ABSTRACT
We derive a rigorous analytical formalism and propose a numerical method for the quantitative evaluation of the electrostatic interactions between dielectric particles in an external electric field. This formalism also allows for inhomogeneous charge distributions, and, in particular, for the presence of pointlike charges on the particle surface. The theory is based on a boundary integral equation framework and yields analytical expressions for the interaction energy and net forces that can be computed in linear scaling cost, with respect to the number of interacting particles. We include numerical results that validate the proposed method and show the limitations of the fixed dipole approximation at small separation between interacting particles. The proposed method is also applied to study the stability and melting of ionic colloidal crystals in an external electric field.
ABSTRACT
In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by the eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in human metaphase II oocytes and bipronuclear (2PN) one-cell embryos. High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo gene expression changes. This confirmed transcript depletion following fertilization (maternal RNA degradation) but also uncovered low-magnitude upregulation of hundreds of spliced transcripts. Gene expression analysis predicted embryonic processes including cell-cycle progression and chromosome maintenance as well as transcriptional activators that included cancer-associated gene regulators. Transcription was disrupted in abnormal monopronuclear (1PN) and tripronuclear (3PN) one-cell embryos. These findings indicate that human embryonic transcription initiates at the one-cell stage, sooner than previously thought. The pattern of gene upregulation promises to illuminate processes involved at the onset of human development, with implications for epigenetic inheritance, stem-cell-derived embryos, and cancer.
Subject(s)
Embryo, Mammalian , Genome, Human , Blastocyst , Embryo, Mammalian/metabolism , Embryonic Development/genetics , Gene Expression Regulation, Developmental , Humans , OocytesABSTRACT
Most filoviruses cause severe disease in humans. For example, Ebola virus (EBOV) is responsible for the two most extensive outbreaks of filovirus disease to date, with case fatality rates of 66% and 40%, respectively. In contrast, Reston virus (RESTV) is apparently apathogenic in humans, and while transmission of RESTV from domestic pigs to people results in seroconversion, no signs of disease have been reported in such cases. The determinants leading to these differences in pathogenicity are not well understood, but such information is needed in order to better evaluate the risks posed by the repeated spillover of RESTV into the human population and to perform risk assessments for newly emerging filoviruses with unknown pathogenic potential. Interestingly, RESTV and EBOV already show marked differences in their growth in vitro, with RESTV growing slower and reaching lower end titers. In order to understand the basis for this in vitro attenuation of RESTV, we used various life cycle modeling systems mimicking different aspects of the virus life cycle. Our results showed that viral RNA synthesis was markedly slower when using the ribonucleoprotein (RNP) components from RESTV, rather than those for EBOV. In contrast, the kinetics of budding and entry were indistinguishable between these two viruses. These data contribute to our understanding of the molecular basis for filovirus pathogenicity by showing that it is primarily differences in the robustness of RNA synthesis by the viral RNP complex that are responsible for the impaired growth of RESTV in tissue culture.
ABSTRACT
Exercise stimulates the release of inflammatory cytokines and supplementation with n-3 fatty acids reduces inflammation. The effects of different doses of docosahexaenoic acid (DHA) on inflammation in polo horses submitted to field lactate threshold tests (LT) were analyzed. We hypothesized that higher doses of DHA would reduce postexercise inflammation. Twenty polo horses were assigned to different treatments: control group fed (n = 5) grain and hay, 3 treatment groups (n = 5) fed 10, 20, or 50 g/day of DHA with grain and free choice hay during 60 days. Horses underwent LT tests before start, 30, and 60 days of supplementation. Blood samples were taken at rest for blood cytokine expression (CEx), plasma cytokine enzyme-linked immunosorbent assay (CEL), fatty acid, vitamin E, and creatine kinase (CK) analysis, after LT for CEx analysis (interferon gamma, tumor necrosis factor alpha [TNF-α], interleukin-1 [IL-1], interleukin-6 [IL-6], interleukin-10 [IL-10]), CEL, and CK analysis. Effects of treatment, time, and exercise were analyzed by analysis of variance, significant results compared by least square means analysis, and significance set at P < .05. There was a dose-dependent increase in plasma DHA, and highest arachidonic acid was found in 20 and 50 g. Vitamin E was lowest in 20 and 50 g. LT did not change IL-6, downregulated IL-1 and TNF-α, upregulated IL-10, and interferon gamma. The 10 g led to postexercise downregulation of interferon gamma and IL-10 CEx compared to other treatments. A lack of antioxidants in the supplements may have led to the absence of treatment effects in the 20 and 50 g. 10 g DHA helped moderate postexercise inflammation.
Subject(s)
Docosahexaenoic Acids , Fatty Acids, Omega-3 , Animals , Dietary Supplements , Horses , Interleukin-6 , Lactic AcidABSTRACT
Sequences for Lloviu virus (LLOV), a putative novel filovirus, were first identified in Miniopterus schreibersii bats in Spain following a massive bat die-off in 2002, and also recently found in bats in Hungary. However, until now it is unclear if these sequences correspond to a fully functional, infectious virus, and whether it will show a pathogenic phenotype like African filoviruses, such as ebola- and marburgviruses, or be apathogenic for humans, like the Asian filovirus Reston virus. Since no infectious virus has been recovered, the only opportunity to study infectious LLOV is to use a reverse genetics-based full-length clone system to de novo generate LLOV. As a first step in this process, and to investigate whether the identified sequences indeed correspond to functional viral proteins, we have developed life cycle modelling systems for LLOV, which allow us to study genome replication and transcription as well as entry of this virus. We show that all LLOV proteins fulfill their canonical role in the virus life cycle as expected based on the well-studied related filovirus Ebola virus. Further, we have analysed the intergenus-compatibility of proteins that have to act in concert to facilitate the virus life cycle. We show that some but not all proteins from LLOV and Ebola virus are compatible with each other, emphasizing the close relationship of these viruses, and informing future studies of filovirus biology with respect to the generation of genus-chimeric proteins in order to probe virus protein-protein interactions on a functional level.
Subject(s)
Filoviridae/physiology , Recombinant Proteins/metabolism , Viral Proteins/metabolism , Virus Replication , Filoviridae/genetics , Genetic Complementation Test , HEK293 Cells , Humans , Recombinant Proteins/genetics , Reverse Genetics , Viral Proteins/geneticsABSTRACT
PURPOSE: Benign tumors are known to grow or develop sometimes during pregnancy. We present a case report about a young woman with a growing sternal tumor. METHODS: After her second pregnancy, a 32-year-old female presented with a rapid growing sternal tumor. Computed tomography (CT) scan revealed a tumor measuring 10 × 8 × 7 cm with an intrathoracic bulk, compressing the heart and the upper margin of the liver. RESULTS: Resection of the tumor was performed uneventfully. Histologic examination of the resected mass revealed a chondroma. CONCLUSION: To the best of our knowledge, this is the first report of a huge sternal chondroma growing in a pregnant patient. There is not often a need to treat these patients before delivery, however, thereafter surgical treatment of growing tumors is recommended.
Subject(s)
Bone Neoplasms/pathology , Chondroma/pathology , Pregnancy Complications, Neoplastic/pathology , Sternum/pathology , Adult , Biopsy , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/surgery , Chondroma/diagnostic imaging , Chondroma/surgery , Female , Humans , Pregnancy , Pregnancy Complications, Neoplastic/diagnostic imaging , Pregnancy Complications, Neoplastic/surgery , Sternum/diagnostic imaging , Sternum/surgery , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Tumor BurdenABSTRACT
Elastofibroma dorsi is a rare benign tumor of the back, located between the latissimus dorsi and the rhomboid muscle. In most cases it is unilateral, but in up to 10% it occurs on both sides. The etiology is still in discussion. Here we report a case of a 51-year-old man with bilateral elastofibroma dorsi. The therapy of choice was surgical resection. No long-term complications were reported in a 6-month follow-up.
ABSTRACT
It is shown that the gradient "free-energy" contained in equilibrium spin vorticity can cause electromagnetic modes, in particular the light wave, to go unstable in a spin quantum plasma of mobile electrons embedded in a neutralizing ion background. For densities characteristic of both the solid state and very high density astrophysical systems, the growth rates are sufficiently high to overcome the expected collisional damping. Preliminary results suggest a powerful spin-inhomogeneity driven mechanism for stimulating light amplification.
ABSTRACT
Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults with a median survival of 14.6 mo under the best available treatment. New treatment strategies are therefore urgently required, for which a profound understanding of tumor biology is necessary. Much effort has been devoted to tumor-specific aberrant signaling processes. Recently it was discovered that the transcription factor Gli1, which is activated by hedgehog signaling, is a highly predictive marker in GBM, as determined by immunohistochemistry. To determine whether GBM cells have transcriptionally active Gli1, we performed experiments with reporter genes with cells isolated from surgically removed human tumors and cell lines. We also determined whether the hedgehog signaling inhibitor cyclopamine influences reporter gene expression and cell viability, and we determined the expression of Gli1, SHH and Patched1 by quantitative real-time RT-PCR. Reporter gene analysis of nine cultures and four cell lines demonstrated a significantly enhanced transcriptional activity in six tumor cell cultures and all cell lines. Analysis of cell viability in the presence of cyclopamine revealed a response of all cell cultures with the exception of one primary culture and one cell line, but only one cell line responded to cyclopamine with reduced hedgehog signaling activity. This indicates that the toxicity of cyclopamine toward GBM cells is independent from hedgehog signaling. Since no correlation between hedgehog activity and SHH, Gli1 and Patched1 mRNA levels was observed we conclude that other mechanisms aside from transcriptional regulation of these factors are responsible for hedgehog activity in tumor cells derived from GBM.