Socio-geography of human mobility: a study using longitudinal mobile phone data

A relationship between people's mobility and their social networks is presented based on an analysis of calling and mobility traces for one year of anonymized call detail records of over one million mobile phone users in Portugal. We find that about 80% of places visited are within just 20 km of their nearest (geographical) social ties' locations. This figure rises to 90% at a 'geo-social radius' of 45 km. In terms of their travel scope, people are geographically closer to their weak ties than strong ties. Specifically, they are 15% more likely to be at some distance away from their weak ties than strong ties. The likelihood of being at some distance from social ties increases with the population density, and the rates of increase are higher for shorter geo-social radii. In addition, we find that area population density is indicative of geo-social radius where denser areas imply shorter radii. For example, in urban areas such as Lisbon and Porto, the geo-social radius is approximately 7 km and this increases to approximately 15 km for less densely populated areas such as Parades and Santa Maria da Feira.     

Activation of a helper and not regulatory human CD4+ T cell response by oncolytic H-1 parvovirus

Background

H-1 parvovirus (H-1 PV), a rodent autonomous oncolytic parvovirus, has emerged as a novel class of promising anticancer agents, because of its ability to selectively find and destroy malignant cells. However, to probe H-1 PV multimodal antitumor potential one of the major prerequisites is to decipher H-1 PV direct interplay with human immune system, and so prevent any risk of impairment.

Methodology/Principal findings

Non activated peripheral blood mononuclear cells (PBMCs) are not sensitive to H-1 PV cytotoxic effect. However, the virus impairs both activated PBMC proliferation ability and viability. This effect is related to H-1 PV infection as evidenced by Western blotting detection of H-1 PV main protein NS1. However, TCID50 experiments did not allow newly generated virions to be detected. Moreover, flow cytometry has shown that H-1 PV preferentially targets B lymphocytes. Despite seeming harmful at first sight, H-1 PV seems to affect very few NK cells and CD8+ T lymphocytes and, above all, clearly does not affect human neutrophils and one of the major CD4+ T lymphocyte subpopulation. Very interestingly, flow cytometry analysis and ELISA assays proved that it even activates human CD4+ T cells by increasing activation marker expression (CD69 and CD30) and both effective Th1 and Th2 cytokine secretion (IL-2, IFN-γ and IL-4). In addition, H-1 PV action does not come with any sign of immunosuppressive side effect. Finally, we have shown the efficiency of H-1 PV on xenotransplanted human nasopharyngeal carcinoma, in a SCID mouse model reconstituted with human PBMC.

Conclusions/Significance

Our results show for the first time that a wild-type oncolytic virus impairs some immune cell subpopulations while directly activating a Helper CD4+ T cell response. Thus, our data open numerous gripping perspectives of investigation and strongly argue for the use of H-1 PV as an anticancer treatment.     

Long time to diagnosis of medulloblastoma in children is not associated with decreased survival or with worse neurological outcome

Background

The long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae.

Patients and Methods

This retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome.

Results

The median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31–121, range 3–457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup.

Conclusions

We found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims.     

Miniaturized bioanalytical systems: enhanced performance through liposomes

Biorecognition-element labeled liposomes are simple and versatile tools used to amplify signals for the detection of analytes of environmental, clinical, food safety, and national security interest. Relying on measurement of encapsulated species via electrochemical or spectroscopic techniques, or properties inherent to liposomes themselves (such as mass, refractive index, or charge), many advances have been made in both bench-scale and microfluidic applications. Some of these measurement techniques are inherently sensitivity limited, but through the inclusion of liposomes, reduced limits of detection potentially broaden the utility towards otherwise challenging levels of analytes. Other advances took advantage of the hydrophobic environment required by many biorecognition elements to expand the target selectivity range or utilized the amphipathic nature of the lipid bilayer to provide enhanced separation capabilities. Novel handling approaches included wavelength-specific release of contents encapsulated within thermosensitive liposomes or application of electric fields to move, concentrate, and strategically lyse liposomes. These and other topics are discussed in terms of either present incorporation or adaptation to microfluidic devices.     

The human hepatocyte cell lines IHH and HepaRG: models to study glucose, lipid and lipoprotein metabolism

Metabolic diseases reach epidemic proportions. A better knowledge of the associated alterations in the metabolic pathways in the liver is necessary. These studies need in vitro human cell models. Several human hepatoma models are used, but the response of many metabolic pathways to physiological stimuli is often lost. Here, we characterize two human hepatocyte cell lines, IHH and HepaRG, by analysing the expression and regulation of genes involved in glucose and lipid metabolism. Our results show that the glycolysis pathway is activated by glucose and insulin in both lines. Gluconeogenesis gene expression is induced by forskolin in IHH cells and inhibited by insulin in both cell lines. The lipogenic pathway is regulated by insulin in IHH cells. Finally, both cell lines secrete apolipoprotein B-containing lipoproteins, an effect promoted by increasing glucose concentrations. These two human cell lines are thus interesting models to study the regulation of glucose and lipid metabolism.     

Targeted gene therapies: tools, applications, optimization

Many devastating human diseases are caused by mutations in a single gene that prevent a somatic cell from carrying out its essential functions, or by genetic changes acquired as a result of infectious disease or in the course of cell transformation. Targeted gene therapies have emerged as potential strategies for treatment of such diseases. These therapies depend upon rare-cutting endonucleases to cleave at specific sites in or near disease genes. Targeted gene correction provides a template for homology-directed repair, enabling the cell's own repair pathways to erase the mutation and replace it with the correct sequence. Targeted gene disruption ablates the disease gene, disabling its function. Gene targeting can also promote other kinds of genome engineering, including mutation, insertion, or gene deletion. Targeted gene therapies present significant advantages compared to approaches to gene therapy that depend upon delivery of stably expressing transgenes. Recent progress has been fueled by advances in nuclease discovery and design, and by new strategies that maximize efficiency of targeting and minimize off-target damage. Future progress will build on deeper mechanistic understanding of critical factors and pathways.     

Effect of two different long-sprint training regimens on sprint performance and associated metabolic responses

The purpose of this study was to analyze 2 different long-sprint training programs (TPs) of equal total work load, completed either with short recovery (SR) or long recovery (LR) between sets and to compare the effects of 6 long-sprint training sessions (TSs) conducted over a 2-week period on a 300-m performance. Fourteen trained subjects performed 3 pretraining maximal sprints (50-, 100-, and 300-m), were paired according to their 300-m performance, and randomly allocated to an LR or SR group, which performed 6 TSs consisting of sets of 150, 200, or 250 m. The recovery in the LR group was double that of the SR group. During the third TS and the 300-m pretest and posttest, blood pH, bicarbonate concentration ([HCO??]), excess-base (EB), and lactate concentration were recorded. Compared with a similar TS performed with SR, the LR training tends to induce a greater alteration of the acid-base balance: pH: 7.09 ± 0.08 (LR) and 7.14 ± 0.05 (SR) (p = 0.10), [HCO??]: 7.8 ± 1.9 (LR) and 9.6 ± 2.7 (SR) (p = 0.04), and EB: -21.1 ± 3.8 (LR) and -17.7 ± 2.8 (SR) (p = 0.11). A significant improvement in the 300-m performance between pre-TP and post-TP (42.45 ± 2.64 vs. 41.52 ± 2.45, p = 0.01) and significant decreases in pH (p < 0.01), EB (p < 0.001) and increase in [La] (p < 0.001) have been observed post-TP compared with those pre-TP. Although sprint training with longer recovery induces higher metabolic disturbances, both sprint training regimens allow a similar 300-m performance improvement with no concomitant significant progress in the 50- and 100-m performance.     

Dry-land strength training vs. electrical stimulation in sprint swimming performance

This study was undertaken to compare the effects of dry-land strength training vs. an electrical stimulation program on swimmers. Twenty-four national-level swimmers were randomly assigned to 3 groups: the dry-land strength training program (S), the electrical stimulation training program (ES), and the control (C) group. The training program lasted 4 weeks. The subjects were evaluated before the training, at the end of the training program, and 4 weeks later. The outcome values ascertained were peak torque during arm extension at different velocities (from -60 to 180°·s(-1)) using an isokinetic dynamometer and performance, stroke rate, and stroke length during a 50-m front crawl. A significant increase in swimming velocity and peak torque was observed for both S and ES at the end of the training and 4 weeks later. Stroke length increased in the S group but not in the ES group. However, no significant differences in swimming velocity between S and ES groups were observed. No significant changes occurred in the C group. Programs combining swimming training with dry-land strength or electrical stimulation programs led to a similar gain in sprint performance and were more efficient than swimming alone.     

Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease

During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted.     

Moving from a Cytotoxic to a Cytokinic Approach in the Blood Purification Labyrinth: Have We Finally Found Ariadne’s Thread?

For almost three decades, researchers have invested in strategies that involved removal of excess inflammatory mediators from the circulation (that is, the “cytotoxic” approach). Blood purification techniques using an extracorporeal device can indeed non-specifically remove a wide array of inflammatory mediators from the circulation. In animal models, this multimediator targeting or pleiotropic approach was shown to downregulate systemic inflammation and to restore immune homeostasis. In this issue, Namas et al. seriously challenge this cytotoxic hypothesis and propose to replace it by a cytokinic approach. In a rodent model of sepsis, these authors elegantly demonstrate that hemoadsorption using a large surface-area polymer could reduce and, more importantly, relocalize and reprogram sepsis-induced acute inflammation, while simultaneously lowering infectious burden and liver damage. Although challenging, this new theory can be considered complementary to the existing cytotoxic hypotheses by coupling reduced endothelial damage at the interstitial level (cytotoxic approach) with the concept of reprogramming leucocytes and mediators toward infected tissue, thus emptying the bloodstream of important promoters of remote organ damages (cytokinic approach).