Intestinal absorption of macromolecules during viral enteritis: an experimental study on rotavirus-infected conventional and germ-free mice.

Epithelial transport and degradation of horseradish peroxidase (HRP), a macromolecular tracer, was studied in conventional and germ-free suckling mice following an experimental infection with rotavirus. Conventional and germ-free mice developed diarrhea from days 2 to 8 postinfection (pi), with growth failure. In mucosal homogenates, infectious virus detected by immunofluorescence on MA 104 cells was present from day 2 through day 8 pi in germ-free mice, but persisted longer (day 13 pi) in conventional mice. Only mild histological lesions were observed during diarrhea, but obvious macrovacuolation of epithelial cells and increased cellular density occurred during the convalescence period (days 9 to 13 pi). Intact and degraded HRP fluxes from mucosa to serosa were measured in vitro on segments of jejunum mounted in Ussing chambers. Both groups of mice developed increased HRP permeability during the experimental period, but at different times after inoculation: during the diarrheal period (days 2 and 3 pi) conventional mouse epithelium absorbed five times more HRP than noninfected controls and during the convalescence period (days 9 to 13 pi) HRP absorption in germ-free mice rose 10-fold as compared to its level before infection. In both cases, this increase in HRP permeability was entirely due to an increase in intact HRP absorption, probably via a transcellular route, and occurred without any alteration in degraded HRP transport. These results indicate that in mice, rotavirus infection causes a transient rise in gut permeability to undegraded proteins. The intestinal microflora seems to affect the timing, magnitude, and duration of this increased permeability

Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ?2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ?60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates

Generating Single Microwave Photons in a Circuit

Electromagnetic signals in circuits consist of discrete photons, though conventional voltage sources can only generate classical fields with a coherent superposition of many different photon numbers. While these classical signals can control and measure bits in a quantum computer (qubits), single photons can carry quantum information, enabling non-local quantum interactions, an important resource for scalable quantum computing. Here, we demonstrate an on-chip single photon source in a circuit quantum electrodynamics (QED) architecture, with a microwave transmission line cavity that collects the spontaneous emission of a single superconducting qubit with high efficiency. The photon source is triggered by a qubit rotation, as a photon is generated only when the qubit is excited. Tomography of both qubit and fluorescence photon shows that arbitrary qubit states can be mapped onto the photon state, demonstrating an ability to convert a stationary qubit into a flying qubit. Both the average power and voltage of the photon source are characterized to verify performance of the system. This single photon source is an important addition to a rapidly growing toolbox for quantum optics on a chip.Comment: 6 pages, 5 figures, hires version at http://www.eng.yale.edu/rslab/papers/single_photon_hires.pd

M-type channels selectively control bursting in rat dopaminergic neurons.

Midbrain dopaminergic neurons in the substantia nigra, pars compacta and ventral tegmental area are critically important in many physiological functions. These neurons exhibit firing patterns that include tonic slow pacemaking, irregular firing and bursting, and the amount of dopamine that is present in the synaptic cleft is much increased during bursting. The mechanisms responsible for the switch between these spiking patterns remain unclear. Using both in-vivo recordings combined with microiontophoretic or intraperitoneal drug applications and in-vitro experiments, we have found that M-type channels, which are present in midbrain dopaminergic cells, modulate the firing during bursting without affecting the background low-frequency pacemaker firing. Thus, a selective blocker of these channels, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride, specifically potentiated burst firing. Computer modeling of the dopamine neuron confirmed the possibility of a differential influence of M-type channels on excitability during various firing patterns. Therefore, these channels may provide a novel target for the treatment of dopamine-related diseases, including Parkinson's disease and drug addiction. Moreover, our results demonstrate that the influence of M-type channels on the excitability of these slow pacemaker neurons is conditional upon their firing pattern.Supported by grant no. 9.4560.03 from the F.R.S.‐FNRS (V.S. and J.‐F.L.), by a grant from the Belgian Science Policy (IAP 6/31) (V.S.), and by grants from the Howard Hughes Medical Institute (T.J.S.), BAEF‐Fulbright (M.B.) and NSF‐NIH (CRCNS) (T.J.S. and M.B.). J.‐F. L. is Research Director of the F.R.S.‐FNRS

The Molecular Clockwork of the Fire Ant Solenopsis invicta

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Drosophila Melanogaster as a Model System for Studies of Islet Amyloid Polypeptide Aggregation

Background: Recent research supports that aggregation of islet amyloid polypeptide (IAPP) leads to cell death and this makes islet amyloid a plausible cause for the reduction of beta cell mass, demonstrated in patients with type 2 diabetes. IAPP is produced by the beta cells as a prohormone, and proIAPP is processed into IAPP by the prohormone convertases PC1/3 and PC2 in the secretory granules. Little is known about the pathogenesis for islet amyloid and which intracellular mechanisms are involved in amyloidogenesis and induction of cell death. Methodology/Principal Findings: We have established expression of human proIAPP (hproIAPP), human IAPP (hIAPP) and the non-amyloidogenic mouse IAPP (mIAPP) in Drosophila melanogaster, and compared survival of flies with the expression driven to different cell populations. Only flies expressing hproIAPP in neurons driven by the Gal4 driver elavC(155,Gal4) showed a reduction in lifespan whereas neither expression of hIAPP or mIAPP influenced survival. Both hIAPP and hproIAPP expression caused formation of aggregates in CNS and fat body region, and these aggregates were both stained by the dyes Congo red and pFTAA, both known to detect amyloid. Also, the morphology of the highly organized protein granules that developed in the fat body of the head in hIAPP and hproIAPP expressing flies was characterized, and determined to consist of 15.8 nm thick pentagonal rod-like structures. Conclusions/Significance: These findings point to a potential for Drosophila melanogaster to serve as a model system for studies of hproIAPP and hIAPP expression with subsequent aggregation and developed pathology.Original Publication: Sebastian Schultz, Peter Nilsson and Gunilla Torstensdotter Westermark, Drosophila Melanogaster as a Model System for Studies of Islet Amyloid Polypeptide Aggregation, 2011, PLoS ONE, (6), 6. http://dx.doi.org/10.1371/journal.pone.0020221 Copyright: Public Library of Science (PLoS) http://www.plos.org/</p