Megakaryocytic features useful for the diagnosis of myeloproliferative disorders can be obtained by a novel unsupervised software analysis

An unsupervised method for megakaryocyte detection and analysis is proposed, in order to validate supplementary tools which can be of help in supporting the pathologist in the classification of Philadelphia negative chronic myeloproliferative disorders with thrombocytosis. The experiment was conducted on high power magnification photomicrographs taken from hematoxylin-and-eosin 3 μm thick sections of formalin fixed, paraffin embedded bone marrow biopsies from patients with reactive thrombocytosis or chronic myeloproliferative disorders. Each megakaryocyte has been isolated in the photos through an image segmentation process, mainly based on mathematical morphology and wavelet analysis. A set of features (e.g. area, perimeter and fractal dimension of the cell and its nucleus, shape complexity via elliptic Fourier transform, and so on) is used to characterize the disorders and discriminate between essential thrombocythemia and idiopathic myelofibrosis. Features related to the general contour of the cell like cytoplasmic area and perimeter are good markers in distinguishing between normal or reactive and pathologic megakaryocytes while nuclear features and global circularity are helpful in the differential diagnosis between ET and prefibrotic IMF. The method proposed should be considered as a fast preprocessing tool for the diagnostic phase and its use can be extended to solve different object recognition problem

Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines

Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compartments and forms the primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized primary human trophoblast (PHT) cells isolated from full-term placentas and human midgestation chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and respond to T. gondii infection. We show that placental syncytiotrophoblasts, multinucleated cells that are in direct contact with maternal blood, restrict T. gondii infection at two distinct stages of the parasite lytic cycle—at the time of attachment and also during intracellular replication. Utilizing comparative transcriptome sequencing (RNA-seq) transcriptional profiling, we also show that human placental trophoblasts from both the second and third trimesters respond uniquely to T. gondii infection compared to trophoblast cell lines, typified by the upregulation of several immunity-related genes. One of the most differentially induced genes was the chemokine CCL22, which relies on the secretion of a parasite effector(s) either during or after invasion for its induction. Collectively, our findings provide new insights into the mechanisms by which the human placenta restricts the vertical transmission of T. gondii at early and late stages of human pregnancy and demonstrate the existence of at least two interferon-independent pathways that restrict T. gondii access to the fetal compartment. IMPORTANCE Toxoplasma gondii is a major source of congenital disease worldwide and must breach the placental barrier to be transmitted from maternal blood to the developing fetus. The events associated with the vertical transmission of T. gondii are largely unknown. Here, we show that primary human syncytiotrophoblasts, the fetus-derived cells that comprise the primary placental barrier, restrict T. gondii infection at two distinct stages of the parasite life cycle and respond to infection by inducing a unique immunomodulatory transcriptional profile. Collectively, our findings provide important insights into the mechanisms by which human syncytiotrophoblasts restrict T. gondii infection at early and late stages of human pregnancy, identify both permissive and resistant human placental cell types, and identify the placenta-enriched signaling pathways induced in response to infection

The Mu3e experiment: Toward the construction of an HV-MAPS vertex detector

The Mu3e experiment searches for the lepton flavor violating decay $\mu^+~\rightarrow~e^+~e^+~e^-$ with an ultimate aimed sensitivity of 1 event in $10^{16}$ decays. This goal can only be achieved by reducing the material budget per tracking layer to $X/X_0 \approx 0.1 \%$. High-Voltage Monolithic Active Pixel Sensors (HV-MAPS) which are thinned to 50 μm serve as sensors. Gaseous helium is chosen as coolant. Results of recent studies related to the sensor prototypes, the helium cooling, and module prototyping are presented. The recent chip submission MuPix10 has proven its functionality regarding efficiency and time resolution. The helium cooling system for the inner tracker could be verified using a full-scale prototype. A complete prototype equipped with MuPix10 chips will be tested inside the Mu3e magnet in summer 2021

The Mu3e experiment: Toward the construction of an HV-MAPS vertex detector

The Mu3e experiment searches for the lepton flavor violating decay $\mu^+~\rightarrow~e^+~e^+~e^-$ with an ultimate aimed sensitivity of 1 event in $10^{16}$ decays. This goal can only be achieved by reducing the material budget per tracking layer to $X/X_0 \approx 0.1 \%$. High-Voltage Monolithic Active Pixel Sensors (HV-MAPS) which are thinned to $50\ \mu m$ serve as sensors. Gaseous helium is chosen as coolant. Results of recent studies related to the sensor prototypes, the helium cooling, and module prototyping are presented. The recent chip submission MuPix10 has proven its functionality regarding efficiency and time resolution. The helium cooling system for the inner tracker could be verified using a full-scale prototype. A complete prototype equipped with MuPix10 chips will be tested inside the Mu3e magnet in summer 2021.Comment: Talk presented at the International Workshop on Future Linear Colliders (LCWS2021), 15-18 March 2021. C21-03-15.

Sialylated N-glycans mediate monocyte uptake of extracellular vesicles secreted from Plasmodium falciparum-infected red blood cells

Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells

Group analysis of structure equations for stars in radiative and convective equilibrium

It is proposed to use the Lie group theory of symmetries of differential equations to investigate the system of equations describing a static star in a radiative and convective equilibrium. It is shown that the action of an admissible group induces a certain algebraic structure in the set of all solutions, which can be used to find a family of new solutions. We have demonstrated that, in the most general case, the equations admit an infinite parameter group of quasi-homologous transformations. We have found invariants of the symmetries group which correspond to the fundamental relations describing a physical characteristic of the stars such as the Hertzsprung-Russell diagram or the mass-luminosity relation. In this way we can suggest that group invariants have not only purely mathematical sense, but their forms are closely associated with the basic empirical relations.Comment: LaTeX2e, 13page

Butyrate down-regulates CD44 transcription and liver colonisation in a highly metastatic human colon carcinoma cell line

Over-expression of the adhesion molecule CD44 and its splice variants, especially CD44v6, is associated with poor prognosis and metastasis. We aimed at regulating the expression of CD44 in the highly metastatic human colon cancer cell line HM7 and thereby affecting its metastatic ability. HM7 cells show constitutive expression of CD44 standard and variants isoforms, which were significantly down-regulated by treatment with butyrate. Butyrate significantly inhibited transcription of the CD44 gene and abolished epidermal growth factor-mediated up-regulation of the reporter gene luciferase subcloned upstream to the CD44 promoter (−1.1 kb) and transfected to HM7 cells. Nuclear proteins from butyrate-treated cells bound to an epidermal growth factor receptor element motif present in the CD44 promoter. Epidermal growth factor receptor element-site directed mutations eliminated the inducibility of the luciferase reporter gene and did not allowed binding of nuclear proteins harvested from butyrate-treated cells. Butyrate induced CD44 gene repression by specifically interacting with an epidermal growth factor receptor element nuclear transcriptional factor. This interaction affects CD44 transcriptional activity vis-à-vis in vivo metastatic ability of HM7 cells. These results provide additional insight into the anticarcinogenic properties of butyrate

The GRONORUN study: is a graded training program for novice runners effective in preventing running related injuries? Design of a Randomized Controlled Trial

BACKGROUND: Running is a popular form of recreational exercise. Beside the positive effects of running on health and fitness, the risk of a running related injury has to be considered. The incidence of injuries in runners is high and varies from 30–79%. However, few intervention studies on prevention of running related injuries have been performed and none of these studies involved novice runners. METHODS: GRONORUN (Groningen Novice Running) is a two armed randomized controlled trial, comparing the effects of two different training programs for novice runners on the incidence of running related injuries. Participants are novice runners, who want to train for a four mile running event. The control group will train according a standard 8 week training program. The intervention group will use a more gradual, 13 week training program which is based on "the ten percent training rule". During the thirteen week follow up participants register information on running and RRI's in an internet based running log. The primary outcome measure is RRI. An injury is defined as a musculoskeletal ailment of the lower extremity or back, causing a restriction of running for at least one week. DISCUSSION: The GRONORUN trial is the first randomized controlled trial to study a preventive intervention in novice runners. Many different training programs for novice runners are offered, but none are evidence based