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Author(s):  
KM Lyons ◽  
RA Stevenson ◽  
AM Owen ◽  
B Stojanoski

AbstractChildren who have been diagnosed with autism spectrum disorder (ASD) often show a marked deficit in measures of social cognition. In autistic adults, measures of social cognition have been shown to relate to differences in brain synchronization (as measured by fMRI) when individuals are processing naturalistic stimuli, such as movies. However, whether children with social impairments, with or without a diagnosis of ASD, differ in their neural responses to movies has not yet been investigated. In the current study, neural synchrony, measured using fMRI, was examined in three groups of children aged 7 to 12, who differed with respect to scores on a measure of autistic traits associated with social impairment and whether or not they had been diagnosed with ASD. While watching the movie ‘Despicable Me’, those diagnosed with ASD had significantly less neural synchrony in areas that have been previously shown to be associated with social cognition (e.g. areas related to ‘theory of mind’), and plot following (e.g. the lateral prefrontal cortex), than those who did not have an ASD diagnosis. In contrast, two groups who differed in their degree of social impairment, but did not have a diagnosis of ASD, showed no significant differences in neural synchrony across the whole brain. These results shed some light on how autistic traits may contribute to an individual’s conscious experience of the world, and how, for children with ASD, that experience may differ markedly from that of those without ASD.


2019 ◽  
Vol 295 (4) ◽  
pp. 1153-1164 ◽  
Author(s):  
Alexander S. Jureka ◽  
Alex B. Kleinpeter ◽  
Jennifer L. Tipper ◽  
Kevin S. Harrod ◽  
Chad M. Petit

A critical role of influenza A virus nonstructural protein 1 (NS1) is to antagonize the host cellular antiviral response. NS1 accomplishes this role through numerous interactions with host proteins, including the cytoplasmic pathogen recognition receptor, retinoic acid–inducible gene I (RIG-I). Although the consequences of this interaction have been studied, the complete mechanism by which NS1 antagonizes RIG-I signaling remains unclear. We demonstrated previously that the NS1 RNA-binding domain (NS1RBD) interacts directly with the second caspase activation and recruitment domain (CARD) of RIG-I. We also identified that a single strain-specific polymorphism in the NS1RBD (R21Q) completely abrogates this interaction. Here we investigate the functional consequences of an R21Q mutation on NS1's ability to antagonize RIG-I signaling. We observed that an influenza virus harboring the R21Q mutation in NS1 results in significant up-regulation of RIG-I signaling. In support of this, we determined that an R21Q mutation in NS1 results in a marked deficit in NS1's ability to antagonize TRIM25-mediated ubiquitination of the RIG-I CARDs, a critical step in RIG-I activation. We also observed that WT NS1 is capable of binding directly to the tandem RIG-I CARDs, whereas the R21Q mutation in NS1 significantly inhibits this interaction. Furthermore, we determined that the R21Q mutation does not impede the interaction between NS1 and TRIM25 or NS1RBD's ability to bind RNA. The data presented here offer significant insights into NS1 antagonism of RIG-I and illustrate the importance of understanding the role of strain-specific polymorphisms in the context of this specific NS1 function.


2019 ◽  
Vol 632 ◽  
pp. A61 ◽  
Author(s):  
S. García-Burillo ◽  
F. Combes ◽  
C. Ramos Almeida ◽  
A. Usero ◽  
A. Alonso-Herrero ◽  
...  

Aims. We investigate the fueling and the feedback of nuclear activity in the nearby (D = 14 Mpc) Seyfert 2 barred galaxy NGC 1068 by studying the distribution and kinematics of molecular gas in the torus and its connections to the host galaxy disk. Methods. We used the Atacama Large Millimeter Array (ALMA ) to image the emission of a set of molecular gas tracers in the circumnuclear disk (CND) and the torus of the galaxy using the CO(2–1), CO(3–2), and HCO+(4–3) lines and their underlying continuum emission with high spatial resolutions (0.03″ − 0.09″ ≃ 2 − 6 pc). These transitions, which span a wide range of physical conditions of molecular gas (n(H2)⊂103 − 107 cm−3), are instrumental in revealing the density radial stratification and the complex kinematics of the gas in the torus and its surroundings. Results. The ALMA images resolve the CND as an asymmetric ringed disk of D ≃ 400 pc in size and ≃1.4 × 108 M⊙ in mass. The CND shows a marked deficit of molecular gas in its central ≃130 pc region. The inner edge of the ring is associated with the presence of edge-brightened arcs of NIR polarized emission, which are identified with the current working surface of the ionized wind of the active galactic nucleus (AGN). ALMA proves the existence of an elongated molecular disk/torus in NGC 1068 of Mtorusgas ≃ 3 × 105 M⊙, which extends over a large range of spatial scales D ≃ 10 − 30 pc around the central engine. The new observations evidence the density radial stratification of the torus: the HCO+(4–3) torus, with a full size DHCO+(4 − 3) = 11 ± 0.6 pc, is a factor of between two and three smaller than its CO(2–1) and CO(3–2) counterparts, which have full sizes of DCO(3 − 2) = 26 ± 0.6 pc and DCO(2 − 1) = 28 ± 0.6 pc, respectively. This result brings into light the many faces of the molecular torus. The torus is connected to the CND through a network of molecular gas streamers detected inside the CND ring. The kinematics of molecular gas show strong departures from circular motions in the torus, the gas streamers, and the CND ring. These velocity field distortions are interconnected and are part of a 3D outflow that reflects the effects of AGN feedback on the kinematics of molecular gas across a wide range of spatial scales around the central engine. In particular, we estimate through modeling that a significant fraction of the gas inside the torus (≃ 0.4 − 0.6 × Mtorusgas) and a comparable amount of mass along the gas streamers are outflowing. However, the bulk of the mass, momentum, and energy of the molecular outflow of NGC 1068 is contained at larger radii in the CND region, where the AGN wind and the radio jet are currently pushing the gas assembled at the Inner Lindblad Resonance (ILR) ring of the nuclear stellar bar. Conclusions. In our favored scenario a wide-angle AGN wind launched from the accretion disk of NGC1068 is currently impacting a sizable fraction of the gas inside the torus. However, a large gas reservoir (≃1.2 − 1.8 × 105 M⊙), which lies close to the equatorial plane of the torus, remains unaffected by the feedback of the AGN wind and can therefore continue fueling the AGN for at least ≃1 − 4 Myr. Nevertheless, AGN fueling currently seems thwarted on intermediate scales (15 pc ≤r ≤ 50 pc).


2018 ◽  
Vol 25 (6) ◽  
pp. 964-986
Author(s):  
Jordi Suriñach ◽  
Josep A Casanovas ◽  
Marién André ◽  
Joaquim Murillo ◽  
Javier Romaní

The day tripper (or day visitor) is a visitor type that represents a high proportion of total visitor trips; however, unlike the tourist, few studies focus their attention specifically on them. Additionally, there is currently a marked deficit of methodological specificity in the definition of the concept and the quantification procedures used in its study. This article examines the various definitions proposed to date of the ‘day trip’, highlighting this lack of specificity, above all with regard to the concept of usual environment. It then proposes a specific methodology for the quantification of day trips in small areas, without discounting official statistics, but seeking to make it independent of other variables (including the size of a territory). We propose linking usual environment with belonging to the same urban system. The article concludes by applying our proposal to the case of the province of Barcelona.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Li Hui ◽  
Hai Sen Xia ◽  
An Shu Tang ◽  
Yi Feng Zhou ◽  
Guang Zhong Yin ◽  
...  

Abstract Although cognitive and sensory deficits have been identified as a core feature of schizophrenia, only a small portion of visual sensorium has been explored. To date, studies on visual system of three-dimensional percepts based on two-dimensional information still are limited. This study is the first to examine the integrity of stereopsis of schizophrenia in a Han Chinese population, and to further investigate the correlation of stereopsis with clinical symptoms. 100 patients with schizophrenia and 80 healthy controls were recruited. We assessed stereoacuity using the Titmus Stereopsis Test and clinical symptoms using Chinese versions of the Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS). There was a significant difference in log seconds of arc between two groups (p < 0.0001). The percentage of patients with correct stereopsis detection was significantly reduced at 400, 200, 140, 100, 80, 60, 50, and 40 seconds of arc than healthy controls (all, p < 0.01). Log seconds of arc in patients was not correlated with total scores and subscores of SAPS and SANS (all, p > 0.05). Our findings support that patients with schizophrenia have a marked deficit of stereopsis in a Han Chinese population. However, clinical symptoms do not influence stereopsis of schizophrenia.


2015 ◽  
Vol 309 (8) ◽  
pp. L902-L913 ◽  
Author(s):  
Yash R. Patankar ◽  
Rodwell Mabaera ◽  
Brent Berwin

The NLRC4 inflammasome is responsible for IL-1β processing by macrophages in response to Pseudomonas aeruginosa infection. We therefore hypothesized that mice that lack ASC, an NLRC4 inflammasome adaptor protein necessary for in vitro IL-1β production by macrophages, would be preferentially protected from a hyperinflammatory lethal challenge that is dependent on bacterial type three secretion system (T3SS) activity. We report herein that lack of ASC does not confer preferential protection in response to P. aeruginosa acute infection and that ASC−/− mice are capable of producing robust amounts of IL-1β comparable with C57BL/6 mice. We now identify that neutrophils represent the ASC-independent source of IL-1β production during the acute phases of infection both in models of acute pneumonia and peritonitis. Consequently, depletion of neutrophils in ASC−/− mice leads to a marked deficit in IL-1β production in vivo. The pulmonary neutrophil IL-1β response is predominantly dependent on caspase-1, which contrasts with data derived from ocular infection. These studies therefore identify a noncanonical mechanism of IL-1β production by neutrophils independent of ASC and demonstrate the first physiological contribution of neutrophils as an important source of IL-1β in response to acute P. aeruginosa infection during acute pneumonia and peritonitis.


2014 ◽  
Vol 57 (6) ◽  
pp. 2234-2245 ◽  
Author(s):  
Lauryn Zipse ◽  
Amanda Worek ◽  
Anthony J. Guarino ◽  
Stefanie Shattuck-Hufnagel

Purpose In this study, the authors tested whether people with aphasia (PWAs) show an impaired ability to process rhythm, both in terms of perception and production. Method Two experiments were conducted. In Experiment 1, 16 PWAs and 15 age-matched control participants performed 3 rhythm tasks: tapping along to short rhythms, tapping these same rhythms from memory immediately after presentation, and making same–different judgments about pairs of tapped rhythms that they heard. Comparison tasks measured same–different judgment ability with visual stimuli and nonverbal working memory (Corsi blocks). In Experiment 2, 14 PWAs and 16 control participants made same–different judgments for pairs of auditory stimuli that differed in terms of rhythm or pitch (for comparison). Results In Experiment 1, PWAs performed worse than control participants across most measures of rhythm processing. In contrast, PWAs and control participants did not differ in their performance on the comparison tasks. In Experiment 2, the PWAs performed worse than control participants across all conditions but with a more marked deficit in stimulus pairs that differed in rhythm than in those that differed in pitch. Conclusions The results support the hypothesis that at least some PWAs exhibit deficits of rhythm and timing. This may have implications for treatments involving tapping or other rhythmic cues.


2013 ◽  
Vol 304 (12) ◽  
pp. C1141-C1149 ◽  
Author(s):  
Joan Clària ◽  
Binh T. Nguyen ◽  
Arin L. Madenci ◽  
C. Keith Ozaki ◽  
Charles N. Serhan

Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The “classic” eicosanoids prostaglandin (PG) E2, PGD2, PGF2α, leukotriene (LT) B4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2αdiffered significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE2.In this tissue, proresolving mediators RvD2 and LXA4were identified in lower levels than the proinflammatory LTB4. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD.


2002 ◽  
Vol 83 (11) ◽  
pp. 2907-2914 ◽  
Author(s):  
M. Baylis ◽  
W. Goldmann ◽  
F. Houston ◽  
D. Cairns ◽  
A. Chong ◽  
...  

In scrapie-affected sheep flocks, host PrP genotype plays a vital role in determining which sheep will succumb to scrapie and the incubation period. Consequently, within-flock scrapie dynamics is best understood within the context of the genotype profile of the flock. Here we describe a 17 month epidemic of scrapie in a commercially farmed flock of 230 genotyped Texel sheep. At the start of the study, 70% of the sheep were of three genotypes only: ARR/ARQ, ARH/ARQ and ARQ/ARQ. Only 15% of sheep encoded the disease-associated VRQ allele and only a single sheep (0·4%) was of the most susceptible VRQ/VRQ genotype. For susceptible genotypes there was a marked deficit (P<0·025) of older animals (⩾3 years), implying that some cases of scrapie had occurred previously. In the ensuing 17 months, 18 sheep of known genotype were confirmed positive for the disease: seven VRQ/ARQ, six VRQ/ARH, two VRQ/ARR, three ARQ/ARQ. Median ages at death were 2·7, 2·8, 4·2 and 3·8 years respectively. Mortality rates were 55, 86, 13 and 3% respectively. Survival analysis revealed a highly significant effect of genotype on survivorship, but no difference between VRQ/ARQ and VRQ/ARH, or between VRQ/ARR and ARQ/ARQ. There was no difference in the survivorship of middle- and older-age cohorts of susceptible sheep. Scrapie risk group (as defined by PrP genotype) was not associated with submission as a scrapie suspect but later found to be negative, or with dying of unknown causes on the farm.


2002 ◽  
Vol 6 (3) ◽  
pp. 527-537 ◽  
Author(s):  
F. Gallart ◽  
P. Llorens ◽  
J. Latron ◽  
D. Regüés

Abstract. The Vallcebre catchments are located in a middle mountain area of the Pyrenean ranges, built up by sedimentary rocks and loamy soils. The vegetation cover is pastures and forests of Pinus sylvestris, mostly occupying former agricultural terraces. Some relatively small, heavily eroded landscapes (badlands) occur in the catchments, playing a relevant hydrological and geomorphic role. Annual precipitation is 924 mm and potential (reference) evapotranspiration is about 700 mm. Rainfall interception in forests represents about 24% of precipitation; interception rates were similar throughout the seasons because of a compensation between rainfall intensities and atmospheric conditions. Soil moisture showed a temporal pattern characterised by the occurrence of marked deficit periods in summer and also, but less pronounced, in winter. During most of the year, subsurface flows on hillslopes drove the spatial organisation of soil moisture and the occurrence of saturated areas. Nevertheless, this spatial organisation was also controlled by the patterns of vegetation cover. During dry periods, subsurface flow ceased, saturated areas disappeared and the spatial patterns of soil moisture changed. Stream flow from these catchments was dominated by storm flow, and the runoff generating mechanisms showed a clear seasonal pattern, controlled mainly by the soil moisture and the extent of saturated areas. During the dry periods, runoff was produced only on impervious areas and badlands. At the end of the dry periods, some large rainfall events generated significant runoff because of the perched saturation of the shallow soil horizons. Thereafter, runoff generation was dominated by the role of saturated areas. Stream waters in catchments with badlands had very high suspended sediment concentrations. The seasonal pattern of erosion processes in badlands was characterised by physical weathering during winter, regolith breakdown and vigorous hillslope erosion during spring and summer, and efficient transport of sediments in autumn.


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