The absence of fetal nasal bones in ultrasound examination between 11 + 0 and 13 + 6 weeks of gestation versus the occurrence of trisomies 21, 18, and 13

Objectives: One part of the ultrasound examination of fetuses in the first trimester of gestation is visualization of the nasal bones. Numerous studies have demonstrated a correlation between the absence of nasal bones and abnormal fetal karyotype. Aim: To assess the utility of ultrasound visualization of nasal bones during the first trimester of pregnancy as a marker of the most common chromosomal trisomies. Material and methods: Ultrasound visualization of nasal bones was carried out in 941 fetuses from a high-risk group between 11 + 0 and 13 + 6 weeks of gestation. Amniocentesis was performed to determine karyotype in all 941 cases. Results: Normal fetal karyotype was observed in 847 cases, trisomy 21 in 45 cases, trisomy 18 in 16 cases and trisomy 13 in 10 cases. Other abnormal karyotypes were detected in the remaining 23 cases. The absence of nasal bones demonstrated 27% sensitivity, 97% specificity and a positive predictive value of 35% as an indicator of trisomy 21 in the study group, and 12% sensitivity, 97% specificity and 12% positive predictive value for trisomies 18 and 13. Conclusions: The absence of nasal bones in ultrasound examination in the first trimester of pregnancy is characterized by low sensitivity and high specificity as a marker of the most common trisomies. Visualization of fetal nasal bone is a poor marker of aneuploidy and should not be taken into account in risk calculation algorithms

Laser-driven plasma waves in capillary tubes

The excitation of plasma waves over a length of up to 8 centimeters is, for the first time, demon- strated using laser guiding of intense laser pulses through hydrogen filled glass capillary tubes. The plasma waves are diagnosed by spectral analysis of the transmitted laser radiation. The dependence of the spectral redshift, measured as a function of filling pressure, capillary tube length and incident laser energy, is in excellent agreement with simulation results. The longitudinal accelerating field inferred from the simulations is in the range 1 -10 GV/m

Familial Alzheimer's Disease Lymphocytes Respond Differently Than Sporadic Cells to Oxidative Stress: Upregulated p53-p21 Signaling Linked with Presenilin 1 Mutants

Familial (FAD) and sporadic (SAD) Alzheimer's disease do not share all pathomechanisms, but knowledge on their molecular differences is limited. We previously reported that cell cycle control distinguishes lymphocytes from SAD and FAD patients. Significant differences were found in p21 levels of SAD compared to FAD lymphocytes. Since p21 can also regulate apoptosis, the aim of this study was to compare the response of FAD and SAD lymphocytes to oxidative stress like 2-deoxy-D-ribose (2dRib) treatment and to investigate the role of p21 levels in this response. We report that FAD cells bearing seven different PS1 mutations are more resistant to 2dRib-induced cell death than control or SAD cells: FAD cells showed a lower apoptosis rate and a lower depolarization of the mitochondrial membrane. Despite that basal p21 cellular content was lower in FAD than in SAD cells, in response to 2dRib, p21 mRNA and protein levels significantly increased in FAD cells. Moreover, we found a higher cytosolic accumulation of p21 in FAD cells. The transcriptional activation of p21 was shown to be dependent on p53, as it can be blocked by PFT-α, and correlated with the increased phosphorylation of p53 at Serine 15. Our results suggest that in FAD lymphocytes, the p53-mediated increase in p21 transcription, together with a shift in the nucleocytoplasmic localization of p21, confers a survival advantage against 2dRib-induced apoptosis. This compensatory mechanism is absent in SAD cells. Thus, therapeutic and diagnostic designs should take into account possible differential apoptotic responses in SAD versus FAD cells

Study of electron acceleration and X-ray radiation as a function of plasma density in capillary-guided laser wakefield accelerators

Laser wakefield electron acceleration in the blow-out regime and the associated betatron X-rayradiation were investigated experimentally as a function of the plasma density in a configuration where the laser is guided. Dielectric capillary tubes were employed to assist the laser keeping self-focused over a long distance by collecting the laser energy around its central focal spot. With a 40 fs, 16 TW pulsed laser, electron bunches with tens of pC charge were measured to be accelerated to an energy up to 300 MeV, accompanied by X-ray emission with a peak brightness of the order of 10 21 ph/s/mm 2 / mrad 2 /0.1%BW. Electron trapping and acceleration were studied using the emitted X-ray beamdistribution to map the acceleration process; the number of betatron oscillations performed by theelectrons was inferred from the correlation between measured X-ray fluence and beam charge. A studyof the stability of electron and X-ray generation suggests that the fluctuation of X-ray emission can be reduced by stabilizing the beam charge. The experimental results are in good agreement with 3D particle-in-cell (PIC) simulation.Fil: Ju, L.. Universite de Paris Xi; Francia;Fil: Svensson, K.. Lund University; SueciaFil: Ferrari, Hugo Emilio. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (centro Atómico Bariloche); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Döpp, A.. Universite de Paris Xi; Francia;Fil: Cassou, K.. Universite de Paris Xi; Francia;Fil: Genoud, G.. Lund University; Suecia;Fil: Wojda, F.. Lund University; Suecia;Fil: Burza, M.. Lund University; Suecia;Fil: Persson, A.. Lund University; Suecia;Fil: Lundh, O.. Lund University; Suecia;Fil: Wahlström, C. G.. Lund University; Suecia;Fil: Cros, B.. Universite de Paris Xi; Francia

Exploring the Bone Proteome to Help Explain Altered Bone Remodeling and Preservation of Bone Architecture and Strength in Hibernating Marmots

Periods of physical inactivity increase bone resorption and cause bone loss and increased fracture risk. However, hibernating bears, marmots, and woodchucks maintain bone structure and strength, despite being physically inactive for prolonged periods annually. We tested the hypothesis that bone turnover rates would decrease and bone structural and mechanical properties would be preserved in hibernating marmots (Marmota flaviventris). Femurs and tibias were collected from marmots during hibernation and in the summer following hibernation. Bone remodeling was significantly altered in cortical and trabecular bone during hibernation with suppressed formation and no change in resorption, unlike the increased bone resorption that occurs during disuse in humans and other animals. Trabecular bone architecture and cortical bone geometrical and mechanical properties were not different between hibernating and active marmots, but bone marrow adiposity was significantly greater in hibernators. Of the 506 proteins identified in marmot bone, 40 were significantly different in abundance between active and hibernating marmots. Monoaglycerol lipase, which plays an important role in fatty acid metabolism and the endocannabinoid system, was 98-fold higher in hibernating marmots compared with summer marmots and may play a role in regulating the changes in bone and fat metabolism that occur during hibernation

Controlling the spectrum of x-rays generated in a laser-plasma accelerator by tailoring the laser wavefront

By tailoring the wavefront of the laser pulse used in a laser-wakefield accelerator, we show that the properties of the x-rays produced due to the electron beam's betatron oscillations in the plasma can be controlled. By creating a wavefront with coma, we find that the critical energy of the synchrotron-like x-ray spectrum can be significantly increased. The coma does not substantially change the energy of the electron beam, but does increase its divergence and produces an energy-dependent exit angle, indicating that changes in the x-ray spectrum are due to an increase in the electron beam's oscillation amplitude within the wakefield.Comment: 7 pages, 2 figures, submitted to Appl. Phys. Let

4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells

Chronic and acute myeloid leukemia evade immune system surveillance and induce immunosuppression by expanding proleukemic Foxp31 regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, leukemia relapse, and shorter survival. However, mechanisms that promote Tregs in myeloid leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers of effector proleukemic Tregs. Using mouse model of leukemia-like disease, we found that Rab27adependent secretion of leukemic EVs promoted leukemia engraftment, which was associated with higher abundance of activated, immunosuppressive Tregs. Leukemic EVs attenuated mTOR-S6 and activated STAT5 signaling, as well as evoked significant transcriptomic changes in Tregs. We further identified specific effector signature of Tregs promoted by leukemic EVs. Leukemic EVs-driven Tregs were characterized by elevated expression of effector/tumor Treg markers CD39, CCR8, CD30, TNFR2, CCR4, TIGIT, and IL21R and included 2 distinct effector Treg (eTreg) subsets: CD301CCR8hiTNFR2hi eTreg1 and CD391TIGIThi eTreg2. Finally, we showed that costimulatory ligand 4-1BBL/CD137L, shuttled by leukemic EVs, promoted suppressive activity and effector phenotype of Tregs by regulating expression of receptors such as CD30 and TNFR2. Collectively, our work highlights the role of leukemic extracellular vesicles in stimulation of immunosuppressive Tregs and leukemia growth. We postulate that targeting of Rab27a-dependent secretion of leukemic EVs may be a viable therapeutic approach in myeloid neoplasms

Thermosensitivity of the Saccharomyces cerevisiae gpp1gpp2 double deletion strain can be reduced by overexpression of genes involved in cell wall maintenance

A Saccharomyces cerevisiae strain in which the GPP1 and GPP2 genes, both encoding glycerol-3-phosphate phosphatase isoforms, are deleted, displays both osmo- and thermosensitive (ts) phenotypes. We isolated genes involved in cell wall maintenance as multicopy suppressors of the gpp1gpp2 ts phenotype. We found that the gpp1gpp2 strain is hypersensitive to cell wall stress such as treatment with β-1,3-glucanase containing cocktail Zymolyase and chitin-binding dye Calcofluor-white (CFW). Sensitivity to Zymolyase was rescued by overexpression of SSD1, while CFW sensitivity was rescued by SSD1, FLO8 and WSC3-genes isolated as multicopy suppressors of the gpp1gpp2 ts phenotype. Some of the isolated suppressor genes (SSD1, FLO8) also rescued the lytic phenotype of slt2 deletion strain. Additionally, the sensitivity to CFW was reduced when the cells were supplied with glycerol. Both growth on glycerol-based medium and overexpression of SSD1, FLO8 or WSC3 had additive suppressing effect on CFW sensitivity of the gpp1gpp2 mutant strain. We also confirmed that the internal glycerol level changed in cells exposed to cell wall perturbation. © 2007 Springer-Verlag

Carbon Monoxide Induced Erythroid Differentiation of K562 Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands

Growing evidence supports the role of erythroblastic islands (EI) as microenvironmental niches within bone marrow (BM), where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule - CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage