bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Inflammasome-Dependent Interleukin 1β Production by Streptococcal NAD
+
-Glycohydrolase: Evidence for Extracellular Activity
Authors: Hancz Dóra , Westerlund Elsa , Bastiat-Sempe Benedicte , Sharma Onkar , Valfridsson Christine , Meyer Lena , Love John F. , O’Seaghdha Maghnus , Wessels Michael R. , Persson Jenny J. 
Published: July 2017

ABSTRACT

Group A
Streptococcus
(GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD
+
-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion. Here, we used a set of isogenic GAS mutants and a macrophage infection model and report that streptococcal NADase inhibits the innate immune response by decreasing inflammasome-dependent interleukin 1β (IL-1β) release from infected macrophages. Regulation of IL-1β was independent of phagocytosis and ensued also under conditions not allowing SLO-dependent translocation of NADase into the host cell cytosol. Thus, our data indicate that NADase not only acts intracellularly but also has an immune regulatory function in the extracellular niche.

IMPORTANCE
In the mid-1980s, the incidence and severity of invasive infections caused by serotype M1 GAS suddenly increased. The results of genomic analyses suggested that this increase was due to the spread of clonal bacterial strains and identified a recombination event leading to enhanced production of the SLO and NADase toxins in these strains. However, despite its apparent importance in GAS pathogenesis, the function of NADase remains poorly understood. In this study, we demonstrate that NADase inhibits inflammasome-dependent IL-1β release from infected macrophages. While previously described functions of NADase pertain to its role upon SLO-mediated translocation into the host cell cytosol, our data suggest that the immune regulatory function of NADase is exerted by nontranslocated enzyme, identifying a previously unrecognized extracellular niche for NADase functionality. This immune regulatory property of extracellular NADase adds another possible explanation to how increased secretion of NADase correlates with bacterial virulence.
Hypertensive encephalopathy mimicking cerebral vasculitis with pontine oedema, cerebellar white matter lesions and multiple cerebral infarctions
Authors: Ceccarelli Daniela , Hargroves David , Balogun Ibrahim , Webb Thomas 
Published: July 2017

A 47-year-old man with poorly controlled hypertension presented with headaches, right-sided weakness and dysarthria. CT and MRI scans of the brain showed widespread abnormalities including significant pontine oedema, basal ganglia and corona radiata infarctions and cerebellar white matter high signal. Imaging of the intracerebral vasculature also demonstrated wall irregularities. Initially a central nervous system inflammatory disorder was thought to be the most likely diagnosis, possibly acute demyelinating encephalomyelitis or cerebral vasculitis, and the patient was treated with high-dose intravenous steroids. The diagnosis of hypertensive encephalopathy was made because (1) the patient was hypertensive and (2) the patients MRI findings resolved with antihypertensive treatment.Blood pressure treatment was instigated from admission, and the patients symptoms improved with resolution of the radiological abnormalities.
Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke
Authors: Tsakanova Gohar , Stepanyan Ani , Nahapetyan Karen , Sim Robert B , Arakelyan Arsen , Boyajyan Anna 
Published: July 2017

AimsThe aim of the current study was to assess the proteolytic activities of collectin-bound MASP-1 and MASP-2 in the blood of patients with ischaemic stroke, as well as the association of their six genetic polymorphisms (rs3203210, rs28945070, rs28945073 inMASP1gene and rs2273343, rs12711521, rs147270785 inMASP2gene) with this pathology.MethodsIn total, 250 patients and 300 healthy subjects were involved in this study. MBL-associated serine protease (MASP)-1 and MASP-2 activities were measured using in-house developed immunofluorescent and enzyme-linked immunosorbent assays, respectively. Sequence specific primer PCR was used to study the association ofMASP1andMASP2genetic polymorphisms with ischaemic stroke.ResultsThe results obtained demonstrate that the activities of collectin-bound MASP-1 and MASP-2 in patients with ischaemic stroke are significantly higher than those in healthy subjects (p<0.001). According to the data obtained for genotyping, the rs3203210 polymorphism in theMASP1gene and the rs147270785 polymorphism in theMASP2gene are associated with ischaemic stroke (p<0.0001).ConclusionsIn conclusion we suggest that the complement lectin pathway serine proteases, MASP-1 and MASP-2, can be associated with ischaemic stroke development risk and may participate in pathological events leading to post-ischaemic brain damage. Moreover rs3203210 and rs147270785 single nucleotide polymorphisms in theMASP1andMASP2genes, respectively, are strongly associated with ischaemic stroke, and the minor rs3203210*C and rs147270785*A alleles of these polymorphisms may be considered as protective factors for ischameic stroke, at least in the Armenian population.
Cyclic period in the CBE model
Authors: Frampton Paul H. 
Published: July 2017

In a cyclic entropy model in which the extroverse is jettisoned at turnaround with a Come Back Empty (CBE) assumption, we address the matching of the contaction scale factor [Formula: see text] to the expansion scale factor [Formula: see text], where [Formula: see text] is the ratio at turnaround of the introverse to the extroverse radii. Such matching is necessary for infinite cyclicity and fixes the CBE period at [Formula: see text] 2.6 Ty.
MICROSTRUCTURE AND CORROSIVE BEHAVIOR OF ENAMEL COATING MODIFIED ON MILD STEEL
Authors: LI Y. L. , HUANG Z. R. , ZHONG Q. D. 
Published: July 2017

Due to the study of marine corrosion of mild steel, in order to simulate the corrosion conditions of enamel coatings in seawater, enamel coatings applied on mild steel were immersed in 3.5[Formula: see text]wt.% NaCl liquor and the related corrosion features and behavior of enamel were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and evaluated by electro-chemical method such as potentiodynamic polarization testing. Under the appropriate heat treatment system, the enamel coatings sintered on the same kind of mild steel at different temperatures were studied: all enamel samples were within the temperature range from 710[Formula: see text]C to 830[Formula: see text]C, the heat treating process at the microstructural level was evaluated and correlated with corrosion resistance properties. All the enamel coatings were characterized and it was observed that the enamel coatings that showed excellent corrosion resistance when sintered at a temperature of 810[Formula: see text]C can offer a better physical barrier than other temperatures because of their better bonding force and dense microstructure with less pores.
Geological studies in tsunami research since the 2011 Tohoku earthquake
Authors: Wallis Simon R. , Fujiwara Osamu , Goto Kazuhisa 
Published: July 2017

Abstract
The 2011 Tohoku earthquake, tsunami and resulting damage is often referred to as 3.11 after the date on which it took place. Leading to almost 20 000 people dead or missing, a major nuclear disaster and severe economic damage, 3.11 represents the biggest challenge faced by Japan since the end of World War II. Before 3.11, the possibility of a Mw 9 earthquake in this area was not generally recognized, highlighting the need to reassess seismic risk in NE Japan. The large amount of new quantitative data covering a range of disciplines and from onshore and offshore studies makes 3.11 an important case study that can contribute to improving our understanding of tsunamis, including their formation, their effects on coastal regions and the effectiveness of defensive measures old and new. Geological studies have a key role to play in this new phase of tsunami studies and this is the only method available for determining recurrence intervals over timescales of thousands of years. Data from 3.11 have improved our ability to identify sedimentary records of tsunami events and to estimate tsunami size from geological data. More complete databases will provide invaluable information for long-term planning of coastal regions in convergent plate margins.
Speed invariance of tactile texture perception
Authors: Boundy-Singer Zoe M. , Saal Hannes P. , Bensmaia Sliman J. 
Published: July 2017

The nervous system achieves stable perceptual representations of objects despite large variations in the activity patterns of sensory receptors. Here, we explore perceptual constancy in the sense of touch. Specifically, we investigate the invariance of tactile texture perception across changes in scanning speed. Texture signals in the nerve have been shown to be highly dependent on speed: temporal spiking patterns in nerve fibers that encode fine textural features contract or dilate systematically with increases or decreases in scanning speed, respectively, resulting in concomitant changes in response rate. Nevertheless, texture perception has been shown, albeit with restricted stimulus sets and limited perceptual assays, to be independent of scanning speed. Indeed, previous studies investigated the effect of scanning speed on perceived roughness, only one aspect of texture, often with impoverished stimuli, namely gratings and embossed dot patterns. To fill this gap, we probe the perceptual constancy of a wide range of textures using two different paradigms: one that probes texture perception along well-established sensory dimensions independently and one that probes texture perception as a whole. We find that texture perception is highly stable across scanning speeds, irrespective of the texture or the perceptual assay. Any speed-related effects are dwarfed by differences in percepts evoked by different textures. This remarkable speed invariance of texture perception stands in stark contrast to the strong dependence of the texture responses of nerve fibers on scanning speed. Our results imply neural mechanisms that compensate for scanning speed to achieve stable representations of surface texture. NEW & NOTEWORTHY Our brain forms stable representations of objects regardless of viewpoint, a phenomenon known as invariance that has been described in several sensory modalities. Here, we explore invariance in the sense of touch and show that the tactile perception of texture does not depend on scanning speed. This perceptual constancy implies neural mechanisms that extract information about texture from the response of nerve fibers such that the resulting neural representation is stable across speeds.
A reduced somatosensory gating response in individuals with multiple sclerosis is related to walking impairment
Authors: Arpin David J. , Gehringer James E. , Wilson Tony W. , Kurz Max J. 
Published: July 2017

When identical stimuli are presented in rapid temporal succession, neural responses to the second stimulation are often weaker than those observed for the first. This phenomenon is termed sensory gating and is believed to be an adaptive feature that helps prevent higher-order cortical centers from being flooded with unnecessary information. Recently, sensory gating in the somatosensory system has been linked to deficits in tactile discrimination. Additionally, studies have linked poor tactile discrimination with impaired walking and balance in individuals with multiple sclerosis (MS). In this study, we examine the neural basis of somatosensory gating in patients with MS and healthy controls and assess the relationship between somatosensory gating and walking performance. We used magnetoencephalography to record neural responses to paired-pulse electrical stimulation applied to the right posterior tibial nerve. All participants also walked across a digital mat, which recorded their spatiotemporal gait kinematics. Our results showed the amplitude of the response to the second stimulation was sharply reduced only in controls, resulting in a significantly reduced somatosensory gating in the patients with MS. No group differences were observed in the amplitude of the response to the first stimulation nor the latency of the neural response to either the first or second stimulation. Interestingly, the altered somatosensory gating responses were correlated with aberrant spatiotemporal gait kinematics in the patients with MS. These results suggest that inhibitory GABA circuits may be altered in patients with MS, which impacts somatosensory gating and contributes to the motor performance deficits seen in these patients. NEW & NOTEWORTHY We aimed to determine whether somatosensory gating in patients with multiple sclerosis (MS) differed compared with healthy controls and whether a relationship exists between somatosensory gating and walking performance. We found reduced somatosensory gating responses in patients with MS, and these altered somatosensory gating responses were correlated with the mobility impairments. These novel findings show that somatosensory gating is impaired in patients with MS and is related to the mobility impairments seen in these patients.
Fructose-1,6-bisphosphatase Inhibits ERK Activation and Bypasses Gemcitabine Resistance in Pancreatic Cancer by Blocking IQGAP1–MAPK Interaction
Authors: Jin Xin , Pan Yunqian , Wang Liguo , Ma Tao , Zhang Lizhi , Tang Amy H. , Billadeau Daniel D. , Wu Heshui , Huang Haojie 
Published: July 2017

AbstractDysregulation of the MAPK pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase-activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and ERK. Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here, we demonstrate that FBP1 acts as a negative modulator of the IQGAP1–MAPK signaling axis in PDAC cells. FBP1 binding to the WW domain of IQGAP1 impeded IQGAP1-dependent ERK1/2 phosphorylation (pERK1/2) in a manner independent of FBP1 enzymatic activity. Conversely, decreased FBP1 expression induced pERK1/2 levels in PDAC cell lines and correlated with increased pERK1/2 levels in patient specimens. Treatment with gemcitabine caused undesirable activation of ERK1/2 in PDAC cells, but cotreatment with the FBP1-derived small peptide inhibitor FBP1 E4 overcame gemcitabine-induced ERK activation, thereby increasing the anticancer efficacy of gemcitabine in PDAC. These findings identify a primary mechanism of resistance of PDAC to standard therapy and suggest that the FBP1–IQGAP1–ERK1/2 signaling axis can be targeted for effective treatment of PDAC. Cancer Res; 77(16); 4328–41. ©2017 AACR.
Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer–Predisposing Mutations in Pheochromocytomas and Paragangliomas
Authors: Remacha Laura , Comino-Méndez Iñaki , Richter Susan , Contreras Laura , Currás-Freixes María , Pita Guillermo , Letón Rocío , Galarreta Antonio , Torres-Pérez Rafael , Honrado Emiliano , Jiménez Scherezade , Maestre Lorena , Moran Sebastian , Esteller Manel , Satrústegui Jorgina , Eisenhofer Graeme , Robledo Mercedes , Cascón Alberto 
Published: July 2017

Abstract
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes.
Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases.
Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1. A variant in GOT2, c.357A&gt;T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio.
Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315–24. ©2017 AACR.
Сучасні предмети догляду за ротовою порожниною, методики чищення зубів у дорослих і дітей
Authors: Melnychuk G. M. , Kushnirenko M. O. , Melnychuk A. S. , Kashivska R. S. 
Published: July 2017

Treatment of any dental diseases: caries and its complications, non-carious lesions, diseases of periodontal tissue and oral mucosa begins with professional oral hygiene and patient's hygienic training.The aim of the study – to describe modern oral care products, including various types of toothbrushes (manual, electrical, ionic, ultrasound), indicate their strengths and weaknesses; describe additional items for oral cavity cleaning, terms of flosses use, interdental brushes and stimulants, tongue cleaners, irigators and basic methods of teethbrushing.Materials and Methods. We conducted a literature review for 1999–2017 years, classified modern items for oral care, found and described the indications and methods of their use.Results and Discussion. We found that use only toothbrush for effective oral hygiene is not sufficient, because today is a large arsenal of available additional items for thorough cleaning of remote areas of teeth; argued that proper brushing skills can be lost with time, that's why patients need hygiene remotivation, repeated conversations and supervised teethbrushing with results visualization every 3 months.Conclusions. Knowledge of teethbrushing methods and choosing the right tools for this has a decisive role in the patient's treatment plan, because a large part of the success depends on the individual oral care and the cooperation of a patient with a doctor.
Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis
Authors: Charidimou Andreas , Turc Guillaume , Oppenheim Catherine , Yan Shenqiang , Scheitz Jan F. , Erdur Hebun , Klinger-Gratz Pascal P. , El-Koussy Marwan , Takahashi Wakoh , Moriya Yusuke , Wilson Duncan , Kidwell Chelsea S. , Saver Jeffrey L. , Sallem Asma , Moulin Solene , Edjlali-Goujon Myriam , Thijs Vincent , Fox Zoe , Shoamanesh Ashkan , Albers Gregory W. , Mattle Heinrich P. , Benavente Oscar R. , Jäger H. Rolf , Ambler Gareth , Aoki Junya , Baron Jean-Claude , Kimura Kazumi , Kakuda Wataru , Takizawa Shunya , Jung Simon , Nolte Christian H. , Lou Min , Cordonnier Charlotte , Werring David J. 
Published: July 2017

Background and Purpose—
We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome.

Methods—
We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2–4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2).

Results—

In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09–2.07;
P
=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73–5.35;
P
<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (
P
=0.014), PH (
P
=0.013), and PHr (
P
<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10–3.12;
P
=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55–10.22;
P
=0.004, respectively).

Conclusions—
Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.
Contradictory Change
Authors: Littmann Greg 
Published: July 2017

Graham Priest has argued that changes occur at a moment of change in which objects are in a contradictory state, being in both the state changed from and the state changed to. In “Moments of Change,” the current author rejected this model on the grounds that every change would require an infinite number of other changes, and that for similar regress problems, the model is not compatible with the Leibniz Continuity Condition that Priest appeals to in the model’s support. In “Contradiction and the Instant of Change Revisited,” Priest rightly points out in response that any regress can be stopped by allowing that some changes can occur without a moment of change and that there are some exceptions to the lcc in the case of change.
It is argued here that while the regress can be stopped by allowing for exceptions to the rules, the more exceptions that must be allowed and the more similar the excepted cases are to cases of supposed contradiction, the less attractive both the contradictory account of change and the lcc should be. Secondly, it is argued that the intuitions that make the contradictory account of change seem appealing are likely to disappear if we adopt an eternalist model of spacetime, which we should do in any case in order to best accommodate the special theory of relativity. In particular, eternalism undermines our intuitions that there must be a moment of change in order for change to occur, that contradictory moments are required to allow for a Laplacian universe, that motion must be intrinsic to an object at a time, and that change obeys the lcc.