Protection of CpG islands against de novo DNA methylation during oogenesis is associated with the recognition site of E2f1 and E2f2

BACKGROUND: Epigenetic reprogramming during early mammalian embryonic and germ cell development is a genome-wide process. CpG islands (CGIs), central to the regulation of mammalian gene expression, are exceptional in terms of whether, when and how they are affected by epigenetic reprogramming. RESULTS: We investigated the DNA sequences of CGIs in the context of genome-wide data on DNA methylation and transcription during oogenesis and early embryogenesis to identify signals associated with methylation establishment and protection from de novo methylation in oocytes and associated with post-fertilisation methylation maintenance. We find no evidence for a characteristic DNA sequence motif in oocyte-methylated CGIs. Neither do we find evidence for a general role of regular CpG spacing in methylation establishment at CGIs in oocytes. In contrast, the resistance of most CGIs to de novo methylation during oogenesis is associated with the motif CGCGC, the recognition site of E2f1 and E2f2, transcription factors highly expressed specifically in oocytes. This association is independent of prominent known hypomethylation-associated factors: CGI promoter activity, H3K4me3, Cfp1 binding or R-loop formation potential. CONCLUSIONS: Our results support a DNA sequence-independent and transcription-driven model of de novo CGI methylation during oogenesis. In contrast, our results for CGIs that remain unmethylated are consistent with a model of protection from methylation involving sequence recognition by DNA-binding proteins, E2f1 and E2f2 being probable candidates

One-Shot Multi-Winner Self-Organizing Maps

There exist two different approaches to self-organizing maps (SOMs). One approach, rooted in theoretical neuroscience, uses SOMs as computational models of biological cortex. The other approach, taken in computer science and engineering, views SOMs as tools suitable to perform, for example, data visualization and pattern classification tasks. While the first approach emphasizes fidelity to neurobiological data, the latter stresses computational efficiency and effectiveness. In the research reported here, I developed and studied a class of SOMs that incorporates the multiple, simultaneous winner nodes implicit in many biologically-oriented SOMs, but determines the winners using the same efficient one-shot algorithm employed by computationally-oriented, single-winner SOMs. This was achieved by generalizing single-winner SOMs, using localized competitions. The resulting one-shot multi-winner SOM was found to support the formation of multiple adjacent, mirror-symmetric topographic maps. It constitutes the first computational model of mirror-image map formation, and raises questions about the role of Hebbian-type synaptic changes in the formation of mirror-symmetric maps that are often observed in the sensory neocortex of many species, including humans. The model unexpectedly predicted the occasional occurrence of adjacent, rotationally symmetric maps. It is natural to speculate that such atypically oriented maps might contribute to abnormal cortical information processing in some neurodevelopmental disorders. Traditional SOMs lack applicability to problems where the inputs are not single patterns, but temporal sequences of patterns. Several SOM extensions have been proposed as a remedy, but there is no standard for processing temporal sequences with SOMs. I focused on the task of learning unique spatial representations for non-trivial sets of temporal sequences. The one-shot multi-winner SOM extended by temporally-asymmetric Hebbian synapses proved effective when applied to this task. The learned representations retained information about sequence similarity. The feature maps that formed show that temporal sequence processing and map formation are not mutually exclusive. Since the sequence processing one-shot multi-winner SOM was trained with phonetic transcriptions of spoken words, the results can be related to the internalization of spoken words during language acquisition. A final redesign of the network and the subsequent multi-objective optimization of its parameters using a genetic algorithm produced a more effective system

Influence of Dilution upon Cation Exchange Equilibrium

Ion exchange equilibria in batch systems have been examined to see how the distribution of ions between the ion exchanger and the solution depends on the dilution of the solution. The exchanger was Amberlite IR-120. The following exchanges were studied· K +-H+ Mg++-Ca ++ Ca++ -H+ Ba++ -H+ Ce3 +-H+ and La3 + H+. It has been found that dilution of the system causes the ion of higher affinity to pass into the resin phase. This effect is more pronounced for the exchange of ions of unequal charge than for those of the same charge

Auswirkungen der demographischen Entwicklung auf die Zahl der Pflegefälle: Vorausschätzungen bis 2020 mit Ausblick auf 2050

In general, demographic development is expected to increase the number of cases needing nursing care. In order to explore the possible dynamics in this area, this papers employs a demographic model of the DIW which integrates among others a steadily increasing life expectancy. Grouping by sex, age and intensity of nursing care, the model calculates in advance the number of nursing cases. Calculations include patients both from the statutory and from the private nursing care insurance. According to the calculations presented, the number of patients needing nursing care is expected to increase by 52 % or by one million cases by 2020. By the year 2050, the number of patients needing nursing care will reach 4.7 million cases which increases the current level by a factor of 2.5. As the number of cases needing intensive or most intensive nursing care will increase more than the number of cases just needing significant nursing care, the average intensity in care needed will grow. Need for care and assistance will thus grow more dynamically than the number of cases. Demographic factors alone make the need for inpatient nursing care increase more strongly than that for outpatient assistance. This trend is further pushed forward by the changing structure of families and households, by the increasing participation of women in the labour market and by increasing age of those family members who render nursing care. The increase in the number of cases needing nursing care does not only challenge social security. More than that, the increase in demand for outpatient care as well as for partly or full inpatient nursing care makes up a significant potential for new employment. This potential can be realised by setting the respective framework conditions. Even if there is political consensus for an increase in private insurance of the risk of nursing care, the contribution rate to the Von der demographischen Entwicklung wird allgemein eine Zunahme der Zahl Pflegebedürftiger erwartet. Um die mögliche Dynamik in diesem Bereich aufzuzeigen, wird mit Hilfe des DIW-Bevölkerungsmodells, das u.a. die weiterhin steigende Lebenserwartung modelliert, die Zahl der Pflegefälle differenziert nach Geschlecht, Altersgruppen und Schweregrad der Pflegebedürftigkeit vorausberechnet. Die Zahl der Pflegefälle umfasst hier sowohl die Leistungsempfänger aus der sozialen als auch aus der privaten Pflegeversicherung. Nach den hier vorgelegten Berechnungen dürfte die Zahl Pflegebedürftiger bis 2020 um 52 % oder rund 1 Million steigen. Im Jahre 2050 wird die Zahl der Pflegebedürftigen mit 4,7 Millionen das 2,5fache des heutigen Niveaus erreichen. Da die Zahl der Schwer- und Schwerstpflegebedürftigen stärker steigt als die der "Erheblich Pflegebedürftigen", wird sich der Grad der durchschnittlichen Pflegebedürftigkeit erhöhen. Der Versorgungs- und Betreuungsbedarf weist damit ein dynamischeres Wachstum auf als die Zahl der Pflegefälle. Bereits rein demographisch bedingt wird die Nachfrage nach stationären Pflegediensten stärker steigen als nach ambulanter Betreuung. Diese Tendenz wird durch die veränderten Familien- und Haushaltsstrukturen, die weiterhin steigende Erwerbsbeteiligung der Frauen sowie die Alterung der familiären Pflegekräfte verstärkt. Die Zunahme der Zahl Pflegebedürftiger stellt nicht nur für die soziale Sicherung eine Herausforderung dar, die Nachfragesteigerung nach ambulanten, teilstationären und vollstationären Pflegediensten eröffnet auch merkliche Beschäftigungspotentiale. Diese gilt es durch entsprechende Rahmenbedingungen zu erschließen. Auch wenn es einen politischen Konsens für eine stärkere private Absicherung des Pflegerisikos geben sollte, wird der heute auf 1,7 % festgeschriebene Beitragssatz keinesfalls ausreichen. Erforderlich ist zudem eine Aufwertung der Pflegediensttätigkeiten, um qualifiziertes Personal für die entsprechenden Berufsfelder gewinnen zu können.Ageing population, Long-term care, potential of new employment, estimations for 2020

Cadomian and Variscan metamorphic events in the Léon Domain (Armorican Massif) resolved by trace element analysis in monazite and garnet

The question, whether crustal domains are allochthonous terranes or not is crucial for plate tectonic models of the Ibero-Armorican segment of the Variscan belt. The Léon Domain in the Armorican Massif appears as a displaced crustal block as it bears a resemblance to the South Armorican Domain of the internal Variscan belt (Le Corre et al. 1989). In the central part of the Léon, the amphibolite-facies Conquet- Penze Micaschist Unit (CPMU) overlies the high-grade Lesneven Gneiss Unit (LGU). At the base of the LGU, a high-pressure stage at 700°C/>13 kbar, recorded by garnet-clinopyroxene assemblages in eclogites was followed by a high-temperature event at 800°C/8 kbar with garnet and cordierite in aluminous paragneisses. Maximal temperatures in the upper parts of the LGU were 630°C/6 kbar. In the micaschists of the Conquet-Penze Unit, microstructures indicate a crystallization of garnet and then staurolite during the development of S1 and S2 foliations. Zoned garnet in assemblages with staurolite recorded prograde P–T paths from 490– 610°C at 5–8 kbar in the upper and at 6– 9 kbar in the lower parts of the CPMU. The foliation S2 was overprinted by shear bands with a top-to- SW directed normal sense of shear, corresponding to a dextral strike-slip movement (Balé & Brun 1986). A younger population of monazite with variable Y contents displays Variscan Th-U-Pb ages (EMP dating method) between 340 and 300Ma. In contrast, an older population of Cadomian monazite at 552–517Ma is uniformly rich in Y and was observed in samples with only few or even no garnet. As the 330–340Ma Saint Renan- Kersaint granite postdates the foliations S1 and S2 with peak metamorphic assemblages one can conclude that 340–300Ma Variscan monazites should postdate garnet crystallization.conferenc

Upregulation of miRNA hsa-miR-342-3p in experimental and idiopathic prion disease

The aim of our study was to analyze the differential expression of miRNAs in the brains of BSE-infected cynomolgus macaques as a model for Creutzfeldt-Jakob disease (CJD). MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression by mRNA targeting. Among other functions they contribute to neuronal development and survival. Recently, the lack of miRNA processing has been shown to promote neurodegeneration and deregulation of several miRNAs has been reported to be associated with Scrapie in mice. Therefore, we hypothesized that miRNAs are also regulated in response to human prion disease. We have applied miRNA-microarrays to identify deregulated miRNA candidates in brains of BSE-infected macaques. Shock-frozen brain sections of six BSE-infected and five non-infected macaques were used to validate regulated miRNA candidates by two independent qRT-PCR-based methods. Our study revealed significant upregulation of hsa-miR-342-3p and hsa-miR-494 in the brains of BSE-infected macaques compared to non-infected animals. In a pilot study we could show that hsa-miR-342-3p was also upregulated in brain samples of human type 1 and type 2 sporadic CJD. With respect to the reported regulation of this miRNA in Scrapie-infected mice, we propose that upregulation of hsa-miR-342-3p may be a general phenomenon in late stage prion disease and might be used as a novel marker for animal and human TSEs

Chromosome-wide identification of novel imprinted genes using microarrays and uniparental disomies

Genomic imprinting refers to a specialized form of epigenetic gene regulation whereby the expression of a given allele is dictated by parental origin. Defining the extent and distribution of imprinting across genomes will be crucial for understanding the roles played by imprinting in normal mammalian growth and development. Using mice carrying uniparental disomies or duplications, microarray screening and stringent bioinformatics, we have developed the first large-scale tissue-specific screen for imprinted gene detection. We quantify the stringency of our methodology and relate it to previous non-tissue-specific large-scale studies. We report the identification in mouse of four brain-specific novel paternally expressed transcripts and an additional three genes that show maternal expression in the placenta. The regions of conserved linkage in the human genome are associated with the Prader–Willi Syndrome (PWS) and Beckwith–Wiedemann Syndrome (BWS) where imprinting is known to be a contributing factor. We conclude that large-scale systematic analyses of this genre are necessary for the full impact of genomic imprinting on mammalian gene expression and phenotype to be elucidated

Study related factors associated with study engagement and student burnout among German university students

IntroductionStudent burnout has become a health concern in higher education systems. Its prevalence rates are high due to specific demands in this life situation. It leads not only to increased academic dropout rates but is also associated with negative health outcomes both physically and mentally. Its counterpart is study engagement, which is a positive, fulfilling, study-related attitude characterized by energy, dedication, and absorption. There has not been a systematical approach covering the demands directly posed by the academic environment itself. Additionally, academic subject fields apart from medicine and nursing sciences have been mostly neglected in regards to this research field. The aim of the study is therefore to identify contributing factors for both burnout and engagement within the academic environment in a sample of different subject fields at a German university.MethodsIn a cross-sectional study, a sample of 3,451 students of all academic subjects at a technical university in Germany has been analyzed using an online survey. Sociodemographic data, study engagement, student burnout, study satisfaction, academic workload, number of semesters and occupational liabilities have been analyzed. Binary logistic regression was used to determine the associations of burnout symptoms and study engagement.ResultsAlmost a third of the students showed frequent burnout symptoms, while 42.5% showed a high degree of study engagement with no differences in gender. Age was identified as a risk factor for frequent signs of cynicism (OR = 1.073). Study satisfaction (OR between 0.459 and 0.702), semester progression (OR = 0.959) and working moderately (OR between 0.605 and 0.637) was associated with fewer symptoms in different burnout-dimensions. Study satisfaction is positively associated with study engagement (OR = 2.676). Academic workload is positively related to both burnout (OR between 1.014 and 1.021) and study engagement (OR = 1.014).DiscussionA substantial number of students show frequent symptoms of burnout and the majority is not highly engaged. The included factors contribute to the model to various degrees and show that university-bound factors play a major role. Fostering a supportive environment is key for study engagement, health and well-being. The inclusion of further, individual factors should be a future concern in order to find and promote strategies for a healthy education system