The strong present-day Asian monsoons are thought to have originated between 25 and 22 million years (Myr) ago, driven by Tibetan-Himalayan uplift. However, the existence of older Asian monsoons and ...their response to enhanced greenhouse conditions such as those in the Eocene period (55-34 Myr ago) are unknown because of the paucity of well-dated records. Here we show late Eocene climate records revealing marked monsoon-like patterns in rainfall and wind south and north of the Tibetan-Himalayan orogen. This is indicated by low oxygen isotope values with strong seasonality in gastropod shells and mammal teeth from Myanmar, and by aeolian dust deposition in northwest China. Our climate simulations support modern-like Eocene monsoonal rainfall and show that a reinforced hydrological cycle responding to enhanced greenhouse conditions counterbalanced the negative effect of lower Tibetan relief on precipitation. These strong monsoons later weakened with the global shift to icehouse conditions 34 Myr ago.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epithelial ovarian tumors present a complex clinical, diagnostic and therapeutic challenge because of the difficulty of early detection, lack of known precursor lesions and high mortality rates. ...Endometrioid ovarian carcinomas are frequently associated with endometriosis, but the mechanism for this association remains unknown. Here we present the first genetic models of peritoneal endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele. In addition, we find that expression of oncogenic K-ras or conditional Pten deletion within the ovarian surface epithelium gives rise to preneoplastic ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic endometrioid ovarian adenocarcinomas with complete penetrance and a disease latency of only 7 weeks. The ovarian cancer model described in this study recapitulates the specific tumor histomorphology and metastatic potential of the human disease.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Objective Epithelioid trophoblastic tumor (ETT) is a rare form of gestational trophoblastic neoplasm which is distinct based on its development from intermediate trophoblast cells and ...nodular growth pattern. The aim of this study is to describe a case series from a single institution with a review of the literature to better understand the clinical characteristics and outcomes for patients with ETT. Methods A retrospective review was performed using the IRB approved New England Trophoblastic Disease Center (NETDC) database from 1998 to 2014. Eight patients were identified of which seven had complete records. Follow-up data was obtained from the longitudinal medical records. Results Four (57.1%) patients presented with vaginal bleeding and two (28.6%) patients were asymptomatic at presentation. Three (42.9%) patients had extrauterine disease. All three patients with extrauterine disease who received chemotherapy had stable or progressive disease at follow-up. Only two (29%) patients who presented with non-metastatic disease and underwent hysterectomy were alive with no evidence of disease. The mean interval following antecedent pregnancy was 104 months. All patients with an interval > 4 years demonstrated stable or progressive disease despite intensive chemotherapy. Two patients with non-metastatic disease who declined hysterectomy developed stable or progressive disease despite chemotherapy. Conclusions This series highlights several features of ETT including the potential for asymptomatic presentation of extrauterine disease. The series also demonstrates chemoresistance, even with multi-agent therapy and a poor prognosis with extrauterine disease and an interval greater than 4 years following the antecedent pregnancy suggesting that surgery remains critical in disease control.
To understand the origins and function of the human germ cell lineage and to identify germ cell-specific markers we have isolated a human ortholog of the Drosophila gene vasa. The gene was mapped to ...human chromosome 5q (near the centromere) by radiation hybrid mapping. We show by Northern analysis of fetal and adult tissues that expression of the human VASA gene is restricted to the ovary and testis and is undetectable in somatic tissues. We generated polyclonal antibodies that bind to the VASA protein in formalin-fixed, paraffin-embedded tissue and characterized VASA protein expression in human germ cells at various stages of development. The VASA protein is cytoplasmic and expressed in migratory primordial germ cells in the region of the gonadal ridge. VASA protein is present in fetal and adult gonadal germ cells in both males and females and is most abundant in spermatocytes and mature oocytes. The gene we have isolated is thus a highly specific marker of germ cells and should be useful for studies of human germ cell determination and function.
Although somatic mutations in a number of genes have been associated with development of human tumors, such as lipomas, relatively few examples exist of germline mutations in these genes. Here we ...describe an 8-year-old boy who has a de novo pericentric inversion of chromosome 12, with breakpoints at p11.22 and q14.3, and a phenotype including extreme somatic overgrowth, advanced endochondral bone and dental ages, a cerebellar tumor, and multiple lipomas. His chromosomal inversion was found to truncate
HMGA2, a gene that encodes an architectural factor involved in the etiology of many benign mesenchymal tumors and that maps to the 12q14.3 breakpoint. Similar truncations of murine
Hmga2 in transgenic mice result in somatic overgrowth and, in particular, increased abundance of fat and lipomas, features strikingly similar to those observed in the child. This represents the first report of a constitutional rearrangement affecting
HMGA2 and demonstrates the role of this gene in human growth and development. Systematic genetic analysis and clinical studies of this child may offer unique insights into the role of
HMGA2 in adipogenesis, osteogenesis, and general growth control.
Bone diseases such as osteoporosis, osteoarthritis and rheumatoid arthritis, impinge on the performance of orthopaedic implants by impairing bone regeneration. For this reason, the development of ...effective surface modifications supporting the ingrowth of implants in morbid bone tissue is essential. Our study is designed to elucidate if cells with restricted cell-function limiting adhesion processes benefit from plasma polymer deposition on titanium. We used the actin filament disrupting agent cytochalasin D (CD) as an experimental model for cells with impaired actin cytoskeleton. Indeed, the cell's capacity to adhere and spread was drastically reduced due to shortened actin filaments and vinculin contacts that were smaller. The coating of titanium with a positively charged nanolayer of plasma polymerised allylamine (PPAAm) abrogated these disadvantages in cell adhesion and the CD-treated osteoblasts were able to spread significantly. Interestingly, PPAAm increased spreading by causing enhanced vinculin number and contact length, but without significantly reorganising actin filaments. PPAAm with the monomer allylamine was deposited in a microwave-excited low-pressure plasma-processing reactor. Cell physiology was monitored by flow cytometry and confocal laser scanning microscopy, and the length and number of actin filaments was quantified by mathematical image processing. We showed that biomaterial surface modification with PPAAm could be beneficial even for osteoblasts with impaired cytoskeleton components. These insights into in vitro conditions may be used for the evaluation of future strategies to design implants for morbid bone tissue.
The feasibility and safety of magnetic resonance (MR) imaging-guided focused ultrasound surgery for uterine leiomyomas is reported. Sequential sonications were delivered to nine targets. ...Temperature-sensitive phase-difference MR imaging monitored the location of the focus and measured tissue temperature elevations, ensuring therapeutic dose. MR images and hysterectomy specimens were evaluated. Six leiomyomas received full therapeutic doses, and 98.5% of the sonications were visualized. MR thermometry was successful in all sonications and cases. Focal necrotic lesions were seen in all cases at MR, and five were pathologically confirmed. MR imaging-guided focused ultrasound causes thermocoagulation and necrosis in uterine leiomyomas and is feasible and safe, without serious consequences.
Hybridisation of labelled fragments was done in the presence of excess herring sperm competitor DNA, and hybridised membranes were washed at 60°C with 0.15 M NaCl/0.015 M sodium citrate/0.1 % sodium ...dodecyl sulphate (SDS) for 30 minutes.\n 3, 17 Anosmin 1 interacts with heparan and chondroitin sulphates to promote cell adhesion and neuronal outgrowth, and has been implicated in the migration of gonadotropin releasing hormone (GnRH) producing neurones and olfactory axonal fibres, though the receptor system through which it acts remains uncertain. 18 Notably, FGFR1 activation by binding to FGF ligands involves receptor dimerisation that also requires heparan sulphate proteoglycan binding. 19 Indeed, FGF2 ligand and FGFR1 have been co-crystallised with heparin, and the structure of the complex defined. 20 The common association with heparan sulphates and the similar effects of KAL1 and FGFR1 inactivating mutations support the suggestion that the FGFR1 signalling pathway participates directly in mediating anosmin 1 function. 8, 21 The translocation patient reported here and the KS patients reported by others also support the view that haploinsufficiency for FGFR1 is a cause of cleft lip and palate. 7, 8, 16 Interestingly, FGFR1 gain of function mutations have previously been associated with the craniosynostosis of Pfeiffer's syndrome and in the Jackson-Weiss syndrome. 22, 23 These syndromes can also be caused by mutations in FGFR2, which has also been associated with cleft palate in Apert's syndrome, indicating that the two receptors may function in the same signalling pathway. 24 This suggests that FGFR2, located at 10q26, may be an excellent candidate for an additional KS or idiopathic hypogonadotropic hypogonadism locus. ...it would be of interest to determine whether FGFR2 is disrupted by translocation in a KS patient with a de novo unbalanced der(1)t(1;10)(q44;q26).
Between 8 and 6 million years ago, there was a global increase in the biomass of plants using C4 photosynthesis as indicated by changes in the carbon isotope ratios of fossil tooth enamel in Asia, ...Africa and elsewhere.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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