576 research outputs found
Tetrachlorophthalimides as Organocatalytic Acceptors for Electron Donor-Acceptor Complex Photoactivation
Excitation of photoactive electron donor-acceptor (EDA) complexes is an effective way to generate radicals. Applications in a catalytic regime typically use catalytic donors. Herein, we report that readily available electron-poor tetrachlorophthalimides can act as effective organocatalytic acceptors to trigger the formation of EDA complexes with a variety of radical precursors not amenable to previous catalytic methods. Excitation with visible light generates carbon radicals under mild conditions. The versatility of this EDA complex catalytic platform allowed us to develop mechanistically distinct radical reactions, including in combination with a cobalt-based catalytic system. Quantum yield measurements established that a closed catalytic cycle is operational, which hints at the ability of tetrachlorophthalimides to readily turn over and govern each catalytic cycle
Human Arm Motion Tracking by Kinect Sensor Using Kalman Filter for Collaborative Robotics
The rising interest in collaborative robotics leads to research solutions in order to increase robot interaction with the environment. The development of methods that permit robots to recognize and track human motion is relevant for safety and collaboration matters. A large quantity of data can be measured in real time by Microsoft Kinect®, a well-known low-cost depth sensor, able to recognize human presence and to provide postural information by extrapolating a skeleton. However, the Kinect sensor tracks motion with relatively low accuracy and jerky behavior. For this reason, the effective use in industrial applications in which the measurement of arm velocity is required can be unsuitable. The present work proposes a filtering method that allows the measurement of more accurate velocity values of human arm, based on row data provided by the Kinect sensor. The estimation of arm motion is achieved by a Kalman filter based on a kinematic model and by the imposition of fixed lengths for the skeleton links detected by the sensor. The development of the method is supported by experimental tests. The achieved results suggest the practical applicability of the developed algorithms
Increased angiogenic factor secretion by decidual natural killer cells from pregnancies with high uterine artery resistance alters trophoblast function.
STUDY QUESTION
Are the concentrations of factors secreted by decidual natural killer (dNK) cells from pregnancies at high risk of poor spiral artery remodelling different to those secreted from pregnancies at low risk?
SUMMARY ANSWER
Expression levels of PLGF, sIL-2R, endostatin and angiogenin were significantly increased by dNK cells from high-risk pregnancies, and angiogenin and endostatin were found to alter trophoblast function.
WHAT IS KNOWN ALREADY
During early pregnancy, maternal uterine spiral arteries are remodelled from small diameter, low-flow, high-resistance vessels into larger diameter, higher flow vessels, with low-resistance. This change is essential for the developing fetus to obtain sufficient oxygen and nutrients. dNK cells have been implicated in this process.
STUDY DESIGN, SIZE, DURATION
dNK cells were isolated from first trimester terminations of pregnancies (obtained with local ethical approval) screened for normal- or high-resistance index, indicative of cases least (21%) likely to have developed pre-eclampsia had the pregnancy not been terminated (n = 18 each group). Secreted factors and the effects of these on the trophoblast cell line, SGHPL-4, were assessed in vitro.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A multiplex assay was used to assess dNK cell-secreted factors. SGHPL-4 cell functions were assessed using time-lapse microscopy, 3D invasion assays, endothelial-like tube formation ability and western blot analysis.
MAIN RESULTS AND THE ROLE OF CHANCE
The expression levels of PLGF (P < 0.01), sIL-2R (P < 0.01), endostatin (P < 0.05) and angiogenin (P < 0.05) were significantly increased by dNK cells from high-risk pregnancies. Endostatin significantly decreased SGHPL-4 invasion (P < 0.05), SGHPL-4 tube formation (P < 0.05) and SGHPL-4 Aktser473 phosphorylation (P < 0.05). Angiogenin significantly decreased SGHPL-4 invasion (P < 0.05), but increased SGHPL-4 tube formation (P < 0.01) and decreased SGHPL-4 Aktser473 phosphorylation (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION
The culture of dNK cells and protein concentrations in vitro may not fully represent the in vivo situation. Although SGHPL-4 cells are extravillous trophoblast derived, further studies would be needed to confirm the roles of angiogenin and endostatin in vivo.
WIDER IMPLICATIONS OF THE FINDINGS
The altered expression of secreted factors of dNK cells may contribute to pregnancy disorders associated with poor spiral artery remodelling.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Wellcome Trust (project reference 091550). R.F. was a recipient of a PhD studentship from the Division of Biomedical Sciences, St. George's, University of London. The authors have no conflict of interests
Assessment of Streptococcus pneumoniae pilus islet-1 prevalence in carried and transmitted isolates from mother–infant pairs on the Thailand–Burma border
AbstractStreptococcus pneumoniae pilus islet-1 (PI–1)-encoded pilus enhances in vitro adhesion to the respiratory epithelium and may contribute to pneumococcal nasopharyngeal colonization and transmission. The pilus subunits are regarded as potential protein vaccine candidates. In this study, we sought to determine PI–1 prevalence in carried pneumococcal isolates and explore its relationship with transmissibility or carriage duration. We studied 896 pneumococcal isolates collected during a longitudinal carriage study that included monthly nasopharyngeal swabbing of 234 infants and their mothers between the ages of 1 and 24 months. These were cultured according to the WHO pneumococcal carriage detection protocol. PI-1 PCR and genotyping by multilocus sequence typing were performed on isolates chosen according to specific carriage and transmission definitions. Overall, 35.2% of the isolates were PI-1-positive, but PI-1 presence was restricted to ten of the 34 serotypes studied and was most frequently associated with serotypes 19F and 23F; 47.5% of transmitted and 43.3% of non-transmitted isolates were PI-1-positive (OR 1.2; 95% CI 0.8-1.7; p 0.4). The duration of first-ever infant pneumococcal carriage was significantly longer with PI-1-positive organisms, but this difference was not significant at the individual serotype level. In conclusion, PI-1 is commonly found in pneumococcal carriage isolates, but does not appear to be associated with pneumococcal transmissibility or carriage duration
Analysis of the muscarinic receptor subtype mediating inhibition of the neurogenic contractions in rabbit isolated vas deferens by a series of polymethylene tetra-amines
1. The pharmacological characteristics of the presynaptic muscarinic receptor subtype, which mediates inhibition of the neurogenic contractions in the prostatic portion of rabbit vas deferens, have been investigated by using a series of polymethylene tetra-amines, which were selected for their ability to differentiate among muscarinic receptor subtypes. 2. It was found that all tetra-amines antagonized McN-A-343-induced inhibition in electrically stimulated rabbit vas deferens in a competitive manner and with affinity values (pA2) ranging between 6.27 ± 0.09 (spirotramine) and 8.51 ± 0.02 (AM170). 3. Competition radioligand binding studies, using native muscarinic receptors from rat tissues (M1, cortex; M2, heart; M3, submaxillary gland) or from NG 108-15 cells (M4) and human cloned muscarinic M1-M4 receptors expressed in CHO-K1 cells, were undertaken with the same tetraamines employed in functional assays. All antagonists indicated a one-site fit. 4. The affinity estimates (pKi) of tetra-amines calculated in binding assays using native receptors were similar to those obtained using cloned receptors. Among these compounds some displayed selectivity between muscarinic receptor subtypes, indicating that they may be valuable tools in receptor characterization. Spirotramine was selective for M1 receptors versus all other subtypes (pKi native: M1, 7.32 ± 0.10; M2, 6.50 ± 0.11; M3, 6.02 ± 0.13; M4, 6.28 ± 0.16; pKi cloned: M1, 7.69 ± 0.08; M2, 6.22 ± 0.14; M3, 6.11 ± 0.16; 6.35 ± 0.11) whereas CC8 is highly selective for M2 receptors versus the other subtypes (pKi native: M1 7.50 ± 0.04; M2, 9.01 ± 0.12; M3, 6.70 ± 0.08; M4, 7.56 ± 0.04; pKi cloned: M1, 7.90 ± 0.20; M2, 9.04 ± 0.08; M3, 6.40 ± 0.07; M4, 7.40 ± 0.04). Furthermore, particularly relevant for this investigation were tetra-amines dipitramine and AM172 for their ability to significantly differentiate M1 and M4 receptors. 5. The apparent affinity values (pA2) obtained for tetra-amines in functional studies using the prostatic portion of rabbit vas deferens correlated most closely with the values (pKi) obtained at either native or human recombinant muscarinic M4 receptors. This supports the view that the muscarinic receptor mediating inhibition of neurogenic contractions of rabbit vas deferens may not belong to the M1 type but rather appears to be of the M4 subtype
Glucagon-Like Peptide-1 Counteracts Oxidative Stress-Dependent Apoptosis of Human Cardiac Progenitor Cells by Inhibiting the Activation of the c-Jun N-terminal Protein Kinase Signaling Pathway
AbstractIncreased apoptosis of cardiac progenitor cells (CPCs) has been proposed as a mechanism of myocardial damage and dysfunction. Glucagon-like peptide-1 (GLP-1) has been shown to improve heart recovery and function after ischemia and to promote cell survival. The protective effects of GLP-1 on oxidative stress-induced apoptosis were investigated in human CPCs isolated from human heart biopsies. Mesenchymal-type cells were isolated from human heart biopsies, exhibited the marker profile of CPCs, differentiated toward the myocardiocyte, adipocyte, chondrocyte, and osteocyte lineages under appropriate culture conditions, and expressed functional GLP-1 receptors. CPCs were incubated with GLP-1 with or without hydrogen peroxide (H2O2). Phospho- and total proteins were detected by immunoblotting and immunofluorescence analysis. Gene expression was evaluated by quantitative RT-PCR. The role of the canonical GLP-1 receptor was assessed by using the receptor antagonist exendin(9–39) and receptor-specific silencer small interfering RNAs. Cell apoptosis was quantified by an ELISA assay and by flow cytometry-detected Annexin V. Exposure of CPCs to H2O2 induced a 2-fold increase in cell apoptosis, mediated by activation of the c-Jun N-terminal protein kinase (JNK) pathway. Preincubation of CPCs with GLP-1 avoided H2O2-triggered JNK phosphorylation and nuclear localization, and protected CPCs from apoptosis. The GLP-1 effects were markedly reduced by coincubation with the receptor antagonist exendin(9–39), small interfering RNA-mediated silencing of the GLP-1 receptor, and pretreatment with the protein kinase A inhibitor H89. In conclusion, activation of GLP-1 receptors prevents oxidative stress-mediated apoptosis in human CPCs by interfering with JNK activation and may represent an important mechanism for the cardioprotective effects of GLP-1
Linearly π-conjugated oligothiophenes as simple metal-free sensitizers for dye-sensitized solar cells
Four linear oligothiophenes containing 4, 5 and 7 thiophene rings substituted by a variable number of octyl chains attached at the beta-position of some of the thiophene rings and possessing a terminal cyanoacrylic acid anchoring group have been synthesized. Results of UV-Vis absorption spectroscopy and cyclic voltammetry show that as expected the extension of the π-conjugated system leads to a decrease of the optical gap with an increase of the HOMO level. The four compounds have been evaluated as sensitizers in dye-sensitized solar cells (DSSCs) using a iodide/triiodide liquid electrolyte and the results are discussed in terms of the structure–property relationship with regard to the extension of the conjugated system and the number and position of the octyl side chains using N719 as the reference system. A power conversion efficiency of ~7.30% corresponding to 90% of the value given by N719 under identical conditions has been obtained with one of the heptamers
Targeting the leukemic stem cell: the Holy Grail of leukemia therapy
Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological
properties have been elucidated, including their distinct replicative properties, cell surface
phenotypes, their increased resistance to chemo-therapeutic drugs and the involvement of growthpromoting
chromosomal translocations. Of particular importance is their ability to transfer
malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice.
Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at
the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we
will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In
addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include
the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with smallmolecule
inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with
effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a
variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding
cassette transporter proteins are being extensively studied, as they are important in drug resistance
â a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field,
it is a highly promising battleground that may reveal the Holy Grail of cancer therapy. Originally published Leukemia, Vol. 23, No. 1, Jan 200
- …