Future prospects of relic bog dweller Carabus menetriesi in the face of climate change

Der Hochmoorlaufkäfer (Carabus menetriesi pacholei) ist eine prioritäre Anhang-Art der FFH-Richtlinie und Art mit hoher Schutzverantwortung Deutschlands. Seine Lebensräume liegen in noch weitgehend intakten Hoch-, Übergangs- und Hochlagen-Quellmooren einschließlich von Moorwäldern. In einem prognostizierten, wärmer und trockener werdenden Klima werden einige Vorkommen außerhalb der hier vorgelegten Klimahülle zu liegen kommen und daher für die Art voraussichtlich verloren gehen. Das gilt in besonderem Maße für die endemischen Vorkommen im Voralpengebiet. Andere Vorkommen werden nur zu halten sein, wenn jegliche Anstrengungen unternommen werden, einen naturnahen Wasserhaushalt wiederherzustellen. Die Klimahülle für die Nominatform reicht etwas weiter in den trockenen und auch warmen Bereich, erfordert aber ebenfalls sämtliche Bemühungen zu ihrem Erhalt. Zu den notwendigen Maßnahmen gehört unter anderem auch die konsequente Erhaltung naturnaher Moor- und Moorrandwälder. Eine Theorie zur Erklärung der disjunkten Verbreitung im Voralpengebiet basierend auf der Vereisungsgeschichte wird präsentiert, da die Klimaverhältnisse allein die Verbreitung nicht erklären können.The raised bog large ground beetle (Carabus menetriesi pacholei) is listed as a priority species in Annex II of the EU Habitat Directive, and is a subspecies for which Germany has a very high conservation responsibility. Its habitats are largely intact raised and transitional bogs and high-elevation spring bogs, including bog forests. In the future climate that is predicted to be warmer and drier, some of this species’ habitats will likely be lost. This is particularly true for the endemic subspecies living in the pre-Alps. Other sites will only be retained if measures are undertaken to reestablish a semi-natural water regime. Among other necessary management measures is strict conservation of all natural and semi-natural bog forests and bog-edge forests. Although the climate envelope for the nominate subspecies extends farther into a drier and also slightly warmer climate, measures to protect its habitat are also warranted. A theory explaining the limited distribution in the prealpine region based on the Ice Age history is presented, since its distribution cannot be explained by the present climatic conditions alone

Carboxylate ion pairing with alkali-metal ions for β-Lactoglobulin and its role on aggregation and interfacial adsorption

We report a combined experimental and computational study of the whey protein β-lactoglobulin (BLG) in different electrolyte solutions. Vibrational sum-frequency generation (SFG) and ellipsometry were used to investigate the molecular structure of BLG modified air–water interfaces as a function of LiCl, NaCl, and KCl concentrations. Molecular dynamics (MD) simulations and thermodynamic integration provided details of the ion pairing of protein surface residues with alkali-metal cations. Our results at pH 6.2 indicate that BLG at the air–water interface forms mono- and bilayers preferably at low and high ionic strength, respectively. Results from SFG spectroscopy and ellipsometry are consistent with intimate ion pairing of alkali-metal cations with aspartate and glutamate carboxylates, which is shown to be more effective for smaller cations (Li⁺ and Na⁺). MD simulations show not only carboxylate–alkali-metal ion pairs but also ion multiplets with the alkali-metal ion in a bridging position between two or more carboxylates. Consequently, alkali-metal cations can bridge carboxylates not only within a monomer but also between monomers, thus providing an important dimerization mechanism between hydrophilic surface patches

The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus of male mice

Disturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic, and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. We here demonstrate that the deletion of Fkbp5 in Sim1(+) neurons dampens the acute stress response and increases GR sensitivity. In contrast, Fkbp5 overexpression in the PVN results in a chronic HPA axis over-activation, and a PVN-specific rescue of Fkbp5 expression in full Fkbp5 KO mice normalizes the HPA axis phenotype. Single-cell RNA sequencing revealed the cell-type-specific expression pattern of Fkbp5 in the PVN and showed that Fkbp5 expression is specifically upregulated in Crh(+) neurons after stress. Finally, Crh-specific Fkbp5 overexpression alters Crh neuron activity, but only partially recapitulates the PVN-specific Fkbp5 overexpression phenotype. Together, the data establish the central and cell-type-specific importance of Fkbp5 in the PVN in shaping HPA axis regulation and the acute stress response

Tumor Invasion of Salmonella enterica Serovar Typhimurium Is Accompanied by Strong Hemorrhage Promoted by TNF-α

BACKGROUND:Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS:We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION:Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Molekulare und funktionelle Charakterisierung kommunizierender Kanäle

Pannexin (Panx) 1 und 2 sind multimere Kanalproteine, deren Eigenschaften in dieser Arbeit untersucht wurden. Durch Koexpressionsstudien und TEVC Messungen in $\textit {X. laevis}$ Oozyten wurde eine Formation heteromerer Kanäle ausgeschlossen. Die Analyse chimärer Proteine zeigte, dass in beiden Proteinen eine Interaktion des C- und des N-terminalen Teils gegeben sein muss. Sequenzanalysen zu Panx2 ergaben, dass die Expression zweier Isoformen von 664 oder 674 Aminosäuren (aa) Länge durch zwei Startcodons möglich ist. Panx2-674 bildet spannungsgesteuerte Kanäle und stellt die native Form des Panx2 Proteins dar. Durch Trunkierung wurde die C-terminale Domäne von Panx1 untersucht. Der C-Terminus ist für die Spannungssensitivität nicht verantwortlich. Eine Interaktionsstelle für den Inhibitor Cbx wurde zwischen aa 327 - 347 lokalisiert. Überlebensstudien zeigten, dass sich die Position der in der Apoptose wichtigen Casp3/7 Schnittstelle evolutiv unter hohem selektivem Druck entwickelt haben muss

Zu den Auswirkungen des SanInsFoG auf die umsatzsteuerliche Organschaft bei vorläufiger Eigenverwaltung: Zugleich Einordnung des BMF-Schreibens vom 22.06.2021 (22.06.2021, III C 2 – S 7105/20/10001 :001)

National audienceZum 01.01.2021 traten im Rahmen des Sanierungsfortentwicklungsgesetzes (SanInsFoG) umfangreiche Änderungen der InsO in Kraft, welche sich ua auf das Eigenverwaltungsverfahren (§§ 270 ff. InsO) beziehen. Vor diesem Hintergrund reagierte die Finanzverwaltung, ergänzte das BMF-Schreiben vom 04.03.2021 und erweiterte den Umsatzsteueranwendungserlass in Abschn. 2.8 Abs. 12 UStAE um Satz 7. Damit ist § 276a InsO a.F. für vorläufige Eigenverwaltungsverfahren, die zwischen dem 01.01.2021 und dem 31.12.2021 angeordnet werden – unter Maßgabe des § 5 Abs. 1 COVInsAG – weiter anwendbar. Der vorliegende Beitrag diskutiert umsatzsteuerliche Implikationen des ergänzten BMF-Schreibens im Rahmen der vorläufigen Eigenverwaltung

Mixed Layers of β‑Lactoglobulin and SDS at Air–Water Interfaces with Tunable Intermolecular Interactions

Mixtures of β-lactoglobulin (BLG) and sodium dodecyl sulfate (SDS) were studied at pH 3.8 and 6.7 under equilibrium conditions. At these pH conditions, BLG carries either a positive or a negative net charge, respectively, which enables tunable electrostatic interactions between anionic SDS surfactants and BLG proteins. For pH 3.8, vibrational sum-frequency generation (SFG) and ellipsometry indicate strong BLG–SDS complex formation at air–water interfaces that is caused by attractive electrostatic interactions. The latter complexes are already formed in the bulk solution which was confirmed by a thermodynamic study of BLG–SDS mixtures using isothermal titration calorimetry (ITC). For acidic conditions we determine from our ITC data an exothermal binding enthalpy of −40 kJ mol^–1. Increasing SDS/BLG molar ratios above 10 leads to a surface excess of SDS and thus to a charge reversal from a positive net charge with BLG as the dominating surface adsorbed species to a negatively charged layer with SDS as the dominating surface species. The latter is evidenced by a pronounced minimum in SFG intensities that is also accompanied by a phase change of O–H stretching bands due to a reorientation of H₂O within the local electric field. This phase change which occurs at SDS/BLG molar ratio between 1 and 10 causes a polarity change in SFG intensities from BLG aromatic C–H stretching vibrations. Conclusions from SFG spectra are corroborated by ellipsometry which shows a dramatic increase in layer thicknesses at molar ratios where a charge reversal occurs. The formation of interfacial multilayers comprising SDS-BLG complexes is, thus, caused by cancellation of electrostatic interactions which leads to agglomeration at the interface. In contrast to pH 3.8, behavior of BLG–SDS mixtures at pH 6.7 is different due to repulsive electrostatic interactions between SDS and BLG which lead to a significantly reduced binding enthalpy of −17 kJ mol^–1. Finally, it has to be mentioned that SFG spectra show a coexistence of BLG and SDS molecules at the interface for BLG–SDS molar ratios > 2