Beobachtungen über Veränderungen des Gehaltes an organischen Säuren im Blutungssaft von Birke (Betula alba) und Ahorn (Acer Pseudoplatanus)

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Über die Aufzucht Isolierter Teile des Amphibienkeimes

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Witterungseinflüsse auf die Pigmentbildung der Wiesenpflanzen und den Vitamin A-Gehalt der Milchfette

Zusammenfassung Der Carotin-, Chlorophyll a- und b-Gehalt (Pigment) in Gras von Weiden in 600 m Höhe am nördlichen Alpenrand (Südbayern) und der Vitamin A-Gehalt im Milchfett von Kühen im Stall nach Fütterung mit dem Gras wurde bestimmt und mit den Ergebnissen der meteorologischen Beobachtungen verglichen. Die Pigmentbildung in den Pflanzen wurde durch warme strahlungsreiche Witterung gefördert und durch starke TemperaturrückgÄnge und Bodenfröste gehemmt. Sie war ausserdem vom Standort abhÄngig: an S-HÄngen und auf Höhen in strahlungsgünstiger Lage war in sonnigen Perioden der Carotingehalt hoch, in Niederungen mit hÄufiger Nebelbildung, auf schattigen HÄngen und in Tallagen mit Kaltluft tief. In Witterungsperioden mit Bewölkung glich der höhere Anteil der Himmelsstrahlung die Expositionsunterschiede wieder aus. Extrem grosse Licht- und WÄrmeeinwirkungen sommerlicher Hitzeperioden hemmten die Pigmentbildung; der Milch Vitamin A-Gehalt zeigte gleichsinnige Schwankungen.

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Carotine, chlorophyll a and b (pigment) in some types of meadow grass (600 m) at the northern rim of the Alps and the vitamin A content in milk from cows in stables fed on this grass was determined and correlated with meteorological data. The pigment formation in the grass was enhanced by radiation-rich warm weather and was impeded by a fall in temperature and ground frosts. The carotine content was high in grass from south slopes and on hills in a favourable position for radiation during sunny periods and low in grass from low sites with cold air.During periods of cloudy weather the greater amount of sky radiation compensated for the smaller amount of exposure in the less favourable sites. Extremely strong effects of light and warmth during summer heat periods inhibited the pigment formation and there was also a similar change in the vitamin A content of the milk.

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Résumé La teneur en carotène et en chlorophylle a et b (pigment) de quelques herbes de prairies du nord des Alpes (Bavière) et la teneur en vitamine A du lait des vaches qui en furent nourries en étables ont été comparées à des données méteorologiques. La formation des pigments des herbages était accrue par un temps chaud et ensoleillé et était diminué par les chutes de température et le refroidissement du sol. Le taux de carotène des herbes des pentes exposées au sud et sur les collines était élevé durant les périodes de soleil, et bas dans les fonds de vallées exposées à l'air froid et sur les pentes à l'ombre. Pendant les périodes nuageuses, la plus grande luminosité du ciel compensait les différences dans 1'exposition.La formation de pigments était ralentie en été pendant les périodes de grandes chaleurs et d'irradiation extrèmes. Le contenu du lait en vitamine A montrait des variations dans le mÊme sens.

     

The Antibody Light-Chain Linker Regulates Domain Orientation and Amyloidogenicity

The antibody light chain (LC) consists of two domains and is essential for antigen binding in mature immunoglobulins. The two domains are connected by a highly conserved linker that comprises the structurally important Arg108 residue. In antibody light chain (AL) amyloidosis, a severe protein amyloid disease, the LC and its N-terminal variable domain (V_L) convert to fibrils deposited in the tissues causing organ failure. Understanding the factors shaping the architecture of the LC is important for basic science, biotechnology and for deciphering the principles that lead to fibril formation. In this study, we examined the structure and properties of LC variants with a mutated or extended linker. We show that under destabilizing conditions, the linker modulates the amyloidogenicity of the LC. The fibril formation propensity of LC linker variants and their susceptibility to proteolysis directly correlate implying an interplay between the two LC domains. Using NMR and residual dipolar coupling-based simulations, we found that the linker residue Arg108 is a key factor regulating the relative orientation of the V_L and C_L domains, keeping them in a bent and dense, but still flexible conformation. Thus, inter-domain contacts and the relative orientation of V_L and C_L to each other are of major importance for maintaining the structural integrity of the full-length LC.     

Suppression of oxidative phosphorylation confers resistance against bevacizumab in experimental glioma

Although bevacizumab initially shows high response rates in gliomas and other tumours, therapy resistance usually develops later. Because anti‐angiogenic agents are supposed to induce hypoxia, we asked whether rendering glioma cells independent of oxidative phosphorylation modulates their sensitivity against hypoxia and bevacizumab. LNT‐229 glioma cells without functional mitochondria (rho⁰) and control (rho⁺) cells were generated. LNT‐229 rho⁰‐cells displayed reduced expression of oxidative phosphorylation‐related genes and diminished oxygen consumption. Conversely, glycolysis was up‐regulated in these cells, as shown by increased lactate production and stronger expression of glucose transporter‐1 and lactate dehydrogenase‐A. However, hypoxia‐induced cell death in vitro was nearly completely abolished in the LNT‐229 rho⁰‐cells, these cells were more sensitive towards glucose restriction and the treatment with the glycolysis inhibitor 2‐deoxy‐D‐glucose. In an orthotopic mouse xenograft experiment, bevacizumab induced hypoxia as reflected by elevated Hypoxia‐inducible factor 1‐alpha staining in both, rho⁺‐ and rho⁰‐tumours. However, it prolonged survival only in the mice bearing rho⁺‐tumours (74 days vs. 105 days, p  = 0.024 log‐rank test) and had no effect on survival in mice carrying LNT‐229 rho⁰‐tumours (75 days vs. 70 days, p  = 0.52 log‐rank test). Interestingly, inhibition of glycolysis in vivo with 2‐deoxy‐D‐glucose re‐established sensitivity of rho⁰‐tumours against bevacizumab (98 days vs. 80 days, p  = 0.0001). In summary, ablation of oxidative phosphorylation in glioma cells leads to a more glycolytic and hypoxia‐resistant phenotype and is sufficient to induce bevacizumab‐refractory tumours. These results add to increasing evidence that a switch towards glycolysis is one mechanism how tumour cells may evade anti‐angiogenic treatments and suggest anti‐glycolytic strategies as promising approaches to overcome bevacizumab resistance.