Complementing T Cells’ Functions: Bringing in Metabolism Matters

Components of the complement system act directly on T cells to alter conventional and regulatory T cell subsets. In this issue of Immunity, Kolev, Dimeloe, Le Friec et al. (2015) provide evidence of a mechanism by which the complement stimulates sustained mTORC1 activation and regulates cellular metabolism

A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B

Class II (Ia) major histocompatibility complex molecules are cell surface proteins normally expressed by a limited subset of cells of the immune system. These molecules regulate the activation of T cells and are required for the presentation of antigens and the initiation of immune responses. The expression of Ia in B cells is determined by both the developmental stage of the B cell and by certain external stimuli. It has been demonstrated previously that treatment of B cells with lipopolysaccharide (LPS) results in increased surface expression of Ia protein. However, we have confirmed that LPS treatment results in a significant decrease in mRNA encoding the Ia proteins which persists for at least 18 h. Within the upstream regulatory region of A alpha k, an NF-kappa B-like binding site is present. We have identified an LPS-induced DNA-binding protein in extracts from athymic mice whose spleens consist predominantly of B cells. Binding activity is present in low levels in unstimulated spleen cells and is increased by LPS treatment. This protein binds to two sites in a regulatory region of the Ia A alpha k gene, one of which contains the NF-kappa B-like binding site. DNA fragments containing these sites cross-compete for protein binding. Analysis by DNase I footprinting identified a target binding sequence, named the LPS-responsive element. Although this target sequence contains an NF-kappa B-like binding site, competition with a mutant oligonucleotide demonstrated that bases critical for NF-kappa B binding are not required for binding of the LPS-inducible protein. Therefore, we hypothesized that this inducible protein represents a new mediator of LPS action, distinct from NF-kappa B, and may be one mechanism to account for the decrease in mRNA encoding the Ia proteins

Quantum error mitigation in quantum annealing

Quantum Error Mitigation (QEM) presents a promising near-term approach to reduce error when estimating expectation values in quantum computing. Here, we introduce QEM techniques tailored for quantum annealing, using Zero-Noise Extrapolation (ZNE). We implement ZNE through zero-temperature extrapolation as well as energy-time rescaling. We conduct experimental investigations into the quantum critical dynamics of a transverse-field Ising spin chain, demonstrating the successful mitigation of thermal noise through both of these techniques. Moreover, we show that energy-time rescaling effectively mitigates control errors in the coherent regime where the effect of thermal noise is minimal. Our ZNE results agree with exact calculations of the coherent evolution over a range of annealing times that exceeds the coherent annealing range by almost an order of magnitude.Comment: 10 pages, 5 figure

Quantum critical dynamics in a 5000-qubit programmable spin glass

Experiments on disordered alloys suggest that spin glasses can be brought into low-energy states faster by annealing quantum fluctuations than by conventional thermal annealing. Due to the importance of spin glasses as a paradigmatic computational testbed, reproducing this phenomenon in a programmable system has remained a central challenge in quantum optimization. Here we achieve this goal by realizing quantum critical spin-glass dynamics on thousands of qubits with a superconducting quantum annealer. We first demonstrate quantitative agreement between quantum annealing and time-evolution of the Schr\"odinger equation in small spin glasses. We then measure dynamics in 3D spin glasses on thousands of qubits, where simulation of many-body quantum dynamics is intractable. We extract critical exponents that clearly distinguish quantum annealing from the slower stochastic dynamics of analogous Monte Carlo algorithms, providing both theoretical and experimental support for a scaling advantage in reducing energy as a function of annealing time

Reintegration of child soldiers in Burundi: A tracer study

Background Substantial attention and resources are aimed at the reintegration of child soldiers, yet rigorous evaluations are rare. Methods This tracer study was conducted among former child soldiers (N=452) and never-recruited peers (N=191) who participated in an economic support program in Burundi. Socio-economic outcome indicators were measured retrospectively for the period before receiving support (T1; 2005–06); immediately afterwards (T2; 2006–07); and at present (T3; 2010). Participants also rated present functional impairment and mental health indicators. Results Participants reported improvement on all indicators, especially economic opportunity and social integration. At present no difference existed between both groups on any of the outcome indicators. Socio-economic functioning was negatively related with depression- and, health complaints and positively with intervention satisfaction. Conclusion The present study demonstrates promising reintegration trajectories of former child soldiers after participating in a support program

Comparative genomics of the tardigrades <i>Hypsibius dujardini</i> and <i>Ramazzottius varieornatus</i>

Tardigrada, a phylum of meiofaunal organisms, have been at the center of discussions of the evolution of Metazoa, the biology of survival in extreme environments, and the role of horizontal gene transfer in animal evolution. Tardigrada are placed as sisters to Arthropoda and Onychophora (velvet worms) in the superphylum Panarthropoda by morphological analyses, but many molecular phylogenies fail to recover this relationship. This tension between molecular and morphological understanding may be very revealing of the mode and patterns of evolution of major groups. Limnoterrestrial tardigrades display extreme cryptobiotic abilities, including anhydrobiosis and cryobiosis, as do bdelloid rotifers, nematodes, and other animals of the water film. These extremophile behaviors challenge understanding of normal, aqueous physiology: how does a multicellular organism avoid lethal cellular collapse in the absence of liquid water? Meiofaunal species have been reported to have elevated levels of horizontal gene transfer (HGT) events, but how important this is in evolution, and particularly in the evolution of extremophile physiology, is unclear. To address these questions, we resequenced and reassembled the genome of H. dujardini, a limnoterrestrial tardigrade that can undergo anhydrobiosis only after extensive pre-exposure to drying conditions, and compared it to the genome of R. varieornatus, a related species with tolerance to rapid desiccation. The 2 species had contrasting gene expression responses to anhydrobiosis, with major transcriptional change in H. dujardini but limited regulation in R. varieornatus. We identified few horizontally transferred genes, but some of these were shown to be involved in entry into anhydrobiosis. Whole-genome molecular phylogenies supported a Tardigrada+Nematoda relationship over Tardigrada+Arthropoda, but rare genomic changes tended to support Tardigrada+Arthropoda