Mutational analysis of Sse1 (Hsp110) suggests an integral role for this chaperone in yeast prion propagation in vivo.

The yeast Hsp110 chaperone Sse1 is a conserved protein that is a noncanonical member of the Hsp70 protein superfamily. Sse1 influences the cellular response to heat stress and has also been implicated in playing a role in the propagation of prions in yeast. Sse1 can seemingly exert its effects in vivo through direct or indirect actions by influencing the nucleotide exchange activity of canonical cytosolic Hsp70s. Using a genetic screen based on the inability to propagate the yeast [PSI(+)] prion, we have identified 13 new Sse1 mutants that are predicted to alter chaperone function through a variety of different mechanisms. Not only are these new Sse1 mutants altered in the ability to propagate and cure yeast prions but also to varying degrees in the ability to grow at elevated temperatures. The expression levels of chaperone proteins known to influence yeast prion propagation are unaltered in the Sse1 mutants, suggesting that the observed phenotypic effects are caused by direct functional alterations in these mutants. Mapping the location of the mutants onto the Sse1 crystal structure suggests that more than one functional alteration in Sse1 may result in changes in prion propagation and ability to function at elevated temperatures. All Sse1 mutants isolated provide essential functions in the cell under normal growth conditions, further demonstrating that essential chaperone functions in vivo can to some degree at least be detached from those related to propagation of prions. Our results suggest that Sse1 can influence prion propagation through a variety of different mechanisms

Self-propulsion of flapping bodies in viscous fluids: Recent advances and perspectives

Flapping-powered propulsion is used by many animals to locomote through air or water. Here we review recent experimental and numerical studies on self-propelled mechanical systems powered by a flapping motion. These studies improve our understanding of the mutual interaction between actively flapping bodies and surrounding fluids. The results obtained in these works provide not only new insights into biolocomotion but also useful information for the biomimeticdesign of artificial flyers and swimmers.</div

Quantum-Classical Correspondence of Dynamical Observables, Quantization and the Time of Arrival Correspondence Problem

We raise the problem of constructing quantum observables that have classical counterparts without quantization. Specifically we seek to define and motivate a solution to the quantum-classical correspondence problem independent from quantization and discuss the general insufficiency of prescriptive quantization, particularly the Weyl quantization. We demonstrate our points by constructing time of arrival operators without quantization and from these recover their classical counterparts

The β6/β7 region of the Hsp70 substrate-binding domain mediates heat-shock response and prion propagation.

Hsp70 is a highly conserved chaperone that in addition to providing essential cellular functions and aiding in cell survival following exposure to a variety of stresses is also a key modulator of prion propagation. Hsp70 is composed of a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). The key functions of Hsp70 are tightly regulated through an allosteric communication network that coordinates ATPase activity with substrate-binding activity. How Hsp70 conformational changes relate to functional change that results in heat shock and prion-related phenotypes is poorly understood. Here, we utilised the yeast [PSI +] system, coupled with SBD-targeted mutagenesis, to investigate how allosteric changes within key structural regions of the Hsp70 SBD result in functional changes in the protein that translate to phenotypic defects in prion propagation and ability to grow at elevated temperatures. We find that variants mutated within the β6 and β7 region of the SBD are defective in prion propagation and heat-shock phenotypes, due to conformational changes within the SBD. Structural analysis of the mutants identifies a potential NBD:SBD interface and key residues that may play important roles in signal transduction between domains. As a consequence of disrupting the β6/β7 region and the SBD overall, Hsp70 exhibits a variety of functional changes including dysregulation of ATPase activity, reduction in ability to refold proteins and changes to interaction affinity with specific co-chaperones and protein substrates. Our findings relate specific structural changes in Hsp70 to specific changes in functional properties that underpin important phenotypic changes in vivo. A thorough understanding of the molecular mechanisms of Hsp70 regulation and how specific modifications result in phenotypic change is essential for the development of new drugs targeting Hsp70 for therapeutic purposes

Surgery for Dupuytren’s contracture of the fingers (Review)

Background - Dupuytren's disease is a benign fibroproliferative disorder that causes the fingers to be drawn into the palm via formation of new tissue under the glabrous skin of the hand. This disorder causes functional limitations, but it can be treated through a variety of surgical techniques. As a chronic condition, it tends to recur. Objectives - To assess the benefits and harms of different surgical procedures for treatment of Dupuytren's contracture of the index, middle, ring and little fingers

Exploring the Effect of Crowd Management Measures on Passengers’ Behaviour at Metro Stations

To reduce problems of interaction at the platform train interface (PTI) platform edge doors (PEDs) and markings on the platform are used as door positions indicators. The common methods to study the effect of these measures are based on average values of density using Fruin’s Level of Service (LOS), however identification cannot be made of which part of the PTI is more congested. To solve this problem, a new method is proposed. The method included a conceptual model in which the PTI was discretised into 40 cm square cells to identify which part of the platform is more congested. Passengers’ behaviour was recorded considering two situations before the train arrives: i) passengers waiting in front of the doors; ii) passengers waiting beside the doors. Observation was done at existing stations at Metro de Santiago and London Underground. Results show that PEDs changed the behaviour of passengers as they were located beside the doors rather than in front of them. In addition, when markings were used on the platform, then this behaviour was reinforced. Therefore, it is recommended to use this method to better design the PTI rather than the LOS which is used to design the whole platform. Further research is needed to study the effect of PEDs on passengers with reduced mobility

Magnetic Catalysis and Quantum Hall Ferromagnetism in Weakly Coupled Graphene

We study the realization in a model of graphene of the phenomenon whereby the tendency of gauge-field mediated interactions to break chiral symmetry spontaneously is greatly enhanced in an external magnetic field. We prove that, in the weak coupling limit, and where the electron-electron interaction satisfies certain mild conditions, the ground state of charge neutral graphene in an external magnetic field is a quantum Hall ferromagnet which spontaneously breaks the emergent U(4) symmetry to U(2)XU(2). We argue that, due to a residual CP symmetry, the quantum Hall ferromagnet order parameter is given exactly by the leading order in perturbation theory. On the other hand, the chiral condensate which is the order parameter for chiral symmetry breaking generically obtains contributions at all orders. We compute the leading correction to the chiral condensate. We argue that the ensuing fermion spectrum resembles that of massive fermions with a vanishing U(4)-valued chemical potential. We discuss the realization of parity and charge conjugation symmetries and argue that, in the context of our model, the charge neutral quantum Hall state in graphene is a bulk insulator, with vanishing longitudinal conductivity due to a charge gap and Hall conductivity vanishing due to a residual discrete particle-hole symmetry.Comment: 35 page

Single valley Dirac fermions in zero-gap HgTe quantum wells

Dirac fermions have been studied intensively in condensed matter physics in recent years. Many theoretical predictions critically depend on the number of valleys where the Dirac fermions are realized. In this work, we report the discovery of a two dimensional system with a single valley Dirac cone. We study the transport properties of HgTe quantum wells grown at the critical thickness separating between the topologically trivial and the quantum spin Hall phases. At high magnetic fields, the quantized Hall plateaus demonstrate the presence of a single valley Dirac point in this system. In addition, we clearly observe the linear dispersion of the zero mode spin levels. Also the conductivity at the Dirac point and its temperature dependence can be understood from single valley Dirac fermion physics.Comment: version 2: supplementary material adde

Structure Modeling of All Identified G Protein–Coupled Receptors in the Human Genome

G protein–coupled receptors (GPCRs), encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER) method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(α) root-mean-squared deviation from native of 4.6 Å, with a root-mean-squared deviation in the transmembrane helix region of 2.1 Å. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness and robustness of the in silico models for GPCR functional analysis. All predicted GPCR models are freely available for noncommercial users on our Web site (http://www.bioinformatics.buffalo.edu/GPCR)

Secure and Internet-Less Connectivity to a Blockchain Network for Limited Connectivity Bank Users

Over the past few years, we have seen the emergence of a wide range of banking architectures, technologies, and applications made possible by the significant improvements in hardware, software, and networking technologies. Nowadays, innovative solutions are being developed by banks to leverage the benefits of blockchain, to improve their business agility and performance, and to make their business operations more efficient and secure. However, there are still cases where regular access to Internet is impossible or unreliable due to saturated networks or harsh environments, hence limiting the deployment of typical blockchain based solutions. In this context, an approach using a new connectivity technology is needed in order to increase mobile Internet services for any device to reach nearly 95% of the world population, instantly, simply by drawing on existing mobile phone networks, with no additional infrastructure development. We aim to give the user full bank access from their device, even if the device is not a smart one, using ordinary mobile phone networks. However, providing efficient and secure communications over lossy and low bandwidth networks remains a challenge. The main objective of this paper will be to design an end-to-end and low overhead secure solution for the communications between mobile devices and their corresponding remote application servers that using blockchain via ordinary mobile networks