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"Nicholls, Peter"
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السينما الخيالية
يتناول هذا الكتاب نوعية من الأفلام لم تتطرق إليها أفلام الكتاب إلا فيما نذر، وفيه يتعرف القارئ والسينمائي العربي معا على هذه النوعية التي تتعدد جوانبها لتشمل أفلام الخيال العلمي والرعب والفانتازيا، والسيريالية. والواقع أن هناك أفلاما أجنبية كثيرة تقع داخل نطاق هذه النوعية مما نتداوله في دور العرض أو عن طريق شريط الفيديو. والكتاب يلقى الضوء عليها ويساعد القارئ والمشاهد على فهمها. ولعل ذلك يساعد بدوره على تطعيم الأفلام الأخرى بدماء جديدة تسمح لها بالانطلاق إلى آفاق أوسع من الخيال الحر. والفيلموجرافية التي يضمها الكتاب في آخره تمثل معينا عمليا للقارئ في توسيع معلوماته عن الأفلام التي تشملها وتضم سبعمائة فيلم.
Book
Mammalian germ cells are determined after PGC colonization of the nascent gonad
Mammalian primordial germ cells (PGCs) are induced in the embryonic epiblast, before migrating to the nascent gonads. In fish, frogs, and birds, the germline segregates even earlier, through the action of maternally inherited germ plasm. Across vertebrates, migrating PGCs retain a broad developmental potential, regardless of whether they were induced or maternally segregated. In mammals, this potential is indicated by expression of pluripotency factors, and the ability to generate teratomas and pluripotent cell lines. How the germline loses this developmental potential remains unknown. Our genome-wide analyses of embryonic human and mouse germlines reveal a conserved transcriptional program, initiated in PGCs after gonadal colonization, that differentiates germ cells from their germline precursors and from somatic lineages. Through genetic studies in mice and pigs, we demonstrate that one such gonad-induced factor, the RNA-binding protein DAZL, is necessary in vivo to restrict the developmental potential of the germline; DAZL’s absence prolongs expression of a Nanog pluripotency reporter, facilitates derivation of pluripotent cell lines, and causes spontaneous gonadal teratomas. Based on these observations in humans, mice, and pigs, we propose that germ cells are determined after gonadal colonization in mammals. We suggest that germ cell determination was induced late in embryogenesis—after organogenesis has begun—in the common ancestor of all vertebrates, as in modern mammals, where this transition is induced by somatic cells of the gonad. We suggest that failure of this process of germ cell determination likely accounts for the origin of human testis cancer.
Journal Article
Licensing of Primordial Germ Cells for Gametogenesis Depends on Genital Ridge Signaling
In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell licensing has been considered to be a cell-autonomous and gonad-independent event, based on observations that some PGCs, having migrated not to the gonad but to the adrenal gland, nonetheless enter meiosis in a time frame parallel to ovarian germ cells -- and do so regardless of the sex of the embryo. Here we test the hypothesis that germ cell licensing is cell-autonomous by examining the fate of PGCs in Gata4 conditional mutant (Gata4 cKO) mouse embryos. Gata4, which is expressed only in somatic cells, is known to be required for genital ridge initiation. PGCs in Gata4 cKO mutants migrated to the area where the genital ridge, the precursor of the gonad, would ordinarily be formed. However, these germ cells did not undergo licensing and instead retained characteristics of PGCs. Our results indicate that licensing is not purely cell-autonomous but is induced by the somatic genital ridge.
Journal Article
Retinoic Acid and Germ Cell Development in the Ovary and Testis
Retinoic acid (RA), a derivative of vitamin A, is critical for the production of oocytes and sperm in mammals. These gametes derive from primordial germ cells, which colonize the nascent gonad, and later undertake sexual differentiation to produce oocytes or sperm. During fetal development, germ cells in the ovary initiate meiosis in response to RA, whereas those in the testis do not yet initiate meiosis, as they are insulated from RA, and undergo cell cycle arrest. After birth, male germ cells resume proliferation and undergo a transition to spermatogonia, which are destined to develop into haploid spermatozoa via spermatogenesis. Recent findings indicate that RA levels change periodically in adult testes to direct not only meiotic initiation, but also other key developmental transitions to ensure that spermatogenesis is precisely organized for the prodigious output of sperm. This review focuses on how female and male germ cells develop in the ovary and testis, respectively, and the role of RA in this process.
Journal Article
The Cambridge history of twentieth-century English literature
Covering a full range of English, Scottish, Welsh, and Irish literature, this title traces the development of writing during the 20th century. It also looks at how the advent of new technologies - such as radio and television - has shaped literary patterns over the years.
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The magma plumbing system for the 1971 Teneguía eruption on La Palma, Canary Islands
The 1971 Teneguía eruption is the most recent volcanic event of the Cumbre Vieja rift zone on La Palma. The eruption produced basanite lavas that host xenoliths, which we investigate to provide insight into the processes of differentiation, assimilation and magma storage beneath La Palma. We compare our results to the older volcano magmatic systems of the island with the aim to reconstruct the temporal development of the magma plumbing system beneath La Palma. The 1971 lavas are clinopyroxene-olivine-phyric basanites that contain augite, sodic-augite and aluminium augite. Kaersutite cumulate xenoliths host olivine, clinopyroxene including sodic-diopside, and calcic-amphibole, whereas an analysed leucogabbro xenolith hosts plagioclase, sodic-augite-diopside, calcic-amphibole and hauyne. Mineral thermobarometry and mineral-melt thermobarometry indicate that clinopyroxene and plagioclase in the 1971 Teneguía lavas crystallised at 20–45 km depth, coinciding with clinopyroxene and calcic-amphibole crystallisation in the kaersutite cumulate xenoliths at 25–45 km and clinopyroxene, calcic-amphibole and plagioclase crystallisation in the leucogabbro xenolith at 30–50 km. Combined mineral chemistry and thermobarometry suggest that the magmas had already crystallised, differentiated and formed multiple crystal populations in the oceanic lithospheric mantle. Notably, the magmas that supplied the 1949 and 1971 events appear to have crystallised deeper than the earlier Cumbre Vieja magmas, which suggests progressive underplating beneath the Cumbre Vieja rift zone. In addition, the lavas and xenoliths of the 1971 event crystallised at a common depth, indicating a reused plumbing system and progressive recycling of Ocean Island plutonic complexes during subsequent magmatic activity.
Journal Article
ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum
Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with \"severe\" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.
Journal Article
Analysis of a mouse germ cell tumor model establishes pluripotency-associated miRNAs as conserved serum biomarkers for germ cell cancer detection
Malignant testicular germ cells tumors (TGCTs) are the most common solid cancers in young men. Current TGCT diagnostics include conventional serum protein markers, but these lack the sensitivity and specificity to serve as accurate markers across all TGCT subtypes. MicroRNAs (miRNAs) are small non-coding regulatory RNAs and informative biomarkers for several diseases. In humans, miRNAs of the miR-371-373 cluster are detectable in the serum of patients with malignant TGCTs and outperform existing serum protein markers for both initial diagnosis and subsequent disease monitoring. We previously developed a genetically engineered mouse model featuring malignant mixed TGCTs consisting of pluripotent embryonal carcinoma (EC) and differentiated teratoma that, like the corresponding human malignancies, originate in utero and are highly chemosensitive. Here, we report that miRNAs in the mouse miR-290-295 cluster, homologs of the human miR-371-373 cluster, were detectable in serum from mice with malignant TGCTs but not from tumor-free control mice or mice with benign teratomas. miR-291-293 were expressed and secreted specifically by pluripotent EC cells, and expression was lost following differentiation induced by the drug thioridazine. Notably, miR-291-293 levels were significantly higher in the serum of pregnant dams carrying tumor-bearing fetuses compared to that of control dams. These findings reveal that expression of the miR-290-295 and miR-371-373 clusters in mice and humans, respectively, is a conserved feature of malignant TGCTs, further validating the mouse model as representative of the human disease. These data also highlight the potential of serum miR-371-373 assays to improve patient outcomes through early TGCT detection, possibly even prenatally.
Journal Article