Clinical utility of chromogranin A and octreotide in large cell neuro endocrine carcinoma of the uterine corpus

Primary neuroendocrine tumors of the female genital tract have been described in the cervix, ovaries and uterus. Large cell neuroendocrine carcinoma (LCNC) of the uterine corpus is the least common and appears to behave the most aggressively. We report a rare case of a large cell neuroendocrine tumor of the endometrium. These tumors are not well characterized, unlike neuroendocrine tumors of the uterine cervix. Consequently, the optimal management remains still unclear. The treatment of our case consisted of surgery, radiotherapy, chemotherapy, and octreotide. Despite the aggressive treatment, the patient died of disease progression 12 months after the initial diagnosis. We discuss the diagnosis, prognosis, and treatment options for LCNC of the genital tract, and potential future therapeutics

Rapid Acquisition of X-Ray Scattering Data from Droplet-Encapsulated Protein Systems

Encapsulating reacting biological or chemical samples in microfluidic droplets has the great advantage over single-phase flows of providing separate reaction compartments. These compartments can be filled in a combinatoric way and prevent the sample from adsorbing to the channel walls. In recent years, small-angle X-ray scattering (SAXS) in combination with microfluidics has evolved as a nanoscale method of such systems. Here, we approach two major challenges associated with combining droplet microfluidics and SAXS. First, we present a simple, versatile, and reliable device, which is both suitable for stable droplet formation and compatible with in situ X-ray measurements. Second, we solve the problem of “diluting” the sample signal by the signal from the oil separating the emulsion droplets by multiple fast acquisitions per droplet and data thresholding. We show that using our method, even the weakly scattering protein vimentin provides high signal-to-noise ratio data

X‑rays Reveal the Internal Structure of Keratin Bundles in Whole Cells

In recent years, X-ray imaging of biological cells has emerged as a complementary alternative to fluorescence and electron microscopy. Different techniques were established and successfully applied to macromolecular assemblies and structures in cells. However, while the resolution is reaching the nanometer scale, the dose is increasing. It is essential to develop strategies to overcome or reduce radiation damage. Here we approach this intrinsic problem by combing two different X-ray techniques, namely ptychography and nanodiffraction, in one experiment and on the same sample. We acquire low dose ptychography overview images of whole cells at a resolution of 65 nm. We subsequently record high-resolution nanodiffraction data from regions of interest. By comparing images from the two modalities, we can exclude strong effects of radiation damage on the specimen. From the diffraction data we retrieve quantitative structural information from intracellular bundles of keratin intermediate filaments such as a filament radius of 5 nm, hexagonal geometric arrangement with an interfilament distance of 14 nm and bundle diameters on the order of 70 nm. Thus, we present an appealing combined approach to answer a broad range of questions in soft-matter physics, biophysics and biology

Following DNA Compaction During the Cell Cycle by X‑ray Nanodiffraction

X-ray imaging of intact biological cells is emerging as a complementary method to visible light or electron microscopy. Owing to the high penetration depth and small wavelength of X-rays, it is possible to resolve subcellular structures at a resolution of a few nanometers. Here, we apply scanning X-ray nanodiffraction in combination with time-lapse bright-field microscopy to nuclei of 3T3 fibroblasts and thus relate the observed structures to specific phases in the cell division cycle. We scan the sample at a step size of 250 nm and analyze the individual diffraction patterns according to a generalized Porod’s law. Thus, we obtain information on the aggregation state of the nuclear DNA at a real space resolution on the order of the step size and in parallel structural information on the order of few nanometers. We are able to distinguish nucleoli, heterochromatin, and euchromatin in the nuclei and follow the compaction and decompaction during the cell division cycle

Tropomyosin variants describe distinct functional subcellular domains in differentiated vascular smooth muscle cells

Tropomyosin (Tm) is known to be an important gatekeeper of actin function. Tm isoforms are encoded by four genes, and each gene produces several variants by alternative splicing, which have been proposed to play roles in motility, proliferation, and apoptosis. Smooth muscle studies have focused on gizzard smooth muscle, where a heterodimer of Tm from the α-gene (Tmsm-α) and from the β-gene (Tmsm-β) is associated with contractile filaments. In this study we examined Tm in differentiated mammalian vascular smooth muscle (dVSM). Liquid chromatography-tandem mass spectrometry (LC MS/MS) analysis and Western blot screening with variant-specific antibodies revealed that at least five different Tm proteins are expressed in this tissue: Tm6 (Tmsm-α) and Tm2 from the α-gene, Tm1 (Tmsm-β) from the β-gene, Tm5NM1 from the γ-gene, and Tm4 from the δ-gene. Tm6 is by far most abundant in dVSM followed by Tm1, Tm2, Tm5NM1, and Tm4. Coimmunoprecipitation and coimmunofluorescence studies demonstrate that Tm1 and Tm6 coassociate with different actin isoforms and display different intracellular localizations. Using an antibody specific for cytoplasmic γ-actin, we report here the presence of a γ-actin cortical cytoskeleton in dVSM cells. Tm1 colocalizes with cortical cytoplasmic γ-actin and coprecipitates with γ-actin. Tm6, on the other hand, is located on contractile bundles. These data indicate that Tm1 and Tm6 do not form a classical heterodimer in dVSM but rather describe different functional cellular compartments

Les Écoles dans la guerre

L'École n’est pas hors du monde et hors du temps. Lorsque les « malheurs de la guerre » frappent un territoire et ses habitants, les acteurs éducatifs et les structures scolaires sont touchés. La mobilisation des hommes pour le combat atteint les personnels et les plus grands élèves ainsi que les étudiants, qui délaissent la plume et le verbe pour l’épée et le fusil. À l’arrière, les acteurs de l’École tentent de maintenir en vie les structures scolaires et universitaires et de les mobiliser pour la victoire alors que nombre de bâtiments sont aussi réquisitionnés pour d’autres missions. Lorsque la guerre, devenue défaite temporaire ou plus durable, débouche sur l’occupation par des forces ennemies ou sur l’installation d’un nouveau régime politique (tel le Régime de Vichy), les Écoles doivent apprendre à « survivre » en terrain hostile, marquant souvent par leur présence une forme de résistance. Le positionnement des acteurs éducatifs, dans ces périodes « noires » s’avère complexe. L’École, qui peut être un outil de formation au service de l’esprit raisonnable et de la paix entre les hommes, peut aussi, sous certaines conditions, devenir un instrument au service de la préparation de la guerre. Ce sont là les thématiques majeures proposées par ce livre qui, autour de 24 contributions inédites, croisant les échelles spatiales, fait aussi le choix de la longue durée (xviie-xxe siècles), même si elles portent surtout sur les deux guerres mondiales du xxe siècle