Nuclear magnetic resonance as a quantitative tool to study interactions in biomacromolecules

High-resolution nuclear magnetic resonance (NMR) has emerged as one of the most versatile tools for the quantitative study of structure, kinetics, and thermodynamics of biomolecules and their interactions at atomic resolution. Traditionally, nuclear Overhauser enhancements (NOEs) and chemical shift perturbation methods are used to determine molecular geometries and to identify contact surfaces, but more recently, weak anisotropic orientation, anisotropic diffusion, and scalar couplings across hydrogen bonds provide additional information. Examples of such technologies are shown as applied to the quantitative characterization of function and thermodynamics of several biomacromolecules. In particular, (1) the structural and dynamical changes of the TipA multidrug resistance protein are followed upon antibiotic binding, (2) the trimer-monomer equilibrium and thermal unfolding of foldon, a small and very efficient trimerization domain of the T4 phagehead, is described in atomic detail, and (3) the changes of individual protein hydrogen bonds during thermal unfolding are quantitatively followed by scalar couplings across hydrogen bond

An experimental study to discriminate between the validity of diffraction theories for off-Bragg replay

We show that experiments clearly verify the assumptions made by the first-order two-wave coupling theory for one dimensional lossless unslanted planar volume holographic gratings using the beta-value method rather than Kogelnik's K-vector closure method. Apart from the fact that the diffraction process is elastic, a much more striking difference between the theories becomes apparent particularly in the direction of the diffracted beam in off-Bragg replay. We therefore monitored the direction of the diffracted beam as a function of the off-Bragg replay angle in two distinct cases: [a] the diffracted beam lies in the plane of incidence and [b] the sample surface normal, the grating vector and the incoming beam do not form a plane which calls for the vectorial theory and results in conical scattering.Comment: Corrected Eqs. (3) & (6); 14 pages, 8 figure

Body Shape and Life Style of the Extinct Balearic Dormouse Hypnomys (Rodentia, Gliridae): New Evidence from the Study of Associated Skeletons

Hypnomys is a genus of Gliridae (Rodentia) that occurred in the Balearic Islands until Late Holocene. Recent finding of a complete skeleton of the chronospecies H. morpheus (Late Pleistocene-Early Holocene) and two articulated skeletons of H. cf. onicensis (Late Pliocene) allowed the inference of body size and the calculation of several postcranial indexes. We also performed a Factorial Discriminant Analysis (FDA) in order to evaluate locomotory behaviour and body shape of the taxa. Using allometric models based on skull and tooth measurements, we calculated a body weight between 173 and 284 g for H. morpheus, and direct measurements of articulated skeletons yielded a Head and Body Length (HBL) of 179 mm and a Total Body Length of 295 mm for this species. In addition to the generally higher robustness of postcranial bones already recorded by previous authors, H. morpheus, similar to Canariomys tamarani, another extinct island species, displayed elongated zygopodium bones of the limbs and a wider distal humerus and femur than in an extant related taxon, Eliomys quercinus. Indexes indicated that Hypnomys was more terrestrial and had greater fossorial abilities than E. quercinus. This was also corroborated by a Discriminant Analysis, although no clear additional inference of locomotory abilities could be calculated

Pericoronary radiomics texture features associated with hypercholesterolemia on a photon-counting-CT

IntroductionPericoronary adipose tissue (PCAT) stands in complex bidirectional interaction with the surrounding arteries and is known to be connected to many cardiovascular diseases involving vascular inflammation. PCAT texture may be influenced by other cardiovascular risk factors such as hypercholesterolemia. The recently established photon-counting CT could improve texture analysis and help detect those changes by offering higher spatial resolution and signal-to-noise ratio.MethodsIn this retrospective, single-center, IRB-approved study, PCAT of the left and right coronary artery was manually segmented and radiomic features were extracted using pyradiomics. The study population consisted of a test collective and a validation collective. The collectives were each divided into two groups defined by the presence or absence of hypercholesterolemia, taken from self-reported conditions and confirmed by medical records. Mean and standard deviation were calculated with Pearson correlation coefficient for correlation of features and visualized as boxplots and heatmaps using R statistics. Random forest feature selection was performed to identify differentiating features between the two groups. 66 patients were enrolled in this study (34 female, mean age 58 years).ResultsTwo radiomics features allowing differentiation between PCAT texture of the groups were identified (p-values between 0.013 and 0.24) and validated. Patients with hypercholesterolemia presented with a greater concentration of high-density values as indicated through analysis of specific texture features as “gldm_HighGrayLevelEmphasis” (23.95 vs. 22.99) and “glrlm_HighGrayLevelRunEmphasis” (24.21 vs. 23.31).DiscussionTexture analysis of PCAT allowed differentiation between patients with and without hypercholesterolemia offering a potential imaging biomarker for this specific cardiovascular risk factor

Identification and characterization of secreted and pathogenesis-related proteins in Ustilago maydis

Interactions between plants and fungal pathogens require a complex interplay at the plant–fungus interface. Extracellular effector proteins are thought to play a crucial role in establishing a successful infection. To identify pathogenesis-related proteins in Ustilago maydis we combined the isolation of secreted proteins using a signal sequence trap approach with bioinformatic analyses and the subsequent characterization of knock-out mutants. We identified 29 secreted proteins including hydrophobins and proteins with a repetitive structure similar to the repellent protein Rep1. Hum3, a protein containing both, a hydrophobin domain and a repetitive Rep1-like region, is shown to be processed during passage through the secretory pathway. While single knock-outs of hydrophobin or repellent-like genes did not affect pathogenicity, we found a strong effect of a double knock-out of hum3 and the repetitive rsp1. Yeast-like growth, mating, aerial hyphae formation and surface hydrophobicity were unaffected in this double mutant. However, pathogenic development in planta stops early after penetration leading to a complete loss of pathogenicity. This indicates that Hum3 and Rsp1 are pathogenicity proteins that share an essential function in early stages of the infection. Our results demonstrate that focusing on secreted proteins is a promising way to discover novel pathogenicity proteins that might be broadly applied to a variety of fungal pathogens

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project

To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological communit

Understanding Performance Limiting Interfacial Recombination in pin Perovskite Solar Cells

Funder: Alexander von Humboldt Foundation; Id: http://dx.doi.org/10.13039/100005156Abstract: Perovskite semiconductors are an attractive option to overcome the limitations of established silicon based photovoltaic (PV) technologies due to their exceptional opto‐electronic properties and their successful integration into multijunction cells. However, the performance of single‐ and multijunction cells is largely limited by significant nonradiative recombination at the perovskite/organic electron transport layer junctions. In this work, the cause of interfacial recombination at the perovskite/C60 interface is revealed via a combination of photoluminescence, photoelectron spectroscopy, and first‐principle numerical simulations. It is found that the most significant contribution to the total C60‐induced recombination loss occurs within the first monolayer of C60, rather than in the bulk of C60 or at the perovskite surface. The experiments show that the C60 molecules act as deep trap states when in direct contact with the perovskite. It is further demonstrated that by reducing the surface coverage of C60, the radiative efficiency of the bare perovskite layer can be retained. The findings of this work pave the way toward overcoming one of the most critical remaining performance losses in perovskite solar cells

Septation of Infectious Hyphae Is Critical for Appressoria Formation and Virulence in the Smut Fungus Ustilago Maydis

Differentiation of hyphae into specialized infection structures, known as appressoria, is a common feature of plant pathogenic fungi that penetrate the plant cuticle. Appressorium formation in U. maydis is triggered by environmental signals but the molecular mechanism of this hyphal differentiation is largely unknown. Infectious hyphae grow on the leaf surface by inserting regularly spaced retraction septa at the distal end of the tip cell leaving empty sections of collapsed hyphae behind. Here we show that formation of retraction septa is critical for appressorium formation and virulence in U. maydis. We demonstrate that the diaphanous-related formin Drf1 is necessary for actomyosin ring formation during septation of infectious hyphae. Drf1 acts as an effector of a Cdc42 GTPase signaling module, which also consists of the Cdc42-specific guanine nucleotide exchange factor Don1 and the Ste20-like kinase Don3. Deletion of drf1, don1 or don3 abolished formation of retraction septa resulting in reduced virulence. Appressorium formation in these mutants was not completely blocked but infection structures were found only at the tip of short filaments indicating that retraction septa are necessary for appressorium formation in extended infectious hyphae. In addition, appressoria of drf1 mutants penetrated the plant tissue less frequently