The modulation rate transfer function of a harbour porpoise (Phocoena phocoena)

During echolocation, toothed whales produce ultrasonic clicks at extremely rapid rates and listen for the returning echoes. The auditory brainstem response (ABR) duration was evaluated in terms of latency between single peaks: 5.5 ms (from peak I to VII), 3.4 ms (I–VI), and 1.4 ms (II–IV). In comparison to the killer whale and the bottlenose dolphin, the ABR of the harbour porpoise has shorter intervals between the peaks and consequently a shorter ABR duration. This indicates that the ABR duration and peak latencies are possibly related to the relative size of the auditory structures of the central nervous system and thus to the animal’s size. The ABR to a sinusoidal amplitude modulated stimulus at 125 kHz (sensitivity threshold 63 dB re 1 μPa rms) was evaluated to determine the modulation rate transfer function of a harbour porpoise. The ABR showed distinct envelope following responses up to a modulation rate of 1,900 Hz. The corresponding calculated equivalent rectangular duration of 263 μs indicates a good temporal resolution in the harbour porpoise auditory system similar to the one for the bottlenose dolphin. The results explain how the harbour porpoise can follow clicks and echoes during echolocation with very short inter click intervals.     

T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer

High-level microsatellite-unstable (MSI-H) colorectal carcinomas (CRC) represent a distinct subtype of tumors commonly characterized by dense infiltration with cytotoxic T cells, most likely due to expression of MSI-H-related frameshift peptides (FSP). The contribution of FSP and classical antigens like MUC1 and CEA to the cellular immune response against MSI-H CRC had not been analyzed so far. We analyzed tumor-infiltrating and peripheral T cells from MSI-H (n = 4 and n = 14, respectively) and microsatellite-stable (MSS) tumor patients (n = 26 and n = 17) using interferon gamma ELISpot assays. Responses against 4 FSP antigens and peptides derived from MUC1 to CEA were compared with and without depletion of regulatory T cells, and the results were related to the presence of the respective antigens in tumor tissue. Preexisting FSP-specific T cell responses were detected in all (4 out of 4) tumor-infiltrating and in the majority (10 out of 14) of peripheral T cell samples from MSI-H CRC patients, but rarely observed in MSS CRC patients. Preexisting T cell responses in MSI-H CRC patients were significantly more frequently directed against FSP tested in the present study than against peptides derived from classical antigens MUC1 or CEA (p = 0.049). Depletion of regulatory T cells increased the frequency of effector T cell responses specific for MUC1/CEA-derived peptides and, to a lesser extent, T cell responses specific for FSP. Our data suggest that the analyzed FSP may represent an immunologically relevant pool of antigens capable of eliciting antitumoral effector T cell responses.     

Seasonal Variation in Human Salivary Cortisol Concentration

Measurement of cortisol concentration can contribute important information about an individual's ability to adjust to various environmental demands of both physical and psychosocial origin. However, one uncertainty that affects the possibilities of correctly interpreting and designing field studies is the lack of observations of the impact of seasonal changes on cortisol excretion. For this reason, the month‐to‐month changes in diurnal cortisol concentration, the awakening cortisol response (ACR), maximum morning concentration, and fall during the day were studied in a group of 24 healthy men and women 32 to 61 yrs of age engaged in active work. On one workday for 12 consecutive months, participants collected saliva at four time points for determination of cortisol: at awakening, +30 min, +8 h, and at 21:00 h. Data were analyzed by a repeated measures design with month (12 levels) and time‐of‐day (4 levels) as categorical predictors. Cortisol concentrations were analyzed on a log scale. The diurnal pattern of cortisol was similar across months (interaction between month and time of day: p>0.4). The main effects of month and time‐of‐day were statistically significant (p <0.001). Highest concentrations were observed in February, March, and April, and lowest concentrations were observed in July and August. There were no statistically significant effects in any of the other measures, or between men and women. In conclusion, a seasonal variation in salivary cortisol concentrations was detected in an occupationally active population. Thus, seasonal variation needs to be taken into account when designing and evaluating field studies and interventions and when making comparisons across studies.     

A brief pre-exercise nap may alleviate physical performance impairments induced by short-term sustained operations with partial sleep deprivation – A field-based study

ABSTRACT

The purpose of the study was to evaluate the recuperative efficacy of pre-exercise napping on physical capacity after military sustained operations (SUSOPS) with partial sleep deprivation. Before and after a 2-day SUSOPS, 61 cadets completed a battery of questionnaires, and performed a 2-min lunges trial and a 3,000-m running time-trial. After the completion of SUSOPS, subjects were randomized to either a control [without pre-exercise nap (CON); n = 32] or a nap [with a 30-min pre-exercise nap (NAP); n = 29] group. SUSOPS enhanced perceived sleepiness and degraded mood in both groups. Following SUSOPS, the repetitions of lunges, in the CON group, were reduced by ~ 2.3%, albeit the difference was not statistically significant (p = 0.62). In the NAP group, however, the repetitions of lunges were increased by ~ 7.1% (p = 0.01). SUSOPS impaired the 3,000-m running performance in the CON group (~ 2.3%; p = 0.02), but not in the NAP group (0.3%; p = 0.71). Present results indicate, therefore, that a relatively brief pre-exercise nap may mitigate physical performance impairments ensued by short-term SUSOPS.     

When similar beginnings lead to different ends: Constraints and diversity in cirripede larval development

Summary

Cirripedes are fascinating models for studying both functional constraints and diversity in larval development. Adult cirripedes display an amazing variation in morphology from sessile suspension feeders that still retain many crustacean characters to parasites that have lost virtually all arthropod traits. In contrast, cirripede larval development follows a common scheme with pelagic larvae comprising a series of nauplii followed by a cyprid. Variations are mostly concerned with whether or not the nauplii are feeding and the degree of abbreviation of development, culminating in species where the larvae hatch as cyprids. The cypris larvae are very similar among the ingroups of the Cirripedia, but interesting variations occur in structures used for substrate location and attachment. The cyprid is specialized to both swim through the water and actively explore the substratum by walking on the antennules and using an array of sensory organs in search for a suitable site to attach. This unique morphology and behavior of the cyprid have enabled the Cirripedia to colonize widely different habitats ranging from hard rock to soft animal tissue. Yet, the cyprid can metamorphose into juveniles as different as a setose feeding barnacle and the vermiform stages of the parasitic forms. This emphasizes the importance of the cyprid as one of the key features for the evolutionary success of the Cirripedia.     

Pressure pain sensitivity and hardness along human normal and sensitized muscle

The spatial distribution of pressure sensitivity and muscle hardness was examined on normal muscle tissue and muscle tissue after induction of delayed onset muscle soreness (DOMS). The pressure sensitivity and muscle hardness were assessed at nine sites on the tibialis muscle from the proximal to distal tendon on two separate days. In total 37 healthy volunteers participated in three experiments. In the first experiment pressure pain threshold (PPT) and pressure pain tolerance (PPTO) were assessed. Decreased PPT and PPTO were found on day 2, 7 days after day 1. Proximal and distal stimulation sites were harder compared to muscle belly sites. In a second experiment two different probe sizes were used. Variation in PPT between the nine sites was found for the large probe with muscle belly being less sensitive to pressure stimulation compared to proximal and distal sites. The most proximal stimulation site was harder compared to muscle belly sites. In a third experiment PPT and muscle hardness were assessed before and 48?h after eccentric exercise. PPT at two muscle belly sites was significantly decreased during DOMS. No specific sites were harder during DOMS, the average muscle hardness across sites was however significantly increased. Decreased PPT and increased muscle hardness did not correlate. In conclusion, within subjects the pressure sensitivity varies along the musculoskeletal unit. In DOMS, specific muscle belly sites were more sensitive to pressure stimulation. Muscle–tendon sites were harder compared to muscle belly sites.     

High relative air humidity and continuous light reduce stomata functionality by affecting the ABA regulation in rose leaves

Plants developed under high (90%) relative air humidity (RH) have previously been shown to have large, malfunctioning stomata, which results in high water loss during desiccation and reduced dark induced closure. Stomatal movement is to a large extent regulated by abscisic acid (ABA). It has therefore been proposed that low ABA levels contribute to the development of malfunctioning stomata. In this study, we investigated the regulation of ABA content in rose leaves, through hormone analysis and β‐glucosidase quantification. Compared with high RH, rose plants developed in moderate RH (60%) and 20 h photoperiod contained higher levels of ABA and β‐glucosidase activity. Also, the amount of ABA increased during darkness simultaneously as the ABA‐glucose ester (GE) levels decreased. In contrast, plants developed under high RH with 20 h photoperiod showed no increase in ABA levels during darkness, and had low β‐glucosidase activity converting ABA‐GE to ABA. Continuous lighting (24 h) resulted in low levels of β‐glucosidase activity irrespective of RH, indicating that a dark period is essential to activate β‐glucosidase. Our results provide new insight into the regulation of ABA under different humidities and photoperiods, and clearly show that β‐glucosidase is a key enzyme regulating the ABA pool in rose plants.     

The mitochondrial oxoglutarate carrier: from identification to mechanism

The 2-oxoglutarate carrier (OGC) belongs to the mitochondrial carrier protein family whose members are responsible for the exchange of metabolites, cofactors and nucleotides between the cytoplasm and mitochondrial matrix. Initially, OGC was characterized by determining substrate specificity, kinetic parameters of transport, inhibitors and molecular probes that form covalent bonds with specific residues. It was shown that OGC specifically transports oxoglutarate and certain carboxylic acids. The substrate specificity combination of OGC is unique, although many of its substrates are also transported by other mitochondrial carriers. The abundant recombinant expression of bovine OGC in Escherichia coli and its ability to functionally reconstitute into proteoliposomes made it possible to deduce the individual contribution of each and every residue of OGC to the transport activity by a complete set of cys-scanning mutants. These studies give experimental support for a substrate binding site constituted by three major contact points on the even-numbered α-helices and identifies other residues as important for transport function through their crucial positions in the structure for conserved interactions and the conformational changes of the carrier during the transport cycle. The results of these investigations have led to utilize OGC as a model protein for understanding the transport mechanism of mitochondrial carriers.     

Stabilization,Characterization, and Selective Removal of Cystatin C Amyloid Oligomers

The pathophysiological process in amyloid disorders usually involves the transformation of a functional monomeric protein via potentially toxic oligomers into amyloid fibrils. The structure and properties of the intermediary oligomers have been difficult to study due to their instability and dynamic equilibrium with smaller and larger species. In hereditary cystatin C amyloid angiopathy, a cystatin C variant is deposited in arterial walls and cause brain hemorrhage in young adults. In the present investigation, we use redox experiments of monomeric cystatin C, stabilized against domain swapping by an intramolecular disulfide bond, to generate stable oligomers (dimers, trimers, tetramers, decamers, and high molecular weight oligomers). These oligomers were characterized concerning size by gel filtration, polyacrylamide gel electrophoresis, and mass spectrometry, shape by electron and atomic force microscopy, and, function by assays of their capacity to inhibit proteases. The results showed the oligomers to be highly ordered, domain-swapped assemblies of cystatin C and that the oligomers could not build larger oligomers, or fibrils, without domain swapping. The stabilized oligomers were used to induce antibody formation in rabbits. After immunosorption, using immobilized monomeric cystatin C, and elution from columns with immobilized cystatin C oligomers, oligomer-specific antibodies were obtained. These could be used to selectively remove cystatin C dimers from biological fluids containing both dimers and monomers.     

Collagen-binding Microbial Surface Components Recognizing Adhesive Matrix Molecule (MSCRAMM) of Gram-positive Bacteria Inhibit Complement Activation via the Classical Pathway

Members of a family of collagen-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) from Gram-positive bacteria are established virulence factors in several infectious diseases models. Here, we report that these adhesins also can bind C1q and act as inhibitors of the classical complement pathway. Molecular analyses of Cna from Staphylococcus aureus suggested that this prototype MSCRAMM bound to the collagenous domain of C1q and interfered with the interactions of C1r with C1q. As a result, C1r₂C1s₂ was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens.