Identification of a Novel ACVRL1 Gene Mutation (c.100T>A, p.Cys34Ser) in a Japanese Patient with Possible Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease)

Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease) is an autosomal dominant genetic disorder that causes frequent epistaxis, mucocutaneous telangiectasia, and visceral arteriovenous malformations. Four genes (ENG, ACVRL1, SMAD4, and GDF2) have been identified as pathogenic in HHT. We describe the case of a 50-year-old Japanese man highly suspected of having HHT due to recurrent epistaxis, mucocutaneous telangiectasia, and a family history. Genomic analysis revealed a novel missense mutation of c.100T>A, p.Cys34Ser in the patient’s ACVRL1 gene. We used 6 freeware programs to perform an in silico analysis of this mutation. The results demonstrated the mutation’s high pathogenicity

Traffic jams without bottlenecks-experimental evidence for the physical mechanism of the formation of a jam

A traffic jam on a highway is a very familiar phenomenon. From the physical viewpoint, the system of vehicular flow is a non-equilibrium system of interacting particles (vehicles). The collective effect of the many-particle system induces the instability of a free flow state caused by the enhancement of fluctuations, and the transition to a jamming state occurs spontaneously if the average vehicle density exceeds a certain critical value. Thus, a bottleneck is only a trigger and not the essential origin of a traffic jam. In this paper, we present the first experimental evidence that the emergence of a traffic jam is a collective phenomenon like 'dynamical' phase transitions and pattern formation in a non-equilibrium system. We have performed an experiment on a circuit to show the emergence of a jam with no bottleneck. In the initial condition, all the vehicles are moving, homogeneously distributed on the circular road, with the same velocity. The average density of the vehicles is prepared for the onset of the instability. Even a tiny fluctuation grows larger and then the homogeneous movement cannot be maintained. Finally, a jam cluster appears and propagates backward like a solitary wave with the same speed as that of a jam cluster on a highway.Sugiyamal Y., Fukui M., Kikuchi M., et al. Traffic jams without bottlenecks-experimental evidence for the physical mechanism of the formation of a jam. New Journal of Physics 10, 033001 (2008); https://doi.org/10.1088/1367-2630/10/3/033001

Phase transition in traffic jam experiment on a circuit

The emergence of a traffic jam is considered to be a dynamical phase transition in a physics point of view; traffic flow becomes unstable and changes phase into a traffic jam when the car density exceeds a critical value. In order to verify this view, we have been performing a series of circuit experiments. In our previous work (2008 New J. Phys. 10 033001), we demonstrated that a traffic jam emerges even in the absence of bottlenecks at a certain high density. In this study, we performed a larger indoor circuit experiment in the Nagoya Dome in which the positions of cars were observed using a high-resolution laser scanner. Over a series of sessions at various values of density, we found that jammed flow occurred at high densities, whereas free flow was conserved at low densities. We also found indications of metastability at an intermediate density. The critical density is estimated by analyzing the fluctuations in speed and the density-flow relation. The value of this critical density is consistent with that observed on real expressways. This experiment provides strong support for physical interpretations of the emergence of traffic jams as a dynamical phase transition.Tadaki S.I., Kikuchi M., Fukui M., et al. Phase transition in traffic jam experiment on a circuit. New Journal of Physics 15, 103034 (2013); https://doi.org/10.1088/1367-2630/15/10/103034

Physics of Transport and Traffic Phenomena in Biology: from molecular motors and cells to organisms

Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitaive analysis of models of these traffic-like collective phenomena as these systems are intrinsically far from equilibrium. In this review we critically examine the current status of our understanding, expose the limitations of the existing methods, mention open challenging questions and speculate on the possible future directions of research in this interdisciplinary area where physics meets not only chemistry and biology but also (nano-)technology.Comment: 33 page Review article, REVTEX text, 29 EPS and PS figure

Plastid signalling under multiple conditions is accompanied by a common defect in RNA editing in plastids

Retrograde signalling from the plastid to the nucleus, also known as plastid signalling, plays a key role in coordinating nuclear gene expression with the functional state of plastids. Inhibitors that cause plastid dysfunction have been suggested to generate specific plastid signals related to their modes of action. However, the molecules involved in plastid signalling remain to be identified. Genetic studies indicate that the plastid-localized pentatricopeptide repeat protein GUN1 mediates signalling under several plastid signalling-related conditions. To elucidate further the nature of plastid signals, investigations were carried out to determine whether different plastid signal-inducing treatments had similar effects on plastids and on nuclear gene expression. It is demonstrated that norflurazon and lincomycin treatments and the plastid protein import2-2 (ppi2-2) mutation, which causes a defect in plastid protein import, all resulted in similar changes at the gene expression level. Furthermore, it was observed that these three treatments resulted in defective RNA editing in plastids. This defect in RNA editing was not a secondary effect of down-regulation of pentatricopeptide repeat protein gene expression in the nucleus. The results indicate that these three treatments, which are known to induce plastid signals, affect RNA editing in plastids, suggesting an unprecedented link between plastid signalling and RNA editing

Involvement of Girdin in the Determination of Cell Polarity during Cell Migration

Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701