Adaptations of intestinal macrophages to an antigen-rich environment

Intestinal macrophages, preferentially located in the subepithelial lamina propria, represent in humans the largest pool of tissue macrophages. To comply with their main task, i.e. the efficient removal of microbes and particulate matter that might have gained access to the mucosa from the intestinal lumen while maintaining local tissue homeostasis, several phenotypic and functional adaptations evolved. Most notably, microbe-associated molecular pattern (MAMP) receptors, including the lipopolysaccharide receptors CD14 and TLR4, but also the Fc receptors for IgA and IgG are absent on most intestinal Mø. Here we review recent findings on the phenotypic and functional adaptations of intestinal Mø and their implications for the pathogenesis of inflammatory bowel diseases.

Microwear, mechanics and the feeding adaptations of Australopithecus africanus

Recent studies of dental microwear and craniofacial mechanics have yielded contradictory interpretations regarding the feeding ecology and adaptations of Australopithecus africanus. As part of this debate, the methods used in the mechanical studies have been criticized. In particular, it has been claimed that finite element analysis has been poorly applied to this research question. This paper responds to some of these mechanical criticisms, highlights limitations of dental microwear analysis, and identifies avenues of future research.

Muscle transcriptome adaptations with mild eccentric ergometer exercise

The muscle has a wide range of possibilities to adapt its phenotype. Repetitive submaximal concentric exercise (i.e., shortening contractions) mainly leads to adaptations of muscle oxidative metabolism and endurance while eccentric exercise (i.e., lengthening contractions) results in muscle growth and gain of muscle strength. Modified gene expression is believed to mediate these exercise-specific muscle adjustments. In the present study, early alterations of the gene expression signature were monitored by a muscle-specific microarray. Transcript profiling was performed on muscle biopsies of vastus lateralis obtained from six male subjects before and in a 24-h time course after a single bout of mild eccentric ergometer exercise. The eccentric exercise consisted of 15 min of eccentric cycling at 50% of the individual maximal concentric power output leading to muscle soreness (5.9 on a 0-10 visual analogue scale) and limited muscle damage (1.7-fold elevated creatine kinase activity). Muscle impairment was highlighted by a transient reduction in jumping height after the eccentric exercise. On the gene expression level, we observed a general early downregulation of detected transcripts, followed by a slow recovery close to the control values within the first 24 h post exercise. Only very few regulatory factors were increased. This expression signature is different from the signature of a previously published metabolic response after an intensive endurance-type concentric exercise as well as after maximal eccentric exercise. This is the first description of the time course of changes in gene expression as a consequence of a mild eccentric stimulus.

Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy

The efficacy of specifically targeted anti-viral therapy for hepatitis C virus (HCV) (STAT-C), including HCV protease and polymerase inhibitors, is limited by the presence of drug-specific viral resistance mutations within the targeted proteins. Genetic diversity within these viral proteins also evolves under selective pressures provided by host human leukocyte antigen (HLA)-restricted immune responses, which may therefore influence STAT-C treatment response. Here, the prevalence of drug resistance mutations relevant to 27 developmental STAT-C drugs, and the potential for drug and immune selective pressures to intersect at sites along the HCV genome, is explored. HCV nonstructural (NS) 3 protease or NS5B polymerase sequences and HLA assignment were obtained from study populations from Australia, Switzerland, and the United Kingdom. Four hundred five treatment-naïve individuals with chronic HCV infection were considered (259 genotype 1, 146 genotype 3), of which 38.5% were coinfected with human immunodeficiency virus (HIV). We identified preexisting STAT-C drug resistance mutations in sequences from this large cohort. The frequency of the variations varied according to individual STAT-C drug and HCV genotype/subtype. Of individuals infected with subtype 1a, 21.5% exhibited genetic variation at a known drug resistance site. Furthermore, we identified areas in HCV protease and polymerase that are under both potential HLA-driven pressure and therapy selection and identified six HLA-associated polymorphisms (P

Chinese Internet language: A sociolinguistic analysis of adaptations of the Chinese writing system

This paper examines the adaptations of the writing system in Internet language in mainland China from a sociolinguistic perspective. A comparison is also made of the adaptations in mainland China with those that Su (2003) found in Taiwan. In Computer-Mediated Communication (CMC), writing systems are often adapted to compensate for their inherent inadequacies (such as difficulty in input). Su (2003) investigates the creative uses of the writing system on the electronic bulletin boards (BBS) of two college student organizations in Taipei, Taiwan, and identifies four popular and creative uses of the Chinese writing system: stylized English, stylized Taiwanese-accented Mandarin, stylized Taiwanese, and the recycling of a transliteration alphabet used in elementary education. According to Coupland (2001; cited in Su 2003), stylization is “the knowing deployment of culturally familiar styles and identities that are marked as deviating from those predictably associated with the current speaking context”. Within this framework and drawing on the data in previous publications on Internet language and online sources, this study identifies five types of adaptations in mainland China’s Internet language: stylized Mandarin (e.g., 漂漂 piāopiāo for 漂亮 ‘beautiful’), stylized dialect-accented Mandarin (e.g., 灰常 huīcháng for 非常 ‘very much’), stylized English (e.g., 伊妹儿 yīmèier for ‘email’), stylized initials (e.g., bt 变态 biàntài for ‘abnormal’; pk, short form for ‘player kill’), and stylized numbers (e.g., 9494 jiùshi jiùshi 就是就是 ‘that is it’). The Internet community is composed of highly mobile individuals and thus forms a weak-tie social network. According to Milroy and Milroy (1992), a social network with weak ties is often where language innovation takes place. Adaptations of the Chinese writing system in Internet language provide interesting evidence for the innovations within a weak-tie social network. Our comparison of adaptations in mainland China and Taiwan shows that, in maximizing the effectiveness and functionality of their communication, participants of Internet communication are confronted with different language resources and situations, including differences in Romanization systems, English proficiency level, and attitudes towards English usage. As argued by Milroy and Milroy (1992), a weak-tie social network model can bridge the social class and social network. In the Internet community, the degree of diversity of the stylized linguistic varieties indexes the virtual and/or social status of its participants: the more diversified one’s Internet language is, the higher is his/her virtual and/or social status.

Neuromechanical gait adaptations in women with joint hypermobility - an exploratory study

BACKGROUND Joint hypermobility is known to be associated with joint and muscle pain, joint instability and osteoarthritis. Previous work suggested that those individuals present an altered neuromuscular behavior during activities such as level walking. Therefore, the aim of this study was to explore the differences in ground reaction forces, temporal parameters and muscle activation patterns during gait between normomobile and hypermobile women, including symptomatic and asymptomatic hypermobile individuals. METHODS A total of 195 women were included in this cross-sectional study, including 67 normomobile (mean 24.8 [SD 5.4] years) and 128 hypermobile (mean 25.8 [SD 5.4] years), of which 56 were further classified as symptomatic and 47 as asymptomatic. The remaining 25 subjects could not be further classified. Ground reaction forces and muscle activation from six leg muscles were measured while the subjects walked at a self-selected speed on an instrumented walkway. Temporal parameters were derived from ground reaction forces and a foot accelerometer. The normomobile and hypermobile groups were compared using independent samples t-tests, whereas the normomobile, symptomatic and asymptomatic hypermobile groups were compared using one-way ANOVAs with Tukey post-hoc tests (significance level=0.05). FINDINGS Swing phase duration was higher among hypermobile (P=0.005) and symptomatic hypermobile (P=0.018) compared to normomobile women. The vastus medialis (P=0.049) and lateralis (P=0.030) and medial gastrocnemius (P=0.011) muscles showed higher mean activation levels during stance in the hypermobile compared to the normomobile group. INTERPRETATION Hypermobile women might alter their gait pattern in order to stabilize their knee joint.

Understanding diversity of hepatic metabolism and related adaptations in the early lactating dairy cow.

The onset of lactation in dairy cows represents a major metabolic challenge that involves large adaptations in glucose, fatty acid, and mineral metabolism to support lactation and to avoid metabolic dysfunction. The complex system of adaptation can differ considerably between cows, and may have a genetic base. In the present review, the variation in adaptive reactions in dairy cows is discussed. In these studies, the liver being a key metabolic regulator for understanding the variation in adaptive performance of the dairy cow was the main focus of research. Liver function was evaluated through gene expression measurements; to explain the associated phenotypic variability and to identify descriptors for metabolic robustness in dairy cows. Hence, the identified genes involved act as a connecting link between the genotype encoded on the DNA and the phenotypic expression of the target factors at a protein level. The integration of phenotypic data, including gene expression profiles, and genomic data will facilitate a better characterization of the complex interplay between these levels, and will improve the genetic understanding necessary to unravel a certain trait or multi-trait such as metabolic robustness in dairy cows.

The evolution of host associations in the parasitic wasp genus Ichneumon (Hymenoptera: Ichneumonidae): convergent adaptations to host pupation sites

Background: The diversification of organisms with a parasitic lifestyle is often tightly linked to the evolution of their host associations. If a tight host association exists, closely related species tend to attack closely related hosts; host associations are less stable if associations are determined by more plastic traits like parasitoid searching and oviposition behaviour. The pupal-parasitoids of the genus Ichneumon attack a variety of macrolepidopteran hosts.They are either monophagous or polyphagous, and therefore offer a promissing system to investigate the evolution of host associations. Ichneumon was previously divided into two groups based on general body shape; however, a stout shape has been suggested as an adaptation to buried host pupation sites, and might thus not represent a reliable phylogenetic character. Results: We here reconstruct the first molecular phylogeny of the genus Ichneumon using two mitochondrial (CO1 and NADH1) and one nuclear marker (28S). The resulting phylogeny only supports monophyly of Ichneumon when Ichneumon lugens Gravenhorst, 1829 (formerly in Chasmias, stat. rev.) and Ichneumon deliratorius Linnaeus, 1758 (formerly Coelichneumon) are included. Neither parasitoid species that attack hosts belonging to one family nor those attacking butterflies (Rhopalocera) form monophyletic clades. Ancestral state reconstructions suggest multiple transitions between searching for hosts above versus below ground and between a stout versus elongated body shape. A model assuming correlated evolution between the two characters was preferred over independent evolution of host-searching niche and body shape. Conclusions: Host relations, both in terms of phylogeny and ecology, evolved at a high pace in the genus Ichneumon. Numerous switches between hosts of different lepidopteran families have occurred, a pattern that seems to be the rule among idiobiont parasitoids. A stout body and antennal shape in the parasitoid female is confirmed as an ecological adaptation to host pupation sites below ground and has evolved convergently several times. Morphological characters that might be involved in adaptation to hosts should be avoided as diagnostic characters for phylogeny and classification, as they can be expected to show high levels of homoplasy.

A virtual environment for the assessment and the rehabilitation of the visuo-constructional ability in dementia patients

This study proposes a VE that offers a reliable diagnosis of the stage of cognitive decline in dementia patients and assists the delay of this decline in terms of the visuo-constructional ability. The proposed VE, in the case of the assessment, presents a visuo-constructional completion task, which requires spatial perception, motor memory and the perception of the target object. In the case of the rehabilitation the VE uses sound as audio-feedback that, with the aid of the music perception, tends to develop an enhancement in the visuo-construction ability of the dementia patients that can be generalized even outside of the VE. The study examined 30 subjects that were normal controls (N), 30 patients suffering from memory disorders (Age-Associated Memory Impairment--AAMI) and 30 suffering from Alzheimer's Disease (AD). The results showed that there is a significant correlation between the performance in the visuo-constructional task and the dementia diagnosis. It also seems that the visuo-constructional ability of the (AD) patients can be statistically improved by the audio experience in the VE. The empirical results of this study offer an alternative diagnosis and treatment of dementia patients and could share some light in the brain sub-systems that are responsible for the visuo-constructional ability. Further studies are required in order to investigate the nature of this phenomenon more.

Cell and matrix morphology in articular cartilage from adult human knee and ankle joints suggests depth-associated adaptations to biomechanical and anatomical roles

OBJECTIVE Marked differences exist between human knee and ankle joints regarding risks and progression of osteoarthritis (OA). Pathomechanisms of degenerative joint disease may therefore differ in these joints, due to differences in tissue structure and function. Focussing on structural issues which are design goals for tissue engineering, we compared cell and matrix morphologies in different anatomical sites of adult human knee and ankle joints. METHODS Osteochondral explants were acquired from knee and ankle joints of deceased persons aged 20 to 40 years and analyzed for cell, matrix and tissue morphology using confocal and electron microscopy and unbiased stereological methods. Variations associated with joint (knee versus ankle) and biomechanical role (convex versus concave articular surfaces) were identified by 2-way analysis of variance and post-hoc analysis. RESULTS Knee cartilage exhibited higher cell densities in the superficial zone than ankle cartilage. In the transitional zone, higher cell densities were observed in association with convex versus concave articular surfaces, without significant differences between knee and ankle cartilage. Highly uniform cell and matrix morphologies were evident throughout the radial zone in the knee and ankle, regardless of tissue biomechanical role. Throughout the knee and ankle cartilage sampled, chondron density was remarkably constant at approximately 4.2×10(6) chondrons/cm(3). CONCLUSION Variation of cartilage cell and matrix morphologies with changing joint and biomechanical environments suggests that tissue structural adaptations are performed primarily by the superficial and transitional zones. Data may aid the development of site-specific cartilage tissue engineering, and help identify conditions where OA is likely to occur.

Metabolic adaptations and changes of the mammary immune response during beta-hydroxybutyrate administration

Elevation of ketone bodies occurs frequently after parturition during negative energy balance in high yielding dairy cows. Previous studies illustrated that hyperketonemia interferes with metabolism and it is assumed that it impairs the immune response. However, a causative effect of ketone bodies could not be shown in vivo before, because spontaneous hyperketonemia comes usually along with high NEFA and low glucose concentrations. The objective was to study effects of beta-hydroxybutyrate (BHBA) infusion and an additional intramammary lipopolysaccharide (LPS) challenge on metabolism and immune response in dairy cows. Thirteen dairy cows received intravenously either a BHBA infusion (group BHBA, n=5) to induce hyperketonemia (1.7 mmol/L), or an infusion with a 0.9 % saline solution (Control, n=8) for 56 h. Infusions started at 0900 on day 1 and continue up to 1700 two days later. Two udder quarters were challenged with 200 μg Escherichia coli-LPS 48 h after the start of infusion. Blood samples were taken one week and 2 h before the start of infusions as reference samples and hourly during the infusion. Liver and mammary gland biopsies were taken one week before the start of the infusion, 48 h after the start of the infusion, and mammary tissues was additionally taken 8 h after LPS challenge (56 h after the start of infusions). Rectal temperature (RT) and somatic cell count (SCC) was measured before and 48 h after the start of infusions and hourly during LPS challenge. Blood samples were analyzed for plasma glucose, BHBA, NEFA, triglyceride, urea, insulin, glucagon, and cortisol concentration. The mRNA abundance of factors related to potential adaptations of metabolism and immune system was measured in liver and mammary tissue biopsies. Differences between blood constituents, RT, SCC, and mRNA abundance before and 48 h after the start of infusions, and differences between mRNA abundance before and after LPS challenges were tested for significance by GLM of SAS procedure with treatment as fixed effect. Area under the curve was calculated for blood variables during 48 h BHBA infusion and during the LPS challenge, and additionally for RT and SCC during the LPS challenge. Most surprisingly, both plasma glucose and glucagon concentration decreased during the 48 h of BHBA infusion (P<0.05). During the 48 h of BHBA infusion, serum amyloid A mRNA abundance in mammary gland was increased (P<0.01), and haptoglobin (Hp) mRNA abundance tended to increase in cows treated with BHBA compared to control group (P= 0.07). RT, SCC, and candidate genes related to immune response in the liver were not affected by BHBA infusion. However, during LPS challenge the expected increase of both plasma glucose and glucagon concentration was much less pronounced in the animals treated with BHBA (P<0.05) and also SCC increased much less pronounced in the animals infused with BHBA (P<0.05) than in the controls. An increased BHBA infusion rate to maintain plasma BHBA constant could not fully compensate for the decreased plasma BHBA during the LPS challenge which indicates that BHBA is used as an energy source during the immune response. In addition, BHBA infused animals showed a more pronounced increase of mRNA abundance of IL-8, IL-10, and citrate synthase in the mammary tissue of LPS challenged quarters (P<0.05) than control animals. Results demonstrate that infusion of BHBA affects metabolism through decreased plasma glucose concentration which is likely related to a decreased release of glucagon during hyperketonemia and during additional inflammation. It also affects the systemic and mammary immune response which may reflect the increased susceptibility for mastitis during spontaneous hyperketonemia. The obviously reduced gluconeogenesis in response to BHBA infusion may be a mechanism to stimulated the use of BHBA as an energy source instead of glucose, and/or to save oxaloacetate for the citric acid cycle instead of gluconeogenesis and as a consequence to reduce ketogenesis.

Development of a novel driving behavior adaptations questionnaire

ABSTRACT Background: Driving a car requires adapting one's behavior to current task demands taking into account one's capacities. With increasing age, driving-relevant cognitive performance may decrease, creating a need for risk-reducing behavioral adaptations. Three different kinds of behavioral adaptations are known: selection, optimization, and compensation. These can occur on the tactical and the strategic level. Risk-reducing behavioral adaptations should be considered when evaluating older drivers' traffic-related risks. Methods: A questionnaire to assess driving-related behavioral adaptations in older drivers was created. The questionnaire was administered to 61 years older (age 65-87 years; mean age = 70.2 years; SD = 5.5 years; 30 female, 31 male) and 31 younger participants (age 22-55 years; mean age = 30.5 years; SD = 6.3 years; 16 female and 15 male) to explore age and gender differences in behavioral adaptations. Results: Two factors were extracted from the questionnaire, a risk-increasing factor and a risk-reducing factor. Group comparisons revealed significantly more risk-reducing behaviors in older participants (t(84.5) = 2.21, p = 0.013) and females (t(90) = 2.52, p = 0.014) compared, respectively, to younger participants and males. No differences for the risk-increasing factor were found (p > 0.05). Conclusions: The questionnaire seems to be a useful tool to assess driving-related behavioral adaptations aimed at decreasing the risk while driving. The possibility to assess driving-related behavioral adaptations in a systematic way enables a more resource-oriented approach in the evaluation of fitness to drive in older drivers.