Mouse prion protein polymorphism Phe-108/Val-189 affects the kinetics of fibril formation and the response to seeding: evidence for a two-step nucleation polymerization mechanism

Prion diseases are fatal neurodegenerative disorders associated with the polymerization of the cellular form of prion protein (PrP(C)) into an amyloidogenic β-sheet infectious form (PrP(Sc)). The sequence of host PrP is the major determinant of host prion disease susceptibility. In mice, the presence of allele a (Prnp(a), encoding the polymorphism Leu-108/Thr-189) or b (Prnp(b), Phe-108/Val-189) is associated with short or long incubation times, respectively, following infection with PrP(Sc). The molecular bases linking PrP sequence, infection susceptibility, and convertibility of PrP(C) into PrP(Sc) remain unclear. Here we show that recombinant PrP(a) and PrP(b) aggregate and respond to seeding differently in vitro. Our kinetic studies reveal differences during the nucleation phase of the aggregation process, where PrP(b) exhibits a longer lag phase that cannot be completely eliminated by seeding the reaction with preformed fibrils. Additionally, PrP(b) is more prone to propagate features of the seeds, as demonstrated by conformational stability and electron microscopy studies of the formed fibrils. We propose a model of polymerization to explain how the polymorphisms at positions 108 and 189 produce the phenotypes seen in vivo. This model also provides insight into phenomena such as species barrier and prion strain generation, two phenomena also influenced by the primary structure of PrP.FWN – Publicaties zonder aanstelling Universiteit Leide

Musicoterapia en una Unidad de Cuidados Intensivos Neonatales: experiencia benéfica para el binomio

ResumenIntroducciónDesde hace varios años se está utilizando la música como herramienta terapéutica y preventiva en la neonatología, se han documentado en un gran número de artículos de investigación, sin embargo, en México esta técnica es poco utilizada.ObjetivoMejorar las condiciones de los neonatos atendidos en una Unidad de Cuidados Intensivos (UCIN) y sus familiares, mediante el uso de musicoterapia, para minimizar el estrés y los daños colaterales.Materiales y métodosUn grupo de 2 neonatólogos, 3 residentes de pediatría, 10 enfermeras y un concertista profesional de violín, llevaron a cabo 6 sesiones musicales semanales en la Unidad de Cuidados Intensivos Neonatales Externos del Hospital Civil de Guadalajara. Durante el concierto se valoró individualmente a cada neonato, registrando los signos vitales por monitorización electrónica, además se registró el estado anímico de los familiares.ResultadosDurante las sesiones de música los neonatales no presentaron cambios significativos en sus constantes vitales, en el personal de la UCIN y en los padres de recién nacidos hospitalizados se vieron efectos benéficos, refiriendo disminución del estrés y altos índices de satisfacción.ConclusionesLa música puede tener un efecto positivo como terapia coadyuvante en neonatos de alto riesgo, principalmente en prematuros. Se recomienda difundir y aplicar esta metodología en las UCIN del país.AbstractIntroductionSince several years ago, music has been used as a therapeutic and preventive tool in neonatology. A great number of research papers have been written on the subject; however, this technique is rarely used in Mexico.ObjectiveTo improve the condition of neonates at Neonatal Intensive Care Units (NICU) and their relatives, in order to minimize any stress and collateral damage.Material and methods: A group of two neonatologists, 3 residents, 10 nurses and a professional concert violinist, conducted six weekly music sessions in the Outpatient Neonatal Intensive Care Unit (ONICU) of our institution. During the concert, we individually assessed each newborn, recording vital signs through electronic monitoring; additionally, we recorded the mood of any other family members present.ResultsDuring the music sessions, the neonatal patients showed no significant changes in vital signs; yet, ONICU staff and the parents/relatives of hospitalized newborns showed beneficial effects, reporting decreased stress and high levels of satisfaction.ConclusionsMusic can have a positive effect as adjunctive therapy in high-risk newborns, especially in premature babies. We therefore recommend applying this methodology in the ONICU

Spin-based all-optical quantum computation with quantum dots: understanding and suppressing decoherence

We present an all-optical implementation of quantum computation using semiconductor quantum dots. Quantum memory is represented by the spin of an excess electron stored in each dot. Two-qubit gates are realized by switching on trion-trion interactions between different dots. State selectivity is achieved via conditional laser excitation exploiting Pauli exclusion principle. Read-out is performed via a quantum-jump technique. We analyze the effect on our scheme's performance of the main imperfections present in real quantum dots: exciton decay, hole mixing and phonon decoherence. We introduce an adiabatic gate procedure that allows one to circumvent these effects, and evaluate quantitatively its fidelity

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Stability of cupuaçu (Theobroma grandiflorum) nectar during storage

A shelf-life study on cupuaçu nectar (Theobroma grandiflorum) was carried out in two parts. Part I studied the microbial stability of the regular nectar (batch R) and the same nectar fortified with synthetic ascorbic acid (AA) (batch F), pasteurized at 90 °C for 3 min and hot filled in glass bottles. Total Plate Count (TPC), yeast and molds as well as pH, total soluble solids (TTS), titratable acidity and hidroxymethylfurfural (HMF) were followed along 43 storage days at 4, 25 and 35 °C. At the end of the storage period neither TPC nor molds or yeast had recovered the initial loads observed before pasteurization, for both R and F batches. Right after pasteurization, acidity increased slightly, pH decreased from 3.52 to 3.3, and TSS increased from 18.7 to 19.0 °Brix, with all stabilizing afterwards.Part II evaluated ascorbic (AA) and dehydroascorbic (DHAA) acids’ stabilization in the two batches, R and F, and dissolved oxygen (DO) was monitored. Both batches were stored at the same temperatures as in Part I for two months. For batch R, the AA degradation results followed a reversible first order reaction (EaAA(R)=-34±6 kJ/mol, kAA(R)25°C=0.006±0.003 days-1, C0AA(R)=0.92±0.01 and C∞AA(R)= 0.43±0.19). For the (F) nectar, the experimental data fitted a first order model well (EaAA(F)=30±17 kJ/mol, kAA(F)25°C =0.0016±0.0004 days-1). DO was modeled as a fractional conversion model (EaDO= 67±17 kJ/mol, kDO25°C= 1.94±0.94 days-1, C0DO=0.97±0.03 and C∞DO= 0.55±0.01). For both nectars, storage at environmental temperatures was preferred (AA retention above 80%) to refrigeration, due to the slower rate of diffusion of DO at lower temperatures.</p

mRNA expression profile of multidrug resistance genes in childhood acute lymphoblastic leukemia : low expression levels associated with a higher risk of toxic death

Increased activity of multidrug resistance (MDR) genes has been associated with treatment failure in acute leukemias, although with controversial reports. The objective of the present study was to assess the expression profile of the genes related to MDR: ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP in terms of the clinical and biological variable and the survival of children with acute lymphoblastic leukemia (ALL). The levels of mRNA expression of the drug resistance genes ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP were analyzed by quantitative real‐time PCR using the median values as cut‐off points, in consecutive samples from 140 children with ALL at diagnosis. Expression levels of the ABCG2 gene in the patient group as a whole (P = 0.05) and of the ABCG2 and ABCC1 genes in patients classified as being at high risk were associated with higher rates of 5‐year event‐free survival (EFS) (P = 0.04 and P = 0.01). Expression levels of the ABCG2 gene below the median were associated with a greater chance of death related to treatment toxicity for the patient group as a whole (P = 0.009) and expression levels below the median of the ABCG2 and ABCC1 genes were associated with a greater chance of death due to treatment toxicity for the high‐risk group (P = 0.02 and P = 0.03, respectively). The present data suggest a low participation of the drug efflux genes in treatment failure in patients with childhood ALL. However, the low expression of some of these genes may be associated with a higher death risk related to treatment toxicity. Pediatr Blood Cancer 2009;53:996–1004. © 2009 Wiley‐Liss, Inc5369961004FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2001/13206‐9; 2002/03182‐8; 2005/50731‐