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https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#1
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913465/aplastic-anemia-and-clonal-evolution-germ-line-and-somatic-genetics
#2
Akiko Shimamura
Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913189/construction-and-analysis-of-a-human-testis-sperm-enriched-interaction-network-unraveling-the-ppp1cc2-interactome
#3
Joana Vieira Silva, Sooyeon Yoon, Pieter-Jan De Bock, Alexander V Goltsev, Kris Gevaert, José Fernando F Mendes, Margarida Fardilha
BACKGROUND: Phosphoprotein phosphatase 1 catalytic subunit gamma 2 (PPP1CC2), a PPP1CC tissue-specific alternative splice restricted to testicular germ cells and spermatozoa, is essential for spermatogenesis and spermatozoa motility. The key to understand PPP1CC2 regulation lies on the characterization of its interacting partners. METHODS: We construct a testis/sperm-enriched protein interaction network and analyzed the topological properties and biological context of the network...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912078/mouse-double-minute-2-homolog-actively-suppresses-p53-activity-in-oocytes-during-mouse-folliculogenesis
#4
Chen-Xi Zhang, Qin Zhang, Yin-Yin Xie, Xue-Yan He, Cong Xiang, Xiao-Shuang Hou, Ying Zhou, Lai Chen, Guo-Xin Zhang, Geng Liu
The p53 signaling network is indispensible in cellular stress responses and tumor suppression. Negative regulations of p53 by mouse double minute 2 and 4 homologs (MDM2) and (MDM4) are an integrated component of the network and have been implicated in regulating the stress responses and the maintenance of normal development and homeostasis of multiple somatic cell lineages. However, the regulatory role of MDM2 on p53 and stress responses in female germ cells remains undetermined. Here, we used the Cre-loxP system to delete Mdm2 in oocytes at different stages of folliculogenesis in mice...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27911843/impact-of-the-gut-microbiota-on-enhancer-accessibility-in-gut-intraepithelial-lymphocytes
#5
Nicholas P Semenkovich, Joseph D Planer, Philip P Ahern, Nicholas W Griffin, Charles Y Lin, Jeffrey I Gordon
The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to define chromatin accessibility in predicted enhancer regions of intestinal αβ(+) and γδ(+) intraepithelial lymphocytes purified from germ-free mice, their conventionally raised (CONV-R) counterparts, and mice reared germ free and then colonized with CONV-R gut microbiota at the end of the suckling-weaning transition...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911225/successful-treatment-of-mixed-yolk-sac-tumor-and-mature-teratoma-in-the-spinal-cord-case-report
#6
Akitake Mukasa, Shunsuke Yanagisawa, Kuniaki Saito, Shota Tanaka, Keisuke Takai, Junji Shibahara, Masachika Ikegami, Yusuke Nakao, Katsushi Takeshita, Masao Matsutani, Nobuhito Saito
Primary spinal germ cell tumors are rare, and spinal nongerminomatous germ cell tumors represent an even rarer subset for which no standard therapy has been established. The authors report the case of a 24-year-old woman with multifocal primary spinal germ cell tumors scattered from T-12 to L-5 that consisted of yolk sac tumor and mature teratoma. After diagnostic partial resection, the patient was treated with 30 Gy of craniospinal irradiation and 30 Gy of local spinal irradiation, followed by 8 courses of chemotherapy based on ifosfamide, cisplatin, and etoposide (ICE)...
December 2, 2016: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/27911186/rna-decay-evolution-and-the-testis
#7
Samantha H Jones, Miles Wilkinson
NMD is a highly conserved pathway that degrades specific subsets of RNAs. There is increasing evidence for roles of NMD in development. In this commentary, we focus on spermatogenesis, a process dramatically impeded upon loss or disruption of NMD. NMD requires strict regulation for normal spermatogenesis, as loss of a newly discovered NMD repressor, UPF3A, also causes spermatogenic defects, most prominently during meiosis. We discuss the unusual evolution of UPF3A, whose paralog, UPF3B, has the opposite biochemical function and acts in brain development...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27909618/clinico-pathological-outcomes-of-post-primary-and-salvage-chemotherapy-retroperitoneal-lymph-node-dissection-for-mixed-germ-cell-tumors-king-hussein-cancer-center-experience
#8
Kholoud Alqasem, Ibrahim Abukhiran, Judy Jasser, Tamer Bisharat, Riyad T Ellati, Jakub Khzouz, Ibrahim Al-Saidi, Ali Al-Daghamin
OBJECTIVE: We sought to characterize clinical and pathologic outcomes of advanced mixed germ cell tumors after retroperitoneal lymph node dissection for post-chemotherapy residual masses. MATERIAL AND METHODS: Between January 2006 and November 2015, 56 patients underwent retroperitoneal lymph node dissection (RPLND) for residual masses of greater than 1 cm after receiving either primary chemotherapy or salvage chemotherapy. Retrospective review of the patients' characteristics, clinical, pathological, and treatment outcomes were performed after institutional review board (IRB) and ethics committee approval...
December 2016: Turkish Journal of Urology
https://www.readbyqxmd.com/read/27906881/stem-cells-and-clinical-practice-new-advances-and-challenges-at-the-time-of-emerging-problems-with-induced-pluripotent-stem-cell-therapies
#9
Mariusz Z Ratajczak, Kamila Bujko, Wojciech Wojakowski
Humans, like other species that reproduce sexually, originate from a fertilized oocyte (zygote), which is a totipotent stem cell giving rise to an adult organism. During the process of embryogenesis, stem cells at different levels of the developmental hierarchy establish all 3 germ layers and give rise to tissue‑committed stem cells, which are responsible for rejuvenation of a given tissue or organ. The robustness of the stem cell compartment is one of the major factors that directly impact life quality as well as lifespan...
November 10, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/27906710/who-s-your-daddy-paternal-inheritance-of-metabolic-disease-risk
#10
Elvira Isganaitis, Harumi Suehiro, Connie Cardona
PURPOSE OF REVIEW: Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. RECENT FINDINGS: The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation...
November 30, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27906587/differentiation-of-mouse-ovarian-stem-cells-toward-oocyte-like-structure-by-coculture-with-granulosa-cells
#11
Soraya Parvari, Hossein Yazdekhasti, Zahra Rajabi, Valliollah Gerayeli Malek, Tayebeh Rastegar, Mehdi Abbasi
An increasing body of evidence has confirmed existence and function of ovarian stem cells (OSCs). In this study, a novel approach on differentiation of OSCs into oocyte-like cells (OLCs) has been addressed. Recently, different methods have been recruited to isolate and describe aspects of OSCs, but newer and more convenient strategies in isolation are still growing. Herein, a morphology-based method was used to isolate OSCs. Cell suspension of mouse neonatal ovaries was cultured and formed colonies were harvested mechanically and cultivated on mouse embryonic fibroblasts...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27906584/effects-of-the-transforming-growth-factor-beta-signaling-pathway-on-the-differentiation-of-chicken-embryonic-stem-cells-into-male-germ-cells
#12
Yani Zhang, Yingjie Wang, Qisheng Zuo, Dong Li, Wenhui Zhang, Chao Lian, Beibei Tang, Tianrong Xiao, Man Wang, Kehua Wang, Bichun Li
The objectives of the present study were to screen for key gene and signaling pathways involved in the production of male germ cells in poultry and to investigate the effects of the transforming growth factor beta (TGF-β) signaling pathway on the differentiation of chicken embryonic stem cells (ESCs) into male germ cells. The ESCs, primordial germ cells, and spermatogonial stem cells (SSCs) were sorted using flow cytometry for RNA sequencing (RNA-seq) technology. Male chicken ESCs were induced using 40 ng/mL of bone morphogenetic protein 4 (BMP4)...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27906056/umbilical-cord-blood-derived-non-hematopoietic-stem-cells-retrieved-and-expanded-on-bone-marrow-derived-extracellular-matrix-display-pluripotent-characteristics
#13
Junjie Wu, Yun Sun, Travis J Block, Milos Marinkovic, Zhi-Liang Zhang, Richard Chen, Yixia Yin, Juquan Song, David D Dean, Zhongding Lu, Xiao-Dong Chen
BACKGROUND: Umbilical cord blood (UCB) not only contains hematopoietic stem cells (HSCs), but also non-hematopoietic stem cells (NHSCs) that are able to differentiate into a number of distinct cell types. Based on studies published to date, the frequency of NHSCs in UCB is believed to be very low. However, the isolation of these cells is primarily based on their adhesion to tissue culture plastic surfaces. METHODS AND RESULTS: In the current study, we demonstrate that this approach overlooks some of the extremely immature NHSCs because they lack the ability to adhere to plastic...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27905446/genomic-evolution-and-chemoresistance-in-germ-cell-tumours
#14
Amaro Taylor-Weiner, Travis Zack, Elizabeth O'Donnell, Jennifer L Guerriero, Brandon Bernard, Anita Reddy, G Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L Carter, Michelle S Hirsch, Anthony Letai, Christopher Sweeney, Eliezer M Van Allen
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27904699/generation-of-induced-pluripotent-stem-cells-with-high-efficiency-from-human-embryonic-renal-cortical-cells
#15
Ling Yao, Ruifang Chen, Pu Wang, Qi Zhang, Hailiang Tang, Huaping Sun
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902973/cd147-regulates-extrinsic-apoptosis-in-spermatocytes-by-modulating-nf%C3%AE%C2%BAb-signaling-pathways
#16
Chaoqun Wang, Kin Lam Fok, Zhiming Cai, Hao Chen, Hsiao Chang Chan
CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901106/the-role-of-pim1-pim2-kinases-in-tumors-of-the-male-reproductive-system
#17
Manuel Pedro Jiménez-García, Antonio Lucena-Cacace, María José Robles-Frías, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899190/genetic-changes-associated-with-testicular-cancer-susceptibility
#18
REVIEW
Louise C Pyle, Katherine L Nathanson
Testicular germ cell tumor (TGCT) is a highly heritable cancer primarily affecting young white men. Genome-wide association studies (GWAS) have been particularly effective in identifying multiple common variants with strong contribution to TGCT risk. These loci identified through association studies have implicated multiple genes as associated with TGCT predisposition, many of which are unique among cancer types, and regulate processes such as pluripotency, sex specification, and microtubule assembly. Together these biologically plausible genes converge on pathways involved in male germ cell development and maturation, and suggest that perturbation of them confers susceptibility to TGCT, as a developmental defect of germ cell differentiation...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27898696/regulation-of-gonad-morphogenesis-in-drosophila-melanogaster-by-btb-family-transcription-factors
#19
Diane Silva, Kenneth W Olsen, Magdalena N Bednarz, Andrew Droste, Christopher P Lenkeit, Edwin Chaharbakhshi, Emily R Temple-Wood, Jennifer C Jemc
During embryogenesis, primordial germ cells (PGCs) and somatic gonadal precursor cells (SGPs) migrate and coalesce to form the early gonad. A failure of the PGCs and SGPs to form a gonad with the proper architecture not only affects germ cell development, but can also lead to infertility. Therefore, it is critical to identify the molecular mechanisms that function within both the PGCs and SGPs to promote gonad morphogenesis. We have characterized the phenotypes of two genes, longitudinals lacking (lola) and ribbon (rib), that are required for the coalescence and compaction of the embryonic gonad in Drosophila melanogaster...
2016: PloS One
https://www.readbyqxmd.com/read/27897161/remodelling-germ-cells-by-intercellular-cannibalism
#20
Jennifer K Heppert, Bob Goldstein
Work from the early 1980s reported strange lobes protruding from Caenorhabditis elegans germ cell precursors. However, the fate and potential significance of these lobes remained unexplored for decades. Now, neighbouring endodermal cells are shown to sever and digest these lobes, in an unexpected process of 'intercellular cannibalism', which could play an important part in regulating primordial germ cells.
November 29, 2016: Nature Cell Biology
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