of moving the robots from the current situation to match the case controllable features. The case adaptation includes a best match between the positions of the robots in the past case and in the new situation. The robots are assigned an adapted position to which they move to maximize the match to the retrieved case. Case retrieval and reuse are achieved within the distributed team of robots through communication and sharing of own internal states and actions. We evaluate our approach, both in simulation and with real robots, in laboratory scenarios with two attacking robots versus two defending robots as well as versus a defender and a goalie. We show that we achieve the desired coordinated passing behavior, and also outperform a reactive action selection approach.     

A unified approach to modelling the performance of concurrent systems

Quantitative design is crucial to ICT and it is therefore important to integrate performance modelling techniques into support environments that facilitate the correct construction of computer systems. We consider Performance Modelling Interchange Formats (PMIFs), which allow models to be specified in a uniform way and ported to a number of tools that solve them. We focus on extending the class of models describable in a PMIF that can be solved analytically – specifically, yielding a product-form solution for their equilibrium state probabilities. We use an extension of an established theorem, called the ‘reversed compound agent theorem’ (RCAT) as the basis of the analytical modelling tool into which the extended PMIF feeds models. We describe the RCAT methodology in practical terms, how it is integrated into an extended PMIF, and illustrate our methodology with three examples.