Trypanosomes and mammalian sperm: one of a kind?

Flagellar-mediated motility is an indispensable function for cell types as evolutionarily distant as mammalian sperm and kinetoplastid parasites, a large group of flagellated protozoa that includes several important human pathogens. Despite the obvious importance of flagellar motility, little is known about the signalling processes that direct the frequency and wave shape of the flagellar beat, or those that provide the motile cell with the necessary environmental cues that enable it to aim its movement. Similarly, the energetics of the flagellar beat and the problem of a sufficient ATP supply along the entire length of the beating flagellum remain to be explored. Recent proteome projects studying the flagella of mammalian sperm and kinetoplastid parasites have provided important information and have indicated a surprising degree of similarities between the flagella of these two cell types.

Content comparison of health-related quality of life instruments for COPD

BACKGROUND: Due to the increasing importance of quality of life assessments in chronic obstructive pulmonary disease (COPD) patients, and the increased use of the International Classification of Functioning, Disability and Health (ICF) for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQL) instruments and the ICF. OBJECTIVE: The objective of this study was to compare the content of recommended COPD-specific HRQL instruments using the ICF as reference. COPD-specific instruments mentioned in widely accepted guidelines were linked to the ICF using standardized linking rules. The degree of agreement between various health professionals was assessed by calculating the kappa statistic. RESULTS: Eleven instruments were included. They varied strongly in the number of concepts contained and the number of ICF categories used to map these concepts. A total of 548 concepts were identified and linked to 60 different ICF categories. Only the single category 'dyspnea' was covered by all instruments, whilst 21 categories were unique to specific instruments. The relationships of the measures with the ICF were identified. CONCLUSIONS: This study may aid researchers and clinicians to choose the most appropriate instrument for a specific purpose as well as help compare studies that have used different instruments for HRQL assessment.

Content comparison of health-related quality of life instruments for obstructive sleep apnea

BACKGROUND AND PURPOSE: Due to the increasing importance of quality of life assessments in obstructive sleep apnea (OSA) patients and due to an increased use of the International Classification of Functioning, Disability and Health (ICF), for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQOL) instruments and the ICF. The purpose of this study was to compare the content covered by OSA-specific instruments using the ICF. PATIENTS AND METHODS: OSA-specific instruments were identified, including the Calgary Sleep Apnea Quality of Life Index, the Functional Outcomes of Sleep Questionnaire, the Obstructive Sleep Apnea Patient-Oriented Severity Index, and the Quebec Sleep Questionnaire, and linked to the ICF by six health professionals according to standardized guidelines. The degree of agreement between health professionals was calculated by means of the kappa statistic. RESULTS: A total of 308 concepts were identified and linked to 78 different ICF categories; 35 categories of the component body function, one category of the component body structure, 38 categories of the component activities and participation, and four categories of the component environmental factors. Only contents within the chapters mental functions, mobility and social life were addressed by all instruments. Forty-seven categories were covered by only one instrument. CONCLUSION: The ICF proved highly useful for the comparison of HRQOL instruments. This analysis may help researchers and clinicians to choose the most appropriate HRQOL instrument for a specific purpose as well as help to compare study outcomes of studies using different instruments for HRQOL assessment.

Field performance of two rapid screening tests in active surveillance of transmissible spongiform encephalopathies in small ruminants

Recently, screening tests for monitoring the prevalence of transmissible spongiform encephalopathies specifically in sheep and goats became available. Although most countries require comprehensive test validation prior to approval, little is known about their performance under normal operating conditions. Switzerland was one of the first countries to implement 2 of these tests, an enzyme-linked immunosorbent assay (ELISA) and a Western blot, in a 1-year active surveillance program. Slaughtered animals (n = 32,777) were analyzed in either of the 2 tests with immunohistochemistry for confirmation of initial reactive results, and fallen stock samples (n = 3,193) were subjected to both screening tests and immunohistochemistry in parallel. Initial reactive and false-positive rates were recorded over time. Both tests revealed an excellent diagnostic specificity (>99.5%). However, initial reactive rates were elevated at the beginning of the program but dropped to levels below 1% with routine and enhanced staff training. Only those in the ELISA increased again in the second half of the program and correlated with the degree of tissue autolysis in the fallen stock samples. It is noteworthy that the Western blot missed 1 of the 3 atypical scrapie cases in the fallen stock, indicating potential differences in the diagnostic sensitivities between the 2 screening tests. However, an estimation of the diagnostic sensitivity for both tests on field samples remained difficult due to the low disease prevalence. Taken together, these results highlight the importance of staff training, sample quality, and interlaboratory comparison trials when such screening tests are implemented in the field.

Direct and indirect associations between plant species richness and productivity in grasslands: regional differences preclude simple generalization of productivity-biodiversity relationships

Plant species richness of permanent grasslands has often been found to be significantly associated with productivity. Concentrations of nutrients in biomass can give further insight into these productivity- plant species richness relationships, e.g. by reflecting land use or soil characteristics. However, the consistency of such relationships across different regions has rarely been taken into account, which might significantly compromise our potential for generalization. We recorded plant species richness and measured above-ground biomass and concentrations of nutrients in biomass in 295 grasslands in three regions in Germany that differ in soil and climatic conditions. Structural equation modelling revealed that nutrient concentrations were mostly indirectly associated with plant species richness via biomass production. However, negative associations between the concentrations of different nutrients and biomass and plant species richness differed considerably among regions. While in two regions, more than 40% of the variation in plant species richness could be attributed to variation in biomass, K, P, and to some degree also N concentrations, in the third region only 15% of the variation could be explained in this way. Generally, highest plant species richness was recorded in grasslands where N and P were co-limiting plant growth, in contrast to N or K (co-) limitation. But again, this pattern was not recorded in the third region. While for two regions land-use intensity and especially the application of fertilizers are suggested to be the main drivers causing the observed negative associations with productivity, in the third region the little variance accounted for, low species richness and weak relationships implied that former intensive grassland management, ongoing mineralization of peat and fluctuating water levels in fen grasslands have overruled effects of current land-use intensity and productivity. Finally, we conclude that regional replication is of major importance for studies seeking general insights into productivity-diversity relationships.

Impacted maxillary canines and root resorptions of neighbouring teeth: a radiographic analysis using cone-beam computed tomography

The study analyses the location of impacted maxillary canines and factors influencing root resorptions of adjacent teeth using cone-beam computed tomography (CBCT). In addition, the interrater reliability between observers of two different dental specialties for radiographic parameters will be evaluated. CBCT images of patients who were referred for radiographic localization of impacted maxillary canines and/or suspicion of root resorptions of adjacent teeth were included. The study analysed the exact three-dimensional location of the impacted canines in the anterior maxilla, frequency and extent of root resorptions, and potential influencing factors. To assess interrater agreement, Cohen's correlation parameters were calculated. This study comprises 113 patients with CBCT scans, and 134 impacted canines were analysed retrospectively. In the patients evaluated, 69 impacted canines were located palatally (51.49 per cent), 41 labially (30.60 per cent), and 24 (17.91 per cent) in the middle of the alveolar process. Root resorptions were found in 34 lateral incisors (25.37 per cent), 7 central incisors (5.22 per cent), 6 first premolars (4.48 per cent), and 1 second premolar (0.75 per cent). There was a significant correlation between root resorptions on adjacent teeth and localization of the impacted canine in relation to the bone, as well as vertical localization of the canine. Interrater agreement showed values of 0.546-0.877. CBCT provides accurate information about location of the impacted canine and prevalence and degree of root resorption of neighbouring teeth with high interrater correlation. This information is of great importance for surgeons and orthodontists for accurate diagnostics and interdisciplinary treatment planning.

Clinical and pathological analysis of epidural inflammation in intervertebral disk extrusion in dogs

BACKGROUND Little is known about the pathologic changes in the epidural space after intervertebral disk (IVD) extrusion in the dog. OBJECTIVES To analyze the pathology of the epidural inflammatory response, and to search for correlations between this process and clinical findings. METHODS Clinical data from 105 chondrodystrophic (CD) and nonchondrodystrophic (NCD) dogs with IVD extrusion were recorded. Epidural material from these dogs was examined histopathologically and immunohistochemically. Using statistical analysis, we searched for correlations between severity of epidural inflammation and various clinical and pathologic variables. RESULTS Most dogs exhibited an epidural inflammatory response, ranging from acute invasion of neutrophils to formation of chronic granulation tissue. The mononuclear inflammatory infiltrates consisted mostly of monocytes and macrophages and only few T and B cells. Surprisingly, chronic inflammatory patterns also were found in animals with an acute clinical history. Severity of the epidural inflammation correlated with degree of the epidural hemorrhage and nucleus pulposus calcification (P = .003 and .040), but not with age, chondrodystrophic phenotype, neurologic grade, back pain, pretreatment, or duration. The degree of inflammation was statistically (P = .021) inversely correlated with the ability to regain ambulation. CONCLUSION AND CLINICAL IMPORTANCE Epidural inflammation occurs in the majority of dogs with IVD extrusion and may develop long before the onset of clinical signs. Presence of calcified IVD material and hemorrhage in the epidural space may be the triggers of this lesion rather than an adaptive immune response to the nucleus pulposus as suggested in previous studies. Because epidural inflammation may affect outcome, further research is warranted.

Characteristics and functional relevance of apolipoprotein-A1 and cholesterol binding in mammary gland tissues and epithelial cells

Cholesterol in milk is derived from the circulating blood through a complex transport process involving the mammary alveolar epithelium. Details of the mechanisms involved in this transfer are unclear. Apolipoprotein-AI (apoA-I) is an acceptor of cellular cholesterol effluxed by the ATP-binding cassette (ABC) transporter A1 (ABCA1). We aimed to 1) determine the binding characteristics of (125)I-apoA-I and (3)H-cholesterol to enriched plasma membrane vesicles (EPM) isolated from lactating and non-lactating bovine mammary glands (MG), 2) optimize the components of an in vitro model describing cellular (3)H-cholesterol efflux in primary bovine mammary epithelial cells (MeBo), and 3) assess the vectorial cholesterol transport in MeBo using Transwell(®) plates. The amounts of isolated EPM and the maximal binding capacity of (125)I-apoA-I to EPM differed depending on the MG's physiological state, while the kinetics of (3)H-cholesterol and (125)I-apoA-I binding were similar. (3)H-cholesterol incorporated maximally to EPM after 25±9 min. The time to achieve the half-maximum binding of (125)I-apoA-I at equilibrium was 3.3±0.6 min. The dissociation constant (KD) of (125)I-apoA-I ranged between 40-74 nmol/L. Cholesterol loading to EPM increased both cholesterol content and (125)I-apoA-I binding. The ABCA1 inhibitor Probucol displaced (125)I-apoA-I binding to EPM and reduced (3)H-cholesterol efflux in MeBo. Time-dependent (3)H-cholesterol uptake and efflux showed inverse patterns. The defined binding characteristics of cholesterol and apoA-I served to establish an efficient and significantly shorter cholesterol efflux protocol that had been used in MeBo. The application of this protocol in Transwell(®) plates with the upper chamber mimicking the apical (milk-facing) and the bottom chamber corresponding to the basolateral (blood-facing) side of cells showed that the degree of (3)H-cholesterol efflux in MeBo differed significantly between the apical and basolateral aspects. Our findings support the importance of the apoA-I/ABCA1 pathway in MG cholesterol transport and suggest its role in influencing milk composition and directing cholesterol back into the bloodstream.

Region Specific Response of Intervertebral Disc Cells to Complex Dynamic Loading: An Organ Culture Study Using a Dynamic Torsion-Compression Bioreactor

The spine is routinely subjected to repetitive complex loading consisting of axial compression, torsion, flexion and extension. Mechanical loading is one of the important causes of spinal diseases, including disc herniation and disc degeneration. It is known that static and dynamic compression can lead to progressive disc degeneration, but little is known about the mechanobiology of the disc subjected to combined dynamic compression and torsion. Therefore, the purpose of this study was to compare the mechanobiology of the intervertebral disc when subjected to combined dynamic compression and axial torsion or pure dynamic compression or axial torsion using organ culture. We applied four different loading modalities 1. control: no loading (NL), 2. cyclic compression (CC), 3. cyclic torsion (CT), and 4. combined cyclic compression and torsion (CCT) on bovine caudal disc explants using our custom made dynamic loading bioreactor for disc organ culture. Loads were applied for 8 h/day and continued for 14 days, all at a physiological magnitude and frequency. Our results provided strong evidence that complex loading induced a stronger degree of disc degeneration compared to one degree of freedom loading. In the CCT group, less than 10\% nucleus pulposus (NP) cells survived the 14 days of loading, while cell viabilities were maintained above 70\% in the NP of all the other three groups and in the annulus fibrosus (AF) of all the groups. Gene expression analysis revealed a strong up-regulation in matrix genes and matrix remodeling genes in the AF of the CCT group. Cell apoptotic activity and glycosaminoglycan content were also quantified but there were no statistically significant differences found. Cell morphology in the NP of the CCT was changed, as shown by histological evaluation. Our results stress the importance of complex loading on the initiation and progression of disc degeneration.

Representation Matters: The Impact of Descriptive Women's Representation on the Political Involvement of Women

In a cross-country comparison of 33 European countries, we tested whether a high degree of female representation attenuates the assumed negative impact of gender on political involvement. Our multilevel analyses show positive interactive effects of female representation: the degree to which the representation of women in a given country's national parliament was descriptively adequate was positively related to women's ratings of the importance of politics and self-reported political interest. With respect to political participation, the findings are mixed.

The importance of biotic interactions and local adaptation for plant response to environmental changes: field evidence along an elevational gradient

Predicting the response of species to environmental changes is a great and on-going challenge for ecologists, and this requires a more in-depth understanding of the importance of biotic interactions and the population structuration in the landscape. Using a reciprocal transplantation experiment, we tested the response of five species to an elevational gradient. This was combined to a neighbour removal treatment to test the importance of local adaptation and biotic interactions. The trait studied was performance measured as survival and biomass. Species response varied along the elevational gradient, but with no consistent pattern. Performance of species was influenced by environmental conditions occurring locally at each site, as well as by positive or negative effects of the surrounding vegetation. Indeed, we observed a shift from competition for biomass to facilitation for survival as a response to the increase in environmental stress occurring in the different sites. Unlike previous studies pointing out an increase of stress along the elevation gradient, our results supported a stress gradient related to water availability, which was not strictly parallel to the elevational gradient. For three of our species, we observed a greater biomass production for the population coming from the site where the species was dominant (central population) compared to population sampled at the limit of the distribution (marginal population). Nevertheless, we did not observe any pattern of local adaptation that could indicate adaptation of populations to a particular habitat. Altogether, our results highlighted the great ability of plant species to cope with environmental changes, with no local adaptation and great variability in response to local conditions. Our study confirms the importance of taking into account biotic interactions and population structure occurring at local scale in the prediction of communities’ responses to global environmental changes.

Evidence of species-specific neighborhood effects in the dipterocarpaceae of a Bornean rain forest

Although accumulating evidence indicates that local intraspecific density-dependent effects are not as rare in species-rich communities as previously suspected, there are still very few detailed and systematic neighborhood analyses of species-rich communities. Here, we provide such an analysis with the overall goal of quantifying the relative importance of inter- and intraspecific interaction strength in a primary, lowland dipterocarp forest located at Danum, Sabah, Malaysia. Using data on 10 abundant overstory dipterocarp species from two 4-ha permanent plots, we evaluated the effects of neighbors on the absolute growth rate of focal trees (from 1986 to 1996) over increasing neighborhood radii (from 1 to 20 m) with multiple regressions. Only trees 10 cm to < 100 cm girth at breast height in 1986 were considered as focal trees. Among neighborhood models with one neighbor term, models including only conspecific larger trees performed best in five out of 10 species. Negative effects of conspecific larger neighbors were most apparent in large overstory species such as those of the genus Shorea. However, neighborhood models with separate terms and radii for heterospecific and conspecific neighbors accounted for more variability in absolute growth rates than did neighborhood models with one neighbor term. The conspecific term was significant for nine out of 10 species. Moreover, in five out of 10 species, trees without conspecific neighbors had significantly higher absolute growth rates than trees with conspecific neighbors. Averaged over the 10 species, trees without conspecific neighbors grew 32.4 cm(2) in basal area from 1986 to 1996, whereas trees with conspecific neighbors only grew 14.7 cm(2) in basal area, although there was no difference in initial basal area between trees in the two groups. Averaged across the six species of the genus Shorea, negative effects of conspecific larger trees were significantly stronger than for heterospecific larger neighbors. Thus, high local densities within neighborhoods of 20 m may lead to strong intraspecific negative and, hence, density-dependent, effects even in species rich communities with low overall densities at larger spatial scales. We conjecture that the strength of conspecific effects may be correlated with the degree of host specificity of ectomycorrhizae.

Temporal Changes in Randomness of Bird Communities across Central Europe

Many studies have examined whether communities are structured by random or deterministic processes, and both are likely to play a role, but relatively few studies have attempted to quantify the degree of randomness in species composition. We quantified, for the first time, the degree of randomness in forest bird communities based on an analysis of spatial autocorrelation in three regions of Germany. The compositional dissimilarity between pairs of forest patches was regressed against the distance between them. We then calculated the y-intercept of the curve, i.e. the ‘nugget’, which represents the compositional dissimilarity at zero spatial distance. We therefore assume, following similar work on plant communities, that this represents the degree of randomness in species composition. We then analysed how the degree of randomness in community composition varied over time and with forest management intensity, which we expected to reduce the importance of random processes by increasing the strength of environmental drivers. We found that a high portion of the bird community composition could be explained by chance (overall mean of 0.63), implying that most of the variation in local bird community composition is driven by stochastic processes. Forest management intensity did not consistently affect the mean degree of randomness in community composition, perhaps because the bird communities were relatively insensitive to management intensity. We found a high temporal variation in the degree of randomness, which may indicate temporal variation in assembly processes and in the importance of key environmental drivers. We conclude that the degree of randomness in community composition should be considered in bird community studies, and the high values we find may indicate that bird community composition is relatively hard to predict at the regional scale.

Novel radiotherapy techniques for involved-field and involved-node treatment of mediastinal Hodgkin lymphoma: when should they be considered and which questions remain open?

PURPOSE Hodgkin lymphoma (HL) is a highly curable disease. Reducing late complications and second malignancies has become increasingly important. Radiotherapy target paradigms are currently changing and radiotherapy techniques are evolving rapidly. DESIGN This overview reports to what extent target volume reduction in involved-node (IN) and advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy-compared with involved-field (IF) and 3D radiotherapy (3D-RT)- can reduce high doses to organs at risk (OAR) and examines the issues that still remain open. RESULTS Although no comparison of all available techniques on identical patient datasets exists, clear patterns emerge. Advanced dose-calculation algorithms (e.g., convolution-superposition/Monte Carlo) should be used in mediastinal HL. INRT consistently reduces treated volumes when compared with IFRT with the exact amount depending on the INRT definition. The number of patients that might significantly benefit from highly conformal techniques such as IMRT over 3D-RT regarding high-dose exposure to organs at risk (OAR) is smaller with INRT. The impact of larger volumes treated with low doses in advanced techniques is unclear. The type of IMRT used (static/rotational) is of minor importance. All advanced photon techniques result in similar potential benefits and disadvantages, therefore only the degree-of-modulation should be chosen based on individual treatment goals. Treatment in deep inspiration breath hold is being evaluated. Protons theoretically provide both excellent high-dose conformality and reduced integral dose. CONCLUSION Further reduction of treated volumes most effectively reduces OAR dose, most likely without disadvantages if the excellent control rates achieved currently are maintained. For both IFRT and INRT, the benefits of advanced radiotherapy techniques depend on the individual patient/target geometry. Their use should therefore be decided case by case with comparative treatment planning.

Role of the Salmonella pathogenicity island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice.

Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium) induces enterocolitis in humans and cattle. The mechanisms of enteric salmonellosis have been studied most extensively in calf infection models. The previous studies established that effector protein translocation into host cells via the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (TTSS) is of central importance in serovar Typhimurium enterocolitis. We recently found that orally streptomycin-pretreated mice provide an alternative model for serovar Typhimurium colitis. In this model the SPI-1 TTSS also plays a key role in the elicitation of intestinal inflammation. However, whether intestinal inflammation in calves and intestinal inflammation in streptomycin-pretreated mice are induced by the same SPI-1 effector proteins is still unclear. Therefore, we analyzed the role of the SPI-1 effector proteins SopB/SigD, SopE, SopE2, and SipA/SspA in elicitation of intestinal inflammation in the murine model. We found that sipA, sopE, and, to a lesser degree, sopE2 contribute to murine colitis, but we could not assign an inflammation phenotype to sopB. These findings are in line with previous studies performed with orally infected calves. Extending these observations, we demonstrated that in addition to SipA, SopE and SopE2 can induce intestinal inflammation independent of each other and in the absence of SopB. In conclusion, our data corroborate the finding that streptomycin-pretreated mice provide a useful model for studying the molecular mechanisms of serovar Typhimurium colitis and are an important starting point for analysis of the molecular events triggered by SopE, SopE2, and SipA in vivo.