How genomic DNA is folded during cell division to form the characteristic rod-shaped mitotic chromosomes essential for faithful genome inheritance is a long-standing open question in biology. Here, we use nanoscale DNA-tracing in single dividing cells to directly visualize how the 3D fold of genomic DNA changes during mitosis, at scales from single loops to entire chromosomes. Our structural analysis reveals a characteristic genome scaling minimum at 6-8 Mbp in mitosis.
View Article and Find Full Text PDFThe individualization of chromosomes during early mitosis and their clustering upon exit from cell division are two key transitions that ensure efficient segregation of eukaryotic chromosomes. Both processes are regulated by the surfactant-like protein Ki-67, but how Ki-67 achieves these diametric functions has remained unknown. Here, we report that Ki-67 radically switches from a chromosome repellent to a chromosome attractant during anaphase in human cells.
View Article and Find Full Text PDFHow cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over two hours. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes and are sufficient to build the first interphase TAD structures.
View Article and Find Full Text PDFCryo-electron tomography (cryo-ET) allows for label-free high-resolution imaging of macromolecular assemblies in their native cellular context. However, the localization of macromolecules of interest in tomographic volumes can be challenging. Here we present a ligand-inducible labeling strategy for intracellular proteins based on fluorescent, 25-nm-sized, genetically encoded multimeric particles (GEMs).
View Article and Find Full Text PDFExtending the service life of ageing infrastructure, transportation structures, and processing and manufacturing plants in an era of limited resources has spurred extensive research and development in structural health monitoring systems and their integration. Even though piezoelectric transducers are not the only sensor technology for SHM, they are widely used for data acquisition from, e.g.
View Article and Find Full Text PDFQuasi-static or cyclic loading of an artificial starter crack in unidirectionally fibre-reinforced composite test coupons yields fracture mechanics data-the toughness or strain-energy release rate (labelled G)-for characterising delamination initiation and propagation. Thus far, the reproducibility of these tests is typically between 10 and 20%. However, differences in the size and possibly the shape, but also in the fibre lay-up, between test coupons and components or structures raise additional questions: Is G from a coupon test a suitable parameter for describing the behaviour of delaminations in composite structures? Can planar, two-dimensional, delamination propagation in composite plates or shells be properly predicted from essentially one-dimensional propagation in coupons? How does fibre bridging in unidirectionally reinforced test coupons relate to delamination propagation in multidirectional lay-ups of components and structures? How can multiple, localised delaminations-often created by impact in composite structures-and their interaction under service loads with constant or variable amplitudes be accounted for? Does planar delamination propagation depend on laminate thickness, thickness variation or the overall shape of the structure? How does exposure to different, variable service environments affect delamination initiation and propagation? Is the microscopic and mesoscopic morphology of FRP composite structures sufficiently understood for accurate predictive modelling and simulation of delamination behaviour? This contribution will examine selected issues and discuss the consequences for test development and analysis.
View Article and Find Full Text PDFNuclear pore complexes (NPCs) are channels within the nuclear envelope that mediate nucleocytoplasmic transport. NPCs form within the closed nuclear envelope during interphase or assemble concomitantly with nuclear envelope reformation in late stages of mitosis. Both interphase and mitotic NPC biogenesis require coordination of protein complex assembly and membrane deformation.
View Article and Find Full Text PDFAutomated tape placement with in-situ consolidation (ATPisc) is a layer-wise manufacturing process in which the achievement of proper interlayer bonding constitutes one of the most challenging aspects. In the present study, unidirectional carbon fiber reinforced thermoplastic laminates were produced following different manufacturing protocols using ATPisc. The interlayer bonding of the laminates produced was characterized by mode I fatigue fracture tests with double cantilever beam (DCB) specimens.
View Article and Find Full Text PDFThe emergence of atomically thin van der Waals magnets provides a new platform for the studies of two-dimensional magnetism and its applications. However, the widely used measurement methods in recent studies cannot provide quantitative information of the magnetization nor achieve nanoscale spatial resolution. These capabilities are essential to explore the rich properties of magnetic domains and spin textures.
View Article and Find Full Text PDFAdipokines secreted from white adipose tissue play a role in metabolic crosstalk and homeostasis, whereas the brown adipose secretome is less explored. We performed high-sensitivity mass-spectrometry-based proteomics on the cell media of human adipocytes derived from the supraclavicular brown adipose and from the subcutaneous white adipose depots of adult humans. We identified 471 potentially secreted proteins covering interesting categories such as hormones, growth factors, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated between brown and white adipocytes.
View Article and Find Full Text PDFTerminal alkynes (RCCH) are homologated by a sequence of ruthenium-catalyzed anti-Markovnikov hydration of alkyne to aldehyde (RCH2CHO), followed by Bestmann-Ohira alkynylation of aldehyde to chain-elongated alkyne (RCH2CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of (13)C-labeled Bestmann-Ohira reagent (dimethyl ((1-(13)C)-1-diazo-2-oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply (13) C-labeled alkynes.
View Article and Find Full Text PDFShigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Glycoconjugate vaccines consisting of bacterial surface polysaccharides conjugated to carrier proteins are the most effective vaccines for controlling invasive bacterial infections. Nevertheless, the development of a multivalent conjugate vaccine to prevent Shigellosis has been hampered by the complex manufacturing process as the surface polysaccharide for each strain requires extraction, hydrolysis, chemical activation and conjugation to a carrier protein.
View Article and Find Full Text PDFB7-H3 is a transmembrane protein and a member of the B7 family of immune regulatory ligands. It exerts both inhibitory and stimulatory effects on the activation of T cells. We investigated the expression of B7-H3 in invasive squamous cell carcinoma (ISCC) of the uterine cervix by immunohistochemistry, and aimed to determine whether expression of this factor is involved in the progression of the morphologic spectrum from normal cervical epithelia to cervical intraepithelial neoplasia and cervical ISCC.
View Article and Find Full Text PDFPhotonic structures in diamond are key to most of its application in quantum technology. Here, we demonstrate tapered nanowaveguides structured directly onto the diamond substrate hosting shallow-implanted nitrogen vacancy (NV) centers. By optimization based on simulations and precise experimental control of the geometry of these pillar-shaped nanowaveguides, we achieve a net photon flux up to ∼ 1.
View Article and Find Full Text PDFSOX2 is a transcription factor controlling pluripotency in both embryonic stem cells and adult tissue-specific stem cells. SOX2 has been reported as an important factor in squamous cell carcinomas (SCC) of different locations and is involved in tumorigenesis. We evaluated the expression of SOX2 in vulvar non-neoplastic and neoplastic epithelia to test whether it is related to neoplastic progression.
View Article and Find Full Text PDFWe report on three-body recombination of a single trapped Rb(+) ion and two neutral Rb atoms in an ultracold atom cloud. We observe that the corresponding rate coefficient K(3) depends on collision energy and is about a factor of 1000 larger than for three colliding neutral Rb atoms. In the three-body recombination process large energies up to several 0.
View Article and Find Full Text PDFBackground: In an aging population an increasing number of breast cancers is diagnosed in elderly women. Tumor characteristics and patterns of metastasation have been extensively elucidated in younger triple negative breast cancer (TNBC) patients, but data regarding TNBC in elderly women are missing. The goal of this investigation was to compare clinical pathological characteristics of younger and elderly TNBC patients in order to assess their relevance for TNBC in an aging population.
View Article and Find Full Text PDFObjective: B7-H3, a member of the B7 family of immune regulatory ligands regulates T cell-mediated peripheral immune response. The purpose of this study was to correlate the expression of B7-H3 and number of lymphocytes in patients with endometrial cancer.
Material And Methods: A total of 107 patients with primary endometrial carcinoma (type I/endometrioid, n=81; type II, n=18) and endometrial hyperplasia (n=8) were investigated.
Survivin inhibits apoptosis and is involved in the regulation of cell cycle progression and in the mitotic spindle formation. It is overexpressed in many cancers. The histone γ-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions.
View Article and Find Full Text PDFNocturia is a common problem in adults, which adversely affects quality of sleep and quality of life. This review summarizes the definition, epidemiology, clinical presentation, pathophysiology, diagnostic evaluation, and the therapeutic options with regard to a female population. Based on the degree of bother nocturia is classified as two or more episodes per night.
View Article and Find Full Text PDFObjective: The objective of the study was to evaluate the association between human papillomavirus (HPV) infection and clinical-pathological parameters in primary squamous cell carcinoma of the vagina and assess the value of HPV infection as a prognostic parameter.
Methods: In our retrospective study, we identified 37 consecutive patients with primary invasive squamous cell carcinoma of the vagina; 35 patients were eligible for further investigations. Human papillomavirus detection was assessed by in situ hybridization assays from paraffin-embedded tissue blocks.
OBJECTIVE.: The most frequently mutated gene in human cancer is p53, a gene that functions in the checkpoint response to DNA double-strand breaks. γ-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and their precursor lesions.
View Article and Find Full Text PDFThe histone γ-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions, indicating a role in oncogenic transformation. Epidermal growth factor receptor (EGFR) is overexpressed in many kinds of epithelial neoplasms. This study aimed to determine whether immunohistochemical expression of γ-H2AX is involved in the progression of the morphological spectrum from normal squamous cervical epithelia (NE, n=33) to cervical intraepithelial neoplasia (CIN; CIN1, n=9; CIN2/3, n=33) and cervical invasive squamous cell carcinoma (ISCC, n=33), whether γ-H2AX expression follows the pattern of proliferation of atypical squamous cells as shown by EGFR immunoreactivity, and whether it is correlated with clinicopathologic variables in ISCC.
View Article and Find Full Text PDFObjective: Primary invasive squamous cell carcinoma of the vagina is a rare neoplasm. Investigations concerning the potential of new therapeutic targets are limited.
Study Design: A total of 34 patients with primary invasive squamous cell carcinoma of the vagina was identified, who were treated at our institution between 1994 and 2008.