Dirac and Weyl Equations on a Lattice as Quantum Cellular Automata

A discretized time evolution of the wave function for a Dirac particle on a cubic lattice is represented by a very simple quantum cellular automaton. In each evolution step the updated value of the wave function at a given site depends only on the values at the nearest sites, the evolution is unitary and preserves chiral symmetry. Moreover, it is shown that the relationship between Dirac particles and cellular automata operating on two component objects on a lattice is indeed very close. Every local and unitary automaton on a cubic lattice, under some natural assumptions, leads in the continuum limit to the Weyl equation. The sum over histories is evaluated and its connection with path integrals and theories of fermions on a lattice is outlined.Comment: 6, RevTe

Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure

PrP(Sc)-specific antibodies with the ability to immunodetect prion oligomers.

The development of antibodies with binding capacity towards soluble oligomeric forms of PrPSc recognised in the aggregation process in early stage of the disease would be of paramount importance in diagnosing prion diseases before extensive neuropathology has ensued. As blood transfusion appears to be efficient in the transmission of the infectious prion agent, there is an urgent need to develop reagents that would specifically recognize oligomeric forms of the abnormally folded prion protein, PrPSc.To that end, we show that anti-PrP monoclonal antibodies (called PRIOC mAbs) derived from mice immunised with native PrP-coated microbeads are able to immunodetect oligomers/multimers of PrPSc. Oligomer-specific immunoreactivity displayed by these PRIOC mAbs was demonstrated as large aggregates of immunoreactive deposits in prion-permissive neuroblastoma cell lines but not in equivalent non-infected or prn-p(0/0) cell lines. In contrast, an anti-monomer PrP antibody displayed diffuse immunoreactivity restricted to the cell membrane. Furthermore, our PRIOC mAbs did not display any binding with monomeric recombinant and cellular prion proteins but strongly detected PrPSc oligomers as shown by a newly developed sensitive and specific ELISA. Finally, PrioC antibodies were also able to bind soluble oligomers formed of Aβ and α-synuclein. These findings demonstrate the potential use of anti-prion antibodies that bind PrPSc oligomers, recognised in early stage of the disease, for the diagnosis of prion diseases in blood and other body fluids

Polyploidy in chronic lymphocytic leukemia with p53 deletion detected by fish: a case report

We report a case of chronic lymphocytic leukemia with a characteristic cytogenetics finding detected by fluorescent in situ hybridization. This case has deletion in p53 gene in 50% of interphase nuclei studied in the peripheral blood and polyploidy in 30% of cells. To our knowledge polyploidy is not commonly reported with chronic lymphocytic leukemia patients

The Interplay of Youth and Care Characteristics with a Positive Social Climate in Therapeutic Residential Youth Care

Background: Limited research exists on how therapeutic residential youth care (TRC) achieves treatment outcomes. More specifically, little is known about the association between contextual factors such as treatment organization, youth characteristics, and experienced social climate in TRC. Therefore, this study aims to investigate differences between latent classes of TRC and youth characteristics and their association with a positive perceived social TRC climate. Method: We applied a person-centered approach in a cross-sectional design with a sample of 400 adolescents and 142 staff leaders. We analyzed youth and TRC characteristics in a latent class analysis and established associations with social climate for these two groupings. Results: The two types of TRC settings we found, i.e., larger TRC settings and family-style TRC settings, show small differences in social climate. These settings only differed on youth activities and staff shifts type (more cohabitation and unorganized activities outside TRC in family-style TRC). We identified four adolescent classes: A severe problems group, youth with incidental problems, family problems, and a migrant background group. The migrant background group showed the most positive perceptions of social climate, followed by youth with incidental problems, family problems, and severe problems. Conclusions: TRC staff should acknowledge how perceived social climate is connected to TRC characteristics and the heterogeneity of adolescents in care. As social climate is subjective and dynamic, a continuous dialogue about TRC social climate between staff and youth is recommended. Future research should investigate how these aspects are associated with treatment outcomes to increase our understanding of achieving positive outcomes in TRC

The mediating role of social climate in the association of youth and residential service characteristics and quality of life

Previous research has shown that social climate (SC) is important for the daily life of youths living in therapeutic residential youth care (TRC). However, little is known on how SC can promote a positive quality of life (QoL) for the heterogeneous TRC population. This study, therefore, investigates how TRC and youth characteristics are associated with SC and QoL. We employed a combination of person-centered and variable-centered approaches in a cross-sectional design using a sample of 400 Norwegian youths. We used previously established TRC and youth classes in a structural equation model, where these classes were regressed on latent SC and QoL. Both direct and indirect effects were analyzed. All youth classes were associated with SC and QoL, such that youth with family problems, incidental problems, and the migrant background class scored higher on SC and QoL compared to the severe problems class. In addition, SC mediated the association of the incidental problems and migrant background classes on QoL. TRC staff should acknowledge that a positive SC can strengthen the QoL of youths with severe problems. Future research should longitudinally investigate these associations to establish long-term effects on QoL during stay in TRC.</p

3-[(E)-(4-Chloro­benzyl­idene)amino]-1-phenyl­thio­urea

In the title compound, C14H12ClN3S, the dihedral angle between the terminal benzene rings is 56.6 (2)°; the benzene rings lie to the same side of the mol­ecule. The major twist in the mol­ecule occurs around the Car—N bond (ar is aromatic) [C—N—C—C = 49.9 (5)°]. The configuration about the N=C bond [1.271 (4) Å] is E. The amine H atoms lie on opposite sides of the mol­ecule with one forming an intra­molecular N—H⋯N(imine) hydrogen bond and an S(5) ring. In the crystal, centrosymmetric dimers are formed via {⋯HNC=S}2 synthons

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Heparan sulfate proteoglycans are ubiquitously found at the cell surface and extracellular matrix in all the animal species. This review will focus on the structural characteristics of the heparan sulfate proteoglycans related to protein interactions leading to cell signaling. The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation. The role of the heparan sulfate proteoglycans in cellular signaling and endocytic uptake pathways is also discussed.Proteoglicanos de heparam sulfato são encontrados tanto superfície celular quanto na matriz extracelular em todas as espécies animais. Esta revisão tem enfoque nas características estruturais dos proteoglicanos de heparam sulfato e nas interações destes proteoglicanos com proteínas que levam à sinalização celular. As cadeias de heparam sulfato, devido a sua variedade estrutural, são capazes de se ligar e interagir com ampla gama de proteínas, como fatores de crescimento, quimiocinas, morfógenos, componentes da matriz extracelular, enzimas, entreoutros. Existe uma especificidade estrutural que direciona as interações dos heparam sulfatos e proteínas alvo. Esta especificidade está relacionada com a estrutura da cadeia do polissacarídeo e os motivos conservados da cadeia polipeptídica das proteínas envolvidas nesta interação. Os heparam sulfatos possuem papel na sinalização celular como receptores ou coreceptores para diferentes ligantes. Esta ligação dispara vias de sinalização celular levam à fosforilação de diversas proteínas citosólicas ou com ou sem interações diretas com o citoesqueleto, culminando na regulação gênica. O papel dos proteoglicanos de heparam sulfato na sinalização celular e vias de captação endocítica também são discutidas nesta revisão.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de BioquímicaUniversidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaUNIFESP, Depto. de BioquímicaUNIFESP, Depto. de OftalmologiaSciEL

Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is beta-sheet rich, infectious and self-perpetuating in nature. These infectious proteins show several remarkable biological activities, including the ability to form multiple infectious prion conformations, also known as strains or variants, encoding unique biological phenotypes, and to establish and overcome prion species (transmission) barriers. In this Perspective, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher such biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and we propose approaches to accelerate the understanding of these enigmatic, infectious conformers