Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific ...immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
The 1.28 GHz MeerKAT Galactic Center Mosaic Heywood, I.; Rammala, I.; Camilo, F. ...
Astrophysical journal/The Astrophysical journal,
02/2022, Letnik:
925, Številka:
2
Journal Article
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Abstract
The inner ∼200 pc region of the Galaxy contains a 4 million M
⊙
supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic-ray energy densities ...that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation-driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total-intensity and spectral-index mosaics of the region from 20 pointings (144 hr on-target in total), covering 6.5 square degrees with an angular resolution of 4″ at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT’s high sensitivity, exceptional
u
,
v
-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new nonthermal filament complexes, and enhanced views of the Radio Arc bubble, Sagittarius A, and Sagittarius B regions. This project is a South African Radio Astronomy Observatory public legacy survey, and the image products are made available with this article.
Vitamin D has been linked with improved survival after breast cancer diagnosis but little is known about prescribing rates. This study investigates trends in vitamin D supplement use in both a ...general female and breast cancer population.
Women with a breast cancer diagnosis were identified from the National Cancer Registry of Ireland (n = 19870). Women who had any vitamin D claim between 2005 and 2011 were identified from pharmacy claims data (n = 8556). Prevalence rates were calculated as a proportion of all eligible women and by age (< 55 years, ≥ 55 years). Poisson regression was used to compare rates of vitamin D prescribing across years (risk ratio (RR), 95% CI).
There was a statistically significant increase in women with a claim for vitamin D between 2005-2011, with the largest increase among breast cancer patients aged ≥ 55 years (RR = 2.26; 95% CI, 2.11-2.42).
This may have significant public health implications if associations between vitamin D and improved breast cancer survival prove to be causal.
The 1.28 GHz MeerKAT DEEP2 Image Cotton, W. D.; Matthews, A. M.; Abbott, T. D. ...
Astrophysical journal/The Astrophysical journal,
01/2020, Letnik:
888, Številka:
2
Journal Article
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We present the confusion-limited 1.28 GHz MeerKAT DEEP2 image covering one primary-beam area with θ = 7 6 FWHM resolution and rms noise. Its J2000 center position = 04h 13m 26 4, δ = −80° 00′ 00″ was ...selected to minimize artifacts caused by bright sources. We introduce the new 64-element MeerKAT array and describe commissioning observations to measure the primary-beam attenuation pattern, estimate telescope pointing errors, and pinpoint (u, v) coordinate errors caused by offsets in frequency or time. We constructed a 1.4 GHz differential source count by combining a power-law count fit to the DEEP2 confusion P(D) distribution from 0.25 to 10 Jy with counts of individual DEEP2 sources between 10 Jy and 2.5 mJy. Most sources fainter than S ∼ 100 Jy are distant star-forming galaxies (SFGs) obeying the far-IR/radio correlation, and sources stronger than 0.25 Jy account for ∼93% of the radio background produced by SFGs. For the first time, the DEEP2 source count has reached the depth needed to reveal the majority of the star formation history of the universe. A pure luminosity evolution of the 1.4 GHz local luminosity function consistent with the Madau & Dickinson model for the evolution of SFGs based on UV and infrared data underpredicts our 1.4 GHz source count in the range .
Accumulated evidence suggests that a variant within the CR1 gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences β-amyloid (Aβ) deposition in ...brain tissue. Given the biologic overlap between AD and cerebral amyloid angiopathy (CAA), a leading cause of intracerebral hemorrhage (ICH) in elderly individuals, we investigated whether rs6656401 increases the risk of CAA-related ICH and influences vascular Aβ deposition.
We performed a case-control genetic association study of 89 individuals with CAA-related ICH and 280 individuals with ICH unrelated to CAA and compared them with 324 ICH-free control subjects. We also investigated the effect of rs6656401 on risk of recurrent CAA-ICH in a prospective longitudinal cohort of ICH survivors. Finally, association with severity of histopathologic CAA was investigated in 544 autopsy specimens from 2 longitudinal studies of aging.
rs6656401 was associated with CAA-ICH (odds ratio OR = 1.61, 95% confidence interval CI 1.19-2.17, p = 8.0 × 10(-4)) as well as with risk of recurrent CAA-ICH (hazard ratio = 1.35, 95% CI 1.04-1.76, p = 0.024). Genotype at rs6656401 was also associated with severity of CAA pathology at autopsy (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Adjustment for parenchymal amyloid burden did not cancel this effect, suggesting that, despite the correlation between parenchymal and vascular amyloid pathology, CR1 acts independently on both processes, thus increasing risk of both AD and CAA.
The CR1 variant rs6656401 influences risk and recurrence of CAA-ICH, as well as the severity of vascular amyloid deposition.
Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless ...fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported. Given the patchy and asymmetric nature of the malformations, ECCL has been hypothesized to be due to a post-zygotic, mosaic mutation. Despite phenotypic overlap with several other disorders associated with mutations in the RAS-MAPK and PI3K-AKT pathways, the molecular etiology of ECCL remains unknown. Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each. These two residues are the most commonly mutated residues in FGFR1 in human cancers and are associated primarily with CNS tumors. Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1. Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling. In addition to identifying the molecular etiology of ECCL, our results support the emerging overlap between mosaic developmental disorders and tumorigenesis.
Talent identification in youth soccer is a complex decision-making process that requires selectors to judge an individual's future potential. While there has been considerable research into the ...performance characteristics of talented players, investigators have limited consensus on the best approach to assess soccer skills. Most of the research explains why we should measure skill instead of how we go about assessing skill. Therefore, the current scoping review aimed to synthesize and analyse skill assessments in youth soccer. Four electronic databases (EBSCO, ProQuest, PubMed, and Scopus) were searched for relevant studies. Information regarding the sample characteristics and methodological design of the skill assessments were extracted, synthesised, and presented in a qualitative analysis. Overall, 226 skill assessments were used across the 93 included studies. Male players from different ages (U/7-U/23) and playing levels comprised most (89%) of the collective sample. The majority of assessments were performed in settings not representative of football match-play (68%), focused on offensive skills (99%), and included skill outcome measures (95%). The variability of assessments highlights some confusion about the best way to assess soccer skill, potentially limiting selectors ability to identify skilful players. Ultimately, this will impact the number of quality players within the talent pool.
GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, ...schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABA
receptor-associated protein (GABARAP) to stabilize cell surface GABA
receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.
Stevens, CJ, Bennett, KJM, Sculley, DV, Callister, R, Taylor, L, and Dascombe, BJ. A comparison of mixed-method cooling interventions on preloaded running performance in the heat. J Strength Cond Res ...31(3): 620-629, 2017-The purpose of this investigation was to assess the effect of combining practical methods to cool the body on endurance running performance and physiology in the heat. Eleven trained male runners completed 4 randomized, preloaded running time trials (20 minutes at 70% VCombining Dot AboveO2max and a 3 km time trial) on a nonmotorized treadmill in the heat (33° C). Trials consisted of precooling by combined cold-water immersion and ice slurry ingestion (PRE), midcooling by combined facial water spray and menthol mouth rinse (MID), a combination of all methods (ALL), and control (CON). Performance time was significantly faster in MID (13.7 ± 1.2 minutes; p < 0.01) and ALL (13.7 ± 1.4 minutes; p = 0.04) but not PRE (13.9 ± 1.4 minutes; p = 0.24) when compared with CON (14.2 ± 1.2 minutes). Precooling significantly reduced rectal temperature (initially by 0.5 ± 0.2° C), mean skin temperature, heart rate and sweat rate, and increased iEMG activity, whereas midcooling significantly increased expired air volume and respiratory exchange ratio compared with control. Significant decreases in forehead temperature, thermal sensation, and postexercise blood prolactin concentration were observed in all conditions compared with control. Performance was improved with midcooling, whereas precooling had little or no influence. Midcooling may have improved performance through an attenuated inhibitory psychophysiological and endocrine response to the heat.
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