Science that "knows" and science that "asks"

Clinician-researchers and experimental scientists do not speak the same language; they have different professional environments and different end-points in their research. This creates considerable problems of comprehension and communication, which constitute a major drawback in multidisciplinary work such as translational medicine. A stereotypic representation of both these worlds is presented as a starting point to encourage debate on this issue

SDSS-IV MaNGA: Spatially resolved star formation histories in galaxies as a function of galaxy mass and type

© 2016 The Authors. We study the internal gradients of stellar population propertieswithin 1.5 Re for a representative sample of 721 galaxies, with stellar masses ranging between 109M⊙ and 1011.5M⊙ from the SDSS-IV MaNGA Integral-Field-Unit survey. Through the use of our full spectral fitting code FIREFLY, we derive light- and mass-weighted stellar population properties and their radial gradients, as well as full star formation and metal enrichment histories. We also quantify the impact that different stellar population models and full spectral fitting routines have on the derived stellar population properties and the radial gradient measurements. In our analysis, we find that age gradients tend to be shallow for both early-type and late-type galaxies. Mass-weighted age gradients of early-types arepositive (~0.09 dex/Re) pointing to 'outside- in' progression of star formation, while late-type galaxies have negative light-weighted age gradients (~-0.11 dex/Re), suggesting an 'inside-out' formation of discs. We detect negative metallicity gradients in both early- and late-type galaxies, but these are significantly steeper in late-types, suggesting that the radial dependence of chemical enrichment processes and the effect of gas inflow and metal transport are far more pronounced in discs. Metallicity gradients of both morphological classes correlate with galaxy mass, with negative metallicity gradients becoming steeper with increasing galaxy mass. The correlation with mass is stronger for late-type galaxies, with a slope of d(∇[Z/H])/d(logM) ~ -0.2 ± 0.05, compared to d(∇[Z/H])/d(logM) ~ -0.05 ± 0.05 for early-types. This result suggests that the merger history plays a relatively small role in shaping metallicity gradients of galaxies

Regulator of G Protein Signaling 3 Modulates Wnt5b Calcium Dynamics and Somite Patterning

Vertebrate development requires communication among cells of the embryo in order to define the body axis, and the Wnt-signaling network plays a key role in axis formation as well as in a vast array of other cellular processes. One arm of the Wnt-signaling network, the non-canonical Wnt pathway, mediates intracellular calcium release via activation of heterotrimeric G proteins. Regulator of G protein Signaling (RGS) proteins can accelerate inactivation of G proteins by acting as G protein GTPase-activating proteins (GAPs), however, the possible role of RGS proteins in non-canonical Wnt signaling and development is not known. Here, we identify rgs3 as having an overlapping expression pattern with wnt5b in zebrafish and reveal that individual knockdown of either rgs3 or wnt5b gene function produces similar somite patterning defects. Additionally, we describe endogenous calcium release dynamics in developing zebrafish somites and determine that both rgs3 and wnt5b function are required for appropriate frequency and amplitude of calcium release activity. Using rescue of gene knockdown and in vivo calcium imaging assays, we demonstrate that the activity of Rgs3 requires its ability to interact with Gα subunits and function as a G protein GAP. Thus, Rgs3 function is necessary for appropriate frequency and amplitude of calcium release during somitogenesis and is downstream of Wnt5 activity. These results provide the first evidence for an essential developmental role of RGS proteins in modulating the duration of non-canonical Wnt signaling

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape

Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (<it>PGRN</it>) gene.</p> <p>Results</p> <p>Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying <it>PGRN </it>mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of <it>PGRN </it>mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.</p> <p>Conclusions</p> <p>Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by <it>PGRN </it>mutations and provides new insight into potential future therapeutic options.</p

P2 receptors are involved in the mediation of motivation-related behavior

The importance of purinergic signaling in the intact mesolimbic–mesocortical circuit of the brain of freely moving rats is reviewed. In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y1 receptor stimulation. Similar mechanisms may regulate the release of glutamate in both areas of the brain. Dopamine and glutamate determine in concert the activity of the accumbal GABAergic, medium-size spiny neurons thought to act as an interface between the limbic cortex and the extrapyramidal motor system. These neurons project to the pallidal and mesencephalic areas, thereby mediating the behavioral reaction of the animal in response to a motivation-related stimulus. There is evidence that extracellular ADP/ATP promotes goal-directed behavior, e.g., intention and feeding, via dopamine, probably via P2Y1 receptor stimulation. Accumbal P2 receptor-mediated glutamatergic mechanisms seem to counteract the dopaminergic effects on behavior. Furthermore, adaptive changes of motivation-related behavior, e.g., by chronic succession of starvation and feeding or by repeated amphetamine administration, are accompanied by changes in the expression of the P2Y1 receptor, thought to modulate the sensitivity of the animal to respond to certain stimuli

Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites

Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches

Design of a randomized controlled trial for multiple cancer risk behaviors among Spanish-speaking Mexican-origin smokers

Background: Smoking, poor diet, and physical inactivity account for as much as 60% of cancer risk. Latinos experience profound disparities in health behaviors, as well as the cancers associated with them. Currently, there is a dearth of controlled trials addressing these health behaviors among Latinos. Further, to the best of our knowledge, no studies address all three behaviors simultaneously, are culturally sensitive, and are guided by formative work with the target population. Latinos represent 14% of the U. S. population and are the fastest growing minority group in the country. Efforts to intervene on these important lifestyle factors among Latinos may accelerate the elimination of cancer-related health disparities