Limit on Lorentz and CPT violation of the bound Neutron Using a Free Precession 3He/129Xe co-magnetometer

We report on the search for Lorentz violating sidereal variations of the frequency difference of co-located spin-species while the Earth and hence the laboratory reference frame rotates with respect to a relic background field. The co-magnetometer used is based on the detection of freely precessing nuclear spins from polarized 3He and 129Xe gas samples using SQUIDs as low-noise magnetic flux detectors. As result we can determine the limit for the equatorial component of the background field interacting with the spin of the bound neutron to be bn < 3.7 x 10^{-32} GeV (95 C.L.).Comment: 5 pages, 4 figure

A dietary carbohydrate–gut Parasutterella–human fatty acid biosynthesis metabolic axis in obesity and type 2 diabetes

Recent rodent microbiome experiments suggest that besides Akkermansia, Parasutterella sp. are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize Parasutterella in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent Canadian cohort (n = 438). In addition, we examined Parasutterella abundance in response to a weight loss intervention (n = 55). Parasutterella was positively associated with BMI and type 2 diabetes independently of the reduced microbiome α/β diversity and low-grade inflammation commonly found in obesity. Nutritional analysis revealed a positive association with the dietary intake of carbohydrates but not with fat or protein consumption. Out of 126 serum metabolites differentially detectable by untargeted HPLC-based MS-metabolomics, L-cysteine showed the strongest reduction in subjects with high Parasutterella abundance. This is of interest, since Parasutterella is a known high L-cysteine consumer and L-cysteine is known to improve blood glucose levels in rodents. Furthermore, metabolic network enrichment analysis identified an association of high Parasutterella abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This is supported by a significant reduction of the Parasutterella abundance during our weight loss intervention. Together, these data indicate a role for Parasutterella in human type 2 diabetes and obesity, whereby the link to L-cysteine might be relevant in type 2 diabetes development and the link to the fatty acid biosynthesis pathway for body weight gain in response to a carbohydrate-rich diet in obesity development

Depression does not affect the treatment outcome of CBT for panic and agoraphobia: results from a multicenter randomized trial

BACKGROUND: Controversy surrounds the questions whether co-occurring depression has negative effects on cognitive-behavioral therapy (CBT) outcomes in patients with panic disorder (PD) and agoraphobia (AG) and whether treatment for PD and AG (PD/AG) also reduces depressive symptomatology. METHODS: Post-hoc analyses of randomized clinical trial data of 369 outpatients with primary PD/AG (DSM-IV-TR criteria) treated with a 12-session manualized CBT (n = 301) and a waitlist control group (n = 68). Patients with comorbid depression (DSM-IV-TR major depression, dysthymia, or both: 43.2% CBT, 42.7% controls) were compared to patients without depression regarding anxiety and depression outcomes (Clinical Global Impression Scale [CGI], Hamilton Anxiety Rating Scale [HAM-A], number of panic attacks, Mobility Inventory [MI], Panic and Agoraphobia Scale, Beck Depression Inventory) at post-treatment and follow-up (categorical). Further, the role of severity of depressive symptoms on anxiety/depression outcome measures was examined (dimensional). RESULTS: Comorbid depression did not have a significant overall effect on anxiety outcomes at post-treatment and follow-up, except for slightly diminished post-treatment effect sizes for clinician-rated CGI (p = 0.03) and HAM-A (p = 0.008) when adjusting for baseline anxiety severity. In the dimensional model, higher baseline depression scores were associated with lower effect sizes at post-treatment (except for MI), but not at follow-up (except for HAM-A). Depressive symptoms improved irrespective of the presence of depression. CONCLUSIONS: Exposure-based CBT for primary PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbid depression or depressive symptomatology

Magnetorelaxometry Assisting Biomedical Applications of Magnetic Nanoparticles

Due to their biocompatibility and small size, iron oxide magnetic nanoparticles (MNP) can be guided to virtually every biological environment. MNP are susceptible to external magnetic fields and can thus be used for transport of drugs and genes, for heat generation in magnetic hyperthermia or for contrast enhancement in magnetic resonance imaging of biological tissue. At the same time, their magnetic properties allow one to develop sensitive and specific measurement methods to non-invasively detect MNP, to quantify MNP distribution in tissue and to determine their binding state. In this article, we review the application of magnetorelaxometry (MRX) for MNP detection. The underlying physical properties of MNP responsible for the generation of the MRX signal with its characteristic parameters of relaxation amplitude and relaxation time are described. Existing single and multi-channel MRX devices are reviewed. Finally, we thoroughly describe some applications of MRX to cellular MNP quantification, MNP organ distribution and MNP-based binding assays. Providing specific MNP signals, a detection limit down to a few nanogram MNP, in-vivo capability in conscious animals and measurement times of a few seconds, MRX is a valuable tool to improve the application of MNP for diagnostic and therapeutic purposes

MOS11: A New Component in the mRNA Export Pathway

Nucleocytoplasmic trafficking is emerging as an important aspect of plant immunity. The three related pathways affecting plant immunity include Nuclear Localization Signal (NLS)–mediated nuclear protein import, Nuclear Export Signal (NES)–dependent nuclear protein export, and mRNA export relying on MOS3, a nucleoporin belonging to the Nup107–160 complex. Here we report the characterization, identification, and detailed analysis of Arabidopsis modifier of snc1, 11 (mos11). Mutations in MOS11 can partially suppress the dwarfism and enhanced disease resistance phenotypes of snc1, which carries a gain-of-function mutation in a TIR-NB-LRR type Resistance gene. MOS11 encodes a conserved eukaryotic protein with homology to the human RNA binding protein CIP29. Further functional analysis shows that MOS11 localizes to the nucleus and that the mos11 mutants accumulate more poly(A) mRNAs in the nucleus, likely resulting from reduced mRNA export activity. Epistasis analysis between mos3-1 and mos11-1 revealed that MOS11 probably functions in the same mRNA export pathway as MOS3, in a partially overlapping fashion, before the mRNA molecules pass through the nuclear pores. Taken together, MOS11 is identified as a new protein contributing to the transfer of mature mRNA from the nucleus to the cytosol

Multifaceted SlyD from Helicobacter pylori: implication in [NiFe] hydrogenase maturation

SlyD belongs to the FK506-binding protein (FKBP) family with both peptidylprolyl isomerase (PPIase) and chaperone activities, and is considered to be a ubiquitous cytosolic protein-folding facilitator in bacteria. It possesses a histidine- and cysteine-rich C-terminus binding to selected divalent metal ions (e.g., Ni2+, Zn2+), which is important for its involvement in the maturation processes of metalloenzymes. We have determined the solution structure of C-terminus-truncated SlyD from Helicobacter pylori (HpSlyDΔC). HpSlyDΔC folds into two well-separated, orientation-independent domains: the PPIase-active FKBP domain and the chaperone-active insert-in-flap (IF) domain. The FKBP domain consists of a four-stranded antiparallel β-sheet with an α-helix on one side, whereas the IF domain folds into a four-stranded antiparallel β-sheet accompanied by a short α-helix. Intact H. pylori SlyD binds both Ni2+ and Zn2+, with dissociation constants of 2.74 and 3.79 μM respectively. Intriguingly, binding of Ni2+ instead of Zn2+ induces protein conformational changes around the active sites of the FKBP domain, implicating a regulatory role of nickel. The twin-arginine translocation (Tat) signal peptide from the small subunit of [NiFe] hydrogenase (HydA) binds the protein at the IF domain. Nickel binding and the recognition of the Tat signal peptide by the protein suggest that SlyD participates in [NiFe] hydrogenase maturation processes

Essential Roles for Soluble Virion-Associated Heparan Sulfonated Proteoglycans and Growth Factors in Human Papillomavirus Infections

A subset of human papillomavirus (HPV) infections is causally related to the development of human epithelial tumors and cancers. Like a number of pathogens, HPV entry into target cells is initiated by first binding to heparan sulfonated proteoglycan (HSPG) cell surface attachment factors. The virus must then move to distinct secondary receptors, which are responsible for particle internalization. Despite intensive investigation, the mechanism of HPV movement to and the nature of the secondary receptors have been unclear. We report that HPV16 particles are not liberated from bound HSPG attachment factors by dissociation, but rather are released by a process previously unreported for pathogen-host cell interactions. Virus particles reside in infectious soluble high molecular weight complexes with HSPG, including syndecan-1 and bioactive compounds, like growth factors. Matrix mellatoproteinase inhibitors that block HSPG and virus release from cells interfere with virus infection. Employing a co-culture assay, we demonstrate HPV associated with soluble HSPG-growth factor complexes can infect cells lacking HSPG. Interaction of HPV-HSPG-growth factor complexes with growth factor receptors leads to rapid activation of signaling pathways important for infection, whereas a variety of growth factor receptor inhibitors impede virus-induced signaling and infection. Depletion of syndecan-1 or epidermal growth factor and removal of serum factors reduce infection, while replenishment of growth factors restores infection. Our findings support an infection model whereby HPV usurps normal host mechanisms for presenting growth factors to cells via soluble HSPG complexes as a novel method for interacting with entry receptors independent of direct virus-cell receptor interactions

State of the art of immunoassay methods for B-type natriuretic peptides: An update

The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1–32, should reduce the systematic differences between methods and result in better harmonization of results

Ion homeostasis in the Chloroplast

peer reviewedThe chloroplast is an organelle of high demand for macro- and micro-nutrient ions, which are required for the maintenance of the photosynthetic process. To avoid deficiency while preventing excess, homeostasis mechanisms must be tightly regulated. Here, we describe the needs for nutrient ions in the chloroplast and briefly highlight their functions in the chloroplastidial metabolism. We further discuss the impact of nutrient deficiency on chloroplasts and the acclimation mechanisms that evolved to preserve the photosynthetic apparatus. We finally present what is known about import and export mechanisms for these ions. Whenever possible, a comparison between cyanobacteria, algae and plants is provided to add an evolutionary perspective to the description of ion homeostasis mechanisms in photosynthesis