The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

We thank Manuel Kulagin for technical help, Pierre Bonnaventure for portal vein blood sampling, Francisco Sepulveda for technical assistance in GS-MS acquisition, and Dorothee Hahne (Metabolomics Australia, University of Western Australia) for human samples SCFA isolation, acquisition, and analysis. We also thank Cristina Cartoni (Phenotyping Unit, EPFL) for Milliplex analysis, Jessica Dessimoz and her team from the Histology Core Facility (EPFL), Miguel Garcia and his team from the Flow Cytometry Core Facility (EPFL), and staff from the EPFL CPG animal house for excellent animal care. The computations were partially performed at the Vital-IT Center for high-performance computing of the SIB Swiss Institute of Bioinformatics (http://www.vital-it.ch). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 310948. Funding for A.W.W. and a subset of the 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

WHOI Hawaii Ocean Timeseries Station (WHOTS) : WHOTS-10 2013 mooring turnaround cruise report

The Woods Hole Oceanographic Institution (WHOI) Hawaii Ocean Timeseries Site (WHOTS), 100 km north of Oahu, Hawaii, is intended to provide long-term, high-quality air-sea fluxes as a part of the NOAA Climate Observation Program. The WHOTS mooring also serves as a coordinated part of the Hawaii Ocean Timeseries (HOT) program, contributing to the goals of observing heat, fresh water and chemical fluxes at a site representative of the oligotrophic North Pacific Ocean. The approach is to maintain a surface mooring outfitted for meteorological and oceanographic measurements at a site near 22.75°N, 158°W by successive mooring turnarounds. These observations will be used to investigate air–sea interaction processes related to climate variability. This report documents recovery of the ninth WHOTS mooring (WHOTS-9) and deployment of the tenth mooring (WHOTS-10). Both moorings used Surlyn foam buoys as the surface element and were outfitted with two Air–Sea Interaction Meteorology (ASIMET) systems. Each ASIMET system measures, records, and transmits via Argos satellite the surface meteorological variables necessary to compute air–sea fluxes of heat, moisture and momentum. The upper 155 m of the moorings were outfitted with oceanographic sensors for the measurement of temperature, conductivity and velocity in a cooperative effort with R. Lukas of the University of Hawaii. A pCO2 system and ancillary sensors were installed on the buoys in cooperation with Chris Sabine at the Pacific Marine Environmental Laboratory. A set of radiometers were installed in cooperation with Sam Laney at WHOI. The WHOTS mooring turnaround was done on the NOAA ship Hi’ialakai by the Upper Ocean Processes Group of the Woods Hole Oceanographic Institution. The cruise took place between 9 and 16 July 2013. Operations began with deployment of the WHOTS-10 mooring on 10 July. This was followed by meteorological intercomparisons and CTDs. Recovery of the WHOTS-9 mooring took place on 14 July. This report describes these cruise operations, as well as some of the in-port operations and pre-cruise buoy preparations.Funding was provided by the National Oceanic and Atmospheric Administration under Grant. No. NA090AR4320129 and the Cooperative Institute for the North Atlantic Region (CINAR

WHOI Hawaii Ocean Timeseries Station (WHOTS): WHOTS-11 2014 mooring Turnaround Cruise Report

The Woods Hole Oceanographic Institution (WHOI) Hawaii Ocean Timeseries Site (WHOTS), 100 km north of Oahu, Hawaii, is intended to provide long-term, high-quality air-sea fluxes as a part of the NOAA Climate Observation Program. The WHOTS mooring also serves as a coordinated part of the Hawaii Ocean Timeseries (HOT) program, contributing to the goals of observing heat, fresh water and chemical fluxes at a site representative of the oligotrophic North Pacific Ocean. The approach is to maintain a surface mooring outfitted for meteorological and oceanographic measurements at a site near 22.75°N, 158°W by successive mooring turnarounds. These observations will be used to investigate air–sea interaction processes related to climate variability. This report documents recovery of the tenth WHOTS mooring (WHOTS-10) and deployment of the eleventh mooring (WHOTS-11). Both moorings used Surlyn foam buoys as the surface element and were outfitted with two Air–Sea Interaction Meteorology (ASIMET) systems. Each ASIMET system measures, records, and transmits via Argos satellite the surface meteorological variables necessary to compute air–sea fluxes of heat, moisture and momentum. The upper 155 m of the moorings were outfitted with oceanographic sensors for the measurement of temperature, conductivity and velocity in a cooperative effort with R. Lukas of the University of Hawaii. A pCO2 system and ancillary sensors were installed on the buoys in cooperation with Chris Sabine at the Pacific Marine Environmental Laboratory. A set of radiometers were installed in cooperation with Sam Laney at WHOI. The WHOTS mooring turnaround was done on the NOAA ship Hi’ialakai by the Upper Ocean Processes Group of the Woods Hole Oceanographic Institution. The cruise took place between 15 and 23 July 2014. Operations began with deployment of the WHOTS-11 mooring on 16 July. This was followed by meteorological intercomparisons and CTDs. Recovery of the WHOTS-10 mooring took place on 20 July. This report describes these cruise operations, as well as some of the in-port operations and pre-cruise buoy preparations.Funding was provided by the National Oceanic and Atmospheric Administration under Grant No. NA140AR4320158 and the Cooperative Institute for the North Atlantic Region (CINAR

Finite-temperature form factors in the free Majorana theory

We study the large distance expansion of correlation functions in the free massive Majorana theory at finite temperature, alias the Ising field theory at zero magnetic field on a cylinder. We develop a method that mimics the spectral decomposition, or form factor expansion, of zero-temperature correlation functions, introducing the concept of "finite-temperature form factors". Our techniques are different from those of previous attempts in this subject. We show that an appropriate analytical continuation of finite-temperature form factors gives form factors in the quantization scheme on the circle. We show that finite-temperature form factor expansions are able to reproduce expansions in form factors on the circle. We calculate finite-temperature form factors of non-interacting fields (fields that are local with respect to the fundamental fermion field). We observe that they are given by a mixing of their zero-temperature form factors and of those of other fields of lower scaling dimension. We then calculate finite-temperature form factors of order and disorder fields. For this purpose, we derive the Riemann-Hilbert problem that completely specifies the set of finite-temperature form factors of general twist fields (order and disorder fields and their descendants). This Riemann-Hilbert problem is different from the zero-temperature one, and so are its solutions. Our results agree with the known form factors on the circle of order and disorder fields.Comment: 40 pp.; v2: 42 pp., refs and acknowledgment added, typos corrected, description of general matrix elements corrected and extended; v3: 47 pp., appendix adde

The ansamycin antibiotic, rifamycin SV, inhibits BCL6 transcriptional repression and forms a complex with the BCL6-BTB/POZ domain

BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ~40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Quantum memories at finite temperature

To use quantum systems for technological applications one first needs to preserve their coherence for macroscopic time scales, even at finite temperature. Quantum error correction has made it possible to actively correct errors that affect a quantum memory. An attractive scenario is the construction of passive storage of quantum information with minimal active support. Indeed, passive protection is the basis of robust and scalable classical technology, physically realized in the form of the transistor and the ferromagnetic hard disk. The discovery of an analogous quantum system is a challenging open problem, plagued with a variety of no-go theorems. Several approaches have been devised to overcome these theorems by taking advantage of their loopholes. The state-of-the-art developments in this field are reviewed in an informative and pedagogical way. The main principles of self-correcting quantum memories are given and several milestone examples from the literature of two-, three- and higher-dimensional quantum memories are analyzed

Integral equations and large-time asymptotics for finite-temperature Ising chain correlation functions

This work concerns the dynamical two-point spin correlation functions of the transverse Ising quantum chain at finite (non-zero) temperature, in the universal region near the quantum critical point. They are correlation functions of twist fields in the massive Majorana fermion quantum field theory. At finite temperature, these are known to satisfy a set of integrable partial differential equations, including the sinh-Gordon equation. We apply the classical inverse scattering method to study them, finding that the ``initial scattering data'' corresponding to the correlation functions are simply related to the one-particle finite-temperature form factors calculated recently by one of the authors. The set of linear integral equations (Gelfand-Levitan-Marchenko equations) associated to the inverse scattering problem then gives, in principle, the two-point functions at all space and time separations, and all temperatures. From them, we evaluate the large-time asymptotic expansion ``near the light cone'', in the region where the difference between the space and time separations is of the order of the correlation length

Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly

Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here, we show that individuals 70 years or older (median age 73, range 70-75) who received a primary two-dose schedule with AZD1222 and booster third dose with mRNA vaccine achieve significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared with those younger than 70 (median age 66, range 54-69) at 1 month post booster. Impaired neutralization potency and breadth post third dose in the elderly is associated with circulating "atypical" spike-specific B cells expressing CD11c and FCRL5. However, when considering individuals who received three doses of mRNA vaccine, we did not observe differences in neutralization or enrichment in atypical B cells. This work highlights the finding that AdV and mRNA COVID-19 vaccine formats differentially instruct the memory B cell response