Transcriptomic Profiling of Plaque Psoriasis and Cutaneous T-Cell Subsets during Treatment with Secukinumab.

The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4 and CD8 T effector cells and CD4 T regulatory cells across 12 weeks of treatment.

Seroprevalence and correlates of SARS-CoV-2 neutralizing antibodies from a population-based study in Bonn, Germany.

To estimate the seroprevalence and temporal course of SARS-CoV-2 neutralizing antibodies, we embedded a multi-tiered seroprevalence survey within an ongoing community-based cohort study in Bonn, Germany. We first assessed anti-SARS-CoV-2 immunoglobulin G levels with an immunoassay, followed by confirmatory testing of borderline and positive test results with a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (PRNT). Those with a borderline or positive immunoassay result were retested after 4 to 5 months.

Metabolic Cost of a Nutritional Symbiont Manifests in Delayed Reproduction in a Grain Pest Beetle.

Animals engage in a plethora of mutualistic interactions with microorganisms that can confer various benefits to their host but can also incur context-dependent costs. The sawtoothed grain beetle harbors nutritional, intracellular Bacteroidetes bacteria that supplement precursors for the cuticle synthesis and thereby enhance desiccation resistance of its host. Experimental elimination of the symbiont impairs cuticle formation and reduces fitness under desiccation stress but does not disrupt the host's life cycle.

Magnetic assessment and modelling of the Aramis undulator beamline.

Within the SwissFEL project at the Paul Scherrer Institute (PSI), the hard X-ray line (Aramis) has been equipped with short-period in-vacuum undulators, known as the U15 series. The undulator design has been developed within the institute itself, while the prototyping and the series production have been implemented through a close collaboration with a Swiss industrial partner, Max Daetwyler AG, and several subcontractors. The magnetic measurement system has been built at PSI, together with all the data analysis tools.

Packing Density of the Amyloid Precursor Protein in the Cell Membrane.

Plasma membrane proteins organize into structures named compartments, microdomains, rafts, phases, crowds, or clusters. These structures are often smaller than 100 nm in diameter. Despite their importance in many cellular functions, little is known about their inner organization.

Ancient symbiosis confers desiccation resistance to stored grain pest beetles.

Microbial symbionts of insects provide a range of ecological traits to their hosts that are beneficial in the context of biotic interactions. However, little is known about insect symbiont-mediated adaptation to the abiotic environment, for example, temperature and humidity. Here, we report on an ancient clade of intracellular, bacteriome-located Bacteroidetes symbionts that are associated with grain and wood pest beetles of the phylogenetically distant families Silvanidae and Bostrichidae.

The EIGER detector for low-energy electron microscopy and photoemission electron microscopy.

EIGER is a single-photon-counting hybrid pixel detector developed at the Paul Scherrer Institut, Switzerland. It is designed for applications at synchrotron light sources with photon energies above 5 keV. Features of EIGER include a small pixel size (75 µm × 75 µm), a high frame rate (up to 23 kHz), a small dead-time between frames (down to 3 µs) and a dynamic range up to 32-bit.

Transverse gradient in Apple-type undulators.

Apple-type undulators are globally recognized as the most flexible devices for the production of variable polarized light in the soft X-ray regime, both at synchrotron and free-electron laser facilities. Recently, the implementation of transverse gradient undulators has been proposed to enhance the performance of new generation light sources. In this paper it is demonstrated that Apple undulators do not only generate linear and elliptical polarized light but also variable transverse gradient under certain conditions.

The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells.

Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1 GC B cells increases during the course of an immune response with Ephrin-B1 GC B cells displaying elevated levels of Bcl6, , and relative to their Ephrin-B1 counterparts.

Isotropic thin PTCDA films on GaN(0 0 0 1).

The growth of 3, 4, 9, 10-perylene tetracarboxylic dianhydride (PTCDA) on the Ga-polar GaN(0 0 0 1) surface has been studied by x-ray photoelectron spectroscopy (XPS), spot profile analysis low-energy electron diffraction (SPA-LEED), near edge x-ray absorption fine structure (NEXAFS), and scanning tunneling microscopy (STM). The stoichiometric ratios derived from XPS indicate that the molecules remain intact upon adsorption on the surface. Furthermore, no chemical shifts can be observed in the C 1s and O 1s core levels with progressing deposition of PTCDA, suggesting none or only weak interactions between the molecules and the substrate.

Morphology and chemical composition of cobalt germanide islands on Ge(001).

The reactive growth of cobalt germanide on Ge(001) was investigated by means of in situ x-ray absorption spectroscopy photoemission electron microscopy (XAS-PEEM), micro-illumination low-energy electron diffraction (μ-LEED), and ex situ atomic force microscopy (AFM). At a Co deposition temperature of 670 °C, a rich morphology with different island shapes and dimensions is observed, and a correlation between island morphology and stoichiometry is found. By combining XAS-PEEM and μ-LEED, we were able to identify a large part of the islands to consist of CoGe2, with many of them having an unusual epitaxial relationship: CoGe2 [Formula: see text] [Formula: see text] Ge [Formula: see text].

Oligomerization of the Tetraspanin CD81 via the Flexibility of Its δ-Loop.

Tetraspanins are master organizers in the plasma membrane, forming tetraspanin-enriched microdomains with one another and other surface molecules. Their rod-shaped structure includes a large extracellular loop (LEL) that plays a pivotal role in tetraspanin network formation. We performed comparative atomistic and coarse-grain molecular-dynamics simulations of the LEL in isolation and full-length CD81, and reproduced LEL flexibility patterns known from wet-lab experiments in which the LEL δ-loop region showed a pronounced flexibility.

Concentration Dependent Ion-Protein Interaction Patterns Underlying Protein Oligomerization Behaviours.

Salts and proteins comprise two of the basic molecular components of biological materials. Kosmotropic/chaotropic co-solvation and matching ion water affinities explain basic ionic effects on protein aggregation observed in simple solutions. However, it is unclear how these theories apply to proteins in complex biological environments and what the underlying ionic binding patterns are.

Computer simulations suggest direct and stable tip to tip interaction between the outer membrane channel TolC and the isolated docking domain of the multidrug RND efflux transporter AcrB.

One way by which bacteria achieve antibiotics resistance is preventing drug access to its target molecule for example through an overproduction of multi-drug efflux pumps of the resistance nodulation division (RND) protein super family of which AcrAB-TolC in Escherichia coli is a prominent example. Although representing one of the best studied efflux systems, the question of how AcrB and TolC interact is still unclear as the available experimental data suggest that either both proteins interact in a tip to tip manner or do not interact at all but are instead connected by a hexamer of AcrA molecules. Addressing the question of TolC-AcrB interaction, we performed a series of 100 ns - 1 µs-molecular dynamics simulations of membrane-embedded TolC in presence of the isolated AcrB docking domain (AcrB(DD)).

Where Biology Meets Physics--A Converging View on Membrane Microdomain Dynamics.

For several decades, the phenomenon of membrane component segregation into microdomains has been a well-known and highly debated subject, and varying concepts including the raft hypothesis, the fence-and-picket model, hydrophobic-mismatch, and specific protein-protein interactions have been offered as explanations. Here, we review the level of insight into the molecular architecture of membrane domains one is capable of obtaining through biological experimentation. Using SNARE proteins as a paradigm, comprehensive data suggest that several dozens of molecules crowd together into almost circular spots smaller than 100 nm.

Cutaneous Findings and Systemic Associations in Women With Polycystic Ovary Syndrome.

Importance: Understanding of the associations among cutaneous findings, systemic abnormalities, and fulfillment of the diagnostic criteria in women suspected of having polycystic ovary syndrome (PCOS) is incomplete.

Objective: To identify cutaneous and systemic features of PCOS that help distinguish women who do and do not meet the diagnostic criteria.

Design, Setting, And Participants: Retrospective cross-sectional study of a racially diverse referred sample of women seen at the University of California, San Francisco, Polycystic Ovary Syndrome Multidisciplinary Clinic over a 6-year period between May 18, 2006, and October 25, 2012.

Growth and evolution of nickel germanide nanostructures on Ge(001).

Nickel germanide is deemed an excellent material system for low resistance contact formation for future Ge device modules integrated into mainstream, Si-based integrated circuit technologies. In this study, we present a multi-technique experimental study on the formation processes of nickel germanides on Ge(001). We demonstrate that room temperature deposition of ∼1 nm of Ni on Ge(001) is realized in the Volmer-Weber growth mode.

Evidence-based approach to cutaneous hyperandrogenism in women.

Hirsutism, acne, and androgenetic alopecia are classically considered signs of cutaneous hyperandrogenism (CHA). These common skin findings have significant impacts on the quality of patients' lives and pose the diagnostic challenge of excluding underlying disorders. Many with CHA have normal serum androgen levels.

Attitudes toward Human Papilloma Virus Vaccination and Head and Neck Cancer Prevention in a Diverse, Urban Population.

Objective: (1) To understand if awareness of the human papilloma virus (HPV) vaccination's potential to prevent head and neck cancer improves acceptability of the vaccine in a large urban population and (2) to identify characteristics of those in whom such discussions would have the greatest impact.

Study Design: In-person, anonymous survey.

Setting: Academic public hospital between March 2014 and June 2014.

Structural dynamics of the cell wall precursor lipid II in the presence and absence of the lantibiotic nisin.

Representing a physiological "Achilles' heel", the cell wall precursor lipid II (LII) is a prime target for various classes of antibiotics. Over the years LII-binding agents have been recognized as promising candidates and templates in the search for new antibacterial compounds to complement or replace existing drugs. To elucidate the molecular structural basis underlying LII functional mechanism and to better understand if and how lantibiotic binding alters the molecular behavior of LII, we performed molecular dynamics (MD) simulations of phospholipid membrane-embedded LII in the absence and presence of the LII-binding lantibiotic nisin.

The extracellular δ-domain is essential for the formation of CD81 tetraspanin webs.

CD81 is a ubiquitously expressed member of the tetraspanin family. It forms large molecular platforms, so-called tetraspanin webs that play physiological roles in a variety of cellular functions and are involved in viral and parasite infections. We have investigated which part of the CD81 molecule is required for the formation of domains in the cell membranes of T-cells and hepatocytes.