Atmospheric CO2 forcing on Mediterranean biomes during the past 500 kyrs.

There is growing concern on the survival of Mediterranean forests under the projected near-future droughts as a result of anthropogenic climate change. Here we determine the resilience of Mediterranean forests across the entire range of climatic boundary conditions realized during the past 500 kyrs based on continuous pollen and geochemical records of (sub)centennial-scale resolution from drillcores from Tenaghi Philippon, Greece. Using convergent cross-mapping we provide empirical confirmation that global atmospheric carbon dioxide (CO2) may affect Mediterranean vegetation through forcing on moisture availability. Our analysis documents two stable vegetation regimes across the wide range of CO2 and moisture levels realized during the past four glacial-interglacial cycles, with abrupt shifts from forest to steppe biomes occurring when a threshold in precipitation is crossed. Our approach highlights that a CO2-driven moisture decrease in the near future may bear an impending risk for abrupt vegetation regime shifts prompting forest loss in the Mediterranean region.

Identification and optimization of a novel series of selective PIP5K inhibitors.

Phosphatidyl inositol (4,5)-bisphosphate (PI(4,5)P2) plays several key roles in human biology and the lipid kinase that produces PI(4,5)P2, PIP5K, has been hypothesized to provide a potential therapeutic target of interest in the treatment of cancers. To better understand and explore the role of PIP5K in human cancers there remains an urgent need for potent and specific PIP5K inhibitor molecules. Following a high throughput screen of the AstraZeneca collection, a novel, moderately potent and selective inhibitor of PIP5K, 1, was discovered. Detailed exploration of the SAR for this novel scaffold resulted in the considerable optimization of both potency for PIP5K, and selectivity over the closely related kinase PI3Kα, as well as identifying several opportunities for the continued optimization of drug-like properties. As a result, several high quality in vitro tool compounds were identified (8, 20 and 25) that demonstrate the desired biochemical and cellular profiles required to aid better understanding of this complex area of biology.

Palynological data for the Late Glacial and Holocene (14.5-0 ka BP) from Füramoos, Southern Germany.

We here present high-resolution palynological data from the Füramoos peat bog, located in the alpine foreland of Southern Germany. The data represent raw pollen counts of major arboreal pollen as well as agricultural indicator taxa for the Late Glacial and Holocene (14.5 ka BP to present) at Füramoos with an average temporal resolution of 100 years (50 years during critical intervals). The data are also provided as percentages, which are calculated based on the total sum of pollen grains, excluding pollen grains of sedges (Cyperaceae) and strictly aquatic taxa. The data yield insight into the vegetation dynamics in Central Europe in response to climatic and anthropogenic forcing, which are an integral part of the original research article (Kern et al., 2021). Considering its high temporal resolution and the robust age-depth model, the dataset is ideally suited to be included in regional syntheses of vegetation dynamics in Central Europe from the Late Glacial onwards. In addition to the data, we provide a detailed description of the Füramoos site and detail the palynological processing and analysing techniques used.

XRF core scanning yields reliable semiquantitative data on the elemental composition of highly organic-rich sediments: Evidence from the Füramoos peat bog (Southern Germany).

X-ray fluorescence core scanning (XRF-CS) has become a standard tool in paleoenvironmental studies. Allowing rapid, inexpensive and non-destructive analysis of the elemental composition of sediment cores at high spatial resolution, it is ideally suited for the reconstruction of short-term climatic change. However, its applicability to cores consisting of peat and other highly organic-rich sediments has yet remained poorly explored. We have therefore investigated the application of XRF-CS to two cores consisting of ombrotrophic peat and of fen peat and organic-rich muds of Late Glacial-Holocene and Eemian age, respectively, from a peat bog in Southern Germany using an Avaatech 4th-generation XRF core scanner. The XRF-CS-derived distributions of elements widely used in (paleo)environmental research (i.e., Al, Ca, Fe, K, Mg, Mn, S, Si, and Ti) were systematically compared to the results of inductively coupled plasma optical emission spectrometry analyses. For the Late Glacial-Holocene peat core, XRF-CS yielded reliable semiquantitative data for the majority of the investigated elements (i.e., Ca, Fe, K, Mn, S, Si, and Ti), with R2 ≥ 0.5. XRF-CS of the Eemian fen peat and organic-rich muds yielded reliable data for Al, K, S, and Ti (R2 ≥ 0.5) and, to a lesser extent, for Fe (R2 = 0.46). and Si (R2 = 0.25). This indicates that XRF-CS allows to semiquantitatively reconstruct the distribution of the majority of paleoclimatically relevant elements in peat and other highly organic-rich sediments. Hence, XRF-CS is well suited to complement the analytical toolbox for the paleoenvironmental study of such sediments.

Design, synthesis, and biological evaluation of an allosteric inhibitor of HSET that targets cancer cells with supernumerary centrosomes.

Centrosomes associate with spindle poles; thus, the presence of two centrosomes promotes bipolar spindle assembly in normal cells. Cancer cells often contain supernumerary centrosomes, and to avoid multipolar mitosis and cell death, these are clustered into two poles by the microtubule motor protein HSET. We report the discovery of an allosteric inhibitor of HSET, CW069, which we designed using a methodology on an interface of chemistry and biology. Using this approach, we explored millions of compounds in silico and utilized convergent syntheses. Only compound CW069 showed marked activity against HSET in vitro. The inhibitor induced multipolar mitoses only in cells containing supernumerary centrosomes. CW069 therefore constitutes a valuable tool for probing HSET function and, by reducing the growth of cells containing supernumerary centrosomes, paves the way for new cancer therapeutics.

A novel isocyanide based three component reaction.

A three component reaction involving an isocyanide, a carboxylic acid and an epoxide or aziridine is described.