The Complete Structure of the Core Oligosaccharide from Edwardsiella tarda EIB 202 Lipopolysaccharide

The chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharide of pathogenic Edwardsiella tarda strain EIB 202 were studied for the first time. The complete gene assignment for all LPS core biosynthesis gene functions was acquired. The complete structure of core oligosaccharide was investigated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry MSn, and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. The following structure of the undecasaccharide was established: The heterogeneous appearance of the core oligosaccharide structure was due to the partial lack of β-d-Galp and the replacement of α-d-GlcpNAcGly by α-d-GlcpNGly. The glycine location was identified by mass spectrometry

Measurement report: Receptor modeling for source identification of urban fine and coarse particulate matter using hourly elemental composition

The elemental composition of the fine (PM2.5) and coarse (PM2.5−10) fraction of atmospheric particulate matter was measured at an hourly time resolution by the use of a streaker sampler during a winter period at a Central European urban background site in Warsaw, Poland. A combination of multivariate (Positive Matrix Factorization) and wind- (Conditional Probability Function) and trajectory-based (Cluster Analysis) receptor models was applied for source apportionment. It allowed for the identification of five similar sources in both fractions, including sulfates, soil dust, road salt, and traffic- and industry-related sources. Another two sources, i.e., Cl-rich and wood and coal combustion, were solely identified in the fine fraction. In the fine fraction, aged sulfate aerosol related to emissions from domestic solid fuel combustion in the outskirts of the city was the largest contributing source to fine elemental mass (44 %), while traffic-related sources, including soil dust mixed with road dust, road dust, and traffic emissions, had the biggest contribution to the coarse elemental mass (together accounting for 83 %). Regional transport of aged aerosols and more local impact of the rest of the identified sources played a crucial role in aerosol formation over the city. In addition, two intensive Saharan dust outbreaks were registered on 18 February and 8 March 2016. Both episodes were characterized by the long-range transport of dust at 1500 and 3000 m over Warsaw and the concentrations of the soil component being 7 (up to 3.5 µg m−3) and 6 (up to 6.1 µg m−3) times higher than the mean concentrations observed during non-episodes days (0.5 and 1.1 µg m−3) in the fine and coarse fractions, respectively. The set of receptor models applied to the high time resolution data allowed us to follow, in detail, the daily evolution of the aerosol elemental composition and to identify distinct sources contributing to the concentrations of the different PM fractions, and it revealed the multi-faceted nature of some elements with diverse origins in the fine and coarse fractions. The hourly resolution of meteorological conditions and air mass back trajectories allowed us to follow the transport pathways of the aerosol as well.</p

Somato-dendritic vasopressin and oxytocin secretion in endocrine and autonomic regulation

Somato‐dendritic secretion was first demonstrated over 30 years ago. However, although its existence has become widely accepted, the function of somato‐dendritic secretion is still not completely understood. Hypothalamic magnocellular neurosecretory cells were among the first neuronal phenotypes in which somato‐dendritic secretion was demonstrated and are among the neurones for which the functions of somato‐dendritic secretion are best characterised. These neurones secrete the neuropeptides, vasopressin and oxytocin, in an orthograde manner from their axons in the posterior pituitary gland into the blood circulation to regulate body fluid balance and reproductive physiology. Retrograde somato‐dendritic secretion of vasopressin and oxytocin modulates the activity of the neurones from which they are secreted, as well as the activity of neighbouring populations of neurones, to provide intra‐ and inter‐population signals that coordinate the endocrine and autonomic responses for the control of peripheral physiology. Somato‐dendritic vasopressin and oxytocin have also been proposed to act as hormone‐like signals in the brain. There is some evidence that somato‐dendritic secretion from magnocellular neurosecretory cells modulates the activity of neurones beyond their local environment where there are no vasopressin‐ or oxytocin‐containing axons but, to date, there is no conclusive evidence for, or against, hormone‐like signalling throughout the brain, although it is difficult to imagine that the levels of vasopressin found throughout the brain could be underpinned by release from relatively sparse axon terminal fields. The generation of data to resolve this issue remains a priority for the field.http://wileyonlinelibrary.com/journal/jne2021-04-17hj2020Immunolog

UV cross-linked polyvinylpyrrolidone electrospun fibres as antibacterial surfaces

Many bacteria become progressively more resistant to antibiotics and it remains a challenging task to control their overall levels. Polymers combined with active biomolecules come to the forefront for the design of antibacterial materials that can address this encounter. In this work, we investigated the photo-crosslinking approach of UV-sensitive benzophenone molecule (BP) with polyvinylpyrrolidone (PVP) polymer within electrospun fibres. The BP and PVP solutions allowed fabricating polymer mats that were subsequently functionalised with antibacterial lysozyme. The physical properties of the crosslinked electrospun fibres were investigated by scanning electron microscopy and atomic force microscopy. The average diameter of the obtained fibres decreased from 290 ± 50 nm to 270 ± 70 nm upon the addition of the crosslinking molecules and then to 240 ± 80 nm and 180 ± 90 nm after subsequent crosslinking reaction at an increasing time: 3 and 5 h, respectively. The peak force quantitative nanomechanical mapping (PF-QNM) indicated the increase of DMT modulus of obtained cross-linked fibres from 4.1 ± 0.8 GPa to 7.2 ± 0.5 GPa. Furthermore, the successful crosslinking reaction of PVP and BP solution into hydrogels was investigated in terms of examining photo-crosslinking mechanism and was confirmed by rheology, Raman, Fourier transform infrared and nuclear magnetic resonance. Finally, lysozyme was successfully encapsulated within cross-linked PVP-BP hydrogels and these were successfully electrospun into mats which were found to be as effective antibacterial agents as pure lysozyme molecules. The dissolution rate of photo cross-linked PVP mats was observed to increase in comparison to pure PVP electrospun mats which opened a potential route for their use as antibacterial, on-demand, dissolvable coatings for various biomedical applications

EHMTI-0026. Neuroprolotherapy and acupuncture for clinical trial of acute and chronic migraine treatment

Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR) are Ca2+-mobilizing messengers important for modulating cardiac excitation–contraction coupling and pathophysiology. CD38, which belongs to the ADP-ribosyl cyclase family, catalyzes synthesis of both NAADP and cADPR in vitro. However, it remains unclear whether this is the main enzyme for their production under physiological conditions. Here we show that membrane fractions from WT but not CD38−/− mouse hearts supported NAADP and cADPR synthesis. Membrane permeabilization of cardiac myocytes with saponin and/or Triton X-100 increased NAADP synthesis, indicating that intracellular CD38 contributes to NAADP production. The permeabilization also permitted immunostaining of CD38, with a striated pattern in WT myocytes, whereas CD38−/− myocytes and nonpermeabilized WT myocytes showed little or no staining, without striation. A component of β-adrenoreceptor signaling in the heart involves NAADP and lysosomes. Accordingly, in the presence of isoproterenol, Ca2+ transients and contraction amplitudes were smaller in CD38−/− myocytes than in the WT. In addition, suppressing lysosomal function with bafilomycin A1 reduced the isoproterenol-induced increase in Ca2+ transients in cardiac myocytes from WT but not CD38−/− mice. Whole hearts isolated from CD38−/− mice and exposed to isoproterenol showed reduced arrhythmias. SAN4825, an ADP-ribosyl cyclase inhibitor that reduces cADPR and NAADP synthesis in mouse membrane fractions, was shown to bind to CD38 in docking simulations and reduced the isoproterenol-induced arrhythmias in WT hearts. These observations support generation of NAADP and cADPR by intracellular CD38, which contributes to effects of β-adrenoreceptor stimulation to increase both Ca2+ transients and the tendency to disturb heart rhythm

Elite athletes' genetic predisposition for altered risk of complex metabolic traits

BACKGROUND: Genetic variants may predispose humans to elevated risk of common metabolic morbidities such as obesity and Type 2 Diabetes (T2D). Some of these variants have also been shown to influence elite athletic performance and the response to exercise training. We compared the genotype distribution of five genetic Single Nucleotide Polymorphisms (SNPs) known to be associated with obesity and obesity co-morbidities (IGF2BP2 rs4402960, LPL rs320, LPL rs328, KCJN rs5219, and MTHFR rs1801133) between athletes (all male, n = 461; endurance athletes n = 254, sprint/power athletes n = 207), and controls (all male, n = 544) in Polish and Russian samples. We also examined the association between these SNPs and the athletes’ competition level (‘elite’ and ‘national’ level). Genotypes were analysed by Single-Base Extension and Real-Time PCR. Multinomial logistic regression analyses were conducted to assess the association between genotypes and athletic status/competition level. RESULTS: IGF2BP2 rs4402960 and LPL rs320 were significantly associated with athletic status; sprint/power athletes were twice more likely to have the IGF2BP2 rs4402960 risk (T) allele compared to endurance athletes (OR = 2.11, 95% CI = 1.03-4.30, P <0.041), and non-athletic controls were significantly less likely to have the T allele compared to sprint/power athletes (OR = 0.62, 95% CI =0.43-0.89, P <0.0009). The control group was significantly more likely to have the LPL rs320 risk (G) allele compared to endurance athletes (OR = 1.26, 95% CI = 1.05-1.52, P <0.013). Hence, endurance athletes were the “protected” group being significantly (p < 0.05) less likely to have the risk allele compared to sprint/power athletes (IGF2BP2 rs4402960) and significantly (p < 0.05) less likely to have the risk allele compared to controls (LPL rs320). The other 3 SNPs did not show significant differences between the study groups. CONCLUSIONS: Male endurance athletes are less likely to have the metabolic risk alleles of IGF2BP2 rs4402960 and LPL rs320, compared to sprint/power athletes and controls, respectively. These results suggest that some SNPs across the human genome have a dual effect and may predispose endurance athletes to reduced risk of developing metabolic morbidities, whereas sprint/power athletes might be predisposed to elevated risk

Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis

OBJECTIVE: We have recently shown a significant reduction in cytokine-induced transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC-7) as a possible mechanism by which TSA exerts its antifibrotic function. METHODS: Skin fibroblasts from patients with SSc were treated with TSA and/or transforming growth factor beta. Expression of HDACs 1-11, extracellular matrix proteins, connective tissue growth factor (CTGF), and intercellular adhesion molecule 1 (ICAM-1) was analyzed by real-time polymerase chain reaction, Western blotting, and the Sircol collagen assay. HDAC-7 was silenced using small interfering RNA. RESULTS: SSc fibroblasts did not show a specific pattern of expression of HDACs. TSA significantly inhibited the expression of HDAC-7, whereas HDAC-3 was up-regulated. Silencing of HDAC-7 decreased the constitutive and cytokine-induced production of type I and type III collagen, but not fibronectin, as TSA had done. Most interestingly, TSA induced the expression of CTGF and ICAM-1, while silencing of HDAC-7 had no effect on their expression. CONCLUSION: Silencing of HDAC-7 appears to be not only as effective as TSA, but also a more specific target for the treatment of SSc, because it does not up-regulate the expression of profibrotic molecules such as ICAM-1 and CTGF. This observation may lead to the development of more specific and less toxic targeted therapies for SSc

The ACTN3 R577X Polymorphism across Three Groups of Elite Male European Athletes

The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter being usually low, which makes comparisons difficult. In this case:control genetic study we determined the association between elite athletic status and the ACTN3 R577X polymorphism within three cohorts of European Caucasian men, i.e. Spanish, Polish and Russian [633 cases (278 elite endurance and 355 power athletes), and 808 non-athletic controls]. The odds ratio (OR) of a power athlete harbouring the XX versus the RR genotype compared with sedentary controls was 0.54 [95% confidence interval (CI): 0.34–0.48; P = 0.006]. We also observed that the OR of an endurance athlete having the XX versus the RR genotype compared with power athletes was 1.88 (95%CI: 1.07–3.31; P = 0.028). In endurance athletes, the OR of a “world-class” competitor having the XX genotype versus the RR+RX genotype was 3.74 (95%CI: 1.08–12.94; P = 0.038) compared with those of a lower (“national”) competition level. No association (P>0.1) was noted between the ACTN3 R577X polymorphism and competition level (world-class versus national-level) in power athletes. Our data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance