Nonlinear interactions in the thalamocortical loop in essential tremor: A model-based frequency domain analysis.

There is increasing evidence to suggest that essential tremor has a central origin. Different structures appear to be part of the central tremorogenic network, including the motor cortex, the thalamus and the cerebellum. Some studies using electroencephalogram (EEG) and magnetoencephalography (MEG) show linear association in the tremor frequency between the motor cortex and the contralateral tremor electromyography (EMG). Additionally, high thalamomuscular coherence is found with the use of thalamic local field potential (LFP) recordings and tremulous EMG in patients undergoing surgery for deep brain stimulation (DBS). Despite a well-established reciprocal anatomical connection between the thalamus and cortex, the functional association between the two structures during "tremor-on" periods remains elusive. Thalamic (Vim) LFPs, ipsilateral scalp EEG from the sensorimotor cortex and contralateral tremor arm EMG recordings were obtained from two patients with essential tremor who had undergone successful surgery for DBS. Coherence analysis shows a strong linear association between thalamic LFPs and contralateral tremor EMG, but the relationship between the EEG and the thalamus is much less clear. These measurements were then analyzed by constructing a novel parametric nonlinear autoregressive with exogenous input (NARX) model. This new approach uncovered two distinct and not overlapping frequency "channels" of communication between Vim thalamus and the ipsilateral motor cortex, defining robustly "tremor-on" versus "tremor-off" states. The associated estimated nonlinear time lags also showed non-overlapping values between the two states, with longer corticothalamic lags (exceeding 50ms) in the tremor active state, suggesting involvement of an indirect multisynaptic loop. The results reveal the importance of the nonlinear interactions between cortical and subcortical areas in the central motor network of essential tremor. This work is important because it demonstrates for the first time that in essential tremor the functional interrelationships between the cortex and thalamus should not be sought exclusively within individual frequencies but more importantly between cross-frequency nonlinear interactions. Should our results be successfully reproduced on a bigger cohort of patients with essential tremor, our approach could be used to create an on-demand closed-loop DBS device, able to automatically activate when the tremor is on

High-yield production of a human monoclonal IgG by rhizosecretion in hydroponic tobacco cultures.

Rhizosecretion of recombinant pharmaceuticals from in vitro hydroponic transgenic plant cultures is a simple, low cost, reproducible and controllable production method. Here, we demonstrate the application and adaptation of this manufacturing platform to a human antivitronectin IgG1 monoclonal antibody (mAb) called M12. The rationale for specific growth medium additives was established by phenotypic analysis of root structure and by LC-ESI-MS/MS profiling of the total protein content profile of the hydroponic medium. Through a combination of optimization approaches, mAb yields in hydroponic medium reached 46 μg/mL in 1 week, the highest figure reported for a recombinant mAb in a plant secretion-based system to date. The rhizosecretome was determined to contain 104 proteins, with the mAb heavy and light chains the most abundant. This enabled evaluation of a simple, scalable extraction and purification protocol and demonstration that only minimal processing was necessary prior to protein A affinity chromatography. MALDI-TOF MS revealed that purified mAb contained predominantly complex-type plant N-glycans, in three major glycoforms. The binding of M12 purified from hydroponic medium to vitronectin was comparable to its Chinese hamster ovary (CHO)-derived counterpart. This study demonstrates that in vitro hydroponic cultivation coupled with recombinant protein rhizosecretion can be a practical, low-cost production platform for monoclonal antibodies

Muon Track Reconstruction and Data Selection Techniques in AMANDA

The Antarctic Muon And Neutrino Detector Array (AMANDA) is a high-energy neutrino telescope operating at the geographic South Pole. It is a lattice of photo-multiplier tubes buried deep in the polar ice between 1500m and 2000m. The primary goal of this detector is to discover astrophysical sources of high energy neutrinos. A high-energy muon neutrino coming through the earth from the Northern Hemisphere can be identified by the secondary muon moving upward through the detector. The muon tracks are reconstructed with a maximum likelihood method. It models the arrival times and amplitudes of Cherenkov photons registered by the photo-multipliers. This paper describes the different methods of reconstruction, which have been successfully implemented within AMANDA. Strategies for optimizing the reconstruction performance and rejecting background are presented. For a typical analysis procedure the direction of tracks are reconstructed with about 2 degree accuracy.Comment: 40 pages, 16 Postscript figures, uses elsart.st

lncRNAdb: a reference database for long noncoding RNAs

Large numbers of long RNAs with little or no protein-coding potential [long noncoding RNAs (lncRNAs)] are being identified in eukaryotes. In parallel, increasing data describing the expression profiles, molecular features and functions of individual lncRNAs in a variety of systems are accumulating. To enable the systematic compilation and updating of this information, we have developed a database (lncRNAdb) containing a comprehensive list of lncRNAs that have been shown to have, or to be associated with, biological functions in eukaryotes, as well as messenger RNAs that have regulatory roles. Each entry contains referenced information about the RNA, including sequences, structural information, genomic context, expression, subcellular localization, conservation, functional evidence and other relevant information. lncRNAdb can be searched by querying published RNA names and aliases, sequences, species and associated protein-coding genes, as well as terms contained in the annotations, such as the tissues in which the transcripts are expressed and associated diseases. In addition, lncRNAdb is linked to the UCSC Genome Browser for visualization and Noncoding RNA Expression Database (NRED) for expression information from a variety of sources. lncRNAdb provides a platform for the ongoing collation of the literature pertaining to lncRNAs and their association with other genomic elements. lncRNAdb can be accessed at: http://www.lncrnadb.org/

Unusual butterfly-shaped magnetization signals and spin-glass-like behaviour in highly oriented pyrolytic graphite

We report a novel investigation on the relationship between magnetic-ordering and graphitic-structure in highly-oriented-pyrolytic-graphite (HOPG). By employing orientation-dependent-X-ray-diffraction, Raman-spectroscopy and temperature-dependent-superconductive-quantum-interference-device (T-SQUID) we examined the presence of ferromagnetic- and superconductive-ordering in HOPG systems with 1) disordered (HOPG1, containing carbon-vacancy-rich weak-Bernal-stacking and Moiré-superlattices with θmisfit ∼ 0.5°) and 2) ordered (HOPG2, containing higher-degree of Bernal-stacking and Moiré-superlattices with θmisfit ∼ 0.5°, 0.8°, 11°) graphitic-layer-arrangement. A perfect-HOPG is expected to exhibit a diamagnetic-response to an applied-magnetic-field. Instead, additional 1) ferromagnetic-signals presenting a characteristic width-enhancement with the field increasing in HOPG1 and 2) complex butterfly-shaped ferromagnetic signals in HOPG2, are demonstrated. Temperature-dependent-magnetometry evidenced further the presence of randomly oriented ferromagnetic clusters originating from topological disorder in both HOPG1 and HOPG2. These magnetic signals were explained on the basis of the percolative-type model

Multifaceted link between cancer and inflammation

10.1042/BSR20100136Bioscience Reports3211-15BRPT

Mechanisms and consequences of TGF-ß overexpression by podocytes in progressive podocyte disease

In patients with progressive podocyte disease, such as focal segmental glomerulosclerosis (FSGS) and membranous nephropathy, upregulation of transforming growth factor-ß (TGF-ß) is observed in podocytes. Mechanical pressure or biomechanical strain in podocytopathies may cause overexpression of TGF-ß and angiotensin II (Ang II). Oxidative stress induced by Ang II may activate the latent TGF-ß, which then activates Smads and Ras/extracellular signal-regulated kinase (ERK) signaling pathways in podocytes. Enhanced TGF-ß activity in podocytes may lead to thickening of the glomerular basement membrane (GBM) by overproduction of GBM proteins and impaired GBM degradation in podocyte disease. It may also lead to podocyte apoptosis and detachment from the GBM, and epithelial-mesenchymal transition (EMT) of podocytes, initiating the development of glomerulosclerosis. Furthermore, activated TGF-ß/Smad signaling by podocytes may induce connective tissue growth factor and vascular endothelial growth factor overexpression, which could act as a paracrine effector mechanism on mesangial cells to stimulate mesangial matrix synthesis. In proliferative podocytopathies, such as cellular or collapsing FSGS, TGF-ß-induced ERK activation may play a role in podocyte proliferation, possibly via TGF-ß-induced EMT of podocytes. Collectively, these data bring new mechanistic insights into our understanding of the TGF-ß overexpression by podocytes in progressive podocyte disease