The very many faces of presenilins and the γ-secretase complex

Presenilin is a central, catalytic component of the γ-secretase complex which conducts intramembrane cleavage of various protein substrates. Although identified and mainly studied through its role in the development of amyloid plaques in Alzheimer disease, γ-secretase has many other important functions. The complex seems to be evolutionary conserved throughout the Metazoa, but recent findings in plants and Dictyostelium discoideum as well as in archeons suggest that its evolution and functions might be much more diversified than previously expected. In this review, a selective survey of the multitude of functions of presenilins and the γ-secretase complex is presented. Following a brief overview of γ-secretase structure, assembly and maturation, three functional aspects are analyzed: (1) the role of γ-secretase in autophagy and phagocytosis; (2) involvement of the complex in signaling related to endocytosis; and (3) control of calcium fluxes by presenilins

TGF superfamily and MMP2, MMP9, TIMP1 genes expression in the endometrium of women with impaired reproduction.

During the putative "implantation window", a period of maximal endometrial receptivity that spans 7-9 days after ovulation, a series of changes on the structural and molecular level occur that render the endometrium susceptible to implantation for the human embryo. Many members of the TGFbetas are expressed by human endometrium at different stages of menstrual cycle. Also studies regarding the MMP2 gene expression and activity of MMP2 in the implantation window have shown a higher expression and activity of MMP2 in women with impaired fertility. We have examined by RT-PCR the expression of TGFbeta2 and MMP2, MMP9 and TIMP1 in 28 patients with idiopathic infertility, 16 patients with unexplained recurrent miscarriage and 16 control women were enrolled in this study. Seven to nine days after ovulation endometrial biopsy by Pipelle or hysteroscopy was performed to assess the expression of TGFbeta2 , MMP2, MMP9 and TIMP1. We found that in endometria from women with idiopathic infertility TGFbeta2 expression was 2.8 fold higher than in endometria from control group and 2.1 fold higher in endometrial samples from women with unexplained recurrent miscarriage compared to the control group. The MMP2, MMP9 and TIMP1 expression in endometrial samples revealed no significant differences between the study groups and control group. There was a statistically significant negative correlation between TGFbeta2 and MMP9 expression in endometria from women in control group. The present investigations suggest that dysregulated TGFbeta2, MMP2, MMP9 and TIMP1 expression are associated with infertility and early pregnancy loss. However the exact mechanism of how overexpression of endometrial TGFbetaand MMPs interferes with implantation may be more complex

Complement inhibitory proteins expression in placentas of thrombophilic women

Factors controlling complement activation appear to exert a protective effect on pregnancy. This isparticularly important in women with thrombophilia. The aim of this study was to determine the transcript andprotein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in theplacentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry stainingof inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Westernblot. We observed a higher transcript (p < 0.05) and protein (p < 0.001) levels of DAF and MCP in the placentasof thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblastmembranes, but the assessment of staining in all groups did not differ. The observed higher expression level ofproteins that control activation of complement control proteins is only seemingly contradictory to the changesobserved for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changesassociated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas isan effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.Factors controlling complement activation appear to exert a protective effect on pregnancy. This isparticularly important in women with thrombophilia. The aim of this study was to determine the transcript andprotein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in theplacentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry stainingof inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Westernblot. We observed a higher transcript (p < 0.05) and protein (p < 0.001) levels of DAF and MCP in the placentasof thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblastmembranes, but the assessment of staining in all groups did not differ. The observed higher expression level ofproteins that control activation of complement control proteins is only seemingly contradictory to the changesobserved for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changesassociated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas isan effect of proinflammatory cytokines, which accompanies thrombophilia, is probable

Complications rate and pregnancy outcome in women who underwent early and mid trimester amniocentesis

Objectives: Evaluation of the complications rate, as well as pregnancy outcome, in women who underwent early and mid-trimester amniocentesis. Material and Methods: The study was conducted among 454 patients, including 162 women after the procedure performed before 15 gestational week and 292 patients who underwent classic amniocentesis. All patients were hospitalized in Division of Reproduction of University of Medical Sciences in Poznan between 1999 and 2005. The analysis, based both on clinical observations and questionnaire sent to patients, concerned especially the frequency of following complications: miscarriage, premature rupture of membranes and club foot in newborns. Results: Total pregnancy loss rate due to amniocentesis amounted to 1,2% and 0,3% in early and mid-trimester amniocentesis, respectively, not reaching statistical significance. The frequency of club foot in newborns of mothers who underwent amniocentesis did not differ significantly between the groups, although it was four times higher in early amniocentesis group than in patients in whom mid-trimester amniocentesis had been performed. Conclusions: The safety of early amniocentesis is comparable with safety of mid-trimester amniocentesis

Results of cytogenetic examinations in fetuses with increased nuchal translucency

Objectives: The analysis of karyotypes in fetuses with increased nuchal translucency (NT) and the assessment of correlations between NT thickness, presence of other fetal anomalies and the result of karyotype. Material and methods: The study was conducted among 121 singleton fetuses with increased NT thickness. In all fetuses the karyotype was assessed following amniocentesis. The results of karyotypes were analyzed in the whole studied group, as well as in specific subgroups of patients according to NT value: 1) increased NT, but not exceeding 3,5mm, 2) 3,5-4,4mm, 3) 4,5-5,4mm, 4) 5,5-6,4mm, and 5) ≥6,5mm. Results: Abnormal results of the karyotype were found in 41 out of 121 fetuses (33,9%). The most common aberration was trisomy 21. A percentage of abnormal fetal karyotypes increased with the degree of NT thickening and was 15,9% in fetuses with increased NT which did not exceed 3,5 mm and 54,5% in fetuses with NT ≥6,5 mm. The abnormal karyotype was diagnosed in 54,5% of fetuses with increased NT and other abnormalities found in ultrasound. Conclusions: 1. Around 65% of the fetuses with an increased NT have normal karyotype. 2. A percentage of abnormal karyotypes in fetuses increases with the degree of NT thickening. 3. An ultrasound finding of an increased NT and other abnormalities in a fetus is associated with higher risk of chromosomal aberrations in comparison to cases when there is only an increased nuchal translucency

Histologic changes in placenta and chorion of women with antiphospholipid syndrome and inherited thrombophilia

Summary Background: The aim of the study was a histologic evaluation of placentas and chorions from pregnancies complicated by antiphospholipid syndrome (APS) and inherited thrombophilia in women treated with anticoagulants and in a group of women without the anticoagulant treatment. Material: 24 placentas from 18 patients with acquired and inherited thrombophilia and 23 chorions from 19 miscarriages in women with the same diagnosis were included in the study. There were 33 chorions from miscarriages from healthy women and 25 placentas from uneventful pregnancies in the control group. Biopsies from placentas and chorions were stained with eosin and hematoxylin and evaluated for the presence of villous thrombosis, fibrin deposits, intraplacental hematomas, thrombosis in fetal circulation and other histological findings. Results: In the placentas from pregnancies complicated with APS and inherited thrombophilia, the presence of fibrin deposits in the basal and villous plate, stasis in the fetal circulation and thrombosis in the villous plate and villous vessels, were statistically more frequent (

Characterization of the γ-secretase subunit interactome in Arabidopsis thaliana

Gamma secretase is a multi-subunit complex with aspartic intramembrane protease activity that is involved in the pathogenesis of Alzheimer's disease in humans. In Arabidopsis thaliana, -secretase subunits are localized to endomembrane system compartments and interact with each other in a similar manner to their human counterparts. Here, we identified the protein partners of two plant -secretase subunits, presenilin 2 and PEN-2, by tandem affinity purification and co-immunoprecipitation, respectively. Integral membrane proteins were found to interact with presenilin 2, whereas secreted proteins were found to interact with PEN-2. Microscopy screening revealed that the reticulon family protein, RTNLB1, and two single transmembrane domain proteins, TIR-X and the phytolongin PHYL1.1, interact with presenilins. Finally, we show that RTNLB1 interacts with TIR-X. These results represent a step toward elucidating the functions of -secretase subunits in plant cells

Combined use of companion planting and PGPR for the assisted phytoextraction of trace metals (Zn, Pb, Cd)

Biomass production and metal accumulation in plant tissue (bioconcentration) are two critical factors limiting the phytoextraction rate.Metal translocation to aboveground organs should be accounted for as the third most important factor, as harvesting of the plant roots is usually economically disadvantageous. These three parameters could be potentially increased with the use of companion planting, a well-known agricultural technique, and inoculation with plant growth–promoting bacteria (PGPB). The aim of the study was to determine whether intercropping and inoculation with endophytic PGPB (Burkholderia phytofirmans PsJNT) can increase the efficiency of phytoextraction of Zn, Pb, and Cd. The study was conducted on Brassica juncea (L.) Czern. “Małopolska” grown in a monoculture or co-planted with Zea mays L. “Codimon” and Medicago sativa L. “Sanditi.” Results show that companion planting and inoculation with rhizobacteria can increase the efficiency of metal phytoextraction, mainly by increasing the yield of dry biomass and the survival rate of plants grown on contaminated soil.We have shown that the simultaneous planting of B. juncea with M. sativa and inoculation with PGPB were the most efficient variants of assisted phytoextraction reaching a recovery of 95% Zn, 90% Cd, and on average about 160% Pb compared with control B. juncea plants grown in monoculture

Flora robotica -- An Architectural System Combining Living Natural Plants and Distributed Robots

Key to our project flora robotica is the idea of creating a bio-hybrid system of tightly coupled natural plants and distributed robots to grow architectural artifacts and spaces. Our motivation with this ground research project is to lay a principled foundation towards the design and implementation of living architectural systems that provide functionalities beyond those of orthodox building practice, such as self-repair, material accumulation and self-organization. Plants and robots work together to create a living organism that is inhabited by human beings. User-defined design objectives help to steer the directional growth of the plants, but also the system's interactions with its inhabitants determine locations where growth is prohibited or desired (e.g., partitions, windows, occupiable space). We report our plant species selection process and aspects of living architecture. A leitmotif of our project is the rich concept of braiding: braids are produced by robots from continuous material and serve as both scaffolds and initial architectural artifacts before plants take over and grow the desired architecture. We use light and hormones as attraction stimuli and far-red light as repelling stimulus to influence the plants. Applied sensors range from simple proximity sensing to detect the presence of plants to sophisticated sensing technology, such as electrophysiology and measurements of sap flow. We conclude by discussing our anticipated final demonstrator that integrates key features of flora robotica, such as the continuous growth process of architectural artifacts and self-repair of living architecture.Comment: 16 pages, 12 figure