The identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3AB

AbstractHuman enterovirus 71 (EV71) belongs to the genus Enterovirus in the family Picornaviridae and has been recognized as one of the most important pathogens that cause emerging infectious disease. Despite of the importance of EV71, the nonstructural protein 3AB from this virus is little understood for its function during EV71 replication. Here we expressed EV71 3AB protein as recombinant protein in a eukaryotic expression system and uncovered that this protein possesses a nucleic acid helix-destabilizing and strand annealing acceleration activity in a dose-dependent manner, indicating that EV71 3AB is a nucleic acid chaperone protein. Moreover, we characterized the RNA chaperone activity of EV71 3AB, and revealed that divalent metal ions, such as Mg2+ and Zn2+, were able to inhibit the RNA helix-destabilizing activity of 3AB to different extents. Moreover, we determined that 3B plus the last 7 amino acids at the C-terminal of 3A (termed 3B+7) possess the RNA chaperone activity, and five amino acids, i.e. Lys-80, Phe-82, Phe-85, Tyr-89, and Arg-103, are critical and probably the active sites of 3AB for its RNA chaperone activity. This report reveals that EV71 3AB displays an RNA chaperone activity, adds a new member to the growing list of virus-encoded RNA chaperones, and provides novel knowledge about the virology of EV71

Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models.

Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small intestine, which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but not sufficient, while additional vitamin D deficiency (VDD) as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD), the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD), Helicobacter hepaticus, a known murine hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor (VDR) knockout mice exhibit similar phenotypes, showing down regulation of alpha-defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored eubiosys, showing suppression of Helicobacter hepaticus and increase of Akkermansia muciniphila in association with resolving metabolic disorders and fatty liver in the HFD+VDD mice. An in vitro analysis showed that DEFA5 peptide could directly suppress Helicobacter hepaticus. Thus, the results of this study reveal critical roles of a vitamin D/VDR axis in optimal expression of defensins and tight junction genes in support of intestinal integrity and eubiosis to suppress NAFLD and metabolic disorders

Proof-of-Concepts of Distributed Detection with Privacy

The concept of distributed detection is a fundamental method in statisticalinference which has many applications in real life. However, the informationtransmitted between the sensors and fusion node cannot always be consideredto be secure. Therefore, in some works, the concept has been extended to includean eavesdropper in the system setup.The overall goal of this master thesis is to develop a proof-of-concept of thetheoretical works on distributed detection with privacy. This is done by usingthe data provided by the HVAC system deployed on the second oor of Q buildingin KTH. Two models which describe the sensor measurement(observations)related to the considered hypothesis are proposed.The results show that the models are reasonable. Therefore, the target ofthis project is fullled. Improvements and some ideas about future work arealso proposed.Konceptetdistribuerad detektering ar en fundamental metod inom statistiskinferenssomhar manga tillampningar i praktiken. Informationen som sands mellansensorerna och fusionsnoden ar daremot inte alltid saker. Pa grund av dettahar konceptet utvidgats till att inkludera en tjuvlyssnare i systemkongurationen.Det overgripande malet med avhandlingen ar attskapa ett bevis bakom teorindistribuerad detektering och sakerhet. Detta har gjorts genom att anvandadatansom givits av HVAC systemet, som utvecklats pa andra vaningen av Qbyggnaden pa KTH. Tva modeller som beskriver sensormatningen (observationerna)relaterade till den behandlade hypotesen foreslas.Resultaten visar att modellerna ar rimliga. Malet med projektet ar darmeduppfyllt. Forbattringar samt forslag pa framtida arbeten namns dessutom

MANAGEMENT MANUAL FOR JIANGXI DOHR CASING CO., LTD.

The purpose of thesis is to develop a management manual according to the guideline of ISO 9001:2008 for Jiangxi Dohr Casing Co., Ltd. The management manual is based on the ISO9001: 2008 quality standard system and with reference of the conditions of Jiangxi Dohr Casing Co.,Ltd. This manual aims to provide continuous improvement and foundation for better customer satisfaction, to regulate the internal management and to enhance employee quality awareness and improve operational efficiency

Prey-Predator models on graphs

In this paper, we study the Lotka-Volterra prey-predator models consisting of two species on finite connected graphs under Neumann condition and the condition that there is no boundary condition. We establish the global stability of the unique constant equilibrium solution of each system

A Climate Shift Model with Free Boundary: Enhanced Invasion

We examine how climate change enhances the spreading of an invading species through a nonlinear diffusion equation of the form ut = duxx+A (x − ct) u−bu2 with a free boundary, where climate change causes more favourable environment shifting into the habitat of the species with a constant speed c > 0. The free boundary represents the invading front of the expanding population range. We show that the long-time dynamics of this model obeys a spreading-vanishing dichotomy, which is best illustrated by using a suitably parameterised family of initial functions 0. The free boundary represents the invading front of the expanding population range. We show that the long-time dynamics of this model obeys a spreading-vanishing dichotomy, which is best illustrated by using a suitably parameterised family of initial functions u0σ increasing continuously in σ: there exists a critical value σ∗ ∈ (0,∞) so that the species vanishes ultimately when σ ∈ (0, σ∗], and it spreads successfully when σ > σ∗ . However, when spreading is successful, there exist two threshold speeds c0 c1 that divide the spreading profile into strikingly different patterns. For example, when c c0 the profile of the population density function u(t, x) approaches a propagating pair composed of a traveling wave with speed c and a semi-wave with speed c0; when c0 c c1, it approaches a semi-wave with speed c, and when c > c1, it approaches a semi-wave with speed c1