Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death.

Remodeling of the uterine spiral arteries during pregnancy transforms them from high to low resistance vessels that lack vasoconstrictive properties. This process is essential to meet the demand for increased blood flow imposed by the growing fetus. Loss of endothelial and smooth muscle cells (SMC) is evident in remodeled arteries but the mechanisms underlying this transformation remain unknown. This study investigated the hypothesis that fetal trophoblast invading from the placenta instigate remodeling by triggering cell death in vascular SMC. Specifically, a role for trophoblast-derived death inducing cytokine tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) was investigated. Expression of the activating TRAIL receptors R1 and R2 was detected by flow cytometry on human aortic SMC and by immunohistochemistry on spiral artery SMC. Recombinant human TRAIL induced human aortic SMC apoptosis, which was inhibited by antibodies against TRAIL-R1 or -R2. Perfusion of denuded spiral artery segments with recombinant human TRAIL also induced SMC apoptosis. Trophoblasts isolated from first trimester placenta expressed membrane-associated TRAIL and induced apoptosis of human aortic SMC; apoptosis was significantly inhibited by a recombinant human TRAIL-R1:Fc construct. Trophoblast within the first trimester placental bed also expressed TRAIL. These data show that: 1) TRAIL causes SMC death; 2) trophoblast produce the apoptotic cytokine TRAIL; and 3) trophoblast induce SMC apoptosis via a TRAIL-dependent mechanism. We conclude that TRAIL produced by trophoblast causes apoptosis of SMC and thus may contribute to SMC loss during spiral artery remodeling in pregnancy

Muscle fiber and motor unit behavior in the longest human skeletal muscle

The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers

Inhibitory, GABAergic nerve terminals decrease at sites of focal epilepsy.

Using an immunocytochemical method for the localization of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (GAD), we have observed GABAergic nerve terminals distributed throughout all layers of normal monkey sensorimotor cortex. These terminals displayed ultrastructural characteristics that suggested that they arose from aspinous and sparsely spinous stellate neurons. In monkeys (Macaca mulatta and M. fascicularis) made epileptic by cortical application of alumina gel, a highly significant numerical decrease of GAD-positive nerve terminals occurred at sites of seizure foci indicating a functional loss of GABAergic inhibitory synapses. A loss of such inhibition at seizure foci could lead to epileptic activity of cortical pyramidal neurons

The regional economic impact of more graduates in the labour market: a “micro-to-macro” analysis for Scotland

This paper explores the system-wide impact of graduates on the regional economy. Graduates enjoy a significant wage premium, often interpreted as reflecting their greater productivity relative to non-graduates. If this is so there is a clear and direct supply-side impact of HEI activities on regional economies. We use an HEI-disaggregated computable general equilibrium model of Scotland to estimate the impact of the growing proportion of graduates in the Scottish labour force that is implied by the current participation rate and demographic change, taking the graduate wage premium in Scotland as an indicator of productivity enhancement. While the detailed results vary with alternative assumptions about the extent to which wage premia reflect productivity, they do suggest that the long-term supply-side impacts of HEIs provide a significant boost to regional GDP. Furthermore, the results suggest that the supply-side impacts of HEIs are likely to be more important than the expenditure impacts that are the focus of most HEI impact studies

Safeguarding children in dentistry: 1. Child protection training, experience and practice of dental professionals with an interest in paediatric dentistry

* Few dental professionals with child protection training have experience of making referrals. * There is a wide gap in practice between recognising signs of child abuse and neglect and responding effectively. * This may indicate missed opportunities to save children from continuing abuse. * There is a need for improved child protection information, support and training for dental professionals. Abstract Following several highly publicised inquiries into the deaths of children from abuse and neglect, there has been much recent interest in the role and responsibility of all health professionals to protect children at risk of maltreatment. The findings of a postal questionnaire, sent in March 2005 to 789 dentists and dental care professionals with an interest in paediatric dentistry working in varied settings in the UK, are presented in a two-part report and discussed in the context of current multi-agency good practice in safeguarding and promoting the welfare of children. This first part explores reported child protection training, experience and practice. There was a significant gap between recognising signs of abuse and responding effectively: 67% of respondents had suspected abuse or neglect of a child patient at some time in their career but only 29% had ever made a child protection referral. The dental profession is alerted to the need to ensure necessary appropriate action to safeguard children is always taken when child abuse or neglect are suspected

Mononuclear phenolate diamine zinc hydride complexes and their Reactions with CO2

[Image: see text] The synthesis, characterization, and zinc coordination chemistry of the three proligands 2-tert-butyl-4-[tert-butyl (1)/methoxy (2)/nitro (3)]-6-{[(2′-dimethylaminoethyl)methylamino]methyl}phenol are described. Each of the ligands was reacted with diethylzinc to yield zinc ethyl complexes 4–6; these complexes were subsequently reacted with phenylsilanol to yield zinc siloxide complexes 7–9. Finally, the zinc siloxide complexes were reacted with phenylsilane to produce the three new zinc hydride complexes 10–12. The new complexes 4–12 have been fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The structures of the zinc hydride complexes have been probed using VT-NMR spectroscopy and X-ray diffraction experiments. These data indicate that the complexes exhibit mononuclear structures at 298 K, both in the solid state and in solution (d(8)-toluene). At 203 K, the NMR signals broaden, consistent with an equilibrium between the mononuclear and dinuclear bis(μ-hydrido) complexes. All three zinc hydride complexes react rapidly and quantitatively with carbon dioxide, at 298 K and 1 bar of pressure over 20 min, to form the new zinc formate complexes 13–15. The zinc formate complexes have been analyzed by NMR spectroscopy and VT-NMR studies, which reveal a temperature-dependent monomer–dimer equilibrium that is dominated by the mononuclear species at 298 K

Data mining in HIV-AIDS surveillance system: application to portuguese data

The Human Immunodeficiency Virus (HIV) is an infectious agent that attacks the immune system cells. Without a strong immune system, the body becomes very susceptible to serious life threatening opportunistic diseases. In spite of the great progresses on medication and prevention over the last years, HIV infection continues to be a major global public health issue, having claimed more than 36 million lives over the last 35 years since the recognition of the disease. Monitoring, through registries, of HIV-AIDS cases is vital to assess general health care needs and to support long-term health-policy control planning. Surveillance systems are therefore established in almost all developed countries. Typically, this is a complex system depending on several stakeholders, such as health care providers, the general population and laboratories, which challenges an efficient and effective reporting of diagnosed cases. One issue that often arises is the administrative delay in reports of diagnosed cases. This paper aims to identify the main factors influencing reporting delays of HIV-AIDS cases within the portuguese surveillance system. The used methodologies included multilayer artificial neural networks (MLP), naive bayesian classifiers (NB), support vector machines (SVM) and the k-nearest neighbor algorithm (KNN). The highest classification accuracy, precision and recall were obtained for MLP and the results suggested homogeneous administrative and clinical practices within the reporting process. Guidelines for reductions of the delays should therefore be developed nationwise and transversally to all stakeholders.- A. Rita Gaio was partially supported by CMUP (UID/MAT/00144/2013), which is funded by FCT (Portugal) with national (MEC) and European structural funds (FEDER), under the partnership agreement PT2020. Luis Paulo Reis was partially by the European Regional Development Fund through the programme COMPETE by FCT (Portugal) in the scope of the project PEst - UID/ CEC/00027/2015 Luis Paulo Reis and Brigida Monica Faria were partially funded by QVida+: Estimacao Continua de Qualidade de Vida para Auxilio Eficaz a Decisao Clinica, NORTE-01-0247-FEDER-003446, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement

Increased MicroRNA-34b and -34c Predominantly Expressed in Stromal Tissues Is Associated with Poor Prognosis in Human Colon Cancer

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Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip

Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics