Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Periprosthetic fractures of the femur after total knee arthroplasty

Periprosthetic fracture following total knee arthroplasty is a potentially serious complication. This injury can involve the distal femur, proximal tibia or the patella. This review article analyzes the prevalence, risk factors, classification and treatment options for periprosthetic fractures of the femur

Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

<p>Abstract</p> <p>Background</p> <p>The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X₇receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X₇system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X₇action.</p> <p>Methods</p> <p>Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X₇-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X₇pore formation) were determined by confocal laser microscopy.</p> <p>Results</p> <p>(a) Co-application on the skin of the P2X₇specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X₇-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X₇receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X₇receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.</p> <p>Conclusion</p> <p>(a) P2X₇-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X₇-dependent apoptosis is mediated by calcium influx via P2X₇pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X₇receptor. (d) Activation of P2X₇-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.</p

Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics

Macrophages are versatile immune cells that can detect a variety of pathogen-associated molecular patterns through their Toll-like receptors (TLRs). In response to microbial challenge, the TLR-stimulated macrophage undergoes an activation program controlled by a dynamically inducible transcriptional regulatory network. Mapping a complex mammalian transcriptional network poses significant challenges and requires the integration of multiple experimental data types. In this work, we inferred a transcriptional network underlying TLR-stimulated murine macrophage activation. Microarray-based expression profiling and transcription factor binding site motif scanning were used to infer a network of associations between transcription factor genes and clusters of co-expressed target genes. The time-lagged correlation was used to analyze temporal expression data in order to identify potential causal influences in the network. A novel statistical test was developed to assess the significance of the time-lagged correlation. Several associations in the resulting inferred network were validated using targeted ChIP-on-chip experiments. The network incorporates known regulators and gives insight into the transcriptional control of macrophage activation. Our analysis identified a novel regulator (TGIF1) that may have a role in macrophage activation

Monkeys and Humans Share a Common Computation for Face/Voice Integration

Speech production involves the movement of the mouth and other regions of the face resulting in visual motion cues. These visual cues enhance intelligibility and detection of auditory speech. As such, face-to-face speech is fundamentally a multisensory phenomenon. If speech is fundamentally multisensory, it should be reflected in the evolution of vocal communication: similar behavioral effects should be observed in other primates. Old World monkeys share with humans vocal production biomechanics and communicate face-to-face with vocalizations. It is unknown, however, if they, too, combine faces and voices to enhance their perception of vocalizations. We show that they do: monkeys combine faces and voices in noisy environments to enhance their detection of vocalizations. Their behavior parallels that of humans performing an identical task. We explored what common computational mechanism(s) could explain the pattern of results we observed across species. Standard explanations or models such as the principle of inverse effectiveness and a “race” model failed to account for their behavior patterns. Conversely, a “superposition model”, positing the linear summation of activity patterns in response to visual and auditory components of vocalizations, served as a straightforward but powerful explanatory mechanism for the observed behaviors in both species. As such, it represents a putative homologous mechanism for integrating faces and voices across primates

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Measurement of b hadron lifetimes in exclusive decays containing a J/psi in p-pbar collisions at sqrt(s)=1.96TeV

We report on a measurement of $b$-hadron lifetimes in the fully reconstructed decay modes B^+ -->J/Psi K+, B^0 --> J/Psi K*, B^0 --> J/Psi Ks, and Lambda_b --> J/Psi Lambda using data corresponding to an integrated luminosity of 4.3 ${\rm fb}^{-1}$, collected by the CDF II detector at the Fermilab Tevatron. The measured lifetimes are $\tau$B^+ = $1.639 \pm 0.009 ({\rm stat}) \pm 0.009 {\rm (syst) ~ ps}$, $\tau$B^0 = $1.507 \pm 0.010 ({\rm stat}) \pm 0.008 {\rm (syst) ~ ps}$ and $\tau$Lambda_b = $1.537 \pm 0.045 ({\rm stat}) \pm 0.014 {\rm (syst) ~ ps}$. The lifetime ratios are $\tau$B^+/$\tau$B^0 = $1.088 \pm 0.009 ({\rm stat})\pm 0.004 ({\rm syst})$ and $\tau$Lambda_b/$\tau$B^0 = $1.020 \pm 0.030 ({\rm stat})\pm 0.008 ({\rm syst})$. These are the most precise determinations of these quantities from a single experiment.Comment: revised version. accepted for PRL publicatio