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Zusammenfassung Hintergrund Mit einer Prävalenz von ca. 10 % ist Diabetes mellitus eine der häufigsten chronischen Erkrankungen in Deutschland. Diese geht einher mit erhöhten Raten an depressiven Störungen, Angststörungen und Anpassungsstörungen, die einen besonderen psychotherapeutischen Versorgungsbedarf begründen. Ziel der Arbeit Ziel der Studie ist es, in einer Psychotherapieinanspruchnahmepopulation den Anteil von Patienten mit Diabetes mellitus zu bestimmen und die Charakteristika der Versorgung auch im Vergleich zu Inanspruchnahmepatienten ohne chronische körperliche Erkrankung zu beschreiben. Material und Methoden Ausgehend von einer bevölkerungsrepräsentativen Screeningstichprobe von n = 32.573 wurde im Rahmen des Projektes „Evaluation der Strukturreform der Richtlinien-Psychotherapie – Vergleich von komplex und nicht-komplex erkrankten Patienten“ (ES-RiP) eine Befragung von n = 1544 Patienten, die eine ambulante Psychotherapie in Anspruch genommen haben, durchgeführt. Outcomes waren Inanspruchnahme, Zuweisungswege, Beschwerden und Beschwerdeverlauf, Lebensqualität, Zufriedenheit mit der Behandlung und unerwünschte Nebenwirkungen. Ergebnisse In einer Psychotherapieinanspruchnahmepopulation wiesen in der Selbstangabe 6,7 % (n = 104) einen Diabetes mellitus auf. Gedrückte/schwankende Stimmung, Angststörungen und Probleme im Umgang mit körperlichen Erkrankungen werden von den Inanspruchnahmepatienten mit Diabetes mellitus im Vergleich zu Inanspruchnahmepatienten ohne chronische körperliche Erkrankung signifikant häufiger als zur Therapie motivierende Beschwerden genannt. Bei einer sehr hohen Zufriedenheit mit der Behandlung werden von 81,7 % deutliche Verbesserungen der Beschwerden und von 79,0 % eine Zunahme der Lebensqualität benannt. Über unerwünschte Nebenwirkungen der Psychotherapie berichten 45,7 % der diabeteserkrankten Patienten. Diskussion Der Anteil an Patienten mit Diabetes mellitus in einer Inanspruchnahmepopulation liegt unter der aufgrund von epidemiologischen Daten erwartbaren Prävalenz. In die psychotherapeutische Versorgung führen diese Patienten eine Vielzahl von Belastungen. Das Versorgungssystem sollte durch spezifische Angebote auf diese Patientengruppe eingehen.

Confined thin structures are ubiquitous in nature. Spatial and length constraints have led to a number of novel packing strategies at both the micro-scale, as when DNA packages inside a capsid, and the macro-scale, seen in plant root development and the arrangement of the human intestinal tract. By varying the arc length of an elastic loop injected into an array of monodisperse, soft, spherical grains at varying initial number density, we investigate the resulting packing behaviors between a growing slender structure constrained by deformable boundaries. At low initial packing fractions, the elastic loop deforms as though it were hitting a flat surface by periodically folding into the array. Above a critical packing fraction $��_c$, local re-orientations within the granular medium create an effectively curved surface leading to the emergence of a distinct circular packing morphology in the adjacent elastic structure. These results will bring new insight into the packing behavior of wires and thin sheets and will be relevant to modeling plant root morphogenesis, burrowing and locomotive strategies of vertebrates & invertebrates, and developing smart, steerable needles., 6 pages, 6 figures

Frustration arises for a broad class of physical systems where confinement (geometric) or the presence of a perturbation (kinematic) prevents equilibration to a minimum energy state. By varying the diameter ratio and packing fraction in granular arrays surrounding a slowly elongating elastica, we characterize the resulting elastogranular interactions taking place in a transitional, amorphous medium. For low number density packings prepared with moderate to large bidispersity, we find the critical injected arclength to elicit jamming follows the same scaling law observed in monodisperse arrays. Beyond the jamming point, the elastica is seen to relax its bending energy within packings with progressively larger diameter ratios towards the shape expected when deforming within more fluid-like media., Comment: 6 pages, 4 figures

The contributions of phosphorylation-mediated signaling networks to colon cancer metastasis are poorly defined. To interrogate constitutive signaling alterations in cancer progression, the global phosphoproteomes of patient-matched SW480 (primary colon tumor origin) and SW620 (lymph node metastasis) cell lines were compared with TiO2 and immobilized metal affinity chromatography phosphopeptide enrichment followed by liquid chromatography–tandem mass spectrometry. Network analysis of the significantly altered phosphosites revealed differential regulation in cellular adhesion, mitosis, and messenger RNA translational machinery. Messenger RNA biogenesis and splicing, transport through the nuclear pores, initiation of translation, and stability and degradation were also affected. Although alterations in these processes have been associated with oncogenic transformation, control of messenger RNA stability has typically not been associated with cancer progression. Notably, the single phosphosite with the greatest relative change in SW620 cells was Ser2 on eukaryotic translation initiation factor 2 subunit 2, suggesting that SW620 cells translate faster or with greater efficiency than SW480 cells. These broad changes in the regulation of translation also occur without overexpression of eukaryotic translation initiation factor 4E. The findings suggest that metastatic cells exhibit constitutive changes to the phosphoproteome, and that messenger RNA stability and translational efficiency may be important targets of deregulation during cancer progression.

Phosphopeptide enrichment from complicated peptide mixtures is an essential step for mass spectrometry-based phosphoproteomic studies to reduce sample complexity and ionization suppression effects. Typical methods for enriching phosphopeptides include immobilized metal affinity chromatography (IMAC) or titanium dioxide (TiO2) beads, which have selective affinity and can interact with phosphopeptides. In this study, the IMAC enrichment method was compared with the TiO2 enrichment method, using a multistep enrichment strategy from whole cell lysate, to evaluate their abilities to enrich for different types of phosphopeptides. The peptide-to-beads ratios were optimized for both IMAC and TiO2 beads. Both IMAC and TiO2 enrichments were performed for three rounds to enable the maximum extraction of phosphopeptides from the whole cell lysates. The phosphopeptides that are unique to IMAC enrichment, unique to TiO2 enrichment, and identified with both IMAC and TiO2 enrichment were analyzed for their characteristic...

Confinement of a slender body into a granular array induces stress localization in the geometrically nonlinear structure, and jamming, reordering, and vertical dislocation of the surrounding granular medium. By varying the initial packing density of grains and the length of a confined elastica, we identify the critical length necessary to induce jamming, and demonstrate an intricate coupling between folds that localize along grain boundaries. Above the jamming threshold, the characteristic length of elastica deformation is shown to scale with the length over which force field fluctuations propagate in a jammed state, suggesting the ordering of the granular array governs the deformation of the slender structure. However, over confinement of the elastica will induce a form of stress relaxation in the granular medium by dislocating grains through two distinct mechanisms that depend on the geometry of the confined structure., 7 pages, 7 figures; including Supplemental Material

(a) Introductory sentence Antibody enrichment and liquid chromatography mass spectrometry (LC-MS) were used to profile lysine acetylation and arginine mono-methylation in triple negative breast cancer patient sera without prior immunodepletion of abundant proteins. (b) Brief description of experiments Triple negative breast cancer (TNBC) is the most aggressive type of breast tumor and there are currently no approved targeted therapies. Better biomarkers are needed for early detection and for therapeutically informative subtyping of this genetically heterogeneous disease. We recently reported a methodology to enrich post-translationally modified peptides from serum (Gu et al, Mol Cell Proteomics 2015) and found acetyl lysine (AcK) and mono-methyl arginine (RMe) to be some of the most abundant post-translational modifications (PTMs) in the sera of cancer patients. This method has the advantage of profiling serum samples without prior depletion of abundant serum proteins, a major limitation of current proteomic methods. To develop a biomarker signature of TNBC, these two PTMs were profiled in the sera of 10 patients with stage I-IIA TNBC and 10 healthy female controls. Serum proteins were trypsin digested prior to immunoaffinity enrichment of the modified peptides with PTM-specific antibodies. The enriched peptides were analyzed by LC-MS and relative abundance of peptides across samples was measured using label-free quantification. (c) Summary of new, unpublished data PTM enrichment quantified hundreds of AcK and RMe sites across samples. AcK levels decreased globally in patients compared to controls, suggestive of increased lysine deacetylase or decreased acetyltransferase activity. Of these, a number of sites were found significantly altered between TNBC patient samples and normal controls at the p (d) Statement of conclusions AcK and Rme peptide signatures were identified that correlate with disease status, tumor grade, and stage. Patient follow-up over time will allow for investigation of markers of treatment response and disease progression as well. AcK and Rme are known to affect gene transcription profiles in cancer. Drug molecules targeting multiple families of AcK interacting proteins, including KATs, HDACs, and BET proteins, have entered clinical trials for breast and other cancers. AcK was globally downregulated in the samples surveyed, which suggests that these tumors may be responsive to some of these drug classes. Further analysis will correlate the AcK and RMe profiles to identify a PTM signature of therapeutically vulnerable epigenetic regulators in TNBC. Citation Format: Alissa J. Schunter, Hongbo Gu, Jian Min Ren, Vicky Yang, Matthew P. Stokes. Mass spectrometry-based profiling of lysine acetylation and arginine methylation for biomarker discovery in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2704.