Warburg effect and translocation-induced genomic instability: two yeast models for cancer cells

Yeast has been established as an efficient model system to study biological principles underpinning human health. In this review we focus on yeast models covering two aspects of cancer formation and progression (i) the activity of pyruvate kinase (PK), which recapitulates metabolic features of cancer cells, including the Warburg effect, and (ii) chromosome bridge-induced translocation (BIT) mimiking genome instability in cancer. Saccharomyces cerevisiae is an excellent model to study cancer cell metabolism, as exponentially growing yeast cells exhibit many metabolic similarities with rapidly proliferating cancer cells. The metabolic reconfiguration includes an increase in glucose uptake and fermentation, at the expense of respiration and oxidative phosphorylation (the Warburg effect), and involves a broad reconfiguration of nucleotide and amino acid metabolism. Both in yeast and humans, the regulation of this process seems to have a central player, PK, which is up-regulated in cancer, and to occur mostly on a post-transcriptional and post-translational basis. Furthermore, BIT allows to generate selectable translocation-derived recombinants ("translocants"), between any two desired chromosomal locations, in wild-type yeast strains transformed with a linear DNA cassette carrying a selectable marker flanked by two DNA sequences homologous to different chromosomes. Using the BIT system, targeted non-reciprocal translocations in mitosis are easily inducible. An extensive collection of different yeast translocants exhibiting genome instability and aberrant phenotypes similar to cancer cells has been produced and subjected to analysis. In this review, we hence provide an overview upon two yeast cancer models, and extrapolate general principles for mimicking human disease mechanisms in yeast

Towards temperature-induced topological phase transition in SnTe: A first principles study

The temperature renormalization of the bulk band structure of a topological crystalline insulator, SnTe, is calculated using first principles methods. We explicitly include the effect of thermal-expansion-induced modification of electronic states and their band inversion on electron-phonon interaction. We show that the direct gap decreases with temperature, as both thermal expansion and electron-phonon interaction drive SnTe towards the phase transition to a topologically trivial phase as temperature increases. The band gap renormalization due to electron-phonon interaction exhibits a non-linear dependence on temperature as the material approaches the phase transition, while the lifetimes of the conduction band states near the band edge show a non-monotonic behavior with temperature. These effects should have important implications on bulk electronic and thermoelectric transport in SnTe and other topological insulators.Comment: 10 pages, 8 figures. Accepted for publication in Phys. Rev. B on June 8, 202

Exact exchange-correlation potential of a ionic Hubbard model with a free surface

We use Lanczos exact diagonalization to compute the exact exchange-correlation (xc) potential of a Hubbard chain with large binding energy ("the bulk") followed by a chain with zero binding energy ("the vacuum"). Several results of density functional theory in the continuum (sometimes controversial) are verified in the lattice. In particular we show explicitly that the fundamental gap is given by the gap in the Kohn-Sham spectrum plus a contribution due to the jump of the xc-potential when a particle is added. The presence of a staggered potential and a nearest-neighbor interaction V allows to simulate a ionic solid. We show that in the ionic regime in the small hopping amplitude limit the xc-contribution to the gap equals V, while in the Mott regime it is determined by the Hubbard U interaction. In addition we show that correlations generates a new potential barrier at the surface

Morphometrical analysis of transbronchial cryobiopsies

The recent introduction of bronchoscopically recovered cryobiopsy of lung tissue has opened up new possibilities in the diagnosis of neoplastic and non-neoplastic lung diseases in various aspects. Most notably the morphological diagnosis of peripheral lung biopsies promises to achieve a better yield with a high quality of specimens. To better understand this phenomenon, its diagnostic options and perspectives, this study morphometrically compares 15 cryobiopsies and 18 transbronchial forceps biopsies of peripheral lung tissue a priori without considering clinical hit ratio or integration of results in the clinical diagnostic processing. Cryotechnically harvested specimens were significantly larger (mean: 17.1 ± 10.7 mm2 versus 3.8 ± 4.0 mm2) and contained alveolar tissue more often. If present, the alveolar part in cryobiopsies exceeded the one of forceps biopsies. The alveolar tissue of crybiopsy specimens did not show any artefacts. Based on these results cryotechnique seems to open up new perspectives in bronchoscopic diagnosis of lung disease

Global Health Governance and the Commercial Sector: A Documentary Analysis of Tobacco Company Strategies to Influence the WHO Framework Convention on Tobacco Control

Heide Weishaar and colleagues did an analysis of internal tobacco industry documents together with other data and describe the industry's strategic response to the proposed World Health Organization Framework Convention on Tobacco Control

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function.

Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected

Theoretical study of the electronic spectra of small molecules that incorporate analogues of the copper-cysteine bond

The copper-sulphur bond which binds cysteinate to the metal centre is a key factor in the spectroscopy of blue copper proteins. We present theoretical calculations describing the electronically excited states of small molecules, including CuSH, CuSCH_3, (CH_3)_2SCuSH, (imidazole)-CuSH and (imidazole)_2-CuSH, derived from the active site of blue copper proteins that contain the copper-sulphur bond in order to identify small molecular systems that have electronic structure that is analogous to the active site of the proteins. Both neutral and cationic forms are studied, since these represent the reduced and oxidised forms of the protein, respectively. For CuSH and CuSH^+, excitation energies from time-dependent density functional theory with the B97-1 exchange-correlation functional agree well with the available experimental data and multireference configuration interaction calculations. For the positive ions, the singly occupied molecular orbital is formed from an antibonding combination of a 3d orbital on copper and a 3pπ orbital on sulphur, which is analogous to the protein. This leads several of the molecules to have qualitatively similar electronic spectra to the proteins. For the neutral molecules, changes in the nature of the low lying virtual orbitals leads the predicted electronic spectra to vary substantially between the different molecules. In particular, addition of a ligand bonded directly to copper results in the low-lying excited states observed in CuSH and CuSCH_33 to be absent or shifted to higher energies

Spin dynamics from time-dependent density functional perturbation theory

We present a new method to model spin-wave excitations in magnetic solids, based on the Liouville-Lanczos approach to time-dependent density functional perturbation theory. This method avoids computationally expensive sums over empty states and naturally deals with the coupling between spin and charge fluctuations, without ever explicitly computing charge-density susceptibilities. Spin-wave excitations are obtained with one Lanczos chain per magnon wave-number and polarization, avoiding the solution of the linear-response problem for every individual value of frequency, as other state-of-the-art approaches do. Our method is validated by computing magnon dispersions in bulk Fe and Ni, resulting in agreement with previous theoretical studies in both cases, and with experiment in the case of Fe. The disagreement in the case of Ni is also comparable with that of previous computations