Juvenile ecology drives adult morphology in two insect orders.

Most animals undergo ecological niche shifts between distinct life phases, but such shifts can result in adaptive conflicts of phenotypic traits. Metamorphosis can reduce these conflicts by breaking up trait correlations, allowing each life phase to independently adapt to its ecological niche. This process is called adaptive decoupling. It is, however, yet unknown to what extent adaptive decoupling is realized on a macroevolutionary scale in hemimetabolous insects and if the degree of adaptive decoupling is correlated with the strength of ontogenetic niche shifts. It is also unclear whether the degree of adaptive decoupling is correlated with phenotypic disparity. Here, we quantify nymphal and adult trait correlations in 219 species across the whole phylogeny of earwigs and stoneflies to test whether juvenile and adult traits are decoupled from each other. We demonstrate that adult head morphology is largely driven by nymphal ecology, and that adult head shape disparity has increased with stronger ontogenetic niche shifts in some stonefly lineages. Our findings implicate that the hemimetabolan metamorphosis in earwigs and stoneflies does not allow for high degrees of adaptive decoupling, and that high phenotypic disparity can even be realized when the evolution of distinct life phases is coupled.

Micrometer-resolution X-ray tomographic full-volume reconstruction of an intact post-mortem juvenile rat lung.

In this article, we present an X-ray tomographic imaging method that is well suited for pulmonary disease studies in animal models to resolve the full pathway from gas intake to gas exchange. Current state-of-the-art synchrotron-based tomographic phase-contrast imaging methods allow for three-dimensional microscopic imaging data to be acquired non-destructively in scan times of the order of seconds with good soft tissue contrast. However, when studying multi-scale hierarchically structured objects, such as the mammalian lung, the overall sample size typically exceeds the field of view illuminated by the X-rays in a single scan and the necessity for achieving a high spatial resolution conflicts with the need to image the whole sample. Several image stitching and calibration techniques to achieve extended high-resolution fields of view have been reported, but those approaches tend to fail when imaging non-stable samples, thus precluding tomographic measurements of large biological samples, which are prone to degradation and motion during extended scan times. In this work, we demonstrate a full-volume three-dimensional reconstruction of an intact rat lung under immediate post-mortem conditions and at an isotropic voxel size of (2.75 µm)3. We present the methodology for collecting multiple local tomographies with 360° extended field of view scans followed by locally non-rigid volumetric stitching. Applied to the lung, it allows to resolve the entire pulmonary structure from the trachea down to the parenchyma in a single dataset. The complete dataset is available online ( https://doi.org/10.16907/7eb141d3-11f1-47a6-9d0e-76f8832ed1b2 ).

Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms.

Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic polymorphisms of tandem-repeated noncoding DNA. These polymorphisms may serve as predictive biomarkers of various forms of epilepsy. ACAP3 is the protein regulating morphogenesis of neurons and neuronal migration and is an integral component of important signaling pathways. This study aimed to carry out an association analysis of the length polymorphism and DNA methylation of the UPS29 minisatellite of the ACAP3 gene in patients with epilepsy. We revealed an association of short UPS29 alleles with increased risk of development of symptomatic and cryptogenic epilepsy in women, and also with cerebrovascular pathologies, structural changes in the brain, neurological status, and the clinical pattern of seizures in both women and men. The increase of frequency of hypomethylated UPS29 alleles in men with symptomatic epilepsy, and in women with both symptomatic and cryptogenic epilepsy was observed. For patients with hypomethylated UPS29 alleles, we also observed structural changes in the brain, neurological status, and the clinical pattern of seizures. These associations had sex-specific nature similar to a genetic association. In contrast with length polymorphism epigenetic changes affected predominantly the long UPS29 allele. We suppose that genetic and epigenetic alterations UPS29 can modify ACAP3 expression and thereby affect the development and clinical course of epilepsy.

Impact of Air Pollution and Outdoor Temperature on the Rate of Chronic Obstructive Pulmonary Disease Exacerbations.

BACKGROUND: Environmental pollution can be one of the main risk factors for acute exacerbations of chronic obstructive pulmonary disease (COPD). AIM: To study the relationship between air pollution, outdoor temperature and exacerbations of COPD. MATERIALS AND METHODS: COPD patients (n=1432) were followed up for one year. The levels of particulate matter up to 10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and outside temperatures were collected from the Environmental Agency database. RESULTS: A total of 309 acute COPD exacerbations (AECOPD) were recorded in the analysis. The daily mean concentrations of PM10 were found to correlate significantly with the daily mean concentrations of NO2 and SO2 (ρ 0.34 and ρ 0.49, respectively; p=0.0001). The negative correlations between the daily mean temperature and the daily mean levels of PM10, NO2 and SO2 were also significant (ρ -0.44, ρ -0.11, and ρ -0.37, respectively; p=0.0001). The daily number of AECOPD correlated with the mean levels of PM10 in the previous six days (ρ 0.14; p=0.02) and the lower outdoor temperature (ρ -0.2; p=0.001). The negative correlation between the daily number of AECOPD and the mean daily temperature was stronger in days with levels of PM10 above 50 µg/m3 (ρ -0.3 p=0.02 vs. ρ -0.18 p= 0.01). CONCLUSION: Lower daily mean temperatures were associated with the levels of air pollutants. The level of PM10 correlated with the levels of the other air pollutants. The daily number of AECOPD was found to correlate weakly, but signifi cantly with the mean level of PM10 in the previous six days.

Himasthla elongata: Implantation of rediae to the specific iteroparous long-living host, Littorina littorea, results in the immune rejection.

All semelparous short-lived gastropods studied so far for the experimental transplantation of trematode parthenitae, from one specific host to another, showed more or less successful acceptance of implanted parasites. We implanted echinostomatid rediae, Himasthla elongata, to the specific iteroparous long-living host, coenogastropod Littorina littorea. Using simple and low-invasive implantation techniques we have tested 680 snails injected with 75 redia microhemipopulations (MHP) harvested from naturally infected snails. Neither young nor mature rediae were able to survive in the recipient periwinkles in the course of 30 days post-implantation. A strong immune response from the host was already evident within the first week after implantation: initial inactivation of motile rediae with toxic humoral immune factors, following encapsulation of the implants and increased hemocyte counts. In contrast, rediae from the same MHPs showed perfect survival rates in primary in vitro axenic cultures. The failure of the transplantation experiments is explained in terms of the compatibility matching phenotype model. In the studied host-parasite combination all periwinkles are potentially susceptible and all rediae MHPs are potentially infective, however the probability of the compatible phenotypes matching is virtually low. Low investment in L. littorea annual reproduction would result in increased investment in self maintenance and immune mechanisms, causing the general resistance to the trematode infestation. Presumably, this resistance is relatively higher in long-lived iteroparous gastropods compare to semelparous short-lived mollusks such as pulmonates.

Molecular cloning of α-2-macroglobulin from hemocytes of common periwinkle Littorina littorea.

We report the sequence of the proteinase inhibitor with a wide inhibition spectrum, α-2-macroglobulin (α2M), belonging to the thioester superfamily of proteins. This is the first α2M sequence from coenogastropod prosobranch snails. The full-length cDNA was cloned by RACE method, spans 7897 bp and contains an open reading frame of 5460 bp. The ORF encodes a protein of 1819 amino acids. The deduced mature protein contains 1795 amino acids with a molecular weight of 200 kDa and isoelectric point of 5.00. Littorina littorea α2M bears 4 conserved α2M domains and one internal thioester. Phylogenetic analysis showed that the sequence forms well supported cluster with Mollusca species and other representatives of Lophotrochozoa.

Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis.

Reduction in tumor necrosis factor (αTNF) and interleukin-6 (IL-6) activities is a widely utilized strategy for the treatment of rheumatoid arthritis (RA) with a high success rate. Despite both schemes targeting the deprivation of inflammatory reactions caused by the excessive activity of cytokines, their mechanisms of action and the final output are still unequal. This was a comparative longitudinal study that lasted for 24 weeks and aimed to find the answer to why the two schemes of therapy can pass out of proportion in attitude of their efficiency. What are the differences in metabolic and proteomic responses among patients who were being treated by either the anti-TNF or anti-IL-6 strategy? We found increased levels of immunoglobulins A and G (more than 2-fold in anti-IL-6 and more than 4-5-fold in anti-TNF groups) at the final stage (24 weeks) of monitoring but the most profound increase was determined for µ-chains of immunoglobulins in both groups of study. Metabolomic changes displayed main alterations with regard to arginine metabolism and collagen maintenance, where arginine increased 8.86-fold (p < 0.001) in anti-TNF and 5.71-fold (p < 0.05) in anti-IL-6 groups but patients treated by the anti-TNF scheme suffered a higher depletion of arginine before the start of therapy. Some indicators of matrix and bone tissue degradation also increased 4-hydroxyproline (4-HP) more than 6-fold (p < 0.001) in anti-TNF and more than 2-fold (p < 0.05) in the anti-IL-6 group, but the growth dynamics in the anti-IL6 group was delayed (gradually raised at week 24) compared to the anti-TNF group (raised at week 12) following a smooth reduction. The ELISA analysis of IL-6 and TNFα concentration in the study population supported proteomic and metabolomic data. A positive correlation between ΔCDAI and ΔDAS28 indicators and ESR and CRP was established for the majority of patients after 24 weeks of treatment where ESR and CRP reduced by 20% and 40% finally, respectively. A regression model using the Forest Plot was estimated to elucidate the impact of the most significant clinical, biochemical, and anthropometric indicators for the evaluation of differences between considered anti-TNF and anti-IL-6 schemes of therapy.

Airspace Diameter Map-A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases.

(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (ßENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with µCT, sugges-ting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.

A previously unknown feeding mode in millipedes and the convergence of fluid feeding across arthropods.

We report fluid feeding with a sucking pump in the arthropod class Diplopoda, using a combination of synchrotron tomography, histology, electron microscopy, and three-dimensional reconstructions. Within the head of nine species of the enigmatic Colobognatha, we found a pumping chamber, which acts as positive displacement pump and is notably similar to that of insects, showing even fine structural convergences. The sucking pump of these millipedes works together with protractible mouthparts and externally secreted saliva for the acquisition of liquid food. Fluid feeding is one of the great evolutionary innovations of terrestrial arthropods, and our study suggests that it evolved with similar biomechanical solutions convergent across all major arthropod taxa. While fluid-feeding insects are megadiverse today, it remains unclear why other lineages, such as Colobognatha, are comparably species poor.

Effect of Retinohypothalamic Tract Dysfunction on Melatonin Level in Patients with Chronic Disorders of Consciousness.

OBJECTIVE: The aim of this study is to compare the secretion level of nocturnal melatonin and the characteristics of the peripheral part of the visual analyzer in patients with chronic disorders of consciousness (DOC). MATERIALS AND METHODS: We studied the level of melatonin in 22 patients with chronic DOC and in 11 healthy volunteers. The fundus condition was assessed using the ophthalmoscopic method. RESULTS: The average level of nocturnal melatonin in patients with DOC differed by 80% from the level of indole in healthy volunteers. This reveals a direct relationship between etiology, the level of consciousness, gaze fixation, coma recovery scale-revised score and the level of melatonin secretion. Examination by an ophthalmologist revealed a decrease in the macular reflex in a significant number of DOC patients, which in turn correlates negatively with the time from brain injury and positively with low values of nocturnal melatonin.

Magnetically Addressable Shape-Memory and Stiffening in a Composite Elastomer.

With a specific stimulus, shape-memory materials can assume a temporary shape and subsequently recover their original shape, a functionality that renders them relevant for applications in fields such as biomedicine, aerospace, and wearable electronics. Shape-memory in polymers and composites is usually achieved by exploiting a thermal transition to program a temporary shape and subsequently recover the original shape. This may be problematic for heat-sensitive environments, and when rapid and uniform heating is required. In this work, a soft magnetic shape-memory composite is produced by encasing liquid droplets of magneto-rheological fluid into a poly(dimethylsiloxane) matrix. Under the influence of a magnetic field, this material undergoes an exceptional stiffening transition, with an almost 30-fold increase in shear modulus. Exploiting this transition, fast and fully reversible magnetic shape-memory is demonstrated in three ways, by embossing, by simple shear, and by unconstrained 3D deformation. Using advanced synchrotron X-ray tomography techniques, the internal structure of the material is revealed, which can be correlated with the composite stiffening and shape-memory mechanism. This material concept, based on a simple emulsion process, can be extended to different fluids and elastomers, and can be manufactured with a wide range of methods.

Lectin-like molecules in transcriptome of Littorina littorea hemocytes.

The common periwinkle Littorina littorea was introduced in the list of models for comparative immunobiology as a representative of phylogenetically important taxon Caenogastropoda. Using Illumina sequencing technology, we de novo assembled the transcriptome of Littorina littorea hemocytes from 182 million mRNA-Seq pair-end 100 bp reads into a total of 15,526 contigs clustered in 4472 unigenes. The transcriptome profile was analyzed for presence of carbohydrate-binding molecules in a variety of architectural contexts. Hemocytes' repertoire of lectin-like proteins bearing conserved carbohydrate-recognition domains (CRDs) is highly diversified, including 11 of 15 lectin families earlier described in animals, as well as the novel members of lectin family found for the first time in mollusc species. The new molluscan lineage-specific domain combinations were confirmed by cloning and sequencing, including the fuco-lectin related molecules (FLReMs) composed of N-terminal region with no sequence homology to any known protein, a middle Fucolectin Tachylectin-4 Pentaxrin (FTP) domain, and a C-terminal epidermal growth factor (EGF) repeat region. The repertoire of lectin-like molecules is discussed in terms of their potential participation in the receptor phase of immune response. In total, immune-associated functions may be attributed to 70 transcripts belonging to 6 lectin families. These lectin-like genes show low overlap between species of invertebrates, suggesting relatively rapid evolution of immune-associated genes in the group. The repertoire provides valuable candidates for further characterization of the gene functions in mollusc immunity.

Equipment and skills shortage in Uzbekistan.

In this article, supplied with the help of the International Federation of Hospital Engineering (IFHE), five co-authors from the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ)--a German organisation that seeks to encourage and co-ordinate international cooperation in areas ranging from sustainable development to fund management, and its partner organisation, IFHE member, the Republican Research Center of Emergency Medicine (RRCEM) in Uzbekistan, discuss the use of medical technology in the central Asian country. They also explain how a GIZ project is helping to boost the number of skilled staff, improve quality assurance and management in procurement, logistics, and maintenance, and promote good training of medical and technical staff, across Uzbekistan.