Landbouweffectrapport Romeins Aquaduct Tongeren (Tongeren, provincie Limburg)

Het Romeins aquaduct in Tongeren is een uniek monument. Een gedeelte van het aquaduct (het deel op de Beukenberg) is al langer beschermd. Ten tijde van deze studie was er eveneens een beschermingsdossier in opmaak om ook een ander gedeelte te beschermen als archeologisch monument. De restanten van het aquaduct worden immers aangetast door bodemerosie, vooral veroorzaakt door de intensieve landbouw in het gebied. Het beschermingsdossier op zich zou weinig beperkingen opleggen aan de landbouw. Het doel van deze studie was dan ook enerzijds om dit dossier te onderbouwen, maar ook en vooral om te kijken of er een draagvlak aanwezig is om verder te gaan dan een bescherming die louter op papier bestaat. Binnen de perimeter van het aquaduct bevinden er zich 20,25ha landbouwgronden, die deel uitmaken van 38 percelen en in gebruik zijn bij 20 gebruikers. Het gaat om een erg waardevol landbouwgebied, vooral door de goede perceelsstructuren (een gevolg van ruilverkaveling Widooie), de algemene bemestingsnormen en de vruchtbare leemgronden. Het grondgebruik bestaat hoofdzakelijk uit akkerbouw, met in mindere mate fruitteelt en grove groenteteelt. Grasland komt slechts in zeer beperkte mate voor. De landbouwbedrijven met gronden in het gebied zijn in hoofdzaak akkerbouw- en vleesveebedrijven, met ook enkele fruittelers en varkenshouders. De meeste bedrijven zijn vrij grote, dynamische ondernemingen, al zitten er ook een paar hobbybedrijven tussen. De landbouwers zijn overwegend nog vrij jong of hebben opvolgers voor hun bedrijf. Slechts twee of drie bedrijven kunnen als uitbollend worden beschouwd. Deze factoren samen maken het moeilijk om maatregelen te nemen om het aquaduct te beschermen. De landbouwers zelf zijn overwegend ook vrij sceptisch en zien vaak het nut er niet van in. Voor de bescherming van het aquaduct zou het ideale scenario zijn dat de overheid de gronden binnen de perimeter zou kunnen verwerven en dat de percelen onder grasland zouden worden gelegd. Dit lijkt op dit moment echter weinig realistisch. Immers is er slechts één bedrijf op vrij korte termijn bereid om zijn gronden te verkopen. Nog enkele bedrijven zijn eventueel bereid om hun gronden in het gebied te ruilen tegen andere gronden in de omgeving, al dan niet via een lokale grondenbank. Hierbij blijft echter het probleem dat eerst in de omgeving grond verworven moet kunnen worden alvorens men kan ruilen. Bovendien hebben deze bedrijven de betrokken gronden meestal alleen maar in pacht en niet in eigendom, wat de ruilmogelijkheden sterk beperkt. Het inzetten van beheersovereenkomsten om de achteruitgang van het aquaduct tegen te gaan biedt allicht meer mogelijkheden. Vooral de beheersovereenkomsten erosiebestrijding zijn mogelijk interessant. Verschillende landbouwers bleken geïnteresseerd om hierin mee te stappen. Een gerichte inzet van deze beheersovereenkomsten, geconcentreerd op het gebied, zou mogelijk de verdere achteruitgang van het aquaduct kunnen afremmen. Toch zal men er rekening mee moeten houden dat de effectieve bescherming van het aquaduct een werk van lange adem zal zijn

HORACE: software for the analysis of data from single crystal spectroscopy experiments at time-of-flight neutron instruments

The HORACE suite of programs has been developed to work with large multiple-measurement data sets collected from time-of-flight neutron spectrometers equipped with arrays of position-sensitive detectors. The software allows exploratory studies of the four dimensions of reciprocal space and excitation energy to be undertaken, enabling multi-dimensional subsets to be visualized, algebraically manipulated, and models for the scattering to simulated or fitted to the data. The software is designed to be an extensible framework, thus allowing user-customized operations to be performed on the data. Examples of the use of its features are given for measurements exploring the spin waves of the simple antiferromagnet RbMnF$_{3}$ and ferromagnetic iron, and the phonons in URu$_{2}$Si$_{2}$.Comment: 14 pages, 6 figure

Methionine sulfoxide reductase B from Corynebacterium diphtheriae catalyzes sulfoxide reduction via an intramolecular disulfide cascade

Corynebacterium diphtheriae is a human pathogen that causes diphtheria. In response to immune system–induced oxidative stress, C. diphtheriae expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic mechanism of the Msr enzymes have been reported, several details still await full elucidation. Here, we solved the solution structure of C. diphtheriae MsrB (Cd-MsrB) and unraveled its catalytic and oxidation-protection mechanisms. Cd-MsrB catalyzes methionine sulfoxide reduction involving three redox-active cysteines. Using NMR heteronuclear single-quantum coherence (HSQC) spectra, kinetics, biochemical assays, and MS analyses, we show that the conserved nucleophilic residue Cys122 is S-sulfenylated after substrate reduction, which is then resolved by a conserved cysteine, Cys66, or by the non-conserved residue Cys127. We noted that the overall structural changes during the disulfide cascade expose the Cys122–Cys66 disulfide to recycling through thioredoxin (Trx). In the presence of hydrogen peroxide, Cd-MsrB formed reversible intra- and intermolecular disulfides without losing its Cys-coordinated Zn2+, and only the non-conserved Cys127 reacted with the low-molecular-weight (LMW) thiol mycothiol, protecting it from overoxidation. In summary, our structure–function analyses reveal critical details of the Cd-MsrB catalytic mechanism, including a major structural rearrangement that primes the Cys122–Cys66 disulfide for Trx reduction and a reversible protection against excessive oxidation of the catalytic cysteines in Cd-MsrB through intra- and intermolecular disulfide formation and S-mycothiolation

Structural and Biophysical Characterization of Staphylococcus Aureus SaMazF Shows Conservation of Functional Dynamics

The Staphylococcus aureus genome contains three toxin-antitoxin modules, including one mazEF module, SamazEF. Using an on-column separation protocol we are able to obtain large amounts of wild-type SaMazF toxin. The protein is well-folded and highly resistant against thermal unfolding but aggregates at elevated temperatures. Crystallographic and nuclear magnetic resonance (NMR) solution studies show a well-defined dimer. Differences in structure and dynamics between the X-ray and NMR structural ensembles are found in three loop regions, two of which undergo motions that are of functional relevance. The same segments also show functionally relevant dynamics in the distantly related CcdB family despite divergence of function. NMR chemical shift mapping and analysis of residue conservation in the MazF family suggests a conserved mode for the inhibition of MazF by MazE

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor

Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases

Characterization of the Interaction and Cross-Regulation of Three Mycobacterium tuberculosis RelBE Modules

RelBE represents a typical bacterial toxin-antitoxin (TA) system. Mycobacterium tuberculosis H37Rv, the pathogen responsible for human tuberculosis, contains three RelBE-like modules, RelBE, RelFG, and RelJK, which are at least partly expressed in human macrophages during infection. RelBE modules appear to be autoregulated in an atypical manner compared to other TA systems; however, the molecular mechanisms and potential interactions between different RelBE modules remain to be elucidated. In the present study, we characterized the interaction and cross-regulation of these Rel toxin-antitoxin modules from this unique pathogen. The physical interactions between the three pairs of RelBE proteins were confirmed and the DNA-binding domain recognized by three RelBE-like pairs and domain structure characteristics were described. The three RelE-like proteins physically interacted with the same RelB-like protein, and could conditionally regulate its binding with promoter DNA. The RelBE-like modules exerted complex cross-regulation effects on mycobacterial growth. The relB antitoxin gene could replace relF in cross-neutralizing the relG toxin gene. Conversely, relF enhanced the toxicity of the relE toxin gene, while relB increased the toxicity of relK. This is the first report of interactions between different pairs of RelBE modules of M. tuberculosis

Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study

BACKGROUND: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population. METHODS: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing. FINDINGS: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases). INTERPRETATION: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes. FUNDING: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre

Txe, an endoribonuclease of the enterococcal Axe–Txe toxin–antitoxin system, cleaves mRNA and inhibits protein synthesis

The axe–txe operon encodes a toxin–antitoxin (TA) pair, Axe–Txe, that was initially identified on the multidrug-resistance plasmid pRUM in Enterococcus faecium. In Escherichia coli, expression of the Txe toxin is known to inhibit cell growth, and co-expression of the antitoxin, Axe, counteracts the toxic effect of Txe. Here, we report the nucleotide sequence of pS177, a 39 kb multidrug-resistant plasmid isolated from vancomycin-resistant Ent. faecium, which harbours the axe–txe operon and the vanA gene cluster. RT-PCR analysis revealed that the axe–txe transcript is produced by strain S177 as well as by other vancomycin-resistant enteroccoci. Moreover, we determine the mechanism by which the Txe protein exerts its toxic activity. Txe inhibits protein synthesis in E. coli without affecting DNA or RNA synthesis, and inhibits protein synthesis in a cell-free system. Using in vivo primer extension analysis, we demonstrate that Txe preferentially cleaves single-stranded mRNA at the first base after an AUG start codon. We conclude that Txe is an endoribonuclease which cleaves mRNA and inhibits protein synthesis