PL - 030 The effects of ACE gene polymorphisms on ACE content before and after High-Intensity Interval Exercise

Objective Angiotensin Converting Enzyme (ACE) is expressed in human skeletal muscle.  The ACE I/D polymorphism (rs4341) has been associated with athletic performance in some studies. Studies suggested that the ACE I/D gene polymorphism is associated with ACE enzyme content in serum, however, the effect of ACE I/D on ACE protein content in human skeletal muscle in unclear. Angiotensin-converting enzyme 2 (ACE2) is a new component of the renin-angiotensin system (RAS), which is counter-regulatory to the ACE enzyme. The polymorphisms in the ACE2 gene (rs1978124 and rs2285666) have been reported to be associated with hypertension, however, their effects on ACE content in the blood and in skeletal muscle have yet to be explored. Utilising the Gene SMART cohort (n=81), we investigated whether the ACE I/D gene polymorphism (rs4341) and two ACE2 gene polymorphisms (rs1978124 and rs2285666) were associated with ACE enzyme content in the blood and skeletal muscle at baseline, and following a single session of High-Intensity Interval Exercise (HIIE). Methods ACE and ACE2 gene polymorphisms were determined using the TaqMan SNP assay (Applied Biosystems, Foster City, California, United States) by Mastercycler® ep realplex2 (Eppendorf, Hamburg, Germany), and QuantStudio™ 7 Flex Real-Time PCR System (Applied Biosystems, Foster City, California, United States). For quantitation of ACE content in the plasma, Abcam Human ELISA Kit (ab119577 –ACE (CD143)) was used (Abcam, Cambridge, United Kingdom). Western blots were used to measure ACE content in skeletal muscle. We used robust linear models adjusted for age to test the effect of the ACE I/D polymorphism on outcomes at baseline, using the MASS package in the R statistical software. p-values were adjusted for multiple comparisons using the Benjamini and Hochberg method, and all reported p-values are adjusted p-values. An adjusted p value < 0.005 was considered significant. Results We found that the ACE I/D gene polymorphism was associated with ACE content in the blood (p<0.005) at baseline, but not the ACE protein content in skeletal muscle at baseline. The ACE2 polymorphisms (rs1978124 and rs2285666) were not associated with ACE enzyme content in the blood or in skeletal muscle at baseline. A single session of HIIE tended (0.005 < p < 0.05) to increase blood ACE content immediately post exercise, while skeletal muscle ACE protein content was lower 3 hours post  a single session of HIIE (p<0.005). However, those changes were not related to ACE I/D or ACE2 polymorphisms. Conclusions The ACE I/D gene polymorphism influences ACE enzyme content in the blood but not the ACE protein content of human skeletal muscle. ACE I/D gene polymorphism does not influence the changes of ACE content after a single session of HIIE. ACE2 gene polymorphisms seem to have no effect on ACE content in the blood and skeletal muscle, before or after a session of HIIE

ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study

Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort (n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood (P \u3c 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 \u3c P \u3c 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE (P \u3c 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE (P \u3c 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle. NEW & NOTEWORTHY: This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content

Update on neutrophil function in severe inflammation

Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation

Multicomponent polysaccharide alginate-based bioinks

3D-Bioprinting has seen a rapid expansion in the last few years, with an increasing number of reported bioinks. Alginate is a natural biopolymer that forms hydrogels by ionic cross-linking with calcium ions. Due to its biocompatibility and ease of gelation, it is an ideal ingredient for bioinks. This review focuses on recent advances on bioink formulations based on the combination of alginate with other polysaccharides. In particular, the molecular weight of the alginate and its loading level has an impact on materials performance, as well as the loading of the divalent metal salt and its solubility, which affects the cross-linking of the gel. Alginate is often combined with other polysaccharides that can sigificantly modify the properties of the gel, and can optimise alginate for use in different biological applications. It is also possible to combine alginate with sacrificial polymers, which can temporarily reinforce the 3D printed construct, but then be removed at a later stage. Other additives can be formulated into the gels to enhance performance, including nanomaterials that tune rheological properties, peptides to encourage cell adhesion, or growth factors to direct stem cell differentiation. The ease of formulating multiple components into alginate gels gives them considerable potential for further development. In summary, this review will facilitate the identification of different alginate-polysaccharide bioink formulations and their optimal applications, and help inform the design of second generation bioinks, allowing this relatively simple gel system to achieve more sophisticated control over biological processes

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Resistance mechanisms of

Introduction. Root-knot nematodes (Meloidogyne sp.) cause significant economic damage to Prunus species in China. One of the most economical and environmentally sustainable methods to reduce the impact of root-knot nematodes is the use of resistant rootstock cultivars. Our aim was to examine resistance to M. incognita and its mechanisms. Materials and methods. Four rootstocks were assessed: Tsukuba-4 (P. persica), Tsukuba-5 (P. persica), Nanking cherry (P. tomentosa) and wild peach (P. persica). The susceptible tomato (Lycopersicon esculentum Mill.) cultivar ‘Baiguoqiangfeng’ was used as a positive control. Results. Nematodes did not penetrate roots of Tsukuba-4 and Tsukuba-5, which were considered to be immune varieties. Nanking cherry was highly resistant to M. incognita, whereas wild peach was susceptible. Conclusion. The differences in resistance among the rootstocks were not attributed to differences in effects of root diffusates, but were related to the different structural organizations of the root tips. The epidermal structure of Tsukuba-4 and Tsukuba-5 completely prevented the penetration of second-stage juveniles of M. incognita (J2). In Nanking cherry, penetration of J2 juveniles was reduced, and the development of nematodes from the J2 to female stage was delayed