Canine recurrent flank alopecia: a synthesis of theory and practice

Canine recurrent flank alopecia is a non-inflammatory, non-scarring alopecia of unknown etiology and has a visually striking clinical presentation. Although this disease entity is relatively common in the northern hemisphere, there is only scant information in the literature regarding case descriptions. The aim of this article was to review the literature and to describe clinical presentations recognized in practice, which are not always extensively documented in the literature

Comparison of seven portable Raman spectrometers : beryl as a case study

In this paper, a series of beryl varieties with the accent on emeralds was investigated using seven portable Raman spectrometers equipped mainly with 785- and 532-nm excitation lasers. Additionally, one dual system and a new portable sequentially shifted excitation Raman spectrometer were applied. The advantage of using handheld instrumentation for investigations to be carried out outside the laboratory is well documented. For major part of beryls (emeralds and aquamarines), the most intense Raman bands are found at correct positions +/-2 to 4cm(-1) using all the instruments (with the exception of one). Unambiguous identification of beryls is ensured by obtaining the strong characteristic of Raman features (1070 and 686 cm(-1)) of the whole spectrum. Spectroscopic performance and differences existing between the instruments not only from the construction and ergonomic point of view are discussed. All the instruments tested EzRaman-I Dual (Enwave Optronics), RaPort (EnSpectr), FirstGuard (Rigaku), FirstDefender XL and FirstDefender RM (Thermo Scientific), Inspector Raman (Delta Nu) and Bravo (Bruker) can be used for common gemmological and mineralogical work in situ. Two instruments (the RaPort and the sequentially shifted excitation Raman spectrometer Bravo) allow recording excellent quality Raman spectra comparable with laboratory dispersive Raman microspectrometers

Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation

Aberrant detection of endogenous nucleic acids by the immune system can cause inflammatory disease. The scaffold function of the signaling kinase RIPK1 limits spontaneous activation of the nucleic acid sensor ZBP1. Consequently, loss of RIPK1 in keratinocytes induces ZBP1-dependent necroptosis and skin inflammation. Whether nucleic acid sensing is required to activate ZBP1 in RIPK1-deficient conditions and which immune pathways are associated with skin disease remained open questions. Using knock-in mice with disrupted ZBP1 nucleic acid–binding activity, we report that sensing of endogenous nucleic acids by ZBP1 is critical in driving skin pathology characterized by antiviral and IL-17 immune responses. Inducing ZBP1 expression by interferons triggers necroptosis in RIPK1-deficient keratinocytes, and epidermis-specific deletion of MLKL prevents disease, demonstrating that cell-intrinsic events cause inflammation. These findings indicate that dysregulated sensing of endogenous nucleic acid by ZBP1 can drive inflammation and may contribute to the pathogenesis of IL-17–driven inflammatory skin conditions such as psoriasis

La boxa, Clint i jo (I)

Abstract not availabl

Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes

Cancer immunotherapy can induce durable antitumor responses. However, many patients poorly respond to such therapies. Here we describe a generic antitumor therapy that is based on the intratumor delivery of mRNA that codes for the necroptosis executioner mixed lineage kinase domain-like (MLKL) protein. This intervention stalls primary tumor growth and protects against distal and disseminated tumor formation in syngeneic mouse melanoma and colon carcinoma models. Moreover, MLKL-mRNA treatment combined with immune checkpoint blockade further improves the antitumor activity. MLKL-mRNA treatment rapidly induces T cell responses directed against tumor neo-antigens and requires CD4(+) and CD8(+) T cells to prevent tumor growth. Type I interferon signaling and Batf3-dependent dendritic cells are essential for this mRNA treatment to elicit tumor antigen-specific T cell responses. Moreover, MLKL-mRNA treatment blunts the growth of human lymphoma in mice with a reconstituted human adaptive immune system. MLKL-based treatment can thus be exploited as an effective antitumor immunotherapy

Necroptosis in immuno-oncology and cancer immunotherapy

Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To "break" cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy

Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice

TNF is an important mediator in numerous inflammatory diseases, e.g., in inflammatory bowel diseases (IBDs). In IBD, acute increases in TNF production can lead to disease flares. Glucocorticoids (GCs), which are steroids that bind and activate the glucocorticoid receptor (GR), are able to protect animals and humans against acute TNF-induced inflammatory symptoms. Mice with a poor transcriptional response of GR dimer-dependent target genes were studied in a model of TNF-induced lethal inflammation. In contrast to the GRWT/WT mice, these GRdim/dim mice displayed a substantial increase in TNF sensitivity and a lack of protection by the GC dexamethasone (DEX). Unchallenged GRdim/dim mice had a strong IFN-stimulated gene (ISG) signature, along with STAT1 upregulation and phosphorylation. This ISG signature was gut specific and, based on our studies with antibiotics, depended on the gut microbiota. GR dimers directly bound to short DNA sequences in the STAT1 promoter known as inverted repeat negative GRE (IR-nGRE) elements. Poor control of STAT1 in GRdim/dim mice led to failure to repress ISG genes, resulting in excessive necroptosis induction by TNF. Our findings support a critical interplay among gut microbiota, IFNs, necroptosis, and GR in both the basal response to acute inflammatory challenges and pharmacological intervention by GCs

Informaticawetenschappen in het leerplichtonderwijs

Dit standpunt bepleit en beargumenteert de noodzaak om elke jongere een opleiding informaticawetenschappen aan te bieden die toelaat om ’informaticavaardig’ te worden. Informaticavaardigheid gaat verder dan louter ‘digitale geletterdheid’, en houdt ook in dat de jongere in staat moet zijn ‘computationeel’ te denken. Computers zijn onmisbaar geworden, zowel in het professionele leven als in de privésfeer. Om de technologische evolutie te kunnen volgen is het van groot belang dat alle jongeren niet alleen de bestaande technologie leren gebruiken, maar ook de onderliggende werking leren begrijpen. Om de technologische evolutie te kunnen sturen, is het nodig dat voldoende jongeren in staat en gemotiveerd zijn om nieuwe technologie te creëren. Om deze doelstellingen te realiseren, dient het onderwijs van de informatica in het leerplichtonderwijs grondig hervormd te worden. In het basis- en secundair onderwijs dient een basisopleiding informaticawetenschappen opgenomen te worden, waarop in specifieke STEM richtingen voortgebouwd wordt. Een nieuw leerprogramma, goed opgeleide leraars en een goede informatica-infrastructuur zijn broodnodig. Ons leerplichtonderwijs is de belangrijkste actor om volgende generaties voor te bereiden op het leven, zowel professioneel als privé. De digitalisering van onze maatschappij kan haar voordelen alleen waarmaken als het onderwijs aangepast is aan deze digitale realiteit. Informatica- wetenschappen is een autonome wetenschap geworden met haar eigen manier van denken, en haar eigen basisbegrippen, te vergelijken met wiskunde, natuurkunde, en andere wetenschap- pen, die haar plaats in het onderwijs verdient. Het moet duidelijk zijn dat het hier niet gaat over het onderwijs van de traditionele vakken met de steun van informaticahulpmiddelen maar wel over de informaticawetenschappen zelf als vormend vak. Dit standpunt kwam tot stand binnen een werkgroep, opgericht door de KVAB en de Jonge Academie en samengesteld met leden uit diverse academische disciplines, onderwijsdeskundi- gen en actoren uit de bedrijfswereld