Zum morphologischen Bau und zur funktionellen Bedeutung der Ocellen der Libellen (Odonata).

Bei den Anisopteren und den Zygopteren weisen die in Dreiecksform auf der Vertexregion untergebrachten Stirnaugen hinsichtlich ihrer Aperturen deutliche Unterschiede auf. Während sich bei den Großlibellen der größere Frontalocellus mehr nach vorn, also in der Hauptflugrichtung, die beiden kleineren seitlichen Punktaugen lateralwärts öffnen, sind bei den Kleinlibellen die Aperturen aller drei Scheitelaugen aufwärts gerichtet. Bei den „Ungleichflüglern" erfährt das Ocellusdreieck — eine Ausnahme bilden die Angehörigen der Gomphidae, einerseits durch die mächtige Ausbildung der Komplexaugen und den vor denselben befindlichen Chitinwulst und andererseits durch die halbkugelig aufgeblähte Stirnblase eine räumliche Einengung. Der auf diese Weise entstehende Eindruck einer grubenartigen Versenkung der Stirnaugen, dies gilt besonders von dem Medianocellus, weniger von den beiden Lateralocellen, ist gegenüber der offenen und freien Lage der Stirnocellen bei den Zygopteren mit einer gewissen Einschränkung des Lichteinfalles verbunden, welche sich aber für die Perzeption der in der Hauptflugrichtung das mittlere Punktauge treffenden Lichtstrahlen günstig auswirken muß. Da sich bei den Vertretern der beiden Unterordnungen der Odonaten die Scheitelaugen in verschiedenen Niveaus „installiert" befinden, kann von einer raumdimensionalen Anordnung derselben gesprochen werden. Über die Breiten- und Längendurchmesser der ellipsoidisch geformten Cornealinsen, welche als Kondensatoren die elektromagnetischen Schwingungen auf die photorezeptorischen und -transformierenden Elemente der Retina leiten, werden durch genaue Messungen dieser dioptrisch arbeitenden "Hilfsorgane der zusammengesetzten Augen" bei einer Reihe von Anisopteren- und Zygopteren-Arten genaue Angaben gemacht. Die größeren Dimensionen der Stirnaugen der Großlibellen, welche sicherlich mit einem stärkeren Differenzierungsgrad der die elektromagnetischen Schwingungen perzipierenden und transformierenden Zellelemente der Retina verbunden sind, gegenüber denen der Kleinlibellen werden mit den besseren Flugleistungen der ersteren in Zusammenhang gebracht. Der Umstand, daß bei den zu Dämmerungsflügen tendierenden Anisopteren der Medianocellus auffallend groß ausgebildet ist, rechtfertigt die in der Literatur von anderen Insekten vertretene Annahme, daß auch die Libellenocellen als Rezeptoren für geringe Lichtintensitäten aufzufassen sind, die auf Grund dieser Funktion die Leistungen der Facettenaugen nachhaltig unterstützen. Durch verhaltenskundliche Experimente, welche ohne Ausnahme in der freien Natur ausgeführt wurden, wird weiter bestätigt, daß auch den Stirnaugen der Odonaten die Aufgabe einer photokinetischen und phototaktischen Stimulation zufällt. Auf Grund der von Ruck mit dem elektrophysiologischen Verfahren auch bei den Libellen erzielten ERGs sind bei diesen Insekten die Ocellen ob ihrer phasischen Eigenschaften geradezu für die Perzeption von Helligkeitsänderungen prädestiniert. Aus diesem Grunde wäre bei der experimentellen Erprobung der photokinetischen Reaktionsfähigkeit statt einer Heranziehung stationären Lichtes die Verwendung einer Lichtquelle mit schnell aufeinanderfolgenden Helligkeitsänderungen notwendig gewesen. Da sich eine wirklich leistungsfähige Quelle zur Erzeugung von Flimmerlicht in freier Natur nicht in Betrieb setzen ließ, mußte auf eine entsprechende Ausweitung meiner Experimente verzichtet werden. Weil das Verhalten der Libellen weitgehend von den thermischen Gegebenheiten mitbestimmt wird, experimentierte ich nicht bei direktem Sonnenlicht, sondern unter diffusem Tageslicht. Dies war wohl auch der Hauptgrund, daß die Versuche nicht befriedigten, durch welche geklärt werden sollte, welcher Wellenbereich des Lichtes für die photokinetische Reaktion der Versuchstiere verantwortlich gemacht werden darf. Durch Freilassen der ocellengeblendeten Odonaten, deren Flügelunterseiten mit einem Farbaerosol weithin sichtbar gekennzeichnet worden waren, sollte geklärt werden, ob die Scheitelaugen als lebenswichtige Organe zu werten sind. Es wird der Nachweis erbracht, daß die ocellengeblendeten Anisopteren (Versuchstier: Cordulegaster boltonii) einige Tage, die Zygopteren (Versuchstier: Lestes sponsa) sogar einige Wochen den Eingriff überleben können. Diese Beobachtungstatsache darf wohl so gedeutet werden, daß die Ocellenfunktionen zum Teil von den Komplexaugen mitübernommen bzw. beim Ausfall der ersteren von Seiten der letzteren teilweise kompensiert werden können. Gegenüber den intakt gelassenen Artgenossen zeigt sich aber das Verhalten der ocellengeblendeten Odonaten (Cordulegaster boltonii und Lestes sponsa) ungünstig beeinflußt, so daß wichtige Lebensfunktionen nicht mehr ausgeübt werden können. Demnach dürfen bei den Libellen die Stirnaugen weit mehr als z.B. bei den Bienen nach den Untersuchungen von Lindauer & Schricker als lebensnotwendige Einrichtungen betrachtet werden. - Auf Grund der raumdimensionalen Anordnung und größenmäßig wegen ihrer unterschiedlichen Ausbildung dürften mit größter Wahrscheinlichkeit die Ocellen der Odonaten ihre Träger auch über die Richtung der einfallenden Lichtstrahlen informieren.The ocelli of the Odonata form a triangle in the vertex region. The apertures of the larger median frontal eye of Anisoptera open in the main direction of flight and those of their smaller lateral ocelli open sideways, while the ocellus lenses of Zygoptera look in a more upward direction. Apart from the Gomphidae, the ocellus triangle of the great dragon-flies is compressed in space and consequently has a reduced incidence of light, which must have a favourable influence, however, on the perception of light in the direction of flight. The larger dimensions of the frontal eyes of Anisoptera, which certainly are connected with a greater degree of differentiation of the structural elements of the retina, are seen in relation with the better flight performance of the great dragon-flies. The fact that the median ocelli of Anisoptera, which tend to fly in twilight, are especially large, confirms their interpretation as "receptors for light of low intensity". The results of behavioural experiments suggest that the ocelli of dragon-flies also have the function of both phototactic and photokinetic stimulation. Their arrangement in space and dimension indicates that they inform also of the direction of the incident light rays

Identification of Cellular Pathogenicity Markers for SIL1 Mutations Linked to Marinesco-Sjögren Syndrome.

Background and objective: Recessive mutations in the SIL1 gene cause Marinesco-Sjögren syndrome (MSS), a rare neuropediatric disorder. MSS-patients typically present with congenital cataracts, intellectual disability, cerebellar ataxia and progressive vacuolar myopathy. However, atypical clinical presentations associated with SIL1 mutations have been described over the last years; compound heterozygosity of SIL1 missense mutations even resulted in a phenotype not fulfilling the clinical diagnostic criteria of MSS. Thus, a read-out system to evaluate reliably the pathogenicity of amino acid changes in SIL1 is needed. Here, we aim to provide suitable cellular biomarkers enabling the robust evaluation of pathogenicity of SIL1 mutations. Methods: Five SIL1 variants including one polymorphism (p.K132Q), three known pathogenic mutations (p.V231_I232del, p.G312R, and p.L457P) and one ambiguous missense variant (p.R92W) were studied along with the wild-type proteins in Hek293 in vitro models by cell biological assays, immunoprecipitation, immunoblotting, and immunofluorescence as well as electron microscopy. Moreover, the SIL1-interactomes were interrogated by tandem-affinity-purification and subsequent mass spectrometry. Results: Our combined studies confirmed the pathogenicity of p.V231_I232del, p.G312R, and p.L457P by showing instability of the proteins as well as tendency to form aggregates. This observation is in line with altered structure of the ER-Golgi system and vacuole formation upon expression of these pathogenic SIL1-mutants as well as the presence of oxidative or ER-stress. Reduced cellular fitness along with abnormal mitochondrial architecture could also be observed. Notably, both the polymorphic p.K132Q and the ambiguous p.R92W variants did not elicit such alterations. Study of the SIL1-interactome identified POC1A as a novel binding partner of wild-type SIL1; the interaction is disrupted upon the presence of pathogenic mutants but not influenced by the presence of benign variants. Disrupted SIL1-POC1A interaction is associated with centrosome disintegration. Conclusions: We developed a combination of cellular outcome measures to evaluate the pathogenicity of SIL1 variants in suitable in vitro models and demonstrated that the p. R92W missense variant is a polymorphism rather than a pathogenic mutation leading to MSS

Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone DNAJC3.

Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, β-amyloid accumulation, and impairment of mitochondrial oxidative phosphorylation

Homozygous WASHC4 variant in two sisters causes a syndromic phenotype defined by dysmorphisms, intellectual disability, profound developmental disorder, and skeletal muscle involvement.

Funder: European Regional Development Fund; Id: http://dx.doi.org/10.13039/501100008530Recessive variants in WASHC4 are linked to intellectual disability complicated by poor language skills, short stature, and dysmorphic features. The protein encoded by WASHC4 is part of the Wiskott-Aldrich syndrome protein and SCAR homolog family, co-localizes with actin in cells, and promotes Arp2/3-dependent actin polymerization in vitro. Functional studies in a zebrafish model suggested that WASHC4 knockdown may also affect skeletal muscles by perturbing protein clearance. However, skeletal muscle involvement has not been reported so far in patients, and precise biochemical studies allowing a deeper understanding of the molecular etiology of the disease are still lacking. Here, we report two siblings with a homozygous WASHC4 variant expanding the clinical spectrum of the disease and provide a phenotypical comparison with cases reported in the literature. Proteomic profiling of fibroblasts of the WASHC4-deficient patient revealed dysregulation of proteins relevant for the maintenance of the neuromuscular axis. Immunostaining on a muscle biopsy derived from the same patient confirmed dysregulation of proteins relevant for proper muscle function, thus highlighting an affliction of muscle cells upon loss of functional WASHC4. The results of histological and coherent anti-Stokes Raman scattering microscopic studies support the concept of a functional role of the WASHC4 protein in humans by altering protein processing and clearance. The proteomic analysis confirmed key molecular players in vitro and highlighted, for the first time, the involvement of skeletal muscle in patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Redox Modulation at Work: Natural Phytoprotective Polysulfanes From Alliums Based on Redox-Active Sulfur

Purpose of review: This article provides a brief overview of natural phytoprotective products of allium with a special focus on the therapeutic potential of diallyl polysulfanes from garlic, their molecular targets and their fate in the living organisms. A comprehensive overview of antimicrobial and anticancer properties of published literature is presented for the reader to understand the effective concentrations of polysulfanes and their sensitivity towards different human pathogenic microbes, fungi, and cancer cell lines. Recent findings: The article finds polysulfanes potentials as new generation novel antibiotics and chemo preventive agent. The effective dose rates of polysulfanes for antimicrobial properties are in the range of 0.5–40 mg/L and for anticancer 20–100 μM. The molecular targets for these redox modulators are mainly cellular thiols as well as inhibition and/or activation of certain cellular proteins in cancer cell lines. Summary: Antimicrobial and anticancer activities of polysulfanes published in the literature indicate that with further development, they could be promising candidates for cancer prevention due to their selectivity towards abnormal cells

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 08, Revision 5 (FGE.08Rev5): Aliphatic and alicyclic mono-, di-, tri-, and polysulphides with or without additional oxygenated functional groups from chemical groups 20 and 30

<p>The CEF Panel of the European Food Safety Authority was requested to evaluate 80 flavouring substances in the Flavouring Group Evaluation 08, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. Since the publication of the last revision of this FGE, the EFSA has been requested to evaluate additional toxicological data submitted for two flavouring substances, one substance 2,5-dihydroxy-2,5-dimethyl-1,4-dithiane [FL-no: 15.006], which support the evaluation of the candidate substance 2,5-dihydroxy-1,4-dithiane [FL-no: 15.134] and one on the candidate substance spiro(2,4-dithia-1-methyl-8-oxabicyclo[3.3.0]octane-3,3’-(1’-oxa-2’-methyl)-cyclopentane) and spiro(2,4-dithia-6-methyl-7-oxabicyclo[3.3.0]octane-3,3’-(1’-oxa-2’-methyl)-cyclopentane) [FL-no: 15.007], which have been included in the present revision of FGE.08. For the substances methyl methanethiosulphonate [FL-no: 12.159], 2-methylbutane-2-thiol [FL-no: 12.172], 2-methylpropane-2-thiol [FL-no: 12.174], ethyl-2-mercapto-2-methyl propanoate [FL-no: 12.304] and 2,4,4-trimethyl-1,3-oxathiane [FL-no: 16.057] there is an indication of a genotoxic potential in vitro. Therefore, without further genotoxicity data, the Panel concluded that the Procedure could not be applied to these five substances. For four substances, 3-mercaptooctanal [FL-no: 12.268], 3-mercaptodecanal [FL-no: 12.269], methanedithiol diacetate [FL-no: 12.271] and 3,5-dimethyl-1,2-dithiolane-4-one [FL-no: 12.295] no data on use as flavouring substances in Europe are available and no intake figures could be calculated, which preclude the evaluation of the four substances using the Procedure. The remaining 71 substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that 59 substances do not rise safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For 12 substances [FL-no: 12.093, 12.094, 12.097, 12.100, 12.112, 12.116, 12.120, 12.164, 12.167, 12.199, 15.102 and 15.125], evaluated through the Procedure, no appropriate NOAEL was available and additional data are required. The specifications for the materials of commerce have also been considered and for three substances, information on the specifications is lacking.</p&gt