Ökophysiologische Konsequenzen und Bewältigung hoher Habitattemperaturen bei mediterranen Landschnecken

Heiße und trockene Umgebungsbedingungen, wie sie im mediterranen Sommer üblich sind, stellen Organismen mit hohem Wassergehalt, wie zum Beispiel Schnecken, vor schwerwiegende Probleme. Dennoch kommen unterschiedliche Landschneckenarten, darunter auch Xeropicta derbentina [Krynicki 1836], zum Teil in großen Mengen im mediterranen Raum vor. Die dort lebenden Arten müssen also Anpassungen in ihrem Verhalten und ihrer Körperphysiologie entwickelt haben, um den ungünstigen Umgebungsbedingungen entgegenzuwirken und diese zu tolerieren. Durch die vorliegende Arbeit konnten neue Erkenntnisse zu physiologischen Grenzen und Anpassungen von X. derbentina an ihr südfranzösisches Habitat erzielt werden. Im Fokus standen hierbei subzelluläre Anpassungen und Untersuchungen zu Stoffwechsel, Sauerstoffverbrauch und Wasserverlust der Tiere. Bei Untersuchungen zur Tages- und Jahreskinetik des intrazellulär protektiv wirkenden Hsp70 Schutzsystems konnte gezeigt werden, dass der messbare Hsp70-Level von der umgebenden Temperatur abhängig ist und den Tagesverlauf der Umgebungstemperatur widerspiegelt. Dabei waren die messbaren Hsp70-Level im Frühjahr niedriger als in den deutlich heißeren Sommermonaten Juni und August. In allen Fällen war eine positive Korrelation zwischen Hsp70-Level und Temperatur zu finden. Im Herbst jedoch konnte eine negative Korrelation der Umgebungstemperatur mit dem gemessenen Hsp70-Level gefunden werden, was auf einen energetischen Trade-off zwischen Aufrechterhaltung eines Schutzmechanismus und der zu dieser Jahreszeit einsetzenden Reproduktion gewertet wurde. Bei Laborversuchen zur Induzierbarkeit des Hsp70-Levels bei verschieden gefärbten Individuen der Feldpopulation und bei Versuchen zum Einfluss der Länge der Hitzeeinwirkung auf den Hsp70-Level der Tiere konnte gezeigt werden, dass die Hsp70-Induktion bei 38 bis 40°C einen Maximalwert erreichte. Beim Überschreiten dieser Temperatur konnte ein deutlicher Rückgang im Hsp70-Level, der als Überlast des Systems gewertet wurde, aufgezeigt werden. Die intermediär gefärbten Individuen der Population wiesen bei den durchgeführten Experimenten bis 40°C einen höheren Hsp70-Level auf als die anders gefärbten Individuen. Doch waren es ebenfalls Individuen dieser Färbung, die bei Temperaturen jenseits von 40°C den niedrigsten Hsp70-Level zeigten. Variierten sowohl die Temperatur als auch die Expositionszeit, so konnte ein Erreichen eines Maximalwertes umso schneller beobachtet werden, je höher die Temperatur war. Bei Untersuchungen zur ebenfalls bei Hitze auftretenden Lipidperoxidation und der Aktivität antioxidativ wirkender Enzyme konnte gezeigt werden, dass der Grad der Lipidperoxidation immer dann besonders hoch war, wenn auch ein maximaler Hsp70-Level gemessen werden konnte. Die Aktivität der beiden antioxidativ wirkenden Enzyme Katalase (CAT) und Glutathionperoxidase (GPx) war bei Temperaturen ab 40°C erhöht (CAT) oder maximal (GPx). Mit abnehmendem Hsp70-Level bei Temperaturen über 40°C war ebenfalls ein Rückgang des Grades der Lipidperoxidation zu verzeichnen, was hierbei auf die Aktivität obiger Enzyme schließen ließ. Auch hier ist von einem energetischen Trade-off auszugehen. In Phasen geringer Hitzelast reichen der Schnecke die konstitutiv vorhandenen Level an antioxidativ wirkenden Enzymen und Hsp70 aus um der Umgebungstemperatur entgegenzuwirken. Mit zunehmender Hitze müssen die Tiere mehr Energie aufwenden um die Schutzsysteme aufrecht zu erhalten. Bei Untersuchungen zum Wasserverlust durch die Schale und die versiegelte Schalenöffnung war ein steigender, aber nicht lebensbedrohlicher Wasserverlust mit steigender Temperatur zu beobachten. Je länger die Temperaturexposition dauerte, umso höher war der Wasserverlust. Überschritt die Temperatur 40°C, so war ein deutlich erhöhter Wasserverlust der Schnecken zu verzeichnen, der schnell kritische Werte annahm. Bei reaktionskalorimetrischen Untersuchungen zum Stoffwechsel der Tiere konnten zwei Phasen des Stoffwechsels eindeutig getrennt werden, die sich um den Faktor 3 bis 5 unterschieden. Dabei zeigte sich, dass höhere Temperaturen auch höhere Stoffwechselraten mit sich zogen. Sowohl kleinere als auch große Tiere waren in der Lage ihren Stoffwechsel stark zu reduzieren und somit Energie zu sparen. Bei Messungen zum Sauerstoffverbrauch der Tiere konnte eine Abhängigkeit zwischen der Schalengröße und dem Sauerstoffverbrauch ermittelt werden. Dabei verbrauchten kleinere Tiere weniger Sauerstoff als größere Tiere. Bei Erhöhung der Temperatur über 38°C waren es Individuen mittleren und großen Schalendurchmessers, die in der Lage waren ihren Sauerstoffverbrauch im Vergleich zu niedrigeren Temperaturen zu reduzieren, was abermals als Energiesparmaßnahme gewertet wurde. Zusammenfassend stellte sich heraus, dass Temperaturen zwischen 38 und 42°C physiologische Maxima darstellen, bei deren Überschreiten weitere Anpassungen vonnöten sind um erfolgreich zu überleben. Letztlich zeigt jedoch die hohe Abundanz von Xeropicta derbentina in Südfrankreich, dass die untersuchten Anpassungen dieser Art erfolgreich helfen in ihrem Habitat zu überleben

Loss of control in pattern-directed nucleation: a theoretical study

The properties of template-directed nucleation are studied close to the transition where full nucleation control is lost and additional nucleation occurs beyond the pre-patterned regions. First, kinetic Monte Carlo simulations are performed to obtain information on a microscopic level. Here the experimentally relevant cases of 1D stripe patterns and 2D square lattice symmetry are considered. The nucleation properties in the transition region depend in a complex way on the parameters of the system, i.e. the flux, the surface diffusion constant, the geometric properties of the pattern and the desorption rate. Second, the properties of the stationary concentration field in the fully controlled case are studied to derive the remaining nucleation probability and thus to characterize the loss of nucleation control. Using the analytically accessible solution of a model system with purely radial symmetry, some of the observed properties can be rationalized. A detailed comparison to the Monte Carlo data is included

DIZZYNET 2020: basic and clinical vestibular research united

Objective!#!To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient's clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN).!##!Methods!#!Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development): Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation): Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II.!##!Results!#!48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12) (mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p < .001; two-sided t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%).!##!Conclusions!#!Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy

The Longitudinal Effect of Vertigo and Dizziness Symptoms on Psychological Distress Symptom-Related Fears and Beliefs as Mediators

Despite the frequent observation that vertigo and dizziness (VD) disorders may trigger or exacerbate secondary psychiatric comorbidities, there is limited understanding of the mechanisms underlying this development. To address this gap, we investigated whether symptom-related fears and cognitions as indicated by questionnaire-based measures are mediators of the longitudinal effect of VD symptoms on anxiety and depression after 1 year. We analyzed data from a large study with patients of a treatment center specialized in vertigo (N = 210). Simple and multiple parallel mediation models strengthened our hypothesis that fear of bodily sensations and cognitions about these symptoms play a mediating role in the relationship between VD symptoms and psychopathology at follow-up after baseline scores of the outcome were controlled for. Results are discussed within a cognitive theory framework and point to the potential benefits of interventions that modify symptom-related beliefs and fears via cognitive psychotherapy in this therapeutically underserved population

A Prospective Analysis of Lesion-Symptom Relationships in Acute Vestibular and Ocular Motor Stroke

Background: Diagnosing stroke as a cause of acute vertigo, dizziness, or double vision remains a challenge, because symptom characteristics can be variable. The purpose of this study was to prospectively investigate lesion-symptom relationships in patients with acute vestibular or ocular motor stroke. Methods: Three hundred and fifty one patients with acute and isolated vestibular or ocular motor symptoms of unclear etiology were enrolled in the EMVERT lesion trial. Symptom quality was assessed by the chief complaint (vertigo, dizziness, double vision), symptom intensity by the visual analog scale, functional impairment by EQ-5D-5L, and symptom duration by daily rating. Acute vestibular and ocular motor signs were registered by videooculography. A standardized MRI (DWI-/FLAIR-/T2-/T2*-/3D-T1-weighted sequences) was recorded within 7 days of symptom onset. MRIs with DWI lesions were further processed for voxel-based lesion-symptom mapping (VLSM). Results: In 47 patients, MRI depicted an acute unilateral stroke (13.4%). The chief complaints were dizziness (42.5%), vertigo (40.4%) and double vision (17.0%). Lesions in patients with vertigo or dizziness showed a large overlap in the cerebellar hemisphere. VLSM indicated that strokes in the medial cerebellar layers 7b, 8, 9 were associated with vertigo, strokes in the lateral cerebellar layer 8, crus 1, 2 with dizziness, and pontomesencephalic strokes with double vision. Symptom intensity and duration varied largely between patients. Higher symptom intensity and longer duration were associated with medial cerebellar lesions. Hemispheric lesions of the cortex were rare and presented with milder symptoms of shorter duration. Conclusions: Prospective evaluation of patients with acute vestibular or ocular motor stroke revealed that symptom quality, intensity and duration were not suited to differentiating peripheral from central etiologies. Lesions in the lateral cerebellum, thalamus, or cortex presented with unspecific, mild and transient symptoms prone to being misdiagnosed

Gait analysis in PSP and NPH Dual-task conditions make the difference

Objective To test whether quantitative gait analysis of gait under single- and dual-task conditions can be used for a differential diagnosis of progressive supranuclear palsy (PSP) and idiopathic normalpressure hydrocephalus (iNPH). Methods In this cross-sectional study, temporal and spatial gait parameters were analyzed in 38 patients with PSP (Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy diagnostic criteria), 27 patients with iNPH (international iNPH guidelines), and 38 healthy controls. A pressure-sensitive carpet was used to examine gait under 5 conditions: single task (preferred, slow, and maximal speed), cognitive dual task (walking with serial 7 subtractions), and motor dual task (walking while carrying a tray). Results The main results were as follows. First, both patients with PSP and those with iNPH exhibited significant gait dysfunction, which was worse in patients with iNPH with a more broad-based gait (p < 0.001). Second, stride time variability was increased in both patient groups, more pronounced in PSP (p = 0.009). Third, cognitive dual task led to a greater reduction of gait velocity in PSP (PSP 34.4% vs iNPH 16.9%, p = 0.002). Motor dual task revealed a dissociation of gait performance: patients with PSP considerably worsened, but patients with iNPH tended to improve. Conclusion Patients with PSP seem to be more sensitive to dual-task perturbations than patients with iNPH. An increased step width and anisotropy of the effect of dual-task conditions (cognitive vs motor) seem to be good diagnostic tools for iNPH

Three-dimensional pathological size assessment in primary breast carcinoma

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P=0.0003, TV: P=0.0009, TSA: P<0.0001; multivariate analyses: MD: P=0.0018, TV: P=0.0109, TSA: P=0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alon

doRiNA: a database of RNA interactions in post-transcriptional regulation

In animals, RNA binding proteins (RBPs) and microRNAs (miRNAs) post-transcriptionally regulate the expression of virtually all genes by binding to RNA. Recent advances in experimental and computational methods facilitate transcriptome-wide mapping of these interactions. It is thought that the combinatorial action of RBPs and miRNAs on target mRNAs form a post-transcriptional regulatory code. We provide a database that supports the quest for deciphering this regulatory code. Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs. Users are free to take a target (mRNA) or regulator (RBP and/or miRNA) centric view on the data. We have implemented a database framework with short query response times for complex searches (e.g. asking for all targets of a particular combination of regulators). All search results can be browsed, inspected and analyzed in conjunction with a huge selection of other genome-wide data, because our database is directly linked to a local copy of the UCSC genome browser. At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes. For computational miRNA target site predictions, we provide an update of PicTar predictions

Functional Plasticity after Unilateral Vestibular Midbrain Infarction in Human Positron Emission Tomography

The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group subtraction analyses and comparisons with healthy controls were performed with Statistic Parametric Mapping for the PET data. A comparison of PET A of acute-stage patients with that of healthy controls showed increases in glucose metabolism in the cerebellum, motion-sensitive visual cortex areas, and inferior temporal lobe, but none in vestibular cortex areas. At the supratentorial level bilateral signal decreases dominated in the thalamus, frontal eye fields, and anterior cingulum. These decreases persisted after clinical recovery in contrast to the increases. The transient activations can be attributed to ocular motor and postural recovery (cerebellum) and sensory substitution of vestibular function for motion perception (visual cortex). The persisting deactivation in the thalamic nuclei and frontal eye fields allows alternative functional interpretations of the thalamic nuclei: either a disconnection of ascending sensory input occurs or there is a functional mismatch between expected and actual vestibular activity. Our data support the view that both thalami operate separately for each hemisphere but receive vestibular input from ipsilateral and contralateral midbrain integration centers. Normally they have gatekeeper functions for multisensory input to the cortex and automatic motor output to subserve balance and locomotion, as well as sensorimotor integration

Determinants of functioning and health-related quality of life after vestibular stroke

BackgroundStroke accounts for 5–10% of all presentations with acute vertigo and dizziness. The objective of the current study was to examine determinants of long-term functioning and health-related quality of life (HRQoL) in a patient cohort with vestibular stroke.MethodsThirty-six patients (mean age: 66.1 years, 39% female) with an MRI-proven vestibular stroke were followed prospectively (mean time: 30.2 months) in the context of the EMVERT (EMergency VERTigo) cohort study at the Ludwig-Maximilians Universität, Munich. The following scores were obtained once in the acute stage (1 year after stroke): European Quality of Life Scale-five dimensions-five levels questionnaire (EQ-5D-5L) and Visual Analog Scale (EQ-VAS) for HRQoL, Dizziness Handicap Inventory (DHI) for symptom severity, and modified Rankin Scale (mRS) for general functioning and disability. Anxiety state and trait were evaluated by STAI-S/STAI-T, and depression was evaluated by the Patient Health Questionnaire-9 (PHQ-9). Voxel-based lesion mapping was applied in normalized MRIs to analyze stroke volume and localization. Multiple linear regression models were calculated to determine predictors of functional outcome (DHI, EQ-VAS at follow-up).ResultsMean DHI scores improved significantly from 45.0 in the acute stage to 18.1 at follow-up (p ConclusionThe average functional outcome of strokes with the chief complaint of vertigo and dizziness is favorable. The most relevant predictors for individual outcomes are the personal anxiety trait (especially in combination with the female sex), the initial symptom intensity, and lesion volume. These factors should be considered for therapeutic decisions both in the acute stage of stroke and during subsequent rehabilitation.</p