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Adhesive and degradative properties of human placental cytotrophoblast cells in vitro.
Human fetal development depends on the embryo rapidly gaining access to the maternal circulation. The trophoblast cells that form the fetal portion of the human placenta have solved this problem by transiently exhibiting certain tumor-like properties. Thus, during early pregnancy fetal cytotrophoblast cells invade the uterus and its arterial network. This process peaks during the twelfth week of pregnancy and declines rapidly thereafter, suggesting that the highly specialized, invasive behavior of the cytotrophoblast cells is closely regulated. Since little is known about the actual mechanisms involved, we developed an isolation procedure for cytotrophoblasts from placentas of different gestational ages to study their adhesive and invasive properties in vitro. Cytotrophoblasts isolated from first, second, and third trimester human placentas were plated on the basement membrane-like extracellular matrix produced by the PF HR9 teratocarcinoma cell line. Cells from all trimesters expressed the calcium-dependent cell adhesion molecule cell-CAM 120/80 (E-cadherin) which, in the placenta, is specific for cytotrophoblasts. However, only the first trimester cytotrophoblast cells degraded the matrices on which they were cultured, leaving large gaps in the basement membrane substrates and releasing low molecular mass 3H-labeled matrix components into the medium. No similar degradative activity was observed when second or third trimester cytotrophoblast cells, first trimester human placental fibroblasts, or the human choriocarcinoma cell lines BeWo and JAR were cultured on radiolabeled matrices. To begin to understand the biochemical basis of this degradative behavior, the substrate gel technique was used to analyze the cell-associated and secreted proteinase activities expressed by early, mid, and late gestation cytotrophoblasts. Several gelatin-degrading proteinases were uniquely expressed by early gestation, invasive cytotrophoblasts, and all these activities could be abolished by inhibitors of metalloproteinases. By early second trimester, the time when cytotrophoblast invasion rapidly diminishes in vivo, the proteinase pattern of the cytotrophoblasts was identical to that of term, noninvasive cells. These results are the first evidence suggesting that specialized, temporally regulated metalloproteinases are involved in trophoblast invasion of the uterus. Since the cytotrophoblasts from first trimester and later gestation placentas maintain for several days the temporally regulated degradative behavior displayed in vivo, the short-term cytotrophoblast outgrowth culture system described here should be useful in studying some of the early events in human place
Structural Simplification of Bedaquiline: the Discovery of 3-(4-(N,N-dimethylaminomethyl)phenyl)quinoline Derived Antitubercular Lead Compounds
Bedaquiline (BDQ) is a novel and highly potent last-line antituberculosis drug that was approved by the US FDA in 2013. Owing to its stereo-structural complexity, chemical synthesis and compound optimization are rather difficult and expensive. This study describes the structural simplification of bedaquiline while preserving antitubercular activity. The compound's structure was split into fragments and reassembled in various combinations while replacing the two chiral carbon atoms with an achiral linkage instead. Four series of analogues were designed; these candidates retained their potent antitubercular activity at sub-microgram per mL concentrations against both sensitive and multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Six out of the top nine MIC-ranked candidates were found to inhibit mycobacterial ATP synthesis activity with IC50 values between 20 and 40 μm, one had IC50>66 μm, and two showed no inhibition, despite their antitubercular activity. These results provide a basis for the development of chemically less complex, lower-cost bedaquiline derivatives and describe the identification of two derivatives with antitubercular activity against non-ATP synthase related targets
Comparative transcriptome analyses of adzuki bean weevil (<i>Callosobruchus chinensis</i>) response to hypoxia and hypoxia/hypercapnia
Stored product insects show high adaption to hypoxia and hypercapnia, but the underlying mechanism is still unclear. Herein, a comparative transcriptome on 4(th) adzuki bean weevil (Callosobruchus chinensis) instar larvae was studied to clarify the response mechanisms to hypoxia (HA) and hypoxia/hypercapnia (HHA) using NextSeq500 RNA-Seq. Transcript profiling showed a significant difference in HA or HHA exposure both quantitatively and qualitatively. Compared with control, 631 and 253 genes were significantly changed in HHA and HA, respectively. Comparing HHA with HA, 1135 differentially expressed genes (DEGs) were identified. The addition of hypercapnia made a complex alteration on the hypoxia response of bean weevil transcriptome, carbohydrate, energy, lipid and amino acid metabolism were the most highly enriched pathways for genes significantly changed. In addition, some biological processes that were not significantly enriched but important were also discussed, such as immune system and signal transduction. Most of the DEGs related to metabolism both in HHA and HA were up-regulated, while the DEGs related to the immune system, stress response or signal transduction were significantly down-regulated or suppressed. This research reveals a comparatively full-scale result in adzuki bean weevil hypoxia and hypoxia/hypercapnia tolerance mechanism at transcription level, which might provide new insights into the genomic research of this species
Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films
Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B)
and phosphorous (P) ions. Different samples, prepared by varying the ion
dose in the range to 5 x and ion energy in the range
150-350 keV, were investigated by the Raman spectroscopy, photoluminescence
(PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman
results from dose dependent B implanted samples show red-shifted and
asymmetrically broadened Raman line-shape for B dose greater than
ions cm. The asymmetry and red shift in the Raman line-shape is
explained in terms of quantum confinement of phonons in silicon nanostructures
formed as a result of ion implantation. PL spectra shows size dependent visible
luminescence at 1.9 eV at room temperature, which confirms the presence
of silicon nanostructures. Raman studies on P implanted samples were also
done as a function of ion energy. The Raman results show an amorphous top SOS
surface for sample implanted with 150 keV P ions of dose 5 x ions
cm. The nanostructures are formed when the P energy is increased to
350 keV by keeping the ion dose fixed. The GAXRD results show consistency with
the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in
SILICON(SPRINGER
LHC Searches for Non-Chiral Weakly Charged Multiplets
Because the TeV-scale to be probed at the Large Hadron Collider should shed
light on the naturalness, hierarchy, and dark matter problems, most searches to
date have focused on new physics signatures motivated by possible solutions to
these puzzles. In this paper, we consider some candidates for new states that
although not well-motivated from this standpoint are obvious possibilities that
current search strategies would miss. In particular we consider vector
representations of fermions in multiplets of with a lightest neutral
state. Standard search strategies would fail to find such particles because of
the expected small one-loop-level splitting between charged and neutral states.Comment: 16 pages, 9 figure
Resonances in and
A partial wave analysis is presented of and
from a sample of 58M events in the BES II detector. The
is observed clearly in both sets of data, and parameters of the
Flatt\' e formula are determined accurately: (stat)
(syst) MeV/c, MeV/c, . The data also exhibit a strong peak
centred at MeV/c. It may be fitted with and a
dominant signal made from interfering with a smaller
component. There is evidence that the signal is
resonant, from interference with . There is also a state in with MeV/c and
MeV/c; spin 0 is preferred over spin 2. This state, , is
distinct from . The data contain a strong peak due to
. A shoulder on its upper side may be fitted by interference
between and .Comment: 17 pages, 6 figures, 1 table. Submitted to Phys. Lett.
Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0
Using 58 million J/psi and 14 million psi' decays obtained by the BESII
experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The
result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous
measurements.Comment: 9 pages, 8 figures, RevTex
Search for K_S K_L in psi'' decays
K_S K_L from psi'' decays is searched for using the psi'' data collected by
BESII at BEPC, the upper limit of the branching fraction is determined to be
B(psi''--> K_S K_L) < 2.1\times 10^{-4} at 90% C. L. The measurement is
compared with the prediction of the S- and D-wave mixing model of the
charmonia, based on the measurements of the branching fractions of J/psi-->K_S
K_L and psi'-->K_S K_L.Comment: 5 pages, 1 figur
First observation of psi(2S)-->K_S K_L
The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data
collected with the Beijing Spectrometer (BESII) at the Beijing Electron
Positron Collider (BEPC); the branching ratio is determined to be
B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with
J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the
prediction of the perturbative QCD ``12%'' rule. The result, together with the
branching ratios of psi(2S) decays to other pseudoscalar meson pairs
(\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the
three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let
First Measurements of eta_c Decaying into K^+K^-2(pi^+pi^-) and 3(pi^+pi^-)
The decays of eta_c to K^+K^-2(pi^+pi^-) and 3(pi^+pi^-) are observed for the
first time using a sample of 5.8X10^7 J/\psi events collected by the BESII
detector. The product branching fractions are determined to be B(J/\psi-->gamma
eta_c)*B(eta_c-->K^+K^-pi^+pi^-pi^+pi^-)=(1.21+-0.32+-
0.23)X10^{-4}, and (J/\psi-->gamma eta_c)*
B(eta_c-->pi^+pi^-pi^+pi^-pi^+pi^-)= (2.59+-0.32+-0.48)X10^{-4}. The upper
limit for eta_c-->phi pi^+pi^-pi^+pi^- is also obtained as B(J/\psi-->gamma
eta_c)*B(eta_c--> phi pi^+pi^-pi^+pi^-)< 6.03 X10^{-5} at the 90% confidence
level.Comment: 11 pages, 4 figure
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