Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

Decrease of resistance to air flow with nasal strips as measured with the airflow perturbation device

BACKGROUND: Nasal strips are used by athletes, people who snore, and asthmatics to ease the burden of breathing. Although there are some published studies that demonstrate higher flow with nasal strips, none had directly measured the effect of the strips on nasal resistance using the airflow perturbation device (APD). The APD is an inexpensive instrument that can measure respiratory resistance based on changes in mouth pressure and rate of airflow. METHOD: This study tested forty-seven volunteers (14 men and 33 women), ranging in age from 17 to 51. Each volunteer was instructed to breathe normally into the APD using an oronasal mask with and without nasal strips. The APD measured respiratory resistance during inhalation, exhalation, and an average of the two. RESULTS: Results of a paired mean t-test comparing nasal strip against no nasal strip were statistically significant at the p = 0.05 level. The Breathe Right™ nasal dilator strips lowered nasal resistance by an average of 0.5 cm H(2)0/Lps from an average nasal resistance of 5.5 cm H(2)0/Lps. CONCLUSIONS: Nasal strips reduce nasal resistance when measured with the APD. The effect is equal during exhalation and during inhalation

GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate $\gamma$-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells

Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins

Parent-Completed Developmental Screening in Premature Children: A Valid Tool for Follow-Up Programs

Our goals were to (1) validate the parental Ages and Stages Questionnaires (ASQ) as a screening tool for psychomotor development among a cohort of ex-premature infants reaching 2 years, and (2) analyse the influence of parental socio-economic status and maternal education on the efficacy of the questionnaire. A regional population of 703 very preterm infants (<35 weeks gestational age) born between 2003 and 2006 were evaluated at 2 years by their parents who completed the ASQ, by a pediatric clinical examination, and by the revised Brunet Lezine psychometric test with establishment of a DQ score. Detailed information regarding parental socio-economic status was available for 419 infants. At 2 years corrected age, 630 infants (89.6%) had an optimal neuromotor examination. Overall ASQ scores for predicting a DQ score ≤85 produced an area under the receiver operator curve value of 0.85 (95% Confidence Interval:0.82–0.87). An ASQ cut-off score of ≤220 had optimal discriminatory power for identifying a DQ score ≤85 with a sensitivity of 0.85 (95%CI:0.75–0.91), a specificity of 0.72 (95%CI:0.69–0.75), a positive likelihood ratio of 3, and a negative likelihood ratio of 0.21. The median value for ASQ was not significantly associated with socio-economic level or maternal education. ASQ is an easy and reliable tool regardless of the socio-economic status of the family to predict normal neurologic outcome in ex-premature infants at 2 years of age. ASQ may be beneficial with a low-cost impact to some follow-up programs, and helps to establish a genuine sense of parental involvement

Continental drift and climate change drive instability in insect assemblages

Global change has already had observable effects on ecosystems worldwide, and the accelerated rate of global change is predicted in the future. However, the impacts of global change on the stability of biodiversity have not been systematically studied in terms of both large spatial (continental drift) and temporal (from the last inter-glacial period to the next century) scales. Therefore, we analyzed the current geographical distribution pattern of Plecoptera, a thermally sensitive insect group, and evaluated its stability when coping with global change across both space and time throughout the Mediterranean region—one of the first 25 global biodiversity hotspots. Regional biodiversity of Plecoptera reflected the geography in both the historical movements of continents and the current environmental conditions in the western Mediterranean region. The similarity of Plecoptera assemblages between areas in this region indicated that the uplift of new land and continental drift were the primary determinants of the stability of regional biodiversity. Our results revealed that climate change caused the biodiversity of Plecoptera to slowly diminish in the past and will cause remarkably accelerated biodiversity loss in the future. These findings support the theory that climate change has had its greatest impact on biodiversity over a long temporal scale.This study was supported by a National Research Foundation of Korea (NRF) grant provided by the Korean government (MEST) (No. 2010-0027360)

Hydration level is an internal variable for computing motivation to obtain water rewards in monkeys

In the process of motivation to engage in a behavior, valuation of the expected outcome is comprised of not only external variables (i.e., incentives) but also internal variables (i.e., drive). However, the exact neural mechanism that integrates these variables for the computation of motivational value remains unclear. Besides, the signal of physiological needs, which serves as the primary internal variable for this computation, remains to be identified. Concerning fluid rewards, the osmolality level, one of the physiological indices for the level of thirst, may be an internal variable for valuation, since an increase in the osmolality level induces drinking behavior. Here, to examine the relationship between osmolality and the motivational value of a water reward, we repeatedly measured the blood osmolality level, while 2 monkeys continuously performed an instrumental task until they spontaneously stopped. We found that, as the total amount of water earned increased, the osmolality level progressively decreased (i.e., the hydration level increased) in an individual-dependent manner. There was a significant negative correlation between the error rate of the task (the proportion of trials with low motivation) and the osmolality level. We also found that the increase in the error rate with reward accumulation can be well explained by a formula describing the changes in the osmolality level. These results provide a biologically supported computational formula for the motivational value of a water reward that depends on the hydration level, enabling us to identify the neural mechanism that integrates internal and external variables

Practicing a Musical Instrument in Childhood is Associated with Enhanced Verbal Ability and Nonverbal Reasoning

Background: In this study we investigated the association between instrumental music training in childhood and outcomes closely related to music training as well as those more distantly related. Methodology/Principal Findings: Children who received at least three years (M = 4.6 years) of instrumental music training outperformed their control counterparts on two outcomes closely related to music (auditory discrimination abilities and fine motor skills) and on two outcomes distantly related to music (vocabulary and nonverbal reasoning skills). Duration of training also predicted these outcomes. Contrary to previous research, instrumental music training was not associated with heightened spatial skills, phonemic awareness, or mathematical abilities. Conclusions/Significance: While these results are correlational only, the strong predictive effect of training duration suggests that instrumental music training may enhance auditory discrimination, fine motor skills, vocabulary, and nonverba

Food Sharing across Borders

Evolutionary models consider hunting and food sharing to be milestones that paved the way from primate to human societies. Because fossil evidence is scarce, hominoid primates serve as referential models to assess our common ancestors’ capacity in terms of communal use of resources, food sharing, and other forms of cooperation. Whereas chimpanzees form male-male bonds exhibiting resource-defense polygyny with intolerance and aggression toward nonresidents, bonobos form male-female and female-female bonds resulting in relaxed relations with neighboring groups. Here we report the first known case of meat sharing between members of two bonobo communities, revealing a new dimension of social tolerance in this species. This observation testifies to the behavioral plasticity that exists in the two Pan species and contributes to scenarios concerning the traits of the last common ancestor of Pan and Homo. It also contributes to the discussion of physiological triggers of in-group/out-group behavior and allows reconsideration of the emergence of social norms in prehuman societies

Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes

The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system