julilili42/papers huggingface dataset:
Brain–computer interfaces: communication and restoration of movement in paralysis
2007-01-19

The review describes the status of brain–computer or brain–machine interface research. We focus on non‐invasive brain–computer interfaces (BCIs) and their clinical utility for direct brain communication in paralysis and motor restoration in stroke. A large gap between the promises of invasive animal and human BCI preparations and the clinical reality characterizes the literature: while intact monkeys learn to execute more or less complex upper limb movements with spike patterns from motor brain regions alone without concomitant peripheral motor activity usually after extensive training, clinical applications in human diseases such as amyotrophic lateral sclerosis and paralysis from stroke or spinal cord lesions show only limited success, with the exception of verbal communication in paralysed and locked‐in patients. BCIs based on electroencephalographic potentials or oscillations are ready to undergo large clinical studies and commercial production as an adjunct or a major assisted communication device for paralysed and locked‐in patients. However, attempts to train completely locked‐in patients with BCI communication after entering the complete locked‐in state with no remaining eye movement failed. We propose that a lack of contingencies between goal directed thoughts and intentions may be at the heart of this problem. Experiments with chronically curarized rats support our hypothesis; operant conditioning and voluntary control of autonomic physiological functions turned out to be impossible in this preparation. In addition to assisted communication, BCIs consisting of operant learning of EEG slow cortical potentials and sensorimotor rhythm were demonstrated to be successful in drug resistant focal epilepsy and attention deficit disorder. First studies of non‐invasive BCIs using sensorimotor rhythm of the EEG and MEG in restoration of paralysed hand movements in chronic stroke and single cases of high spinal cord lesions show some promise, but need extensive evaluation in well‐controlled experiments. Invasive BMIs based on neuronal spike patterns, local field potentials or electrocorticogram may constitute the strategy of choice in severe cases of stroke and spinal cord paralysis. Future directions of BCI research should include the regulation of brain metabolism and blood flow and electrical and magnetic stimulation of the human brain (invasive and non‐invasive). A series of studies using BOLD response regulation with functional magnetic resonance imaging (fMRI) and near infrared spectroscopy demonstrated a tight correlation between voluntary changes in brain metabolism and behaviour.
Role of cholinergic‐activated KCa1.1 (BK), KCa3.1 (SK4) and KV7.1 (KCNQ1) channels in mouse colonic Cl− secretion
2007-01-19

Abstract Aim: Colonic crypts are the site of Cl − secretion. Basolateral K + channels provide the driving force for luminal cystic fibrosis transmembrane regulator‐mediated Cl − exit. Relevant colonic epithelial K + channels are the intermediate conductance Ca 2+ ‐activated K Ca 3.1 (SK4) channel and the cAMP‐activated K V 7.1 (KCNQ1) channel. In addition, big conductance Ca 2+ ‐activated K Ca 1.1 (BK) channels may play a role in Ca 2+ ‐activated Cl − secretion. Here we use K Ca 1.1 and K Ca 3.1 knock‐out mice, and the K V 7.1 channel inhibitor 293B (10 μ m ) to investigate the role of K Ca 1.1, K Ca 3.1 and K V 7.1 channels in cholinergic‐stimulated Cl − secretion. Methods: A Ussing chamber was used to quantify agonist‐stimulated increases in short circuit current ( I sc ) in distal colon. Chloride secretion was activated by bl. forskolin (FSK, 2 μ m ) followed by bl. carbachol (CCH, 100 μ m ). Luminal Ba 2+ (5 m m ) was used to inhibit K Ca 1.1 channels. Results: K Ca 1.1 WT and KO mice displayed identical FSK and CCH‐stimulated I sc changes, indicating that K Ca 1.1 channels are not involved in FSK‐ and cholinergic‐stimulated Cl − secretion. CCH‐stimulated Δ I sc was significantly reduced in K Ca 3.1 KO mice, underscoring the known relevance of this channel in the activation of Cl − secretion by an intracellular Ca 2+ increasing agonist. The residual CCH effect observed in K Ca 3.1 KO mice suggests that yet another K + channel is driving the CCH‐stimulated Cl − secretion. In the presence of the specific K V 7.1 channel blocker 293B, the residual CCH effect was abolished. Conclusions: This demonstrates that both K Ca 3.1 and K V 7.1 channels are activated by cholinergic agonists and drive Cl − secretion. In contrast, K Ca 1.1 channels are not involved in stimulated electrogenic Cl − secretion.
Adenosine metabolism and its effect on methylation potential in cultured cells: methodological considerations.
2007-01-21

Cell culture models are frequently used to study the role of adenosine in several physiological and pathological processes. In the present study, we have shown that adenosine deaminase activity in medium supplemented with calf serum significantly reduces adenosine concentration in culture medium. In the presence of HepG2 cells, the adenosine concentration in culture medium is decreased much faster, because a large amount of exogenous adenosine is metabolized by cellular enzyme. In order to measure intracellular adenosine, inosine, adenine nucleotides, S-adenosylhomocysteine (AdoHcy) and Sadenosylmethionine (AdoMet) contents, two methods for cell harvesting were compared. First, cells were removed with trypsin/EDTA, second, cells were lysed in cell culture dishes immediately after removing culture medium. Our results show that exact determination of adenosine metabolites requires immediate inactivation of metabolism by cell lysis in culture dishes. Application of adenosine (1mM) resulted in a time-dependent increase in intracellular adenosine, inosine, AMP, ATP, AdoHcy and AdoMet concentration. Since AdoHcy levels increased to a larger extent than AdoMet, the methylation potential, expressed as the ratio of AdoMet/AdoHcy, was reduced from 51.8 (control) to 2.9 (adenosine 1 mM, 2 hrs), suggesting that AdoMet-dependent methylation reactions might be impaired. In conclusion our data demonstrate that extracellular adenosine concentration and intracellular metabolite concentration strongly depend on the methods used to culture and harvest the cells.
In vivo and ex vivo comparative transcriptional profiling of invasive and non‐invasive Candida albicans isolates identifies genes associated with tissue invasion
2007-01-22

Summary The human pathogenic fungus Candida albicans can cause a wide range of infections and invade multiple organs. To identify C. albicans genes that are expressed during invasion of the liver, we used genome‐wide transcriptional profiling in vivo and ex vivo . By analysing the different phases of intraperitoneal infection from attachment to tissue penetration in a time‐course experiment and by comparing the profiles of an invasive with those of a non‐invasive strain, we identified genes and transcriptional pattern which are associated with the invasion process. This includes genes involved in metabolism, stress, and nutrient uptake, as well as transcriptional programmes regulating morphology and environmental sensing. One of the genes identified as associated with liver invasion was DFG16 , a gene crucial for pH‐dependent hyphal formation, correct pH sensing, invasion at physiological pH and systemic infection.
Interactions of PIN and PGP auxin transport mechanisms
2007-01-22

Polarized transport of the plant hormone auxin influences multiple growth processes in plants and is regulated by plasma-membrane-localized efflux and uptake carriers. The PGP (P-glycoprotein) ABC transporters (ATP-binding-cassette transporters), PIN (pin-formed) subfamily of major facilitator proteins and members of AUX/LAX families have been shown to independently transport auxin both in planta and in heterologous systems. However, PIN- and PGP-mediated transport in heterologous systems exhibits decreased substrate specificity and inhibitor-sensitivity compared with what is seen in plants and plant cells. To determine whether PIN–PGP interactions enhance transport specificity, we analysed interactions of the representative auxin-transporting PGPs with PIN1 and AUX1 in planta and in heterologous systems. Here, we provide evidence that PINs and PGPs interact and function both independently and co-ordinately to control polar auxin transport and impart transport specificity and directionality. These interactions take place in protein complexes stabilized by PGPs in detergent-resistant microdomains.
Analysis of the monovalent ion fluxes in U937 cells under the balanced ion distribution: Recognition of ion transporters responsible for changes in cell ion and water balance during apoptosis
2007-01-22

Abstract Unidirectional 22 Na, Li + and Rb + fluxes and net fluxes of Na + and K + were measured in U937 human leukemic cells before and after induction of apoptosis by staurosporine (1 μM, 4 h) to answer the question which ion transporter(s) are responsible for changes in cell ion and water balance at apoptosis. The original version of the mathematical model of cell ion and water balance was used for analysis of the unidirectional ion fluxes under the balanced distribution of major monovalent ions across the cell membrane. The values of all major components of the Na + and K + efflux and influx, i.e. fluxes via the Na + ,K + ‐ATPase pump, Na + channels, K + channels, Na/Na exchanger and Na‐Cl symport were determined. It is concluded that apoptotic cell shrinkage and changes in Na + and K + fluxes typical of apoptosis in U937 cells induced by staurosporine are caused by a complex decrease in the pump activity, Na‐Cl symport and integral Na + channel permeability.
The astrocytic response towards invasive meningiomas
2007-01-22

Invasive meningiomas disrupt the pial–glial basement membrane. This membrane is closely attached to the subpial glial endfeet forming the glia limitans. The fate of subpial astrocytes during the course of brain invasion by meningiomas is not known. In the present study we immunolabelled sections of 35 brain‐invasive meningiomas (14 meningothelial meningiomas WHO grade I, 11 atypical WHO grade II and 10 anaplastic WHO grade III) using anti‐collagen IV to label basement membrane material, and antibodies against astrocytic markers CD44, SPARC (secreted protein, acidic and rich in cysteine) and glial fibrillary acidic protein (GFAP). Astrocytes were present at the tumour–brain interface of 14/14 WHO grade I meningiomas, 9/11 WHO grade II tumours and 9/10 WHO grade III tumours. The presence of astrocytes was associated with an intact basement membrane in 11/14 WHO grade I meningiomas ( P &lt; 0.01), 6/9 WHO grade II tumours, and 6/9 WHO grade III tumours. However, tumour embedded in deep brain parenchyma lacked both an astrocytic reaction and basement membrane material. In conclusion, astrocytes eventually disappear from the tumour–brain interface during the course of meningioma infiltration. This observation might indicate that the survival of subpial astrocytes is dependent on an intact pial–glial basement membrane.
Phosphoinositide 3‐kinase inhibitor LY294002 but not serum withdrawal suppresses proliferation of murine embryonic stem cells
2007-01-22

Abstract Mouse embryonic stem (mES) cells have short duration of their cell cycle and are capable of proliferating in the absence of growth factors. To find out which signaling pathways contribute to the regulation of the mES cell cycle, we used pharmacological inhibitors of MAP and PI3 kinase cascades. The MAP kinase inhibitors as well as serum withdrawal did not affect mES cell cycle distribution, whereas the inhibitor of PI3K activity, LY294002, induced accumulation of cells in G 1 phase followed by apoptotic cell death. Serum withdrawal also causes apoptosis, but it does not change the content and activity of cell cycle regulators. In contrast, in mES cells treated with LY294002, the activities of Cdk2 and E2F were significantly decreased. Interestingly, LY294002 had a much stronger effect on cell cycle distribution in low serum conditions, implying that serum can promote G 1 → S transition of mES cells by a LY294002‐resistant mechanism. Thus, proliferation of mES cells is maintained by at least two separate mechanisms: a LY294002‐sensitive pathway, which is active even in the absence of serum, and LY294002‐resistant, but serum‐dependent, pathway.
De novo erythropoietin receptor (EPO‐R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival
2007-01-22

The erythropoietin receptor (EPO‐R) is mainly known as a regulator of erythropoiesis. However, recent studies revealed that the EPO‐R is not exclusively expressed in haematopoietic tissues but also in various cancer cell types and normal tissue such as the central nervous system (CNS). EPO‐R is up‐regulated under hypoxia and is able to counteract the deleterious effects of hypoxia on tumour growth, metastasis and treatment resistance. Therefore, the EPO–EPO‐R signalling pathway is considered as a possible target for tumour treatment. Here, we investigated brain tumour samples obtained from patients between 1993 and 2003 to study EPO‐R expression in vivo . Tissue samples included 194 gliomas of different WHO grades, additionally 25 infiltration zone samples and 31 relapses of WHO grade IV glioblastomas as well as 23 normal CNS tissue specimens to address the in vivo situation. Immunohistochemistry of the tissue microarray samples revealed significantly higher levels of EPO‐R expression in neoplastic glial cells compared with glial cells derived from normal brain. EPO‐R expression showed a highly significant decrease from low‐ to high‐grade gliomas. Age‐stratified Kaplan‐Meier analysis revealed longer survival for patients exhibiting high EPO‐R status in high‐grade gliomas. Our results show a grade‐dependent EPO‐R down‐regulation and might contribute to the understanding of high‐grade glioma resistance to radio‐ and chemotherapy as both were shown to be improved by a well functioning EPO–EPO‐R pathway in previous studies. Further studies are needed to investigate to what extent the decreased mortality in age‐stratified patient groups with high EPO‐R levels reflects a direct beneficial role of EPO‐R expression.
Diagnostic value of serum antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis patients
2007-01-23

Abstract Specific serum antibodies could be helpful in defining the status of Pseudomonas aeruginosa infection as well as the response to early intervention treatment in patients with cystic fibrosis (CF). We used 1,791 serum samples from 375 European CF patients with known respiratory microbiology status to define titers of P. aeruginosa antibodies directed against alkaline protease (AP), elastase (ELA), and exotoxin A (ExoA). Pseudomonas antibody titers were also measured in a separate cohort of 56 patients undergoing antibiotic treatment for eradication of P. aeruginosa . At a specificity of 97.5%, the sensitivity was highest for antibodies against AP (85.4%), followed by ELA (76.2%) and ExoA (72.0%). AP, ELA, or ExoA antibody titers were significantly higher ( P &lt; 0.001) in patients chronically infected with P. aeruginosa compared to patients with negative cultures. The sensitivity of the combined three ELISAs was higher than that for any single ELISA alone. Based on the newly defined cut‐off levels, positive serum antibody titers against at least one of the three antigens were present in 43% of patients with new onset of P. aeruginosa infection. Longitudinal assessment of antibody titers assessed before and after inhaled antibiotic therapy in patients with first P . aeruginosa isolation showed a significant decrease in antibody titers against AP and ExoA in patients clearing P. aeruginosa infection, whereas titers increased in patients in whom antibiotic therapy failed to eradicate the organism. Antibody testing against AP, ELA, and ExoA offers high sensitivity and specificity for the presence of P. aeruginosa in respiratory cultures of CF patients. Although serum antibody titers are on average low at the time of first P. aeruginosa isolation from respiratory specimens, they may be useful to monitor response to therapy. However, because variability between patients is considerable, treatment decisions should not be based on P. aeruginosa antibody levels alone. Pediatr Pulmonol. 2007; 42:249–255. © 2007 Wiley‐Liss, Inc.
Precopulatory stabbing, hypodermic injections and unilateral copulations in a hermaphroditic sea slug
2007-01-23

Reciprocity constitutes the prevalent mating mechanism among simultaneous hermaphrodites. Yet, when copulations in the female role confer fitness costs through male manipulation, it becomes advantageous sometimes to mate unilaterally in the male role only. In the sea slug Siphopteron quadrispinosum , acting males stab their partner with a bipartite penis, which not only hypodermically injects prostate fluids, but also apparently mechanically enforces unilateral male matings. Despite a pronounced male mating drive in both partners, unilaterality ensued when one slug stabbed more rapidly than its partner. The acting male may thus avoid the costs inflicted by traumatic injections and penial spines. While future studies need to elucidate the net fitness consequences of stabbing, our behavioural evidence is in line with the hypothesis that mating in S. quadrispinosum represents conflicting rather than complementary mating interests between mates.
Distortion product otoacoustic emissions measured as vibration on the eardrum of human subjects
2007-01-23

It has previously not been possible to measure eardrum vibration of human subjects in the region of auditory threshold. It is proposed that such measurements should provide information about the status of the mechanical amplifier in the cochlea. It is this amplifier that is responsible for our extraordinary hearing sensitivity. Here, we present results from a laser Doppler vibrometer that we designed to noninvasively probe cochlear mechanics near auditory threshold. This device enables picometer-sized vibration measurements of the human eardrum in vivo . With this sensitivity, we found the eardrum frequency response to be linear down to at least a 20-dB sound pressure level (SPL). Nonlinear cochlear amplification was evaluated with the cubic distortion product of the otoacoustic emissions (DPOAEs) in response to sound stimulation with two tones. DPOAEs originate from mechanical nonlinearity in the cochlea. For stimulus frequencies, f 1 and f 2 , with f 2 / f 1 = 1.2 and f 2 = 4–9.5 kHz, and intensities L 1 and L 2 , with L 1 = 0.4 L 2 + 39 dB and L 2 = 20–65 dB SPL, the DPOAE displacement amplitudes were no more than 8 pm across subjects ( n = 20), with hearing loss up to 16 dB. DPOAE vibration was nonlinearly dependent on vibration at f 2 . The dependence allowed the hearing threshold to be estimated objectively with high accuracy; the standard deviation of the threshold estimate was only 8.6 dB SPL. This device promises to be a powerful tool for differentially characterizing the mechanical condition of the cochlea and middle ear with high accuracy.
Synthesis of 3,4-disaccharides from pyranosides and furanosides monomers, a novel class of potential bioactive disaccharides
2007-01-23

A new class of synthetically and pharmacologically important disaccharides containing epoxide moieties were synthesized from pyranoside and furanoside monomers in good to excellent yields.The scope and limitations for the formation of the linkage were evaluated.
Increased trehalose biosynthesis in Hartig net hyphae of ectomycorrhizas
2007-01-24

To obtain photoassimilates in ectomycorrhizal symbiosis, the fungus has to create a strong sink, for example, by conversion of plant-derived hexoses into fungus-specific compounds. Trehalose is present in large quantities in Amanita muscaria and may thus constitute an important carbon sink. In Amanita muscaria-poplar (Populus tremula x tremuloides) ectomycorrhizas, the transcript abundances of genes encoding key enzymes of fungal trehalose biosynthesis, namely trehalose-6-phosphate synthase (TPS), trehalose-6-phosphate phosphatase (TPP) and trehalose phosphorylase (TP), were increased. When mycorrhizas were separated into mantle and Hartig net, TPS, TPP and TP expression was specifically enhanced in Hartig net hyphae. Compared with the extraradical mycelium, TPS and TPP expression was only slightly increased in the fungal sheath, while the increase in the expression of TP was more pronounced. TPS enzyme activity was also elevated in Hartig net hyphae, displaying a direct correlation between transcript abundance and turnover rate. In accordance with enhanced gene expression and TPS activity, trehalose content was 2.7 times higher in the Hartig net. The enhanced trehalose biosynthesis at the plant-fungus interface indicates that trehalose is a relevant carbohydrate sink in symbiosis. As sugar and nitrogen supply affected gene expression only slightly, the strongly increased expression of the investigated genes in mycorrhizas is presumably developmentally regulated.
Ring‐Opening Reactions of Benzotriazoles with Wittig Reagents.
2007-01-24

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication
2007-01-25

Our findings extend clinical, genetic, and genealogical research on the Lister family complex. The genetic basis for familial parkinsonism is an SNCA-MMRN11 multiplication, but whereas SNCA-MMRN1 duplication in the Swedish proband (Branch J) leads to late-onset autonomic dysfunction and parkinsonism, SNCA-MMRN1 triplication in the Swedish American family (Branch I) leads to early-onset Parkinson disease and dementia.
Genome-Wide Expression Profiling of the Retinoschisin-Deficient Retina in Early Postnatal Mouse Development
2007-01-25

purpose. The Rs1h knockout mouse displays retinal features typical for X-linked juvenile retinoschisis (RS). Consequently, this mouse line represents an excellent model to study early molecular events in RS. methods. Whole genome expression profiling using DNA-microarrays was performed on total RNA extracts from retinoschisin-deficient and wild-type murine retinas from postnatal days 7, 9, 11, and 14. Quantitative real-time RT-PCR (qRT-PCR) analysis of additional time points facilitated the refinement of the temporal expression profile of differentially regulated transcripts. Differential protein expression was confirmed by Western blot analysis. results. Based on biostatistic and knowledge-based DNA-microarray analyses we have identified differentially regulated retinal genes in early postnatal stages of the Rs1h-deficient mouse defining key molecular pathways including adhesion, cytoskeleton, vesicular trafficking, and immune response. A significant upregulation of Egr1 at P11 and several microglia/glia-related transcripts starting at P11 with a peak at P14 were identified in the diseased retina. The results provided evidence that macrophage/microglia activation precedes apoptotic photoreceptor cell death. Finally, the role of Egr1 in the pathogenesis of Rs1h-deficiency was investigated, and the results indicated that activation of the MAPK Erk1/2 pathway occurs as early as P7. Analyses of Rs1h −/Y /Egr1 −/− double-knockout mice suggest that Egr1 upregulation is not a prerequisite for macrophage/microglia activation or apoptosis. conclusions. The findings imply that microglia/glia activation may be triggering events in the photoreceptor degeneration of retinoschisin-deficient mice. Furthermore, the data point to a role of Erk1/2-Egr1 pathway activation in RS pathogenesis.