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This paper uses matched data from the CSMAR database and the China City Statistical Yearbook through a fixed effects model to examine the impact of business credit environment on small and medium-sized enterprises (SMEs) exports at the city level in China. Considering the possible endogenous problems, this paper chooses the number of scholars in Ming and Qing dynasties as the instrumental variable of urban commercial credit environment. The empirical results show that: Firstly, the improvement of urban business credit environment has a significant contribution to the export growth of enterprises; Secondly, the mechanism of the role of urban business credit environment on SMEs exports is mainly expressed through promoting R&D investment and enhancing market dynamics; Thirdly, the business credit environment is more obvious to state-owned enterprises, eastern regions and cities with less trade freedom. With the development of urban business credit environment, individuals or companies join the competition in the industry through new start-ups to stimulate corporate exports, and existing SMEs promote corporate exports through local preferential policies, increased investment in R&D, and optimized innovation policies as well as resource allocation. [ABSTRACT FROM AUTHOR]

This paper offers a framework for understanding the origin of market-preserving government. The paper shows that when parties in a Hobbesian society end in an arms race rather than war, they can create a market-preserving government to maintain the no-war equilibrium at lower cost. The government can be small yet effective or larger and more efficient. Under certain conditions, the parties are better off completely disarming themselves, paving the road for a modern society with equal rights for all citizens and a government monopoly on violence. The war-economic theory of political development sheds light on historical experiences and contemporary policy issues.

P0 protein of some polerovirus members can target ARGONAUTE1 (AGO1) to suppress RNA silencing. Although P0 harbors an F-box-like motif reported to be essential for interaction with S phase kinase-associated protein 1 (SKP1) and RNA silencing suppression, it is the autophagy pathway that was shown to contribute to AGO1 degradation. Therefore, the role of P0-SKP1 interaction in silencing suppression remains unclear. We conducted global mutagenesis and comparative functional analysis of P0 encoded by Brassica yellows virus (BrYV) (P0Br ). We found that several residues within P0Br are required for local and systemic silencing suppression activities. Remarkably, the F-box-like motif mutant of P0Br , which failed to interact with SKP1, is destabilized in vivo. Both the 26S proteasome system and autophagy pathway play a role in destabilization of the mutant protein. Furthermore, silencing of a Nicotiana benthamiana SKP1 ortholog leads to the destabilization of P0Br . Genetic analyses indicated that the P0Br -SKP1 interaction is not directly required for silencing suppression activity of P0Br , but it facilitates stability of P0Br to ensure efficient RNA silencing suppression. Consistent with these findings, efficient systemic infection of BrYV requires P0Br . Our results reveal a novel strategy used by BrYV for facilitating viral suppressors of RNA silencing stability against degradation by plant cells.

Cotton is a multipurpose crop grown globally, including the United States. Cotton leafroll dwarf virus (CLRDV), a phloem-limited virus (Solemoviridae) transmitted by aphids, causes significant economic losses to cotton cultivation. CLRDV strains (CLRDV-typical and atypical) that were previously prevalent in other countries cause severe symptoms leading to high yield loss. Recently, a new isolate of CLRDV (CLRDV-AL) has been characterized from infected cotton plants in Alabama that are often asymptomatic and difficult to detect, implying a low titer and pathogenicity within the host. Different pathogenicity among certain strains within the same species often correlates with both environmental and molecular factors. Thus, better management and control of the vector-borne disease can be achieved by elucidating host-pathogen interaction, such as host immune response and pathogen counter-response. In this study, we demonstrate the ability of CLRDV-AL to suppress a major host defense response known as RNA silencing and compare the potency of silencing suppression to other strains of the same virus. Also, we discuss the difference in pathogenicity among them by evaluating the observations based on the amino acid variation within the functional domain. Our study provides and suggests a future direction for specifying the strategy to mitigate potential cotton disease severity.

Through considerable efforts and investments of resources, adolescent pregnancy and birth rates in the United States have decreased significantly over the past two decades. Nonetheless, large disparities persist for many populations of youth. Reducing unintended adolescent pregnancies is considered a “winnable public health battle,” but one that will require innovative thinking and continued persistence. This paper reviews the recent research literature and innovative programmatic efforts to identify six promising strategies that address the challenge of adolescent pregnancy in new ways. These strategies aim to: (1) understand and address the complexity of adolescent lives; (2) expand the provision of quality sexual health education; (3) engage youth through technology and media; (4) increase access to contraceptives and other sexual health services; (5) create tailored interventions for populations with special needs; and (6) create a supportive policy environment. By building upon lessons learned from past efforts, we can move the field toward the development, strengthening, and promotion of future strategies that enhance the sexual well-being of all adolescents.

The polerovirus (family Solemoviridae , genus Polerovirus) genome consists of single-, positive-strand RNA organized in overlapping open reading frames (ORFs) that, in addition to others, code for protein 0 (P0, a gene silencing suppressor), a coat protein (CP, ORF3), and a read-through domain (ORF5) that is fused to the CP to form a CP-read-through (RT) protein. The genus Polerovirus contains twenty-six virus species that infect a wide variety of plants from cereals to cucurbits, to peppers. Poleroviruses are transmitted by a wide range of aphid species in the genera Rhopalosiphum, Stiobion, Aphis , and Myzus. Aphid transmission is mediated both by the CP and by the CP-RT. In viruses, mutational robustness and structural flexibility are necessary for maintaining functionality in genetically diverse sets of host plants and vectors. Under this scenario, within a virus genome, mutations preferentially accumulate in areas that are determinants of host adaptation or vector transmission. In this study, we profiled genomic variation in poleroviruses. Consistent with their multifunctional nature, single-nucleotide variation and selection analyses showed that ORFs coding for P0 and the read-through domain within the CP-RT are the most variable and contain the highest frequency of sites under positive selection. An order/disorder analysis showed that protein P0 is not disordered. In contrast, proteins CP-RT and virus protein genome-linked (VPg) contain areas of disorder. Disorder is a property of multifunctional proteins with multiple interaction partners. The results described here suggest that using contrasting mechanisms, P0, VPg, and CP-RT mediate adaptation to host plants and to vectors and are contributors to the broad host and vector range of poleroviruses. Profiling genetic variation across the polerovirus genome has practical applications in diagnostics, breeding for resistance, and identification of susceptibility genes and contributes to our understanding of virus interactions with their host, vectors, and environment. [ABSTRACT FROM AUTHOR]

A peptide from the P0 acidic ribosomal protein (pP0) of ticks conjugated to keyhole limpet hemocyanin from Megathura crenulata has shown to be effective against different tick species when used in host vaccination. Turning this peptide into a commercial anti-tick vaccine will depend on finding the appropriate, technically and economically feasible way to present it to the host immune system. Two conjugates (p64K-Cys1pP0 and p64K-βAla1pP0) were synthesized using the p64K carrier protein from Neisseria meningitidis produced in Escherichia coli, the same cross-linking reagent, and two analogues of pP0. The SDS-PAGE analysis of p64K-Cys1pP0 showed a heterogeneous conjugate compared to p64K-βAla1pP0 that was detected as a protein band at 91kDa. The pP0/p64K ratio determined by MALDI-MS for p64K-Cys1pP0 ranged from 1 to 8, being 3-5 the predominant ratio, while in the case of p64K-βAla1pP0 this ratio was 5-7. Cys1pP0 was partially linked to 35 out of 39 Lys residues and the N-terminal end, while βAla1pP0 was mostly linked to the six free cysteine residues, to the N-terminal end, and, in a lesser extent, to Lys residues. The assignment of the conjugation sites and side reactions were based on the identification of type 2 peptides. Rabbit immunizations showed the best anti-pP0 titers and the highest efficacy against Rhipicephalus sanguineus ticks when the p64K-Cys1pP0 was used as vaccine antigen. The presence of high molecular mass aggregates observed in the SDS-PAGE analysis of p64K-Cys1pP0 could be responsible for a better immune response against pP0 and consequently for its better efficacy as an anti-tick vaccine. [ABSTRACT FROM AUTHOR]

Public Entrepreneurship, Citizenship and Self-Governance (PECS), is the latest installment of Aligica Aligica's ongoing effort to clarify and extend the ideas and inquiries of the Bloomington School of Political Economy (e.g., Aligica and Boettke 2009; Aligica 2014). It is a remarkable book. I say that even though there are many points on which Aligica and I disagree, or at least points at which we draw quite divergent inferences from common observations. In these remarks I aim both to underscore points at which Aligica and I agree and to provoke future critical exchanges. [ABSTRACT FROM AUTHOR]

• CMT 1B with atypical characteristics and overlapping immune polyneuropathy. • Unique description of a MPZ p.Ser63del mutation and concomitant immune neuropathy. • Reversible conduction block and clinical improvement in response to treatment. Charcot Marie Tooth (CMT) due to myelin protein zero (MPZ) mutations, may cause a wide variation of phenotypes, depending on the localization of the mutation within the gene. Among the most common phenotypes are: an infantile onset disease with extremely slow nerve conduction velocities (CMT1B) and an adult onset phenotype with nerve velocities in the axonal range (CMT2I). We reported a patient with CMT1B (MPZ p.Ser63del mutation) which developed an overlapping immune mediated polyradiculoneuropathy with recurrent episodes of quadriparesis and cranial nerve involvement. We observed reversible conduction block on serial neurophysiologic studies, non-uniform demyelination and good clinical response to prednisone and cyclophosphamide, as evidenced by objective functional recovery. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like characteristics have not yet been described associated with a MPZ p.Ser63del mutation. This description adds evidence indicating that a defective structural myelin protein may predispose peripheral nerves to immune attacks. [ABSTRACT FROM AUTHOR]

Brassica yellows virus (BrYV) is a tentative species of the genus Polerovirus, which has at least three genotypes (A, B, and C) in China. The P0 protein of BrYV-A (P0BrA) has been identified as a viral suppressor of RNA silencing (VSR), which can also induce cell death in infiltrated Nicotiana benthamiana leaves. In this study, we demonstrated that the cell death induced by P0BrA was accompanied by the accumulation of reactive oxygen species (ROS) and increased Pathogenesis-related protein genes-1 (PR1) expression. Meanwhile, this cell death phenotype was delayed by salicylic acid (SA) pretreatment. Biological function comparison of the three P0 proteins showed that transiently expressed P0BrB or P0BrC induced a significantly delayed and milder cell death response compared with P0BrA. However, like P0BrA, they also suppressed local and systemic RNA silencing. Six residues of P0BrA essential for inducing cell death were identified by comparative analysis and amino acid substitution assay. We also show that all three BrYV genotypes have synergistic interactions with pea enation mosaic virus 2 (PEMV 2) in N. benthamiana. This study provides theoretical guidance for controlling the viral disease caused by poleroviruses in the future.

The article describes 5 countries from the world: South Korea, Japan, Singapore, Hong Kong, Finland that have the best and unusual educational systems. Thanks to the new approach to the teaching, students become very well-educated when graduate. The text emphasises the importance of foreign language knowledge. It is very interesting how much different is the approach to students in Asian countries and in Finland but both systems eventually provide very good education level to their students. The another part of the article bases for characteristic of two other EU countries – Romania and Poland. In these countries, the internal educational systems are quite similar to each other and guarantee their students very good education level. Thanks to the attendance in Erasmus exchange programme, Romanian and Polish students can broaden their mind abroad.

#WalkAway signifies walking away from the Democratic Party. The movement was launched in June 2018 by Brandon Straka, when he uploaded what became the prototypical video of an individual telling his or her story about walking away. During 130 days, 150 erstwhile Democrats provided video testimonials at Straka's official YouTube channel. Of the 150 erstwhile Democrats, 23% report catching a lot of grief, plus another 16% report catching some grief, for questioning or deviating from leftist opinions. Most importantly, 70% suggest a civility gap between the left and non-left. These are lower bounds, since the testimonials are spontaneous monologues, not replies to questions. Many other observed features are reported, to deepen our thinking about ideological migration. However, filters involved in the sample must be borne in mind. A linked Excel file contains complete data. [ABSTRACT FROM AUTHOR]

A synthetic 20 amino acid peptide of the ribosomal protein P0 from ticks, when conjugated to keyhole limpet hemocyanin from Megathura crenulata and used as an immunogen against Rhipicephalus microplus and Rhipicephalus sanguineus s.l. species, has shown efficacies of around 90%. There is also experimental evidence of a high efficacy of this conjugate against Amblyomma mixtum and Ixodes ricinus species, which suggest that this antigen could be a good broad-spectrum anti-tick vaccine candidate. In this study, the P0 peptide (pP0) was chemically conjugated to Bm86 as a carrier protein. SDS-PAGE analysis of this conjugate demonstrated that it is highly heterogeneous in size, carrying from 1 to 18 molecules of pP0 per molecule of Bm86. Forty-nine out of the 54 lysine residues and the N-terminal end of Bm86 were found partially linked to pP0 by using LC-MS/MS analysis and the combination of four different softwares. Several post-translational modifications of Bm86 protein were also identified by mass spectrometry. High immunogenicity and efficacy were achieved when dogs and cattle were vaccinated with the pP0–Bm86 conjugate and challenged with R. sanguineus s.l. and R. microplus, respectively. These results encourage the development of this antigen with promising possibilities as an anti-tick vaccine.

Abstract: Donald Trump has sought to change US trading relationships by raising protection at home and taxing the offshore activities of US companies abroad. These measures, which both use and violate trade rules, have provoked retaliation from other countries. Such friction has restricted and distorted trade and investment, undermined the rules‐based trading system and perhaps permanently damaged global value chains that depend on stable rules for market access. Trump has justified some of his measures as a response to China's alleged unfair practices and indeed, China has adopted industrial and technology policies that are formally neutral between domestic and foreign firms but in practice have led foreign firms to complain about discriminatory practices that favor Chinese firms. The US friction with China is unfortunate because instead of trying to bully China into submission in a tariff war, the US could have dealt with many of its concerns more effectively by cooperating with other countries and taking actions that are consistent with maintaining the rules‐based system. While the US has undermined its leadership role, the overall damage to the trading system could still be limited if other countries, especially China, take actions that sustain and strengthen it. [ABSTRACT FROM AUTHOR]

In interactions between poleroviruses and their hosts, few cellular proteins have been identified that directly interact with the multifunctional virus P0 protein. To help explore the functions of P0, we identified a Brassica yellows virus genotype A (BrYV-A) P0BrA-interacting protein from Nicotiana benthamiana, Rubisco assembly factor 2 (NbRAF2), which localizes in the nucleus, cell periphery, chloroplasts, and stromules. We found that its C-terminal domain (amino acids 183-211) is required for self-interaction. A split ubiquitin membrane-bound yeast two-hybrid system and co-immunoprecipitation assays showed that NbRAF2 interacted with P0BrA, and co-localized in the nucleus and at the cell periphery. Interestingly, the nuclear pool of NbRAF2 decreased in the presence of P0BrA and during BrYV-A infection, and the P0BrA-mediated reduction of nuclear NbRAF2 required dual localization of NbRAF2 in the chloroplasts and nucleus. Tobacco rattle virus-based virus-induced gene silencing of NbRAF2 promoted BrYV-A infection in N. benthamiana, and the overexpression of nuclear NbRAF2 inhibited BrYV-A accumulation. Potato leafroll virus P0PL also interacted with NbRAF2 and decreased its nuclear accumulation, indicating that NbRAF2 may be a common target of poleroviruses. These results suggest that nuclear NbRAF2 possesses antiviral activity against BrYV-A infection, and that BrYV-A P0BrA interacts with NbRAF2 and alters its localization pattern to facilitate virus infection. [ABSTRACT FROM AUTHOR]

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In this paper, we present iterative or successive approximation methods for solving the coupled Hamilton-Jacobi-Isaacs equations (HJIEs) arising in nonzero-sum differential game for affine nonlinear systems. We particularly consider the ones arising in mixed $${\mathcal H}_{2}/{\mathcal H}_{\infty }$$ control. However, the approach is perfectly general and can be applied to any others including those arising in the N-player case. The convergence of the method is established under fairly mild assumptions, and examples are solved to demonstrate the utility of the method. The results are also specialized to the coupled algebraic Riccati equations arising typically in mixed $${\mathcal H}_{2}/{\mathcal H}_{\infty }$$ linear control. In this case, a bound within which the optimal solution lies is established. Finally, based on the iterative approach developed, a local existence result for the solution of the coupled-HJIEs is also established. [ABSTRACT FROM AUTHOR]

Although the Index of Economic Freedom appears in many economic textbooks, their coverage of the index misses opportunities to teach statistical and policy-related concepts important for the principles course. The standard textbook presentation passes up an opportunity to examine the statistical issues of weighting in composite index numbers and correlation versus causation. In addition, textbook presentations fail to examine the assumptions made in the indexes about key economic concepts. These include inflation rate targets, appropriate government spending levels, tax rates, labor standards, financial regulation, monetary policy, property rights, government regulation, and even the meaning of economic freedom. This study explores how examining economic freedom index assumptions can help students understand key economic policy debates. [ABSTRACT FROM AUTHOR]

Using a new dataset of extreme rainfall covering 130 countries from 1979 to 2009, this paper investigates whether and how extreme rainfall-driven flooding affects democratic conditions. Our key finding indicates that extreme rainfall-induced flooding exerts two opposing effects on democracy. On one hand, flooding leads to corruption in the chains of emergency relief distribution and other post-disaster assistance, which in turn impels the citizenry to demand more democracy. On the other hand, flooding induces autocratic tendencies in incumbent regimes because efficient post-disaster management with no dissent, chaos or plunder might require government to undertake repressive actions. The net estimated effect is an improvement in democratic conditions. [ABSTRACT FROM AUTHOR]

We present an analytical approach to institutional analysis that draws inspiration from control process engineering in the physical sciences. We characterize smart institutions as having three foundational features. First, smart institutions are context sensitive and expressly allow for a unified consideration of social, political and economic factors, thereby providing a richer and more eclectic approach to their operation. Second, smart institutions are forward-looking in their operation rather than deriving from their past functions and purpose in contrast to most generic institutions. Third, as opposed to generic institutions, smart institutions emphasize the role of information and specifically that of subjective social feedback on institutional performance. A theory of smart institutions, consequently, presents distinct advantages over traditional institutional analysis. [ABSTRACT FROM AUTHOR]

In this paper we intend to empirically examine the impact of political rivalry on four selected macroeconomic variables: public investments in education, school enrollment, GDP per capita and income inequality. We first construct a political rivalry indicator and examine how it varies across different groups of countries. We then perform a series of regressions and find that in lower income countries there is a significant negative impact of political rivalry on the selected variables, while in higher income countries the impact is weaker. This suggests that the channels linking political rivalry to macroeconomic variables differ with the development level. [ABSTRACT FROM AUTHOR]

Our patient is a 65-year-old woman presenting with bilateral pes cavus, pronounced distal muscle wasting, weakness and areflexia. Electrophysiological findings included diffuse unrecordable motor and sensory responses. While the CMT phenotype was evident, the lack of family history and the severe, but unspecific electrophysiological impairment, was a challenge for genetic diagnosis. A sural nerve biopsy was performed, showing a severe loss of myelinated fibers with residual axons surrounded by myelin outfoldings. Whereas myelin outfoldings are a pathological hallmark of autosomal recessive CMT4B1 and CMT4B2, due to mutations in myotubularin-related 2 ( MTMR2) and 13 ( MTMR13) genes respectively, they may also occur in nerve biopsies from CMT1B patients. By direct sequencing, a novel heterozygous transversion c. 410G>T in MPZ gene was demonstrated, producing an amino acid change from glycine to valine in position 108 (p. G108V). In HeLa cells the fusion P0G108V- EGFP was normally trafficked to the cell membrane, but with decreased P0 adhesion function, compared with wild-type P0, thus supporting a pathogenic role of the new variant. In conclusion this case highlights the relevance, in selected cases, of sural nerve biopsy to orient the genetic/molecular tests, while in vitro analyses may strengthen the pathogenic role of novel mutations. [ABSTRACT FROM AUTHOR]

The yellow dwarf viruses (YDVs) of the Luteoviridae family represent the most widespread group of cereal viruses worldwide. They include the Barley yellow dwarf viruses (BYDVs) of genus Luteovirus, the Cereal yellow dwarf viruses (CYDVs) and Wheat yellow dwarf virus (WYDV) of genus Polerovirus. All of these viruses are obligately aphid transmitted and phloem-limited. The first described YDVs (initially all called BYDV) were classified by their most efficient vector. One of these viruses, BYDV-RMV, is transmitted most efficiently by the corn leaf aphid, Rhopalosiphum maidis. Here we report the complete 5612 nucleotide sequence of the genomic RNA of a Montana isolate of BYDV-RMV (isolate RMV MTFE87, Genbank accession no. KC921392). The sequence revealed that BYDV-RMV is a polerovirus, but it is quite distantly related to the CYDVs or WYDV, which are very closely related to each other. Nor is BYDV-RMV closely related to any other particular polerovirus. Depending on the gene that is compared, different poleroviruses (none of them a YDV) share the most sequence similarity to BYDV-RMV. Because of its distant relationship to other YDVs, and because it commonly infects maize via its vector, R. maidis, we propose that BYDV-RMV be renamed Maize yellow dwarf virus-RMV (MYDV-RMV).

The structure of the large ribosomal subunit from the halophilic archaeon Haloarcula marismortui (Hma) is the only crystal structure of an archaeal ribosomal particle that has been determined to date. However, the first model of the Hma 50S ribosomal subunit contained some gaps: the structures of functionally important mobile lateral protuberances were not visualized. Subsequently, some parts of the P (L12) stalk base were visualized at 3.0 Å resolution [Kavran & Steitz (2007), J. Mol. Biol. 371, 1047-1059]: the RNA-binding domain of r-protein P0 (L10), the C-terminal domain of L11 and helices 43 and 44 of the 23 S rRNA. Here, the 2.4 Å resolution electron-density map of the Hma 50S ribosomal subunit was revisited and approximately two-thirds of the P0 protein, residues 1-58 of the N-terminal domains of two P1 protein molecules, residues 130-156 of L11, the full-length r-protein LX, nucleotides 2137-2149 and 2226-2237 of the 23S rRNA helix H76 forming the L1 stalk, nucleotides 2339-2343 of the 23S rRNA (contacting L5 protein) and loops 29-34 and 108-128 of protein L5 could be visualized. Thus, this paper provides a supplemented version of the Hma 50S ribosomal subunit model. [ABSTRACT FROM AUTHOR]

This paper examines scientist entrepreneurship at universities in Saudi Arabia. It is the first paper to examine scientist research in the context of the Middle East and, in particular, Saudi Arabia. In this paper we hypothesize that scientist entrepreneurship is positively influenced by experience, gender, social capital, human capital, and university and other institutional policies encouraging commercialization activities. To test our hypotheses, we use data from a unique survey of scientists from three universities in Saudi Arabia. The paper finds that there are key elements to scientist entrepreneurship that provide a sharp contrast to what has been established in the literature based on studies from the OECD countries. Finally, managerial implications are discussed and future research is recommended. [ABSTRACT FROM AUTHOR]

We report a case of late-onset predominantly axonal Charcot-Marie-Tooth disease resulting from a novel mutation in the MPZ gene encoding myelin protein zero (P0). Neurological examination, electrophysiological examination and genetic testing were performed on three members of a Finnish family (family A) and one member of a German family (family B). Three other members of the Finnish family were interviewed and genetically tested. Genetic testing was also performed on 95 healthy Finnish controls. Three members in two generations of family A and the member of family B were affected with late-onset axonal more than demyelinating, motor and sensory polyneuropathy. Heterozygous c.316C>T mutation in MPZ leading to p.Arg106Cys in P0 was found in all the affected subjects, but not in the three unaffected members of the Finnish family. None of 95 healthy Finnish controls harbored the mutation. The findings of this study indicate that p.Arg106Cys allele in MPZ causes late-onset predominantly axonal sensory and motor neuropathy. [ABSTRACT FROM AUTHOR]

The potential application of mRNA for the identification of biological fluids using molecular techniques has been a recent development in forensic serology. Constitutively expressed housekeeping genes can assess the amount of mRNA recovered from a sample, establish its suitability for downstream applications, and provide a reference point to corroborate the identity of the fluid. qPCR was utilized to compare the expression levels of housekeeping genes from forensic-like body fluid stains to establish the most appropriate assessment of human mRNA quantity prior to profiling. Although variability was observed between fluids and individuals, results indicated that beta-2 microglobulin exhibited the highest expression for all body fluids examined and across donors. A one-way analysis of variance was performed for housekeeping gene variability between donors (at the α, 0.05, significance level), and the results indicated significant differences for semen, vaginal secretions, and menstrual blood. [ABSTRACT FROM AUTHOR]

Abstract: The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the plant''s RNA silencing machinery. Here we identified a silencing suppressor protein (SSP), P0PE, in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal yellow dwarf virus have strong local and systemic SSP activity, while the P1 of Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear localized P0PE has no discernable sequence conservation with known SSPs, but proved to be a strong suppressor of local silencing and a moderate suppressor of systemic silencing. Like the P0s from poleroviruses, P0PE destabilizes AGO1 and this action is mediated by an F-box-like domain. Therefore, despite the lack of any sequence similarity, the poleroviral and enamoviral SSPs have a conserved mode of action upon the RNA silencing machinery. [Copyright &y& Elsevier]

Abstract: Objectives: We report the clinical and cellular phenotypes of two novel MPZ mutations associated with CMT1B. Methods: The two families were evaluated clinically, electrophysiologically, and genetically. The wild-type and mutant P0 fused with fluorescent proteins were expressed in vitro to monitor their intracellular trafficking. Adhesion assay was also performed to evaluate the adhesiveness of cells. Results: The two novel heterozygous MPZ mutations, p.I135M and p.Q187PfsX63, are associated with a childhood-onset demyelinating polyneuropathy. The median motor nerve conduction velocities of the two index patients carrying each mutation were 12.9 and 13.6m/s, respectively. Fluorescence analysis demonstrated that the P0 I135M protein was located on the cell membrane, but the P0 Q187PfsX63 protein was retained ectopically in the endoplasmic reticulum and Golgi apparatus. Adhesion assay demonstrated a defective adhesiveness of cells expressing either mutant P0 protein, and P0 Q187PfsX63 had a more prominent defect of self-adhesive ability than P0 I135M. Conclusions: This study expanded the spectrum of the MPZ mutations and revealed two disparate mechanisms of MPZ mutations associated with a typical CMT1B phenotype. Other modifying genetic, epigenetic, or environmental factors on CMT1B may exist to explain the discrepancy between the cellular phenotypes. [Copyright &y& Elsevier]

Abstract: Besides in vivo models, co-cultures systems making use of Rat dorsal root ganglion explants/Schwann cells (SC) are widely used to essentially study myelination in vitro. In the case of animal models of demyelinating diseases, it is expected to reproduce a pathological process; conversely the co-cultures are primarily developed to study the myelination process and in the aim to use them to replace animals in experiences of myelin destruction or functional disturbances. We describe (in terms of protein expression kinetic) a new in vitro model of sensory neurons/SC co-cultures presenting the following advantages: both sensory neurons and SC originate from the same individual; sensory neurons and SC being dissociated, they can be co-cultured in monolayer, allowing an easier microscope observation; the co-culture can be maintained in a serum-free medium for at less three months, allowing kinetic studies of myelin formation both at a molecular and cellular level. Optimizing culture conditions permits to use 96-well culture plates; image analyses conducted with an automatic image analyzer allows rapid, accurate and quantitative expression of results. Finally, this system was proved by measuring the apparition of myelin protein to mimic in vitro the physiological process of in vivo myelination. [Copyright &y& Elsevier]

Abstract: We studied the effects of fasudil, a selective Rho-kinase inhibitor, on experimental autoimmune neuritis (EAN). Continuous parenteral administration of fasudil prevented the development of EAN induced by P0 peptide 180–199 in Lewis rats while it also reduced EAN severity when administered after disease onset. Immunohistochemical examination disclosed a marked decrease in the amount of inflammatory cell infiltration and attenuation of demyelination and axonal degeneration. Specific proliferation of lymphocytes from fasudil-treated rats in response to P0 peptide was significantly reduced as compared with those from phosphate-buffered saline (PBS)-treated rats. Fasudil treatment was associated with a significant reduction in secretion of IFN-γ; by contrast, secretion of IL-4 was almost the same in the fasudil- and PBS-treated groups. As a result, the IFN-γ/IL-4 ratio in the supernatant was significantly deceased in fasudil-treated rats compared with PBS-treated ones. Therefore, our results indicate a beneficial effect of selective blockade of Rho-kinase in animals with autoimmune inflammation of the peripheral nerves, and may provide a rationale for the selective blockade of Rho-kinase as a new therapy for Guillain-Barré syndrome. [Copyright &y& Elsevier]