Marked mitochondrial DNA depletion associated with a novel SUCLG1 gene mutation resulting in lethal neonatal acidosis,multi-organ failure,and interrupted aortic arch

The aim of this study was to identify the causative genetic lesion in two apparently unrelated newborns having lethal lactic acidosis, multi-organ failure and congenital malformations including interrupted aortic arch, who exhibited mild methylmalonic aciduria, combined mitochondrial respiratory chain deficiency, and marked muscle mitochondrial DNA depletion. A novel mutation in the SUCLG1 gene was identified. Phenotype severity in Succinate-CoA ligase dysfunction appears to be more correlated to the muscle mtDNA content than to the tissue distribution of the heterodimer subunits. Prominent impairment of mitochondrial respiratory chain may result in deep ravages in developmental tissues leading to multiple organ failure and malformations.     

Plasmacytoid myoepithelioma of the soft palate. Report of a case with cytologic, immunohistochemical and electron microscopic studies

BACKGROUND: The plasmacytoid variant is a rare and controversial subtype of myoepithelioma that lacks myogenic differentation and the cytologic findings of which have not been reported previously. CASE: A 46-year-old man presented with a painless tumor located in the soft palate. Fine needle aspiration cytology (FNAC) showed odd-shaped cellular aggregates and single cells with round nuclei and finely granular cytoplasm resembling plasma cells together with strands of metachromatic stroma. The light, immunohistochemical and ultrastructural studies performed on the surgical specimen confirmed the initial cytologic diagnosis. CONCLUSION: Recognition of the cytologic findings of plasmacytoid myoepithelioma on needle aspirates allows a reliable and quick diagnosis that prompts correct management.     

The Tau/A152T mutation,a risk factor for frontotemporal‐spectrum disorders,leads to NR2B receptor‐mediated excitotoxicity

We report on a novel transgenic mouse model expressing human full‐length Tau with the Tau mutation A152T (hTau^AT), a risk factor for FTD‐spectrum disorders including PSP and CBD. Brain neurons reveal pathological Tau conformation, hyperphosphorylation, mis‐sorting, aggregation, neuronal degeneration, and progressive loss, most prominently in area CA3 of the hippocampus. The mossy fiber pathway shows enhanced basal synaptic transmission without changes in short‐ or long‐term plasticity. In organotypic hippocampal slices, extracellular glutamate increases early above control levels, followed by a rise in neurotoxicity. These changes are normalized by inhibiting neurotransmitter release or by blocking voltage‐gated sodium channels. CA3 neurons show elevated intracellular calcium during rest and after activity induction which is sensitive to NR2B antagonizing drugs, demonstrating a pivotal role of extrasynaptic NMDA receptors. Slices show pronounced epileptiform activity and axonal sprouting of mossy fibers. Excitotoxic neuronal death is ameliorated by ceftriaxone, which stimulates astrocytic glutamate uptake via the transporter EAAT2/GLT1. In summary, hTau^AT causes excitotoxicity mediated by NR2B‐containing NMDA receptors due to enhanced extracellular glutamate.     

Intracellular lifestyle of Brucella spp. Common genes with other animal pathogens, plant pathogens, and endosymbionts

Brucella spp. are intracellular pathogens that belong, like Agrobacterium, Rhizobium and Rickettsia, to the alpha-2-subgroup of proteobacteria. The genome organization of most Brucella spp. is characterized by the presence of two chromosomes. The intracellular lifestyle of Brucella, as well as the possible genes involved in pathogenesis and host cell signaling, are discussed, including the presence of genes with high similarity to those from other animal pathogens, plant pathogens and endosymbionts.     

Delivery of a Salmonella Typhi exotoxin from a host intracellular compartment

Salmonella Typhi, an exclusive human pathogen and the cause of typhoid fever, expresses a functional cytolethal distending toxin for which only the active subunit, CdtB, has been identified. Here, we show that PltA and PltB, which are encoded in the same pathogenicity islet as cdtB, associate with CdtB to form a multipartite toxin. PltA and PltB are homologs of components of the pertussis toxin, including its ADP-ribosyl transferase subunit. We also show that PltA and PltB are required for the delivery of CdtB from an intracellular compartment to target cells via autocrine and paracrine pathways. We hypothesize that this toxin, which we have named "typhoid toxin," and its delivery mechanism may contribute to S. Typhi's unique virulence properties.