A new find of Trematosuchus (Amphibia, Temnospondyli) from the Cynognathus Zone of South Africa

Some aspects of the cranial morphology of Trematosuchus sobeyi, a temnospondylous Trematosaurid amphibian from the South African Cynognathus Zone, are described in detail for the first time from a new fossil find referred to this form. The new specimen is similar in size to that of the holotype of Trematosuchus sobeyi but differs in the more moderate elongation of the snout. Apart from the presence of the septomaxilla, the validity of the genus Trematosuchus is reconfirmed inter alia by its much larger size and the position of the supraorbital sensory groove alongside the lachrymal margin rather than crossing this bone. This last characteristic differentiates Trematosuchus from all other trematosauroids. T. Sobeyi is of particular importance since it represents the only purely freshwater Gondwanan form closely comparable to the European Trematosaurus. The presence of T. Sobeyi in the lowermost strata of the Cynognathus Zone in South Africa, in association with some other forms related to the Upper Olenekian (Middle Buntsandstein) tetrapod assemblage of Europe, indicates that these strata belong to the Scythian in contrast to the higher strata of the Cynognathus Zone which are Anisian

Disturbances of attitudes and behaviours related to eating in black and white females at high school and university in South Africa

This paper reports two studies, which contribute to the increasing evidence that the attitudes and behaviours associated with eating disorders, are encountered among both black and white females in South Africa. In Study One, the Eating Disorders Inventory EDI was administered to black (n=39) and white (n=41) female students in Natal. There were no significant differences between black and white on the sub-scales which measure disturbed eating behaviour directly (Drive for Thinness, Bulimia, Body Dissatisfaction). However black respondents scrored higher on Perfectionism, Interpersonal Distrust and Maturity Fears, variables believed to predispose individuals to eating disorders. In Study Two, the Bulimia Test (BULIT) was administered to black and white females at three educational levels. There was no significant effect of Ethnicity, but there was a significant effect of Age: Standard 6 respondents had significantly higher scores than University students. In both studies, Body mass index (BMI) was significantly higher among blacks than whites. In Study One there was no significant correlation between BMI and Drive for Thinness in either blacks or whites. However in Study Two, the correlation between BMI and BULIT full scale was significant in the case of both blacks (r = 0,39; p <,01) and whites (r = 0,38; p<,05). These findings are consistent with those of other recent studies, which find disturbances in eating-related attitudes and behaviour in all ethnic groups in South Africa

Psychological distress and depression in urbanising elderly black persons

The findings of a comparative community survey of the socioeconomic, cultural and psychiatric state of elderly black persons in a newly settled township (Khayelitsha - 170 persons) and a long established one (Langa - 195 persons) revealed marked differences. Symptoms of psychological distress, depression and limitation of daily activities were generally more marked in the former and strikingly so among women: 66% had symptoms warranting further investigation and 44% would have been treated for a depressive disorder if seen by a psychiatrist. Extreme poverty existed in both townships but the Khayelitsha subjects were less well educated, their accommodation was poorer, and fewer had old-age pensions. Elderly black women in newly settled townships have therefore been identified as having high priority for psychiatric and social services

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

Overexpression and/or activity of c-Src non-receptor tyrosine kinase is associated with progression of several human epithelial cancers including breast cancer. c-Src activity in ‘pure' ductal carcinoma in situ (DCIS) was measured to assess whether this predicts recurrence and/or correlates with HER2 expression and other clinical parameters. Activated c-Src levels were evaluated in DCIS biopsies from 129 women, with median follow-up at 60 months. High levels of activated c-Src correlated with HER2 positivity, high tumour grade, comedo necrosis and elevated epithelial proliferation. In univariate analysis, high activated c-Src level associated with lower recurrence-free survival at 5 years (P=0.011). Thus, high c-Src activity may identify a subset of DCIS with high risk of recurrence or progression to invasive cancer where therapeutics targeting c-Src may benefit this patient subset

Diversity of Matriptase Expression Level and Function in Breast Cancer

Overexpression of matriptase has been reported in a variety of human cancers and is sufficient to trigger tumor formation in mice, but the importance of matriptase in breast cancer remains unclear. We analysed matriptase expression in 16 human breast cancer cell lines and in 107 primary breast tumors. The data revealed considerable diversity in the expression level of this protein indicating that the significance of matriptase may vary from case to case. Matriptase protein expression was correlated with HER2 expression and highest expression was seen in HER2-positive cell lines, indicating a potential role in this subgroup. Stable overexpression of matriptase in two breast cancer cell lines had different consequences. In MDA-MB-231 human breast carcinoma cells the only noted consequence of matriptase overexpression was modestly impaired growth in vivo. In contrast, overexpression of matriptase in 4T1 mouse breast carcinoma cells resulted in visible changes in morphology, actin staining and cell to cell contacts. This correlated with downregulation of the cell-cell adhesion molecule E-cadherin. These results suggest that the functions of matriptase in breast cancer are likely to be variable and cell context dependent

TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappa B

Aneurysmal bone cyst (ABC) is an aggressive, pediatric bone tumor characterized by extensive destruction of the surrounding bone. Though first described over 60 years ago, its molecular etiology remains poorly understood. Recent work revealed that ABCs harbor translocation of TRE17/USP6, leading to its transcriptional upregulation. TRE17 encodes a ubiquitin-specific protease (USP), and a TBC domain that mediates binding to the Arf6 GTPase. However, the mechanisms by which TRE17 overexpression contributes to tumor pathogenesis, and the role of its USP and TBC domains are unknown. ABCs are characterized by osteolysis, inflammatory recruitment, and extensive vascularization, processes in which matrix proteases play a prominent role. This led us to explore whether TRE17 regulates the production of matrix metalloproteinases (MMPs). In the current study, we demonstrate that TRE17 is sufficient to induce expression of MMP-9 and MMP-10, in a manner requiring its USP activity, but not its ability to bind Arf6. TRE17 induces transcription of MMP-9 through activation of NFκB, mediated in part by the GTPase RhoA and its effector kinase, ROCK. Furthermore, xenograft studies demonstrate that TRE17 induces formation of tumors that reproduce multiple features of ABC, including a high degree of vascularization, with an essential role for the USP domain. In sum, these studies reveal that TRE17 is sufficient to initiate tumorigenesis, identify MMPs as novel TRE17 effectors that likely contribute to ABC pathogenesis, and define the underlying signaling mechanism of their induction

Absent in Melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers

Absent in Melanoma 2 (AIM2) is a member of the HIN-200 family of hematopoietic, IFN-inducible, nuclear proteins, associated with both, infection defense and tumor pathology. Recently, AIM2 was found to act as a DNA sensor in innate immunity. In addition, we and others have previously demonstrated a high frequency of AIM2-alterations in microsatellite unstable (MSI-H) tumors. To further elucidate AIM2 function in colorectal tumors, we here addressed AIM2-responsive target genes by microarray based gene expression profiling of 22 244 human genes. A total of 111 transcripts were significantly upregulated, whereas 80 transcripts turned out to be significantly downregulated in HCT116 cells, constitutively expressing AIM2, compared with AIM2-negative cells. Among the upregulated genes that were validated by quantitative PCR and western blotting we recognized several interferon-stimulated genes (ISGs: IFIT1, IFIT2, IFIT3, IFI6, IRF7, ISG15, HLA-DRA, HLA-DRB, TLR3 and CIITA), as well as genes involved in intercellular adhesion and matrix remodeling. Expression of ISGs correlated with expression of AIM2 in 10 different IFN-γ treated colorectal cancer cell lines. Moreover, small interfering RNA-mediated knock-down of AIM2 resulted in reduced expression of HLA-DRA, HLA-DRB and CIITA in IFN-γ-treated cells. IFN-γ independent induction of HLA-DR genes and their encoded proteins was also demonstrated upon doxycyclin-regulated transient induction of AIM2. Luciferase reporter assays revealed induction of the HLA-DR promoter upon AIM2 transfection in different cell lines. STAT-signaling was not involved in IFN-γ independent induction of ISGs, arguing against participation of cytokines released in an autostimulating manner. Our data indicate that AIM2 mediates both IFN-γ dependent and independent induction of several ISGs, including genes encoding the major histocompatibility complex (MHC) class II antigens HLA-DR-α and -β. This suggests a novel role of the IFN/AIM2/ISG cascade likewise in cancer cells

Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer

<p>Abstract</p> <p>Background</p> <p>The HIV-1 Env glycoprotein mediates virus entry by catalyzing direct fusion between the virion membrane and the target cell plasma membrane. Env is composed of two subunits: gp120, which binds to CD4 and the coreceptor, and gp41, which is triggered upon coreceptor binding to promote the membrane fusion reaction. Env on the surface of infected cells is a trimer consisting of three gp120/gp41 homo-dimeric protomers. An emerging question concerns cooperative interactions between the protomers in the trimer, and possible implications for Env function.</p> <p>Results</p> <p>We extended studies on cooperative subunit interactions within the HIV-1 Env trimer, using analysis of functional complementation between coexpressed inactive variants harboring different functional deficiencies. In assays of Env-mediated cell fusion, complementation was observed between variants with a wide range of defects in both the gp120 and gp41 subunits. The former included gp120 subunits mutated in the CD4 binding site or incapable of coreceptor interaction due either to mismatched specificity or V3 loop mutation. Defective gp41 variants included point mutations at different residues within the fusion peptide or heptad repeat regions, as well as constructs with modifications or deletions of the membrane proximal tryptophan-rich region or the transmembrane domain. Complementation required the defective variants to be coexpressed in the same cell. The observed complementation activities were highly dependent on the assay system. The most robust activities were obtained with a vaccinia virus-based expression and reporter gene activation assay for cell fusion. In an alternative system involving Env expression from integrated provirus, complementation was detected in cell fusion assays, but not in virus particle entry assays.</p> <p>Conclusion</p> <p>Our results indicate that Env function does not require every subunit in the trimer to be competent for all essential activities. Through cross-talk between subunits, the functional determinants on one defective protomer can cooperatively interact to trigger the functional determinants on an adjacent protomer(s) harboring a different defect, leading to fusion. Cooperative subunit interaction is a general feature of the Env trimer, based on complementation activities observed for a highly diverse range of functional defects.</p