Pi3k/pten/akt signaling pathways in germ cell development and their involvement in germ cell tumors and ovarian dysfunctions

Several studies indicate that the PI3K/PTEN/AKT signaling pathways are critical regulators of ovarian function including the formation of the germ cell precursors, termed primordial germ cells, and the follicular pool maintenance. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/AKT pathways during primordial germ cell development and the dynamics of the ovarian primordial follicle reserve and how dysregulation of these signaling pathways may contribute to the development of some types of germ cell tumors and ovarian dysfunctions

Functional fat injection under local anesthesia to treat severe postsurgical dysphagia, case report

Background: In this study, we present the first application of functional fat injection performed under local anesthesia in the treatment of severe dysphagia secondary to head and neck cancer surgery. Methods: Functional fat injection was performed using a transcervical approach. Control of injection depth and site was performed through a transnasal flexible endoscope. The effect of surgery was evaluated through videofluoroscopy (VFS), Fiberendoscopic Evaluation of Swallowing (FEES), Functional Oral Intake Scale (FOIS), and Eating Assessment Tool-10 (EAT-10). Results: Before the functional fat injection, the patient was dependent on permanent tube feeding; the VFS and FEES revealed a severe impairment of swallowing abilities. The EAT-10 scored 26. Twelve months after surgery, the patient was on oral diet, the VFS demonstrated mild to moderate dysphagia, the FEES demonstrated aspiration only with liquids and the EAT-10 improved. Conclusion: Functional fat injection under local anesthesia could be useful in the treatment of chronic dysphagia in selected patients

Self-Referential Noise and the Synthesis of Three-Dimensional Space

Generalising results from Godel and Chaitin in mathematics suggests that self-referential systems contain intrinsic randomness. We argue that this is relevant to modelling the universe and show how three-dimensional space may arise from a non-geometric order-disorder model driven by self-referential noise.Comment: Figure labels correcte

To be or not to be a germ cell: The extragonadal germ cell tumor paradigm

In the human embryo, the genetic program that orchestrates germ cell specification in-volves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neo-plasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types

Human adipose-derived stromal cells transplantation prolongs reproductive lifespan on mouse models of mild and severe premature ovarian insufficiency

Background Although recent studies have investigated the ability of Mesenchymal Stromal Cells (MSCs) to alleviate short-term ovarian damage in animal models of chemotherapy-induced Premature Ovarian Insufficiency (POI), no data are available on reproductive lifespan recovery, especially in a severe POI condition. For this reason, we investigated the potential of MSCs isolated from human adipose tissue (hASCs), since they are easy to harvest and abundant, in ameliorating the length and performance of reproductive life in both mild and severe chemotherapy-induced murine POI models. Methods Mild and severe POI models were established by intraperitoneally administering a light (12 mg/kg busulfan + 120 mg/kg cyclophosphamide) or heavy (30 mg/kg busulfan + 120 mg/kg cyclophosphamide) dose of chemotherapy, respectively, in CD1 mice. In both cases, a week later, 1 × 106 hASCs were transplanted systemically through the tail vein. After four additional weeks, some females were sacrificed to collect ovaries for morphological evaluation. H&E staining was performed to assess stroma alteration and to count follicle numbers; immunofluorescence staining for αSMA was used to analyse vascularization. Of the remaining females, some were mated after superovulation to collect 2-cell embryos in order to evaluate their pre-implantation developmental capacity in vitro, while others were naturally mated to monitor litters and reproductive lifespan length. F1 litters’ weight, ovaries and reproductive lifespan were also analysed. Results hASC transplantation alleviated ovarian weight loss and size decrease and reduced alterations on ovarian stroma and vasculature, concurrently preventing the progressive follicle stockpile depletion caused by chemotherapy. These effects were associated with the preservation of the oocyte competence to develop into blastocyst in vitro and, more interestingly, with a significant decrease of chemotherapy-induced POI features, like shortness of reproductive lifespan, reduced number of litters and longer time to plug (the latter only presented in the severe POI model). Conclusion Human ASC transplantation was able to significantly reduce all the alterations induced by the chemotherapeutic treatment, while improving oocyte quality and prolonging reproductive functions, thus counteracting infertility. These results, strengthened by the use of an outbred model, support the potential applications of hASCs in women with POI, nowadays mainly induced by anticancer therapies

Analysis of Secreted Proteins from Prepubertal Ovarian Tissues Exposed In Vitro to Cisplatin and LH

It is well known that secreted and exosomal proteins are associated with a broad range of physiological processes involving tissue homeostasis and differentiation. In the present paper, our purpose was to characterize the proteome of the culture medium in which the oocytes within the primordial/primary follicles underwent apoptosis induced by cisplatin (CIS) or were, for the most part, protected by LH against the drug. To this aim, prepubertal ovarian tissues were cultured under control and in the presence of CIS, LH, and CIS + LH. The culture media were harvested after 2, 12, and 24 h from chemotherapeutic drug treatment and analyzed by liquid chromatography–mass spectrometry (LC-MS). We found that apoptotic conditions generated by CIS in the cultured ovarian tissues and/or oocytes are reflected in distinct changes in the extracellular microenvironment in which they were cultured. These changes became evident mainly from 12 h onwards and were characterized by the inhibition or decreased release of a variety of compounds, such as the proteases Htra1 and Prss23, the antioxidants Prdx2 and Hbat1, the metabolic regulators Ldha and Pkm, and regulators of apoptotic pathways such as Tmsb4x. Altogether, these results confirm the biological relevance of the LH action on prepuberal ovaries and provide novel information about the proteins released by the ovarian tissues exposed to CIS and LH in the surrounding microenvironment. These data might represent a valuable resource for future studies aimed to clarify the effects and identify biomarkers of these compounds’ action on the developing ovary

Precision measurements of Linear Scattering Density using Muon Tomography

We demonstrate that muon tomography can be used to precisely measure the properties of various materials. The materials which have been considered have been extracted from an experimental blast furnace, including carbon (coke) and iron oxides, for which measurements of the linear scattering density relative to the mass density have been performed with an absolute precision of 10%. We report the procedures that are used in order to obtain such precision, and a discussion is presented to address the expected performance of the technique when applied to heavier materials. The results we obtain do not depend on the specific type of material considered and therefore they can be extended to any application.Comment: 16 pages, 4 figure

Curvature invariants in type N spacetimes

Scalar curvature invariants are studied in type N solutions of vacuum Einstein's equations with in general non-vanishing cosmological constant Lambda. Zero-order invariants which include only the metric and Weyl (Riemann) tensor either vanish, or are constants depending on Lambda. Even all higher-order invariants containing covariant derivatives of the Weyl (Riemann) tensor are shown to be trivial if a type N spacetime admits a non-expanding and non-twisting null geodesic congruence. However, in the case of expanding type N spacetimes we discover a non-vanishing scalar invariant which is quartic in the second derivatives of the Riemann tensor. We use this invariant to demonstrate that both linearized and the third order type N twisting solutions recently discussed in literature contain singularities at large distances and thus cannot describe radiation fields outside bounded sources.Comment: 17 pages, to appear in Class. Quantum Gra

The Microhardness of Enamel and Dentin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68055/2/10.1177_00220345580370041301.pd