Analysis of the vertical movement of active GNSS stations as a result of semidiurnal tides

Ireland is subject to the constant effects and influence of semidiurnal tides. Western coastal regions are exposed to tidal ranges up to and exceeding five metres, consequentially introducing varied water volumes with temporal intervals. In addition, the Earth is elastic in composition, resulting in morphing and warping at the hands of celestial and oceanic forces. This study looked at Online Precise Point Positioning (PPP) service to accurately monitor the vertical movement of coastal lands. In addition, GNSS Static Post-processing was conducted to discern which method of the global navigation satellite system (GNSS) processing is best for detecting VLM (vertical land motion). The study took place throughout 2020, focusing on the tidal peaks and troughs of the 21st of each month. Six-hour time windows were created around tidal peaks and troughs using data from the Marine Institute. GNSS data files replicating these time windows were processed using both PPP and manual network adjustment methods. MATLAB Online analysis aided in concluding the study. Results were inconclusive in determining which method of GNSS processing were best for identifying VLM. Based on the evidence provided by this study, the influence of semidiurnal tidal peaks and troughs cannot be deemed significant in magnitude to require mitigation. Western Irish coastal zones are therefore not subjected to large scale VLM. Similar studies of coastal zones that experience tidal ranges exceeding five metres would be recommended. An extended study period would also be recommended to better understand semidiurnal tidal influences in Ireland

Sequestosome‐1 (p62) expression reveals chaperone‐assisted selective autophagy in immune‐mediated necrotizing myopathies

Diffuse myofiber necrosis in the context of inflammatory myopathy is the hallmark of immune-mediated necrotizing myopathy (IMNM). We have previously shown that skeletal muscle fibers of IMNM patients may display nonrimmed vacuoles and sarcoplasmic irregularities. The dysfunctional chaperone activity has been linked to the defective assembly of skeletal muscle proteins and their degradation via lysosomes, autophagy and the proteasomal machinery. This study was undertaken to highlight a chaperone-assisted selective autophagy (CASA) pathway, functionally involved in protein homeostasis, cell stress and the immune response in skeletal muscle of IMNM patients. Skeletal muscle biopsies from 54 IMNM patients were analyzed by immunostaining, as well as by qPCR. Eight biopsies of sIBM patients served as pathological controls, and eight biopsies of nondisease control subjects were included. Alteration of autophagy was detectable in all IMNM biopsy samples highlighted via a diffuse sarcoplasmic staining pattern by p62 and LC3 independent of vacuoles. This pattern was at variance with the coarse focal staining pattern mostly confined to rimmed vacuoles in sIBM. Colocalization of p62 with the chaperone proteins HSP70 and alpha B-crystalline points to the specific targeting of misfolded proteins to the CASA machinery. Bcl2-associated athanogene 3 (BAG3) positivity of these fibers emphasizes the selectivity of autophagy processes and these fibers also express MHC class I sarcolemma. Expression of genes involved in autophagy and endoplasmic reticulum (ER) stress pathways studied here is significantly upregulated in IMNM. We highlight that vacuoles without sarcolemmal features may arise in IMNM muscle biopsies, and they must not be confounded with sIBM-specific vacuoles. Further, we show the activation of selective autophagy and emphasize the role of chaperones in this context. CASA occurs in IMNM muscle, and specific molecular pathways of autophagy differ from the ones in sIBM, with p62 as a unique identifier of this process

Relationship of Circulating Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels to Disease Control in Asthma and Asthmatic Pregnancy

Asthma has a high burden of morbidity if not controlled and may frequently complicate pregnancy, posing a risk for pregnancy outcomes. Elevated plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is related to a worse prognosis in many conditions such as infectious, autoimmune, or pregnancy-related diseases; however the value of suPAR in asthma and asthmatic pregnancy is unknown. The present study aimed to investigate the suPAR, CRP and IL-6 levels in asthma (asthmatic non-pregnant, ANP; N = 38; female N = 27) and asthmatic pregnancy (AP; N = 15), compared to healthy non-pregnant controls (HNP; N = 29; female N = 19) and to healthy pregnant women (HP; N = 58). The relationship between suPAR levels and asthma control was also evaluated. The diagnostic efficacy of suPAR in asthma control was analyzed using ROC analysis. IL-6 and CRP levels were comparable in all study groups. Circulating suPAR levels were lower in HP and AP than in HNP and ANP subjects, respectively (2.01 [1.81-2.38] and 2.39 [2.07-2.69] vs. 2.60 [1.82-3.49] and 2.84 [2.33-3.72] ng/mL, respectively, p = 0.0001). suPAR and airway resistance correlated in ANP (r = 0.47, p = 0.004). ROC analysis of suPAR values in ANP patients with PEF above and below 80% yielded an AUC of 0.75 (95% CI: 0.57-0.92, p = 0.023) and with ACT total score above and below 20 an AUC of 0.80 (95% CI: 0.64-0.95, p = 0.006). The cut-off value of suPAR to discriminate between controlled and not controlled AP and ANP was 4.04 ng/mL. In conclusion, suPAR may help the objective assessment of asthma control, since it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease in circulating suPAR levels detected both in healthy and asthmatic pregnant women presumably represents pregnancy induced immune tolerance

Physicochemical properties of pore residues predict activation gating of CaV1.2: A correlation mutation analysis

Single point mutations in pore-forming S6 segments of calcium channels may transform a high-voltage-activated into a low-voltage-activated channel, and resulting disturbances in calcium entry may cause channelopathies (Hemara-Wahanui et al., Proc Natl Acad Sci U S A 102(21):7553–7558, 16). Here we ask the question how physicochemical properties of amino acid residues in gating-sensitive positions on S6 segments determine the threshold of channel activation of CaV1.2. Leucine in segment IS6 (L434) and a newly identified activation determinant in segment IIIS6 (G1193) were mutated to a variety of amino acids. The induced leftward shifts of the activation curves and decelerated current activation and deactivation suggest a destabilization of the closed and a stabilisation of the open channel state by most mutations. A selection of 17 physicochemical parameters (descriptors) was calculated for these residues and examined for correlation with the shifts of the midpoints of the activation curve (ΔVact). ΔVact correlated with local side-chain flexibility in position L434 (IS6), with the polar accessible surface area of the side chain in position G1193 (IIIS6) and with hydrophobicity in position I781 (IIS6). Combined descriptor analysis for positions I781 and G1193 revealed that additional amino acid properties may contribute to conformational changes during the gating process. The identified physicochemical properties in the analysed gating-sensitive positions (accessible surface area, side-chain flexibility, and hydrophobicity) predict the shifts of the activation curves of CaV1.2

Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food

EFSA wishes to thank the Working Group members: Manolis Kogevinas (until 14 September 2016), George Loizou (until 23 January 2017), and the hearing experts: Matteo Bonzini, Jane Burns, Claude Emond, Aleksander Giwercman, Russ Hauser, Lidia Mínguez‐Alarcón and Paolo Mocarelli, for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data on PCDD/Fs and DL‐PCBs in food and feed, and supported the data collection for the Comprehensive European Food Consumption Database.Peer reviewedPublisher PD

Effect of Standard Tuberculosis Treatment on Plasma Cytokine Levels in Patients with Active Pulmonary Tuberculosis

CITATION: Riou, C. et al. 2012. Effect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis. PLoS ONE, 7(5): e36886, doi:10.1371/journal.pone.0036886.The original publication is available at http://journals.plos.org/plosoneBackground: Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy. Methods: Twenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion. Results: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators. Conclusions: These data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036886Publisher's versio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms