Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective knockdown of ceramide synthases reveals complex interregulation of sphingolipid metabolism[S]

Mammalian ceramide synthases 1 to 6 (CerS1–6) generate Cer in an acyl-CoA-dependent manner, and expression of individual CerS has been shown to enhance the synthesis of ceramides with particular acyl chain lengths. However, the contribution of each CerS to steady-state levels of specific Cer species has not been evaluated. We investigated the knockdown of individual CerS in the MCF-7 human breast adenocarcinoma cell line by using small-interfering RNA (siRNA). We found that siRNA-induced downregulation of each CerS resulted in counter-regulation of nontargeted CerS. Additionally, each CerS knockdown produced unique effects on the levels of multiple sphingolipid species. For example, downregulation of CerS2 decreased very long-chain Cer but increased levels of CerS4, CerS5, and CerS6 expression and upregulated long-chain and medium-long-chain sphingolipids. Conversely, CerS6 knockdown decreased C16:0-Cer but increased CerS5 expression and caused non-C16:0 sphingolipids to be upregulated. Knockdown of individual CerS failed to decrease total sphingolipids or upregulate sphingoid bases. Treatment with siRNAs targeting combined CerS, CerS2, CerS5, and CerS6, did not change overall Cer or sphingomyelin mass but caused upregulation of dihydroceramide and hexosylceramide and promoted endoplasmic reticulum stress. These data suggest that sphingolipid metabolism is robustly regulated by both redundancy in CerS-mediated Cer synthesis and counter-regulation of CerS expression.
Elevated Serum S100B Levels Indicate a Higher Risk of Hemorrhagic Transformation After Thrombolytic Therapy in Acute Stroke

Background and Purpose— Intracerebral hemorrhage constitutes an often fatal sequela of thrombolytic therapy in patients with ischemic stroke. Early blood–brain barrier disruption may play an important role, and the astroglial protein S100B is known to indicate blood–brain barrier dysfunction. We investigated whether elevated pretreatment serum S100B levels predict hemorrhagic transformation (HT) in thrombolyzed patients with stroke. Methods— We retrospectively included 275 patients with ischemic stroke (mean age of 69±13 years; 46% female) who had received thrombolytic therapy within 6 hours of symptom onset. S100B levels were determined from pretreatment blood samples. Follow-up brain scans were obtained 24 hours after admission, and HT was classified as either hemorrhagic infarction (1, 2) or parenchymal hemorrhage (1, 2). Results— HT occurred in 80 patients (29%; 45 hemorrhagic infarction, 35 parenchymal hemorrhage). Median S100B values were significantly higher in patients with HT (0.14 versus 0.11 &mgr;g/L; P=0.017). An S100B value in the highest quintile corresponded to an OR for any HT of 2.87 (95% CI: 1.55 to 5.32; P=0.001) in univariate analysis and of 2.80 (1.40 to 5.62; P=0.004) after adjustment for age, sex, symptom severity, timespan from symptom onset to hospital admission, vascular risk factors, and storage time of serum probes. A pretreatment S100B value above 0.23 &mgr;g/L had only a moderate sensitivity (0.46) and specificity (0.82) for predicting severe parenchymal bleeding (parenchymal hemorrhage 2). Conclusions— Elevated S100B serum levels before thrombolytic therapy constitute an independent risk factor for HT in patients with acute stroke. Unfortunately, the diagnostic accuracy of S100B is too low for it to function in this context as a reliable biomarker in clinical practice.
Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex

Objective Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients’ neuropsychological profile at presentation or their long-term cognitive outcome. Methods We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Results Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. Conclusions The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.
Abandoning first generation supraglottic airway devices

ABW were constructed using methods previously described [4], based on the relevant equations [1]. Each nomogram includes a list of relevant perioperative drugs (Fig. 3). The nomograms were evaluated using a randomly generated dataset of 100 simulated patient values for height and weight. Two investigators performed calculations of LBW and ABW using printed A4 copies of each nomogram and a straight edged ruler. Bland-Altman analysis was used to compare the values for LBW and ABW calculated using the nomogram with corresponding values calculated using a spreadsheet. The mean (SD) LBW nomogram bias was 0.09 (0.10) kg, with limits of agreement 0.10 to 0.28 and mean (SD) percentage error 0.15 (0.17) %. The ABW nomogram bias was 0.06 (0.09) kg, with limits of agreement 0.23 to 0.11 and percentage error 0.06 (0.11) %. This demonstrates a high degree of agreement between the nomograms and the calculated values. Nomograms have been validated and used in the healthcare setting for some time and their advantages include accuracy, low cost and convenience. Similar nomograms for LBW calculations in paediatric obesity have been shown to be quicker and less likely to result in mistakes than equations performed with the aid of a calculator [4]. Each nomogram is designed to be reproduced as an A4 sheet and can be laminated and placed within the anaesthetic room or in the departmental ‘obesity pack’. Alternatively, the nomograms may be printed and filed in the patient’s records for future reference.
Energy Expenditure During a 160 km Endurance Race

Introduction In endurance racing, horses are required to complete distances of up to 160 km in a single day. To date, the energy expenditure (EE) of such effort has not been quantified. This study aimed to evaluate EE during a 160 km endurance race from heart rate (HR) monitoring. Methods Three weeks before competing, two endurance horses (H1 and H2) were submitted to a field exercise test to determine their individual VO2-HR relationship. VO2 and HR were recorded simultaneously at trot (13–14 km/h for 10 min), and at canter (18–19 km/h for 10 min, and 22–23 km/h for 5 min), using the equine K4b2, a portable metabolic measurement system. H1 was then enrolled in Monpazier CEI and H2 in Florac CEI. HR was monitored from 2 minutes before the start to the finishing line of each loop. EE of exercise was calculated from individual VO2-HR relationship and caloric equivalent of oxygen. Results H1 and H2 completed the race at an average speed of 17.02 and 14.46 km/h, respectively. Mean HR was 108 ± 8 and 124 ± 24 and peak HR was 169 and 204 for H1 and H2, respectively. The proportion of time spent at HR≥180 was 0 and 2.7% for H1 and H2 respectively. EE of exercise was evaluated at 177 and 240 MJ for H1 and H2 respectively. Conclusions A 160-km endurance race might present a considerable energy cost, at least 5 times the EE of non-working state. Ethical Animal Research The project was conducted under license from the Department of Health and Animal Care of the French Veterinary Authority (no. A21002) and ethics committee approval n° B0710. Sources of funding: Burgundy Region and AgroSup Dijon. Competing interests: none.
Altered vitamin E status in Niemann-Pick type C disease

Vitamin E (α-tocopherol) is the major lipid-soluble antioxidant in many species. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene, which regulates lipid transport through the endocytic pathway. NPC disease is characterized by massive intracellular accumulation of unesterified cholesterol and other lipids in lysosomal vesicles. We examined the roles that NPC1/2 proteins play in the intracellular trafficking of tocopherol. Reduction of NPC1 or NPC2 expression or function in cultured cells caused a marked lysosomal accumulation of vitamin E in cultured cells. In vivo, tocopherol significantly accumulated in murine Npc1-null and Npc2-null livers, Npc2-null cerebella, and Npc1-null cerebral cortices. Plasma tocopherol levels were within the normal range in Npc1-null and Npc2-null mice, and in plasma samples from human NPC patients. The binding affinity of tocopherol to the purified sterol-binding domain of NPC1 and to purified NPC2 was significantly weaker than that of cholesterol (measurements kindly performed by R. Infante, University of Texas Southwestern Medical Center, Dallas, TX). Taken together, our observations indicate that functionality of NPC1/2 proteins is necessary for proper bioavailability of vitamin E and that the NPC pathology might involve tissue-specific perturbations of vitamin E status.
STED: a system for topic enumeration and distillation

Search services on hyperlinked data are becoming popular among users because of the huge amount of data available and the consequent difficulty of retrieving and filtering relevant documents. Traditional term-based search engines are not very useful for this purpose since the resulting ranking depends on the users's precision in expressing the query. Current research, instead, takes a different approach, called topic distillation, which consists of finding documents related to the query topic, but these do not necessarily contain the query string. Current algorithms for topic distillation first compute a base set containing all the relevant pages and then apply an iterative procedure to obtain the authoritative pages. In this paper we present STED, a system for topic distillation and enumeration (i.e. identification of different communities) of Web documents. The system is based on a technique which computes authoritative pages by analyzing the structure of the base set. More specifically, the system applies a statistical approach to the co-citation matrix associated with the base set, to find the most co-cited pages and analyzes both the link structure and the content of pages. Several experiments have demonstrated the effectiveness and efficiency of the system.
Using visual rating to diagnose dementia: a critical evaluation of MRI atrophy scales

Visual rating scales, developed to assess atrophy in patients with cognitive impairment, offer a cost-effective diagnostic tool that is ideally suited for implementation in clinical practice. By focusing attention on brain regions susceptible to change in dementia and enforcing structured reporting of these findings, visual rating can improve the sensitivity, reliability and diagnostic value of radiological image interpretation. Brain imaging is recommended in all current diagnostic guidelines relating to dementia, and recent guidelines have also recommended the application of medial temporal lobe atrophy rating. Despite these recommendations, and the ease with which rating scales can be applied, there is still relatively low uptake in routine clinical assessments. Careful consideration of atrophy rating scales is needed to verify their diagnostic potential and encourage uptake among clinicians. Determining the added value of combining scores from visual rating in different brain regions may also increase the diagnostic value of these tools.
Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells[S]

Lipoprotein lipase (LPL) is secreted into the interstitial spaces by adipocytes and myocytes but then must be transported to the capillary lumen by GPIHBP1, a glycosylphosphatidylinositol-anchored protein of capillary endothelial cells. The mechanism by which GPIHBP1 and LPL move across endothelial cells remains unclear. We asked whether the transport of GPIHBP1 and LPL across endothelial cells was uni- or bidirectional. We also asked whether GPIHBP1 and LPL are transported across cells in vesicles and whether this transport process requires caveolin-1. The movement of GPIHBP1 and LPL across cultured endothelial cells was bidirectional. Also, GPIHBP1 moved bidirectionally across capillary endothelial cells in live mice. The transport of LPL across endothelial cells was inhibited by dynasore and genistein, consistent with a vesicular transport process. Also, transmission electron microscopy (EM) and dual-axis EM tomography revealed GPIHBP1 and LPL in invaginations of the plasma membrane and in vesicles. The movement of GPIHBP1 across capillary endothelial cells was efficient in the absence of caveolin-1, and there was no defect in the internalization of LPL by caveolin-1-deficient endothelial cells in culture. Our studies show that GPIHBP1 and LPL move bidirectionally across endothelial cells in vesicles and that transport is efficient even when caveolin-1 is absent.
Emergence of an imaging biomarker for amyotrophic lateral sclerosis: is the end point near?

A diagnostic and treatment biomarker for amyotrophic lateral sclerosis (ALS) remains a holy grail.1 ,2 From a neuroimaging perspective, diffusion tensor imaging (DTI) has been increasingly utilised to identify brain-related upper motor neuron changes in ALS. In particular, the corticospinal tract, anterior corpus callosum and hippocampal fractional anisotropy (FA) white matter changes have been closely linked with ALS pathology3 ,4 and associated with the underlying neuropathological spread of TAR DNA binding protein 43 (TDP-43). 5 Thus, DTI emerges as an ideal neuroimaging biomarker end point for disease-modifying trials in ALS. However, most advanced trials are run on a multicentre basis, and currently it is not clear how DTI signatures across centres in ALS hold-up, in particular with varying imaging sequences and scanner variabilities. The study by Muller and colleagues6 addresses this point directly, by conducting a multicentre …
Immuno-friendly use of BCG-cell wall skeleton remarkably improves the survival rate of various cancer patients

About 25 years ago, the study of cancer immunotherapy (IT) was done without paying due attention to patients' own immunogenicity, resulting in the failure in its clinical trials. This fact suggested that IT should be performed independently of other conventional chemo- and/or radiation therapies after removing as many tumor cells as possible. Between 1975 and 1997, total 235 cancer patients have been treated by IT with BCG-cell wall skeleton (CWS) alone, most just after surgical operations, and some after chemo- and/or radiation therapies. Appropriate dose (10 to 200μg) of BCG-CWS depending on the patients' biological responses, inoculated intracutaneously every 4 weeks, monitoring their immunogenicity with IFN-γ induction test. In this pilot study, clinical effect of the immuno-friendly use of BCG-CWS was shown most clearly in the effect of IFN-γ induction and cancer stages on the survival rate. In fact this therapy was really effective for various kinds of cancers and for the patients in Stage I-III, but not for those in Stage IV or in immunologically impaired state. Further in 84 postoperative primary lung cancer patients, especially in the group of 46 Stage III patients, the effect was statistically significant (χ2=8.546, p=0.0035). These clinical and statistical analyses suggest that the IT with BCG-CWS alone displays its effect on cancers attacking their lymphnode metastasis.
A generic map based environment representation for driver assistance systems applied to detect convoy tracks

Future Advanced Driver Assistance Systems (ADAS) require generic map based representations to process environment information measured by different sensors. In contrast to today's widespread grid based maps, such environment representations have to be a compact, scalable and easy-to-interpret. In order to fulfill these requirements, we propose a new generic map representation, the two dimensional interval map. One example of information that can be represented in this data structure are convoy tracks. Convoy tracks describe the common motion of vehicles driving in convoys. These tracks can serve as an additional, independent input parameter for longitudinal and lateral control in highly automated ADAS. Experimental results show the general ability of the new data structure to provide sufficiently precise results at low computation time and memory consumption. The developed methodology to detect convoy tracks is capable of extracting multiple common convoy attributes even in complex scenarios with lane change maneuvers.
Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1′ structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses.
Salicylate improves macrophage cholesterol homeostasis via activation of Ampk[S]

Atherosclerosis stems from imbalances in lipid metabolism and leads to maladaptive inflammatory responses. The AMP-activated protein kinase (Ampk) is a highly conserved serine/threonine kinase that regulates many aspects of lipid and energy metabolism, although its specific role in controlling macrophage cholesterol homeostasis remains unclear. We sought to address this question by testing the effects of direct Ampk activators in primary bone marrow-derived macrophages from Ampk β1-deficient (β1−/−) mice. Macrophages from Ampk β1−/− mice had enhanced lipogenic capacity and diminished cholesterol efflux, although cholesterol uptake was unaffected. Direct activation of Ampk β1 via salicylate (the unacetylated form of aspirin) or A-769662 (a small molecule activator), decreased the synthesis of FAs and sterols in WT but not Ampk β1−/− macrophages. In lipid-laden macrophages, Ampk activation decreased cholesterol content (foam cell formation) and increased cholesterol efflux to HDL and apoA-I, effects that occurred in an Ampk β1-dependent manner. Increased cholesterol efflux was also associated with increased gene expression of the ATP binding cassette transporters, Abcg1 and Abca1. Moreover, in vivo reverse cholesterol transport was suppressed in mice that received Ampk β1−/− macrophages compared with the WT control. Our data highlight the therapeutic potential of targeting macrophage Ampk with new or existing drugs for the possible reduction in foam cell formation during the early stages of atherosclerosis.
Are Natural Environments Unnatural? A Survey of Early Intervention Service Providers

Increasingly, early intervention services f o r infants and toddlers with disabilities are provided in natural environments. Natural environments are settings that are natural or normal for the child'S nondisabled peers, such as the home, childcare settings, playgrounds-any place the child is. This study surveyed early intervention service providers about natural environments. Results indicated most children received individual services in natural environments and group services at an early intervention (EI) center: There were statistically significant differences in service providers' perceptions of how appropriate different types of services were when provided in natural environments versus the EI center: Problems with natural environments included: lack of private space, distractions, access to supplies/equipment, and transportation. When choosing the "best" location for early intervention, the interventionists surveyed believed both natural environments and the EI center were valuable resources.
Real-time obstacle detection using stereo vision for autonomous ground vehicles: A survey

One of the most important features for any intelligent ground vehicle is based on how is reliable and complete the perception of the environment and the capability to discriminate what an obstacle is. Obstacle Detection (OD) is one of the most widely discussed topics in literature. Many approaches have been presented for different application fields and scenarios; in last years most of them have been revisited using stereo vision or 2D/3D sensor technologies. In this paper we present a brief survey about Obstacle Detection techniques based on stereo vision for intelligent ground vehicles, describing and comparing the most interesting approaches. In order to provide a generic overview of these techniques, it has been decided to focus the study only on the algorithms that have provided a major contribution through real-time experiments in unsupervised scenarios.
Shiga toxin glycosphingolipid receptors of Vero-B4 kidney epithelial cells and their membrane microdomain lipid environment1[S]

Shiga toxins (Stxs) are produced by enterohemorrhagic Escherichia coli (EHEC), which cause human infections with an often fatal outcome. Vero cell lines, derived from African green monkey kidney, represent the gold standard for determining the cytotoxic effects of Stxs. Despite their global use, knowledge about the exact structures of the Stx receptor glycosphingolipids (GSLs) and their assembly in lipid rafts is poor. Here we present a comprehensive structural analysis of Stx receptor GSLs and their distribution to detergent-resistant membranes (DRMs), which were prepared from Vero-B4 cells and used as lipid raft equivalents. We identified globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) as the GSL receptors for Stx1a, Stx2a, and Stx2e subtypes using TLC overlay detection combined with MS. The uncommon Stx receptor, globopentaosylceramide (Gb5Cer, Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer), which was specifically recognized (in addition to Gb3Cer and Gb4Cer) by Stx2e, was fully structurally characterized. Lipoforms of Stx receptor GSLs were found to mainly harbor ceramide moieties composed of sphingosine (d18:1) and C24:0/C24:1 or C16:0 fatty acid. Moreover, co-occurrence with lipid raft markers, SM and cholesterol, in DRMs suggested GSL association with membrane microdomains. This study provides the basis for further exploring the functional impact of lipid raft-associated Stx receptors for toxin-mediated injury of Vero-B4 cells.