Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

Quantum physics in inertial and gravitational fields

Covariant generalizations of well-known wave equations predict the existence of inertial-gravitational effects for a variety of quantum systems that range from Bose-Einstein condensates to particles in accelerators. Additional effects arise in models that incorporate Born reciprocity principle and the notion of a maximal acceleration. Some specific examples are discussed in detail.Comment: 25 pages,1 figure,to appear in "Relativity in Rotating Frame

Dusty Planetary Systems

Extensive photometric stellar surveys show that many main sequence stars show emission at infrared and longer wavelengths that is in excess of the stellar photosphere; this emission is thought to arise from circumstellar dust. The presence of dust disks is confirmed by spatially resolved imaging at infrared to millimeter wavelengths (tracing the dust thermal emission), and at optical to near infrared wavelengths (tracing the dust scattered light). Because the expected lifetime of these dust particles is much shorter than the age of the stars (>10 Myr), it is inferred that this solid material not primordial, i.e. the remaining from the placental cloud of gas and dust where the star was born, but instead is replenished by dust-producing planetesimals. These planetesimals are analogous to the asteroids, comets and Kuiper Belt objects (KBOs) in our Solar system that produce the interplanetary dust that gives rise to the zodiacal light (tracing the inner component of the Solar system debris disk). The presence of these "debris disks" around stars with a wide range of masses, luminosities, and metallicities, with and without binary companions, is evidence that planetesimal formation is a robust process that can take place under a wide range of conditions. This chapter is divided in two parts. Part I discusses how the study of the Solar system debris disk and the study of debris disks around other stars can help us learn about the formation, evolution and diversity of planetary systems by shedding light on the frequency and timing of planetesimal formation, the location and physical properties of the planetesimals, the presence of long-period planets, and the dynamical and collisional evolution of the system. Part II reviews the physical processes that affect dust particles in the gas-free environment of a debris disk and their effect on the dust particle size and spatial distribution.Comment: 68 pages, 25 figures. To be published in "Solar and Planetary Systems" (P. Kalas and L. French, Eds.), Volume 3 of the series "Planets, Stars and Stellar Systems" (T.D. Oswalt, Editor-in-chief), Springer 201

Streptococcus agalactiae in adults at chiang mai university hospital: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Infection caused by <it>Streptococcus agalactiae</it>, a Group B streptococcus, is an emerging disease in non-pregnant adults. This study describes the epidemiological, clinical, and microbiological characteristics of <it>S. agalactiae </it>infection in adult patients in northern Thailand.</p> <p>Methods</p> <p>A retrospective study was conducted between January 1, 2006 and December 31, 2009 at Chiang Mai University Hospital among patients aged ≥15 years, whose clinical specimens obtained from normally sterile sites grew <it>S. agalactiae</it>.</p> <p>Results</p> <p>One-hundred and eighty-six patients and 197 specimens were identified during the 4-year period. Among 186 patients, 82 were documented as having invasive infection; 42 patients were male (51.2%) with the mean age of 48.5 ± 19.4 years (range 17, 83). Fifty-three patients (64.6%) had underlying medical conditions; 17 patients (20.7%), 10 (12.2%), 8 (9.7%) had diabetes, chronic renal diseases, and malignancy, respectively. Among 40 patients (48.8%) with bloodstream infection, no other site of infection was determined in 29 (35.4%) patients. In the remaining 11 patients, 5 patients (6.1%), 5 (6.1%), and 1 (1.2%) had meningitis, arthritis, and meningitis with arthritis, respectively. Forty-two patients (51.2%) presented with localized infection, i.e., subcutaneous abscess (19 patients, 23.2%), chorioamnionitis (10 patients, 12.2%), urinary tract infection (5 patients, 6.1%), arthritis (3 patients, 3.7%), meningitis (2 patients, 2.4%), and spontaneous bacterial peritonitis, uveitis, and tracheobronchitis (1 patient each, 1.2%). The overall mortality was 14.6% (12 patients).</p> <p>Conclusions</p> <p><it>S. agalactiae </it>infection is a growing problem in non-pregnant patients, particularly in those with underlying medical conditions. Physicians should add <it>S. agalactiae </it>infection in the list of differential diagnoses in patients with meningitis and/or septicemia.</p

Pharmacy Participation in Non-Prescription Syringe Sales in Los Angeles and San Francisco Counties, 2007

Increasing sterile syringe access for injection drug users (IDUs) is one way to prevent HIV and hepatitis C virus (HCV) transmission in this population. In 2005, California Senate Bill 1159 allowed counties to adopt the Disease Prevention Demonstration Project (DPDP). Where enacted, the DPDP allows pharmacies that register with the county to sell up to ten syringes to adults without a prescription. In the current study, we describe pharmacy participation in nonprescription syringe sales (NPSS) in two counties in California and examine factors associated with NPSS. Telephone and in-person interviews were conducted in Los Angeles (LA) and San Francisco (SF) with 238 pharmacies in 2007 (n = 67 in SF; n = 171 in LA). Quantitative survey items captured pharmacy registration with the county, pharmacy policies/practices, episodes and conditions of NPSS and refusals to sell, potential negative consequences of NPSS, and staff attitudes regarding HIV and HCV prevention for IDUs. Overall, 42% of pharmacies reported NPSS (28% in LA and 81% in SF), although only 34% had registered with the county (17% in LA and 76% in SF). Many pharmacies required proof of a medical condition (80% in LA and 30% in SF) and refused NPSS if the customer was a suspected IDU (74% in LA, 33% in SF). Few negative consequences of NPSS were reported. In multivariate logistic regression analysis, we found that the odds of NPSS were significantly higher among pharmacists who thought syringe access was important for preventing HIV among IDUs [adjusted odds ratio (AOR) = 2.95; 95% confidence interval (CI) = 1.10–7.92], were chain pharmacies (AOR = 12.5; 95% CI = 4.55–33.33), and were located in SF (AOR = 4.88; 95% CI = 1.94–12.28). These results suggest that NPSS were influenced by pharmacists’ perception. NPSS might be increased through greater educational efforts directed at pharmacists, particularly those in non-chain pharmacies

Protocol for Nearly Full-Length Sequencing of HIV-1 RNA from Plasma

Nearly full-length genome sequencing of HIV-1 using peripheral blood mononuclear cells (PBMC) DNA as a template for PCR is now a relatively routine laboratory procedure. However, this has not been the case when using virion RNA as the template and this has made full genome analysis of circulating viruses difficult. Therefore, a well-developed procedure for sequencing of full-length HIV-1 RNA directly from plasma was needed. Plasma from U.S. donors representing a range of viral loads (VL) was used to develop the assay. RNA was extracted from plasma and reverse-transcribed. Two or three overlapping regions were PCR amplified to cover the entire viral genome and sequenced for verification. The success of the procedure was sensitive to VL but was routinely successful for VL greater than 105 and the rate declined in proportion to the VL. While the two-amplicon strategy had an advantage of increasing the possibility of amplifying a single species of HIV-1, the three-amplicon strategy was more successful in amplifying samples with low viral loads. This protocol provides a useful tool for molecular analysis to understand the HIV epidemic and pathogenesis, as well as diagnosis, therapy and future vaccine strategies

Parity- and Time-Reversal-Violating Moments of Light Nuclei

I present the calculation of parity- and time-reversal-violating moments of the nucleon and light nuclei, originating from the QCD theta term and effective dimension-six operators. By applying chiral effective field theory these calculations are performed in a unified framework. I argue that measurements of a few light-nuclear electric dipole moments would shed light on the mechanism of parity and time-reversal violation.Comment: 8 pages, contribution to the proceedings of the 5th International Symposium on Symmetries in Subatomic Physics (SSP2012), June 18-22, 2012, Groningen, The Netherland

The Confrontation between General Relativity and Experiment

The status of experimental tests of general relativity and of theoretical frameworks for analysing them is reviewed. Einstein's equivalence principle (EEP) is well supported by experiments such as the Eotvos experiment, tests of special relativity, and the gravitational redshift experiment. Future tests of EEP and of the inverse square law are searching for new interactions arising from unification or quantum gravity. Tests of general relativity at the post-Newtonian level have reached high precision, including the light deflection, the Shapiro time delay, the perihelion advance of Mercury, and the Nordtvedt effect in lunar motion. Gravitational-wave damping has been detected in an amount that agrees with general relativity to better than half a percent using the Hulse-Taylor binary pulsar, and other binary pulsar systems have yielded other tests, especially of strong-field effects. When direct observation of gravitational radiation from astrophysical sources begins, new tests of general relativity will be possible.Comment: 89 pages, 8 figures; an update of the Living Review article originally published in 2001; final published version incorporating referees' suggestion