Diffusion of Point Defects in Two-Dimensional Colloidal Crystals

We report the first study of the dynamics of point defects, mono and di-vacancies, in a confined 2-D colloidal crystal in real space and time using digital video microscopy. The defects are introduced by manipulating individual particles with optical tweezers. The diffusion rates are measured to be $D_{mono}/a^{2}\cong3.27\pm0.03$Hz for mono-vacancies and $D_{di}/a^{2}\cong3.71\pm0.03$Hz for di-vacancies. The elementary diffusion processes are identified and it is found that the diffusion of di-vacancies is enhanced by a \textit{dislocation dissociation-recombination} mechanism. Furthermore, the defects do not follow a simple random walk but their hopping exhibits memory effects, due to the reduced symmetry (compared to the triangular lattice) of their stable configurations, and the slow relaxation rates of the lattice modes.Comment: 6 pages (REVTEX), 5 figures (PS

Differential Effects of Concomitant Use of Vitamins C and E on Trophoblast Apoptosis and Autophagy between Normoxia and Hypoxia-Reoxygenation

Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR.Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Validity and reliability of a modified english version of the physical activity questionnaire for adolescents

BACKGROUND: Adaptation of physical activity self-report questionnaires is sometimes required to reflect the activity behaviours of diverse populations. The processes used to modify self-report questionnaires though are typically underreported. This two-phased study used a formative approach to investigate the validity and reliability of the Physical Activity Questionnaire for Adolescents (PAQ-A) in English youth. Phase one examined test content and response process validity and subsequently informed a modified version of the PAQ-A. Phase two assessed the validity and reliability of the modified PAQ-A. METHODS: In phase one, focus groups (n = 5) were conducted with adolescents (n = 20) to investigate test content and response processes of the original PAQ-A. Based on evidence gathered in phase one, a modified version of the questionnaire was administered to participants (n = 169, 14.5 ± 1.7 years) in phase two. Internal consistency and test-retest reliability were assessed using Cronbach’s alpha and intra-class correlations, respectively. Spearman correlations were used to assess associations between modified PAQ-A scores and accelerometer-derived physical activity, self-reported fitness and physical activity self-efficacy. RESULTS: Phase one revealed that the original PAQ-A was unrepresentative for English youth and that item comprehension varied. Contextual and population/cultural-specific modifications were made to the PAQ-A for use in the subsequent phase. In phase two, modified PAQ-A scores had acceptable internal consistency (α = 0.72) and test-retest reliability (ICC = 0.78). Modified PAQ-A scores were significantly associated with objectively assessed moderate-to-vigorous physical activity (r = 0.39), total physical activity (r = 0.42), self-reported fitness (r = 0.35), and physical activity self-efficacy (r = 0.32) (p ≤ 0.01). CONCLUSIONS: The modified PAQ-A had acceptable internal consistency and test-retest reliability. Modified PAQ-A scores displayed weak-to-moderate correlations with objectively measured physical activity, self-reported fitness, and self-efficacy providing evidence of satisfactory criterion and construct validity, respectively. Further testing with more diverse English samples is recommended to provide a more complete assessment of the tool. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13690-016-0115-2) contains supplementary material, which is available to authorized users

Active microrheology and simultaneous visualization of sheared phospholipid monolayers

Two-dimensional films of surface-active agents—from phospholipids and proteins to nanoparticles and colloids—stabilize fluid interfaces, which are essential to the science, technology and engineering of everyday life. The 2D nature of interfaces present unique challenges and opportunities: coupling between the 2D films and the bulk fluids complicates the measurement of surface dynamic properties, but allows the interfacial microstructure to be directly visualized during deformation. Here we present a novel technique that combines active microrheology with fluorescence microscopy to visualize fluid interfaces as they deform under applied stress, allowing structure and rheology to be correlated on the micron-scale in monolayer films. We show that even simple, single-component lipid monolayers can exhibit viscoelasticity, history dependence, a yield stress and hours-long time scales for elastic recoil and aging. Simultaneous visualization of the monolayer under stress shows that the rich dynamical response results from the cooperative dynamics and deformation of liquid-crystalline domains and their boundaries

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study

<p>Abstract</p> <p>Background</p> <p>Over expression of 9-<it>O-</it>acetylated sialoglycoproteins (Neu5,9Ac₂-GPs, abbreviated as <it>O</it>AcSGP) has been demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). Achatinin-H, a lectin, has selective affinity towards terminal 9-<it>O-</it>acetylated sialic acids-α2-6-<it>N</it>acetylated galactosamine. Exploring this affinity, enhanced expression of <it>O</it>AcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD) responsible for relapse. Our aim was to select a suitable template by using the differential expression of <it>O</it>AcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB) and bone marrow (BM) of Indian patients with B- or T-ALL during treatment and correlate it with the disease status.</p> <p>Methods</p> <p>A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667) and BM (n = 999) were monitored by flow cytometry. Three templates selected for this investigation were <it>O</it>AcSGP⁺CD10⁺CD19⁺or <it>O</it>AcSGP⁺CD34⁺CD19⁺for B-ALL and <it>O</it>AcSGP⁺CD7⁺CD3⁺for T-ALL.</p> <p>Results</p> <p>Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR). 81.65% of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well.</p> <p>Conclusion</p> <p>A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 ± 0.01% (PB) and 0.05 ± 0.015% (BM). These patients may not be stated as normal with respect to the presence of MRD. Hence, MRD study beyond two-years follow-up is necessary to investigate further reduction in MRD, thereby ensuring their disease-free survival. Therefore, we suggest use of these templates for MRD detection, during and post-chemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.</p

Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells