Distinct amino acid compositional requirements for formation and maintenance of the [PSI+] prion in yeast

Multiple yeast prions have been identified that result from the structural conversion of proteins into a self-propagating amyloid form. Amyloid-based prion activity in yeast requires a series of discrete steps. First, the prion protein must form an amyloid nucleus that can recruit and structurally convert additional soluble proteins. Subsequently, maintenance of the prion during cell division requires fragmentation of these aggregates to create new heritable propagons. For the Saccharomyces cerevisiae prion protein Sup35, these different activities are encoded by different regions of the Sup35 prion domain. An N-terminal glutamine/asparagine-rich nucleation domain is required for nucleation and fiber growth, while an adjacent oligopeptide repeat domain is largely dispensable for prion nucleation and fiber growth but is required for chaperone-dependent prion maintenance. Although prion activity of glutamine/asparagine-rich proteins is predominantly determined by amino acid composition, the nucleation and oligopeptide repeat domains of Sup35 have distinct compositional requirements. Here, we quantitatively define these compositional requirements in vivo. We show that aromatic residues strongly promote both prion formation and chaperone-dependent prion maintenance. In contrast, nonaromatic hydrophobic residues strongly promote prion formation but inhibit prion propagation. These results provide insight into why some aggregation-prone proteins are unable to propagate as prions

Ocorrencia e abundância de espécies de plantas ameaçadas de extinção no entorno do reservatório da UHE Barra Grande.

Modelos de ocorrência e abundância de espécies são ferramentas atuais que devem ser incorporadas na conservação da biodiversidade no entorno de reservatórios de usinas hidroelétricas, prevendo ou planejando ações necessárias para mitigar os impactos ambientais destes empreendimentos. Neste estudo, nossos objetivos foram: modelar a ocorrência e abundância de espécies de plantas ameaçadas de extinção, verificar a relação entre a ocorrência prevista e a abundância observada e avaliar se os modelos baseados em abundância são mais eficientes em predizer a ocorrência do que aqueles baseados em dados de ocorrência (0/1). Representantes individuais de nove espécies (Araucaria angustifolia (Bertol.) Kuntze (Araucariaceae), Butia eriospatha (Mart. ex Drude) Becc. (Arecaceae), Clethra scabra Pers. (Clethraceae), Dicksonia sellowiana (Presl.) Hook. (Dicksoniaceae), Erythrina falcata Benth. (Fabaceae), Maytenus ilicifolia (Schrad.) Planch. (Celastraceae), Myrocarpus frondosus Allemão (Fabaceae), Podocarpus lambertii Klotzsch ex Endl. (Podocarpaceae) e Trithrinax brasiliensis Mart (Arecaceae)) foram contados em 388 parcelas (10x50m) aleatoriamente alocadas e georreferenciadas no entorno do reservatório da UHE Barra Grande (SC/RS). Modelamos sua relação com 15 variáveis ambientais utilizando dados de ocorrência (GLM) e abundância (Modelos Hurdle e Zero-inflado). Em geral, os modelos de ocorrência foram mais precisos do que os modelos de abundância. Para todas as espécies, a abundância observada foi correlacionada com a probabilidade de ocorrência, sugerindo que estudos futuros poderiam utilizar esta informação, em vez da abundância. Reconstruir padrões de abundância e de ocorrência é uma importante ferramenta para o planejamento de ações de conservação e manejo de espécies ameaçadas, permitindo que sejam indicadas as melhores áreas para a coleta e reintrodução de germoplasma vegetal ou mesmo a escolha de áreas de conservação com maior probabilidade de manter populações viáveis

youth Digital Skills Indicator:German questionnaire

The youth Digital Skills Indicator was developed as part of the ‘Youth Skills (ySKILLS)’ project and added to the ‘From Digital Skills to Tangible Outcomes’ digital skills measurement toolkit.Please read the accompanying document on the underlying rationale for these scales and on how to create and use composite scales in the following document: Helsper, E.J., Schneider, L., van Deursen, A.J.A.M., van Laar, E. (2021). The youth Digital Skills Indicator: Report on the conceptualisation and development of the ySKILLS digital skills measure. KU Leuven, Leuven: ySKILLS. Available at: https://yskills.eu

Further functional determinants

Functional determinants for the scalar Laplacian on spherical caps and slices, flat balls, shells and generalised cylinders are evaluated in two, three and four dimensions using conformal techniques. Both Dirichlet and Robin boundary conditions are allowed for. Some effects of non-smooth boundaries are discussed; in particular the 3-hemiball and the 3-hemishell are considered. The edge and vertex contributions to the $C_{3/2}$ coefficient are examined.Comment: 25 p,JyTex,5 figs. on request

The laurentian record of neoproterozoic glaciation, tectonism, and eukaryotic evolution in Death Vally, California

Neoproterozoic strata in Death Valley, California contain eukaryotic microfossils and glacial deposits that have been used to assess the severity of putative Snowball Earth events and the biological response to extreme environmental change. These successions also contain evidence for syn-sedimentary faulting that has been related to the rifting of Rodinia, and in turn the tectonic context of the onset of Snowball Earth. These interpretations hinge on local geological relationships and both regional and global stratigraphic correlations. Here we present new geological mapping, measured stratigraphic sections, carbon and strontium isotope chemostratigraphy, and micropaleontology from the Neoproterozoic glacial deposits and bounding strata in Death Valley. These new data enable us to refine regional correlations both across Death Valley and throughout Laurentia, and construct a new age model for glaciogenic strata and microfossil assemblages. Particularly, our remapping of the Kingston Peak Formation in the Saddle Peak Hills and near the type locality shows for the first time that glacial deposits of both the Marinoan and Sturtian glaciations can be distinguished in southeastern Death Valley, and that beds containing vase-shaped microfossils are slump blocks derived from the underlying strata. These slump blocks are associated with multiple overlapping unconformities that developed during syn-sedimentary faulting, which is a common feature of Cyrogenian strata along the margin of Laurentia from California to Alaska. With these data, we conclude that all of the microfossils that have been described to date in Neoproterozoic strata of Death Valley predate the glaciations and do not bear on the severity, extent or duration of Neoproterozoic Snowball Earth events

PULSED DOPPLER FROM THE SUPRASTERNAL NOTCH SYSTEMATICALLY UNDERESTIMATES MEAN BLOOD FLOW VELOCITY IN THE ASCENDING AORTA COMPARED TO PHASE CONTRAST MRI

Background Continuous pulsed-wave Doppler readings of flow velocity in the ascending aorta from the suprasternal position (sCD) are widely used in estimating stroke volume, particularly during physiological challenge maneuvers such as head-up tilt testing. Stroke volume is derived from velocity time integrals and vessel area. We compared the sCD against an established gold standard. Methods In 12 healthy women and men, we obtained 2D cross sectional, velocity encoded phase contrast MRI of the ascending aorta (2DMRI) and sCD to measure mean blood flow velocity (Vmean) at the ascending aorta. We compared sCD insonation depth to the distance between Doppler probe and sinotubular junction measured by MRI. Within an aortic 4D-Flow dataset, allowing flow measurements in every anatomical point along the ascending aorta, Vmean was determined at the sCD measurement point for comparison. Results sCD significantly underestimated Vmean compared with 2DMRI at the sinotubular junction (Vmean 2DMRI – Vmean sCD = 24.42 cm/s ± 12.55 cm/s, p = <0.001). Moreover, sCD sampled flow velocities 21.8 mm ± 7mm (p = <0.001) or 26% off the sinotubular junction. Yet, depth and velocity differences between sCD and 2DMRI were not correlated with each other (Pearson r = -0.147; p = 0.648). When we applied 4DMRI to assess flow velocity at the sCD measurement site, the Vmean difference between methodologies was reduced to 9.1 cm/s ± 12.38 cm/s (p = 0.035). Conclusion sCD profoundly underestimates Vmean in the ascending aorta compared to 4DMRI. The methodology has important limitations in accessing the ideal position for aortic flow measurements and precise information regarding the position of data acquisition for vessel area quantification cannot be ascertained. Overall, sCD is of limited utility in measuring absolute stroke volum

Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST trial: A221701)

mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher\u27s exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus