Brief stimuli cast a persistent long-term trace in visual cortex

Visual processing is strongly influenced by the recent stimulus history - a phenomenon termed adaptation. Prominent theories cast adaptation as a consequence of optimized encoding of visual information, by exploiting the temporal statistics of the world. However, this would require the visual system to track the history of individual briefly experienced events, within a stream of visual input, to build up statistical representations over longer timescales. Here, using an openly available dataset from the Allen Brain Observatory, we show that neurons in the early visual cortex of the mouse indeed maintain long-term traces of individual past stimuli that persist despite the presentation of several intervening stimuli, leading to long-term and stimulus-specific adaptation over dozens of seconds. Long-term adaptation was selectively expressed in cortical, but not in thalamic neurons, which only showed short-term adaptation. Early visual cortex thus maintains concurrent stimulus-specific memory traces of past input, enabling the visual system to build up a statistical representation of the world to optimize the encoding of new information in a changing environment.SIGNIFICANCE STATEMENTIn the natural world, previous sensory input is predictive of current input over multi-second timescales. The visual system could exploit these predictabilities by adapting current visual processing to the long-term history of visual input. However, it is unclear whether the visual system can track the history of individual briefly experienced images, within a stream of input, to build up statistical representations over such long timescales. Here, we show that neurons in early visual cortex of the mouse brain exhibit remarkably long-term adaptation to brief stimuli, persisting over dozens of seconds, and despite the presentation of several intervening stimuli. The visual cortex thus maintains long-term traces of individual briefly experienced past images, enabling the formation of statistical representations over extended timescales

Changes in biomechanical properties of chemotherapy bone cement after a year in saline storage

Introduction: Acrylic based bone cements are a versatile treatment modality in Orthopaedic surgery due to their wide variety of uses and tolerance to high degree of customization. Bone cement can be used to repair and stabilize pathologic fractures and may potentially prevent recurrence post tumor resection. Chemotherapeutic bone cements are favorable because they can potentially minimize systemic side effects and the need for radiation. Cements can be combined with soluble fillers such as polyethylene glycol (PEG) to optimize drug elution. Even though studies have measured the mechanical properties of bone cement in dry state, the exact change in the mechanical properties of bone cement after drug/soluble filler elution is largely unknown. This study investigates the change in mechanical properties of commercially available bone cements modified with PEG fillers after one year of storage in drug elution medium. Methods: Confidence Ultra, Vertebroplastic, and Palacos cement were used and mixed with varying amounts (0–50%) of PEG and chemotherapy agents (methotrexate or doxorubicin). Bone cement specimens were stored in a saline solution for one year after which they were tested in compression at 1 mm/min until failure. Results: The modulus and compression strength of bone cements decreased with increase in soluble filler composition. Although soluble fillers were shown to weaken the mechanical properties of the bone cement, Palacos and Vertebroplastic cements retained their mechanical properties better than Confidence. Discussion: When using chemotherapeutic bone cements, combining soluble fillers enhances drug elution at the expense of mechanical properties. However, the results showed that mechanical properties of different commercially available bone cements behave differently with similar percentages of soluble filler and drug added making it difficult to predict changes in mechanical properties of bone cement intraoperatively. This elucidates the need for well characterized bone cement optimized for chemotherapy drug delivery

Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography

Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture

Video-rate fluorescence diffuse optical tomography for in vivo sentinel lymph node imaging

We have developed a fiber-based, video-rate fluorescence diffuse optical tomography (DOT) system for noninvasive in vivo sentinel lymph node (SLN) mapping. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established in to depths of >10 mm. In vivo accumulation of indocyanine green (ICG) dye was imaged in the region of the SLN following intradermal injection into the forepaw of rats. These results suggest that video-rate fluorescence DOT has significant potential as a clinical tool for noninvasive mapping of SLN

Early-branching gut fungi possess a large, comprehensive array of biomass-degrading enzymes

available in PMC 2016 November 07The fungal kingdom is the source of almost all industrial enzymes in use for lignocellulose bioprocessing. We developed a systems-level approach that integrates transcriptomic sequencing, proteomics, phenotype, and biochemical studies of relatively unexplored basal fungi. Anaerobic gut fungi isolated from herbivores produce a large array of biomass-degrading enzymes that synergistically degrade crude, untreated plant biomass and are competitive with optimized commercial preparations from Aspergillus and Trichoderma. Compared to these model platforms, gut fungal enzymes are unbiased in substrate preference due to a wealth of xylan-degrading enzymes. These enzymes are universally catabolite-repressed and are further regulated by a rich landscape of noncoding regulatory RNAs. Additionally, we identified several promising sequence-divergent enzyme candidates for lignocellulosic bioprocessing.United States. Dept. of Energy. Office of Science (Biological and Environmental Research (BER) program)United States. Department of Energy (DOE Grant DE-SC0010352)United States. Department of Agriculture (Award 2011-67017-20459)Institute for Collaborative Biotechnologies (grant W911NF-09-0001

Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group Trial 01.04

Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown

Silencing Early Viral Replication in Macrophages and Dendritic Cells Effectively Suppresses Flavivirus Encephalitis

West Nile (WN) and St. Louis encephalitis (SLE) viruses can cause fatal neurological infection and currently there is neither a specific treatment nor an approved vaccine for these infections. In our earlier studies, we have reported that siRNAs can be developed as broad-spectrum antivirals for the treatment of infection caused by related viruses and that a small peptide called RVG-9R can deliver siRNA to neuronal cells as well as macrophages. To increase the repertoire of broad-spectrum antiflaviviral siRNAs, we screened 25 siRNAs targeting conserved regions in the viral genome. Five siRNAs were found to inhibit both WNV and SLE replication in vitro reflecting broad-spectrum antiviral activity and one of these was also validated in vivo. In addition, we also show that RVG-9R delivers siRNA to macrophages and dendritic cells, resulting in effective suppression of virus replication. Mice were challenged intraperitoneally (i.p.) with West Nile virus (WNV) and treated i.v. with siRNA/peptide complex. The peritoneal macrophages isolated on day 3 post infection were isolated and transferred to new hosts. Mice receiving macrophages from the anti-viral siRNA treated mice failed to develop any disease while the control mice transferred with irrelevant siRNA treated mice all died of encephalitis. These studies suggest that early suppression of viral replication in macrophages and dendritic cells by RVG-9R-mediated siRNA delivery is key to preventing the development of a fatal neurological disease

Activity, stability and 3-D structure of the Cu(II) form of a chitin-active lytic polysaccharide monooxygenase from Bacillus amyloliquefaciens

The enzymatic deconstruction of recalcitrant polysaccharide biomass is central to the conversion of these substrates for societal benefit, such as in biofuels. Traditional models for enzyme-catalysed polysaccharide degradation involved the synergistic action of endo-, exo-and processive glycoside hydrolases working in concert to hydrolyse the substrate. More recently this model has been succeeded by one featuring a newly discovered class of mononuclear copper enzymes: lytic polysaccharide monooxygenases (LPMOs; classified as Auxiliary Activity (AA) enzymes in the CAZy classification). In 2013, the structure of an LPMO from Bacillus amyloliquefaciens, BaAA10, was solved with the Cu centre photoreduced to Cu(I) in the X-ray beam. Here we present the catalytic activity of BaAA10. We show that it is a chitin-active LPMO, active on both α and β chitin, with the Cu(II) binding with low nM KD, and the substrate greatly increasing the thermal stability of the enzyme. A spiral data collection strategy has been used to facilitate access to the previously unobservable Cu(II) state of the active centre, revealing a coordination geometry around the copper which is distorted from axial symmetry, consistent with the previous findings from EPR spectroscopy