36 research outputs found
Immunoglobulin domains in Escherichia coli and other enterobacteria: from pathogenesis to applications in antibody technologies
The immunoglobulin (Ig) protein domain is widespread in nature having a well-recognized role in proteins of the immune system. In this review, we describe the proteins containing Ig-like domains in
Escherichia coli and entero-bacteria, reporting their structural and functional properties, protein folding, and diverse biological roles. In addition, we cover the expression of heterolo-gous Ig domains in E. coli owing to its biotechnological application for expression and selection of antibody fragments and full-length IgG molecules. Ig-like domains in E. coli and enterobacteria are frequently found in cell surface proteins and fimbrial organelles playing important functions during host cell
adhesion and invasion of pathogenic strains, being structural components of pilus and nonpilus fimbrial systems and members of the intimin/invasin family of outer membrane (OM) adhesins. Ig-like domains are also found in periplasmic chaperones and OM usher proteins assembling fimbriae, in oxidoreductases and hydrolytic enzymes, ATP-binding cassette transporters, sugar-binding and metal-resistance proteins. The folding of most E. coli Ig-like domains is
assisted by periplasmic chaperones, peptidyl
prolylcis/transisomerases and disulfide bond catalysts that also participate in the folding of antibodies expressed in this bacterium. The technologies for expression and selection of recombinant antibodies in
E. coli are described along with their biotechnological potential.This work has been supported by Grants of the Spanish Ministry of Science and Innovation (BIO2008-05201; BIO2011-26689), the Autonomous Community of Madrid
(S-BIO-236-2006; S2010-BMD-2312), CSIC (PIE 2011 20E049), âla Caixaâ Foundation, and the VI Framework Program from the European Union (FP6-LSHB-CT-2005-512061 NoE âEuroPathogenomicsâ).Peer reviewe
Tumor microenvironment-dependent epigenetic imprinting in the vasculature predicts colon cancer outcome
Observation of Josephson harmonics in tunnel junctions
Approaches to developing large-scale superconducting quantum
processors must cope with the numerous microscopic degrees of freedom
that are ubiquitous in solid-state devices. State-of-the-art superconducting
qubits employ aluminium oxide (AlO) tunnel Josephson junctions as
the sources of nonlinearity necessary to perform quantum operations.
Analyses of these junctions typically assume an idealized, purely sinusoidal
currentâphase relation. However, this relation is expected to hold only in the
limit of vanishingly low-transparency channels in the AlO barrier. Here we
show that the standard currentâphase relation fails to accurately describe
the energy spectra of transmon artificial atoms across various samples
and laboratories. Instead, a mesoscopic model of tunnelling through
an inhomogeneous AlO barrier predicts percent-level contributions
from higher Josephson harmonics. By including these in the transmon
Hamiltonian, we obtain orders of magnitude better agreement between
the computed and measured energy spectra. The presence and impact of
Josephson harmonics has important implications for developing AlOx-based
quantum technologies including quantum computers and parametric
amplifiers. As an example, we show that engineered Josephson harmonics
can reduce the charge dispersion and associated errors in transmon qubits
by an order of magnitude while preserving their anharmonicity
Observation of Josephson Harmonics in Tunnel Junctions
Superconducting quantum processors have a long road ahead to reach
fault-tolerant quantum computing. One of the most daunting challenges is taming
the numerous microscopic degrees of freedom ubiquitous in solid-state devices.
State-of-the-art technologies, including the world's largest quantum
processors, employ aluminum oxide (AlO) tunnel Josephson junctions (JJs) as
sources of nonlinearity, assuming an idealized pure current-phase
relation (CR). However, this celebrated CR is
only expected to occur in the limit of vanishingly low-transparency channels in
the AlO barrier. Here we show that the standard CR fails to
accurately describe the energy spectra of transmon artificial atoms across
various samples and laboratories. Instead, a mesoscopic model of tunneling
through an inhomogeneous AlO barrier predicts %-level contributions from
higher Josephson harmonics. By including these in the transmon Hamiltonian, we
obtain orders of magnitude better agreement between the computed and measured
energy spectra. The reality of Josephson harmonics transforms qubit design and
prompts a reevaluation of models for quantum gates and readout, parametric
amplification and mixing, Floquet qubits, protected Josephson qubits, etc. As
an example, we show that engineered Josephson harmonics can reduce the charge
dispersion and the associated errors in transmon qubits by an order of
magnitude, while preserving anharmonicity
Mass Measurements of Neutron-Deficient Yb Isotopes and Nuclear Structure at the Extreme Proton-Rich Side of the N=82 Shell
International audienceHigh-accuracy mass measurements of neutron-deficient Yb isotopes have been performed at TRIUMF using TITANâs multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). For the first time, an MR-TOF-MS was used on line simultaneously as an isobar separator and as a mass spectrometer, extending the measurements to two isotopes further away from stability than otherwise possible. The ground state masses of Yb150,153 and the excitation energy of Ybm151 were measured for the first time. As a result, the persistence of the N=82 shell with almost unmodified shell gap energies is established up to the proton drip line. Furthermore, the puzzling systematics of the h11/2-excited isomeric states of the N=81 isotones are unraveled using state-of-the-art mean field calculation
Peanutâinduced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry
Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition
Microduplications of 16p11.2 are associated with schizophrenia
Recurrent microdeletions and microduplications of a 600 kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1-3. Here we report the strong association of 16p11.2 microduplications with schizophrenia in two large cohorts. In the primary sample, the microduplication was detected in 12/1906 (0.63%) cases and 1/3971 (0.03%) controls (P=1.2Ă10-5, OR=25.8). In the replication sample, the microduplication was detected in 9/2645 (0.34%) cases and 1/2420 (0.04%) controls (P=0.022, OR=8.3). For the series combined, microduplication of 16p11.2 was associated with 14.5-fold increased risk of schizophrenia (95% C.I. [3.3, 62]). A meta-analysis of multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. The reciprocal microdeletion was associated only with autism and developmental disorders. Analysis of patient clinical data showed that head circumference was significantly larger in patients with the microdeletion compared with patients with the microduplication (P = 0.0007). Our results suggest that the microduplication of 16p11.2 confers substantial risk for schizophrenia and other psychiatric disorders, whereas the reciprocal microdeletion is associated with contrasting clinical features
Microduplications of 16p11.2 are associated with schizophrenia
Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1,2,3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 Ă 10â5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 Ă 10â7), bipolar disorder (P = 0.017) and autism (P = 1.9 Ă 10â7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 Ă 10â13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007)