HTRA3 (HtrA serine peptidase 3)

Review on HTRA3 (HtrA serine peptidase 3), with data on DNA, on the protein encoded, and where the gene is implicated

Preferential consolidation of emotional reactivity during sleep: A systematic review and meta-analysis

Many studies have investigated whether sleep affects cognitively unmodulated reactivity to emotional stimuli. These studies operationalize emotion regulation by using subjective and/or objective measures to compare pre- and post-sleep reactivity to the same emotional stimuli. Findings have been inconsistent: some show that sleep attenuates emotional reactivity, whereas others report enhanced or maintained reactivity. Across-study methodological differences may account for discrepant findings. To resolve the questions of whether sleep leads to the attenuation, enhancement, or maintenance of emotional reactivity, and under which experimental conditions particular effects are observed, we undertook a synthesized narrative and meta-analytic approach. We searched PubMed, PsycINFO, PsycARTICLES, Web of Science, and Cochrane Library databases for relevant articles, using search terms determined a priori and search limits of language = English, participants = human, and dates = January 2006–June 2021. Our final sample included 24 studies that investigated changes in emotional reactivity in response to negatively and/or positively valenced material compared to neutral material over a period of sleep compared to a matched period of waking. Primary analyses used random effects modeling to investigate whether sleep preferentially modulates reactivity in response to emotional stimuli; secondary analyses examined potential moderators of the effect. Results showed that sleep (or equivalent periods of wakefulness) did not significantly affect psychophysiological measures of reactivity to negative or neutral stimuli. However, self-reported arousal ratings of negative stimuli were significantly increased post-sleep but not post-waking. Sub-group analyses indicated that (a) sleep-deprived participants, compared to those who slept or who experienced daytime waking, reacted more strongly and negatively in response to positive stimuli; (b) nap-exposed participants, compared to those who remained awake or who slept a full night, rated negative pictures less negatively; and (c) participants who did not obtain substantial REM sleep, compared to those who did and those exposed to waking conditions, had attenuated reactivity to neutral stimuli. We conclude that sleep may affect emotional reactivity, but that studies need more consistency in methodology, commitment to collecting both psychophysiological and self-report measures, and should report REM sleep parameters. Using these methodological principles would promote a better understanding of under which conditions particular effects are observed

HTRA1 (HtrA serine peptidase 1)

Review on HTRA1 (HtrA serine peptidase 1), with data on DNA, on the protein encoded, and where the gene is implicated

Strength, Endocrine, and Body Composition Alterations Across Four Blocks of Training in an Elite 400 M Sprinter

The ability to produce force rapidly has the potential to directly influence sprinting performance through changes in stride length and stride frequency. This ability is commonly referred to as the rate of force development (RFD). For this reason, many elite sprinters follow a combined program consisting of resistance training and sprint training. The purpose of this study was to investigate the strength, endocrine and body composition adaptations that occur during distinct phases of a block periodized training cycle in a 400 m Olympic level sprinter. The athlete is an elite level 400 m male sprinter (age 31 years, body mass: 74 kg, years of training: 15 and Personal Best (PB): 45.65 s). This athlete completed four distinct training phases of a block periodized training program (16 weeks) with five testing sessions consisting of testosterone:cortisol (T/C) profiles, body composition, vertical jump, and maximum strength testing. Large fluctuations in T/C were found following high volume training and the taper. Minor changes in body mass were observed with an abrupt decrease following the taper which coincided with a small increase in fat mass percentage. Jump height (5.7%), concentric impulse (9.4%), eccentric impulse (3.4%) and power ratio (18.7%) all increased substantially from T1 to T5. Relative strength increased 6.04% from T1 to T5. Lastly, our results demonstrate the effectiveness of a competitive taper in increasing physiological markers for performance as well as dynamic performance variables. Block periodization training was effective in raising the physical capabilities of an Olympic level 400 m runner which have been shown to directly transfer to sprinting performance

Factors Defining the Functional Oligomeric State of Escherichia coli DegP Protease

Escherichia coli DegP protein is a periplasmic protein that functions both as a protease and as a chaperone. In the absence of substrate, DegP oligomerizes as a hexameric cage but in its presence DegP reorganizes into 12 and 24-mer cages with large chambers that house the substrate for degradation or refolding. Here, we studied the factors that determine the oligomeric state adopted by DegP in the presence of substrate. Using size exclusion chromatography and electron microscopy, we found that the size of the substrate molecule is the main factor conditioning the oligomeric state adopted by the enzyme. Other factors such as temperature, a major regulatory factor of the activity of this enzyme, did not influence the oligomeric state adopted by DegP. In addition, we observed that substrate concentration exerted an effect only when large substrates (full-length proteins) were used. However, small substrate molecules (peptides) always triggered the same oligomeric state regardless of their concentration. These results clarify important aspects of the regulation of the oligomeric state of DegP

The Cystic Fibrosis-Like Airway Surface Layer Is not a Significant Barrier for Delivery of Eluforsen to Airway Epithelial Cells

Background: Eluforsen (previously known as QR-010) is a 33-mer antisense oligonucleotide under development for oral inhalation in cystic fibrosis (CF) patients with the delta F508 mutation. Previous work has shown that eluforsen restores CF transmembrane conductance regulator (CFTR) function in vitro and in vivo. To be effective, eluforsen has first to reach its primary target, the lung epithelial cells. Therefore, it has to diffuse through the CF airway surface layer (ASL), which in CF is characterized by the presence of thick and viscous mucus, impaired mucociliary clearance, and persistent infections. The goal of this study was to assess delivery of eluforsen through CF-like ASL. Methods and Results: First, air-liquid interface studies with cultured primary airway epithelial cells revealed that eluforsen rapidly diffuses through CF-like mucus at clinically relevant doses when nebulized once or repeatedly, over a range of testing doses. Furthermore, eluforsen concentrations remained stable in CF patient sputum for at least 48 hours, and eluforsen remained intact in the presence of various inhaled CF medications for at least 24 hours. When testing biodistribution of eluforsen after orotracheal administration in vivo, no differences in lung, liver, trachea, and kidney eluforsen concentration were observed between mice with a CF-like lung phenotype (ENaC-overexpressing mice) and control wild-Type (WT) littermates. Also, eluforsen was visualized in the airway epithelial cell layer of CF-like muco-obstructed mice and WT littermates. Finally, studies of eluforsen uptake and binding to bacteria prevalent in CF lungs, and diffusion through bacterial biofilms showed that eluforsen was stable and not absorbed by, or bound to bacteria. In addition, eluforsen was found to be able to penetrate Pseudomonas aeruginosa biofilms. Conclusions: The thickened and concentrated CF ASL does not constitute a significant barrier for delivery of eluforsen, and feasibility of oral inhalation of eluforsen is supported by these data

Reversal of the ΔdegP Phenotypes by a Novel rpoE Allele of Escherichia coli

RseA sequesters RpoE (σE) to the inner membrane of Escherichia coli when envelope stress is low. Elevated envelope stress triggers RseA cleavage by the sequential action of two membrane proteases, DegS and RseP, releasing σE to activate an envelope stress reducing pathway. Revertants of a ΔdegP ΔbamB strain, which fails to grow at 37°C due to high envelope stress, harbored mutations in the rseA and rpoE genes. Null and missense rseA mutations constitutively hyper-activated the σE regulon and significantly reduced the major outer membrane protein (OMP) levels. In contrast, a novel rpoE allele, rpoE3, resulting from the partial duplication of the rpoE gene, increased σE levels greater than that seen in the rseA mutant background but did not reduce OMP levels. A σE-dependent RybB::LacZ construct showed only a weak activation of the σE pathway by rpoE3. Despite this, rpoE3 fully reversed the growth and envelope vesiculation phenotypes of ΔdegP. Interestingly, rpoE3 also brought down the modestly activated Cpx envelope stress pathway in the ΔdegP strain to the wild type level, showing the complementary nature of the σE and Cpx pathways. Through employing a labile mutant periplasmic protein, AcrAL222Q, it was determined that the rpoE3 mutation overcomes the ΔdegP phenotypes, in part, by activating a σE-dependent proteolytic pathway. Our data suggest that a reduction in the OMP levels is not intrinsic to the σE-mediated mechanism of lowering envelope stress. They also suggest that under extreme envelope stress, a tight homeostasis loop between RseA and σE may partly be responsible for cell death, and this loop can be broken by mutations that either lower RseA activity or increase σE levels

Panton-Valentine Leukocidin Does Play a Role in the Early Stage of Staphylococcus aureus Skin Infections: A Rabbit Model

Despite epidemiological data linking necrotizing skin infections with the production of Panton-Valentine leukocidin (PVL), the contribution of this toxin to the virulence of S. aureus has been highly discussed as a result of inconclusive results of in vivo studies. However, the majority of these results originate from experiments using mice, an animal species which neutrophils - the major target cells for PVL - are highly insensitive to the action of this leukocidin. In contrast, the rabbit neutrophils have been shown to be as sensitive to PVL action as human cells, making the rabbit a better experimental animal to explore the PVL role. In this study we examined whether PVL contributes to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits were injected intradermally with 108 cfu of either a PVL positive community-associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or a PVL complemented knockout strain, and the development of skin lesions was observed. While all strains induced skin infection, the wild type strain produced larger lesions and a higher degree of skin necrosis compared to the PVL knockout strain in the first week after the infection. The PVL expression in the rabbits was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies observed only in the rabbits infected with PVL positive strains. These results indicate that the rabbit model is more suitable for studying the role of PVL in staphylococcal diseases than other animal models. Further, they support the epidemiological link between PVL producing S. aureus strains and necrotizing skin infections