gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins

Regulated intramembrane proteolysis (RIP) of the amyloid precursor protein (APP) produces amyloid beta-protein (Abeta), the probable causative agent of Alzheimer's disease (AD), and is therefore an important target for therapeutic intervention. However, there is a burgeoning consensus that gamma-secretase, one of the proteases that generates Abeta, is also critical for the signal transduction of APP and a growing list of other receptors. APP is a member of a gene family that includes two amyloid precursor-like proteins, APLP1 and APLP2. Although APP and the APLPs undergo similar proteolytic processing, there is little information about the role of their gamma-secretase-generated intracellular domains (ICDs). Here, we show that APLP1 and 2 undergo presenilin-dependent RIP similar to APP, resulting in the release of a approximately 6 kDa ICD for each protein. Each of the ICDs are degraded by an insulin degrading enzyme-like activity, but they can be stabilized by members of the FE65 family and translocate to the nucleus. Given that modulation of APP processing is a therapeutic target and that the APLPs are processed in a manner similar to APP, any strategy aimed at altering APP proteolysis will have to take into account possible effects on signaling by APLP 1 and 2.     

Isolation and characterization of microsatellites in Neogobius kessleri (Perciformes,Gobiidae) and cross‐species amplification within the family Gobiidae

Fourteen polymorphic microsatellites were isolated from Neogobius kessleri, a benthic fish of Ponto‐Caspian origin which has been recently introduced into the Middle and Upper Danube River. Number of alleles and heterozygosity per locus in a sample of 32 fish individuals ranged from two to four and from 0.13 to 0.75, respectively. These primers will be useful in determining the population structure of N. kessleri. In addition, successful cross‐amplification was obtained for four related species, N. melanostomus, N. fluviatilis, N. gymnotrachelus and Proterorhinus marmoratus. These microsatellite loci may be useful for the evaluation of the origin of non‐native goby populations.     

A mRNA landscape of bovine embryos after standard and MAPK-inhibited culture conditions: a comparative analysis

Background

Genes and signalling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analysed.

Results

Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE, the expression of NANOG, SOX2 and POU5F1 was increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was down-regulated.

Conclusion

The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent, epiblast-like state. The inability to culture ICM cells as stem cells in the presence of an inhibitor of MAPK activity together with the reported data indicates that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1448-x) contains supplementary material, which is available to authorized users.     

Juvenile hormone controls egg laying and fertility in Drosophila virilis during starvation

Degradation of juvenile hormone and reproductive function during starvation and experimental increase of the juvenile hormone titer were studied in wild type and mutant D. virilis females incapable to respond to heat stress by changes in juvenile hormone metabolism and fertility. After 24-hour starvation, the females of both lines were characterized by a decreased level of juvenile hormone degradation, 24-hour delay of egg laying, increased egg laying within 3 h after the termination of starvation, and decreased fertility within three days. Application of exogenous juvenile hormone also led to a decreased level of its degradation and 24-hour arrest of egg laying. Experimental increase of the juvenile hormone titer before the beginning of starvation led to a sharply increased fertility (number of laid eggs and number of progenies) within the first 24 h after the termination of starvation. The dynamics of juvenile hormone degradation and of fertility were similar after starvation and upon application of the exogenous hormone. The role of juvenile hormone in the control of egg maturation and laying under stress conditions has been discussed.     

Study of the genesis of pathological EEG patterns in tumor and traumatic lesions of the human brain

Computer-assisted superimposition of the equivalent dipole sources (EDSs) of the main pathological EEG patterns with the results of computer tomography and magnetic resonance imaging of the brain was performed for patients with organic CNS lesions. The greatest degree of structural determination was revealed for local and lateralized (in a traumatic injury) slow waves, whose EDSs mapped to the perifocal zone of the injury focus. The EDSs of epileptiform patterns could be located in the zone of damaged brain substance or in the intact hemisphere (when the limbic structures were damaged), reflecting the formation of secondary functional foci in the latter case. Bilateral paroxysmal patterns were more frequently determined by the functional state of the medial brain structures. The EDSs of pathological (diencephalic, hippocampal) activity were closely associated with the corresponding anatomical brain structures, although without a strict dependence on the degree of their morphological intactness.Translated from Fiziologiya Cheloveka, Vol. 31, No. 1, 2005, pp. 24–32.Original Russian Text Copyright © 2005 by Boldyreva, Sharova, Koptelov, Shchepetkov, Nikitin, Kornienko, Fadeeva.     

Preliminary evaluation of non-native rainbow trout (Oncorhynchus mykiss) impact on the Cederberg ghost frog (Heleophryne depressa) in South Africa’s Cape Fold Ecoregion

We evaluated the impact of non-native rainbow trout Oncorhynchus mykiss on a population of endemic Cedarberg ghost frog Heleophryne depressa in the upper Krom River (Olifants-Doring River Catchment, Cape Fold Ecoregion). We compared H. depressa abundance (using kick-sampling and underwater video analysis) and environmental conditions between sites above and below a waterfall that marks the upper distribution limit of O. mykiss. Heleophryne depressa abundance was significantly greater above the waterfall than that below it, and, because there was no significant difference in measured environmental variables, O. mykiss presence is identified as the most likely explanation for the observed decrease in H. depressa abundance.     

Distribution and conservation of mobile elements in the genus Drosophila

Essentially nothing is known of the origin, mode of transmission, and evolution of mobile elements within the genus Drosophila. To better understand the evolutionary history of these mobile elements, we examined the distribution and conservation of homologues to the P, I, gypsy, copia, and F elements in 34 Drosophila species from three subgenera. Probes specific for each element were prepared from D. melanogaster and hybridized to genomic DNA. Filters were washed under conditions of increasing stringency to estimate the similarity between D. melanogaster sequences and their homologues in other species. The I element homologues show the most limited distribution of all elements tested, being restricted to the melanogaster species group. The P elements are found in many members of the subgenus Sophophora but, with the notable exception of D. nasuta, are not found in the other two subgenera. Copia-, gypsy-, and F-element homologues are widespread in the genus, but their similarity to the D. melanogaster probe differs markedly between species. The distribution of copia and P elements and the conservation of the gypsy and P elements is inconsistent with a model that postulates a single ancient origin for each type of element followed by mating-dependent transmission. The data can be explained by horizontal transmission of mobile elements between reproductively isolated species.      

Morbidity study of acute respiratory diseases to assess the indications for ambulatory care at a student polyclinic

The methods of the retrospective epidemiological analysis of morbidity rate among students attending a specialized polyclinic for students have made it possible to establish the fact that acute respiratory diseases of non-influenza etiology are of the greatest socio-economic importance for students living under the conditions of a hostel. Such importance of these infections is linked with the autonomous character of the epidemic process due to the "mixing" factor, the intensive realization of the drop mechanism of infection transfer, and high morbidity risk in the absence of immunoprophylactic remedies. The results of this study indicate that the student body may be considered a group of primary necessity for prophylactic medical examination aimed at the early detection of the consequences of the past disease and at the organization of timely and effective treatment of young people.     

Temporal and spatial fluctuations of heavy metals in Opa Reservoir,Ile-Ife,Nigeria

The Opa Reservoir, established for water supply to the Obafemi Awolowo University community, over the years has received direct linkage to township drains as a result of the widening and dredging of its river channels. The current study aimed at documenting monthly heavy metal loads at its riverine, transition and lacustrine zones in 2012–2013. Most of the heavy metals, analysed using an atomic absorption spectrophotometer, occurred within wide ranges, with coefficients of variation ranging from 60% to 300%, although the differences in heavy metal loads between the different zones were statistically insignificant at both the surface and bottom levels. The overall order of dominance of the metals was Ni > Cu > Fe > Zn > Cd = Cr > Pb, with nickel concentration being very high throughout. Heavy metal total mean concentration was higher during the rainy season (1.889 mg l?1) than the dry season (1.503 mg l?1) irrespective of sampling sites, having highly significant seasonal differences (p < 0.001) in Ni, Cd, Fe and Cu concentrations. The mean concentrations of Zn (0.074 mg l?1), Fe (0.176 mg l?1), Cu (0.507 mg l?1) and Pb (0.004 mg l?1) were within the WHO acceptable limit. However, the recorded levels of toxic elements Cd (0.031 mg l?1) and Ni (0.905 mg l?1) pose potential health risk to water consumers.     

Trophic ecology and persistence of invasive silver carp Hypophthalmichthys molitrix in an oligotrophic South African impoundment

The alien invasive silver carp Hypophthalmichthys molitrix established a self-sustaining feral population in an oligotrophic impoundment, Flag Boshielo Dam, in South Africa. The ability of this population to persist in a dam with low algal biomass (median annual suspended chlorophyll a = 0.08 µg l^?1), and limited access to rivers considered large enough for successful spawning, has implications for their invasive potential in other systems. Stomach content and stable isotope analysis were used to assess the trophic ecology of H. molitrix, which was then compared with indigenous Mozambique tilapia Oreochromis mossambicus, on a seasonal basis during 2011. Hypophthalmichthys molitrix are generalist filter feeders, with a diet consisting primarily of sediment, vegetative detritus, dinoflagellates and diatoms. The dominance of sediments in their stomachs suggests occasional benthic scavenging. However, H. molitrix occupied a higher trophic level (TL = 2.8) than expected, suggesting that this population subsidised their diet with an unidentified dietary constituent, characterised by enriched nitrogen values. Although the stomach contents indicated dietary overlap between H. molitrix and O. mossambicus, stable isotopes revealed fine-scale resource partitioning, despite both species occupying the same trophic level. Nonetheless, the persistence of this feral H. molitrix population in an oligotrophic impoundment highlights their phenotypic plasticity.