Asymptotic convergence analysis of the proximal point algorithm for metrically regular mappings

This paper studies convergence properties of the proximal point algorithm when applied to a certain class of nonmonotone set-valued mappings. We consider an algorithm for solving an inclusion 0 ∈ T(x), where T is a metrically regular set-valued mapping acting from R(n) into R(m). The algorithm is given by the follwoing iteration: x(0) ∈ R(n) and x(k+1) = α(k)x(k) + (1 - α(k))y(k), for k = 0, 1, 2, ..., where {α(k)} is a sequence in [0, 1] such that α(k) ≤ α < 1, g(k) is a Lipschitz mapping from R(n) into R(m) and y(k) satisfies the following inclusion 0 ∈ g(k)(y(k)) - g(k)(x(k)) + T(y(k)). We prove that if the modulus of regularity of T is sufficiently small then the sequence generated by our algorithm converges to a solution to 0 ∈ T(x)

Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity

Efficient and faithful replication of telomeric DNA is critical for maintaining genome integrity. The G-quadruplex (G4) structure arising in the repetitive TTAGGG sequence is thought to stall replication forks, impairing efficient telomere replication and leading to telomere instabilities. However, pathways modulating telomeric G4 are poorly understood, and it is unclear whether defects in these pathways contribute to genome instabilities in vivo. Here, we report that mammalian DNA2 helicase/nuclease recognizes and cleaves telomeric G4 in vitro. Consistent with DNA2’s role in removing G4, DNA2 deficiency in mouse cells leads to telomere replication defects, elevating the levels of fragile telomeres (FTs) and sister telomere associations (STAs). Such telomere defects are enhanced by stabilizers of G4. Moreover, DNA2 deficiency induces telomere DNA damage and chromosome segregation errors, resulting in tetraploidy and aneuploidy. Consequently, DNA2-deficient mice develop aneuploidy-associated cancers containing dysfunctional telomeres. Collectively, our genetic, cytological, and biochemical results suggest that mammalian DNA2 reduces replication stress at telomeres, thereby preserving genome stability and suppressing cancer development, and that this may involve, at least in part, nucleolytic processing of telomeric G4

Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis

EttA, energy-dependent translational throttle A, is a ribosomal factor that gates ribosome entry into the translation elongation cycle. A detailed understanding of its mechanism of action is limited due to the lack of high-resolution structures along its ATPase cycle. Here we present the cryo-electron microscopy (cryo-EM) structures of EttA from Mycobacterium tuberculosis (Mtb), referred to as MtbEttA, in complex with the Mtb 70S ribosome initiation complex (70SIC) at the pre-hydrolysis (ADPNP) and transition (ADP-VO4) states, and the crystal structure of MtbEttA alone in the post-hydrolysis (ADP) state. We observe that MtbEttA binds the E-site of the Mtb 70SIC, remodeling the P-site tRNA and the ribosomal intersubunit bridge B7a during the ribosomal ratcheting. In return, the rotation of the 30S causes conformational changes in MtbEttA, forcing the two nucleotide-binding sites (NBSs) to alternate to engage each ADPNP in the pre-hydrolysis states, followed by complete engagements of both ADP-VO4 molecules in the ATP-hydrolysis transition states. In the post-hydrolysis state, the conserved ATP-hydrolysis motifs of MtbEttA dissociate from both ADP molecules, leaving two nucleotide-binding domains (NBDs) in an open conformation. These structures reveal a dynamic interplay between MtbEttA and the Mtb ribosome, providing insights into the mechanism of translational regulation by EttA-like proteins

Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome

Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function

Extremely long quasiparticle spin lifetimes in superconducting aluminium using MgO tunnel spin injectors

There has been an intense search in recent years for long-lived spin-polarized carriers for spintronic and quantum-computing devices. Here we report that spin polarized quasi-particles in superconducting aluminum layers have surprisingly long spin-lifetimes, nearly a million times longer than in their normal state. The lifetime is determined from the suppression of the aluminum's superconductivity resulting from the accumulation of spin polarized carriers in the aluminum layer using tunnel spin injectors. A Hanle effect, observed in the presence of small in-plane orthogonal fields, is shown to be quantitatively consistent with the presence of long-lived spin polarized quasi-particles. Our experiments show that the superconducting state can be significantly modified by small electric currents, much smaller than the critical current, which is potentially useful for devices involving superconducting qubits

Intracellular interferons in fish : a unique means to combat viral infection

Peer reviewedPublisher PD

The connectome of the adult Drosophila mushroom body provides insights into function.

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory, and activity regulation. Here, we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work