HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release

Presynaptic densities are specialized structures involved in synaptic vesicle tethering and neurotransmission; however, the mechanisms regulating their function remain understudied. In Drosophila, Bruchpilot is a major constituent of the presynaptic density that tethers vesicles. Here, we show that HDAC6 is necessary and sufficient for deacetylation of Bruchpilot. HDAC6 expression is also controlled by TDP-43, an RNA-binding protein deregulated in amyotrophic lateral sclerosis (ALS). Animals expressing TDP-43 harboring pathogenic mutations show increased HDAC6 expression, decreased Bruchpilot acetylation, larger vesicle-tethering sites, and increased neurotransmission, defects similar to those seen upon expression of HDAC6 and opposite to hdac6 null mutants. Consequently, reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion. Our work identifies HDAC6 as a Bruchpilot deacetylase and indicates that regulating acetylation of a presynaptic release-site protein is critical for maintaining normal neurotransmission

Desynchronization during anticipatory attention for an upcoming stimulus: A comparative EEG/MEG study

Objectives: Our neurophysiological model of anticipatory behaviour (e.g. Acta Psychol 101 (1999) 213; Bastiaansen et al., 1999a) predicts an activation of (primary) sensory cortex during anticipatory attention for an upcoming stimulus. In this paper we attempt to demonstrate this by means of event-related desynchronization (ERD). Methods: Five subjects performed a time estimation task, and were informed about the quality of their time estimation by either visual or auditory stimuli providing Knowledge of Results (KR). EEG and MEG were recorded in separate sessions, and ERD was computed in the 8± 10 and 10±12 Hz frequency bands for both datasets. Results: Both in the EEG and the MEG we found an occipitally maximal ERD preceding the visual KR for all subjects. Preceding the auditory KR, no ERD was present in the EEG, whereas in the MEG we found an ERD over the temporal cortex in two of the 5 subjects. These subjects were also found to have higher levels of absolute power over temporal recording sites in the MEG than the other subjects, which we consider to be an indication of the presence of a `tau' rhythm (e.g. Neurosci Lett 222 (1997) 111). Conclusions: It is concluded that the results are in line with the predictions of our neurophysiological model

Functional Metagenomic Investigations of the Human Intestinal Microbiota

The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host. Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex community and its human host

Recognition of differences in the capacity to deal with floods—A cross-country comparison of flood risk management

Flood risks worldwide are increasing due to climate change. Managing these risks is ever more necessary. Although flood risk management (FRM) is often understood as a technical challenge, it also involves decisions about the distribution of resources and risks in floods, which can be inherently unfair. People are disparately affected by floods due to their location. Because of their various socioeconomic and demographic characteristics, they also differ in their capacity to deal with floods. These differences need to be recognised in FRM to prevent disproportionate impacts on vulnerable communities. However, at present, a knowledge gap exists on how to make FRM more inclusive and just, and discussions on recognition justice in the context of FRM are scarce. This article therefore examines recognition of differences in the capacity of people to deal with floods in FRM in England (United Kingdom), Finland, Flanders (Belgium) and France. We analyse if, and how, these differences are recognised in FRM policy and practice and through decision-making procedures, drawing on examples from the implementation of five FRM strategies in each country (flood risk prevention, flood defence, flood risk mitigation, flood preparation and flood recovery). Furthermore, we aim to highlight opportunity spaces to strengthen recognition justice in future FRM

Adaptive Laboratory Evolution of Antibiotic Resistance Using Different Selection Regimes Lead to Similar Phenotypes and Genotypes

Antibiotic resistance is a global threat to human health, wherefore it is crucial to study the mechanisms of antibiotic resistance as well as its emergence and dissemination. One way to analyze the acquisition of de novo mutations conferring antibiotic resistance is adaptive laboratory evolution. However, various evolution methods exist that utilize different population sizes, selection strengths, and bottlenecks. While evolution in increasing drug gradients guarantees high-level antibiotic resistance promising to identify the most potent resistance conferring mutations, other selection regimes are simpler to implement and therefore allow higher throughput. The specific regimen of adaptive evolution may have a profound impact on the adapted cell state. Indeed, substantial effects of the selection regime on the resulting geno- and phenotypes have been reported in the literature. In this study we compare the geno- and phenotypes of Escherichia coli after evolution to Amikacin, Piperacillin, and Tetracycline under four different selection regimes. Interestingly, key mutations that confer antibiotic resistance as well as phenotypic changes like collateral sensitivity and cross-resistance emerge independently of the selection regime. Yet, lineages that underwent evolution under mild selection displayed a growth advantage independently of the acquired level of antibiotic resistance compared to lineages adapted under maximal selection in a drug gradient. Our data suggests that even though different selection regimens result in subtle genotypic and phenotypic differences key adaptations appear independently of the selection regime

Comparative analysis of a batch and continuous fluidized bed reactors for thermocatalytic decomposition of methane:A CFD-DEM-MGM approach

ThermoCatalytic Decomposition of methane (TCD) has shown great potential for synthesis of valuable carbon nanomaterials as well as hydrogen production, however due to the importance of the phenomena operating at different scales, it is a complex process to model and predict. During the TCD process methane is decomposed to hydrogen gas and solid carbon. Carbon is accumulated on the catalyst particle and leads to larger but less active catalyst particles. In this study, a Computational Fluid Dynamics-Discrete Element Method-Multi Grain Model (CFD-DEM-MGM) was employed to investigate two catalytic fluidized bed reactors for TCD with the same dimensions. Case-1 involved a batch of catalyst particles staying in the reactor during the process, while Case-2 featured a continuous reactor with removal of catalyst particles from the bottom and the introduction of fresh particles from the side. Results showed that the continuous reactor had lower catalyst particle growth and reduced deactivation due to limited residence time, yet demonstrated higher carbon production and gas conversion. Case-1, with larger catalyst particles, experienced reduced bubble formation, while in Case-2 the continuous removal/introduction of particles enhanced solids mixing. Internal diffusion limitations affected reactor performance, emphasizing the CFD-DEM-MGM model’s potential for optimizing fluidized bed reactor design and gas-solid contacting in the TCD process.ThermoCatalytic Decomposition of methane (TCD) has shown great potential for synthesis of valuable carbon nanomaterials as well as hydrogen production, however due to the importance of the phenomena operating at different scales, it is a complex process to model and predict. During the TCD process methane is decomposed to hydrogen gas and solid carbon. Carbon is accumulated on the catalyst particle and leads to larger but less active catalyst particles. In this study, a Computational Fluid Dynamics-Discrete Element Method-Multi Grain Model (CFD-DEM-MGM) was employed to investigate two catalytic fluidized bed reactors for TCD with the same dimensions. Case-1 involved a batch of catalyst particles staying in the reactor during the process, while Case-2 featured a continuous reactor with removal of catalyst particles from the bottom and the introduction of fresh particles from the side. Results showed that the continuous reactor had lower catalyst particle growth and reduced deactivation due to limited residence time, yet demonstrated higher carbon production and gas conversion. Case-1, with larger catalyst particles, experienced reduced bubble formation, while in Case-2 the continuous removal/introduction of particles enhanced solids mixing. Internal diffusion limitations affected reactor performance, emphasizing the CFD-DEM-MGM model’s potential for optimizing fluidized bed reactor design and gas-solid contacting in the TCD process

Catalytic enantioselective aza-Reformatsky reaction with seven-membered cyclic imines dibenzo[b,f][1,4]oxazepines

A catalytic enantioselective aza-Reformatsky reaction is reported with cyclic dibenzo[b,f][1,4]oxazepines and ethyl iodoacetate leading to the synthesis of chiral ethyl 2-(10,11-dihydrodibenzo[b,f][1,4]oxazepin-11-yl)acetate derivatives with excellent yields and high enantioselectivities (up to 98% yield and 97 : 3 er) using a readily available diaryl prolinol L4 as the chiral ligand and Me2Zn as the zinc source under an air atmosphere. Furthermore, different transformations were carried out with the corresponding chiral β-amino esters, preserving in all cases the optical purity

A dual function for Pex3p in peroxisome formation and inheritance

Saccharomyces cerevisiae Pex3p has been shown to act at the ER during de novo peroxisome formation. However, its steady state is at the peroxisomal membrane, where its role is debated. Here we show that Pex3p has a dual function: one in peroxisome formation and one in peroxisome segregation. We show that the peroxisome retention factor Inp1p interacts physically with Pex3p in vitro and in vivo, and split-GFP analysis shows that the site of interaction is the peroxisomal membrane. Furthermore, we have generated PEX3 alleles that support peroxisome formation but fail to support recruitment of Inp1p to peroxisomes, and as a consequence are affected in peroxisome segregation. We conclude that Pex3p functions as an anchor for Inp1p at the peroxisomal membrane, and that this function is independent of its role at the ER in peroxisome biogenesis