Proposal for a Precision Measurement of |Vub|

A new method for a precision measurement of the CKM matrix element |Vub| is discussed, which combines good theoretical control with high efficiency and a powerful discrimination against charm background. The resulting combined theoretical uncertainty on |Vub| is estimated to be 10%.Comment: 4 pages, 2 figures, RevTe

The biodiversity - N cycle relationship: a 15^{15}N tracer experiment with soil from plant mixtures of varying diversity to model N pool sizes and transformation rates

We conducted a $^{15}$N tracer experiment in laboratory microcosms with field-fresh soil samples from a biodiversity xperiment to evaluate the relationship between grassland biodiversity and N cycling. To embrace the complexity of the N cycle, we determined N exchange between five soil N pools (labile and recalcitrant organic N, dissolved NH$_{4}$$^{+}$ and NO3$^{-}$ in soil solution, and exchangeable NH$_{4}$$^{+}$) and eight N transformations (gross N mineralization from labile and recalcitrant organic N, NH$_{4}$$^{+}$ immobilization into labile and recalcitrant organic N, autotrophic nitrification, heterotrophic nitrification, NO$_{3}$$^{-}$ immobilization, adsorption of NH$_{4}$$^{+}$) expected in aerobic soils with the help of the N-cycle model Ntrace. We used grassland soil of the Jena Experiment, which includes plant mixtures with 1 to 60 species and 1 to 4 functional groups (legumes, grasses, tall herbs, small herbs). The 19 soil samples of one block of the Jena Experiment were labeled with either 15NH$_{4}$$^{+}$ or 15NO3- or both. In the presence of legumes, gross N mineralization and autotrophic nitrification increased significantly because of higher soil N concentrations in legume-containing plots and high microbial activity. Similarly, the presence of grasses significantly increased the soil NH$_{4}$$^{+}$ pool, gross N mineralization, and NH$_{4}$$^{+}$immobilization, likely because of enhanced microbial biomass and activity by providing large amounts of rhizodeposits through their dense root systems. In our experiment, previously reported plant species richness effects on the N cycle, observed in a larger-scale field experiment within the Jena Experiment, were not seen. However, specific plant functional groups had a significant positive impact on the N cycling in the incubated soil samples

Profound influence of different methods for determination of the ankle brachial index on the prevalence estimate of peripheral arterial disease

BACKGROUND: The ankle brachial index (ABI) is an efficient tool for objectively documenting the presence of lower extremity peripheral arterial disease (PAD). However, different methods exist for ABI calculation, which might result in varying PAD prevalence estimates. To address this question, we compared five different methods of ABI calculation using Doppler ultrasound in 6,880 consecutive, unselected primary care patients ≥65 years in the observational getABI study. METHODS: In all calculations, the average systolic pressure of the right and left brachial artery was used as the denominator (however, in case of discrepancies of ≥10 mmHg, the higher reading was used). As nominators, the following pressures were used: the highest arterial ankle pressure of each leg (method #1), the lowest pressure (#2), only the systolic pressure of the tibial posterior artery (#3), only the systolic pressure of the tibial anterior artery (#4), and the systolic pressure of the tibial posterior artery after exercise (#5). An ABI < 0.9 was regarded as evidence of PAD. RESULTS: The estimated prevalence of PAD was lowest using method #1 (18.0%) and highest using method #2 (34.5%), while the differences in methods #3–#5 were less pronounced. Method #1 resulted in the most accurate estimation of PAD prevalence in the general population. Using the different approaches, the odds ratio for the association of PAD and cardiovascular (CV) events varied between 1.7 and 2.2. CONCLUSION: The data demonstrate that different methods for ABI determination clearly affect the estimation of PAD prevalence, but not substantially the strength of the associations between PAD and CV events. Nonetheless, to achieve improved comparability among different studies, one mode of calculation should be universally applied, preferentially method #1

The Role of Magnetic Resonance Imaging to Inform Clinical Decision-Making in Acute Spinal Cord Injury:A Systematic Review and Meta-Analysis

The clinical indications and added value of obtaining MRI in the acute phase of spinal cord injury (SCI) remain controversial. This review aims to critically evaluate evidence regarding the role of MRI to influence decision-making and outcomes in acute SCI. A systematic review and meta-analysis were performed according to PRISMA methodology to identify studies that address six key questions (KQs) regarding diagnostic accuracy, frequency of abnormal findings, frequency of altered decision-making, optimal timing, and differences in outcomes related to obtaining an MRI in acute SCI. A total of 32 studies were identified that addressed one or more KQs. MRI showed no adverse events in 156 patients (five studies) and frequently identified cord compression (70%, 12 studies), disc herniation (43%, 16 studies), ligamentous injury (39%, 13 studies), and epidural hematoma (10%, two studies), with good diagnostic accuracy (seven comparative studies) except for fracture detection. MRI findings often altered management, including timing of surgery (78%, three studies), decision to operate (36%, 15 studies), and surgical approach (29%, nine studies). MRI may also be useful to determine the need for instrumentation (100%, one study), which levels to decompress (100%, one study), and if reoperation is needed (34%, two studies). The available literature consistently concluded that MRI was useful prior to surgical treatment (13 studies) and after surgery to assess decompression (two studies), but utility before/after closed reduction of cervical dislocations was unclear (three studies). One study showed improved outcomes with an MRI-based protocol but had a high risk of bias. Heterogeneity was high for most findings (I(2) > 0.75). MRI is safe and frequently identifies findings alter clinical management in acute SCI, although direct evidence of its impact on outcomes is lacking. MRI should be performed before and after surgery, when feasible, to facilitate improved clinical decision-making. However, further research is needed to determine its optimal timing, effect on outcomes, cost-effectiveness, and utility before and after closed reduction

A Systematic Review of Definitions for Dysphagia and Dysphonia in Patients Treated Surgically for Degenerative Cervical Myelopathy

Study Design: Systematic review. Surgical decompression for degenerative cervical myelopathy (DCM) is associated with perioperative complications, including difficulty or discomfort with swallowing (dysphagia) as well as changes in sound production (dysphonia). This systematic review aims to (1) outline how dysphagia and dysphonia are defined in the literature and (2) assess the quality of definitions using a novel 4-point rating system. Methods: An electronic database search was conducted for studies that reported on dysphagia, dysphonia or other related complications of DCM surgery. Data extracted included study design, surgical details, as well as definitions and rates of surgical complications. A 4-point rating scale was developed to assess the quality of definitions for each complication. Results: Our search yielded 2,673 unique citations, 11 of which met eligibility criteria and were summarized in this review. Defined complications included odynophagia (n = 1), dysphagia (n = 11), dysphonia (n = 2), perioperative swelling complications (n = 2), and soft tissue swelling (n = 3). Rates of dysphagia varied substantially (0.0%-50.0%) depending on whether this complication was patient-reported (4.4%); patient-reported using a modified Swallowing Quality of Life questionnaire (43.1%) or the Bazaz criteria (8.8%-50.0%); or diagnosed using an extensive protocol consisting of clinical assessment, a bedside swallowing test, evaluation by a speech and language pathologist and a modified barium swallowing test/fiberoptic endoscopy (42.9%). The reported incidences of dysphonia also ranged significantly from 0.6% to 38.0%. Conclusion: There is substantial variability in reported rates of dysphagia and dysphonia due to differences in data collection methods, diagnostic strategies, and definitions. Consolidation of nomenclature will improve evaluation of the overall safety of surgery

High-Resolution 3D Structure Determination of Kaliotoxin by Solid-State NMR Spectroscopy

High-resolution solid-state NMR spectroscopy can provide structural information of proteins that cannot be studied by X-ray crystallography or solution NMR spectroscopy. Here we demonstrate that it is possible to determine a protein structure by solid-state NMR to a resolution comparable to that by solution NMR. Using an iterative assignment and structure calculation protocol, a large number of distance restraints was extracted from 1H/1H mixing experiments recorded on a single uniformly labeled sample under magic angle spinning conditions. The calculated structure has a coordinate precision of 0.6 Å and 1.3 Å for the backbone and side chain heavy atoms, respectively, and deviates from the structure observed in solution. The approach is expected to be applicable to larger systems enabling the determination of high-resolution structures of amyloid or membrane proteins

On the enzymatic activity of catalase: an iron L-edge X-ray absorption study of the active centre

Catalase and methaemoglobin have very similar haem groups, which are both ferric, yet catalase decomposes hydrogen peroxide to water and oxygen very efficiently, while methaemoglobin does not. Structural studies have attributed this behaviour to their different distal environments. Here we present Fe L-2,L-3-edge X-ray absorption spectra of these proteins in physiological solutions, which reveal clear differences in their electronic structures, in that pi back-donation of the Fe atom occurs in catalase, which confers on it a partial ferryl (Fe4+) character, while this is not the case in methaemoglobin. The origin of the Fe4+ character stems from the proximal tyrosine residue. We also find that both systems are in a high spin state. Temperature effects influence the spectra of catalase only weakly, in agreement with previous studies of its chemical activity. We conclude that the high activity of catalase is not only determined by its distal environment but also by its partial ferryl character

Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin

Sphingosine-1-phosphate (S1P) participates in inflammation;however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P(3)) and G alpha(q), PLC beta and Ca2+. Intraarterial S1P administration increases leukocyte rolling, while S1P(3) deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P(3). Histamine and epinephrine require S1P(3) for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P1 inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific S1P(1)(-/-) mice. In agreement with a dominant pro-rolling effect of S1P(3),FTY720 inhibits rolling in control and S1P(1)(-/-) but not in S1P(3)(-/-) mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Cold-Induced Changes in the Protein Ubiquitin

Conformational changes are essential for protein-protein and protein-ligand recognition. Here we probed changes in the structure of the protein ubiquitin at low temperatures in supercooled water using NMR spectroscopy. We demonstrate that ubiquitin is well folded down to 263 K, although slight rearrangements in the hydrophobic core occur. However, amide proton chemical shifts show non-linear temperature dependence in supercooled solution and backbone hydrogen bonds become weaker in the region that is most prone to cold-denaturation. Our data suggest that the weakening of the hydrogen bonds in the β-sheet of ubiquitin might be one of the first events that occur during cold-denaturation of ubiquitin. Interestingly, the same region is strongly involved in ubiquitin-protein complexes suggesting that this part of ubiquitin more easily adjusts to conformational changes required for complex formation