Structure and Kinematics of the Nearby Dwarf Galaxy UGCA 105

Owing to their shallow stellar potential, dwarf galaxies possess thick gas disks, which makes them good candidates for studies of the galactic vertical kinematical structure. We present 21 cm line observations of the isolated nearby dwarf irregular galaxy UGCA 105, taken with the Westerbork Synthesis Radio Telescope (WSRT), and analyse the geometry of its neutral hydrogen (HI) disk and its kinematics. The galaxy shows a fragmented HI distribution. It is more extended than the optical disk, and hence allows one to determine its kinematics out to very large galacto-centric distances. The HI kinematics and morphology are well-ordered and symmetric for an irregular galaxy. The HI is sufficiently extended to observe a substantial amount of differential rotation. Moreover, UGCA 105 shows strong signatures for the presence of a kinematically anomalous gas component. Performing tilted-ring modelling by use of the least-squares fitting routine TiRiFiC, we found that the HI disk of UGCA 105 has a moderately warped and diffuse outermost part. Probing a wide range of parameter combinations, we succeeded in modelling the data cube as a disk with a strong vertical gradient in rotation velocity ($\approx -60\,\rm km\,s^{-1}\,kpc^{-1}$), as well as vertically increasing inwards motion ($\approx -70\,\rm km\,s^{-1}\,kpc^{-1}$) within the radius of the stellar disk. The inferred radial gas inflow amounts to $0.06\,\rm M_\odot \rm yr^{-1}$, which is similar to the star formation rate of the galaxy. The observed kinematics are hence compatible with direct or indirect accretion from the intergalactic medium, an extreme backflow of material that has formerly been expelled from the disk, or a combination of both.Comment: 15 pages, 12 figures, accepted for publication in Astronomy & Astrophysic

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Rapid diagnostic tests for molecular surveillance of Plasmodium falciparum malaria -assessment of DNA extraction methods and field applicability

Background: The need for new malaria surveillance tools and strategies is critical, given improved global malaria control and regional elimination efforts. High quality Plasmodium falciparum DNA can reliably be extracted from malaria rapid diagnostic tests (RDTs). Together with highly sensitive molecular assays, wide scale collection of used RDTs may serve as a modern tool for improved malaria case detection and drug resistance surveillance. However, comparative studies of DNA extraction efficiency from RDTs and the field applicability are lacking. The aim of this study was to compare and evaluate different methods of DNA extraction from RDTs and to test the field applicability for the purpose of molecular epidemiological investigations. Methods: DNA was extracted from two RDT devices (Paracheck-PfW and SD Bioline Malaria Pf/Pan (R)), seeded in vitro with 10-fold dilutions of cultured 3D7 P. falciparum parasites diluted in malaria negative whole blood. The level of P. falciparum detection was determined for each extraction method and RDT device with multiple nested-PCR and real-time PCR assays. The field applicability was tested on 855 paired RDT (Paracheck-Pf) and filter paper (Whatman (R) 3MM) blood samples (734 RDT negative and 121 RDT positive samples) collected from febrile patients in Zanzibar 2010. RDT positive samples were genotyped at four key single nucleotide polymorphisms (SNPs) in pfmdr1 and pfcrt as well as for pfmdr1 copy number, all associated with anti-malarial drug resistance. Results: The P. falciparum DNA detection limit varied with RDT device and extraction method. Chelex-100 extraction performed best for all extraction matrixes. There was no statistically significant difference in PCR detection rates in DNA extracted from RDTs and filter paper field samples. Similarly there were no significant differences in the PCR success rates and genotyping outcomes for the respective SNPs in the 121 RDT positive samples. Conclusions: The results support RDTs as a valuable source of parasite DNA and provide evidence for RDT-DNA extraction for improved malaria case detection, molecular drug resistance surveillance, and RDT quality control.ACT Consortium through Bill and Melinda Gates Foundation; Swedish International Development Agency (SIDA) [SWE 2009-193]; Swedish Civil Contingencies Agency (MSB) [2010-7991]; Swedish Medical Research Council (VR) [2009-3785]; Goljes Foundationinfo:eu-repo/semantics/publishedVersio

Controlling photons using electromagnetically induced transparency

It is well known that a dielectric medium can be used to manipulate properties of light pulses. However, optical absorption limits the extent of possible control: this is especially important for weak light pulses. Absorption in an opaque medium can be eliminated via quantum mechanical interference, an effect known as electromagnetically induced transparency. Theoretical and experimental work has demonstrated that this phenomenon can be used to slow down light pulses dramatically, or even bring them to a complete halt. Interactions between photons in such an atomic medium can be many orders of magnitude stronger than in conventional optical materials

Profilin modulates sarcomeric organization and mediates cardiomyocyte hypertrophy

Aims: Heart failure is often preceded by cardiac hypertrophy, which is characterized by increased cell size, altered protein abundance, and actin-cytoskeletal reorganization. Profilin is a well-conserved, ubiquitously expressed, multi-functional actin-binding protein, whose role in cardiomyocytes is largely unknown. Given its involvement in vascular hypertrophy, we aimed to test the hypothesis that profilin-1 is a key mediator of cardiomyocyte-specific hypertrophic remodeling. Methods and Results: Profilin-1 was elevated in multiple mouse models of hypertrophy, and a cardiomyocyte-specific increase of profilin in Drosophila resulted in significantly larger heart tube dimensions. Moreover, adenovirus-mediated overexpression of profilin-1 in neonatal rat ventricular myocytes (NRVMs) induced a hypertrophic response, measured by increased myocyte size and gene expression. Profilin-1 silencing suppressed the response in NRVMs stimulated with phenylephrine or endothelin-1. Mechanistically, we found that profilin-1 regulates hypertrophy, in part, through activation of the ERK1/2 signaling cascade. Confocal microscopy showed that profilin localized to the Z-line of Drosophila myofibrils under normal conditions and accumulated near the M-line when overexpressed. Elevated profilin levels resulted in elongated sarcomeres, myofibrillar disorganization, and sarcomeric disarray, which correlated with impaired muscle function. Conclusion: Our results identify novel roles for profilin as an important mediator of cardiomyocyte hypertrophy. We show that overexpression of profilin is sufficient to induce cardiomyocyte hypertrophy and sarcomeric remodeling, and silencing of profilin attenuates the hypertrophic response

Primate modularity and evolution: first anatomical network analysis of primate head and neck musculoskeletal system

Network theory is increasingly being used to study morphological modularity and integration. Anatomical network analysis (AnNA) is a framework for quantitatively characterizing the topological organization of anatomical structures and providing an operational way to compare structural integration and modularity. Here we apply AnNA for the first time to study the macroevolution of the musculoskeletal system of the head and neck in primates and their closest living relatives, paying special attention to the evolution of structures associated with facial and vocal communication. We show that well-defined left and right facial modules are plesiomorphic for primates, while anthropoids consistently have asymmetrical facial modules that include structures of both sides, a change likely related to the ability to display more complex, asymmetrical facial expressions. However, no clear trends in network organization were found regarding the evolution of structures related to speech. Remarkably, the increase in the number of head and neck muscles – and thus of musculoskeletal structures – in human evolution led to a decrease in network density and complexity in humans

A single-photon transistor using nano-scale surface plasmons

It is well known that light quanta (photons) can interact with each other in nonlinear media, much like massive particles do, but in practice these interactions are usually very weak. Here we describe a novel approach to realize strong nonlinear interactions at the single-photon level. Our method makes use of recently demonstrated efficient coupling between individual optical emitters and tightly confined, propagating surface plasmon excitations on conducting nanowires. We show that this system can act as a nonlinear two-photon switch for incident photons propagating along the nanowire, which can be coherently controlled using quantum optical techniques. As a novel application, we discuss how the interaction can be tailored to create a single-photon transistor, where the presence or absence of a single incident photon in a ``gate'' field is sufficient to completely control the propagation of subsequent ``signal'' photons.Comment: 20 pages, 4 figure

A Machine Learning Model to Aid Detection of Familial Hypercholesterolemia

Background People with monogenic familial hypercholesterolemia (FH) are at an increased risk of premature coronary heart disease and death. With a prevalence of 1:250, FH is relatively common; but currently there is no population screening strategy in place and most carriers are identified late in life, delaying timely and cost-effective interventions. Objectives The purpose of this study was to derive an algorithm to identify people with suspected monogenic FH for subsequent confirmatory genomic testing and cascade screening. Methods A least absolute shrinkage and selection operator logistic regression model was used to identify predictors that accurately identified people with FH in 139,779 unrelated participants of the UK Biobank. Candidate predictors included information on medical and family history, anthropometric measures, blood biomarkers, and a low-density lipoprotein cholesterol (LDL-C) polygenic score (PGS). Model derivation and evaluation were performed in independent training and testing data. Results A total of 488 FH variant carriers were identified using whole-exome sequencing of the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein E, proprotein convertase subtilisin/kexin type 9 genes. A 14-variable algorithm for FH was derived, with an area under the curve of 0.77 (95% CI: 0.71-0.83), where the top 5 most important variables included triglyceride, LDL-C, apolipoprotein A1 concentrations, self-reported statin use, and LDL-C PGS. Excluding the PGS as a candidate feature resulted in a 9-variable model with a comparable area under the curve: 0.76 (95% CI: 0.71-0.82). Both multivariable models (w/wo the PGS) outperformed screening-prioritization based on LDL-C adjusted for statin use. Conclusions Detecting individuals with FH can be improved by considering additional predictors. This would reduce the sequencing burden in a 2-stage population screening strategy for FH