Culturing Pancreatic Islets in Microfluidic Flow Enhances Morphology of the Associated Endothelial Cells

Pancreatic islets are heavily vascularized in vivo with each insulin secreting beta-cell associated with at least one endothelial cell (EC). This structure is maintained immediately post-isolation; however, in culture the ECs slowly deteriorate, losing density and branched morphology. We postulate that this deterioration occurs in the absence of blood flow due to limited diffusion of media inside the tissue. To improve exchange of media inside the tissue, we created a microfluidic device to culture islets in a range of flow-rates. Culturing the islets from C57BL6 mice in this device with media flowing between 1 and 7 ml/24 hr resulted in twice the EC-density and -connected length compared to classically cultured islets. Media containing fluorescent dextran reached the center of islets in the device in a flow-rate-dependant manner consistent with improved penetration. We also observed deterioration of EC morphology using serum free media that was rescued by addition of bovine serum albumin, a known anti-apoptotic signal with limited diffusion in tissue. We further examined the effect of flow on beta-cells showing dampened glucose-stimulated Ca2+-response from cells at the periphery of the islet where fluid shear-stress is greatest. However, we observed normal two-photon NAD(P)H response and insulin secretion from the remainder of the islet. These data reveal the deterioration of islet EC-morphology is in part due to restricted diffusion of serum albumin within the tissue. These data further reveal microfluidic devices as unique platforms to optimize islet culture by introducing intercellular flow to overcome the restricted diffusion of media components

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

Coupling carbon nanotube mechanics to a superconducting circuit

The quantum behaviour of mechanical resonators is a new and emerging field driven by recent experiments reaching the quantum ground state. The high frequency, small mass, and large quality-factor of carbon nanotube resonators make them attractive for quantum nanomechanical applications. A common element in experiments achieving the resonator ground state is a second quantum system, such as coherent photons or superconducting device, coupled to the resonators motion. For nanotubes, however, this is a challenge due to their small size. Here, we couple a carbon nanoelectromechanical (NEMS) device to a superconducting circuit. Suspended carbon nanotubes act as both superconducting junctions and moving elements in a Superconducting Quantum Interference Device (SQUID). We observe a strong modulation of the flux through the SQUID from displacements of the nanotube. Incorporating this SQUID into superconducting resonators and qubits should enable the detection and manipulation of nanotube mechanical quantum states at the single-phonon level

On RAF Sets and Autocatalytic Cycles in Random Reaction Networks

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life context. Although the possibility to reproduce this emergence in laboratory has received considerable attention, this is still far from being achieved. In order to unravel some key properties enabling the emergence of structures potentially able to sustain their own existence and growth, in this work we investigate the probability to observe them in ensembles of random catalytic reaction networks characterized by different structural properties. From the point of view of network topology, an autocatalytic set have been defined either in term of strongly connected components (SCCs) or as reflexively autocatalytic and food-generated sets (RAFs). We observe that the average level of catalysis differently affects the probability to observe a SCC or a RAF, highlighting the existence of a region where the former can be observed, whereas the latter cannot. This parameter also affects the composition of the RAF, which can be further characterized into linear structures, autocatalysis or SCCs. Interestingly, we show that the different network topology (uniform as opposed to power-law catalysis systems) does not have a significantly divergent impact on SCCs and RAFs appearance, whereas the proportion between cleavages and condensations seems instead to play a role. A major factor that limits the probability of RAF appearance and that may explain some of the difficulties encountered in laboratory seems to be the presence of molecules which can accumulate without being substrate or catalyst of any reaction.Comment: pp 113-12

Electromagnetically Induced Transparency and Slow Light with Optomechanics

Controlling the interaction between localized optical and mechanical excitations has recently become possible following advances in micro- and nano-fabrication techniques. To date, most experimental studies of optomechanics have focused on measurement and control of the mechanical subsystem through its interaction with optics, and have led to the experimental demonstration of dynamical back-action cooling and optical rigidity of the mechanical system. Conversely, the optical response of these systems is also modified in the presence of mechanical interactions, leading to strong nonlinear effects such as Electromagnetically Induced Transparency (EIT) and parametric normal-mode splitting. In atomic systems, seminal experiments and proposals to slow and stop the propagation of light, and their applicability to modern optical networks, and future quantum networks, have thrust EIT to the forefront of experimental study during the last two decades. In a similar fashion, here we use the optomechanical nonlinearity to control the velocity of light via engineered photon-phonon interactions. Our results demonstrate EIT and tunable optical delays in a nanoscale optomechanical crystal device, fabricated by simply etching holes into a thin film of silicon (Si). At low temperature (8.7 K), we show an optically-tunable delay of 50 ns with near-unity optical transparency, and superluminal light with a 1.4 microseconds signal advance. These results, while indicating significant progress towards an integrated quantum optomechanical memory, are also relevant to classical signal processing applications. Measurements at room temperature and in the analogous regime of Electromagnetically Induced Absorption (EIA) show the utility of these chip-scale optomechanical systems for optical buffering, amplification, and filtering of microwave-over-optical signals.Comment: 15 pages, 9 figure

Control of microwave signals using circuit nano-electromechanics

Waveguide resonators are crucial elements in sensitive astrophysical detectors [1] and circuit quantum electrodynamics (cQED) [2]. Coupled to artificial atoms in the form of superconducting qubits [3, 4], they now provide a technologically promising and scalable platform for quantum information processing tasks [2, 5-8]. Coupling these circuits, in situ, to other quantum systems, such as molecules [9, 10], spin ensembles [11, 12], quantum dots [13] or mechanical oscillators [14, 15] has been explored to realize hybrid systems with extended functionality. Here, we couple a superconducting coplanar waveguide resonator to a nano-coshmechanical oscillator, and demonstrate all-microwave field controlled slowing, advancing and switching of microwave signals. This is enabled by utilizing electromechanically induced transparency [16-18], an effect analogous to electromagnetically induced transparency (EIT) in atomic physics [19]. The exquisite temporal control gained over this phenomenon provides a route towards realizing advanced protocols for storage of both classical and quantum microwave signals [20-22], extending the toolbox of control techniques of the microwave field.Comment: 9 figure

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA(1c) levels.RESEARCH DESIGN AND METHODS-We studied associations with HbA(1c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA(1c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.RESULTS-Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10(-26)), HFE (rs1800562/P = 2.6 x 10(-20)), TMPRSS6 (rs855791/P = 2.7 x 10(-14)), ANK1 (rs4737009/P = 6.1 x 10(-12)), SPTA1 (rs2779116/P = 2.8 x 10(-9)) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10(-9)), and four known HbA(1c) loci: HK1 (rs16926246/P = 3.1 x 10(-54)), MTNR1B (rs1387153/P = 4.0 X 10(-11)), GCK (rs1799884/P = 1.5 x 10(-20)) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10(-18)). We show that associations with HbA(1c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (%HbA(1c)) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA(1c).CONCLUSIONS-GWAS identified 10 genetic loci reproducibly associated with HbA(1c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA(1c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA(1c) Diabetes 59: 3229-3239, 201

Sex differences in short-term mate preferences and behavioral mimicry: A semi-naturalistic experiment

Item does not contain fulltextStudies on short-term mating (STM) yield sex differences regarding preferences for attractiveness (important towomen, very important to men) and social status (very important to women, not to men) in potential mates. Additionally, men generally report a greater desire to engage in STM than women. So far, this evidence is primarily based on studies using vignettes or surveys. The current study extended the findings on sex differences in STM by examining actual behavior and STM-desires towards real people of the opposite sex. It investigated whether (1) sex differences exist in STM-desire, (2) whether this desire was affected by a confederate's attractiveness and status, and (3) if these sex differences were also reflected in interpersonal behavior (mimicry). In a pub-like laboratory, single heterosexual participants performed a task alongside a confederate of the opposite sex, who differed in attractiveness and social status. Mimicry was observed and explicit STM-desire was assessed. Results showed that men only desired STM more than women in the case of an attractive partner. Women's STMdesire did not vary as a function of status or ttractiveness of the potential partner. Men’s, but not women's, mimicry paralleled these differential STM-desires. These results underline the conditionality of sex differences in STM-desire and provide a useful paradigm to further investigate STM.10 p

Women, wellbeing and Wildlife Management Areas in Tanzania

Community-based wildlife management claims pro-poor, gender-sensitive outcomes. However, intersectional political ecology predicts adverse impacts on marginalised people. Our large-scale quantitative approach draws out common patterns and differentiated ways women are affected by Tanzania’s Wildlife Management Areas (WMAs). This first large-scale, rigorous evaluation studies WMA impacts on livelihoods and wellbeing of 937 married women in 42 villages across six WMAs and matched controls in Northern and Southern Tanzania. While WMAs bring community infrastructure benefits, most women have limited political participation, and experience resource use restrictions and fear of wildlife attacks. Wealth and region are important determinants, with the poorest worst impacted