Inelastic scattering in a monolayer graphene sheet; a weak-localization study

Charge carriers in a graphene sheet, a single layer of graphite, exhibit much distinctive characteristics to those in other two-dimensional electronic systems because of their chiral nature. In this report, we focus on the observation of weak localization in a graphene sheet exfoliated from a piece of natural graphite and nano-patterned into a Hall-bar geometry. Much stronger chiral-symmetry-breaking elastic intervalley scattering in our graphene sheet restores the conventional weak localization. The resulting carrier-density and temperature dependence of the phase coherence length reveal that the electron-electron interaction including a direct Coulomb interaction is the main inelastic scattering factor while electron-hole puddles enhance the inelastic scattering near the Dirac point.Comment: 12 pages, 3 figures, submitted to PR

Comparison of Gravity Wave Temperature Variances from Ray-Based Spectral Parameterization of Convective Gravity Wave Drag with AIRS Observations

The realism of ray-based spectral parameterization of convective gravity wave drag, which considers the updated moving speed of the convective source and multiple wave propagation directions, is tested against the Atmospheric Infrared Sounder (AIRS) onboard the Aqua satellite. Offline parameterization calculations are performed using the global reanalysis data for January and July 2005, and gravity wave temperature variances (GWTVs) are calculated at z = 2.5 hPa (unfiltered GWTV). AIRS-filtered GWTV, which is directly compared with AIRS, is calculated by applying the AIRS visibility function to the unfiltered GWTV. A comparison between the parameterization calculations and AIRS observations shows that the spatial distribution of the AIRS-filtered GWTV agrees well with that of the AIRS GWTV. However, the magnitude of the AIRS-filtered GWTV is smaller than that of the AIRS GWTV. When an additional cloud top gravity wave momentum flux spectrum with longer horizontal wavelength components that were obtained from the mesoscale simulations is included in the parameterization, both the magnitude and spatial distribution of the AIRS-filtered GWTVs from the parameterization are in good agreement with those of the AIRS GWTVs. The AIRS GWTV can be reproduced reasonably well by the parameterization not only with multiple wave propagation directions but also with two wave propagation directions of 45 degrees (northeast-southwest) and 135 degrees (northwest-southeast), which are optimally chosen for computational efficiency

Identification and assessment of markers of biotin status in healthy adults

Human biotin requirements are unknown and the identification of reliable markers of biotin status is necessary to fill this knowledge gap. Here, we used an outpatient feeding protocol to create states of biotin deficiency, sufficiency and supplementation in sixteen healthy men and women. A total of twenty possible markers of biotin status were assessed, including the abundance of biotinylated carboxylases in lymphocytes, the expression of genes from biotin metabolism and the urinary excretion of biotin and organic acids. Only the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) allowed for distinguishing biotin-deficient and biotin-sufficient individuals. The urinary excretion of biotin reliably identified biotin-supplemented subjects, but did not distinguish between biotin-depleted and biotin-sufficient individuals. The urinary excretion of 3-hydroxyisovaleric acid detected some biotin-deficient subjects, but produced a meaningful number of false-negative results and did not distinguish between biotin-sufficient and biotin-supplemented individuals. None of the other organic acids that were tested were useful markers of biotin status. Likewise, the abundance of mRNA coding for biotin transporters, holocarboxylase synthetase and biotin-dependent carboxylases in lymphocytes were not different among the treatment groups. Generally, datasets were characterised by variations that exceeded those seen in studies in cell cultures. We conclude that holo-MCC and holo-PCC are the most reliable, single markers of biotin status tested in the present study

Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

Abstract 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed [1] -hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20- HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 M) increased adipogenesis in a dose dependent manner in these cells ( P \u3c 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation. — Kim, D. H., N. Puri, K. Sodhi, J. R. Falck, N. G. Abraham, J. Shapiro, and M. L. Schwartzman. Cyclooxygenase-2 dependent metabolism of 20-HETE increasesadiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

Smooth muscle archvillin: a novel regulator of signaling and contractility in vascular smooth muscle

The mechanisms by which protein kinase C (PKC) and extracellular-signal-regulated kinases (ERK1/2) govern smooth-muscle contractility remain unclear. Calponin (CaP), an actin-binding protein and PKC substrate, mediates signaling through ERK1/2. We report here that CaP sequences containing the CaP homology (CH) domain bind to the C-terminal 251 amino acids of smooth-muscle archvillin (SmAV), a new splice variant of supervillin, which is a known actin- and myosin-II-binding protein. The CaP-SmAV interaction is demonstrated by reciprocal yeast two-hybrid and blot-overlay assays and by colocalization in COS-7 cells. In differentiated smooth muscle, endogenous SmAV and CaP co-fractionate and co-translocate to the cell cortex after stimulation by agonist. Antisense knockdown of SmAV in tissue inhibits both the activation of ERK1/2 and contractions stimulated by either agonist or PKC activation. This ERK1/2 signaling and contractile defect is similar to that observed in CaP knockdown experiments. In A7r5 smooth-muscle cells, PKC activation by phorbol esters induces the reorganization of endogenous, membrane-localized SmAV and microfilament-associated CaP into podosome-like structures that also contain F-actin, nonmuscle myosin IIB and ERK1/2. These results indicate that SmAV contributes to the regulation of contractility through a CaP-mediated signaling pathway, involving PKC activation and phosphorylation of ERK1/2

Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus

The acute neurotoxicity of oligomeric forms of amyloid-beta 1-42 (A beta) is implicated in the pathogenesis of Alzheimer's disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular A beta, an event that could be important during the early stages of the disease. We show that oligomerised A beta induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSCA) when applied intracellularly. This effect is dependent on postsynaptic Ca2+ and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S8(45)-phosphomutant of GluA1. Significantly, an inhibitor of Ca2+-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSCA. These results suggest that a primary neuronal response to intracellular A beta oligomers is the rapid synaptic insertion of CP-AMPARs114161sciescopu

Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus

The acute neurotoxicity of oligomeric forms of amyloid-beta 1-42 (Abeta) is implicated in the pathogenesis of Alzheimer's disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular Abeta, an event that could be important during the early stages of the disease. We show that oligomerised Abeta induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSCA) when applied intracellularly. This effect is dependent on postsynaptic Ca(2+) and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S845-phosphomutant of GluA1. Significantly, an inhibitor of Ca(2+)-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSCA. These results suggest that a primary neuronal response to intracellular Abeta oligomers is the rapid synaptic insertion of CP-AMPARs

Bacteria in the amniotic fluid without inflammation: Early colonization vs. contamination

Objectives: Intra-amniotic infection, defined by the presence of microorganisms in the amniotic cavity, is often accompanied by intra-amniotic inflammation. Occasionally, laboratories report the growth of bacteria or the presence of microbial nucleic acids in amniotic fluid in the absence of intra-amniotic inflammation. This study was conducted to determine the clinical significance of the presence of bacteria in amniotic fluid samples in the absence of intra-amniotic inflammation. Methods: A retrospective cross-sectional study included 360 patients with preterm labor and intact membranes who underwent transabdominal amniocentesis for evaluation of the microbial state of the amniotic cavity as well as intra-amniotic inflammation. Cultivation techniques were used to isolate microorganisms, and broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was utilized to detect the nucleic acids of bacteria, viruses, and fungi. Results: Patients whose amniotic fluid samples evinced microorganisms but did not indicate inflammation had a similar perinatal outcome to those without microorganisms or inflammation [amniocentesis-to-delivery interval (p=0.31), spontaneous preterm birth before 34 weeks (p=0.83), acute placental inflammatory lesions (p=1), and composite neonatal morbidity (p=0.8)]. Conclusions: The isolation of microorganisms from a sample of amniotic fluid in the absence of intra-amniotic inflammation is indicative of a benign condition, which most likely represents contamination of the specimen during the collection procedure or laboratory processing rather than early colonization or infection

Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS

Glioblastoma (GBM) is an incurable brain cancer with a median survival of less than two years from diagnosis. The standard treatment of GBM is multimodality therapy comprising surgical resection, radiation, and chemotherapy. However, prognosis remains poor, and there is an urgent need for effective anticancer drugs. Since different regions of a single GBM contain multiple cancer subpopulations ("intra-tumor heterogeneity"), this likely accounts for therapy failure as certain cancer cells can escape from immune surveillance and therapeutic threats. Here, we present metabolomic data generated using the Orbitrap secondary ion mass spectrometry (OrbiSIMS) technique to investigate brain tumor metabolism within its highly heterogeneous tumor microenvironment. Our results demonstrate that an OrbiSIMS-based untargeted metabolomics method was able to discriminate morphologically distinct regions (viable, necrotic, and non-cancerous) within single tumors from formalin-fixed paraffin-embedded tissue archives. Specifically, cancer cells from necrotic regions were separated from viable GBM cells based on a set of metabolites including cytosine, phosphate, purine, xanthine, and 8-hydroxy-7-methylguanine. Moreover, we mapped ubiquitous metabolites across necrotic and viable regions into metabolic pathways, which allowed for the discovery of tryptophan metabolism that was likely essential for GBM cellular survival. In summary, this study first demonstrated the capability of OrbiSIMS for in situ investigation of GBM intra-tumor heterogeneity, and the acquired information can potentially help improve our understanding of cancer metabolism and develop new therapies that can effectively target multiple subpopulations within a tumor