Accessing the Next Generation of Synthetic Mussel‐Glue Polymers via Mussel‐Inspired Polymerization

The formation of cysteinyldopa as biogenic connectivity in proteins is used to inspire a chemical pathway toward mussel-adhesive mimics. The mussel-inspired polymerization (MIPoly) exploits the chemically diverse family of bisphenol monomers that is oxidizable with 2-iodoxybenzoic acid to give bisquinones. Those react at room temperature with dithiols in Michael-type polyadditions, which leads to polymers with thiol–catechol connectivities (TCC). A set of TCC polymers proved adhesive behavior even on challenging poly(propylene) substrates, where they compete with commercial epoxy resins in dry adhesive strength. MIPoly promises facile scale up and exhibits high modularity to tailor adhesives, as proven on a small library where one candidate showed wet adhesion on aluminum substrates in both water and sea water models.Verband der Chemischen Industrie http://dx.doi.org/10.13039/100007215Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Peer Reviewe

Muschelinspirierte Polymerisation

Verschiedene marine Lebewesen, wie zum Beispiel Muscheln, zeigen beeindruckende Unterwasserklebefähigkeiten. Vor allem L-3,4-Dihydroxyphenylalanin (Dopa), ein sehr häufig vorkommendes Aminosäurederivat in den Proteinen des Muschelklebesystems, wirkt sich positiv auf die Adhäsions- und Kohäsionsfähigkeit der Muschel aus. Im Rahmen dieser Arbeit dient die Bildung von Cysteinyldopa, welches als biogene Verknüpfung in Proteinen vorkommt, als Inspiration für die Entwicklung eines chemischen Ansatzes zur Synthese muschelmimetischer Klebstoffe. In einem AA+BB-Polyadditionsansatz (muschelinspirierte Polymerisation, MIPoly) werden Dichinone und Dithiole als Monomere eingesetzt. Hierfür werden die Dichinone ausgehend von der chemisch vielfältigen Familie der Bisphenol-Monomere durch Oxidation mit 2-Iodoxybenzoesäure synthetisiert. Die Dichinone und die Dithiole reagieren bei Raumtemperatur in einer Michael-artigen Polyaddition, wodurch Polymeren erhalten werden, die adhäsive Thiol-Catechol-Verknüpfungen (thiol-catechol-connectivities, TCCs) in ihrem Rückgrat aufweisen. Die detaillierte Untersuchung des MIPoly-Prozesses, der gebildeten TCC-Polymere sowie niedermolekularer Modellreaktionen ermöglicht den Nachweis der TCC-Bildung und bestätigte den Michael-artigen-Polyadditionsmechanismus. Dieses chemische MIPoly ist eine robuste Reaktion, die eine einfache Skalierbarkeit verspricht und einen modularen Ansatz für maßgeschneiderte Klebstoffe bietet. Der generische Charakter der untersuchten MIPoly wird durch die Synthese einer TCC-Polymermatrix nachgewiesen. In Klebetests zeigen die synthetisierten TCC-Polymere Hafteigenschaften auf Aluminium und Polypropylen. Darüber hinaus können ausgewählte TCC-Polymere als Unterwasserklebstoffe unter Meerwassermodellbedingungen verwendet werden.Different marine organisms, such as mussels, provide impressive under water gluing capabilities. Mainly L-3,4-dihydroxyphenylalanin (Dopa), which is a highly abundant amino acid derivative in the proteins of the mussel gluing system, was found to have a positive effect on the adhesion and cohesion ability of the mussel. Here, the formation of cysteinyldopa as biogenic connectivity in proteins is used to inspire a chemical pathway toward mussel-adhesive mimics. In an AA+BB polyaddition approach (Mussel-inspired polymerization, MIPoly) bisquinones and dithiols are used as monomers. The bisquinones are synthesized from the chemically diverse family of bisphenol monomers by oxidation with 2-iodoxybenzoic acid. The bisquinones and the dithiols react at room temperature in Michel-type polyaddition, leading to polymers with adhesive thiol-catechol-connectivities (TCCs) in their backbone. The detailed investigation of the MIPoly process, the formed TCC-polymers as well as low molecular model reactions enable the verification of the TCC-formation and confirm the Michael-type polyaddition mechanism. This chemical MIPoly is a robust reaction that promises ease of scale up and provides a modular approach to tailor adhesives. The generic character of the investigated MIPoly process is shown by synthesizing a TCC-polymer matrix. In adhesive tests, the synthesized TCC-polymers show adhesive properties on aluminum and poly(propylene). Furthermore, selected TCC-polymers can be used as underwater adhesives in seawater modeling aqueous environments

Reasons for and Consequences of Low Energy Availability in Female and Male Athletes: Social Environment, Adaptations, and Prevention

Low energy availability (LEA) represents a state in which the body does not have enough energy left to support all physiological functions needed to maintain optimal health. When compared to the normal population, athletes are particularly at risk to experience LEA and the reasons for this are manifold. LEA may result from altered dietary behaviours that are caused by body dissatisfaction, the belief that a lower body weight will result in greater performance, or social pressure to look a certain way. Pressure can also be experienced from the coach, teammates, and in this day and age through social media platforms. While LEA has been extensively described in females and female athletes have started fighting against the pressure to be thin using their social media platforms, evidence shows that male athletes are at risk as well. Besides those obvious reasons for LEA, athletes engaging in sports with high energy expenditure (e.g. rowing or cycling) can unintentionally experience LEA; particularly, when the athletes’ caloric intake is not matched with exercise intensity. Whether unintentional or not, LEA may have detrimental consequences on health and performance, because both short-term and long-term LEA induces a variety of maladaptations such as endocrine alterations, suppression of the reproductive axis, mental disorders, thyroid suppression, and altered metabolic responses. Therefore, the aim of this review is to increase the understanding of LEA, including the role of an athlete’s social environment and the performance effects related to LEA. © 2020, The Author(s)

Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains

BACKGROUND: The purpose of this work was to study the gene expression of transient receptor potential (TRP) channels in the mouse. The application of a standardized and quantitative technique, TaqMan RT-PCR, should give information about the pattern and relative importance of TRP channels for murine tissues and cell types. To verify data sets with an independent method, we studied the occurrence of some of the transcripts by in situ hybridization. RESULTS: We have characterized the mRNA expression of 22 TRP channels in the mouse with a focus on nerve and muscle tissues. This is the first study to describe the expression profiles of all channel isoforms of the four related Group 1 subfamilies (TRPC, TRPV, TRPM and TRPA) with a standardized and quantitative technique. Comparisons of transcript abundance showed a consistent dominance of TRPM7 and TRPC3 in most tissues. We further observed characteristic patterns and differences in gene expression of individual channels ranging over three orders of magnitude. The overall level of TRP channel mRNAs was highest in brain areas followed by kidney, lung, reproductive organs and muscle. In brain TRPM3 and TRPM7 dominated and 19 other isoforms were detected. In lung and kidney TRPV4, TRPV5 and TRPM7 were found in highest levels. TRPM7, TRPC3, TRPC6 and TRPM3 mRNAs were characteristically present in all tested muscle tissues. Most data obtained with the C57Bl/10 mouse strain were confirmed with Balb/c and NOD mice. However, TRPC3, C6, TRPM7, M3, TRPV2 and V4 expression showed marked differences in the three tested mouse strains. In situ hybridization revealed co-expression of transcripts on the cellular level and widely confirmed the data obtained with RT-PCR. CONCLUSION: Transcripts coding for members of the TRPC, TRPV, TRPM and TRPA subfamilies of TRP cation channels are present in a broad spectrum of murine tissues. Several channel isoforms often coexist in a specific tissue or cell type. TRP channel expression does not show typical tissue specific dominance of individual members as is known from other ion channel families. Mouse strain specific variations of TRP channel expression indicate that genetic background or physiological requirements considerably influence expression levels

Implementing Zn2+ ion and pH-value control into artificial mussel glue proteins by abstracting a His-rich domain from preCollagen

A His-rich domain of preCollagen-D found in byssal threads is derivatized with Cys and Dopa flanks to allow for mussel-inspired polymerization. Artificial mussel glue proteins are accessed that combine cysteinyldopa for adhesion with sequences for pH or Zn2+ induced β-sheet formation. The artificial constructs show strong adsorption to Al2O3, the resulting coatings tolerate hypersaline conditions and cohesion is improved by activating the β-sheet formation, that enhances E-modulus up to 60%.Peer Reviewe

Abdominal obesity‐related disturbance of insulin sensitivity is associated with cd8+ emra cells in the elderly

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross‐sectional study, we aimed to investigate the potential mediating role of T‐EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA‐IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower‐weight subgroups. Linear regression analysis revealed that an elevated HOMA‐IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist‐to‐hip ratio on HOMA‐IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Nanoproteomic analysis of ischemia-dependent changes in signaling protein phosphorylation in colorectal normal and cancer tissue

Additional file 1: Table S1. Clinical data for the 20 patients analyzed in the study. Presents patient clinical data including tumor stage and grade

12-week combined strength and endurance exercise attenuates CD8+ T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial

Background: Age-related accumulation of highly differentiated CD8+ effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+ T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50—70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+ T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined. Results: The CD8+ EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p =.02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p =.03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p =.03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p >.05). Conclusions: Combined strength and endurance training seems to be a suitable approach to attenuate CD8+ T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation

Reliability and suitability of physiological exercise response and recovery markers

There is currently insufficient evidence about the reliable quantification of exercise load and athlete’s recovery management for monitoring training processes. Therefore, this test–retest study investigated the reliability of various subjective, muscle force, and blood-based parameters in order to evaluate their suitability for monitoring exercise and recovery cycles. 62 subjects completed two identical 60-min continuous endurance exercise bouts intermitted by a four-week recovery period. Before, immediately after, three, and 24 h after each exercise bout, analysis of parameters were performed. Significant changes over time were found for rating of perceived exertion (RPE), multidimensional mood state questionnaire (MDMQ), maximum voluntary contraction parameters (MVCs), and blood-based biomarkers (p 0.90). A good reliability was found for thiobarbituric acid reactive substances (TBARS) (ICC = 0.79) and haematological markers (ICC = 0.75–0.86). For RPE, MDMQ, interleukin (IL-) 1RA, IL-6, IL-8, IL-15, cortisol, lactate dehydrogenase (LDH), creatine kinase (CK) only moderate reliability was found (ICC < 0.75). Significant associations for IL1-RA and CK to MVC were found. The excellent to moderate reliability of TBARS, LDH, IL-1RA, six measured haematological markers, MVCs and MDMQ implicate their suitability as physiological exercise response and recovery markers for monitoring athletes’ load management. © 2020, The Author(s)