To be or not to be phosphorylated: understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56.

Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral transcription activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in the regulation of this process by recruiting both the regulatory subunit B56 of PP2A and its substrate VP30 to initiate VP30 dephosphorylation and hence viral transcription. Both binding sites are located in close proximity to each other in NP's C-terminal-disordered region.

Mitochondrial phosphoproteomes are functionally specialized across tissues.

Mitochondria are essential organelles whose dysfunction causes human pathologies that often manifest in a tissue-specific manner. Accordingly, mitochondrial fitness depends on versatile proteomes specialized to meet diverse tissue-specific requirements. Increasing evidence suggests that phosphorylation may play an important role in regulating tissue-specific mitochondrial functions and pathophysiology.

Starting the engine of the powerhouse: mitochondrial transcription and beyond.

Mitochondria are central hubs for cellular metabolism, coordinating a variety of metabolic reactions crucial for human health. Mitochondria provide most of the cellular energy via their oxidative phosphorylation (OXPHOS) system, which requires the coordinated expression of genes encoded by both the nuclear (nDNA) and mitochondrial genomes (mtDNA). Transcription of mtDNA is not only essential for the biogenesis of the OXPHOS system, but also generates RNA primers necessary to initiate mtDNA replication.

Artemisinin and its derivatives target mitochondrial c-type cytochromes in yeast and human cells.

Artemisinin and its derivatives kill malaria parasites and inhibit the proliferation of cancer cells. In both processes, heme was shown to play a key role in artemisinin bioactivation. We found that artemisinin and clinical artemisinin derivatives are able to compensate for a mutation in the yeast Bcs1 protein, a key chaperon involved in biogenesis of the mitochondrial respiratory complex III.

Mitochondrial fusion is required for regulation of mitochondrial DNA replication.

Mitochondrial dynamics is an essential physiological process controlling mitochondrial content mixing and mobility to ensure proper function and localization of mitochondria at intracellular sites of high-energy demand. Intriguingly, for yet unknown reasons, severe impairment of mitochondrial fusion drastically affects mtDNA copy number. To decipher the link between mitochondrial dynamics and mtDNA maintenance, we studied mouse embryonic fibroblasts (MEFs) and mouse cardiomyocytes with disruption of mitochondrial fusion.

TEFM regulates both transcription elongation and RNA processing in mitochondria.

Regulation of replication and expression of mitochondrial DNA (mtDNA) is essential for cellular energy conversion via oxidative phosphorylation. The mitochondrial transcription elongation factor (TEFM) has been proposed to regulate the switch between transcription termination for replication primer formation and processive, near genome-length transcription for mtDNA gene expression. Here, we report that is essential for mouse embryogenesis and that levels of promoter-distal mitochondrial transcripts are drastically reduced in conditional -knockout hearts.

Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals.

Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively.

POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA.

Mitochondria are vital in providing cellular energy via their oxidative phosphorylation system, which requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes (mtDNA). Transcription of the circular mammalian mtDNA depends on a single mitochondrial RNA polymerase (POLRMT). Although the transcription initiation process is well understood, it is debated whether POLRMT also serves as the primase for the initiation of mtDNA replication.

Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid.

Mammalian mitochondrial DNA (mtDNA) is packaged by mitochondrial transcription factor A (TFAM) into mitochondrial nucleoids that are of key importance in controlling the transmission and expression of mtDNA. Nucleoid ultrastructure is poorly defined, and therefore we used a combination of biochemistry, superresolution microscopy, and electron microscopy to show that mitochondrial nucleoids have an irregular ellipsoidal shape and typically contain a single copy of mtDNA. Rotary shadowing electron microscopy revealed that nucleoid formation in vitro is a multistep process initiated by TFAM aggregation and cross-strand binding.

Framework for handling asbestos after a tidal surge.

The tidal surge associated with Tropical Cyclone Yasi--a category 5 system--on February 3, 2011, culminated in asbestos-containing material (ACM) becoming comingled with soil, sand, vegetation, and other debris in the communities of Tully Heads and Hull Heads in Queensland, Australia. The situation was a major concern and the area was deemed by the Queensland Government a priority due to the potential public health risk. The immediate challenge was that no agreed-upon operational framework existed between key response organizations for handling ACM after a tidal surge.

TWINKLE is an essential mitochondrial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication.

Replication of the mammalian mitochondrial DNA (mtDNA) is dependent on the minimal replisome, consisting of the heterotrimeric mtDNA polymerase (POLG), the hexameric DNA helicase TWINKLE and the tetrameric single-stranded DNA-binding protein (mtSSB). TWINKLE has been shown to unwind DNA during the replication process and many disease-causing mutations have been mapped to its gene. Patients carrying Twinkle mutations develop multiple deletions of mtDNA, deficient respiratory chain function and neuromuscular symptoms.

The Cbp3-Cbp6 complex coordinates cytochrome b synthesis with bc(1) complex assembly in yeast mitochondria.

Respiratory chain complexes in mitochondria are assembled from subunits derived from two genetic systems. For example, the bc(1) complex consists of nine nuclear encoded subunits and the mitochondrially encoded subunit cytochrome b. We recently showed that the Cbp3-Cbp6 complex has a dual function for biogenesis of cytochrome b: it is both required for efficient synthesis of cytochrome b and for protection of the newly synthesized protein from proteolysis.

Schizosaccharomyces pombe homologs of the Saccharomyces cerevisiae mitochondrial proteins Cbp6 and Mss51 function at a post-translational step of respiratory complex biogenesis.

Complexes III and IV of the mitochondrial respiratory chain contain a few key subunits encoded by the mitochondrial genome. In Saccharomyces cerevisiae, fifteen mRNA-specific translational activators control mitochondrial translation, of which five are conserved in Schizosaccharomyces pombe. These include homologs of Cbp3, Cbp6 and Mss51 that participate in translation and the post-translational steps leading to the assembly of respiratory complexes III and IV.

A genome wide study in fission yeast reveals nine PPR proteins that regulate mitochondrial gene expression.

Pentatricopeptide repeat (PPR) proteins are particularly numerous in plant mitochondria and chloroplasts, where they are involved in different steps of RNA metabolism, probably due to the repeated 35 amino acid PPR motifs that are thought to mediate interactions with RNA. In non-photosynthetic eukaryotes only a handful of PPR proteins exist, for example the human LRPPRC, which is involved in a mitochondrial disease. We have conducted a systematic study of the PPR proteins in the fission yeast Schizosaccharomyces pombe and identified, in addition to the mitochondrial RNA polymerase, eight proteins all of which localized to the mitochondria, and showed some association with the membrane.

Photodynamic therapy with delta-aminolevulinic acid and light-emitting diodes in actinic keratosis.

Background: Photodynamic therapy is a form of treatment in which a photosensitizing substance is applied to tissue and activated by a light source at a specific wavelength, thus selectively destroying cells. New light sources are being evaluated for use in the treatment of actinic keratoses.

Objectives: To evaluate the efficacy of photodynamic therapy with delta-aminolevulinic acid using a light emitting diode device as a light source in the treatment of actinic keratoses of the face and upper limbs.

The human mitochondrial ribosome recycling factor is essential for cell viability.

The molecular mechanism of human mitochondrial translation has yet to be fully described. We are particularly interested in understanding the process of translational termination and ribosome recycling in the mitochondrion. Several candidates have been implicated, for which subcellular localization and characterization have not been reported.

mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG.

Human mitochondria contain their own genome, encoding 13 polypeptides that are synthesized within the organelle. The molecular processes that govern and facilitate this mitochondrial translation remain unclear. Many key factors have yet to be characterized-for example, those required for translation termination.

[2 trephined skulls from Schleswig-Holstein].

In Schleswig-Holstein two trephined skulls are found, one belonging to a man deceased in the first half of adult age, who was buried in a stone grave of Middle Neolithic Age from Nebel on the isle of Amrum (published by Schaefer 1958, 1961). Another well preserved one, but without known site in Schleswig-Holstein, is the calvarium of a young adult presumably male showing a circular trephination without any tendency of healing. There is no symptom of a pathological change at the inner vault of the skull, but for the coronal suture gap .

[Stress deformations of skeletal remains from prehistoric cremation burials].

Vertebrae and parts of joints from long bones from prehistoric cremations of the Late Bronze Age and Early Iron Age are presented, showing marked deformations caused by pressure during cremation when bones exposed to temperatures of 400 degrees-500 degrees Centigrade display minimal hardness. The vertebrae with deformation of the arcus parts are only from the lower vertebral column; on account of the weight of this body region, this suggests that the corpse lay in the dorsal position at the place of cremation. The fact that there were deformed arches only on one side might suggest an irregular structure of the surface on which the corpse lay.

[Cutaneous Crohn disease].

The term "metastatic" Crohn's disease is used to define the cutaneous lesions, distant from the gastrointestinal tract and separated from other ulcerations by normal skin, showing granulomatous histology. A case of Crohn's disease with metastatic ulcerations of the vulva, perineum, submammary folds, groins and abdominal fold is presented. In the literature only 26 similar cases were found.

[The Leser-Trélat sign associated with carcinoma of the cervix uteri. Report of a case and review of the literature].

The sign of Leser-Trélat in a patient with squamous cell carcinoma of the cervix is reported. This seems to be the first report of this association. Literature was reviewed, try to correlate this entity with acanthosis nigricans and to link this sign with internal malignancy or other kind of epidermal stimuli.