Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinectin Is a Key Effector of RhoG Microtubule-Dependent Cellular Activity

ABSTRACT RhoG is a member of the Rho family of GTPases that activates Rac1 and Cdc42 through a microtubule-dependent pathway. To gain understanding of RhoG downstream signaling, we performed a yeast two-hybrid screen from which we identified kinectin, a 156-kDa protein that binds in vitro to conventional kinesin and enhances microtubule-dependent kinesin ATPase activity. We show that RhoGGTP specifically interacts with the central domain of kinectin, which also contains a RhoA binding domain in its C terminus. Interaction was confirmed by coprecipitation of kinectin with active RhoGG12V in COS-7 cells. RhoG, kinectin, and kinesin colocalize in REF-52 and COS-7 cells, mainly in the endoplasmic reticulum but also in lysosomes. Kinectin distribution in REF-52 cells is modulated according to endogenous RhoG activity. In addition, by using injection of anti-kinectin antibodies that challenge RhoG-kinectin interaction or by blocking anti-kinesin antibodies, we show that RhoG morphogenic activity relies on kinectin interaction and kinesin activity. Finally, kinectin overexpression elicits Rac1- and Cdc42-dependent cytoskeletal effects and switches cells to a RhoA phenotype when RhoG activity is inhibited or microtubules are disrupted. The functional links among RhoG, kinectin, and kinesin are further supported by time-lapse videomicroscopy of COS-7 cells, which showed that the microtubule-dependent lysosomal transport is facilitated by RhoG activation or kinectin overexpression and is severely stemmed upon RhoG inhibition. These data establish that kinectin is a key mediator of microtubule-dependent RhoG activity and suggest that kinectin also mediates RhoG- and RhoA-dependent antagonistic pathways.
Development of low temperature co-fired ceramic (LTCC) coatings for electrical conductor wires

Dip coating was employed to apply low temperature co-firing ceramic (LTCC) zinc molybdate coatings to the surfaces of Ni-coated Cu conductor wires. Zinc molybdate ceramic powders were synthesized via a solid state route; ceramic suspensions for dip coating were prepared by mixing the LTCC powders in an organic solution. By optimizing the dip coating parameters and subsequent heat treatment, ceramic films, with a typical insulation thickness of 47.3 μm and dielectric strength of 24.2 kV·mm-1, were formed on the surfaces of Ni test discs. The processing parameters were transferrable to the coating of Ni-coated Cu wires; the resulting wires exhibited an insulation thickness of 40.3 μm and breakdown voltage of 798 V.
Neuroprotective Antioxidants from Marijuana a

Abstract: Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist Δ9‐tetrahydrocannabinol (THC) and cannabidiol, (a non‐psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor‐independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both a‐tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
Current developments in behavioral interventions for tobacco cessation

Purpose of review Tobacco use causes a significant amount of mortality and morbidity globally. The search for optimal cost-effective treatment interventions continues as current treatment modalities at best offer modest success in treatment outcome. This review evaluates current developments in behavioral interventions for tobacco cessation and their effectiveness. Recent findings Most studies of behavioral interventions reported moderate success in quitting tobacco at 6 months. This finding is seen across different professionals providing interventions in diverse settings using various modalities. Behavioral interventions in adolescents and pregnancy seem presently more effective than pharmacotherapy. Technology-driven interventions have gained recent popularity. Combining interventions shows promising results compared with a single intervention. Summary Most tobacco cessation intervention studies are from developed countries and for cigarette smoking. Long-term cessation still poses a challenge. Given the high global morbidity and mortality, there is a need to develop evidence-based, cost-effective intervention in developing countries for both smoking and smokeless tobacco use. Tobacco addiction produces neurobiological and behavioral change and optimal approaches involving behavioral methods and pharmacotherapy need to be developed.
The Effects of Optical Defocus on the Legibility of the Tumbling-E and Landolt-C

Background. The Tumbling-E and Landolt-C are both used to test visual acuity in young, illiterate, or non–English-speaking patients. In this study, we sought to determine how optical blur affects visual acuity thresholds measured with both of these optotypes. Methods. Ten subjects were tested with 4-position Tumbling-E and Landolt-Cs using the method of constant stimuli. The subjects were tested wearing their habitual corrections and with +1.50 D spherical and cylindrical lenses to simulate myopic refractive errors in the optical blur test conditions. Results. Visual acuity thresholds for the Tumbling-E were slightly better for all test conditions, while the largest threshold difference between the test letters was found for the simulated against-the-rule astigmatism. For both test letters, vertical orientations were more difficult to resolve than horizontal. Also, the slopes of the psychometric functions were steeper for the Tumbling-E than for the Landolt-C. Conclusions. The Tumbling-E can be considered comparable with the Landolt-C except for the simulated against-the-rule-astigmatism test condition. Although the ranges are quite large, the average psychometric functions of the Landolt-Cs are flatter, which gives rise to the possibility that more confidence can be placed in the visual acuity thresholds obtained with the Tumbling-E.
Evidence for structural and functional abnormality in the subgenual anterior cingulate cortex in major depressive disorder

Background. The subgenual anterior cingulate cortex (sgACC) is considered to be an important site of abnormality in major depressive disorder. However, structural alterations in this region have not been a consistent finding and functional imaging studies have also implicated additional areas. Method. A total of 32 patients with major depressive disorder, currently depressed, and 64 controls underwent structural imaging with MRI. Also, 26 patients and 52 controls were examined using functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Structural and functional changes were evaluated using whole-brain, voxel-based methods. Results. The depressed patients showed volume reductions in the sgACC and orbitofrontal cortex bilaterally, plus in both temporal poles and the hippocampus/parahippocampal gyrus on the left. Functional imaging revealed task-related hypoactivation in the left lateral prefrontal cortex and other regions, as well as failure of deactivation in a subcallosal medial frontal cortical area which included the sgACC. Conclusions. Whole-brain, voxel-based analysis finds evidence of both structural and functional abnormality in the sgACC in major depressive disorder. The fact that the functional changes in this area took the form of failure of deactivation adds to previous findings of default mode network dysfunction in the disorder.
cAMP and ras signalling independently control spore germination in the filamentous fungus Aspergillus nidulans

The role of cAMP signalling during germination of asexual spores (conidia) of the filamentous fungus Aspergillus nidulans was investigated. A. nidulans strains defective for adenylate cyclase (CyaA) or for the functionally overlapping cAMP‐dependent protein kinase (PkaA) and newly characterized SchA protein kinase, homologous to Saccharomyces cerevisiae Sch9, show altered trehalose mobilization and kinetics of germ tube outgrowth, in addition to other defects in colony formation. cAMP‐dependent trehalose breakdown is triggered by the addition of a carbon source independently of further catabolism, suggesting that cAMP signalling controls early events of conidial germination in response to carbon source sensing. Additional results suggest that cAMP has targets other than PkaA and SchA and that PkaA retains activity in the absence of cAMP. Conversely, PkaA regulates cAMP levels in A. nidulans because these are elevated by ≈ 250‐fold in a strain that lacks PkaA. Furthermore, analysis of mutant strains impaired in both adenylate cyclase and RasA GTPase previously implicated in the control of A. nidulans spore germination suggested that RasA and cAMP signalling proceed independently during germination in A. nidulans.
Evolution of Hepatitis Delta Virus RNA Genome following Long-Term Replication in Cell Culture

ABSTRACT Previous studies have defined a novel cell culture system in which a modified RNA genome of hepatitis delta virus (HDV) is able to maintain a low level of continuous replication for at least 1 year, using a separate and limited DNA-directed source of mRNA for the essential small delta protein. This mode of replication is analogous to that used by plant viroids. An examination was made of the nucleotide changes that accumulated on the HDV RNA during 1 year of replication. The length of the RNA genome was maintained, except for some single-nucleotide deletions and insertions. There was an abundance of single-nucleotide substitutions, with a 22-fold excess of these being base transitions rather than transversions. Of the detected transitions, at least 70% were consistent with being the consequences of posttranscriptional RNA editing by an adenosine deaminase acting on RNA. The remainder of the changes, including the single-nucleotide insertions and deletions, are likely to be the consequence of misincorporation during transcription. In addition, an intermolecular competition assay was used to show that the majority of the genomes present after 1 year of replication were essentially as competent in replication as the original single HDV RNA sequence that was used to initiate the genome replication. A model is provided to explain how, in this experimental system, the observed single-nucleotide changes were essentially neutral in terms of their effect on the ability of the HDV genome to carry out continued rounds of replication.
Atrophy of medial temporal lobes on MRI in “probable” Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates

HISTORICAL PERSPECTIVE In the last decades of the previous century, interest in diagnosing Alzheimer ’s disease (AD) was rising. At the same time, MRI was being discovered as an exciting, noninvasive, high resolution method to study brain changes in vivo. Autopsy studies had shown that the medial temporal lobe structures, including the hippocampus, were the structures affected earliest and most severely in AD. The first quantitative MRI studies assessing hippocampal volumes in AD described a volume reduction of the hippocampus of up to 40% in AD patients compared with control subjects. 3 Since volumetric analysis of brain structures on MRI scans is a time consuming process which is not routinely available, the need arose to have a more user friendly alternative; a quantitative visual rating scale. In the early 1990s, I had been offered the possibility of doing a six month research fellowship while in my training period of neurology at the Department of Radiology, led by Professor Jaap Valk. At that time my good friend and coworker Frederik Barkhof was working on his thesis on MRI in multiple sclerosis and I did my research on MRI in AD. We sat down and discussed ways to rate hippocampal atrophy but the actual development was done drinking beer and using the beer mat to draw on. We became so enthusiastic that we simultaneously developed a rating scale for white matter changes on MRI, published in 1993. From then on, there were two ‘Scheltens’ scales, of which the medial temporal lobe scale has proven to be the most useful. Although everything is seen in a different perspective 20 years later, and may seem to have lasted shorter than in reality, I still think that it took us probably no longer than 30 min to come up with the definite scale that was ultimately presented in our paper ‘Atrophy of medial temporal lobes on MRI in “probable” AD and normal ageing: diagnostic value and neuropsychological correlates’ in 1992. Before submission, however, we had a meeting with the coworkers, including my friend and colleague Didier Leys from Lille (France), in which we practised the use of the scale and did some inter-rater reliability assessments. At that time it was all done with hard copies and I remember the logistics were quite a challenge. It was probably written in the stars already, but 12 years later, he and I joined forces again as editors of JNNP. In this paper, one of my first PhD students that worked on the scale, Laura van de Pol, and I, aim to give an overview of the impact this scale had in further research, 20 years after its ‘conception’.
Effects of the Schroth exercise on idiopathic scoliosis: a meta-analysis.

INTRODUCTION The purpose of this study was to examine the effects of the Schroth exercise on idiopathic scoliosis. The overall effect size was analyzed in 15 primary studies and a subgroup analysis of the standardized mean differences of effect sizes from 15 primary studies was also conducted. EVIDENCE ACQUISITION We used PUBMED, MEDLINE, NDSL, EMBASE, and Web of Science. The key terms used in these searches were "Schroth," "scoliosis-specific exercise," "scoliosis," and "idiopathic scoliosis. " EVIDENCE SYNTHESIS Cobb's angle, asymmetry, angle of trunk rotation (ATR), strength of back extensor, strength of trunk flexor, quality of life (QOL), balance, chest expansion, and pulmonary function were coded as outcome measures for computing effect sizes. Potential moderating variables of the Schroth exercise included: 1) pre-intervention severity of the scoliosis; 2) duration; and 3) specific types of Schroth exercise. CONCLUSIONS The overall effect size of the Schroth exercise is high (g=0.724). In addition, Schroth exercise may be more beneficial for scoliosis patients who have a 10 to 30° Cobb's angle than for those with a greater than 30° Cobb's angle. Patients should practice the exercise for at least one month to have a better effect. Thus, therapists should consider patients' initial curve status and exercise duration before prescribing the Schroth exercise program. Core muscle strength was most influenced, and structural deformity also changed after the Schroth exercise. In sum, the Schroth exercise is a recommended treatment method for scoliosis patients.
Transdermal fentanyl patch for postoperative analgesia in total knee arthroplasty: a randomized double-blind controlled trial

Purpose To assess the efficacy of a transdermal fentanyl patch (TFP) (50 μg/hour) applied 10–12 hours before surgery versus placebo for postoperative pain control of total knee arthroplasty (TKA). Materials and methods We enrolled 40 patients undergoing elective TKA under spinal anesthesia using isobaric or hyperbaric bupivacaine. Subjects were randomized to receive a TFP (Duragesic® 50 μg/hour) or placebo patch applied with a self-adhesive to the anterior chest wall 10–12 hours before spinal anesthesia. Every patient was given patient-controlled morphine for postoperative pain control. Patients were evaluated every 4 hours until 48 hours. Results Morphine consumption at 24 and 48 hours in the TFP group versus the placebo group was 15.40±12.65 and 24.90±20.11 mg versus 33.60±19.06 and 57.80±12.65 mg (P≤0.001). Numeric rating scale scores at rest and during movement over 48 hours were lower in the TFP group. Ambulation and nausea/vomiting scores were statistically greater, but not clinically significant in the TFP group. Sedation scores were low and not statistically significantly different between groups. There was no severe respiratory depression. Conclusion TFP (50 μg/hour) applied 10–12 hours before surgery can effectively and safely decrease morphine consumption and pain scores during the first 48 hours after TKA surgery.
Fluid infusions from catheters into elastic tissue: I. Azimuthally symmetric backflow in homogeneous media

Directly injecting therapeutics into brain tissue has been investigated both experimentally and theoretically. Paul Morrison and others from the National Institutes of Health pointed out the importance of backflow along and outside a catheter inserted into the tissue, once steady state conditions have been reached. Here we investigate and extend their model. We begin with a reformulation of their results and demonstrate an exact solution that exhibits the scaling behavior of the model where the surrounding tissue medium is homogeneous and isotropic. We report on experimental tests of our predictions in agarose gels. We describe the limitations of the assumptions used and the utility of our reformulation. Extensions of the model, including improvements on some of its crude assumptions and generalizations to inhomogeneous media, will be submitted separately.
Wearable sensors objectively measure gait parameters in Parkinson’s disease

Distinct gait characteristics like short steps and shuffling gait are prototypical signs commonly observed in Parkinson’s disease. Routinely assessed by observation through clinicians, gait is rated as part of categorical clinical scores. There is an increasing need to provide quantitative measurements of gait, e.g. to provide detailed information about disease progression. Recently, we developed a wearable sensor-based gait analysis system as diagnostic tool that objectively assesses gait parameter in Parkinson’s disease without the need of having a specialized gait laboratory. This system consists of inertial sensor units attached laterally to both shoes. The computed target of measures are spatiotemporal gait parameters including stride length and time, stance phase time, heel-strike and toe-off angle, toe clearance, and inter-stride variation from gait sequences. To translate this prototype into medical care, we conducted a cross-sectional study including 190 Parkinson’s disease patients and 101 age-matched controls and measured gait characteristics during a 4x10 meter walk at the subjects’ preferred speed. To determine intraindividual changes in gait, we monitored the gait characteristics of 63 patients longitudinally. Cross-sectional analysis revealed distinct spatiotemporal gait parameter differences reflecting typical Parkinson’s disease gait characteristics including short steps, shuffling gait, and postural instability specific for different disease stages and levels of motor impairment. The longitudinal analysis revealed that gait parameters were sensitive to changes by mirroring the progressive nature of Parkinson’s disease and corresponded to physician ratings. Taken together, we successfully show that wearable sensor-based gait analysis reaches clinical applicability providing a high biomechanical resolution for gait impairment in Parkinson’s disease. These data demonstrate the feasibility and applicability of objective wearable sensor-based gait measurement in Parkinson’s disease reaching high technological readiness levels for both, large scale clinical studies and individual patient care.
Effects of hippocampal lesions on the monkey's ability to learn large sets of object‐place associations

Earlier studies found that recognition memory for object‐place associations was impaired in patients with relatively selective hippocampal damage (Vargha‐Khadem et al., Science 1997; 277:376–380), but was unaffected after selective hippocampal lesions in monkeys (Malkova and Mishkin, J Neurosci 2003; 23:1956–1965). A potentially important methodological difference between the two studies is that the patients were required to remember a set of 20 object‐place associations for several minutes, whereas the monkeys had to remember only two such associations at a time, and only for a few seconds. To approximate more closely the task given to the patients, we trained monkeys on several successive sets of 10 object‐place pairs each, with each set requiring learning across days. Despite the increased associative memory demands, monkeys given hippocampal lesions were unimpaired relative to their unoperated controls, suggesting that differences other than set size and memory duration underlie the different outcomes in the human and animal studies. © 2005 Wiley‐Liss, Inc.
Pathophysiological responses following phosgene exposure in the anaesthetized pig

This study aimed to develop a reproducible model of phosgene‐induced lung injury in the pig to facilitate the future development of therapeutic strategies. Ten female young adult large white pigs were used. Following induction of anaesthesia using a halothane/oxygen/nitrous oxide mixture, arterial and venous catheters were inserted together with a pulmonary artery thermodilution catheter, and a suprapubic urinary catheter by laparotomy. Anaesthesia was maintained throughout the experiment by intravenous infusion of ketamine, midazolam and alfentanil. On completion of surgery the animals were allowed to equilibrate for 1 h and then were divided into two groups. Group 1 (n = 5) was exposed to phosgene for 10 min (mean Ct = 2443 ± 35 mg min m−3) while spontaneously breathing, whereas control animals (Group 2 n = 5) were exposed to air. At 30 min post‐exposure, anaesthesia was deepened in order to allow the initiation of intermittent positive pressure ventilation and the animals were monitored for up to 24 h. Cardiovascular and respiratory parameters were monitored every 30 min and blood samples were taken for arterial and mixed venous blood gas analysis and clinical chemistry. A detailed post‐mortem and histopathology was carried out on all animals following death or euthanasia at the end of the 24‐h monitoring period.