IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate cancer cells

The cysteine-type peptidase cathepsin X is highly upregulated in several cancers and presumably promotes tumor invasion through bypassing cellular senescence. Here, we present first evidence that the underlying mechanism may involve the regulation of the insulin-like growth factor (IGF) system, a well-known activator of proliferating tumor cells. Cathepsin X deficiency leads to a reduced phosphorylation of the IGF-I receptor in response to IGF-I stimulation. In addition, downstream signaling through focal adhesion kinase was also affected. Taken together, our results indicate that cathepsin X is able to assist in IGF signaling, which may be an important progress toward understanding cathepsin X-dependent tumorigenesis

Proposal for International Agreement on Ca Notation resulting from discussion at workshops on stable isotope measurement held in Davos (Goldschmidt 2002) and Nice (EGS-AGU-EUG 2003)

A proposal is made to standardise the reporting of Ca isotope data to the δ44Ca/40Ca notation (or δ44Ca/42Ca) and to adopt NIST SRM 915a as the reference standard

Calcium isotopic composition of high-latitude proxy carrier Neogloboquadrina pachyderma (sin.)

International audienceThe accurate reconstruction of sea surface temperature (SST) history in climate-sensitive regions (e.g. tropical and polar oceans) became a challenging task in palaeoceanographic research. However, biogenic shell carbonate SST proxies successfully developed for tropical regions often fail in cool water environments. Their major regional shortcomings and the cryptic diversity now found within the major high latitude proxy carrier Neogloboquadrina pachyderma (sin.) highlight an urgent need to develop complementary SST proxies for these cool water regions. Here we incorporate the genetic component into a calibration study of a new SST proxy for the high latitudes. We found that the calcium isotopic composition (?44/40Ca) of calcite from genotyped net catches and core-top samples of the planktonic foraminifera Neogloboquadrina pachyderma (sin) is strongly related to temperature and unaffected by genetic variations. The temperature sensitivity has been found to be 0.17 (±0.04)? per 1°C highlighting its potential for downcore applications in open marine cool-water environments. Our results further indicate that however in extreme polar environments, below a critical threshold temperature of 2.0 (±0.5)°C and salinity of 33.0 (±0.5)? a prominent shift in biomineralization affect the Ca isotope composition of N. pachyderma (sin.) becoming insensitive to temperature. These findings highlight the need of systematic calibration studies to unravel the influencing factors on Ca isotope fractionation and to validate the proxies' applicability

Getting respected despite our differences: (re-)establishing positive relations through a respectful treatment

Can respect help to re-establish social relations within and between groups- also in situations of intergroup conflict? In the present lines of research, I propose respect to be of fundamental importance for social cohesion within and between groups. I conceive of respect as recognition as an equal (Honneth, 1995, Simon, 2007) and develop an integrative conceptualization and measurement in order to examine its role for intergroup reconciliation (Chapter 2 and 4). I present two studies examining the distinct influence of respect and disrespect as compared to a neutral condition at first within groups and then between groups (Chapter 3). Within groups, a respectful treatment seems equivalent to a neutral treatment and both increased group identification, group-serving motivation, and category salience equivalently when compared to a disrespectful treatment. As opposed, a respectful treatment between groups decreased category salience compared to disrespectful treatment and may benefit to overcome intergroup boundaries. In the context of intergroup conflict, I present five studies (Chapter 5-7) examining the role of respect on the willingness to reconcile between victims and perpetrators (Shnabel & Nadler, 2008). Here, I focused on how the willingness to reconcile is affected by a respectful message in addition to needs-based messages, or alone. Results revealed that respect had a consistent effect on the willingness to reconcile of victims, in addition to the needs-based message. More importantly perceived respect was the central mediating process between manipulated respect and the willingness to reconcile for victims and perpetrators. I discuss theoretical and practical implications of respect for relations within and between groups as well as methodological limitations and challenges in the experimental study of respect (Chapter 8)

Earliest land plants created modern levels of atmospheric oxygen

The progressive oxygenation of the Earth’s atmosphere was pivotal to the evolution of life, but the puzzle of when and how atmospheric oxygen (O2) first approached modern levels (~21%) remains unresolved. Redox proxy data indicate the deep oceans were oxygenated during 435-392 Ma, and the appearance of fossil charcoal indicates O2>15-17% by 420-400 Ma. However, existing models have failed to predict oxygenation at this time. Here we show that the earliest plants, which colonized the land surface from ~470 Ma onwards, were responsible for this mid- Paleozoic oxygenation event, through greatly increasing global organic carbon burial – the net long-term source of O2. We use a trait-based ecophysiological model to predict that cryptogamic vegetation cover could have achieved ~30% of today’s global terrestrial net primary productivity by~445 Ma. Data from modern bryophytes suggests this plentiful early plant material had a much higher molar C:P ratio (~2000) than marine biomass (~100), such that a given weathering flux of phosphorus could support more organic carbon burial. Furthermore, recent experiments suggest that early plants selectively increased the flux of phosphorus (relative to alkalinity) weathered from rocks. Combining these effects in a model of long-term biogeochemical cycling, we reproduce a sustained +2‰ increase in the carbonate carbon isotope (δ13C) record by ~445 Ma, and predict a corresponding rise in O2 to present levels by 420-400 Ma, consistent with geochemical data. This oxygen rise represents a permanent shift in regulatory regime to one where fire-mediated negative feedbacks on organic carbon burial stabilise high O2 levels

Calcium isotope (δ^44/40Ca ) variations of Neogene planktonic foraminifera

Measurements of the calcium isotopic composition (δ44/40Ca) of planktonic foraminifera from the western equatorial Pacific and the Indian sector of the Southern Ocean show variations of about 0.6‰ over the past 24 Myr. The stacked δ44/40Ca record of Globigerinoides trilobus and Globigerina bulloides indicates a minimum in δ44/40Casw (seawater calcium) at 15 to 16 Ma and a subsequent general increase toward the present, interrupted by a second minimum at 3 to 5 Ma. Applying a coupled calcium/carbon cycle model, we find two scenarios that can explain a large portion of the observed δ44/40Casw variations. In both cases, variations in the Ca input flux to the ocean without proportional changes in the carbonate flux are invoked. The first scenario increases the riverine calcium input to the ocean without a proportional increase of the carbonate flux. The second scenario generates an additional calcium flux from the exchange of Ca by Mg during dolomitization. In both cases the calcium flux variations lead to drastic changes in the seawater Ca concentrations on million year timescales. Our δ44/40Casw record therefore indicates that the global calcium cycle may be much more dynamic than previously assumed

Björn Kraus: Relationaler Konstruktivismus - Relationale Soziale Arbeit. Von der systemisch-konstruktivistischen Lebensweltorientierung zu einer Relationalen Theorie Sozialer Arbeit. Weinheim/Basel: Beltz Juventa 2019 (214 S.) [Rezension]

Rezension von: Björn Kraus: Relationaler Konstruktivismus - Relationale Soziale Arbeit. Von der systemisch-konstruktivistischen Lebensweltorientierung zu einer Relationalen Theorie Sozialer Arbeit. Weinheim/Basel: Beltz Juventa 2019 (214 S.; ISBN 978-3-7799-3949-8; 29,95 EUR)

Modulierung der Interaktion zwischen Plasmazellen und der Mikroumgebung zur Behandlung des Multiplen Myeloms

Das Multiple Myelom (MM) gehört zu den häufigsten malignen Erkrankungen des Knochenmarks und betrifft vor allem ältere Menschen. Aufgrund des demografischen Wandels wird in den kommenden Jahren mit einem Anstieg der Fallzahlen gerechnet. Bislang bleibt das MM unheilbar, da die Tumorzellen häufig durch den schützenden Einfluss der Knochenmarksstromazellen (BMSC) sowie durch epigenetische Fehlregulationen eine Resistenz gegenüber Therapien entwickeln. Ziel dieser Arbeit war es, zu untersuchen, ob die epigenetischen Modulatoren Jib-04 und MB-3 die Wirkung der BMSC auf die Resistenzentwicklung im MM verringern können. Jib-04 hemmt die Histon-Demethylierung, während MB-3 die Histonacetylierung blockiert. In verschiedenen Zellkultursystemen wurde die Wirkung der Substanzen auf Zellviabilität und Apoptose untersucht. Die Ergebnisse zeigen, dass in unkonditionierten MM-Zellen Apoptose induziert wurde, während in BMSC-konditionierten Zellen eine synergistische Wirkung erzielt werden konnte. In der Transwell-Kultur nahm der Anteil apoptotischer Zellen ab, und in der direkten Co-Kultur entwickelten die MM-Zellen eine Resistenz gegenüber Jib-04 und MB-3. Dies dürfte vor allem durch parakrine Feedback-Loops und direkte Zell-Zell-Kontakte zwischen BMSC und MM-Zellen bedingt sein. Zudem wurden metabolische Unterschiede in BMSC von Patienten in verschiedenen Krankheitsstadien analysiert, was einen Hinweis auf das Vorliegen des Reverse Warburg Effects bei fortgeschrittenem MM liefert. Insgesamt zeigt die Arbeit, dass BMSC eine zentrale Rolle in der Progression und der Resistenzentwicklung des MM spielen