Genome Sequence of the Moderately Acidophilic Sulfate-Reducing Firmicute Desulfosporosinus acididurans (Strain M1T)

Microbial dissimilatory sulfate reduction is commonplace in many anaerobic environments, though few acidophilic bacteria are known to mediate this process. We report the 4.64-Mb draft genome of the type strain of the moderate acidophile Desulfosporosinus acididurans, which was isolated from acidic sediment in a river draining the Soufrière volcano, Montserrat

Genome Sequence of the Acidophilic Sulfate-Reducing Peptococcaceae Strain CEB3

We report the draft genome of the Peptococcaceae strain CEB3 that originated from an acidic (pH 2.5) stream draining an abandoned copper mine. Strain CEB3 is one of the very few reported acidophilic sulfate-reducing isolates. The 5.04-Mb draft genome harbors 5,069 predicted protein-encoding and 66 RNA genes

Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species

Alzheimer's disease is the most common age-associated neurodegenerative disorder and the most frequent form of dementia in our society. Aging is a complex biological process concurrently shaped by genetic, dietary and environmental factors and natural compounds are emerging for their beneficial effects against age-related disorders. Besides their antioxidant activity often described in simple model organisms, the molecular mechanisms underlying the beneficial effects of different dietary compounds remain however largely unknown. In the present study, we exploit the nematode Caenorhabditis elegans as a widely established model for aging studies, to test the effects of different natural compounds in vivo and focused on mechanistic aspects of one of them, quercetin, using complementary systems and assays. We show that quercetin has evolutionarily conserved beneficial effects against Alzheimer's disease (AD) pathology: it prevents Amyloid beta (A beta)-induced detrimental effects in different C. elegans AD models and it reduces A beta-secretion in mammalian cells. Mechanistically, we found that the beneficial effects of quercetin are mediated by autophagy-dependent reduced expression of Abl tyrosine kinase. In turn, autophagy is required upon Abl suppression to mediate quercetin's protective effects against A beta toxicity. Our data support the power of C. elegans as an in vivo model to investigate therapeutic options for AD

The purinergic receptor P2X7 as a modulator of viral vector-mediated antigen cross-presentation

INTRODUCTION: Modified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8 +T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing. METHODS: To improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells. The infected feeder cells serve as source of antigen and provide signals that help to attract dendritic cells for antigen take up and to license these cells for cross-presentation. RESULTS: We demonstrate that presence of an active P2RX7 in major histocompatibility complex (MHC) class I (MHCI) mismatched feeder cells significantly enhanced MVA-mediated antigen cross-presentation. This was partly regulated by P2RX7-specific processes, such as the increased availability of extracellular particles as well as the altered cellular energy metabolism by mitochondria in the feeder cells. Furthermore, functional P2RX7 in feeder cells resulted in a delayed but also prolonged antigen expression after infection. DISCUSSION: We conclude that a combination of the above mentioned P2RX7-depending processes leads to significantly increased T cell activation via cross- presentation of MVA-derived antigens. To this day, P2RX7 has been mostly investigated in regards to neuroinflammatory diseases and cancer progression. However, we report for the first time the crucial role of P2RX7 for antigen- specific T cell immunity in a viral infection model

Lymphotoxin-β-receptor (LTβR) signaling on hepatocytes is required for liver regeneration after partial hepatectomy

Lymphotoxin-p-receptor deficient (LT beta R-/-) and Tumor Necrosis Factor Receptor p55 deficient (TNFRp55(-/-)) mice show defects in liver regeneration (LR) after partial hepatectomy (PHx) with significantly increased mortality. LT beta R and TNFRp55 belong to the core members of the TNF/TNFR superfamily. Interestingly, combined failure of LT beta R and TNFRp55 signaling after PHx leads to a complete defect in LR. Here, we first addressed the question which liver cell population crucially requires LT beta R signaling for efficient LR. To this end, mice with a conditionally targeted LT beta R allele (LT beta R-fl/fl) were crossed to AlbuminCre and Lysozy-meMCre mouse lines to unravel the function of the LT beta R on hepatocytes and monocytes/macrophages/Kupffer cells, respectively. Analysis of these mouse lines clearly reveals that LT beta R is required on hepatocytes for efficient LR while no deficit in LR was found in LT beta R-fl/fl x LysMCre mice. Second, the molecular basis for the cooperating role of LT beta R and TNFRp55 signaling pathways in LR was investigated by transcriptome analysis of etanercept treated LT beta R-/- (LT beta R-/-/ET) mice. Bioinformatic analysis and subsequent verification by qRT-PCR identified novel target genes (Cyclin-L2, Fas-Binding factor 1, interferon-related developmental regulator 1, Leucyl-tRNA Synthetase 2, and galectin-4) that are upregulated by LT beta R/TNFRp55 signaling after PHx and fail to be upregulated after PHx in LT beta R-/-/ET mice

Siponimod Modulates the Reaction of Microglial Cells to Pro-Inflammatory Stimulation

Siponimod (Mayzent®), a sphingosine 1-phosphate receptor (S1PR) modulator which prevents lymphocyte egress from lymphoid tissues, is approved for the treatment of relapsing-remitting and active secondary progressive multiple sclerosis. It can cross the blood–brain barrier (BBB) and selectively binds to S1PR1 and S1PR5 expressed by several cell populations of the central nervous system (CNS) including microglia. In multiple sclerosis, microglia are a key CNS cell population moving back and forth in a continuum of beneficial and deleterious states. On the one hand, they can contribute to neurorepair by clearing myelin debris, which is a prerequisite for remyelination and neuroprotection. On the other hand, they also participate in autoimmune inflammation and axonal degeneration by producing pro-inflammatory cytokines and molecules. In this study, we demonstrate that siponimod can modulate the microglial reaction to lipopolysaccharide-induced pro-inflammatory activation