Optical Trapping in a Dark Focus

The superposition of a Gaussian mode and a Laguerre-Gauss mode with $\ell=0,p\neq0$ generates the so-called bottle beam: a dark focus surrounded by a bright region. In this paper, we theoretically explore the use of bottle beams as an optical trap for dielectric spheres with a refractive index smaller than that of their surrounding medium. The forces acting on a small particle are derived within the dipole approximation and used to simulate the Brownian motion of the particle in the trap. The intermediate regime of particle size is studied numerically and it is found that stable trapping of larger dielectric particles is also possible. Based on the results of the intermediate regime analysis, an experiment aimed at trapping living organisms in the dark focus of a bottle beam is proposed.Comment: 14 pages, 9 figure

Osteoradionecrosis prevalence and associated factors : a ten years retrospective study

Osteoradionecrosis (ORN) is one of the most serious complications of head and neck radiotherapy and is considered a public health problem worldwide. This study aims to determine the prevalence and associated factors of ORN in patients undergoing radiotherapy for head and neck malignancy. A cross-sectional retrospective study was conducted, in which all medical records of patients undergoing head and neck radiation in the period between 2006 to 2015 (10 years) were examined. Clinical and demographic data were extracted. Multivariate Poisson regression analysis with robust variance was employed to access the relationship between ORN and independent variables (p<0.05; 95% CI). The sample comprised 413 medical records of patients undergoing radiotherapy. The prevalence of ORN was 9.7 %. Most participants were males (78.2%). The mean age of subjects was 55 years (± 14 years). The mandible was the main site of occurrence of ORN (85.0%). The following variables were associated with ORN : presence of oral mucositis (PR = 3.03; 95% CI: 1.30-7.03), history of smoking (PR = 0.23; 95% CI: 0.07-0.74), number of teeth removed before radiotherapy (PR = 1.06; 95% CI: 1.01-1.11) and visit to the dentist before radiation (PR = 0.08; 95% CI: 1.02-1.11). The prevalence of ORN was low and was associated with the presence of oral mucositis and the number of removed teeth before radiation. Visiting the dentist before radiotherapy and stop-ping smoking were protective factors for ORN

Are the hosts of gamma-ray bursts sub-luminous and blue galaxies?

We present K-band imaging observations of ten gamma-ray burst (GRB) host galaxies for which an optical and/or radio afterglow associated with the GRB event was clearly identified. Data were obtained with the Very Large Telescope and New Technology Telescope at ESO (Chile), and with the Gemini-North telescope at Mauna Kea (Hawaii). Adding to our sample nine other GRB hosts with K-band photometry and determined redshifts published in the literature, we compare their observed and absolute K magnitudes as well as their R − K colours with those of other distant sources detected in various optical, nearinfrared, mid-infrared and submillimeter deep surveys. We find that the GRB host galaxies, most of them lying at 0.5 ≲ z ≲ 1.5, exhibit very blue colours, comparable to those of the faint blue star-forming sources at high redshift. They are sub-luminous in the K-band, suggesting a low stellar mass content. We do not find any GRB hosts harbouring R- and K-band properties similar to those characterizing the luminous infrared/submillimeter sources and the extremely red starbursts. Should GRBs be regarded as an unbiased probe of star-forming activity, this lack of luminous and/or reddened objects among the GRB host sample might reveal that the detection of GRB optical afterglows is likely biased toward unobscured galaxies. It would moreover support the idea that a large fraction of the optically-dark GRBs occur within dust-enshrouded regions of star formation. On the other hand, our result might also simply reflect intrinsic properties of GRB host galaxies experiencing a first episode of very massive star formation and characterized by a rather weak underlying stellar population. Finally, we compute the absolute B magnitudes for the whole sample of GRB host galaxies with known redshifts and detected at optical wavelengths. We find that the latter appear statistically even less luminous than the faint blue sources which mostly contributed to the B-band light emitted at high redshift. This indicates that the formation of GRBs could be favoured in particular systems with very low luminosities and, therefore, low metallicities. Such an intrinsic bias toward metal-poor environments would be actually consistent with what can be expected from the currently-favoured scenario of the “collapsar”. The forthcoming launch of the SWIFT mission at the end of 2003 will provide a dramatic increase of the number of GRB-selected sources. A detailed study of the chemical composition of the gas within this sample of galaxies will thus allow us to further analyse the potential effect of metallicity in the formation of GRB events.Instituto de Astrofísica de La PlataFacultad de Ciencias Astronómicas y Geofísica

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3

Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin intermediate, which promote formation of a transient, thioester-bonded HECT∼ubiquitin intermediate. Here we report that the second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. The structure of a chemically trapped proxy for an E3∼ubiquitin-substrate intermediate reveals three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3∼ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize target lysines for ubiquitination. The data allow visualization of an E2-to-E3-to-substrate ubiquitin transfer cascade, and show how HECT-specific ubiquitin interactions driving multiple reactions are repurposed by a major E3 conformational change to promote ligation. DOI:http://dx.doi.org/10.7554/eLife.00828.001

Contribution of Efflux to the Emergence of Isoniazid and Multidrug Resistance in Mycobacterium tuberculosis

Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype. The study was based on the in vitro induction of an isoniazid resistant phenotype by prolonged serial exposure of M. tuberculosis strains to the critical concentration of isoniazid employed for determination of drug susceptibility testing in clinical isolates. Results show that susceptible and rifampicin monoresistant strains exposed to this concentration become resistant to isoniazid after three weeks; and that resistance observed for the majority of these strains could be reduced by means of efflux pumps inhibitors. RT-qPCR assessment of efflux pump genes expression showed overexpression of all tested genes. Enhanced real-time efflux of ethidium bromide, a common efflux pump substrate, was also observed, showing a clear relation between overexpression of the genes and increased efflux pump function. Further exposure to isoniazid resulted in the selection and stabilization of spontaneous mutations and deletions in the katG gene along with sustained increased efflux activity. Together, results demonstrate the relevance of efflux pumps as one of the factors of isoniazid resistance in M. tuberculosis. These results support the hypothesis that activity of efflux pumps allows the maintenance of an isoniazid resistant population in a sub-optimally treated patient from which isoniazid genetically resistant mutants emerge. Therefore, the use of inhibitors of efflux should be considered in the development of new therapeutic strategies for preventing the emergence of MDR-TB during treatment

Very large telescope and Hubble Space Telescope observations of the host galaxy of GRB 990705

We present Very Large Telescope spectroscopic observations of the GRB 990705 host galaxy and highlight the benefits provided by the prompt phase features of gamma-ray bursts (GRBs) to derive the redshifts of the latter. In the host spectrum, we indeed detect an emission feature that we attribute to the [O II] λλ3726, 3729 doublet and derive an unambiguous redshift z = 0.8424 ± 0.0002 for this galaxy. This is in full agreement with the value z ∼ 0.86 ± 0.17 previously derived using a transient absorption edge discovered in the X-ray spectrum of GRB 990705. This burst is therefore the first GRB for which a reliable redshift was derived from the prompt phase emission itself, as opposed to redshift determinations performed using putative host galaxy emission lines or interstellar absorption lines in the GRB afterglows. Deep and high-resolution images of the host of GRB 990705 with the Space Telescope Imaging Spectrograph camera on board the Hubble Space Telescope reveal that the burst occurred in a nearly face-on Sc spiral galaxy typical of disk-dominated systems at 0.75 ≤ z ≤ 1. Assuming a cosmology with H0 = 65 km s-1 Mpc-1, Ωm = 0.3, and Ωλ = 0.7, we derive an absolute B magnitude MB = -21.75 for this galaxy and a star formation rate SFR ≈ 5-8 M⊙ yr-1. Finally, we discuss the implications of using X-ray transient features to derive GRB redshifts with larger burst samples and especially examine the case of short and dark long GRBs.Facultad de Ciencias Astronómicas y Geofísica

Lipidomic Analysis of Extracellular Vesicles from the Pathogenic Phase of Paracoccidioides brasiliensis

Background: Fungal extracellular vesicles are able to cross the cell wall and transport molecules that help in nutrient acquisition, cell defense, and modulation of the host defense machinery.Methodology/Principal Findings: Here we present a detailed lipidomic analysis of extracellular vesicles released by Paracoccidioides brasiliensis at the yeast pathogenic phase. We compared data of two representative isolates, Pb3 and Pb18, which have distinct virulence profiles and phylogenetic background. Vesicle lipids were fractionated into different classes and analyzed by either electrospray ionization- or gas chromatography-mass spectrometry. We found two species of monohexosylceramide and 33 phospholipid species, including phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol. Among the phospholipid-bound fatty acids in extracellular vesicles, C181 predominated in Pb3, whereas C18:2 prevailed in Pb18. the prevalent sterol in Pb3 and Pb18 vesicles was brassicasterol, followed by ergosterol and lanosterol. Inter-isolate differences in sterol composition were observed, and also between extracellular vesicles and whole cells.Conclusions/Significance: the extensive lipidomic analysis of extracellular vesicles from two P. brasiliensis isolates will help to understand the composition of these fungal components/organelles and will hopefully be useful to study their biogenesis and role in host-pathogen interactions.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Institutes of Health (NIH)Universidade Federal de São Paulo, UNIFESP, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79968 USAUniversidade Federal de São Paulo, UNIFESP, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilFAPESP: 06/05095-6FAPESP: 07/04757-8FAPESP: 07/59768-4CNPq: 301666/2010-5National Institutes of Health (NIH): 5G12RR008124-16A1National Institutes of Health (NIH): 5G12RR008124-16A1S1National Institutes of Health (NIH): G12MD007592Web of Scienc

Epidemiological Profile of Children Infected with Bordetella pertussis at Varela Santiago Children’s Hospital: a Retrospective Study

Abstract Background: Pertussis, also called whooping cough, is an acute infectious disease of high transmissibility transmitted through aerosol particles released during the catarrhal phase and paroxysmal cough. Since the 1990s its incidence has increased and atypical clinical forms have been identified, mainly in newborns and adults. We hypothesized that there is a relationship between the high incidence of pertussis infection in children up to 6 months of age and genetic changes in the circulating strains of B. pertussis leading to inefficacy of diphtheria, tetanus, and pertussis vaccine (DTP). Methods: Data were obtained from the medical records of hospitalized patients at the Varela Santiago Children’s Hospital in Brazil from January 1, 2013 to December 31, 2013. Results: A total of 33 cases of pertussis hospitalizations were found, where 75.7% (25/33) of the patients were 6 months of age or younger (6 patients were 30 days old or younger while 19 ranged in age from 31 days to 6 months). Of these, 54.5% (14/25) were in exclusive breastfed children. Only 18.2% (6/33) of the patients had the appropriate administration of DTP doses according to their age. Signs and symptoms were: cough 100%, cyanosis 63.6%, fever 48.5% and inspiratory winch 33.3%. Azithromycin was used as monotherapy in 90% (30/33) of the cases and the mean time of hospitalization was 9.48 days ranging from 6 to 30 days. No patient died. Conclusion: We identified a high prevalence (75.7%) of B. pertussis infection in children up to 6 months of age. This is likely explained by the low vaccination rate (18.2%) and the low percentage of exclusive breastfeeding of the studied population. The low rate of vaccination is unexpected, given that there has been greater access to vaccination in recent decades in Brazil. In addition, the cases evolved with an atypical clinical presentation, since the classic symptoms of the catarrhal stage were absent or had a such short duration that such symptoms were no longer present at the time of hospitalization. Our study does not exclude the possibility that genetic changes are occurring in the circulating strains of B. pertussis and that DTP seems to have less efficacy on these new strains, but future studies will be needed to specifically test this hypothesis. Disclosures All authors: No reported disclosures