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Genetic variants in YWHAZ contribute to psychiatric disorders such as autism spectrum disorder and schizophrenia, and have been related to an impaired neurodevelopment in humans and mice. Here, we have used zebrafish to investigate the mechanisms by which YWHAZ contributes to neurodevelopmental disorders. We observed that ywhaz expression was pan-neuronal during developmental stages and restricted to Purkinje cells in the adult cerebellum, cells that are described to be reduced in number and size in autistic patients. We then performed whole-brain imaging in wild-type and ywhaz CRISPR/Cas9 knockout (KO) larvae and found altered neuronal activity and connectivity in the hindbrain. Adult ywhaz KO fish display decreased levels of monoamines in the hindbrain and freeze when exposed to novel stimuli, a phenotype that can be reversed with drugs that target monoamine neurotransmission. These findings suggest an important role for ywhaz in establishing neuronal connectivity during development and modulating both neurotransmission and behaviour in adults.

The cardiac muscarinic receptor (M2R) regulates heart rate, in part, by modulating the ace-tylcholine (ACh) activated K⁺ current I$_{K,ACh}$ through dissociation of G-proteins, that in turn activate K$_{ ACh}$ channels. Recently, M2Rs were noted to exhibit intrinsic voltage sensitivity, i.e. their affinity for ligands varies in a voltage dependent manner. The voltage sensitivity of M2R implies that the affinity for Ach (and thus the Ach effect) varies throughout the time course of a cardiac electrical cycle. The aim of this study was to investigate the contribution of M2R voltage sensitivity to the rate and shape of the human sinus node action potentials in physiological and pathophysiological conditions. We developed a Markovian model of the I$_{K,ACh}$ modulation by voltage and integrated it into a computational model of human sinus node. We performed simulations with the integrated model varying Ach concentration and voltage sensitivity. Low Ach exerted a larger effect on I$_{K,ACh}$ at hyperpolarized versus depolarized membrane voltages. This led to a slowing of the pacemaker rate due to an attenuated slope of phase 4 depolarization with only marginal effect on action potential duration and amplitude. We also simulated the theoretical effects of genetic variants that alter the voltage sensitivity of M2R. Modest negative shifts in voltage sensitivity, predicted to increase the affinity of the receptor for ACh, slowed the rate of phase 4 depolarization and slowed heart rate, while modest positive shifts increased heart rate. These simulations support our hypothesis that altered M2R voltage sensitivity contributes to disease and provide a novel mechanistic foundation to study clinical disorders such as atrial fibrillation and inappropriate sinus tachycardia.

BACKGROUND: Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence, but at the expense of increased musculoskeletal side-effects, such as carpal tunnel syndrome. The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2-3 years of tamoxifen. METHODS: In the Intergroup Exemestane Study, postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2-3 years of tamoxifen were randomised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment. The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events, analysed in the safety population, which consisted of all patients who had received any trial treatment. As well as case-report forms, questionnaires were distributed retrospectively to gain more details of cases of carpal tunnel syndrome. The relation between musculoskeletal symptoms reported by 6 months from randomisation and survival from 9 months onwards was assessed by Cox proportional hazards models. The trial is registered, number ISRCTN11883920. It has completed accrual and follow-up is continuing for enrolled participants. FINDINGS: After a median follow-up of 91·0 months (IQR 83·0-99·2), carpal tunnel syndrome had been reported for 66 (2·8%) of 2319 patients in the exemestane group compared with 13 (0·6%) of 2338 in the tamoxifen group (odds ratio [OR] 5·23, 99% CI 2·39-11·49; p

2 pages, 2 figures.-- PACS nrs.: 23.20.Lv; 27.60.+j.-- Printed version published Apr 15, 2004., High-spin states of the neutron-rich vibrational nucleus Cd-114 have been studied using the incomplete fusion reaction Pd-110(Li-7, p2n) and the GASP spectrometer in conjunction with the ISIS Si ball. About 50 new states with excitation energies up to 7 MeV and angular momentum I ≤ 18(+) were observed and for many of them, spin and parity could be firmly assigned. The band-like stuctures in Cd-114 are compared to the corresponding ones in the even-even neighbour Cd-112., This work has been supported by the European Commission within the Contract HPRI-1999-CT-00083 and by the DGI, Ministerio de Ciencia y Tecnología, Spain, under the Project BFM2001-0184. A. J. acknowledges support by the Deutsche Forschungsgemeinschaft (DFG) within the Heisenberg program.

14 págs.; 10 figs.; 2 tabs.; PACS number(s): 21.10.Tg, 21.60.Cs, 23.20.Js, 27.60.1j, The recoil-distance Doppler-shift technique was employed for determining lifetimes of high-spin states in the semimagic nucleus 93Tc. The nuclei were populated using the reaction 64Zn(35Cl, α2p) at a beam energy of 135 MeV, and the γ radiation from their decay was detected in the GASP spectrometer. A total of 26 reduced transition probabilities and limits for 19 further transitions were extracted and compared to large-scale shell model calculations, considering different configuration spaces and residual interactions. The information deduced about transition strengths turned out to be essential for the correct assignment of the calculated to the experimental excited states. ©2003 The American Physical Society, This work has been supported by the European Commission through the Contract No. HPRI-1999- CT-00083 and the Deutsches Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (BMBF). A. Jungclaus acknowledges financial support from the Deutsche Forschungsgemeinschaft (DFG) within the Heisenberg program.

The recoil-distance Doppler-shift technique was employed for determining lifetimes of high-spin states in the semimagic nucleus 93Tc. The nuclei were populated using the reaction 64Zn(35Cl,b1;2p) at a beam energy of 135 MeV, and the g radiation from their decay was detected in the GASP spectrometer. A total of 26 reduced transition probabilities and limits for 19 further transitions were extracted and compared to large scale shell model calculations, considering different configuration spaces and residual interactions. The information deduced about transition strengths turned out to be essential for the correct assignment of the calculated to the experimental excited states.

The recoil distance Doppler shift and Doppler shift attenuation techniques were employed to determine for the first time lifetimes of high spin states in Cd-104in the time range 0.3 ps less than equal to tau less than 1.2 ns. The new experimental results are discussed in the frame of the interacting boson plus broken pair model.

High-spin states in 90Y were populated in the 82Se(11B,3n) reaction at a beam energy of 37 MeV. Gamma rays were detected with the spectrometer GASP. The level scheme of 90Y was extended up to J^\pi = (18^+) at 9.6 MeV. Mean lifetimes of four levels were determined using the Doppler-shift-attenuation method. The structure of 90Y was interpreted in terms of the shell model. The calculations were performed in the model space \pi(0f_{5/2},1p_{3/2},1p_{1/2},0g_{9/2}) \nu(1p_{1/2},0g_{9/2},1d_{5/2}) and in an extended space including the \nu(0g_{7/2})$ orbital as well. The calculations in the extended model space reveal a correspondence between states in ^{90}Y and ^{89}Y. Moreover, a combination of the predicted states with J^\pi \geq 14^(+) can be found that reproduces the large B(M1) values of up to about 1 W.u.

Lifetimes of 20 high spin states in Ag-101 in the range between 0.2 and 200 ps have been measuredand interpreted within the boson fermion plus broken pair model.

The recoil distance Doppler shift and Doppler shift attenuation techniques were employed to determine for the first time lifetimes of high spin states in Cd-104in the time range 0.3 ps less than equal to tau less than 1.2 ns. The new experimental results are discussed in the frame of the interacting boson plus broken pair model.

En este trabajo se presenta un cálculo por máquina en lenguaje Algol de la masa de aire óptica. El método incorpora la reducción del tiempo de observación, una corrección diaria para la declinación del sol, la ecuación trigonométrica y, mediante el uso de la tabla de Bemporad modificada con 900 entradas se obtiene la masa de aire relativa y absoluta. El tiempo de cálculo es solo de 1/60" por observación.Los resultados permiten valorar cuantitativamente los efectos del camino óptico y la latitud del lugar así como el error de cálculo cometido al leer directamente el ángulo zenital con el actinómetro en el momento de la observación.

En un trabajo previo hemos presentado un algoritmo (J, m, w, B, α = 1.5) que describe el Campo Actinométrico de Radiación; dadas como condiciones iniciales tres de las variables anteriores, se obtiene la cuarta variable. En el presente artículo se presenta un algoritmo más flexible. El método permite un análisis cuantitativo de las diferentes distribuciones de la constante solar junto con las funciones de transmisión utilizadas. Los resultados muestran estas relaciones para combinaciones de las funciones de entrada en términos de un indicador de todo el proceso, en este caso, el coeficiente B de la turbidez atmosférica. El algoritmo es entonces una técnica útil para el estudio de cualquier combinación deseada de las curvas espectrales de irradiación solar juntamente con las funciones de transmisión dadas; en esta forma las Comisiones Internacionales pueden escoger la mejor combinación y recomendarla para cálculos futuros.

Lifetimes of 20 high spin states in Ag-101 in the range between 0.2 and 200 ps have been measuredand interpreted within the boson fermion plus broken pair model.

High-spin states of 95Ru have been populated using the 35Cl+ 64Zn reaction at a beam energy of 135 MeV. In a recoil-distance Doppler-shift experiment, the lifetimes or lifetime limits of 26 high-spin states have been measured, giving information on a total of 49 reduced transition strengths. The results are compared with shell-model calculations with different model spaces and residual interactions. Several families of states with defined proton and neutron seniorities are proposed. The M1 strengths in the negative-parity yrast sequence show a pronounced staggering which is reproduced by the shell-model calculations.

High-spin states of 89Sr and 90Sr were studied via the reactions 82Se(11B,p4n) and 82Se(11B ,p3n), respectively, at a beam energy of 37 MeV. Gamma rays were detected with the GASP spectrometer. The level schemes of 89Sr and 90Sr were extended up to E ≈ 8 MeV and E ≈ 10 MeV, respectively. The level structures in 89Sr and 90Sr were interpreted in terms of the spherical shell model. The calculations were performed in the configuration space (0f5/2, 1p3/2, 1p1/2, 0g9/2) f or the protons and (1p1/2, 0g9/2, 1d5/2) for the neutrons. High-spin level sequences in 89Sr are characterized by coupling the unpaired d5/2 neutron to proton excitations of the core nucleus 88Sr. An equidistant level sequence with ΔJ = 2 found in 90Sr is well described by the configuration π[(0f5/2-2) (0g9/22)] ν(1d5/22) which favors even spins.

Solid state fermentation (SSF) deals with the cultivation of aerobic and anaerobic microorganisms on the surface or inside porous solid matrices. These solid matrices can act as substrates or as inert supports and absorb the components of the culture medium without liquid draining. Filamentous fungi (#Aspergillus$, #Claviceps$, #Penicillium$, #Rhisopus$, #Trichoderma$) are the most adapted microorganisms for SSF. Ectomycorrhizal fungi (#Lactarious$, #Pisolitus$, #Suillus$) as well as saprophytic fungi (#Lentinus$, #Pleurotus$) grow well on solid media containing different biodegradable and non biodegradable materials. For instance, manioc starch and sugar cane cellulose are biodegrable supports, while amberlite and vermiculite are non biodegradable supports. The growth of these microorganisms is evaluated by respirometry (continuous measurement of CO2 and O2) and the biochemistry of the produced biomass is accomplished by analyzing different cellular constituents. Some studies on physiology and biochemistry of microorganisms such as #Aspergillus niger$, #Penicillium verrucosum$, #Rhizopus oligosporus$, #Schwanniomyces castellii$, #Trichoderma harzianum$, #Pisolitus tintorius$ and #Suillus colinitus$ growing in SSF are presented. (Résumé d'auteur)

The low water activity, the complex nature of the support and/or substrate, the concentation of substrates used and products formed, and the heterogeneity within the system, influence the growth and physiology of the microbial strains used in solid state fermentation (SSF). As a result, the quality and quantity of the products formed from SSF processes significantly differ from those of submerged fermentation (SmF). Some strains that performed well in SmF processes do not perform efficiently in SSF process. Therefore, it is necessary to maximize the potential of the organism through genetic manipulation to suit the SSF process. Some of the desirable characteristics to be considered for the improvement of the microbial strains for SSF are : tolerance to low water activity and elevated temperature, deregulation of stringent metabolic controls, insensitivity to concentrations of the substrates and products. The genes responsible for counteracting the effect of increased osmotic condition, temperature, carbon and nitrogen catabolite repression are to be identified in the SSF organisms. They may be suitable manipulated in the producers or/and may be transferred to the producer organism. (Résumé d'auteur)

Biological wastewaters treatments always incorporate aerobic and anaerobic stages which take place in two reactors in series. Such aerobic and anaerobic stages are often the only way to mineralise toxic compounds. Theoretical arguments are presented in this paper which demonstrate that the two phases can take place within one reactor without compartmentalisation. Experimental results on the application of these concepts to a pentachlorophenol containing wastewaters are also presented. (Résumé d'auteur)

The results of Candida utilis growth on an anionic resin (Amberlite) at high glucose concentration and using ethanol as the sole carbon sources are presented. The yeast consumed 240 mg glucose (g initial dry matter)−1 (IDM) reaching a final population of 5.6x109 cells (g1DM)−1 (initial inoculum size: 1x107 cells (g IDM)−1. It was also shown that respirometry was a reliable on-line method for monitoring growth. The respiratory quotient (RQ) showed the changes in the metabolism of the yeast during glucose consumption, from a fermentative to an oxidative route.When C. utilis was grown on gaseous ethanol enriched air, a final population of 3.25x109 cells (g IDM)−1 was attained. The importance of mineral salts concentration in the nutritive medium was clearly demonstrated. A two fold increase in the population was obtained when the mineral medium was not limiting. Small amounts of acetaldehyde and ethyl acetate were detected at the outlet of the reactor (1.88 µl l−1 and 0.87 µl l−1, respectively). Ethanol accumulated in the reactor up to 120 mg (g 1DM)−1 (probably an inhibitory level for this yeast). RQ remained constant at around 0.6 during the fermentation.