Telomerase activity in gestational trophoblastic disease

Aims - To investigate the pattern of telomerase activity in hydatidiform mole as compared with normal placenta and choriocarcinoma, and to determine the prognostic significance of telomerase activity in hydatidiform mole. Methods - Telomerase activity in 35 cases of hydatidiform mole, 35 normal placentas, one choriocarcinoma sample, and two choriocarcinoma cell lines (JAR, JEG3) was determined using the sensitive polymerase chain reaction based telomeric repeat amplification protocol (TRAP) assay. Two cases of breast carcinoma and two cases of ovarian carcinoma were also included as positive controls in the telomerase assay. Results - Telomerase activity was detected in 11 of 30 early placentas (36.7%), one of five term placentas (20%), five of 27 hydatidiform moles which regressed spontaneously (18.5%), and six of eight hydatidiform moles which developed persistent trophoblastic disease (75%) (including three which developed metastases). Hydatidiform moles which subsequently developed persistent disease, especially those which metastasised, were more likely to express telomerase activity (p < 0.01). However, there was no significant difference in the frequency of telomerase activity between early placentas and hydatidiform mole. Strong telomerase activity was observed in choriocarcinoma tissue, choriocarcinoma cell lines, and ovarian and breast carcinomas. Conclusions - Telomerase activation occurs in hydatidiform mole with a similar incidence to early normal placentas. This supports the concept that hydatidiform mole is essentially an abnormal conceptus. There is an association between telomerase activation and the development of persistent trophoblastic disease. Further study is warrant to confirm the prognostic significance of telomerase activity in hydatidiform mole.published_or_final_versio

Lasing microbottles

Lasing of an optical microbottle resonator at predetermined resonant wavelengths is feasible via spatial engineering of the pump laser beam

The emergence of the 2013 H7N9 and related viruses in China

Promising Investigator ScholarshipPoster Session: News and Views from the H7N9 OutbreakBackground: The novel H7N9 influenza A virus first detected in March 2013 has caused more than 130 cases of human infection in China, resulting in 39 deaths. This virus is a reassortant of H7, N9 and H9N2 avian influenza viruses and carries some amino acids linked to mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully understood. Materials and Methods: Following the initial reports of H7N9 influenza infection in humans, field surveillance was conducted during 4th-18th April in Zhejiang, Shandong and Guangdong provinces. Pairs of oropharyngeal and cloacal samples from chickens and other poultry, together with faecal and water samples from live poultry markets (LPMs), farms and wetlands were collected for virus isolation and whole genomic sequencing. H7, N9, N7 and H9N2 archived isolates, obtained during previous influenza surveillance between 2000-2013 in southern China, were also sequenced and phylogenetically analyzed to pinpoint the genesis of the H7N9 and a related H7N7 virus. The infectivity and pathology of H7N9 and H7N7 viruses were tested in a ferret model. Results: Through a combination of active surveillance, screening of virus archives, and evolutionary analyses, we found that H7 viruses have independently transferred from domestic ducks to chickens in China on at least two occasions. Subsequently they reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related but previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at LPMs that appear to be the immediate source of human infections. In ferrets this virus caused a productive infection and pneumonia. Virus was shed via the nasal route and transmitted to physical contact and some airborne-exposed animals. Like the H7N9 virus, the H7N7 virus was also mainly isolated from chickens at LPMs and it could efficiently infect ferrets, be shed via the nasal and rectal routes, and cause severe pneumonia. Conclusions: These findings provide a clear picture showing how the current H7N9 human viruses emerged. Domestic ducks act as primary vectors to acquire and maintain diversified viruses from migratory birds, and facilitate different subtype combinations between H7 and N9 or N7 viruses and interspecies transmissions to chickens. After being introduced, the H7N9 or H7N7 viruses reassorted with enzootic H9N2 viruses and formed the current reassortant H7N9 or H7N7 viruses seen in chickens. This likely led to outbreaks in chickens, resulting in the rapid spread of the novel reassortant H7N9 virus through LPMs, which then became the source of human infections. Whether the H7N9 outbreak lineage will, or has, become enzootic in China needs further investigation. Our results also indicate that H7 viruses pose a broader threat than the current H7N9 virus. Continued prevalence of this family of H7 viruses in poultry could lead to further sporadic human infections, with an ongoing risk that the virus might acquire efficient human-to-human transmissibility.published_or_final_versio

Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta

Phase I-II clinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury

published_or_final_versionCreative Commons: Attribution 3.0 Hong Kong Licens

The breadth of primary care: a systematic literature review of its core dimensions

Background: Even though there is general agreement that primary care is the linchpin of effective health care delivery, to date no efforts have been made to systematically review the scientific evidence supporting this supposition. The aim of this study was to examine the breadth of primary care by identifying its core dimensions and to assess the evidence for their interrelations and their relevance to outcomes at (primary) health system level. Methods: A systematic review of the primary care literature was carried out, restricted to English language journals reporting original research or systematic reviews. Studies published between 2003 and July 2008 were searched in MEDLINE, Embase, Cochrane Library, CINAHL, King's Fund Database, IDEAS Database, and EconLit. Results: Eighty-five studies were identified. This review was able to provide insight in the complexity of primary care as a multidimensional system, by identifying ten core dimensions that constitute a primary care system. The structure of a primary care system consists of three dimensions: 1. governance; 2. economic conditions; and 3. workforce development. The primary care process is determined by four dimensions: 4. access; 5. continuity of care; 6. coordination of care; and 7. comprehensiveness of care. The outcome of a primary care system includes three dimensions: 8. quality of care; 9. efficiency care; and 10. equity in health. There is a considerable evidence base showing that primary care contributes through its dimensions to overall health system performance and health. Conclusions: A primary care system can be defined and approached as a multidimensional system contributing to overall health system performance and health

The generalized Hamiltonian model for the shafting transient analysis of the hydro turbine generating sets.

yesTraditional rotor dynamics mainly focuses on the steady- state behavior of the rotor and shafting. However, for systems such as hydro turbine generating sets (HTGS) where the control and regulation is frequently applied, the shafting safety and stabilization in transient state is then a key factor. The shafting transient state inevitably involves multiparameter domain, multifield coupling, and coupling dynamics. In this paper, the relative value form of the Lagrange function and its equations have been established by defining the base value system of the shafting. Takingthe rotation angle and the angular speed of the shafting as a link, the shafting lateral vibration and generator equations are integrated into the framework of generalized Hamiltonian system. The generalized Hamiltonian control model is thus established. To make the model more general, additional forces of the shafting are taken as the input excitation in proposed model. The control system of the HTGS can be easily connected with the shafting model to form the whole simulation system of the HTGS. It is expected that this study will build a foundation for the coupling dynamics theory using the generalized Hamiltonian theory to investigate coupling dynamic mechanism among the shafting vibration, transient of hydro turbine generating sets, and additional forces of the shafting.National Natural Science Foundation of China under Grant Nos. 51179079 and 5083900

Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation

<p>Abstract</p> <p>Background</p> <p>Neuroinflammation occurs as a result of microglial activation in response to invading micro-organisms or other inflammatory stimuli within the central nervous system. According to our earlier findings, Krüppel-like factor 4 (Klf4), a zinc finger transcription factor, is involved in microglial activation and subsequent release of proinflammatory cytokines, tumor necrosis factor alpha, macrophage chemoattractant protein-1 and interleukin-6 as well as proinflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated microglial cells. Our current study focuses on finding the molecular mechanism of the anti-inflammatory activities of honokiol in lipopolysaccharide-treated microglia with emphasis on the regulation of Klf4.</p> <p>Methods</p> <p>For <it>in vitro </it>studies, mouse microglial BV-2 cell lines as well as primary microglia were treated with 500 ng/mL lipopolysaccharide as well as 1 μM and 10 μM of honokiol. We cloned full-length Klf4 cDNA in pcDNA3.1 expression vector and transfected BV-2 cells with this construct using lipofectamine for overexpression studies. For <it>in vivo </it>studies, brain tissues were isolated from BALB/c mice treated with 5 mg/kg body weight of lipopolysaccharide either with or without 2.5 or 5 mg/kg body weight of honokiol. Expression of Klf4, cyclooxygenase-2, inducible nitric oxide synthase and phospho-nuclear factor-kappa B was measured using immunoblotting. We also measured the levels of cytokines, reactive oxygen species and nitric oxide in different conditions.</p> <p>Results</p> <p>Our findings suggest that honokiol can substantially downregulate the production of proinflammatory cytokines and inflammatory enzymes in lipopolysaccharide-stimulated microglia. In addition, honokiol downregulates lipopolysaccharide-induced upregulation of both Klf4 and phospho-nuclear factor-kappa B in these cells. We also found that overexpression of Klf4 in BV-2 cells suppresses the anti-inflammatory action of honokiol.</p> <p>Conclusions</p> <p>Honokiol potentially reduces inflammation in activated microglia in a Klf4-dependent manner.</p

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review