Optimizing periodicity and polymodality in noise-induced genetic oscillators

Many cellular functions are based on the rhythmic organization of biological processes into self-repeating cascades of events. Some of these periodic processes, such as the cell cycles of several species, exhibit conspicuous irregularities in the form of period skippings, which lead to polymodal distributions of cycle lengths. A recently proposed mechanism that accounts for this quantized behavior is the stabilization of a Hopf-unstable state by molecular noise. Here we investigate the effect of varying noise in a model system, namely an excitable activator-repressor genetic circuit, that displays this noise-induced stabilization effect. Our results show that an optimal noise level enhances the regularity (coherence) of the cycles, in a form of coherence resonance. Similar noise levels also optimize the multimodal nature of the cycle lengths. Together, these results illustrate how molecular noise within a minimal gene regulatory motif confers robust generation of polymodal patterns of periodicity.Comment: 9 pages, 6 figure

Percepción del estado de salud en varones y mujeres en las últimas etapas de la vida

ResumenObjetivoAnalizar las diferencias en la percepción del estado de salud de los varones y mujeres en las últimas etapas de la vida y explorar su relación con variables sociodemográficas y de salud.MétodosDatos procedentes de la Encuesta de Salud de Cataluña de 1994, de 1.459 varones y 1.993 mujeres de 60 y más años. Se realizó un análisis de la autovaloración del estado de salud según la edad, el sexo, la clase social, la declaración de enfermedades crónicas y la discapacidades y se aplicó un modelo de análisis multivariable de regresión logística teniendo en cuenta el diseño muestral.ResultadosEl 57,3% de las mujeres de 60 y más años declaraba no tener buena salud, frente al 43,6% de los varones. También fue superior la proporción de mujeres que padecía una o más discapacidades (41,2%) respecto a los varones (28,7%), así como la de enfermedades crónicas, el 92,2% de las mujeres y el 85,6% de los varones. En el modelo de regresión logística multivariable continúa manteniéndose una percepción de mala salud superior en las mujeres y aparecen como factores explicativos el número de enfermedades crónicas, padecer discapacidades y pertenecer a las clases sociales más desfavorecidas. La edad en interacción con las enfermedades crónicas amortigua el efecto de éstas en la valoración del estado de salud.ConclusionesEntre la población anciana, la percepción de mala salud fue superior en las mujeres incluso ajustando por otras variables explicativas significativas (clase social, edad, discapacidades y enfermedades crónicas). Padecer enfermedades crónicas y/o discapacidades constituyen los factores explicativos más importantes en la percepción del estado de salud. El impacto del padecimiento de enfermedades crónicas en relación con la percepción de mala salud disminuye a medida que los grupos son de mayor edad.SummaryObjectivesTo analyze the differences in health self-perception between men and women in the later stages of life and to assess their association with sociodemographic and health variables.MethodsData on 1,459 men and 1,993 women aged 60 or older from the 1994 Catalan Health Survey, were collected and an analysis of health self-perception according to age, gender, social class, reporting of chronic disease and handicaps was performed. Multivariate logistic regression analysis was used, taking into account the survey design.ResultsOf the women aged 60 and older, 57.3% reported poor health compared with 43.6% of men of the same age. The proportion of women with one or more handicaps was also greater (41.2%) than that of the men (28.7%), as was the case with chronic disease (92.2% inwomen and 85.6% in men). The multivariate model also revealed that health self-peerception was poorer among women than among men. Other explanatory factors were the number of chronic diseases, having handicaps, and being a member of a lower social class. Age interacted with the number of chronic diseases to mitigate the effect of chronic diseases on perceived health status.ConclusionsIn the elderly population, poor health self-perception was greater among women, even when other significant explanatory variable (social class, age, handicaps and chronic disease) were adjusted for. The most important explanatory factors in health self-perception were having chronic disease and/or handicaps. The impact of chronic disease on poor health self-perception decreased in older age groups

Large scale diffuse light in the Coma cluster: a multi-scale approach

We have obtained wide field images of the Coma cluster in the B, V, R and I bands with the CFH12K camera at CFHT. In order to search for large scale diffuse emission, we have applied to these images an iterative multi scale wavelet analysis and reconstruction technique which allowed to model all the sources (stars and galaxies) and subtract them from the original images. We found various concentrations of diffuse emission present in the central zone around the central galaxies NGC4874 and NGC4889. We characterize the positions, sizes and colors of these concentrations. Some sources do not seem to have strong star formation, while another one probably exhibits spiral-like color. One possible origin for the star forming diffuse emission sources is that in the region of the two main galaxies NGC4874 and NGC4889 spiral galaxies have recently been disrupted and star formation is still active in the dispersed material. We also use the characteristics of the sources of diffuse emission to trace the cluster dynamics. A scenario in which the group around NGC 4874 is moving north is consistent with our data.Comment: 11 pages, accepted in A&A, jpg figure

ESO Imaging Survey: Optical follow-up of 12 selected XMM-Newton fields

(Abridged) This paper presents the data recently released for the XMM-Newton/WFI survey carried out as part of the ESO Imaging Survey (EIS) project. The aim of this survey is to provide optical imaging follow-up data in BVRI for identification of serendipitously detected X-ray sources in selected XMM-Newton fields. In this paper, fully calibrated individual and stacked images of 12 fields as well as science-grade catalogs for the 8 fields located at high-galactic latitude are presented. The data covers an area of \sim 3 square degrees for each of the four passbands. The median limiting magnitudes (AB system, 2" aperture, 5\sigma detection limit) are 25.20, 24.92, 24.66, and 24.39 mag for B-, V-, R-, and I-band, respectively. These survey products, together with their logs, are available to the community for science exploitation in conjunction with their X-ray counterparts. Preliminary results from the X-ray/optical cross-correlation analysis show that about 61% of the detected X-ray point sources in deep XMM-Newton exposures have at least one optical counterpart within 2" radius down to R \simeq 25 mag, 50% of which are so faint as to require VLT observations thereby meeting one of the top requirements of the survey, namely to produce large samples for spectroscopic follow-up with the VLT, whereas only 15% of the objects have counterparts down to the DSS limiting magnitude.Comment: 24 pages, 10 figures, accepted for publication in Astronomy and Astrophysics. Accompanying data releases available at http://archive.eso.org/archive/public_datasets.html (WFI images), http://www.eso.org/science/eis/surveys/release_65000025_XMM.html (optical catalogs), http://www.aip.de/groups/xray/XMM_EIS/ (X-ray data). Full resolution version available at http://www.astro.uni-bonn.de/~dietrich/publications/3785.ps.g

Striatal-Enriched Protein Tyrosine Phosphatase Expression and Activity in Huntington's Disease: A STEP in the Resistance to Excitotoxicity

Striatal-enriched protein tyrosine phosphatase (STEP) is highly expressed in striatal projection neurons, the neuronal population most affected in Huntington's disease. Here, we examined STEP expression and phosphorylation, which regulates its activity, in N-terminal exon-1 and full-length mutant huntingtin mouse models. R6/1 mice displayed reduced STEP protein levels in the striatum and cortex, whereas its phosphorylation was increased in the striatum, cortex, and hippocampus. The early increase in striatal STEP phosphorylation levels correlated with a deregulation of the protein kinase A pathway, and decreased calcineurin activity at later stages further contributes to an enhancement of STEP phosphorylation and inactivation. Accordingly, we detected an accumulation of phosphorylated ERK2 and p38, two targets of STEP, in R6/1 mice striatum at advanced stages of the disease. Activation of STEP participates in excitotoxic-induced cell death. Because Huntington's disease mouse models develop resistance to excitotoxicity, we analyzed whether decreased STEP activity was involved in this process. After intrastriatal quinolinic acid (QUIN) injection, we detected higher phosphorylated STEP levels in R6/1 than in wild-type mice, suggesting that STEP inactivation could mediate neuroprotection in R6/1 striatum. In agreement, intrastriatal injection of TAT-STEP increased QUIN-induced cell death. R6/2, Tet/HD94, and Hdh(Q7/Q111) mice striatum also displayed decreased STEP protein and increased phosphorylation levels. In Tet/HD94 mice striatum, mutant huntingtin transgene shutdown reestablished STEP expression. In conclusion, the STEP pathway is severely downregulated in the presence of mutant huntingtin and may participate in compensatory mechanisms activated by striatal neurons that lead to resistance to excitotoxicity

Assessing sleep health in a European population: results of the catalan health survey 2015

Objective To describe the overall sleep health of the Catalan population using data from the 2015 Catalan Health Survey and to compare the performance of two sleep health indicators: sleep duration and a 5-dimension sleep scale (SATED). Methods Multistage probability sampling representative of the non-institutionalized population aged 15 or more years, stratified by age, gender and municipality size, was used, excluding nightshift-workers. A total of 4385 surveys were included in the analyses. Associations between sleep health and the number of reported chronic diseases were assessed using non-parametric smoothed splines. Differences in the predictive ability of age-adjusted logistic regression models of self-rated health status were assessed. Multinomial logistic regression models were used to assess SATED determinants. Results Overall mean (SD) sleep duration was 7.18 (1.16) hours; and SATED score 7.91 (2.17) (range 0–10), lower (worse) scores were associated with increasing age and female sex. Alertness and efficiency were the most frequently impaired dimensions across age groups. SATED performed better than sleep duration when assessing self-rated health status (area under the curve = 0.856 vs. 0.798; p-value <0.001), and had a linear relationship with the number of reported chronic diseases, while the sleep duration relationship was u-shaped. Conclusions Sleep health in Catalonia is associated with age and gender. SATED has some advantaged compared to sleep duration assessment, as it relates linearly to health indicators, has a stronger association with self-rated health status, and provides a more comprehensive assessment of sleep health. Therefore, the inclusion of multi-dimensional sleep health assessment tools in national surveys should be considered.This work was cofunded by Ministerio de Economía y Competitividad [COFUND2014-51501]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Enzymkatalysierte späte Modifizierungen: Besser spät als nie

From Wiley via Jisc Publications RouterHistory: received 2020-11-08, rev-recd 2021-01-15, pub-electronic 2021-03-08, pub-print 2021-07-26Article version: VoRPublication status: PublishedFunder: EPSRC; Grant(s): EP/S005226/1Funder: BBSRC; Grant(s): EP/S005226/1Funder: AstraZeneca plc; Id: http://dx.doi.org/10.13039/100004325; Grant(s): EP/S005226/1Funder: European Research Council; Id: http://dx.doi.org/10.13039/100010663; Grant(s): 742987-BIO-H-BORROW-ERC-2016-ADG, 788231-ProgrES-ERC-2017-AD

Enzymatic Late‐Stage Modifications: Better Late Than Never

From Wiley via Jisc Publications RouterHistory: received 2020-11-08, rev-recd 2021-01-15, pub-electronic 2021-03-08, pub-print 2021-07-26Article version: VoRPublication status: PublishedFunder: EPSRC; Grant(s): EP/S005226/1Funder: BBSRC; Grant(s): EP/S005226/1Funder: AstraZeneca plc; Id: http://dx.doi.org/10.13039/100004325; Grant(s): EP/S005226/1Funder: European Research Council; Id: http://dx.doi.org/10.13039/100010663; Grant(s): 742987-BIO-H-BORROW-ERC-2016-ADG, 788231-ProgrES-ERC-2017-ADGAbstract: Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late‐stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme‐catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late‐stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development