Provenance signature of a forearc basin modified by spreading ridge subduction: Detrital zircon geochronology and detrital modes from the Paleogene Arkose Ridge Formation, southern Alaska

Upper Paleocene–Eocene boulder conglomerate, cross-stratified sandstone, and laminated carbonaceous mudstone of the Arkose Ridge Formation exposed in the southern Talkeetna Mountains record fluvial-lacustrine deposition proximal to the volcanic arc in a forearc basin modified by Paleogene spreading ridge subduction beneath southern Alaska. U-Pb ages of detrital zircon grains and modal analyses were obtained from stratigraphic sections spanning the 2,000 m thick Arkose Ridge Formation in order to constrain the lithology, age, and location of sediment sources that provided detritus. Detrital modes from 24 conglomerate beds and 54 sandstone thin sections aredominated by plutonic and volcanic clasts and plagioclase feldspar with minor quartz, schist, hornblende, argillite, and metabasalt. Westernmost sandstone and conglomerate strata contain <5% volcanic clasts whereas easternmost sandstone and conglomerate strata contain 40 to >80% volcanic clasts. Temporally, eastern sandstones andconglomerates exhibit an upsection increase in volcanic detritus from <40 to >80% volcanic clasts. U-Pb ages from >1400 detrital zircons in 15 sandstone samples reveal three main populations: late Paleocene–Eocene (60-48 Ma; 16% of all grains), Late Cretaceous–early Paleocene (85–60 Ma; 62%) and Jurassic–Early Cretaceous (200–100 Ma; 12%). A plot of U/Th vs U-Pb ages shows that >97% of zircons are <200 Ma and>99% of zircons have <10 U/Th ratios, consistent with mainly igneous source terranes. Strata show increased enrichment in late Paleocene–Eocene detrital zircons from <2% in the west to >25% in the east. In eastern sections, this younger age population increases temporally from 0% in the lower 50 m of the section to >40% in samples collected >740 m above the base. Integration of the compositional and detrital geochronologic data suggests: (1) Detritus was eroded mainly from igneous sources exposed directly north of the Arkose Ridge Formation strata, mainly Jurassic–Paleocene plutons and Paleocene–Eocenevolcanic centers. Subordinate metamorphic detritus was eroded from western Mesozoic low-grade metamorphic sources. Subordinate sedimentary detritus was eroded from eastern Mesozoic sedimentary sources. (2) Eastern deposystems received higher proportions of juvenile volcanic detritus through time, consistent with construction of adjacent slab-window volcanic centers during Arkose Ridge Formation deposition. (3)Western deposystems transported detritus from Jurassic–Paleocene arc plutons that flank the northwestern basin margin. (4) Metasedimentary strata of the Chugach accretionaryprism, exposed 20-50 km south of the Arkose Ridge Formation, did not contribute abundant detritus. Conventional provenance models predict reduced input of volcanic detritus to forearc basins during exhumation of the volcanic edifice and increasing exposure ofsubvolcanic plutons (Dickinson, 1995; Ingersoll and Eastmond, 2007). In the forearc strata of these conventional models, sandstone modal analyses record progressive increases upsection in quartz and feldspar concomitant with decreases in lithic grains, mainly volcanic lithics. Additionally, as the arc massif denudes through time, theyoungest detrital U-Pb zircon age populations become significantly older than the age of forearc deposition as the arc migrates inboard or ceases magmatism. Westernmost strata of the Arkose Ridge Formation are consistent with this conventional model. However, easternmost strata of the Arkose Ridge Formation contain sandstone modes that record an upsection increase in lithic grains accompanied by a decrease in quartz and feldspar, and detrital zircon age populations that closely match the age of deposition. This deviation from the conventional model is due to the proximity of the easternmost strata to adjacent juvenile volcanic rocks emplaced by slab-window volcanic processes. Provenance data from the Arkose Ridge Formation show that forearc basins modified by spreading ridge subduction may record upsection increases in non-arc, syndepositional volcanic detritusdue to contemporaneous accumulation of thick volcanic sequences at slab-window volcanic centers. This change may occur locally at the same time that other regions of the forearc continue to receive increasing amounts of plutonic detritus as the remnant arc denudes, resulting in complex lateral variations in forearc basin petrofacies and chronofacies.

Atypical scrapie isolates involve a uniform prion species with a complex molecular signature

The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d)). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.

Expression profiling of stem cell-related genes in neoadjuvant-treated gastric cancer: a NOTCH2, GSK3B and β-catenin gene signature predicts survival

Cancer stem cell (CSC) based gene expression signatures are associated with prognosis in various tumour types and CSCs are suggested to be particularly drug resistant. The aim of our study was first, to determine the prognostic significance of CSC-related gene expression in residual tumour cells of neoadjuvant-treated gastric cancer (GC) patients. Second, we wished to examine, whether expression alterations between pre- and post-therapeutic tumour samples exist, consistent with an enrichment of drug resistant tumour cells. The expression of 44 genes was analysed in 63 formalin-fixed, paraffin embedded tumour specimens with partial tumour regression (10-50% residual tumour) after neoadjuvant chemotherapy by quantitative real time PCR low-density arrays. A signature of combined GSK3B(high), β-catenin (CTNNB1)(high) and NOTCH2(low) expression was strongly correlated with better patient survival (p<0.001). A prognostic relevance of these genes was also found analysing publically available gene expression data. The expression of 9 genes was compared between pre-therapeutic biopsies and post-therapeutic resected specimens. A significant post-therapeutic increase in NOTCH2, LGR5 and POU5F1 expression was found in tumours with different tumour regression grades. No significant alterations were observed for GSK3B and CTNNB1. Immunohistochemical analysis demonstrated a chemotherapy-associated increase in the intensity of NOTCH2 staining, but not in the percentage of NOTCH2. Taken together, the GSK3B, CTNNB1 and NOTCH2 expression signature is a novel, promising prognostic parameter for GC. The results of the differential expression analysis indicate a prominent role for NOTCH2 and chemotherapy resistance in GC, which seems to be related to an effect of the drugs on NOTCH2 expression rather than to an enrichment of NOTCH2 expressing tumour cells.

Suspected paradoxical nerve root signature in a dog with right-sided intervertebral lumbar disk extrusion: a case report

A 7 year old male mongrel dog was presented with a 3 weeks history of gait disturbance in the pelvic limbs more pronounced on the left side associated with pain in the lumbar spine. At presentation neurologic deficits consisted of mild bilateral proprioceptive deficits and nerve root signature in the left pelvic limb. A large intervertebral disc herniation L3-L4 located in a right ventrolateral area of the spinal canal was diagnosed by magnetic resonance imaging. The herniated disc was removed through right hemilaminectomy and fenestration. The dog recovered quickly and returned to the owners 4 days after surgery with a slight lameness in the left pelvic limb. On the follow-up examination 2 months later the dog showed normal gait and normal neurological examination. Nerve root signature is not always indicative for the side of the lesion in case of lateralized intervertebral disc herniation

A neurophysiological signature of motivational incongruence: EEG changes related to insufficient goal satisfaction

Human behavior and psychological functioning is motivated and guided by individual goals. Motivational incongruence refers to states of insufficient goal satisfaction and is tightly related to psychological problems and even psychopathology. In the present study, individual levels of motivational incongruence were assessed with the incongruence-questionnaire (INC) in a healthy sample. In addition, multi-channel resting-state EEG was measured. Individual variations of EEG synchronization and spectral power were related to individual levels of motivational incongruence. For significant correlations, the relation to intracerebral sources of electrical brain activity was investigated with sLORETA. The results indicate that, even in a healthy sample with rather low degrees of motivational incongruence, this insufficient goal satisfaction is related to consistent changes in resting state brain activity. Upper Alpha band attenuation seems to be most indicative of increased levels of motivational incongruence. This is reflected not only in significantly reduced functional connectivity, but also in changes regarding the level of brain activation, as indicated by significant effects in the spectral power and LORETA analyses. Results are related to research investigating the upper Alpha band and are discussed in the framework of Grawe's consistency theory.

Strong Dynamical Heterogeneity and Universal Scaling in Driven Granular Fluids

Large-scale simulations of two-dimensional bidisperse granular fluids allow us to determine spatial correlations of slow particles via the four-point structure factor S-4 (q, t). Both cases, elastic (epsilon = 1) and inelastic (epsilon < 1) collisions, are studied. As the fluid approaches structural arrest, i.e., for packing fractions in the range 0.6 <= phi <= 0.805, scaling is shown to hold: S-4 (q, t)/chi(4)(t) = s(q xi(t)). Both the dynamic susceptibility chi(4)(tau(alpha)) and the dynamic correlation length xi(tau(alpha)) evaluated at the alpha relaxation time tau(alpha) can be fitted to a power law divergence at a critical packing fraction. The measured xi(tau(alpha)) widely exceeds the largest one previously observed for three-dimensional (3d) hard sphere fluids. The number of particles in a slow cluster and the correlation length are related by a robust power law, chi(4)(tau(alpha)) approximate to xi(d-p) (tau(alpha)), with an exponent d - p approximate to 1.6. This scaling is remarkably independent of epsilon, even though the strength of the dynamical heterogeneity at constant volume fraction depends strongly on epsilon.

Maintenance of skills, competencies, and performance in allergy and clinical immunology: time to lay the foundation for a universal approach

Allergist/clinical immunologist maintenance of certification and training program reaccreditation are mandatory in some countries. The World Allergy Organization conducted surveys in 2009 and 2011 to assess where such programs were available and to promote the establishment of such programs on a global level. This was done with the presumption that after such an "inventory," World Allergy Organization could offer guidance to its Member Societies on the promotion of such programs to assure the highest standards of practice in the field of allergy and clinical immunology. This review draws on the experience of countries where successful programs are in place and makes recommendations for those wishing to implement such programs for the specialty.

A proteome signature for intrauterine growth restriction derived from multifactorial analysis of mass spectrometry-based cord blood serum profiling

Intrauterine growth restriction (IUGR) is defined as a condition in which the fetus does not reach its genetically given growth potential, resulting in low birth weight. IUGR is an important cause of perinatal morbidity and mortality, thus contributing substantially to medically indicated preterm birth in order to prevent fetal death. We subjected umbilical cord blood serum samples either belonging to the IUGR group (n = 15) or to the control group (n = 15) to fractionation by affinity chromatography using a bead system with hydrophobic interaction capabilities. So prepared protein mixtures were analyzed by MALDI-TOF mass spectrometric profiling. The six best differentiating ion signals at m/z 8205, m/z 8766, m/z 13 945, m/z 15 129, m/z 15 308, and m/z 16 001 were collectively assigned as IUGR proteome signature. Separation confidence of our IUGR proteome signature reached a sensitivity of 0.87 and a specificity of 0.93. Assignment of ion signals in the mass spectra to specific proteins was substantiated by SDS-PAGE in conjunction with peptide mass fingerprint analysis of cord blood serum proteins. One constituent of this proteome signature, apolipoprotein C-III(0) , a derivative lacking glycosylation, has been found more abundant in the IUGR cord blood serum samples, irrespective of gestational age. Hence, we suggest apolipoprotein C-III(0) as potential key-marker of the here proposed IUGR proteome signature, as it is a very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) member and as such involved in triglyceride metabolism that itself is discussed as being of importance in IUGR pathogenesis. Our results indicate that subtle alterations in protein glycosylation need to be considered for improving our understanding of the pathomechanisms in IUGR.