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Another ghost of Gondwana—Progradungula barringtonensis Michalik & Smith, sp. nov., a new species of the relict spider genus Progradungula (Araneae: Gradungulidae) from a temperate rainforest in eastern Australia
Get PDFOdd-clawed spiders (Gradungulinae), which are considered to be ‘living fossils’, are a faunal element of the mesic forests of eastern Australia and the South Island of New Zealand. To date, 16 species in seven genera are known, with most being highly endemic and hard to find, explaining their scarcity in collections worldwide. Particularly noteworthy is the Australian genus Progradungula that includes only two relict species from eastern Australia (Progradungula carraiensis from the Carrai limestone caves in northern New South Wales and Progradungula otwayensis from Nothofagus rainforests in the Otway Range, southern Victoria) and are known from only a handful of adult specimens. Both species are large nocturnal predators with a rather cryptic lifestyle, which construct unique ladder-like catching webs composed of non-combed and combed cribellate silk with exceptional properties. Here, we describe a new relict species, Progradungula barringtonensis Michalik & Smith, sp. nov., from isolated Nothofagus forest patches in Barrington Tops National Park (NSW, Australia). The male of this species is significantly larger than those of P. carraiensis and P. otwayensis and exhibits characteristics of the male genitalia of both species. The webs are similar to those of the other Progradungula species. Field observations revealed that the catching ladder had few looping segments, similar to P. otwayensis, but an immature in captivity constructed webs with more looping segments, similar to P. carraiensis, supporting the previously proposed hypothesis that food availability may explain the plasticity of the catching ladder structure
Die kraniale Knochenfensterung an der Maus als Möglichkeit für eine Untersuchung der Angiogenese und der Leukozyten-Endothel-Interaktion durch den Einsatz von kaltem Atmosphärendruckplasma bei einem chronischen Knochendefekt
Get PDFChronische Knochendefekte treten trotz der Fähigkeit des Knochens zur Wiederherstellung seiner Struktur nach einer Läsion wiederkehrend auf. Deshalb sollten neue therapeutische Strategien zur Verbesserung der Knochenheilung erschlossen werden. Ein Risikofaktor für die Entstehung von chronischen Knochendefekten bildet dabei eine unzureichende Vaskularisation im knöchernen Defektareal. Die lokale Applikation von kaltem Atmosphärendruck Plasma (CAP) fördert die Heilung akuter und chronischer Wunden im Weichgewebe durch eine Unterstützung der Angiogenese und der Diapedese von Leukozyten. Dabei ist es allerdings noch unklar, ob eine Förderung dieser Parameter durch CAP auch im Knochen möglich ist. Zur Beurteilung der Angiogenese, Leukozyten-Endothel Interaktion (LEI) und Mikrozirkulation bedarf es zudem eines geeigneten Modells, welches die Verabreichung von lokalen Therapeutika in einem Knochendefekt ermöglicht. Im Rahmen der vorliegenden Arbeit wurde das Wundheilungsmodell auf der Basis eines Schädelknochenfensters (CBW) zur Beurteilung der Angiogenese, der LEI und der Rheologie anhand einer in-vivo-Bildgebung bei der Maus weiterentwickelt. Danach wurde in einer randomisierten und kontrollierten Studie der Einfluss einer lokalen Therapie des Knochendefekts mit CAP auf die Mikrozirkulation untersucht. Dabei erfolgte eine initiale qualitative makroskopische Beurteilung der Vaskularisation und eine quantitative und qualitative Analyse der Mikrozirkulation durch Intravitalmikroskopie (IVM) nach 7, 14 und 28 Tagen nach der Etablierung des CBWs. Die lokale Therapie mit CAP führte zu einer höheren Gefäßdichte und einer Förderung der LEI im Vergleich mit der Kontrollgruppe. Weil sich keine relevanten Gruppenunterschiede bei der Rheologie ergaben, wurde die Hypothese einer rezeptorvermittelten Intensivierung der LEI als möglicher Wirkmechanismus aufgestellt. Diese Beobachtungen wurden durch das Anfertigen histologischer Präparate zur Deskription des Wundareals ergänzt. Die vorliegende Arbeit verdeutlicht das Potenzial des CBWs als eine Methode zur Beurteilung der Mikrozirkulation bei chronischen Knochendefekten. Außerdem ergab sich eine wichtige Evidenz für die möglichen förderlichen Effekte von CAP auf kritische Parameter der Knochenheilung. Das Modell und die Ergebnisse der Experimente wurden auf der Basis der einschlägigen Literatur kritisch diskutiert
ACES: A new framework for the application of the 2018 periodontal status classification scheme to epidemiological survey data
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To propose a framework for consistently applying the 2018 periodontal status classification scheme to epidemiological surveys (Application of the 2018 periodontal status Classification to Epidemiological Survey data, ACES).
Proposed Framework
We specified data requirements and workflows for either completed or planned epidemiological surveys, utilizing commonly collected measures of periodontal status (clinical attachment levels [CAL], probing depths, bleeding on probing), as well as additional necessary variables for the implementation of the 2018 periodontal status classification (tooth loss due to periodontitis and complexity factors). Following detailed instructions and flowcharts, survey participants are classified as having periodontal health, gingivitis or periodontitis. Rates of edentulism must also be reported. In cases of periodontitis, instructions on how to compute the stage and extent are provided. Assessment of grade can be derived from CAL measurements (or from radiographic alveolar bone loss data) in relation to root length and the participant's age.
Conclusions
ACES is a framework to be used in epidemiological studies of periodontal status that (i) have been completed, and in which stage and grade according to the 2018 classification are inferred retroactively, or (ii) are being planned. Consistent use of the proposed comprehensive approach will facilitate the comparability of periodontitis prevalence estimates across studies
Reduced Levels of Brain-Derived Neurotrophic Factor Affect Body Weight, Brain Weight and Behavior
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Neurotrophins are growth factors that help the brain grow and function well. One of them is called brain-derived neurotrophic factor (BDNF). BDNF affects how much we weigh and how well we learn and remember things. There are mice with reduced levels of BDNF. Mice have been developed that do not express BDNF at all, but they die soon after they are born. So, mice that have only half of the normal BDNF level and mice that have very low BDNF levels in some brain cells, but normal BDNF levels in other brain cells, have been generated. Furthermore, it is possible to generate new mouse lines by breeding these two types of mice together. These new mice have very little BDNF in their brain. They are alive, but they weigh more and have smaller brains than normal mice. They also act differently, especially in how they move.
Abstract
Neurotrophins, which belong to the family of growth factors, not only play crucial roles during development but are also involved in many processes in the postnatal brain. One representative of neurotrophins is brain-derived neurotrophic factor (BDNF). BDNF plays a role in the regulation of body weight and neuronal plasticity and is, therefore, also involved in processes associated with learning and memory formation. Many of the studies on BDNF have been carried out using BDNF-deficient mice. Unfortunately, homozygous deletion of BDNF is lethal in the early postnatal stage, so heterozygous BDNF-deficient mice are often studied. Another possibility is the use of conditional BDNF-deficient mice in which the expression of BDNF is strongly downregulated in some brain cells, for example, in the neurons of the central nervous system, but the expression of BDNF in other cells in the brain is unchanged. To further reduce BDNF expression, we crossed heterozygous BDNF-deficient mice with mice carrying a deletion of BDNF in neurofilament L-positive neurons. These offspring are viable, and the animals with a strong reduction in BDNF in the brain show a strongly increased body weight, which is accompanied by a reduction in brain weight. In addition, these animals show behavioral abnormalities, particularly with regard to locomotion
The Many Roles of Precision in Action
Get PDFActive inference describes (Bayes-optimal) behaviour as being motivated by the minimisation of surprise of one’s sensory observations, through the optimisation of a generative model (of the hidden causes of one’s sensory data) in the brain. One of active inference’s key appeals is its conceptualisation of precision as biasing neuronal communication and, thus, inference within generative models. The importance of precision in perceptual inference is evident—many studies have demonstrated the importance of ensuring precision estimates are correct for normal (healthy) sensation and perception. Here, we highlight the many roles precision plays in action, i.e., the key processes that rely on adequate estimates of precision, from decision making and action planning to the initiation and control of muscle movement itself. Thereby, we focus on the recent development of hierarchical, “mixed” models—generative models spanning multiple levels of discrete and continuous inference. These kinds of models open up new perspectives on the unified description of hierarchical computation, and its implementation, in action. Here, we highlight how these models reflect the many roles of precision in action—from planning to execution—and the associated pathologies if precision estimation goes wrong. We also discuss the potential biological implementation of the associated message passing, focusing on the role of neuromodulatory systems in mediating different kinds of precision
Funktionelle Analyse Oberflächen-assoziierter Lipoproteine von Klebsiella pneumoniae
Get PDFKlebsiella pneumoniae (K. pneumoniae) ist ein Gram-negatives, fakultative anaerobes, stäbchenförmiges Bakterium, dass ubiquitär in der Umwelt vorkommen kann. Als human-pathogener Erreger ist es in der Lage, die humane Schleimhaut zu kolonisieren und eine Vielfalt von Infektionen auszulösen. Neben nosokomialen Infektionen, Harnwegs- und Blutbahninfektionen werden auch Lungenentzündungen verursacht. Hypervirulente Stämme zeigen einen stark mukoiden Phänotyp und können auch Weichteilinfektionen, Leberabszesse und bakterielle Meningitis verursachen. Durch die rasch steigende globale Verbreitung multiresistenter K. pneumoniae Stämme und dem gleichzeitigen Mangel von alternativen Therapieformen steigt auch die Notwendigkeit, neue Präventions- und Therapiemaßnahmen gegen eine K. pneumoniae Infektion zu entwickeln. Mögliche Präventionsmaßnahmen könnten Impfungen darstellen, die meist auf der Nutzung von Proteinen der Pathogenen basiert. Dabei sind in den letzten Jahren sowohl bei Gram-positiven Bakterien wie Streptococcus pneumoniae (S. pneumoniae), als auch Gram-negativen Bakterien wie Neisseria meningitidis (N. meningitidis) Lipoproteine, welche sich auf der bakteriellen Oberfläche befinden, in den Fokus der Impfstoff-Studien gerückt. Ob Lipoproteine auch bei K. pneumoniae einen protektiven Effekt besitzen und somit als Impfstoff-Kandidaten in Frage kommen, ist noch nicht ausreichend untersucht worden. Zu diesem Zwecke wurden in dieser Arbeit zunächst die Lipoproteine von K. pneumoniae ATCC BAA2146 (Kpn2146) in in silico Analysen identifiziert. Von den 93 potentiellen Lipoproteinen wurden 85 Kandidaten in der äußeren Membran vorhergesagt. Von den Kandidaten wurden 32 Proteine aufgrund ihrer Größe (mindestens 150 Aminosäuren) und ihrer bekannten bzw. auch ihrer unbekannten Funktion in weiterführende Studien aufgenommen. Für eine funktionelle Charakterisierung wurden auf Grundlage der Lipoprotein-kodierenden Genen und unter dem Ausschluss der für Lipoproteine charakteristischen Lipobox die Lipoproteine HP7, HslJ, LpoB, MltA, NlpD_1, NlpD_2, NlpI, Pal, QseG, RlpA, Slp und YajI heterolog in E. coli exprimiert. Die rekombinanten Proteine wurden in Immunisierungen von CD1 Mäusen zur Gewinnung von Antiseren gegen die jeweiligen Proteine und in Immunogenitätsstudien mit humanen Seren gesunder Spender und K. pneumoniae-infizierter Patienten eingesetzt. NlpD_1 und NlpD_2 zeigten immunogenes Potential. Antikörper gegen NlpD_1 und Nlp_D2 konnten sowohl in Seren gesunder Spender als auch in Seren von K. pneumoniae infizierten Patienten nachgewiesen werden. Die Oberflächenassoziation der Lipoproteine von K. pneumoniae wurde mit den anti-Lipoprotein IgGs und einer generierten unbekapselten Mutante Kpn2146Δwza in durchflusszytometrischen Analysen analysiert. Die niedrigen gemessenen Fluoreszenzintensitäten haben keinen eindeutigen Schluss auf eine Lokalisation der Lipoproteine auf der extrazellulären Bakterienoberfläche zugelassen.
Für in vitro und Bindungsstudien wurde die kapsellose Mutante Kpn2146Δwza generiert. Diese Mutante wurde in der vorliegenden Arbeit auch eingesetzt, um den Einfluss der Polysaccharidkapsel auf die Adhäsion, das Überleben im Blut und die Invasivität von K. pneumoniae in einem experimentellen Infektionsmodell zu untersuchen. Die Kapsel-defiziente Mutante zeigte ein verringertes Wachstum im Komplexmedium, während es im chemisch definierten Medium keinen Wachstumsunterschied zwischen Wildtyp und der Mutante gab. Die Adhärenz der kapsellosen Mutante Kpn2146Δwza an A549 Lungenepithelzellen war identisch zum Wildtyp. Dagegen wurde eine erhöhte Internalisierung der Mutante Kpn2146Δwza im Vergleich zum Wildtyp nachgewiesen. Die Überlebensstudien von Kpn2146 und der Kapsel-defizienten Mutante in humanem Vollblut zeigten, dass die unbekapselte Mutante weder im Vollblut noch im menschlichen Plasma überleben konnte. Diese Daten wiesen darauf hin, dass die Kapsel für das Überleben, den Schutz von K. pneumoniae vor der Erkennung und Beseitigung durch das menschliche Immunsystem sowie die Komplement-vermittelte Opsonisierung und Eliminierung unerlässlich ist. Infektionen von Galleria mellonella-Larven zeigten ein deutlich verringertes Virulenzpotential der Kapsel-defizienten Mutante. Insgesamt zeigen diese Daten, dass die bakterielle Polysaccharidkapsel eine entscheidende Rolle in en Infektionen und der Immunevasion von K. pneumoniae spielt.Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative, facultative anaerobic, rod-shaped bacterium that can occur ubiquitously in the environment. As a human-pathogenic pathogen, K. pneumoniae is able to colonize the human mucosa and causes a variety of severe infections. In addition to nosocomial, urinary tract and bloodstream infections or pneumonia, hypervirulent strains having a highly mucoid phenotype cause also soft tissue infections, liver abscesses, and bacterial meningitis. Due to the rapidly increasing global spread of multidrug-resistant K. pneumoniae strains and the simultaneous lack of alternative forms of therapy, the need to develop new preventive and therapeutic measures against K. pneumoniae infection is of utmost importance. Possible preventive measures include vaccinations, which are usually based on the use of proteinaceous immunogenic antigens of the pathogen. In recent years, lipoproteins, which are found on the bacterial surface, have become the focus of vaccine studies in both Gram-positive bacteria such as Streptococcus pneumoniae (S. pneumoniae) and Gram-negative bacteria such as Neisseria meningitidis (N. meningitidis). Whether lipoproteins also have a protective effect in K. pneumoniae and could therefore be considered as vaccine candidates has not yet been sufficiently investigated.
Thus, this study initially aims to identify lipoproteins of K. pneumoniae ATCC BAA2146 (Kpn2146) in in silico approaches. Of the 93 potential lipoproteins, 85 candidates were predicted in the outer membrane, of which 32 proteins were included in further studies based on their size (at least 150 amino acids) and known or unknown function. For a functional characterization, the lipoproteins HP7, HslJ, LpoB, MltA, NlpD_1, NlpD_2, NlpI, Pal, QseG, RlpA, Slp and YajI were heterologously expressed in E. coli. The recombinant proteins were subsequently successfully used for the immunization of CD1 mice to obtain antisera against the respective proteins. The immunogenicity was tested with human sera from healthy donors and K. pneumoniae-infected patient sera. NlpD_1 and NlpD_2 emerged as potential immunogenic candidates. The surface localization of candidate lipoproteins was investigated by flow cytometry using the generated anti-lipoprotein IgGs and a onstruced nonencapsulated mutant Kpn2146Δwza.. However, the results did not allow a clear conclusion as to the surface localization of the lipoproteins on the extracellular bacterial surface.
The generated capsule-deficient mutant Kpn2146Δwza was further employed to to investigate the influence of the polysaccharide capsule on bacterial adhesion to and internatlization into A549 lung epithelial cell as well as to assess survival in the blood and invasiveness of K. pneumoniae in an experimental infection model. The capsule-deficient mutant showed reduced growth in complex medium, whereas there was no difference in growth behaviour between the wild-type and Kpn2146Δwza in the chemically defined medium. Likewise, no difference in adhesion was evident between wild-type and capsule-less mutant, whereas internalization data showed a moderately higher invasion of Kpn2146Δwza compared to the wild-type. The results of the comparative survival studies in human whole blood showed that the nonencapsulated mutant could neither survive in whole blood nor in human plasma. These data indicated that the capsule is essential for survival, protection of K. pneumoniae from recognition and clearance by the human immune system, and complement-mediated opsonization and killing as well. Infections of Galleria mellonella larvae showed a significantly reduced virulence potential of the capsule-deficient mutant. Overall, these data show that the bacterial polysaccharide capsule plays a crucial role in vivo
Census of below-ground biota associated with permafrost affected soils of western Greenland, with a focus on trophic structure
Get PDFLarge amounts of terrestrial organic carbon (OC) are stored in Arctic permafrost-affected soils. Through processes of cryoturbation and solifluction, the subsoils can contain subducted topsoil material, which largely contribute to the large OC storage in these soils. While the bacterial, archaeal, and fungal communities in such soils have been studied to some degree, information about protists and meso- and macrofauna is scarce, although these groups might substantially contribute to OC processing, through e.g., food web interactions. Different organic and mineral horizons, including subducted topsoil material, of Arctic soils were investigated using a metatranscriptomics three-domain community profiling approach. Soil horizons were compared in regards to their total microbial community composition including all three domains of life. Furthermore, abundances of different pro- and eukaryotic micropredators were examined and a variety of functional groups involved in the carbon (C) and the nitrogen (N) cycle were analyzed in relation to specific taxonomic groups and abiotic soil parameters. Our study showed that RNA yields positively correlated with the OC content of the horizon and that the composition of the microbial community in subducted topsoil material rather matched that of mineral subsoils instead of organic top horizons. Horizon-resolved profiling revealed heterogeneity in the associated microbiomes and showed major differences in microbiomes of topsoil and subducted topsoil. The abundance of protist and nematode micropredators decreased in subducted topsoil, while predatory myxobacteria remained remarkably constant and comprised high proportions of the total communities in all horizons. Correlations analysis between functional guilds and biotic and abiotic parameters suggest a major impact of predatory myxobacteria on carbon and nitrogen cycles of subducted topsoils. The study adds urgently needed information about the total biota structure in permafrost soils and first insights into the associated soil microbial food webs
Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
Get PDFIn this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. We predicted microbial formate as well as other microbial metabolites, which could alter urine formate production in the host-microbiome personalised models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management
Measuring 3D tree imbalance of plant models using graph-theoretical approaches
Get PDFImbalance in the 3D structure of plants can be an important indicator of insufficient light or nutrient supply, as well as excessive wind, (formerly present) physical barriers, neighbor or storm damage. It can also be a simple means to detect certain illnesses, since some diseases like the apple proliferation disease, an infection with the barley yellow dwarf virus or plant canker can cause abnormal growth, like “witches' brooms” or burls, resulting in a deviating 3D plant architecture. However, quantifying imbalance of plant growth is not an easy task, and it requires a mathematically sound 3D model of plants to which imbalance indices can be applied. Current models of plants are often based on stacked cylinders or voxel matrices and do not allow for measuring the degree of 3D imbalance in the branching structure of the whole plant.
On the other hand, various imbalance indices are readily available for so-called graph-theoretical trees and are frequently used in areas like phylogenetics and computer science. While only some basic ideas of these indices can be transferred to the 3D setting, graph-theoretical trees are a logical foundation for 3D plant models that allow for elegant and natural imbalance measures.
In this manuscript, our aim is thus threefold: We first present a new graph-theoretical 3D model of plants and discuss desirable properties of imbalance measures in the 3D setting. We then introduce and analyze eight different 3D imbalance indices and their properties. Thirdly, we illustrate all our findings using a data set of 63 bush beans. Moreover, we implemented all our indices in the publicly available R-software package treeDbalance accompanying this manuscript. Using this software package, all presented 3D imbalance indices can be computed in linear time (depending on the size of the 3D plant model), and the package also provides an implementation of the algorithm to obtain a perfectly balanced version of a given 3D plant model (also in linear time)
Global functional connectivity reorganization reflects cognitive processing speed deficits and fatigue in multiple sclerosis
Get PDFBackground and purpose
Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting‐state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph‐theory‐based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross‐sectional fMRI analysis.
Methods
Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion‐weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability.
Results
Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median −0.30/−0.06, interquartile range 0.55/0.54; p = 0.009, Mann–Whitney U test), yielding acceptable yet non‐superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/−0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = −0.34, p = 0.010, n = 56) but neither gait nor disability.
Conclusions
kD is a potential biomarker of CI and fatigue warranting further validation