The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity

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Rickettsia slovaca Infection: DEBONEL/TIBOLA

Producción CientíficaThis study describes the epidemiological, clinical, and microbiological characteristics of a new tick-borne disease in Spain—Dermacentor-borne necrosis erythema lymphadenopathy (DEBONEL). The clinical presentations include an eschar at the site of the tick bite, surrounded by an erythema and painful regional lymphadenopathy. The disease appears during the colder months and its vector is Dermacentor marginatus (D. marginatus). From January 1990 to December 2004, 54 patients presented at Hospital of La Rioja with these clinical and epidemiological data. The ratio of females to males was 32/22. The average age was 37 years. In all cases tick bites were located on the upper body (90% on the scalp). The median incubation period was 4.7 days. Signs and symptoms were mild in all cases. Only a small number of patients presented mild and nonspecific abnormalities in a complete blood cell count and mild elevation of erythrocyte sedimentation rates and C-protein reactive and liver enzyme levels. Serological evidence of acute rickettsiosis was observed in 19 patients (61%). In 29% sera tested by polymerase chain reactions (PCRs) were positive. The sequence obtained from a PCR product revealed 98% identity with Rickettsia sp. strains RpA4, DnS14, and DnS28. All ticks removed from patients were PCR-positive. Sequencing showed 8 of them identified as R. slovaca and 2 as Rickettsia sp. strains RpA4, DnS14, and DnS28

A CANDELS WFC3 Grism Study of Emission-Line Galaxies at z~2: A Mix of Nuclear Activity and Low-Metallicity Star Formation

We present Hubble Space Telescope Wide Field Camera 3 slitless grism spectroscopy of 28 emission-line galaxies at z~2, in the GOODS-S region of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). The high sensitivity of these grism observations, with 1-sigma detections of emission lines to f > 2.5x10^{-18} erg/s/cm^2, means that the galaxies in the sample are typically ~7 times less massive (median M_* = 10^{9.5} M_sun) than previously studied z~2 emission-line galaxies. Despite their lower mass, the galaxies have OIII/Hb ratios which are very similar to previously studied z~2 galaxies and much higher than the typical emission-line ratios of local galaxies. The WFC3 grism allows for unique studies of spatial gradients in emission lines, and we stack the two-dimensional spectra of the galaxies for this purpose. In the stacked data the OIII emission line is more spatially concentrated than the Hb emission line with 98.1 confidence. We additionally stack the X-ray data (all sources are individually undetected), and find that the average L(OIII)/L(0.5-10 keV) ratio is intermediate between typical z~0 obscured active galaxies and star-forming galaxies. Together the compactness of the stacked OIII spatial profile and the stacked X-ray data suggest that at least some of these low-mass, low-metallicity galaxies harbor weak active galactic nuclei.Comment: ApJ accepted. 8 pages, 6 figure

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy

Electromagnetic signatures of a strongly coupled anisotropic plasma

In heavy-ion collisions, quark-gluon plasma is likely to be produced with sizable initial pressure anisotropy, which may leave an imprint on electromagnetic observables. In order to model a strongly coupled anisotropic plasma, we use the AdS/CFT correspondence to calculate the current-current correlator of a weakly gauged U(1) subgroup of R symmetry in an N=4 super-Yang-Mills plasma with a (temporarily) fixed anisotropy. The dual geometry, obtained previously by Janik and Witaszczyk, contains a naked singularity which however permits purely infalling boundary conditions and therefore the usual definition of a retarded correlator. We obtain numerical results for the cases of wave vector parallel and orthogonal to the direction of anisotropy, and we compare with previous isotropic results. In the (unphysical) limit of vanishing frequency (infinite time) we obtain a vanishing DC conductivity for any amount of anisotropy, but the anisotropic AC conductivities smoothly approach the isotropic case in the limit of high frequencies. We also discuss hard photon production from an anisotropic plasma and compare with existing hard-loop resummed calculations.Comment: 23 pages, 15 figures. v3: improved figures 1 and

Effect of Maraviroc Intensification on HIV-1-Specific T Cell Immunity in Recently HIV-1-Infected Individuals

The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown. Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro -expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation). Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8 + T cells were indistinguishable between the two arms and did not change over time between the groups. Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

Current State of Conservation Knowledge on Threatened Amphibian Species in Peru

This study documents the current state of conservation knowledge on threatened amphibian species in Peru. Following the International Union for the Conservation of Nature (IUCN) classification system, we considered species in the following categories: Critically Endangered, Endangered, Vulnerable, and Near Threatened. Even though only the first three categories are regarded as threatened by IUCN, we included the fourth category to make comparisons with the list of threatened species issued by the Peruvian government. We used the Global Amphibian Assessment\u27s database and the list issued in Peru for this comparison. We conducted separate field surveys in 17 regions of Peru to evaluate the presence/absence of threatened amphibian species and species that are potentially threatened. We also used the Declining Amphibian Database-DAPTF, to compare our results with previous assessments on population declines, and the World Wildlife Fund\u27s Wildfinder database, to determine in which Neotropical ecoregion each species occurs. We compiled data on 83 species, 44 of which are recognized as threatened by the IUCN and/or the Peruvian government. The remaining 39 species should be re-assessed as they face various threats. A re-evaluation of current estimates is needed as only 8% of all species recorded in Peru are recognized as threatened by the government, whereas the global estimate of threatened species is about 32%. In addition to using IUCN criteria, this re-assessment should follow national guidelines standardized in Peru and be in accordance with the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Because the habitat of almost 40% of threatened species reported herein still remains unprotected, and data on chytridiomycosis and other threats are lacking for most taxa, it is crucial to develop strategies for habitat conservation and research on disease dynamics in natural populations

miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation

MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLAhighISG15+ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response