Über intraepitheliale nervöse Endformationen in mehrschichtigem Plattenepithel

Zusammenfassung Im Anschluß an frühere lichtmikroskopisch erhobene Befunde (Silberimprägnation; 1924, 1928) weist der Verfasser durch elektronenmikroskopische Untersuchungen nach, daß durch die Interzellularspalten des Epithels (Schnauze der weißen Ratte) Nervenfasern hindurchziehen. Diese Nervenfäserchen, ihre Varikositäten und ihre Endknöpfchen liegen in den Spalten zwischen den Epithelzellen. Die Ultrastruktur der nackten, d.h. von Schwannschen Zellen nicht umhüllten terminalen Nervenfasern und ihrer Endigungen im Epithel wird beschrieben.

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On intraepithelial nerve endings in a stratified squamous epithelium

Summary In addition to former light microscopical observations the author demonstrates electronmicroscopically that nerve fibers pass through the intercellular spaces of the epithelium. The nerve fibers, their varicosities and terminal bulbs lie within the spaces between the epithelial cells. The ultrastructure of the terminal nerve fibers in the epithelium is described.

     

1-Alkyl-3-amino-5-aryl-1H-[1,2,4]triazoles: novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF(1)) receptor antagonist activities.

Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF₁ receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF₁ receptor (K_i=9 nM).     

FIM Imaging and FIMtrack: Two New Tools Allowing High-throughput and Cost Effective Locomotion Analysis

The analysis of neuronal network function requires a reliable measurement of behavioral traits. Since the behavior of freely moving animals is variable to a certain degree, many animals have to be analyzed, to obtain statistically significant data. This in turn requires a computer assisted automated quantification of locomotion patterns. To obtain high contrast images of almost translucent and small moving objects, a novel imaging technique based on frustrated total internal reflection called FIM was developed. In this setup, animals are only illuminated with infrared light at the very specific position of contact with the underlying crawling surface. This methodology results in very high contrast images. Subsequently, these high contrast images are processed using established contour tracking algorithms. Based on this, we developed the FIMTrack software, which serves to extract a number of features needed to quantitatively describe a large variety of locomotion characteristics. During the development of this software package, we focused our efforts on an open source architecture allowing the easy addition of further modules. The program operates platform independent and is accompanied by an intuitive GUI guiding the user through data analysis. All locomotion parameter values are given in form of csv files allowing further data analyses. In addition, a Results Viewer integrated into the tracking software provides the opportunity to interactively review and adjust the output, as might be needed during stimulus integration. The power of FIM and FIMTrack is demonstrated by studying the locomotion of Drosophila larvae.     

Transfer factor prevents relapses in herpes keratitis patients: A pilot study

Transfer Factor is a dialysable moiety obtained from immune lymphocytes. It has been successfully used for the treatment of several viral infections including labial and genital herpes. In the present study, thirty-three patients with low immune response to HSV antigens and suffering from herpes ocular infections were orally treated with HSV-specific transfer factor (TF). Their relapse index was reduced from 20.1 before treatment to 0.51 after TF administration, with only 6/33 patients relapsing. Although this is not a placebo-controlled-randomized study, the results suggest that TF specific for HSV antigens may be efficacious for preventing relapses of ocular herpes infections as has been the case with genital and labial localisations.Abbreviations CMI Cell-mediated immunity - CMV Cytomegalo-virus - EBV Epstein-Barr virus - HIV Human immunodeficiency virus - HK Herpes keratitis - HSV Herpes simplex virus - IRI Individual relapse index - KU Kerato-uveitis - LMT Leucocyte migration test - LST Lymphocyte stimulation test - MIF Migration inhibition factor - RHK Relapsing herpes keratitis - TF Transfer factor     

EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients

Background

Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations.

Method/Design

The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement.

Discussion

With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors.

Trial Registration

NCT02544178

     

Does Dysphoria Lead to Divergent Mental Fatigue Effects on a Cognitive Task?

Objective

Tiredness, low energy, and listlessness are common symptoms to be associated with depression. The question remains to what extent these symptoms influence the effects of fatigue on sustained performance tasks, such as impaired task engagement and performance. Based on earlier findings, it was hypothesized that dysphoric (i.e., mildly depressed) individuals, compared to healthy controls, would display earlier fatigue onset and more severe fatigue effects on task engagement and performance during a cognitive task.

Methods

Sixty-one dysphoric and twenty-one non-dysphoric control participants were compared during one hour of continuous performance on a 2-back task. During the task subjective fatigue, subjective engagement, objective task performance, baseline pupil diameter and stimulus-evoked pupil dilation were measured.

Results

While we found that the dysphoric group reported relatively higher subjective fatigue than the healthy control group at the start of the experiment, we did not find any other divergent fatigue effects during the experimental task.

Conclusion

One explanation for the absence of divergent effect is that dysphoria may not have such a profound impact on available cognitive resources, like attention, as initially thought. Based on the results of the present study, we conclude that dysphoria is not necessarily an increased risk factor for impaired sustained performance on cognitive tasks that may induce mental fatigue.     

Diversification of sterol methyltransferase enzymes in plants and a role for β‐sitosterol in oriented cell plate formation and polarized growth

Phytosterols are classified into C24‐ethylsterols and C24‐methylsterols according to the different C24‐alkylation levels conferred by two types of sterol methyltransferases (SMTs). The first type of SMT (SMT1) is widely conserved, whereas the second type (SMT2) has diverged in charophytes and land plants. The Arabidopsis smt2 smt3 mutant is defective in the SMT2 step, leading to deficiency in C24‐ethylsterols while the C24‐methylsterol pathway is unchanged. smt2 smt3 plants exhibit severe dwarfism and abnormal development throughout their life cycle, with irregular cell division followed by collapsed cell files. Preprophase bands are occasionally formed in perpendicular directions in adjacent cells, and abnormal phragmoplasts with mislocalized KNOLLE syntaxin and tubulin are observed. Defects in auxin‐dependent processes are exemplified by mislocalizations of the PIN2 auxin efflux carrier due to disrupted cell division and failure to distribute PIN2 asymmetrically after cytokinesis. Although endocytosis of PIN2–GFP from the plasma membrane (PM) is apparently unaffected in smt2 smt3, strong inhibition of the endocytic recycling is associated with a remarkable reduction in the level of PIN2–GFP on the PM. Aberrant localization of the cytoplasmic linker associated protein (CLASP) and microtubules is implicated in the disrupted endocytic recycling in smt2 smt3. Exogenous C24‐ethylsterols partially recover lateral root development and auxin distribution in smt2 smt3 roots. These results indicate that C24‐ethylsterols play a crucial role in division plane determination, directional auxin transport, and polar growth. It is proposed that the divergence of SMT2 genes together with the ability to produce C24‐ethylsterols were critical events to achieve polarized growth in the plant lineage.