Ichthyosis in Sjögren–Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion

Sjögren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion

Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

EUKARYOME: the rRNA gene reference database for identification of all eukaryotes

Molecular identification of micro- and macroorganisms based on nuclear markers has revolutionized our understanding of their taxonomy, phylogeny and ecology. Today, research on the diversity of eukaryotes in global ecosystems heavily relies on nuclear ribosomal RNA (rRNA) markers. Here, we present the research community-curated reference database EUKARYOME for nuclear ribosomal 18S rRNA, internal transcribed spacer (ITS) and 28S rRNA markers for all eukaryotes, including metazoans (animals), protists, fungi and plants. It is particularly useful for the identification of arbuscular mycorrhizal fungi as it bridges the four commonly used molecular markers-ITS1, ITS2, 18S V4-V5 and 28S D1-D2 subregions. The key benefits of this database over other annotated reference sequence databases are that it is not restricted to certain taxonomic groups and it includes all rRNA markers. EUKARYOME also offers a number of reference long-read sequences that are derived from (meta)genomic and (meta)barcoding-a unique feature that can be used for taxonomic identification and chimera control of third-generation, long-read, high-throughput sequencing data. Taxonomic assignments of rRNA genes in the database are verified based on phylogenetic approaches. The reference datasets are available in multiple formats from the project homepage, http://www.eukaryome.org

Spatial Sequestration and Oligomer Remodeling During \u3cem\u3ede novo\u3c/em\u3e [\u3cem\u3ePSI\u3c/em\u3e\u3csup\u3e+\u3c/sup\u3e] Formation

Prions are misfolded, aggregated, infectious proteins found in a range of organisms from mammals to bacteria. In mammals, prion formation is difficult to study because misfolding and aggregation take place prior to symptom presentation. The study of the yeast prion [PSI+], which is the misfolded infectious form of Sup35p, provides a tractable system to monitor prion formation in real time. Recently, we showed that the de novo formation of prion aggregates begins with the appearance of highly mobile cytoplasmic foci, called early foci, which assemble into larger ring or dot structures. We also observed SDS-resistant oligomers during formation, and lysates containing newly formed oligomers can convert [psi−] cells to the [PSI+] state, suggesting that these oligomers have infectious potential. Here, we further characterize two aspects of prion formation: spatial sequestration of early foci and oligomerization of endogenous Sup35p. Our data provides important insights into the process of prion formation and explores the minimal oligomer requirement for infectivity

Kondo physics in tunable semiconductor nanowire quantum dots

We have observed the Kondo effect in strongly coupled semiconducting nanowire quantum dots. The devices are made from indium arsenide nanowires, grown by molecular beam epitaxy, and contacted by titanium leads. The device transparency can be tuned by changing the potential on a gate electrode, and for increasing transparencies the effects dominating the transport changes from Coulomb Blockade to Universal Conductance Fluctuations with Kondo physics appearing in the intermediate region.Comment: 4 pages, 4 figure

An interesting case of neurocutaneous syndrome

Neuroichthyosis is a group of rare genetically determined disease with cutaneous and neurological manifestations due to abnormalities in any of the following: lipid metabolism, glycoprotein synthesis, or intracellular vesicle trafficking. There are about 16 disorders with known genetic aetiology like Sjogren Larssons syndrome (SLS), Refsum disease, Gauchers disease type 2, ELOVL4 deficiency etc. Among the various neuroicthyosis syndromes, Sjogren Larsson syndrome is the most common entity characterised by ichthyosis, spastic diplegia or tetraplegia, cognitive dysfunction, seizures, and a maculopathy with glistening white dots. We hereby report a case of neuroichthyosis disease who presented to us with developmental delay, spastic paraplegia, seizure and ichthyosis, whose genetic testing showed homozygous mutation in ALDH3A2, suggestive of Sjogren Larsson syndrome

Minimum detection efficiency for a loophole-free atom-photon Bell experiment

In Bell experiments, one problem is to achieve high enough photodetection to ensure that there is no possibility of describing the results via a local hidden-variable model. Using the Clauser-Horne inequality and a two-photon non-maximally entangled state, a photodetection efficiency higher than 0.67 is necessary. Here we discuss atom-photon Bell experiments. We show that, assuming perfect detection efficiency of the atom, it is possible to perform a loophole-free atom-photon Bell experiment whenever the photodetection efficiency exceeds 0.50.Comment: REVTeX4, 4 pages, 1 figur