Palaeomagnetic and synchrotron analysis of \u3e1.95 Ma fossil-bearing palaeokarst at Haasgat, South Africa

Palaeomagnetic analysis indicates that Haasgat, a fossil-bearing palaeocave in the Gauteng Province of South Africa, is dominated by reversed magnetic polarity in its oldest, deepest layers and normal polarity in the younger layers. The presence of in-situ Equus specimens suggests an age of less than ~2.3 Ma, while morphological analysis of faunal specimens from the ex-situ assemblage suggests an age greater than 1.8 Ma. Given this faunal age constraint, the older reversed polarity sections most likely date to the beginning of the Matuyama Chron (2.58–1.95 Ma), while the younger normal polarity deposits likely date to the very beginning of the Olduvai Sub-Chron (1.95–1.78 Ma). The occurrence of a magnetic reversal from reversed to normal polarity recorded in the sequence indicates the deposits of the Bridge Section date to ~1.95 Ma. All the in-situ fossil deposits that have been noted are older than the 1.95 Ma reversal, but younger than 2.3 Ma. Haasgat therefore dates to an interesting time period in South African human evolution that saw the last occurrence of two australopith species at ~2.05–2.02 Ma (Sts5 Australopithecus africanus from Sterkfontein Member 4) to ~1.98 Ma ( Australopithecus sediba from Malapa) and the first occurrence of early Homo (Sk847), Paranthropus and the Oldowan within Swartkrans Member 1 between ~2.0 Ma and ~1.8 Ma

Evidence for orbital ordering in LaCoO3

We present powder and single crystal X-ray diffraction data as evidence for a monoclinic distortion in the low spin (S=0) and intermediate spin state (S=1) of LaCoO3. The alternation of short and long bonds in the ab plane indicates the presence of eg orbital ordering induced by a cooperative Jahn-Teller distortion. We observe an increase of the Jahn-Teller distortion with temperature in agreement with a thermally activated behavior of the Co3+ ions from a low-spin ground state to an intermediate-spin excited state.Comment: Accepted to Phys. Rev.

Magnetic resonance imaging assessment of renal flow distribution patterns during ex vivo normothermic machine perfusion in porcine and human kidneys

Acceptance criteria of deceased donor organs have gradually been extended toward suboptimal quality, posing an urgent need for more objective pre-transplant organ assessment. Ex vivo normothermic machine perfusion (NMP) combined with magnetic resonance imaging (MRI) could assist clinicians in deciding whether a donor kidney is suitable for transplantation. Aim of this study was to characterize the regional distribution of perfusate flow during NMP, to better understand how ex vivo kidney assessment protocols should eventually be designed. Nine porcine and 4 human discarded kidneys underwent 3 h of NMP in an MRI-compatible perfusion setup. Arterial spin labeling scans were performed every 15 min, resulting in perfusion-weighted images that visualize intrarenal flow distribution. At the start of NMP, all kidneys were mainly centrally perfused and it took time for the outer cortex to reach its physiological dominant perfusion state. Calculated corticomedullary ratios based on the perfusion maps reached a physiological range comparable to in vivo observations, but only after 1 to 2 h after the start of NMP. Before that, the functionally important renal cortex appeared severely underperfused. Our findings suggest that early functional NMP quality assessment markers may not reflect actual physiology and should therefore be interpreted with caution

Ligand-hole localization in oxides with unusual valence Fe

Unusual high-valence states of iron are stabilized in a few oxides. A-site-ordered perovskite-structure oxides contain such iron cations and exhibit distinct electronic behaviors at low temperatures, e.g. charge disproportionation (4Fe4+ → 2Fe3+ + 2Fe5+) in CaCu3Fe4O12 and intersite charge transfer (3Cu2+ + 4Fe3.75+ → 3Cu3+ + 4Fe3+) in LaCu3Fe4O12. Here we report the synthesis of solid solutions of CaCu3Fe4O12 and LaCu3Fe4O12 and explain how the instabilities of their unusual valence states of iron are relieved. Although these behaviors look completely different from each other in simple ionic models, they can both be explained by the localization of ligand holes, which are produced by the strong hybridization of iron d and oxygen p orbitals in oxides. The localization behavior in the charge disproportionation of CaCu3Fe4O12 is regarded as charge ordering of the ligand holes, and that in the intersite charge transfer of LaCu3Fe4O12 is regarded as a Mott transition of the ligand holes

The Magnetoelectric Effect in Transition Metal Oxides: Insights and the Rational Design of New Materials from First Principles

The search for materials displaying a large magnetoelectric effect has occupied researchers for many decades. The rewards could include not only advanced electronics technologies, but also fundamental insights concerning the dielectric and magnetic properties of condensed matter. In this article, we focus on the magnetoelectric effect in transition metal oxides and review the manner in which first-principles calculations have helped guide the search for (and increasingly, predicted) new materials and shed light on the microscopic mechanisms responsible for magnetoelectric phenomena.Comment: 24 pages, 12 figure

Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments.

BACKGROUND: Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. RESULTS: Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. CONCLUSIONS: Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment

Mechanisms of Betulinic acid‐induced cell death

The scope of this thesis was to investigate the mechanisms by which BetA induces cell death in cancer cells in more detail. At the start of the studies described in this thesis several questions urgently needed an answer. Although BetA induces cell death via apoptosis, when blocking this form of cell death cancer cells still die. In tumor therapy it is still unclear whether activation of autophagy contributes to cell death or rather represents a resistance/survival mechanism. We therefore investigated the roles of other cell death mechanisms including necroptosis and autophagy in BetA‐induced cell death. The results of this investigation are described in chapter 2. BetA induces cell death independently of BAK/BAX but in a mitochondrial dependent fashion, but no reports exist revealing how this form of cell death occurs, we set off to study the mechanism by which BetA induces cell death in more detail. We found that BetA interferes with lipid cell metabolism. The results of this research are described in chapter 3. Cancer stem cells are tumor resistant and currently no effective therapy has been shown for these cells. BetA is a very potent and broad acting compound therefore we treated colon cancer stem cells with BetA. Results of these experiments are laid out in chapter 4. Finally, we were also interested in the effect of BetA on several lipids in the cell. We set‐up a lipidomics pipeline and used a BetA dataset to test the functionality of this pipeline as well as to investigate the difference in lipids after BetA treatment. Chapter 5 contains these results. In chapter 6 all data of this thesis are discussed in relation to the literature

Betulinic acid kills colon cancer stem cells

Cancer stem cells (CSCs) are considered to be the origin of cancer and it is suggested that they are resistant to chemotherapy. Current therapies fail to eradicate CSCs and therefore selecting a resistant cell subset that is able to facilitate tumor recurrences. Betulinic acid (BetA) is a broad acting natural compound, shown to induce cell death via the inhibition of the stearoyl-CoA- desaturase (SCD- 1). This enzyme converts saturated fatty acids into unsaturated fatty acids and is over-expressed in tumor cells. Here we show that BetA induces rapid cell death in all colon CSCs tested and is able to affect the CSCs directly as shown, via the loss of clonogenic capacity. Similar results were observed with inhibition of SCD-1, suggesting that SCD-1 activity is indeed a vulnerable link in colon CSCs and can be considered an ideal target for therapy in colon cancer