S100B as a potential biomarker and therapeutic target in multiple sclerosis

Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.This work was supported by Medal of Honor L’Oréal for Women in Science (FCT, UNESCO, L’Óreal) and innovation grant (Ordem dos Farmacêuticos) to AF, a post-doctoral grant from Fundação para a Ciência e Tecnologia (FCT-SFRH/BPD/96794/2013) and a DuPré Grant from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to AB, and by FCT-Pest- OE/SAU/UI4013 to iMed.ULisboa.info:eu-repo/semantics/publishedVersio

Die Abgrenzung der Fremdtötung von der eigenverantwortlichen Selbsttötung: Doppelsuizid, erweiterter Suizid oder Homizid-Suizid?

<jats:title>Zusammenfassung</jats:title><jats:p>In der Literatur finden sich vielfach Publikationen und Kasuistiken, die sich mit zeitlich, örtlich, partnerschaftlich und/oder familiär im Zusammenhang stehenden nichtnatürlichen Todesfälle unabhängig von der Art und Weise zweier oder mehrerer Personen auseinandersetzen. Im Nachfolgenden sollen jene Fälle genauer betrachtet werden, bei denen zumindest in einem der Fälle naheliegt, dass es sich beispielsweise aufgrund der Spurenlage um einen freiverantwortlichen Suizidentschluss gehandelt hat. Diese werden u. a. als „erweiterte Suizide“ oder in jüngerer Zeit auch als „Homizid-Suizide“ bezeichnet. Diese theoriespezifizierten Nomenklaturen finden sich nicht zuletzt deshalb berechtigt kritisiert, als dass die Motive, genauen Tatumstände und Tathintergründe oftmals nicht bekannt sind und somit eine (vorgreifende) Wertung erfolgt, ohne dass andere mögliche Tathergänge zur Diskussion gestanden hätten. Daher stellt sich zunächst die Frage nach der generellen und konkreten Eignung dieser Nomenklaturen hinsichtlich ihrer Anwendbarkeit, mit der sich daran anschließenden Überlegung einer neu zu definierenden übergeordneten Bezeichnung. Die Komplexität dieser Begrifflichkeiten soll im Nachfolgenden an dem gemeinsamen Tod eines älteren Ehepaares verdeutlicht werden.</jats:p&gt

Auftragsmord und Anstiftung zum Mord als Varianten des Intimizids

<jats:title>Zusammenfassung</jats:title><jats:p>Dargestellt wird der Fall eines Intimizids, bei dem sich ein Ehemann durch Anstiftung zum Mord seiner Ehefrau entledigen wollte. Auftragsmorde bzw. Anstiftungen zum Mord innerhalb von Paarbeziehungen stellen ein Ausnahmegeschehen dar. Hier sollen die Facetten einer umfangreichen kriminalistischen Fallbearbeitung dargestellt werden, die neben rechtsmedizinischen Erkenntnissen auch wesentliche psychiatrische, psychologische und kriminalistische Aspekte der Tatbegehung bzw. -anstiftung beleuchtet.</jats:p&gt

Preliminary observations of the sequence of damage in excised human juvenile cranial bone at speeds equivalent to falls from 1.6 m

There is much debate within the forensic community around the indications that suggest a head injury sustained by a child resulted from abusive head trauma, rather than from accidental causes, especially when a fall from low height is the explanation given by a caregiver. To better understand this problem, finite element models of the paediatric head have been and continue to be developed. These models require material models that fit the behaviour of paediatric head tissues under dynamic loading conditions. Currently, the highest loading rate for which skull data exists is 2.81 ms-1 19 . This study improves on this by providing preliminary experimental data for a loading rate of 5.65 ± 0.14 ms-1 20 , equivalent to a fall of 1.6 m. Eleven specimens of paediatric cranial bone (frontal, occipital, parietal and temporal) from seven donors (age range 3 weeks – 18 years) were tested in three-point bending with an impactor of radius 2 mm. It was found that prompt brittle fracture with virtually no bending occurring in all specimens but those aged 3 weeks old, where bending preceded brittle fracture. The maximum impact force increased with age (or thickness) and was higher in occipital bone. Energy absorbed to failure followed a similar trend, with values 0.11 and 0.35 mJ/mm3 for age three-weeks, agreeing with previously published static tests, increasing with age up to 9 mJ/mm3 for 18-year-old occipital bone. The preliminary data provided here can help analysts improve pediatric head finite element models that can be used to provide better predictions of the nature of head injuries from both a biomechanical and forensic point of view

Unimolecular ion dissociation and laser-induced coalescence of hydrogenated fullerenes

The ion-fragmentation behaviour of hydrogenated fullerenes has been investigated by tandem mass spectrometry applying sector instrumentation. In addition to the expected loss of hydrogen, unimolecular decay reactions are observed featuring cage rupture by the loss of hydrocarbon moieties. The findings are discussed in comparison with the behaviour of other fullerene derivatives. The gas-phase coalescence reactivity of C60H36 has been studied utilising laser desorption/ionization time-of-flight mass spectrometry. In contrast to pure fullerenes and certain organic fullerene derivatives, hydrogenated fullerenes do not readily undergo laser-induced fusion reactions

Ionic liquids and green chemistry : a lab experiment

Although ionic liquids have been investigated as solvents for many applications and are starting to be used in industrial processes, only a few lab experiments are available to introduce students to these materials. Ionic liquids have been discussed in the context of green chemistry, but few investigations have actually assessed the degree of their greenness. This experiment combines two research areas, ionic liquids and ecological assessment, in an advanced undergraduate lab course. The modular combination of these two research areas allows for the adaptation of the timetable and content. Two ionic liquids are synthesized, and the method of heating (microwave-assisted vs convective), temperature, time, and alkylating agent are varied. In addition to the yield, simple metrics (atom economy, reaction mass efficiency, E-factor) in combination with energy efficiency, prices of chemicals, and ecological impacts of the materials are considered. It is the goal of this experiment to help students realize that a synthetic method leading to quantitative yields is not a priori green: other factors (nature of reactants, energy consumption, etc.) must be assessed as well