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[en] Aortoenteric fistula (AEF) is an uncommon but serious complication occurring after aortic surgery and may occur at any site in the gastrointestinal tract, with the duodenum being the most common. Conventional surgical repair of secondary AEF has high mortality, whereas endovascular repair has emerged as an alternative treatment despite concerns about persistent or recurrent infection. We report the case of a 91-year old man who was admitted with rectal bleeding from an aorto-appendiceal fistula 9 years after open abdominal aortic aneurysm repair. This rare site for AEF was diagnosed on computed tomography, and we present the first case of endovascular treatment of this uncommon complication.
[en] A high-resolution structure of a noncanonical α-mannanase relevant to human health and nutrition has been solved via heavy-atom phasing of a selenomethionine derivative. The large bowel microbiota, a complex ecosystem resident within the gastrointestinal tract of all human beings and large mammals, functions as an essential, nonsomatic metabolic organ, hydrolysing complex dietary polysaccharides and modulating the host immune system to adequately tolerate ingested antigens. A significant member of this community, Bacteroides thetaiotaomicron, has evolved a complex system for sensing and processing a wide variety of natural glycoproducts in such a way as to provide maximum benefit to itself, the wider microbial community and the host. The immense ability of B. thetaiotaomicron as a ‘glycan specialist’ resides in its enormous array of carbohydrate-active enzymes, many of which are arranged into polysaccharide-utilization loci (PULs) that are able to degrade sugar polymers that are often inaccessible to other gut residents, notably α-mannan. The B. thetaiotaomicron genome encodes ten putative α-mannanases spread across various PULs; however, little is known about the activity of these enzymes or the wider implications of α-mannan metabolism for the health of both the microbiota and the host. In this study, SAD phasing of a selenomethionine derivative has been used to investigate the structure of one such B. thetaiotaomicron enzyme, BT2949, which belongs to the GH76 family of α-mannanases. BT2949 presents a classical (α/α)6-barrel structure comprising a large extended surface cleft common to other GH76 family members. Analysis of the structure in conjunction with sequence alignments reveals the likely location of the catalytic active site of this noncanonical GH76
[en] MatP is a small DNA-binding protein of about 18 kDa. In order to understand the DNA-compaction mechanism of MatP at an atomic level, the structures of apo MatP and of the nucleoprotein complex MatP–matS have been studied. The Escherichia coli chromosome is organized into four macrodomains which are found in the replication-origin region (Ori), at the terminus (Ter) and on both its sides (Right and Left). The localization of the macrodomains is subject to programmed changes during the cell cycle. The compaction of the 800 kb Ter macrodomain relies on the binding of the MatP protein to a 13 bp matS motif repeated 23 times. MatP is a small DNA-binding protein of about 18 kDa that shares homology in its C-terminal region with the ribbon–helix–helix (RHH) motifs present in regulatory DNA-binding proteins such as CopG. In order to understand the DNA-compaction mechanism of MatP at an atomic level, it was decided to study the structure of apo MatP and of the nucleoprotein complex MatP–matS by both X-ray diffraction and SAXS analysis. It was demonstrated that MatP forms dimers that bind a single matS motif. Complete native X-ray data sets were collected and phasing of the diffraction data is under way
[en] The structure of the Rem2 G domain bound to GDP is reported in a monoclinic crystal form at 2.66 Å resolution. RGK proteins are atypical small GTP-binding proteins that are involved in the regulation of voltage-dependent calcium channels and actin cytoskeleton remodelling. The structure of the Rem2 G domain bound to GDP is reported here in a monoclinic crystal form at 2.66 Å resolution. It is very similar to the structure determined previously from an orthorhombic crystal form. However, differences in the crystal-packing environment revealed that the switch I and switch II regions are flexible and not ordered as previously reported. Comparison of the available RGK protein structures along with those of other small GTP-binding proteins highlights two structural features characteristic of this atypical family and suggests that the conserved tryptophan residue in the DXWEX motif may be a structural determinant of the nucleotide-binding affinity
[en] Highlights: • We measured the distance distribution between two spin labels on calmodulin by DEER. • Two structural states, open and closed, were resolved at both low and high Ca. • Ca shifted the equilibrium toward the open state by a factor of 13. • Methionine oxidation, simulated by glutamine substitution, decreased the Ca effect. • These results have important implications for aging in muscle and other tissues. - Abstract: We have used electron paramagnetic resonance (EPR) to examine the structural impact of oxidizing specific methionine (M) side chains in calmodulin (CaM). It has been shown that oxidation of either M109 or M124 in CaM diminishes CaM regulation of the muscle calcium release channel, the ryanodine receptor (RyR), and that mutation of M to Q (glutamine) in either case produces functional effects identical to those of oxidation. Here we have used site-directed spin labeling and double electron–electron resonance (DEER), a pulsed EPR technique that measures distances between spin labels, to characterize the structural changes resulting from these mutations. Spin labels were attached to a pair of introduced cysteine residues, one in the C-lobe (T117C) and one in the N-lobe (T34C) of CaM, and DEER was used to determine the distribution of interspin distances. Ca binding induced a large increase in the mean distance, in concert with previous X-ray crystallography and NMR data, showing a closed structure in the absence of Ca and an open structure in the presence of Ca. DEER revealed additional information about CaM’s structural heterogeneity in solution: in both the presence and absence of Ca, CaM populates both structural states, one with probes separated by ∼4 nm (closed) and another at ∼6 nm (open). Ca shifts the structural equilibrium constant toward the open state by a factor of 13. DEER reveals the distribution of interprobe distances, showing that each of these states is itself partially disordered, with the width of each population ranging from 1 to 3 nm. Both mutations (M109Q and M124Q) decrease the effect of Ca on the structure of CaM, primarily by decreasing the closed-to-open equilibrium constant in the presence of Ca. We propose that Met oxidation alters CaM’s functional interaction with its target proteins by perturbing this Ca-dependent structural shift
[en] ShuA from S. dysenteriae was crystallized in several crystallization conditions containing detergents. Adding heavy atoms during crystallization strongly improved the crystal quality and the resolution limits. Diffraction data were collected at an energy remote from the Pb M absorption edges. As part of efforts towards understanding the crystallization of membrane proteins and membrane transport across the outer membrane of Gram-negative bacteria, the TonB-dependent haem outer membrane transporter ShuA of Shigella dysenteriae bound to heavy atoms was crystallized in several crystallization conditions using detergents. The insertion of a His6 tag into an extracellular loop of ShuA, instead of downstream of the Escherichia coli peptide signal, allowed efficient targeting to the outer membrane and the rapid preparation of crystallizable protein. Crystals diffracting X-rays beyond 3.5 Å resolution were obtained by co-crystallizing ShuA with useful heavy atoms for phasing (Eu, Tb, Pb) by the MAD method at the synchrotron, and the SAD or SIRAS method at the Cu wavelength. The authors collected X-ray diffraction data at 2.3 Å resolution using one crystal of ShuA-Pb, and at 3.2 Å resolution at an energy remote from the Pb M absorption edges for phasing on PROXIMA-1 at SOLEIL
[en] Reporting on the climate action of cities and regions in the context of the pandemic and the renewal of national contributions to the Paris Agreement. Each year, the Climate Chance Observatory proposes a summary of the progress made in terms of climate action and published by cities and regions around the world. Although the absence of consolidated and comparable data remains a challenge, this does not mean that there is no action or mobilisation. The analysis of the remarkable evolution of emissions at the local level, the monitoring of the development of the main international initiatives led by networks of local authorities, and publications of academic and specialised literature, make it possible to draw global trends. The formulation, implementation and monitoring-evaluation of local climate actions is a complex process that requires both the support of States and a proper consideration of the inhabitants' needs. This is why our monitoring is accompanied by analyses of multi-level governance and the localisation of Sustainable Development Goals. The reduction of GHG emissions by European cities is encouraging. However, in a context of mass adoption of carbon neutrality objectives, the monitoring of the impact of local climate policies remains scattered and poorly consolidated, even at the national level. The mobilisation of local governments and the structuring of their climate action is continuing. Although international initiatives show a certain dynamism in Latin America, Europe and North Africa, they do not account for the action of Asian cities and regions. Even in times of Covid-19, local governments remain places of innovation and experimentation for climate policies. At the city level, the densification of services is now seen as the remedy to the health and climate crises. Few of the renewed national contributions to the Paris Agreement mention governance mechanisms that integrate local and sub-national governments, except in Latin America. Their sectoral approach to tackling local emissions reduction masks the potential of spatial planning and local governance. Multi-level governance in G20 countries: our first case studies (Germany, Canada, France, Brazil) show that few cities are subject to climate obligations, whose action relies on the disparate support of federal and federated states. The lack of harmonisation of monitoring methods makes it difficult to integrate the potential of cities into national strategies. Agenda 2030: after a few years in the adoption phase, local governments are embracing the Sustainable Development Goals (SDGs) to cushion the socio-economic shocks of climate policies. Despite the lack of funding, driven by the dynamic exchanges between scientists and decision-makers, adaptation to climate change is accelerating within regions and cities.