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https://www.readbyqxmd.com/read/28334154/ethical-issues-of-crispr-technology-and-gene-editing-through-the-lens-of-solidarity
#1
John J Mulvihill, Benjamin Capps, Yann Joly, Tamra Lysaght, Hub A E Zwart, Ruth Chadwick
Background: The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations. Sources of data: This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016. Areas of agreement: CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients...
February 23, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28333934/visualizing-the-structure-of-rna-seq-expression-data-using-grade-of-membership-models
#2
Kushal K Dey, Chiaowen Joyce Hsiao, Matthew Stephens
Grade of membership models, also known as "admixture models", "topic models" or "Latent Dirichlet Allocation", are a generalization of cluster models that allow each sample to have membership in multiple clusters. These models are widely used in population genetics to model admixed individuals who have ancestry from multiple "populations", and in natural language processing to model documents having words from multiple "topics". Here we illustrate the potential for these models to cluster samples of RNA-seq gene expression data, measured on either bulk samples or single cells...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28333312/establishment-maintenance-and-functional-integrity-of-the-blood-testis-barrier-in-organotypic-cultures-of-fresh-and-frozen-thawed-prepubertal-mouse-testes
#3
C Rondanino, A Maouche, L Dumont, A Oblette, N Rives
STUDY QUESTION: Can the spatio-temporal formation of an intact blood-testis barrier (BTB), which is essential for the progression of spermatogenesis, be reproduced in cultures of fresh or frozen/thawed prepubertal mouse testes? SUMMARY ANSWER: Organotypic cultures allow the establishment and maintenance of major BTB components and the formation of a functional BTB in mouse testicular tissues. WHAT IS KNOWN ALREADY: In vitro maturation of prepubertal testicular tissues is a promising approach to restore fertility in adult survivors of childhood cancer...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333300/comparison-of-global-gene-expression-profiles-of-microdissected-human-foetal-leydig-cells-with-their-normal-and-hyperplastic-adult-equivalents
#4
Grete Lottrup, Kirstine Belling, Henrik Leffers, John E Nielsen, Marlene D Dalgaard, Anders Juul, Niels E Skakkebæk, Søren Brunak, Ewa Rajpert-De Meyts
STUDY QUESTION: Do human adult Leydig cells (ALCs) within hyperplastic micronodules display characteristics of foetal LCs (FLCs)? SUMMARY ANSWER: The gene expression profiles of FLCs and all ALC subgroups were clearly different, but there were no significant differences in expressed genes between the normally clustered and hyperplastic ALCs. WHAT IS KNOWN ALREADY: LCs are the primary androgen producing cells in males throughout development and appear in chronologically distinct populations; FLCs, neonatal LCs and ALCs...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333083/divergent-expression-patterns-and-function-implications-of-four-nanos-genes-in-a-hermaphroditic-fish-epinephelus-coioides
#5
Zhi-Hui Sun, Yang Wang, Wei-Jia Lu, Zhi Li, Xiao-Chun Liu, Shui-Sheng Li, Li Zhou, Jian-Fang Gui
Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides. Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332739/gdf9-affects-the-development-and-tight-junction-functions-of-immature-bovine-sertoli-cells
#6
K Tang, L Wang, Y Jin, W Yang, L Yang
Transforming growth factor-β (TGFβ) superfamily are critical regulators of germ cell development that act as extracellular ligands of the signal transduction pathways regulating proliferation, apoptosis and other aspects of cell behaviour. As a member of the TGF-β superfamily, growth differentiation factor 9 (GDF9) plays a critical role in ovarian follicular development and the ovulation rate in females; however, its role in the testis has not been well elucidated. The aim of this study was to investigate the expression of GDF9 and its receptor genes BMPRII and ALK5 in prepuberal bovine Sertoli cells (SCs)...
March 23, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28330620/mad2l2-promotes-open-chromatin-in-embryonic-stem-cells-and%C3%A2-derepresses-the-dppa3-locus
#7
Ali Rahjouei, Mehdi Pirouz, Michela Di Virgilio, Dirk Kamin, Michael Kessel
The chromatin of naive embryonic stem cells (ESCs) has a largely open configuration, as evident by the lack of condensed heterochromatin and the hypomethylation of DNA. Several molecular mechanisms promoting this constellation were previously identified. Here we present evidence for an important epigenetic function of MAD2L2, a protein originally known for its role in DNA damage repair, and for its requirement in germ cell development. We demonstrate using super-resolution microscopy that numerous MAD2L2 microfoci are exclusively associated with euchromatin, similar to other factors of the DNA damage response...
March 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28330469/preclinical-evaluation-of-a-tex101-protein-elisa-test-for-the-differential-diagnosis-of-male-infertility
#8
Dimitrios Korbakis, Christina Schiza, Davor Brinc, Antoninus Soosaipillai, Theano D Karakosta, Christine Légaré, Robert Sullivan, Brendan Mullen, Keith Jarvi, Eleftherios P Diamandis, Andrei P Drabovich
BACKGROUND: TEX101 is a cell membrane protein exclusively expressed by testicular germ cells and shed into seminal plasma. We previously verified human TEX101 as a biomarker for the differential diagnosis of azoospermia, and developed a first-of-its-kind TEX101 ELISA. To demonstrate the clinical utility of TEX101, in this work we aimed at evaluating ELISA performance in a large population of fertile, subfertile, and infertile men. METHODS: Mass spectrometry, size-exclusion chromatography, ultracentrifugation, and immunohistochemistry were used to characterize TEX101 protein as an analyte in seminal plasma...
March 23, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28329872/doxorubicin-has-dose-dependent-toxicity-on-mouse-ovarian-follicle-development-hormone-secretion-and-oocyte-maturation
#9
Shuo Xiao, Jiyang Zhang, Mingjun Liu, Hideyuki Iwahata, Hunter B Rogers, Teresa K Woodruff
Doxorubicin (DOX), one of the most commonly used anticancer medications, has been reported to affect fertility by damaging ovarian follicles; however, the dose-dependent toxicity of DOX on the dynamic follicle development and oocyte maturation has not been well-defined. Our objective is to determine the effects of human-relevant exposure levels of DOX on follicular functions across developmental time. In vitro cultured multilayered secondary mouse follicles were treated with DOX at 0, 2, 20, 100, and 200 nM for 24 hours, and follicle development, hormone secretion, and oocyte maturation were analyzed...
March 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329407/regulatory-requirements-for-genotoxicity-assessment-of-plant-protection-product-active-ingredients-impurities-and-metabolites
#10
REVIEW
Ewan D Booth, Paul J Rawlinson, Priscila Maria Fagundes, Kevin A Leiner
Active ingredients in plant protection products are subject to rigorous safety assessment during their development, including assessment of genotoxicity. Plant protection products are used for agriculture in multiple regions and for the registration of active ingredients it is necessary to satisfy the data requirements of these different regions. There are no overarching global agreements on which genotoxicity studies need to be conducted to satisfy the majority of regulatory authorities. The implementation of new OECD guidelines for the in vitro micronucleus, transgenic rodent somatic and germ cell gene mutation and in vivo comet assays, as well as the revision of a number of other OECD test guidelines has resulted in some changes to data requirements...
March 22, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28329024/toward-developing-recombinant-gonadotropin-based-hormone-therapies-for-increasing-fertility-in-the-flatfish-senegalese-sole
#11
François Chauvigné, Judith Ollé, Wendy González, Neil Duncan, Ignacio Giménez, Joan Cerdà
Captive flatfishes, such as the Senegalese sole, typically produce very low volumes of sperm. This situation is particularly prevalent in the first generation (F1) of reared sole males, which limits the development of artificial fertilization methods and the implementation of selective breeding programs. In this study, we investigated whether combined treatments with homologous recombinant follicle-stimulating (rFsh) and luteinizing (rLh) hormones, produced in a mammalian host system, could stimulate spermatogenesis and enhance sperm production in Senegalese sole F1 males...
2017: PloS One
https://www.readbyqxmd.com/read/28327896/a-randomised-phase-iii-study-of-72%C3%A2-hour-infusional-versus-bolus-bleomycin-in-bep-bleomycin-etoposide-and-cisplatin-chemotherapy-to-treat-igcccg-good-prognosis-metastatic-germ-cell-tumours-te-3
#12
J Shamash, S-J Sarker, R Huddart, S Harland, J K Joffe, D Mazhar, A Birtle, J White, K Chowdhury, P Wilson, M R Marshall, S Vinnicombe
Background: Bleomycin is an integral part of combination chemotherapy in germ cell tumours. Pulmonary toxicity often necessitates drug cessation and death occurs in 1-2% of patients. A continuous infusion of bleomycin might reduce lung toxicity when compared to the conventional weekly boluses given as part of standard BEP chemotherapy. Patients and Methods: A phase 3 trial was conducted based on 212 men with IGCCCG good prognosis metastatic germ cell tumours with 1:1 randomisation...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#13
Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J Abilez, Ryoko Hamaguchi, Joseph C Wu, Marius Wernig, Sean M Wu
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326217/a-rare-adrenal-mass-in-a-3-month-old-a-case-report-and-literature-review
#14
Ashish Garg, Elza Pollak-Christian, Navneetha Unnikrishnan
A three-month-old female infant presented with abdominal distention for 2 months. A large palpable mass in right upper quadrant was noted on physical exam. Abdominal ultrasound revealed a large heterogeneous mass with multiple cystic components. Mass was surgically excised and pathology was consistent with mature adrenal teratoma. Teratoma is a germ cell tumor mainly found in gonadal tissues. Occurrence of adrenal gland teratoma in children is very rare with less than 10 pediatric case reports in English literature...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28325537/midline-extraperitoneal-approach-to-retroperitoneal-lymph-node-dissection-in-testicular-cancer-minimizing-surgical-morbidity
#15
Sumeet Syan-Bhanvadia, Soroush T Bazargani, Thomas G Clifford, Jie Cai, Gus Miranda, Siamak Daneshmand
BACKGROUND: Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant surgical morbidity. OBJECTIVE: To describe our experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT. DESIGN, SETTING, AND PARTICIPANTS: From 2010 to 2015, 122 consecutive patients underwent RPLND from a prospective database. Patients requiring aortic resection or retrocrural dissection or with intraperitoneal disease were excluded...
March 18, 2017: European Urology
https://www.readbyqxmd.com/read/28324259/protective-effect-of-nigella-sativa-seeds-against-spermatocyte-chromosomal-aberrations-and-genotoxicity-induced-by-carbon-tetrachloride-in-mice
#16
Ashraf M Abdel-Moneim, Amina E Essawy, Sherifa S Hamed, Ashgan A Abou-Gabal, Aglal A Alzergy
Nigella sativa is a well-known dietary antioxidant and a valuable inhibitor of clastogenesis and carcinogenesis. The purpose of the present work was to investigate the effects of N. sativa seeds against chromosomal aberrations in primary spermatocytes and early embryonic lethality induced by CCl4 hepatotoxin in Swiss albino mice. One hundred male Swiss albino mice were randomly divided into five groups. Groups I, II, and III received only normal saline, olive oil, and aqueous suspension of N. sativa seeds (50 mg/kg b...
March 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28322735/stella-collaborates-in-distinct-mesendodermal-cell-subpopulations-at-the-fetal-placental-interface-in-the-mouse-gastrula
#17
Adam D Wolfe, Adriana M Rodriguez, Karen M Downs
The allantois-derived umbilical component of the chorio-allantoic placenta shuttles fetal blood to and from the chorion, thereby ensuring fetal-maternal exchange. The progenitor populations that establish and supply the fetal-umbilical interface lie, in part, within the base of the allantois, where the germ line is claimed to segregate from the soma. Results of recent studies in the mouse have reported that STELLA (DPPA-3, PGC7) co-localizes with PRDM1 (BLIMP1), the bimolecular signature of putative primordial germ cells (PGCs) throughout the fetal-placental interface...
March 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28322096/cdx2-immunostaining-in-primary-and-metastatic-germ-cell-tumours-of-the-testis
#18
Fatma Oz Atalay, Berna Aytac Vuruskan, Hakan Vuruskan
Objective To evaluate the immunohistochemical staining pattern of caudal type homeobox 2 (CDX2) protein in germ cell tumours (GCTs) of the testis. Methods This study reassessed archival tissue samples collected from patients diagnosed with primary and metastatic testicular GCTs for CDX2 immunoreactivity using standard immunohistochemical techniques. Positive nuclear immunostaining was evaluated with regard to both the staining intensity and the extent of the staining. Results Tissue sections from primary and metastatic testicular GCTs ( n = 104), germ cell neoplasia in situ (GCNis) ( n = 5) and benign testicles ( n = 15) were analysed...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/28320414/epidermal-growth-factor-receptor-and-epididymis-invasion-as-prognostic-biomarkers-in-clinical-stage-i-testicular-germ-cell-tumours
#19
Miguel F Sanmamed, E Esteban, E Uriol, R Zarate, M Capelan, C Muriel, G Crespo, J P Berros, P Pardo-Coto, Q Perez, C Alvarez-Fernández, P Jiménez Fonseca, M Luque, A Astudillo
BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study...
March 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28319573/vascular-smooth-muscle-cell-maturation-stage-and-ki-67-index-are-diagnostic-biomarkers-for-pathologic-grade-of-ovarian-teratoma
#20
Masako Hongo-Kohama, Atsushi Kurata, Hirotsugu Hashimoto, Koji Fujita, Hajime Horiuchi, Toshitaka Nagao, Masahiko Kuroda
Although immature teratoma of the ovary is a rare disease, its pathologic grading, especially between low-grade (grade 1) and high-grade (grade 2 or 3) immature teratomas, is important for optimal therapy and prognosis. This grading, however, is currently solely dependent on quantitation of neuroepithelial components as judged by subjective assessments. As we have recently successfully studied the maturation of vascular smooth muscle cells (SMCs) in other organs using an h-caldesmon to α-smooth muscle actin (α-SMA) ratio, we decided to use this ratio to investigate a potential link between teratoma grade and SMC maturation, in combination with Ki-67 index...
March 17, 2017: International Journal of Gynecological Pathology
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