The human ovary : a characterization of cell types and adverse ovarian side effects of chemotherapy

The human ovary has a major role in the body’s endocrine and reproductive system. Understanding its cell type composition is crucial in order to study underlying mechanisms of hormonal balance and ovarian follicle maturation in health and disease. The outer lining of the ovary, the cortex, harbors the ovarian reserve. This reserve is made up of follicles that have formed before birth. The prevailing dogma of female fertility sees this reserve as being limited in humans, with follicle numbers decreasing over time. Once the ovarian reserve is depleted, women enter menopause which marks the end of their reproductive period. Premature ovarian insufficiency is characterized by an early depletion of the ovarian reserve and reveals itself, among others, with an altered hormone profile and early menopause onset. Anti-cancer treatment is one of the causes of premature ovarian insufficiency. However, mechanisms underlying chemotherapy-induced altered ovarian tissue morphology and function are not yet fully understood. Therefore, effective treatments to prevent or cure the damage are still missing. One possibility for novel treatments could be offered by oogonial stem cells (OSCs) that have been recently reported to exist in the adult human ovaries. These cells can be isolated with DDX4 antibody (Ab), show a gene expression profile similar to germline stem cells in the developing embryo and have the potential to mature into oocytes. The overall aim of this thesis is to assess the effect of first-line chemotherapy on ovarian follicles and stroma by using a tissue collection from fertility preservation programs and to dissect the structure of human ovarian cortex at single-cell resolution by using advanced single- cell profiling technology. In study I, the effects of first-line chemotherapy that is not considered a risk for future fertility on ovarian follicles and stroma cells from pediatric and young adult ovaries were investigated. Exposure to chemotherapy prior to ovarian tissue cryopreservation revealed an impact on follicle and stroma health. Early ovarian follicles (primordial and intermediary) appeared more atretic and were smaller, while healthy growing follicles (primary) decreased in numbers. Steroid production by treated ovarian tissue in culture decreased and DNA damage as well as fibrotic lesions in the ovarian stroma increased. In study II, we assessed the cellular composition of the adult human ovarian cortex at a single- cell level. Transcriptome and surface proteome analysis revealed six major cell types consistently detected in the ovarian cortex from Cesarean section and gender reassignment patients, namely oocytes, immune cells, granulosa cells, endothelial cells, perivascular cells and stroma cells. In order to investigate the existence of the previously reported OSCs, ovarian cortex cells positive for DDX4 Ab were isolated and analyzed. DDX4 Ab-positive cells did not show a germline-like profile, neither at a transcriptional nor protein level, but instead could be identified as perivascular cells. Furthermore, when integrating published single-cell sequencing data from fetal germ cells, we could not identify any cortex cell with a transcriptome profile of germline stem cells. In conclusion, we demonstrate that first-line chemotherapy treatment has negative effects on the health of ovarian cortex and exposure should be limited before cryopreservation of ovarian tissue, if possible. Adult ovarian cortex is made up of various cell types, but no evidence for the existence of germline-like stem cells was found

Object-Oriented Modeling of a Capacitive Deionization Process

The process of capacitive deionization (CDI) is a cost effective and energy efficient method that offers many opportunities in terms of desalination of brackish water and the removal of ionic contaminants. Current research focusses on evaluating different influence parameters to make the CDI process more competitive to other commercially available methods like reverse osmosis, direct distillation or ion exchange. CDI is based on the adsorption of ions to highly porous electrodes by applying an external voltage difference. Although, remarkable progress in CDI modeling has been achieved during the past decade, so far, only few models exist which fully describe the CDI process and which predict the cell behavior in all its aspects, including e.g., performance under constant voltage and/or constant current control or pH effects including water dissociation. However, in this paper a new approach to CDI modeling is presented, which opens a path to fast and easy implementation of a digital depiction of complex CDI setups having e.g., multiple cells. The model is based on the object-oriented modeling language Modelica that enables the simulation and prediction of the behavior of complete CDI cells by combining chemical, electrochemical and electrical components. Furthermore, there is the possibility to predict complex setups with e.g., complex electrolytes, concentration or voltage fluctuations as they appear due to environmental influences outside laboratory experiments. Besides detailed time courses of species concentrations in the bulk and the electrodes or local electrical potentials, the model enables the prediction of important sum parameters such as the salt adsorption capacity, current efficiency and power consumption. The results of the developed CDI model are validated by using parameter settings from literature and comparing the resulting predictions of equilibrium and kinetics. In addition, the agreement between our own experimental results and the respective model predictions is discussed

Paralingua – A New Speech Corpus for the Studies of Paralinguistic Features

AbstractThis paper introduces “Paralingua” - a new speech corpus created within a larger ongoing project whose primary aim was to develop a speaker recognition and identification system for forensics. The present corpus was designed for the purpose of analysis of selected paralinguistic features in continuous speech and for preliminary examination of the vocal display of affective states. The recorded (and annotated) data include conversational speech in the form of task-oriented dialogues, emotional utterances (realized as emotion portrayals), and an acted court scene. As a reference material, a short read text was provided by each of the speakers

Medikamenteninduzierte Hyponatriämie

Die Arbeit gibt einen Überblick über die unterschiedlichen Formen von Hyponatriämie und geht im speziellen auf die medikamenteninduzierte Hyponatriämie ein. Dazu wurden Patientendaten aus dem Jahr 2008 vom SMZ-Ost gesammelt und auch Charakteristika untersucht. Die Ergebnisse sind zum größten Teil denen aus der untersuchten Literatur sehr ähnlich. Vor allem ältere Frauen waren Hauptsächlich von Hyponatriämien betroffen. Steigende Medikamentenzahlen führten häufiger zu Hyponatriämien. Diuretika, vor allem Thiazide, lösten neue und verstärkten bestehende Hyponatriämien. SSRI führten meist zu schwachen wenig symptomatischen Hyponatriämien. Generell ist bestätigt worden, dass Hyponatriämie eine ernstzunehmende Nebenwirkung vieler Arzneimittel ist

20 Years of Secretagogin: Exocytosis and Beyond

Calcium is one of the most important signaling factors in mammalian cells. Specific temporal and spatial calcium signals underlie fundamental processes such as cell growth, development, circadian rhythms, neurotransmission, hormonal actions and apoptosis. In order to translate calcium signals into cellular processes a vast number of proteins bind this ion with affinities from the nanomolar to millimolar range. Using classical biochemical methods an impressing number of calcium binding proteins (CBPs) have been discovered since the late 1960s, some of which are expressed ubiquitously, others are more restricted to specific cell types. In the nervous system expression patterns of different CBPs have been used to discern different neuronal cell populations, especially before advanced methods like single-cell transcriptomics and activity recording were available to define neuronal identity. However, understanding CBPs and their interacting proteins is still of central interest. The post-genomic era has coined the term “calciomics,” to describe a whole new research field, that engages in the identification and characterization of CBPs and their interactome. Secretagogin is a CBP, that was discovered 20 years ago in the pancreas. Consecutively it was found also in other organs including the nervous system, with characteristic expression patterns mostly forming cell clusters. Its regional expression and subcellular location together with the identification of protein interaction partners implicated, that secretagogin has a central role in hormone secretion. Meanwhile, with the help of modern proteomics a large number of actual and putative interacting proteins has been identified, that allow to anticipate a much more complex role of secretagogin in developing and adult neuronal cells. Here, we review recent findings that appear like puzzle stones of a greater picture

Reply : Revisiting Claims of the Continued Absence of Functional Germline Stem Cells in Adult Ovaries

Non peer reviewe

The Continued Absence of Functional Germline Stem Cells in Adult Ovaries

Ovaries are central to development, fertility, and reproduction of women. A particularly interesting feature of ovaries is their accelerated aging compared to other tissues, leading to loss of function far before other organs senesce. The limited pool of ovarian follicles is generated before birth and once exhausted, menopause will inevitably commence around the age of 50 years marking the end of fertility. Yet, there are reports suggesting the presence of germline stem cells and neo-oogenesis in adult human ovaries. These observations have fueled a long debate, created experimental fertility treatments, and opened business opportunities. Our recent analysis of cell types in the ovarian cortex of women of fertile age could not find evidence of germline stem cells. Like before, our work has been met with critique suggesting methodological shortcomings. We agree that excellence starts with methods and welcome discussion on the pros and cons of different protocols. In this commentary, we discuss the recent re-interpretation of our work.Peer reviewe

A study on the formation environment of the La Cumbre amber deposit, from Santiago Province, the northwestern part of the Dominican Republic

The amber-bearing coaly shale from the La Cumbre deposit (Cordillera Septentrional, Dominican Republic) contains a large quantity of altered, coalified plant detritus. The coals in these shales are in the transition stage from meta-lignite to subbituminous coals. They are composed mainly of inertinite macerals such as fusinite, semifusinite, macrinite and secretinite. Fossil resin found in the deposit occurs in two forms: detrital grains up to several centimetres in size (type I) and very fine authigenic grains, of a few micrometers in size, inside the humic laminae (type II, resinite). The detrital fossil resins are transparent, with few mineral and organic inclusions. In their composition they contain sulfides, which may come from sulfate reduction, inclusions of plants and/or insects or be caused by volcanic activity developed in surrounding coal series. The resinites are strongly saturated with various inclusions and spatially associated with framboidal pyrite aggregates. Both fossil resin types were probably deposited in a shallow coastal lake environment in the zone bordering the floodplain of the river, with periodic floods. The marine environment conditions, which were progressively changing from oxidizing to reducing, are likely associated with the formation of the fossil resin

The BMI1 inhibitor PTC-209 is a potential compound to halt cellular growth in biliary tract cancer cells

BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and is up-regulated in biliary tract cancer (BTC), contributing to aggressive clinical features. In this study we investigated the cytotoxic effects of PTC-209, a recently developed inhibitor of BMI1, in BTC cells. PTC-209 reduced overall viability in BTC cell lines in a dose-dependent fashion (0.04 - 20 μM). Treatment with PTC-209 led to slightly enhanced caspase activity and stop of cell proliferation. Cell cycle analysis revealed that PTC-209 caused cell cycle arrest at the G1/S checkpoint. A comprehensive investigation of expression changes of cell cycle-related genes showed that PTC-209 caused significant down-regulation of cell cycle-promoting genes as well as of genes that contribute to DNA synthesis initiation and DNA repair, respectively. This was accompanied by significantly elevated mRNA levels of cell cycle inhibitors. In addition, PTC-209 reduced sphere formation and, in a cell line-dependent manner, aldehyde dehydrogease-1 positive cells. We conclude that PTC-209 might be a promising drug for future in vitro and in vivo studies in BTC