Although pathogens must infect differentiated host cells that exhibit substantial diversity, documenting the consequences of infection against this heterogeneity is challenging. Single-cell mass ...cytometry permits deep profiling based on combinatorial expression of surface and intracellular proteins. We used this method to investigate varicella-zoster virus (VZV) infection of tonsil T cells, which mediate viral transport to skin. Our results indicate that VZV induces a continuum of changes regardless of basal phenotypic and functional T cell characteristics. Contrary to the premise that VZV selectively infects T cells with skin trafficking profiles, VZV infection altered T cell surface proteins to enhance or induce these properties. Zap70 and Akt signaling pathways that trigger such surface changes were activated in VZV-infected naive and memory cells by a T cell receptor (TCR)-independent process. Single-cell mass cytometry is likely to be broadly relevant for demonstrating how intracellular pathogens modulate differentiated cells to support pathogenesis in the natural host.
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•Application of single-cell mass cytometry to study virus-host interactions•CyTOF analysis of Varicella-infected human tonsil T cells using 40+ parameters•Development of statistical method to determine remodeling in differentiated cells•Observation that varicella-zoster virus uses T cell plasticity to support pathogenesis
Single-cell mass cytometry with multiparametric data analysis permits proteomic deep profiling based on combinatorial expression of many proteins in each cell. Sen et al. now demonstrate that primary human tonsil T cells are remodeled by VZV infection, regardless of their basal phenotypic and functional states, to a configuration promoting viral transport to skin. This approach should be useful in showing how other intracellular pathogens alter the heterogeneous properties of differentiated host cells to support pathogenesis.
Spectroscopy of antihydrogen has the potential to yield high-precision tests of the CPT theorem and shed light on the matter-antimatter imbalance in the Universe. The ALPHA antihydrogen trap at ...CERN’s Antiproton Decelerator aims to prepare a sample of antihydrogen atoms confined in an octupole-based Ioffe trap and to measure the frequency of several atomic transitions. We describe our techniques to directly measure the antiproton temperature and a new technique to cool them to below 10 K. We also show how our unique position-sensitive annihilation detector provides us with a highly sensitive method of identifying antiproton annihilations and effectively rejecting the cosmic-ray background.
Studies with a series of metal/ceria(111) (metal=Co, Ni, Cu; ceria=CeO2) surfaces indicate that metal–oxide interactions can play a very important role for the activation of methane and its reforming ...with CO2 at relatively low temperatures (600–700 K). Among the systems examined, Co/CeO2(111) exhibits the best performance and Cu/CeO2(111) has negligible activity. Experiments using ambient pressure X‐ray photoelectron spectroscopy indicate that methane dissociates on Co/CeO2(111) at temperatures as low as 300 K—generating CHx and COx species on the catalyst surface. The results of density functional calculations show a reduction in the methane activation barrier from 1.07 eV on Co(0001) to 0.87 eV on Co2+/CeO2(111), and to only 0.05 eV on Co0/CeO2−x(111). At 700 K, under methane dry reforming conditions, CO2 dissociates on the oxide surface and a catalytic cycle is established without coke deposition. A significant part of the CHx formed on the Co0/CeO2−x(111) catalyst recombines to yield ethane or ethylene.
Cobalt/ceria (Co/CeO2), with a low loading of cobalt, is an efficient catalyst for methane activation at room temperature, and for dry reforming of methane (DRM) at relatively low temperatures (700 K). Higher temperatures transform Co2+/CeO2 into the highly active catalyst Co0/CeO2−x. DRM activity depends on the metal/CeO2 combination: Co/CeO2> Ni/CeO2, and Cu/CeO2 is inactive.
Ultra-Low Bending Loss Single-Mode Fiber for FTTH Li, M.-J.; Tandon, P.; Bookbinder, D.C. ...
Journal of lightwave technology,
02/2009, Letnik:
27, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
A new ultra-low bending loss single-mode fiber with ring comprising nanometer sized features is designed and manufactured. Bending loss less than 0.1 dB/turn at 1550 nm and a bend radius of 5 mm is ...demonstrated. Other optical parameters of the fiber are fully compatible the standard telecommunications grade single-mode fibers.
High-resolution radar images reveal near-Earth asteroid (66391) 1999 KW4 to be a binary system. The ~1.5-kilometer-diameter primary (Alpha) is an unconsolidated gravitational aggregate with a spin ...period ~2.8 hours, bulk density ~2 grams per cubic centimeter, porosity ~50%, and an oblate shape dominated by an equatorial ridge at the object's potential-energy minimum. The ~0.5-kilometer secondary (Beta) is elongated and probably is denser than Alpha. Its average orbit about Alpha is circular with a radius ~2.5 kilometers and period ~17.4 hours, and its average rotation is synchronous with the long axis pointed toward Alpha, but librational departures from that orientation are evident. Exotic physical and dynamical properties may be common among near-Earth binaries.
As part of a larger study to determine the flow of Campylobacter and Salmonella from food animals to humans during 1982-83, 1,936 swabs were collected for bacteriologic study from pre-market ...chickens, retail poultry, and other retail meats as well as from equipment and work surfaces used to process such foods. Of the 297 samples collected in a poultry processing plant, 56.6 per cent were positive for Campylobacter jejuni/coli (CJC), as were 23.1 per cent of the 862 retail chicken, and 17.2 per cent of the 29 retail game hen samples. CJC was found infrequently in retail turkey, pork, and beef samples. Contamination of retail and pre-market chicken with CJC appeared to increase as the week progressed, and in pre-market chicken, later in the day. Less than 5 per cent of the retail samples of poultry, beef, and pork were found to contain Yersinia or Salmonella. However, Salmonella was cultured from 14.8 per cent of the swabs taken from the processing plant with 68 per cent of 44 Salmonellas being isolated concurrently with CJC. Tetracycline resistance which was plasmid-mediated was the most common antibiotic resistance observed, and was carried by 23.8 per cent of all CJC isolates. Overall, 38.8 per cent of all CJC isolates were resistant to ampicillin, erythromycin, streptomycin, or tetracycline, either singly or in combination.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these mutations are known as mediators of ...endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of ESR1 mutations exclusively in distant but not local recurrences in five independent breast cancer cohorts. In concordance with transcriptomic profiling of ESR1-mutant tumors, genome-edited ESR1 Y537S and D538G-mutant cell models exhibited a reprogrammed cell adhesive gene network via alterations in desmosome/gap junction genes and the TIMP3/MMP axis, which functionally conferred enhanced cell-cell contacts while decreasing cell-extracellular matrix adhesion. In vivo studies showed ESR1-mutant cells were associated with larger multicellular circulating tumor cell (CTC) clusters with increased compactness compared with ESR1 wild-type CTCs. These preclinical findings translated to clinical observations, where CTC clusters were enriched in patients with ESR1-mutated metastatic breast cancer. Conversely, context-dependent migratory phenotypes revealed cotargeting of Wnt and ER as a vulnerability in a D538G cell model. Mechanistically, mutant ESR1 exhibited noncanonical regulation of several metastatic pathways, including secondary transcriptional regulation and de novo FOXA1-driven chromatin remodeling. Collectively, these data provide evidence for ESR1 mutation-modulated metastasis and suggest future therapeutic strategies for targeting ESR1-mutant breast cancer.
Context- and allele-dependent transcriptome and cistrome reprogramming in mutant ESR1 cell models elicit diverse metastatic phenotypes related to cell adhesion and migration, which can be pharmacologically targeted in metastatic breast cancer.
Ebola virus (EBOV) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. Here, we used single-cell ...transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cells during EBOV infection in rhesus monkeys. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation capacity replace conventional monocyte subsets, while lymphocytes upregulate apoptosis genes and decline in abundance. By quantifying intracellular viral RNA, we identify molecular determinants of tropism among circulating immune cells and examine temporal dynamics in viral and host gene expression. Within infected cells, EBOV downregulates STAT1 mRNA and interferon signaling, and it upregulates putative pro-viral genes (e.g., DYNLL1 and HSPA5), nominating pathways the virus manipulates for its replication. This study sheds light on EBOV tropism, replication dynamics, and elicited immune response and provides a framework for characterizing host-virus interactions under maximum containment.
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•Interferon response is suppressed in infected cells but activated in bystander cells•EBOV represses antiviral genes and upregulates pro-viral genes in infected cells•Proliferative CD14– CD16– monocyte precursors expand in circulation during EVD•Identification of expression markers of EBOV tropism for circulating cells in vivo
Single-cell profiling of circulating immune cells during Ebola virus (EBOV) infection in non-human primates resolves molecular correlates of viral tropism, characterizes replication dynamics within infected cells, and distinguishes expression changes that are mediated by viral infection from those due to cytokine signaling.
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