Miracle-dz/UniFAR-FTUs huggingface dataset:
Macromolecule‐suppressed GABA‐edited magnetic resonance spectroscopy at 3T

Edited magnetic resonance spectroscopy makes possible noninvasive studies of the role of the inhibitory neurotransmitter GABA in the healthy brain and in disease processes. A major limitation of the methodology is coediting of macromolecular signals. Although it has previously been shown that macromolecular signal can be suppressed using a symmetrical editing scheme, this approach is rarely applied at field strength of 3T as insufficiently selective pulses result in loss of GABA signal (in addition to the intended suppression of macromolecular signal). In this article, the authors show that increasing the echo time to 80 ms lets more selective editing pulses be used, allowing for symmetric editing‐based suppression of coedited macromolecular signal without loss of GABA signal. The method is applied to acquire macromolecule‐suppressed GABA‐edited spectra in 10 healthy participants. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Implicit and explicit selective attention to smoking cues in smokers indexed by brain potentials

Substance use disorders are characterized by cognitive processing biases, such as automatically detecting and orienting attention towards drug-related stimuli. However, it is unclear how, when and what kind of attention (i.e. implicit, explicit) interacts with the processing of these stimuli. In addition, it is unclear whether smokers are hypersensitive to emotionally significant cues in general or to smoking-related cues in particular. The present event-related potential study aimed to enhance insight in drug-related processing biases by manipulating attention for smoking and other motivationally relevant (emotional) cues in smokers and non-smokers using a visual oddball task. Each of the stimulus categories served as a target (explicit attention; counting) or as a non-target (implicit attention; oddball) category. Compared with non-smokers, smokers’ P300 (350–600 ms) was enhanced to smoking pictures under both attentional conditions. P300 amplitude did not differ between groups in response to positive, negative, and neutral cues. It can be concluded from this study that attention manipulation affects the P300 differently in smokers and non-smokers. Smokers display a specific bias to smoking-related cues, and this bias is present during both explicit and implicit attentional processing. Overall, it can be concluded that both explicit and implicit attentional processes appear to play an important role in drug-related processing bias.
Plasmid Evolution and Interaction between the Plasmid Addiction Stability Systems of Two Related Broad-Host-Range IncQ-Like Plasmids

ABSTRACT Plasmid pTC-F14 contains a plasmid stability system called pas (plasmid addiction system), which consists of two proteins, a PasA antitoxin and a PasB toxin. This system is closely related to the pas of plasmid pTF-FC2 (81 and 72% amino acid identity for PasA and PasB, respectively) except that the pas of pTF-FC2 contains a third protein, PasC. As both pTC-F14 and pTF-FC2 are highly promiscuous broad-host-range plasmids isolated from bacteria that share a similar ecological niche, the plasmids are likely to encounter each other. We investigated the relative efficiencies of the two stability systems and whether they had evolved apart sufficiently for each pas to stabilize a plasmid in the presence of the other. The three-component pTF-FC2 pas was more efficient at stabilization of a heterologous tester plasmid than the two component pas of pTC-F14 in Escherichia coli host cells (±92% and ±60% after 100 generations, respectively). The PasA antidote of each pas was unable to neutralize the PasB toxin of the other plasmid. The pas proteins of each plasmid autoregulated their own expression as well as that of the pas of the other plasmid. The pas of pTF-FC2 was more effective at repressing the pas operon of pTC-F14 than the pas of pTC-F14 was able to repress itself or the pas of pTF-FC2. This increased efficiency was not due to the PasC of pTF-FC2. The effect of this stronger repression was that pTF-FC2 displaced pTC-F14 when the two plasmids were coresident in the same E. coli host cell. Plasmid curing resulted in the arrest of cell growth but did not cause cell death, and plasmid stability was not influenced by the E. coli mazEF genes.
Extractive software product line engineering using model-based delta module generation

To satisfy demand for customized products, companies commonly apply so-called clone-and-own strategies by copying functionality from existing products and modifying it to create product variants that have to be developed, maintained, and evolved in isolation. In previous work, we introduced a variability mining technique to identify variability information (commonalities and differences) in block-based model variants (e.g., MATLAB/Simulink models), which can be used to guide manual transition from clone-and-own to managed reuse of a software product line (SPL). In this paper, we present a procedure that uses the extracted variability information to generate a transformational delta-oriented SPL fully automatically. We generate a delta language specifically tailored to transforming models in the analyzed modeling language and utilize it to generate delta modules expressing variation of the SPL's implementation artifacts. The procedure seamlessly integrates with our variability mining technique and allows to fully adopt a managed reuse strategy (i.e., generation of products from a single code base) without manual overhead. We show the feasibility of the procedure by applying it to state chart and MATLAB/Simulink model variants from two industrial case studies.
Comparative Morphology of the Papillae Linguales and their Connective Tissue Cores in the Tongue of the Greater Japanese Shrew-mole, Urotrichus talpoides

The external morphology of the papillae linguales (papillae filiformes, papillae fungiformes and papillae vallatae) and their connective tissue cores (CTCs) of the greater Japanese shrew‐mole (Urotrichus talpoides) were analysed by optical and scanning electron microscopy. Papillae filiformes were distributed over the dorsal surface of the apex linguae, and on the rostral and caudal regions of the corpus linguae but were less numerous in the mid‐region. They were absent from the radix linguae. A pair of oval papillae vallatae was situated at the border between the corpus linguae and the radix linguae. Papillae foliatae were absent. The epithelial surface of each papilla filiformis consisted of a circular concavity, a ring‐like wall and either a single thumb‐like process or 2–3 slender pointed processes, depending on their location. The morphology of the CTCs of the papillae filiformes also varied regionally. The papillae linguales of the Japanese shrew‐mole were morphologically similar to those of other Talpidae and Soricidae, including the common shrew, particularly with respect to the papillae filiformes in the mid‐ and caudal regions of the corpus linguae.
PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix

During embryonic development signalling pathways act repeatedly in different contexts to pattern the emerging germ layers. Understanding how these different responses are regulated is a central question for developmental biology. In this study, we used mouse embryonic stem cell (mESC) differentiation to uncover a new mechanism for PI3K signalling that is required for endoderm specification. We found that PI3K signalling promotes the transition from naïve endoderm precursors into committed anterior endoderm. PI3K promoted commitment via an atypical activity that delimited epithelial-to-mesenchymal transition (EMT). Akt1 transduced this activity via modifications to the extracellular matrix (ECM) and appropriate ECM could itself induce anterior endodermal identity in the absence of PI3K signalling. PI3K/Akt1-modified ECM contained low levels of Fibronectin (Fn1) and we found that Fn1 dose was key to specifying anterior endodermal identity in vivo and in vitro. Thus, localized PI3K activity affects ECM composition and ECM in turn patterns the endoderm. DOI: http://dx.doi. org/10.7554/eLife.00806. 001
Barrier functionality of porcine and bovine brain capillary endothelial cells.

INTRODUCTION To date, isolated cell based blood-brain barrier (BBB) models have been widely used for brain drug delivery and targeting, due to their relatively proper bioelectrical and permeability properties. However, primary cultures of brain capillary endothelial cells (BCECs) isolated from different species vary in terms of bioelectrical and permeability properties. METHODS To pursue this, in the current investigation, primary porcine and bovine BCECs (PBCECs and BBCECs, respectively) were isolated and used as an in vitro BBB model. The bioelectrical and permeability properties were assessed in BCECs co-cultured with C6 cells with/without hydrocortisone (550 nM). The bioelectrical properties were further validated by means of the permeability coefficients of transcellular and paracellular markers. RESULTS The primary PBCECs displayed significantly higher trans-endothelial electrical resistance (~900 Ω.cm(2)) than BBCECs (~700 Ω.cm(2)) - both cocultured with C6 cells in presence of hydrocortisone. Permeability coefficients of propranolol/diazepam and mannitol/sucrose in PBCECs were ~21 and ~2 (×10(-6) cm.sec(-1)), where these values for BBCECs were ~25 and ~5 (×10(-6) cm.sec(-1)). CONCLUSION Upon our bioelectrical and permeability findings, both models display discriminative barrier functionality but porcine BCECs seem to provide a better platform than bovine BCECs for drug screening and brain targeting.
Heritable and inducible gene knockdown in astrocytes or neurons in vivo by a combined lentiviral and RNAi approach

Gene knockout by homologous recombination is a popular method to study gene functions in the mouse in vivo. However, its lack of temporal control has limited the interpretation of knockout studies because the complete elimination of a gene product often alters developmental processes, and can induce severe malformations or lethality. Conditional gene knockdown has emerged as a compelling alternative to gene knockout, an approach well-established in vitro but that remains challenging in vivo, especially in the adult brain. Here, we report a method for conditional and cell-specific gene knockdown in the mouse brain in vivo that combines Cre-mediated RNA interference (RNAi) with classical and lentivirus-mediated transgenesis. The method is based on the inducible expression of a silencing short hairpin RNA (shRNA) introduced in mice by lentivirus-mediated transgenesis, and on its activation by excision of a floxed stop EGFP reporter with an inducible Cre recombinase expressed in astrocytes or in neurons. This dual system should be of broad utility for comparative studies of gene functions in these two cell types in vivo.
Circadian Modulation of Mentally Simulated Motor Actions: Implications for the Potential Use of Motor Imagery in Rehabilitation

Background. Mental practice through motor imagery improves subsequent motor performance and thus mental training is considered to be a potential tool in neuromotor rehabilitation. Objective. The authors investigated whether a circadian fluctuation of the motor imagery process occurs, which could be relevant in scheduling mental training in rehabilitation programs. Methods. The executed and imagined durations of walking and writing movements were recorded every 3 hours from 8 AM to 11 PM in healthy participants. The authors made a cosinor analysis on the temporal features of these movements to detect circadian rhythms. Temporal differences between executed and imagined movements as well as their variability during the day were also quantified. Results. Circadian rhythms were detected for both the executed and the imagined movements. Furthermore, these rhythms covaried between them and with body temperature. The participants' ability to internally simulate their movements also fluctuated significantly during the day. The isochrony between the executed and the imagined movements was exclusively observed between 2 PM and 8 PM. In the morning (8 AM and 11 AM) and the evening (11 PM), the durations of the imagined movements were significantly longer than the durations of executed movements. Conclusions . Predictive internal models fluctuate in a circadian basis, as do many other physiological parameters. It could be important to take into consideration the time of day in the planning of rehabilitation programs using physical or mental training.
An improved short‐lived fluorescent protein transcriptional reporter for Saccharomyces cerevisiae

Ideal reporter genes for temporal transcription programmes have short half‐lives that restrict their detection to the window in which their transcripts are present and translated. In an effort to meet this criterion for reporters of transcription in individual living cells, we adapted the ubiquitin fusion strategy for programmable N‐end rule degradation to generate an N‐degron version of green fluorescent protein (GFP) with a half‐life of ~7 min. The GFP variant we used here (designated GFP*) has excellent fluorescence brightness and maturation properties, which make the destabilized reporter well suited for tracking the induction and attenuation kinetics of gene expression in living cells. These attributes are illustrated by its ability to track galactose‐ and pheromone‐induced transcription in S. cerevisiae. We further show that the fluorescence measurements using the short‐lived N‐degron GFP* reporter gene accurately predict the transient mRNA profile of the prototypical pheromone‐induced FUS1 gene. Copyright © 2012 John Wiley & Sons, Ltd.
Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia

Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.
Diacylglycerol acyltransferase 2 ( DGAT 2 ) links glucose utilization to fatty acid oxidation in the brown adipocytes

Copyright and reuse: The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.
Use of Lysostaphin in the Isolation of Highly Polymerized Deoxyribonucleic Acid and in the Taxonomy of Aerobic Micrococcaceae

By use of the staphylolytic enzyme lysostaphin, a method was devised for isolating and purifying highly polymerized deoxyribonucleic acid (DNA) from lysostaphinsusceptible Micrococcaceae. Staphylococcus aureus DNA isolated by this procedure gave an estimated molecular weight of ca. 2 × 108 and a residual protein content of 2.3%. The mole percentage of guanine + cytosine (GC) present in the DNA from 21 strains of aerobic Micrococceae was determined by buoyant density in cesium chloride. DNA from 12 biochemically typical members of the genus Staphylococcus gave a mean GC composition of 35.2 ± 0.5 mole per cent. Four biochemically atypical Staphylococcus strains and one biochemically typical strain of the genus Micrococcus (M. candicans) were found to be susceptible to lysostaphin and gave typical Staphylococcus spp. GC base ratios. One biochemically atypical member of the genus Micrococcus (M. varians) was not susceptible to lysostaphin and gave a typical Micrococcus spp. GC base ratio. Lysostaphin susceptibility is an easy test to perform, and the results of this test appear to correlate with GC base ratio studies of the genera of Micrococcaceae.
Preoperative colorectal neoplasia increases risk for pouch neoplasia in patients with restorative proctocolectomy.

BACKGROUND & AIMS Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has substantially reduced the risk for ulcerative colitis (UC)-associated dysplasia or cancer (neoplasia). We characterized features, risk factors, and outcomes of pouch neoplasia in patients with inflammatory bowel disease in a historical cohort study. METHODS A total of 3203 patients with a preoperative diagnosis of inflammatory bowel disease underwent restorative proctocolectomy with IPAA from 1984 to 2009 at the Cleveland Clinic. Demographic, clinical, and endoscopic data were reviewed and samples were examined by histological analyses. Univariable and Cox regression analyses were performed. RESULTS Cumulative incidences for pouch neoplasia at 5, 10, 15, 20, and 25 years were 0.9%, 1.3%, 1.9%, 4.2%, and 5.1%, respectively. Thirty-eight patients (1.19%) had pouch neoplasia, including 11 (0.36%) with adenocarcinoma of the pouch and/or the anal-transitional zone (ATZ), 1 (0.03%) with pouch lymphoma, 3 with squamous cell cancer of the ATZ, and 23 with dysplasia (0.72%). In the Cox model, the risk factor associated with pouch neoplasia was a preoperative diagnosis of UC-associated cancer or dysplasia, with adjusted hazard ratios of 13.43 (95% confidence interval: 3.96-45.53; P < .001) and 3.62 (95% confidence interval: 1.59-8.23; P = .002), respectively. Mucosectomy did not protect against pouch neoplasia. CONCLUSIONS Risk for neoplasia in patients with UC and IPAA is small and not eliminated by colectomy or mucosectomy. A preoperative diagnosis of dysplasia or cancer of colon or rectum is a risk factor for pouch dysplasia or adenocarcinoma.
Comparison of Quantitative and Semiquantitative Enzyme-Linked Immunosorbent Assays for Immunoglobulin G against Chlamydophila pneumoniae to a Microimmunofluorescence Test for Use with Patients with Respiratory Tract Infections

ABSTRACT We previously reported a high degree of variation in the sensitivities of serodiagnostic kits for the detection of Chlamydophila pneumoniae in sera from healthy donors. Since a low predictive value of a test can impair its diagnostic value, we have extended our studies to samples from patients with pneumonia. We focused on the most promising enzyme-linked immunosorbent assays (ELISAs) (SeroCP and SeroCP Quant; Savyon) identified in our previous study and included a new ELISA (sELISA; Medac). The agreement between all ELISAs for immunoglobulin G (IgG) and a reference microimmunofluorescence (MIF) test for IgG (SeroFIA; Savyon) was ≥90% for a collective of 80 patients. The positive predictive values were all ≥93%. The negative predictive values ranged from 68 to 83%. False-negative results were obtained only for samples that had low titers in the MIF test. The correlation of the IgG antibody titers determined by the MIF and SeroCP Quant tests was high (rsp = 0.9). Since the semiquantitative SeroCP and quantitative SeroCP Quant ELISAs achieved the highest sensitivities, they were evaluated further by using a second batch of sera from 50 patients with predominantly medium and low antibody titers in the MIF test and a control collection of sera from 80 children with negative MIF results. Again, the tests showed a high concordance with the MIF results (96%), and the antibody titers in the SeroCP Quant and MIF tests correlated well (rsp = 0.8). The specificities determined with the negative sera were ≥99% for the SeroCP Quant test and 86% for the SeroCP test. These results show that ELISAs that are fast and objective deliver seroprevalence results, sensitivities, and specificities that are very similar to those of the MIF test.
Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis

Background and Purpose— Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. Methods— Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan–Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. Results— 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%–72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%–42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%–35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%–31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52–0.94]). Conclusions— Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes.