Nuclear shell-model simulation in digital quantum computers.

The nuclear shell model is one of the prime many-body methods to study the structure of atomic nuclei, but it is hampered by an exponential scaling on the basis size as the number of particles increases. We present a shell-model quantum circuit design strategy to find nuclear ground states by exploiting an adaptive variational quantum eigensolver algorithm. Our circuit implementation is in excellent agreement with classical shell-model simulations for a dozen of light and medium-mass nuclei, including neon and calcium isotopes. We quantify the circuit depth, width and number of gates to encode realistic shell-model wavefunctions. Our strategy also addresses explicitly energy measurements and the required number of circuits to perform them. Our simulated circuits approach the benchmark results exponentially with a polynomial scaling in quantum resources for each nucleus. This work paves the way for quantum computing shell-model studies across the nuclear chart and our quantum resource quantification may be used in configuration-interaction calculations of other fermionic systems.

cBid, Bax and Bcl-xL exhibit opposite membrane remodeling activities.

The proteins of the Bcl-2 family have a crucial role in mitochondrial outer membrane permeabilization during apoptosis and in the regulation of mitochondrial dynamics. Current models consider that Bax forms toroidal pores at mitochondria that are responsible for the release of cytochrome c, whereas Bcl-xL inhibits pore formation. However, how Bcl-2 proteins regulate mitochondrial fission and fusion remains poorly understood. By using a systematic analysis at the single vesicle level, we found that cBid, Bax and Bcl-xL are able to remodel membranes in different ways. cBid and Bax induced a reduction in vesicle size likely related to membrane tethering, budding and fission, besides membrane permeabilization. Moreover, they are preferentially located at highly curved membranes. In contrast, Bcl-xL not only counterbalanced pore formation but also membrane budding and fission. Our findings support a mechanism of action by which cBid and Bax induce or stabilize highly curved membranes including non-lamellar structures. This molecular activity reduces the energy for membrane remodeling, which is a necessary step in toroidal pore formation, as well as membrane fission and fusion, and provides a common mechanism that links the two main functions of Bcl-2 proteins.

The secrets of the Bcl-2 family.

The Bcl-2 family of proteins is formed by pro- and antiapoptotic members. Together they regulate the permeabilization of the mitochondrial outer membrane, a key step in apoptosis. Their complex network of interactions both in the cytosol and on mitochondria determines the fate of the cell. In the past 2 decades, the members of the family have been identified and classified according to their function. Several competing models have been proposed to explain how the Blc-2 proteins orchestrate apoptosis signaling. However, basic aspects of the action of these proteins remain elusive. This review is focused on the biophysical mechanisms that are relevant for their action in apoptosis and on the challenging gaps in our knowledge that necessitate further exploration to finally understand how the Bcl-2 family regulates apoptosis.

Giant unilamellar vesicles (GUVs) as a new tool for analysis of caspase-8/Bid-FL complex binding to cardiolipin and its functional activity.

Cardiolipin (CL) has recently been shown to be both an anchor and an essential activating platform for caspase-8 on mitochondria. These platforms may be at the mitochondrial contact sites in which truncated Bid (tBid) has been demonstrated to be located. A possible role for CL is to anchor caspase-8 at contact sites (between inner and outer membranes), facilitating its self-activation, Bid-full length (FL) cleavage, tBid generation (and Bax/Bak activation and oligomerization), mitochondrial destabilization and apoptosis. We have developed an in vitro system that mimics the mitochondrial membrane contact site platform. This system involves reconstituting caspase-8, Bid-FL and CL complexes in giant unilamellar vesicles (GUVs). We first validated the system by flow cytometry analysis of light-scattering properties and nonyl acridine orange staining of their CL content. Then, we used flow cytometry analysis to detect the binding of active caspase-8 to CL and the subsequent truncation of bound Bid-FL. The tBid generated interacts with CL and induces GUV breakage and partial re-vesiculation at a smaller size. Our findings suggest an active role for mitochondrial membrane lipids, particularly CL, in binding active caspase-8 and providing a docking site for Bid-FL. This phenomenon was previously only poorly documented and substantially underestimated.

Polymorphism and structure of the gene coding for the alpha 1 subunit of the Artemia franciscana Na/K-ATPase.

Genomic clones coding for one of the two identified Artemia franciscana Na/K-ATPase alpha subunits, the alpha 1 subunit, have been isolated. Several overlapping clones were obtained, although their restriction maps showed a large heterogeneity. Sequencing of their exons showed that they differ in up to 3.46% of their nucleotides in translated regions and 8.18% in untranslated regions. Southern blot analysis of DNA purified from different lots of A. franciscana cysts and from isolated individuals suggests that the variation is due to the existence of multiple Na/K-ATPase alpha 1 subunit alleles in A. franciscana. The Na/K-ATPase alpha 1 subunit gene is divided into 15 exons. Ten of the 14 introns are located in identical positions in this gene as in the human Na/K-ATPase alpha 3 subunit gene. Analysis of the 5' flanking region of the gene has allowed identification of the transcription-initiation sites. The adjacent upstream region has been shown to have functional promoter activity in cultured mammalian cells, suggesting the evolutionary conservation of some of the promoter regulatory sequences.

In situ hybridization analyses of Na, K-ATPase alpha-subunit expression during early larval development of Artemia franciscana.

The spatial pattern of expression of the mRNA encoded by the Na,K-ATPase alpha-subunit cDNA clone pArATNa136 was determined by in situ hybridization of first, second, and third instar Artemia franciscana larvae. This mRNA was expressed at high levels in the salt gland, the antennal gland, and the end of the midgut, which are the three main osmoregulatory organs in Artemia at these stages of development. The pattern of expression was similar at the three stages of development analyzed, although the level of expression increased during development, especially in the salt and antennal glands. The expression of the mRNA coding for another Na, K-ATPase alpha-subunit isoform, the proposed alpha 2-isoform, was also determined and was shown to be limited to the salt gland. These results suggest that the clone pArATNa136 codes for the biochemically defined alpha 1-isoform of the Na,K-ATPase alpha-subunit and reinforce the importance of this isoform in osmoregulation at the three larval stages studied. The alpha 2-isoform may also be involved in osmoregulation during the first stages of larval development.

Gene expression after resumption of development of Artemia franciscana cryptobiotic embryos.

The steady-state levels of six different mRNAs have been studied during Artemia franciscana development. Some of these mRNAs are present in the cryptobiotic cyst, like those coding for cytoplasmic actins, sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase, and the Na+, K(+)-ATPase alpha-subunit isoform coded by the clone pArATNa136. The expression of these mRNAs is markedly induced during cyst development. A small increase in mRNA levels can be observed for some genes at very early stages of development (2 h). The main increase is observed between 4 and 16 h of development for all these genes, although the time course of mRNA accumulation is different for each one of the genes studied. Some other genes, like those coding for muscle actin (actin 3) or the Na+, K(+)-ATPase alpha-subunit isoform coded by the cDNA clone alpha 2850, are not expressed in the cyst before resumption of development and their expression is induced after 10 or 6 h of development, respectively. These data on the kinetic of mRNA accumulation provide the information required to determine transcriptionally active developmental stages, necessary to study in more detail the mechanisms of transcriptional regulation during activation of cryptobiotic cysts and resumption of embryonic development.