Raman ChemLighter: Fiber optic Raman probe imaging in combination with augmented chemical reality

Raman spectroscopy using fiber optic probe combines non‐contacted and label‐free molecular fingerprinting with high mechanical flexibility for biomedical, clinical and industrial applications. Inherently, fiber optic Raman probes provide information from a single point only, and the acquisition of images is not straightforward. For many applications, it is highly crucial to determine the molecular distribution and provide imaging information of the sample. Here, we propose an approach for Raman imaging using a handheld fiber optic probe, which is built around computer vision–based assessment of positional information and simultaneous acquisition of spectroscopic information. By combining this implementation with real‐time data processing and analysis, it is possible to create not only fiber‐based Raman imaging but also an augmented chemical reality image of the molecular distribution of the sample surface in real‐time. We experimentally demonstrated that using our approach, it is possible to determine and to distinguish borders of different bimolecular compounds in a short time. Because the method can be transferred to other optical probes and other spectroscopic techniques, it is expected that the implementation will have a large impact for clinical, biomedical and industrial applications.      

Mouse models of the laminopathies

The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner's syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the A type lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease.     

老年缺血性心力衰竭的心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡的关联

摘要 目的：探讨老年缺血性心力衰竭的心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡的关联性。方法：2019年12月到2021月2月,选择在本院诊治的老年缺血性心力衰竭115例作为心衰组,同期选择在本院体检的非心血管疾病老年人群115例作为对照组。检测心脏DNA甲基化编码重编程、心肌细胞焦亡、铁死亡指标表达情况并进行相关性分析。结果：心衰组的心脏DNA甲基化编码重编程指标-miR-92a、miR-130a相对表达水平高于对照组（P<0.05）。心衰组的Caspase-1蛋白、Caspase-4蛋白相对表达水平高于对照组（P<0.05）。心衰组的铁调素含量高于对照组（P<0.05）。在两组230例入选者中,Spearsman相关分析显示：缺血性心力衰竭与miR-92a、miR-130a、半胱氨酸蛋白酶1（Caspase-1）、半胱氨酸蛋白酶4（Caspase-4）、铁调素存在正向相关性（P<0.05）。Logistic回归分析显示：miR-92a、miR-130a、Caspase-1、Caspase-4、铁调素为导致缺血性心力衰竭发生的重要因素（P<0.05）。结论：老年缺血性心力衰竭患者多伴随有心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡,后三者与缺血性心力衰竭的发生存在关联性,也是导致缺血性心力衰竭发生的重要因素。     

The role of mitochondria in sepsis-induced cardiomyopathy

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial dysfunction, often termed sepsis-induced cardiomyopathy, is a frequent complication and is associated with worse outcomes. Numerous mechanisms contribute to sepsis-induced cardiomyopathy and a growing body of evidence suggests that bioenergetic and metabolic derangements play a central role in its development; however, there are significant discrepancies in the literature, perhaps reflecting variability in the experimental models employed or in the host response to sepsis. The condition is characterised by lack of significant cell death, normal tissue oxygen levels and, in survivors, reversibility of organ dysfunction. The functional changes observed in cardiac tissue may represent an adaptive response to prolonged stress that limits cell death, improving the potential for recovery. In this review, we describe our current understanding of the pathophysiology underlying myocardial dysfunction in sepsis, with a focus on disrupted mitochondrial processes.     

Wie V?gel ihr Auge schützen: Zur Arbeitsteilung von Oberlid, Unterlid und Nickhaut

Zusammenfassung Vögel schließen ihre Augen im Schlaf in einer für die großen Taxa typischen Weise. Entweder geht das Unterlid hoch wie bei der Mehrzahl der Arten, oder das Oberlid bewegt sich abwärts (Psittaciformes, Trochili), oder aber beide Lider schließen die Lidspalte (Strigiformes, Caprimulgi). Solche Kenntnis fehlt von den meisten Ordnungen, oder die Handbücher geben falsche oder widersprüchliche Information. Neben dem tonischen, schlafbegleitenden Augenschluss bewegen Vögel im Wachzustand eines oder beide Lider phasisch und meist schnell. Dieser häufige Lidschlag ist durch ein anderes Bewegungsmuster und durch eine andere Funktion gekennzeichnet. Photodokumente und genaue Beobachtungen führen erstmals zu einer funktionellen Deutung, der zufolge der Lidschlag das Auge mechanisch schützt. Droht dem Auge von vorn oder von oben eine potentielle Schädigung, so schließt das Oberlid bei Tauben, Eulen und Singvögeln, im Sprühwasser gleichzeitig auch das Unterlid (Cinclus). Der unabweisbarste Beleg stammt aus dem Vergleich des Aufpickens dorniger, sperriger Beuteinsekten mit Oberlidschluss gegenüber dem Aufnehmen harmloser Beeren ohne jede Lidbewegung (Gallicolumba). Weiter ist die Antwort des Oberlids, anders als beim Unterlid, öfter seitengerecht reizorientiert, so dass die Bewegung einseitig sein kann. Zudem kann der Schluss des Oberlids auch bei stationärem (Feind-)reiz seitenweise alternieren (Otus). Ausnahmsweise tritt eine adaptive Asymmetrie auch während kurzer Zeiten der Augenöffnung zum Spähen nach Feinden im Schlaf auf, und zwar hier beim Unterlid der bedrohten Seite (Anas).Eine neue Funktion wird auch dem Schlag der Nickhaut (Membrana nictitans) zugeschrieben. Traditionell als die Cornea reinhaltendes Organ gesehen, dient auch sie dem mechanischen Schutz des Auges. Auch sie kann seitenrichtig reizorientiert schlagen, doch ist hierüber wenig bekannt. Dieselben Reize, die den Lidschlag auslösen, können bei anderen Arten die Nickhaut schlagen lassen. Ihre Schlagrate ist schwierig zu messen, da viele Schläge (nur?) mit denen des Oberlides zusammenfallen und so verborgen bleiben (Otus). Diese Synchronie ist mit keiner der bisher vorgeschlagenen Funktionen erklärbar, ebenso wenig wie die verborgenen Schläge bei tonischem Augenschluss (Passer).Die Annahme einer Ausschaltung störender Sinnesinformation, z.B. während rascher Kopfbewegungen, durch die Nickhaut lässt sich aus vier Gründen verwerfen. Die Zunahme der Schlagrate während des Feindalarms (Ficedula) bleibt funktionell unerklärt.In einer bei Vögeln einzigartigen Weise schützt der Samtkleiber (Sitta azurea) sein Auge durch Zusammenziehen des nackten Augenrings (Lidblende), wenn er rücklings an der Unterseite von Ästen nahrungssuchend einem ständigen Regen von losgelösten Rindenteilchen u. ä. ausgesetzt ist.Sekundär haben sich die Bewegungen eines oder beider Lider oder aber der Nickhaut zu optischen Signalen entwickelt, und zwar durch kontrastierende Feder- oder Nickhautfärbung. Die betreffenden blitzschnell aufleuchtenden Signale sind an den Paarpartner (Cinclus, Corvidae,Cepphus), an mögliche Feinde (Anas) oder an bisher unbekannte Empfänger gesichtet (Ficedula).

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On how birds protect their eyes: division of labour between the upper lid, lower lid and the nictitating membrane

Summary Birds close their eyes during sleep in various taxon-specific ways. Either the lower lid moves up as in the majority of species including the Anseres, Accipitres, Falconiformes, Galli, Charadrioidea, Columbiformes, and Oscines; or the upper lid moves down (Psittaciformes, Trochili), or both lids close the eye as in Strigiformes and Caprimulgi. Such information is absent for most orders, or the handbooks provide wrong or conflicting information. Beside the tonic, sleep-related eye closure, birds move one or both lids in a phasic, usually swift mode when awake. These frequent lid movements are typified by their different co-ordination and function. Photographic and observational evidence strongly suggests mechanical protection of the eye as a novel function (where this had not been proposed previously). When an impact from any object is imminent from in front of or above the head, the upper lid shuts in pigeons, owls and oscines, and with water splashing, the lower lid as well (Cinclus). The most convincing evidence for mechanical protection comes from the deployment of the upper lid during the picking up of spiny insect prey as compared to easy-to-swallow berries, when both lids stay at rest (Gallicolumba).Further, the response of the upper lid is more stimulus-oriented so that both upper lids move asymmetrically. But there is also a unilateral, alternating winking of the upper lids when causative (predator) stimuli remain stationary. This never occurs with the lower lids (Otus). As an exception, an adaptive asymmetry occurs during brief phases of unilateral scanning interrupting sleep, designed to detect approaching predators. This scanning involves the lower lid (Anas).A new function is also attributed to the beating of the nictitating membrane (Membrana nictitans). Traditionally viewed as a cleaning device it also serves to protect the eye from mechanical impact, and it also can be tuned to the side from where danger is threatening, though by and large there is a dearth of information from avian taxa. The non-visually elicited action of the membrane seems always to be bilateral (Falco, Harpia). The very stimuli eliciting the blinking of a lid can, in different species, trigger the beat of the membrane, and can cause it to move tonically (Falco). The membrane beats at a rate difficult to measure since many of its beats coincide with the blinking of the upper lid and thus remain hidden (Otus). This coincidence is difficult to account for by any function discussed so far, as are the many hidden beats during tonic eye closure with the lids (Passer).The hypothesis according to which the action of the membrane is filtering out undesirable retinal stimulation during e.g. rapid head movements is dismissed on four different grounds. The increase of the membrane activity during predator alarm (Ficedula) is functionally unaccounted for.In a fashion unique among birds, the Blue Nuthatch (Sitta azurea) protects its eyes by contracting the naked skin surrounding the eye, thereby minimizing the exposure of the cornea; during foraging along the underside of branches, a continual rain of bark particles and debris jeopardizes unimpeded vision.Secondarily, one or both lids or the nictitating membrane have taken on the function of optic signals by virtue of contrasting feather colour or coloration. The phasic (flashing) signal movements involved are directed at the pair mate (Cinclus, Corvidae,Cepphus), predators (Anas) or at unknown parties (Ficedula).

Dies ist Veröffentlichung Nr. 29 des Philippine Endemic Species Conservation Project der Zoologischen Gesellschaft Frankfurt.     

Possible roles of beta-catenin in evagination of the optic primordium in rat embryos

The roles of beta-catenin in evagination of the optic primordium in rat embryos were studied using immunostaining. High levels of beta-catenin appeared transiently in the evaginating optic primordium. Evagination of the optic primordium was suppressed in embryos treated with LiCl. In deficient optic vesicles of these embryos, accumulation of beta-catenin was decreased. Deficient optic vesicles also showed suppression of cyclin D1 accumulation and bromodeoxyuridine incorporation, no break in the deposition of laminin and type IV collagen at the basement membrane (BM) and prevention of the change in distribution of microtubules and microfilaments. These results suggest that beta-catenin regulates cell proliferation, breakdown of BM and changes in cell shape in the evaginating optic primordium to cause optic vesicle formation.     

Serotonin in pain and analgesia

The purpose of this article is to summarize recent findings on the role of serotonin in pain processing in the peripheral nervous system. Serotonin (5-hydroxtryptamine [5-HT]) is present in central and peripheral serotonergic neurons, it is released from platelets and mast cells after tissue injury, and it exerts algesic and analgesic effects depending on the site of action and the receptor subtype. After nerve injury, the 5-HT content in the lesioned nerve increases. 5-HT receptors of the 5-HT₃ and 5-HT_2A subtype are present on C-fibers. 5-HT, acting in combination with other inflammatory mediators, may ectopically excite and sensitize afferent nerve fibers, thus contributing to peripheral sensitization and hyperalgesia in inflammation and nerve injury.     

Ischemic preconditioning ameliorates microcirculatory disturbance through downregulation of TNF-alpha production in a rat cremaster muscle model

Ischemia-reperfusion (I/R) injury is a complex process involving the generation and release of inflammatory cytokines, and the accumulation and infiltration of neutrophils and macrophages, which disturbs the microcirculatory hemodynamics. Nonetheless, ischemic preconditioning (IPC) is known to produce immediate tolerance to subsequent prolonged I/R insults, although its underlying mechanism largely remains unknown. Our study investigated the role of the IB--NF-B-TNF- (tumor necrosis factor-) pathway in IPC's ability to ameliorate I/R-induced microcirculatory disturbances in rat cremaster muscle flaps. Male Sprague-Dawley rats were randomized (n=8 per group) into 3 groups: a sham-operated control group, an I/R group (4 h of pudic epigastric artery ischemia followed by 2 h of reperfusion), and an IPC+I/R group (3 cycles of 10 min of ischemia followed by 10 min reperfusion before I/R). Intravital microscopy was used to observe leukocyte/endothelial cell interactions and quantify functional capillaries in cremaster muscles. I/R markedly increased the number of rolling, adhering, and migrating leukocytes. It was also observed that I/R significantly increased TNF- expression in these injured tissues. On the other hand, IPC prevented I/R-induced increases in leukocyte rolling, adhesion, and transmigration. Moreover, TNF- protein production and its mRNA expression were downregulated in the IPC group. Finally, I/R-induced IB- phosphorylation and NF-B (p65) nuclear translocation were both suppressed by IPC. These results indicated that IPC attenuated NF-B activation and subsequently reduced TNF- expression, which resulted in the amelioration of microcirculatory disturbances in I/R-injured cremaster muscles.