Conophytum bachelorum and its relatives: the introduction of a new conophytum from Namaqualand, C. confusum.

Summary: A reassessment of a group of four closely related taxa of the dwarf succulent genus Conophytum from Namaqualand, South Africa has been undertaken. This has resulted in the description of a newly discovered taxon, namely Conophytum confusum

Leaf epidermal structure in the dwarf succulent genus Conophytum N.E. Br. (Aizoaceae)

The epidermal structure of 66 species and subspecies of the dwarf succulent genus Cono- phytum N.E. Br. was examined using scanning electron microscopy. Taxa within this genus pos- sess a number of adaptations to their arid envi- ronment including sunken stomata, a prominent wax layer and trichomes. The range of epidermal morphologies present in this genus is described and the use of these to inform infrageneric classi- fication in Conophytum is discussed. In many cases the epidermis of closely related species is similar but this is not always the case across the 16 sections that comprise the genus. Whilst this study confirms the assignment of several recently described taxa to existing sections it suggests that the infrageneric classification of Conophytum needs to be re-evaluated

Abrupt Onset of Second Energy Gap at Superconducting Transition of Underdoped Bi2212

The superconducting gap - an energy scale tied to the superconducting phenomena-opens on the Fermi surface at the superconducting transition temperature (TC) in conventional BCS superconductors. Quite differently, in underdoped high-TC superconducting cuprates, a pseudogap, whose relation to the superconducting gap remains a mystery, develops well above TC. Whether the pseudogap is a distinct phenomenon or the incoherent continuation of the superconducting gap above TC is one of the central questions in high-TC research. While some experimental evidence suggests they are distinct, this issue is still under intense debate. A crucial piece of evidence to firmly establish this two-gap picture is still missing: a direct and unambiguous observation of a single-particle gap tied to the superconducting transition as function of temperature. Here we report the discovery of such an energy gap in underdoped Bi2212 in the momentum space region overlooked in previous measurements. Near the diagonal of Cu-O bond direction (nodal direction), we found a gap which opens at TC and exhibits a canonical (BCS-like) temperature dependence accompanied by the appearance of the so-called Bogoliubov quasiparticles, a classical signature of superconductivity. This is in sharp contrast to the pseudogap near the Cu-O bond direction (antinodal region) measured in earlier experiments. The emerging two-gap phenomenon points to a picture of richer quantum configurations in high temperature superconductors.Comment: 16 pages, 4 figures, authors' version Corrected typos in the abstrac

Two Energy Scales and two Quasiparticle Dynamics in the Superconducting State of Underdoped Cuprates

The superconducting state of underdoped cuprates is often described in terms of a single energy-scale, associated with the maximum of the (d-wave) gap. Here, we report on electronic Raman scattering results, which show that the gap function in the underdoped regime is characterized by two energy scales, depending on doping in opposite manners. Their ratios to the maximum critical temperature are found to be universal in cuprates. Our experimental results also reveal two different quasiparticle dynamics in the underdoped superconducting state, associated with two regions of momentum space: nodal regions near the zeros of the superconducting gap and antinodal regions. While antinodal quasiparticles quickly loose coherence as doping is reduced, coherent nodal quasiparticles persist down to low doping levels. A theoretical analysis using a new sum-rule allows us to relate the low-frequency-dependence of the Raman response to the temperature-dependence of the superfluid density, both controlled by nodal excitations.Comment: 16 pages, 5 figure

PI3Kinase signaling in glioblastoma

Glioblastoma (GBM) is the most common primary tumor of the CNS in the adult. It is characterized by exponential growth and diffuse invasiveness. Among many different genetic alterations in GBM, e.g., mutations of PTEN, EGFR, p16/p19 and p53 and their impact on aberrant signaling have been thoroughly characterized. A major barrier to develop a common therapeutic strategy is founded on the fact that each tumor has its individual genetic fingerprint. Nonetheless, the PI3K pathway may represent a common therapeutic target to most GBM due to its central position in the signaling cascade affecting proliferation, apoptosis and migration. The read-out of blocking PI3K alone or in combination with other cancer pathways should mainly focus, besides the cytostatic effect, on cell death induction since sublethal damage may induce selection of more malignant clones. Targeting more than one pathway instead of a single agent approach may be more promising to kill GBM cells

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in many cancer cells without causing toxicity in vivo. However, to date, TRAIL-receptor agonists have only shown limited therapeutic benefit in clinical trials. This can, most likely, be attributed to the fact that 50% of all cancer cell lines and most primary human cancers are TRAIL resistant. Consequently, future TRAIL-based therapies will require the addition of sensitizing agents that remove crucial blocks in the TRAIL apoptosis pathway. Here, we identify PIK-75, a small molecule inhibitor of the p110α isoform of phosphoinositide-3 kinase (PI3K), as an exceptionally potent TRAIL apoptosis sensitizer. Surprisingly, PI3K inhibition was not responsible for this activity. A kinome-wide in vitro screen revealed that PIK-75 strongly inhibits a panel of 27 kinases in addition to p110α. Within this panel, we identified cyclin-dependent kinase 9 (CDK9) as responsible for TRAIL resistance of cancer cells. Combination of CDK9 inhibition with TRAIL effectively induced apoptosis even in highly TRAIL-resistant cancer cells. Mechanistically, CDK9 inhibition resulted in downregulation of cellular FLICE-like inhibitory protein (cFlip) and Mcl-1 at both the mRNA and protein levels. Concomitant cFlip and Mcl-1 downregulation was required and sufficient for TRAIL sensitization by CDK9 inhibition. When evaluating cancer selectivity of TRAIL combined with SNS-032, the most selective and clinically used inhibitor of CDK9, we found that a panel of mostly TRAIL-resistant non-small cell lung cancer cell lines was readily killed, even at low concentrations of TRAIL. Primary human hepatocytes did not succumb to the same treatment regime, defining a therapeutic window. Importantly, TRAIL in combination with SNS-032 eradicated established, orthotopic lung cancer xenografts in vivo. Based on the high potency of CDK9 inhibition as a cancer cell-selective TRAIL-sensitizing strategy, we envisage the development of new, highly effective cancer therapies