Posterior positional plagiocephaly treated with cranial remodeling orthosis.

Since the recommendation that infants sleep in the supine position, there has been an increase in cases of posterior positional plagiocephaly. Even though this condition is a purely cosmetic problem, if it is severe it may affect the child psychologically. Positioning may help in mild or moderate cases, but more active treatment may be necessary in severe cases. A prospective study of 260 children treated by dynamic orthotic cranioplasty for posterior positional plagiocephaly was conducted in Lausanne from 1995 to 2001. Construction of these cranial remodelling helmets is decribed in detail. The treatment lasted 3 months on average, was effective, well tolerated, and had zero morbidity. The ideal period for initiating this therapy is between the ages of 4 and 6 months. The remodelling helmet is a convincing option which can be recommended in infants with posterior positional plagiocephaly whose skull deformity is not satisfactorily corrected by physiotherapy. It should always be used before surgery is considered for patients with recognised positional plagiocephaly in the first year of life

Evidence for a Role of Oxidative Stress in the Carcinogenicity of Ochratoxin A

The in vitro and in vivo evidence compatible with a role for oxidative stress in OTA carcinogenicity has been collected and described. Several potential oxido-reduction mechanisms have been identified in the past. More recently, the possibility of a reduction of cellular antioxidant defense has been raised as an indirect source of oxidative stress. Consequences resulting from the production of oxidative stress are observed at different levels. First, OTA exposure has been associated with increased levels of oxidative DNA, lipid, and protein damage. Second, various biological processes known to be mobilized under oxidative stress were shown to be altered by OTA. These effects have been observed in both in vitro and in vivo test systems. In vivo, active doses were often within doses documented to induce renal tumors in rats. In conclusion, the evidence for the induction of an oxidative stress response resulting from OTA exposure can be considered strong. Because the contribution of the oxidative stress response in the development of cancers is well established, a role in OTA carcinogenicity is plausible. Altogether, the data reviewed above support the application of a threshold-based approach to establish safe level of dietary human exposure to OTA

Noise-based logic: Binary, multi-valued, or fuzzy, with optional superposition of logic states

A new type of deterministic (non-probabilistic) computer logic system inspired by the stochasticity of brain signals is shown. The distinct values are represented by independent stochastic processes: independent voltage (or current) noises. The orthogonality of these processes provides a natural way to construct binary or multi-valued logic circuitry with arbitrary number N of logic values by using analog circuitry. Moreover, the logic values on a single wire can be made a (weighted) superposition of the N distinct logic values. Fuzzy logic is also naturally represented by a two-component superposition within the binary case (N=2). Error propagation and accumulation are suppressed. Other relevant advantages are reduced energy dissipation and leakage current problems, and robustness against circuit noise and background noises such as 1/f, Johnson, shot and crosstalk noise. Variability problems are also nonexistent because the logic value is an AC signal. A similar logic system can be built with orthogonal sinusoidal signals (different frequency or orthogonal phase) however that has an extra 1/N type slowdown compared to the noise-based logic system with increasing number of N furthermore it is less robust against time delay effects than the noise-based counterpart.Comment: Accepted for publication by Physics Letters A, on December 23, 200

A Toxicogenomics Approach to Identify New Plausible Epigenetic Mechanisms of Ochratoxin A Carcinogenicity in Rat

Ochratoxin A (OTA) is a mycotoxin occurring naturally in a wide range of food commodities. In animals, it has been shown to cause a variety of adverse effects, nephrocarcinogenicity being the most prominent. Because of its high toxic potency and the continuous exposure of the human population, OTA has raised public health concerns. There is significant debate on how to use the rat carcinogenicity data to assess the potential risk to humans. In this context, the question of the mechanism of action of OTA appears of key importance and was studied through the application of a toxicogenomics approach. Male Fischer rats were fed OTA for up to 2 years. Renal tumors were discovered during the last 6 months of the study. The total tumor incidence reached 25% at the end of the study. Gene expression profile was analyzed in groups of animals taken in intervals from 7 days to 12 months. Tissue-specific responses were observed in kidney versus liver. For selected genes, microarray data were confirmed at both mRNA and protein levels. In kidney, several genes known as markers of kidney injury and cell regeneration were significantly modulated by OTA. The expression of genes known to be involved in DNA synthesis and repair, or genes induced as a result of DNA damage, was only marginally modulated. Very little or no effect was found amongst genes associated with apoptosis. Alterations of gene expression indicating effects on calcium homeostasis and a disruption of pathways regulated by the transcription factors hepatocyte nuclear factor 4 alpha (HNF4α) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were observed in the kidney but not in the liver. Previous data have suggested that a reduction in HNF4α may be associated with nephrocarcinogenicity. Many Nrf2-regulated genes are involved in chemical detoxication and antioxidant defense. The depletion of these genes is likely to impair the defense potential of the cells, resulting in chronic elevation of oxidative stress in the kidney. The inhibition of defense mechanism appears as a highly plausible new mechanism, which could contribute to OTA carcinogenicit

An Early Cretaceous vertebrate assemblage from the Cabao Formation of NW Libya

Fossil vertebrates from the Cabao Formation discovered in the area of Nalut in northwestern Libya include the hybodont shark Priohybodus, the crocodilian Sarcosuchus, an abelisaurid, a baryonichine spinosaurid and a large sauropod with spatulate teeth. The Cabao Formation may be Hauterivian to Barremian in age, although an earlier Berriasian to Valanginian age cannot be excluded. Its dinosaur assemblage is reminiscent of that of the El Rhaz and Tiouraren formations of Niger and strongly differs from both the Cenomanian assemblages of Morocco and Egypt and the Late Aptian to Albian fauna of Tunisia. Fossil vertebrates may be an important tool to establish the stratigraphical framework of the poorly dated Early Cretaceous continental deposits of Afric

Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers

BACKGROUND: Coffee oil potently raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil also causes elevation of liver enzyme levels in serum. It has been suggested that cafestol is mainly responsible for the effect on serum cholesterol levels and that kahweol is mainly responsible for the effect on liver enzyme levels. The objective of this study was to investigate whether coffee oil that only contains a minute amount of kahweol indeed does not cause elevation of liver enzyme levels. METHODS: The response of serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) to Robusta coffee oil (62 mg/day cafestol, 1.6 mg/day kahweol) was measured in 18 healthy volunteers. RESULTS: After nine days one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times the upper limit of normal (ULN). Another two subjects stopped treatment due to other reasons. After 16 days another two subjects were taken off Robusta oil treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7 ULN. It was then decided to terminate the study. The median response of subjects to Robusta oil after 16 days was 0.27 ULN (n = 15, 25(th),75(th )percentile: 0.09;0.53) for ALAT and 0.06 ULN (25(th),75(th )percentile -0.06;0.22) for ASAT. CONCLUSIONS: We conclude that the effect on liver enzyme levels of coffee oil containing hardly any kahweol is similar to that of coffee oil containing high amounts of kahweol. Therefore it is unlikely that kahweol is the component of coffee oil that is responsible for the effect. Furthermore, we conclude that otherwise unexplained elevation of liver enzyme levels observed in patients might be caused by a switch from consumption of filtered coffee to unfiltered coffee

Structural Basis of Enzymatic Activity for the Ferulic Acid Decarboxylase (FADase) from Enterobacter sp. Px6-4

Microbial ferulic acid decarboxylase (FADase) catalyzes the transformation of ferulic acid to 4-hydroxy-3-methoxystyrene (4-vinylguaiacol) via non-oxidative decarboxylation. Here we report the crystal structures of the Enterobacter sp. Px6-4 FADase and the enzyme in complex with substrate analogues. Our analyses revealed that FADase possessed a half-opened bottom β-barrel with the catalytic pocket located between the middle of the core β-barrel and the helical bottom. Its structure shared a high degree of similarity with members of the phenolic acid decarboxylase (PAD) superfamily. Structural analysis revealed that FADase catalyzed reactions by an “open-closed” mechanism involving a pocket of 8×8×15 Å dimension on the surface of the enzyme. The active pocket could directly contact the solvent and allow the substrate to enter when induced by substrate analogues. Site-directed mutagenesis showed that the E134A mutation decreased the enzyme activity by more than 60%, and Y21A and Y27A mutations abolished the enzyme activity completely. The combined structural and mutagenesis results suggest that during decarboxylation of ferulic acid by FADase, Trp25 and Tyr27 are required for the entering and proper orientation of the substrate while Glu134 and Asn23 participate in proton transfer

A Phylogenetic Perspective on the Evolution of Mediterranean Teleost Fishes

The Mediterranean Sea is a highly diverse, highly studied, and highly impacted biogeographic region, yet no phylogenetic reconstruction of fish diversity in this area has been published to date. Here, we infer the timing and geographic origins of Mediterranean teleost species diversity using nucleotide sequences collected from GenBank. We assembled a DNA supermatrix composed of four mitochondrial genes (12S ribosomal DNA, 16S ribosomal DNA, cytochrome c oxidase subunit I and cytochrome b) and two nuclear genes (rhodopsin and recombination activating gene I), including 62% of Mediterranean teleost species plus 9 outgroups. Maximum likelihood and Bayesian phylogenetic and dating analyses were calibrated using 20 fossil constraints. An additional 124 species were grafted onto the chronogram according to their taxonomic affinity, checking for the effects of taxonomic coverage in subsequent diversification analyses. We then interpreted the time-line of teleost diversification in light of Mediterranean historical biogeography, distinguishing non-endemic natives, endemics and exotic species. Results show that the major Mediterranean orders are of Cretaceous origin, specifically ∼100–80 Mya, and most Perciformes families originated 80–50 Mya. Two important clade origin events were detected. The first at 100–80 Mya, affected native and exotic species, and reflects a global diversification period at a time when the Mediterranean Sea did not yet exist. The second occurred during the last 50 Mya, and is noticeable among endemic and native species, but not among exotic species. This period corresponds to isolation of the Mediterranean from Indo-Pacific waters before the Messinian salinity crisis. The Mediterranean fish fauna illustrates well the assembly of regional faunas through origination and immigration, where dispersal and isolation have shaped the emergence of a biodiversity hotspot

Sensitivity of the IceCube Detector to Astrophysical Sources of High Energy Muon Neutrinos

We present the results of a Monte-Carlo study of the sensitivity of the planned IceCube detector to predicted fluxes of muon neutrinos at TeV to PeV energies. A complete simulation of the detector and data analysis is used to study the detector's capability to search for muon neutrinos from sources such as active galaxies and gamma-ray bursts. We study the effective area and the angular resolution of the detector as a function of muon energy and angle of incidence. We present detailed calculations of the sensitivity of the detector to both diffuse and pointlike neutrino emissions, including an assessment of the sensitivity to neutrinos detected in coincidence with gamma-ray burst observations. After three years of datataking, IceCube will have been able to detect a point source flux of E^2*dN/dE = 7*10^-9 cm^-2s^-1GeV at a 5-sigma significance, or, in the absence of a signal, place a 90% c.l. limit at a level E^2*dN/dE = 2*10^-9 cm^-2s^-1GeV. A diffuse E-2 flux would be detectable at a minimum strength of E^2*dN/dE = 1*10^-8 cm^-2s^-1sr^-1GeV. A gamma-ray burst model following the formulation of Waxman and Bahcall would result in a 5-sigma effect after the observation of 200 bursts in coincidence with satellite observations of the gamma-rays.Comment: 33 pages, 13 figures, 6 table