Increased serum NSE and S100B indicate neuronal and glial alterations in subjects under 71 years with mild neurocognitive disorder/mild cognitive impairment

Background: Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild neurocognitive disorder" (mild NCD) - this diagnosis is still based on clinical criteria.Methods: To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63-79 years old) were selected from the Leipzig-population-based study of adults (LIFE).Results: Serum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age.Conclusion: Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD

Precise determination of the Wtb couplings at LHC

Top pair production at LHC is the ideal place to search for nonstandard Wtb couplings in t -> W b -> l nu b decays. The lb forward-backward asymmetry in the W rest frame is very sensitive to sigma_{mu nu} couplings, and can spot one-loop QCD corrections to the decay vertex with more than 5 sigma statistical significance. We discuss the potential of this asymmetry to signal nonstandard gamma_mu and sigma_{mu nu} couplings and compare with top-antitop spin correlation asymmetries, which have a lower sensitivity. We also briefly summarise the results for Tevatron.Comment: LaTeX, 12 pages, 2 PS figures. One reference added. To be published in PR

Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα

Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in fish. IL-15L genes with intact open reading frames (ORFs) and evidence of transcription, and a recent past of purifying selection, were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL-15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 % overall amino acid identity with IL-15, they share many of the IL-15 residues important for binding to receptor chain IL-15Rα, and recombinant bovine IL-15L was shown to interact with IL-15Rα indeed. Comparison of sequence motifs indicates that capacity for binding IL-15Rα is an ancestral characteristic of the IL-2/15/15L family, in accordance with a recent study which showed that in fish both IL-2 and IL-15 can bind IL-15Rα. Evidence reveals that the species lineage leading to mammals started out with three similar cytokines IL-2, IL-15 and IL-15L, and that later in evolution (1) IL-2 and IL-2Rα receptor chain acquired a new and specific binding mode and (2) IL-15L was lost in several but not all groups of mammals. The present study forms an important step forward in understanding this potent family of cytokines, and may help to improve future strategies for their application in veterinarian and human medicine

Chirality and Symmetry Breaking in a discrete internal Space

In previous papers the permutation group S_4 has been suggested as an ordering scheme for elementary particles, and the appearance of this finite symmetry group was taken as indication for the existence of a discrete inner symmetry space underlying elementary particle interactions. Here it is pointed out that a more suitable choice than the tetrahedral group S_4 is the pyritohedral group A_4 x Z_2 because its vibrational spectrum exhibits exactly the mass multiplet structure of the 3 fermion generations. Furthermore it is noted that the same structure can also be obtained from a primordial symmetry breaking S_4 --> A_4. Since A_4 is a chiral group, while S_4 is achiral, an argument can be given why the chirality of the inner pyritohedral symmetry leads to parity violation of the weak interactions.Comment: 42 pages, 3 table

A new approach to calculate the gluon polarization

We derive the Leading-Order master equation to extract the polarized gluon distribution G(x;Q^2) = x \deltag(x;Q^2) from polarized proton structure function, g1p(x;Q^2). By using a Laplace-transform technique, we solve the master equation and derive the polarized gluon distribution inside the proton. The test of accuracy which are based on our calculations with two different methods confirms that we achieve to the correct solution for the polarized gluon distribution. We show that accurate experimental knowledge of g1p(x;Q^2) in a region of Bjorken x and Q^2, is all that is needed to determine the polarized gluon distribution in that region. Therefore, to determine the gluon polarization \deltag /g,we only need to have accurate experimental data on un-polarized and polarized structure functions (F2p (x;Q^2) and g1p(x;Q^2)).Comment: 12 pages, 5 figure

Radio-frequency discharges in Oxygen. Part 1: Modeling

In this series of three papers we present results from a combined experimental and theoretical effort to quantitatively describe capacitively coupled radio-frequency discharges in oxygen. The particle-in-cell Monte-Carlo model on which the theoretical description is based will be described in the present paper. It treats space charge fields and transport processes on an equal footing with the most important plasma-chemical reactions. For given external voltage and pressure, the model determines the electric potential within the discharge and the distribution functions for electrons, negatively charged atomic oxygen, and positively charged molecular oxygen. Previously used scattering and reaction cross section data are critically assessed and in some cases modified. To validate our model, we compare the densities in the bulk of the discharge with experimental data and find good agreement, indicating that essential aspects of an oxygen discharge are captured.Comment: 11 pages, 10 figure

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

PROTOCOL: Organised crime groups: A systematic review of individual\u2010level risk factors related to recruitment

This article presents the protocol for a systematic review of individual\u2010level risk factors related to recruitment into organised crime group