Hartmut Broszinski, Manuscripta chemica in Quarto

La Landes- und Murhardsche Bibliothek de Kassel possède 259 manuscrits alchimiques, presque tous en allemand et ayant presque tous appartenu à Maurice le Savant, landgrave de Hesse-Kassel (1572-1632). Ce catalogue est le premier à en décrire la partie la plus vaste : les 164 manuscrits in-4°, regroupés sous 108 cotes (restent encore à décrire 34 manuscrits in-folio et 61 in-8°). Dès 1986, H. Broszinski avait publié sur ce fonds exceptionnel un article prometteur (in Die Alchemie in der europä..

Comment les acteurs de l’énergie du Rhin supérieur perçoivent-ils le changement climatique et se configurent-ils par rapport à la transition énergétique ?

La transition énergétique transforme les acteurs de l’énergie en réaction ou en prévoyance face au changement climatique, qui réoriente l’action des collectivités territoriales et incite les fournisseurs d’énergie à proposer des énergies renouvelables dans un contexte marqué par les contraintes du marché et par les incertitudes juridiques liées à ce secteur d’activité. Alors que les collectivités territoriales, parfois partenaires financiers, sont engagées dans une démarche de marketing territorial, les énergéticiens ont généralement des stratégies de place forte dans leur territoire d’implantation et de placement dans leur démarche de croissance externe. L’article analyse le changement climatique comme un phénomène construit socialement et le place dans le cadre du projet Clim’Ability, qui a donné lieu à des interviews dans le contexte du Rhin supérieur, en distinguant l’action des collectivités dans le domaine énergétique, puis l’action des énergéticiens dans leur territoire, en recherchant leur empreinte sur le climat, et enfin sur la détermination d’une typologie des stratégies d’énergéticiens dans le Rhin supérieur.Die Energiewende verändert die Energieakteure als Reaktion auf oder im Vorgriff auf den Klimawandel, was die Maßnahmen der lokalen Behörden neu ausrichtet und die Energieversorger ermutigt, erneuerbare Energien in einem Kontext vorzuschlagen, der durch Marktzwänge und Rechtsunsicherheiten im Zusammenhang mit diesem Wirtschaftszweig gekennzeichnet ist. Während lokale Behörden, manchmal auch Finanzpartner, einen territorialen Marketingansatz verfolgen, verfügen Energieunternehmen in der Regel über starke Marktstrategien in ihrem Hoheitsgebiet und investieren in ihren externen Wachstumsansatz. Der Artikel analysiert den Klimawandel als gesellschaftlich konstruiertes Phänomen und stellt ihn in den Rahmen des Projekts Clim’Ability, das Interviews im Kontext des Oberrheins auslöste, in denen das Handeln der Kommunen im Energiebereich; dann das Handeln der Energieunternehmen in ihrem Gebiet; durch die Suche nach ihrem Klima-Fußabdruck; und schließlich zur Bestimmung einer Typologie von Energiestrategien am Oberrhein.The energy transition is transforming energy players in response to or in anticipation of climate change, which is reorienting the action of local authorities and encouraging energy suppliers to propose renewable energies in a context marked by market constraints and by the legal uncertainties linked to this sector of activity. While local authorities, sometimes financial partners, are engaged in a territorial marketing approach, energy companies generally have strong market strategies in their territory of establishment and investment in their external growth approach. The article analyses climate change as a socially constructed phenomenon and places it within the framework of the Clim’Ability project, which gave rise to interviews in the context of the Upper Rhine, distinguishing the action of local authorities in the energy field; then the action of energy companies in their territory; by seeking their climate footprint; and finally on the determination of a typology of energy strategies in the Upper Rhine

Response to "Toward Unified Satellite Climatology of Aerosol Properties. 3. MODIS Versus MISR Versus AERONET"

A recent paper by Mishchenko et al. compares near-coincident MISR, MODIS, and AERONET aerosol optical depth (AOD) products, and reports much poorer agreement than that obtained by the instrument teams and others. We trace the reasons for the discrepancies primarily to differences in (1) the treatment of outliers, (2) the application of absolute vs. relative criteria for testing agreement, and (3) the ways in which seasonally varying spatial distributions of coincident retrievals are taken into account

The effect of an intracerebroventricular injection of metformin or AICAR on the plasma concentrations of melatonin in the ewe: potential involvement of AMPK?

<p>Abstract</p> <p>Background</p> <p>It is now widely accepted that AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis. Recently, it has been shown to regulate circadian clocks. In seasonal breeding species such as sheep, the circadian clock controls the secretion of an endogenous rhythm of melatonin and, as a consequence, is probably involved in the generation of seasonal rhythms of reproduction. Considering this, we identified the presence of the subunits of AMPK in different hypothalamic nuclei involved in the pre- and post-pineal pathways that control seasonality of reproduction in the ewe and we investigated if the intracerebroventricular (i.c.v.) injection of two activators of AMPK, metformin and AICAR, affected the circadian rhythm of melatonin in ewes that were housed in constant darkness. In parallel the secretion of insulin was monitored as a peripheral metabolic marker. We also investigated the effects of i.c.v. AICAR on the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in brain structures along the photoneuroendocrine pathway to the pineal gland.</p> <p>Results</p> <p>All the subunits of AMPK that we studied were identified in all brain areas that were dissected but with some differences in their level of expression among structures. Metformin and AICAR both reduced (p < 0.001 and p < 0.01 respectively) the amplitude of the circadian rhythm of melatonin secretion independently of insulin secretion. The i.c.v. injection of AICAR only tended (p = 0.1) to increase the levels of phosphorylated AMPK in the paraventricular nucleus but significantly increased the levels of phosphorylated ACC in the paraventricular nucleus (p < 0.001) and in the pineal gland (p < 0.05).</p> <p>Conclusions</p> <p>Taken together, these results suggest a potential role for AMPK on the secretion of melatonin probably acting trough the paraventricular nucleus and/or directly in the pineal gland. We conclude that AMPK may act as a metabolic cue to modulate the rhythm of melatonin secretion.</p

LRP1 Receptor Controls Adipogenesis and Is Up-Regulated In Human and Mouse Obese Adipose Tissue

The cell surface low-density lipoprotein receptor-related protein 1, LRP1, plays a major role in lipid metabolism. The question that remains open concerns the function of LRP1 in adipogenesis. Here, we show that LRP1 is highly expressed in murine preadipocytes as well as in primary culture of human adipocytes. Moreover, LRP1 remains abundantly synthesised during mouse and human adipocyte differentiation. We demonstrate that LRP1 silencing in 3T3F442A murine preadipocytes significantly inhibits the expression of PPARγ, HSL and aP2 adipocyte differentiation markers after adipogenesis induction, and leads to lipid-depleted cells. We further show that the absence of lipids in LRP1-silenced preadipocytes is not caused by lipolysis induction. In addition, we provide the first evidences that LRP1 is significantly up-regulated in obese C57BI6/J mouse adipocytes and obese human adipose tissues. Interestingly, silencing of LRP1 in fully-differentiated adipocytes also reduces cellular lipid level and is associated with an increase of basal lipolysis. However, the ability of mature adipocytes to induce lipolysis is independent of LRP1 expression. Altogether, our findings highlight the dual role of LRP1 in the control of adipogenesis and lipid homeostasis, and suggest that LRP1 may be an important therapeutic target in obesity

The response of the host microcirculation to bacterial sepsis: Does the pathogen matter?

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte-endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure

Chemical Library Screening and Structure-Function Relationship Studies Identify Bisacodyl as a Potent and Selective Cytotoxic Agent Towards Quiescent Human Glioblastoma Tumor Stem-Like Cells

Cancer stem-like cells reside in hypoxic and slightly acidic tumor niches. Such microenvironments favor more aggressive undifferentiated phenotypes and a slow growing "quiescent state" which preserves them from chemotherapeutic agents that essentially target proliferating cells. Our objective was to identify compounds active on glioblastoma stem-like cells, including under conditions that mimick those found in vivo within this most severe and incurable form of brain malignancy. We screened the Prestwick Library to identify cytotoxic compounds towards glioblastoma stem-like cells, either in a proliferating state or in more slow-growing "quiescent" phenotype resulting from non-renewal of the culture medium in vitro. Compound effects were assessed by ATP-level determination using a cell-based assay. Twenty active molecules belonging to different pharmacological classes have thus been identified. Among those, the stimulant laxative drug bisacodyl was the sole to inhibit in a potent and specific manner the survival of quiescent glioblastoma stem-like cells. Subsequent structure-function relationship studies led to identification of 4,4'-dihydroxydiphenyl-2-pyridyl-methane (DDPM), the deacetylated form of bisacodyl, as the pharmacophore. To our knowledge, bisacodyl is currently the only known compound targeting glioblastoma cancer stem-like cells in their quiescent, more resistant state. Due to its known non-toxicity in humans, bisacodyl appears as a new potential anti-tumor agent that may, in association with classical chemotherapeutic compounds, participate in tumor eradication

Wheat germ in vitro translation to produce one of the most toxic sodium channel specific toxins

Envenoming following scorpion sting is a common emergency in many parts of the world. During scorpion envenoming, highly toxic small polypeptides of the venom diffuse rapidly within the victim causing serious medical problems. The exploration of toxin structure-function relationship would benefit from the generation of soluble recombinant scorpion toxins in Escherichia coli. We developed an in vitro wheat germ translation system for the expression of the highly toxic Aah (Androctonus australis hector)II protein that requires the proper formation of four disulphide bonds. Soluble, recombinant N-terminal GST (glutathione S-transferase)-tagged AahII toxin is obtained in this in vitro translation system. After proteolytic removal of the GST-tag, purified rAahII (recombinant AahII) toxin, which contains two extra amino acids at its N terminal relative to the native AahII, is highly toxic after i.c.v. (intracerebroventricular) injection in Swiss mice. An LD50 (median lethal dose)-value of 10 ng (or 1.33 pmol), close to that of the native toxin (LD50 of 3 ng) indicates that the wheat germ in vitro translation system produces properly folded and biological active rAahII. In addition, NbAahII10 (Androctonus australis hector nanobody 10), a camel single domain antibody fragment, raised against the native AahII toxin, recognizes its cognate conformational epitope on the recombinant toxin and neutralizes the toxicity of purified rAahII upon injection in mice