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Biomedical subjects

I Davidson

Publications and source records attributed to I Davidson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Outcome of the depressed elderly living in the community in Liverpool: a 5-year follow-up.

BACKGROUND: Comparatively little is known about the long-term natural history of depressive disorders in the elderly living in the community. This is a follow-up of a subsample of the Continuing Health in the Community study random sample of the elderly population living in Liverpool. METHODS: The investigators followed up 120 cases of depression identified by a semi-structured interview schedule (GMS) for a period of 5 years. A similar number of other subjects defined as subcases of depression, other cases of mental illness and a random selection of non-cases were also included. RESULTS: The 5-year outcome for the cases of depression was worse than the outcome of the non-cases (relative mortality risk of 2.1, 95% confidence interval 1.1 to 3.9). Thirty-four per cent of the cases of depression died and 28% had dropped out during the follow-up. Of the 46 cases of depression who had a complete follow-up, 22% recovered from their symptoms, 30% were found to be AGECAT cases at one of the three follow-up waves, 24% were AGECAT cases at two of the three follow-up waves and the remaining 24% were AGECAT cases at each follow-up wave. Fifteen per cent of the surviving cases of depression were organic cases at the follow-up. Their anxiety comorbid state and depression score were identified as predictors of poor outcome. CONCLUSION: The findings of this study indicate that depressive disorders (most of which were untreated) found in the elderly community have a poor prognosis.

Activities of Daily Living↗
PubMed1998

Development of RT-PCR for turkey meningoencephalitis virus and partial sequence analysis of the NS5 gene.

Turkey meningoencephalitis virus (TMEV) causes paralysis and mortality in turkeys. Because the classical diagnostic methods are complicated, we developed the RT-PCR as a new molecular diagnostic method. Since the nucleic acid sequence of TMEV is unknown, the first step in developing the RT-PCR relied on conserved sequences of viruses belonging to the Flaviviridae family, in which TMEV has been classified serologically. Using primers from the NS5 gene, three amplification products of TMEV RNA were obtained (125 bp, 181 bp and 800 bp). Their sequences were homologous to one another and to the NS5 gene of other flaviviruses.

Animals↗
PubMed1998

Functional and structural analysis of the subunits of human transcription factor TFIID.

The past few years have brought many new insights concerning the structure and function of TAFII proteins. In the future, further biochemical and structural studies will no doubt lead to a greater understanding of the molecular organization of TFIID complexes. A better understanding of the function of metazoan, in particular, mammalian, TAFIIs in cell cycle progression and gene activation will, however, require the use of novel genetic techniques in addition to the biochemical analyses.

Animals↗
PubMed1998

Perturbation of anion balance during inhibition of growth of Escherichia coli by weak acids.

During inhibition of cell growth by weak acids, there is substantial accumulation of the weak acid anions in the cytoplasm. This study was undertaken to determine the impact of anion accumulation on cellular pools. At pH 6, growth in the presence of 8 mM acetate led to an internal pool of greater than 240 mM acetate anion and resulted in reduced levels of glutamate in the cell, but there were no significant changes in K+ and Na+ levels. At low osmolarity, the change in the glutamate pool compensated for only a small fraction of the accumulated acetate anion. However, at high osmolarity, glutamate compensated for over half of the accumulated acetate. Recovery of the normal cytoplasmic pH after the removal of acetate was dependent on the synthesis of glutamate.

Acetates↗
PubMed1998

Interaction of human papillomavirus 8 regulatory proteins E2, E6 and E7 with components of the TFIID complex.

Human papillomavirus 8 (HPV8) is one of the oncogenic HPV types specifically associated with skin cancers of epidermodysplasia verruciformis patients. The early gene products of this virus exert functions in transformation (E2, E6, E7), replication (E1, E2) and in the control of viral transcription (E2, E7). Many viral and cellular transactivators of transcription have been shown to interact selectively and directly with a number of TATA-box-binding protein (TBP)-associated factors (TAFIIs), which then play a role as coactivators. Using glutathione-S-transferase (GST) pull-down experiments, we tested in vitro interactions between GST-HPV8-E1, -E2, -E6 and -E7 and 7 in-vitro-translated TAFIIs in the human (h) system (hTAFII18, hTAFII20, hTAFII28, hTAFII30, hTAFII55, hTAFII100, hTAFIIDeltaN135) or TBP. We could show that GST-HPV8-E2 interacts directly at least with hTAFII55 and TBP. Deletion analysis indicated that a domain overlapping with the C-terminal moiety of HPV8-E2 is required for binding to TBP, whereas determinants for interactions with hTAFII55 are in the central and C-terminal part of the E2 protein. In similar binding studies, GST-HPV8-E6 interacted with hTAFII28, hTAFIIDeltaN135 and TBP, and more weakly with hTAFII20, whereas GST- HPV8-E7 bound to hTAFII20, hTAFII28, hTAFII55, hTAFIIDeltaN135 and TBP. Deletion analysis revealed that the C-terminal part of HPV8-E7 is required for the interaction with these hTAFIIs. In contrast, no interactions were observed between GST-HPV8-E1 and in-vitro-translated hTAFIIs.

Binding Sites↗
PubMed1997

Human TAF(II)135 potentiates transcriptional activation by the AF-2s of the retinoic acid, vitamin D3, and thyroid hormone receptors in mammalian cells.

We report for the first time the cloning of a complete cDNA encoding the human TFIID subunit hTAF(II)135 (hTAF(II)130). Full-length hTAF(II)135 comprises 1083 amino acids and contains two conserved domains present also in dTAF(II)110 and hTAF(II)105. We show that expression of hTAF(II)135 in mammalian cells strongly and selectively potentiates transcriptional stimulation by the activation function-2 (AF-2) of the retinoic acid, thyroid hormone, and vitamin D3 receptors (RAR, TR, and VDR), but does not affect the AF-2s of the estrogen (ER) or retinoid X (RXR) receptors. The coactivator activity requires an hTAF(II)135 region that is located between the conserved domains but is itself not conserved in dTAF(II)110 and hTAF(II)105. Expression of hTAF(II)135 also stimulates RAR AF-2 activity when a promoter with a low-affinity TATA element (TGTA) is used, indicating that hTAF(II)135 overexpression compensates for the low-affinity of TBP for this promoter and may facilitate the recruitment of TFIID by the RAR AF-2.

Amino Acid Sequence↗
PubMed1997

Human TEF-5 is preferentially expressed in placenta and binds to multiple functional elements of the human chorionic somatomammotropin-B gene enhancer.

We report the cloning of a cDNA encoding the human transcription factor hTEF-5, containing the TEA/ATTS DNA binding domain and related to the TEF family of transcription factors. hTEF-5 is expressed in skeletal and cardiac muscle, but the strongest expression is observed in the placenta and in placenta-derived JEG-3 choriocarcinoma cells. In correlation with its placental expression, we show that hTEF-5 binds to several functional enhansons of the human chorionic somatomammotropin (hCS)-B gene enhancer. We define a novel functional element in this enhancer comprising tandemly repeated sites to which hTEF-5 binds cooperatively. In the corresponding region of the hCS-A enhancer, which is known to be inactive, this element is inactivated by a naturally occurring single base mutation that disrupts hTEF-5 binding. We further show that the binding of the previously described placental protein f/chorionic somatomammotropin enhancer factor-1 to TEF-binding sites is disrupted by monoclonal antibodies directed against the TEA domain and that this factor is a proteolytic degradation product of the TEF factors. These results strongly suggest that hTEF-5 regulates the activity of the hCS-B gene enhancer.

Amino Acid Sequence↗
PubMed1997

Human TAF(II)28 interacts with the human T cell leukemia virus type I Tax transactivator and promotes its transcriptional activity.

The Tax protein encoded by human T cell leukemia virus type I transactivates the viral promoter by forming a complex with several cellular factors bound to three repeats of a specific upstream regulatory sequence. We have shown that transactivation by Tax was correlated with its ability to interact with the C-terminal moiety of the TATA box-binding protein (TBP). In the present study, the ability of Tax to interact with several human TBP-associated factors (TAF(II)s) was analyzed. We show that Tax interacts selectively with hTAF(II)28 in transfected HeLa cells. A direct interaction between Tax and hTAF(II)28 was also observed in vitro with purified proteins. In transient expression studies we show that overexpression of hTAF(II)28 significantly increased transactivation by Tax, both in the absence and in the presence of overexpressed TBP. The ability of hTAF(II)28 to potentiate transactivation correlated with the ability of Tax to interact with hTAF(II)28 and also with the ability of hTAF(II)28 to interact with TBP. Coexpression of TBP and hTAF(II)28 resulted in an additive increase in transactivation by Tax. From these observations we propose that transcriptional activation by Tax involves multiple interactions with TFIID via its TBP and hTAF(II)28 subunits.

Animals↗
PubMed1997

The transactivation domain of adenovirus E1A interacts with the C terminus of human TAF(II)135.

The CR3 activation domain of the human adenovirus E1A protein stimulates transcription by forming protein-protein interactions with DNA sequence-specific binding factors and components of the TFIID complex. Here, we demonstrate that CR3 can complex with the extreme C-terminal 105 amino acids of the human TATA box binding-factor-associated protein, hTAF(II)135. Furthermore, the C-terminal region of hTAF(II)135 can block transcriptional stimulation from an E1A-inducible promoter in vivo. This ability of the C terminus of hTAF(II)135 to bind CR3 and to inhibit E1A-inducible activation is highly specific. These results demonstrate for the first time that a discrete fragment of a mammalian TBP-associated factor which targets a specific activator can impair the stimulation of transcription.

Adenovirus E1A Proteins↗
PubMed1997

Temperature and developmental plasticity of muscle phenotype in herring larvae

Myogenesis, the expression of myofibrillar protein isoforms and the development of muscle innervation were investigated in Clyde herring (Clupea harengus L.) in two successive spawning seasons at temperatures ranging from 5 °C to 15 °C. Myotube formation occurred in a rostral to caudal progression at similar somite stages at all temperatures. Superficial mononuclear muscle pioneer fibres were present at the horizontal septum. Myofibrillogenesis was retarded with respect to somite stage at low temperatures; for example, by the 50-somite stage, myofibrils were observed in the muscle pioneers of the first 31 somites at 12 °C, but only the first 20 somites at 5 °C. In the electron microscope, the earliest stages of myofibril assembly were observed in the muscle pioneer cells and in a proportion of the multinucleated myotubes within the same somite. By the end of somitogenesis, the density of myofibrils in the rostral myotomes was much higher at 15 °C than at 5 °C. Embryonic isoforms of myosin light chain 2 (LC2), troponin I and troponin T were identified in the presumptive white muscle using two-dimensional gel electrophoresis. Expression of the embryonic isoforms was gradually switched off during the larval stages. The size range over which embryonic isoforms were present was inversely related to rearing temperature. For example, the adult pattern of myosin LC2 expression was established at 11 mm total length (TL) at 15 °C, but not until 15 mm TL at 5 °C. Acetylcholinesterase staining was apparent at the myosepta in 31-somite stage embryos at 15 °C, but not until approximately the 40-somite stage at 5 °C. The red muscle fibres of larvae were initially innervated only at their myoseptal ends. The temperature at which the red muscle fibres became multiply innervated was inversely related to body size, occurring at 12­14 mm at 12 °C, but not until 16­19 mm at 5 °C. We conclude that the temperature during early development determines the relative timing and degree of expression of the myogenic programme, resulting in significant phenotypic variation in the swimming muscles of the larval stages. Our results highlight a potential mechanism whereby early thermal experience could influence survival and hence the strength of particular year classes of fish.

Journal Article↗
PubMed1996

A novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain.

We describe the molecular cloning of two novel human and murine transcription factors containing the TEA/ATTS DNA binding domain and related to transcriptional enhancer factor-1 (TEF-1). These factors bind to the consensus TEA/ATTS cognate binding site exemplified by the GT-IIC and Sph enhansons of the SV40 enhancer but differ in their ability to bind cooperatively to tandemly repeated sites. The human TEFs are differentially expressed in cultured cell lines and the mouse (m)TEFs are differentially expressed in embryonic and extra-embryonic tissues in early post-implantation embryos. Strikingly, at later stages of embryogenesis, mTEF-3 is specifically expressed in skeletal muscle precursors, whereas mTEF-1 is expressed not only in developing skeletal muscle but also in the myocardium. Together with previous data, these results point to important, partially redundant, roles for these TEF proteins in myogenesis and cardiogenesis. In addition, mTEF-1 is strongly coexpressed with mTEF-4 in mitotic neuroblasts, while accentuated mTEF-4 expression is also observed in the gut and the nephrogenic region of the kidney. These observations suggest additional roles for the TEF proteins in central nervous system development and organogenesis.

Amino Acid Sequence↗
PubMed1996

Multiple interactions between hTAFII55 and other TFIID subunits. Requirements for the formation of stable ternary complexes between hTAFII55 and the TATA-binding protein.

We have cloned and characterized the human TATA-binding protein (TBP)-associated factor hTAFII55. hTAFII55, which has no known Drosophila counterpart, is present in both of the previously described TFIIDalpha and TFIIDbeta subpopulations. We describe the interactions of hTAFII55 with other subunits of the transcription factor TFIID. By cotransfection in COS cells, we show that hTAFII55 interacts with hTAFII250, hTAFII100, hTAFII28, hTAFII20, and hTAFII18, but not with hTAFII30 or TBP. Analysis of the binding of hTAFII55 and TBP to hTAFII28 deletion mutants indicates that distinct regions of hTAFII28 are required for these interactions. Although hTAFII55 does not interact by itself with TBP, stable ternary complexes containing hTAFII55 and TBP can be formed in the presence of hTAFII250, hTAFII100, or hTAFII28. These results not only show that hTAFII100 and hTAFII28 interact with TBP, but also that they can nucleate the formation of partial TFIID complexes.

Amino Acid Sequence↗
PubMed1996

Distinct domains of hTAFII100 are required for functional interaction with transcription factor TFIIF beta (RAP30) and incorporation into the TFIID complex.

TFIID is the DNA binding component of the RNA polymerase II transcriptional machinery and is composed of the TATA binding protein (TBP) and TBP-associated factors (TAFIIs). Here we report the characterization of a new human TAF, hTAFII100, which is the human homologue of Drosophila TAFII80 and yeast TAFII90. hTAFII100 interacts strongly with hTAFII250, hTAFII55 and hTAFII28, less with hTAFII20 and hTAFII18, weakly with TBP and not at all with delta NTAFII135 and hTAFII30. Deletion analysis revealed that the C-terminal half of hTAFII100, which contains six WD-40 repeats, is not required for incorporation into the TFIID complex. Our results suggest that hTAFII100 can be divided into two domains, the N-terminal region responsible for interactions within the TFIID complex and the C-terminal WD repeat-containing half responsible for interactions between hTAFII100 and other factors. An anti-hTAFII100 antibody, raised against a C-terminal epitope, selectively inhibited basal TFIID-dependent in vitro transcription and the specific interaction between hTAFII100 and the 30 kDa subunit of TFIIF (RAP30). We demonstrate that the hTAFII100-TFIIF interaction supports pre-initiation complex formation in the presence of TFIID. Thus, this is the first demonstration that a TAFII functionally interacts with a basal transcription factor in vitro.

Amino Acid Sequence↗
PubMed1996

Human TAF(II28) promotes transcriptional stimulation by activation function 2 of the retinoid X receptors.

Transcriptional activation in vitro involves direct interactions of transactivators with the TATA binding protein (TBP) and the TBP-associated factors (TAF(II)s) which constitute the TFIID complex. However, the role of TAF(II)s in transcriptional regulation in mammalian cells has not been addressed. We show that activation function 2 of the retinoid X receptors (RXR AF-2) does not activate transcription from a minimal promoter in Cos cells. However, coexpression of human (h) TAF(II)28 promotes a strong ligand-dependent activity of the RXR AF-2 on a minimal promoter and potentiates the ability of the RXRalpha AF-2 to activate transcription from a complex promoter. The expression of hTAF(II)28 also potentiated transactivation by several nuclear receptors, notably the oestrogen and vitamin D3 receptors (ER and VDR), whereas other classes of activator were not affected. The effect of hTAFII(28) on RXR AF-2 activities did not appear to require direct RXR-TAFII(28) interactions, but correlated with the ability of hTAFII(28) to interact with TBP. In contrast to Cos cells, the RXR AF-2s had differential abilities to activate transcription from a minimal promoter in HeLa cells, and a lesser increase in their activity was observed upon hTAFII28 coexpression. Moreover, coexpression of hTAFII(28) did not increase but rather repressed activation by the ER and VDR AF-2s in HeLa cells. In agreement with these data, showing that TAF(II)28 is limiting in the AF-2 activation pathway in Cos cells, TAF(II)28 is selectively depleted in Cos cell TFIID.

Amino Acid Sequence↗
PubMed1996

A non-radioactive method for identifying enzyme-amplified products of the reticuloendotheliosis proviral env and LTR genes using psoralen-biotin labelled probes.

A novel polymerase chain reaction (PCR) system based on the env gene of reticuloendotheliosis virus (REV) strain REV-A for the detection of proviral DNA is described. The designed PCR product of 807 bp was identified using an internal probe of 278 bp produced by nested PCR from REV-infected DNA CEF. The env-gene PCR was then compared with the previously described PCR for proviral REV-long terminal repeat and the PCR product served also as the probe. The probes were labelled with the psoralen-biotin system by photoactivation and the southern blot hybridization signal was detected colorimetricaly. The advantages of using a non-radioactive means of probe labelling were demonstrated clearly in that study, as well as the effective labeling of probes with psoralen-biotin and the simple colorimetric method of detection. The env-gene PCR detected all eleven REV strains used in the study. These included three REV prototype strains and eight Israeli REV isolates. Both PCR systems had similar levels of sensitivity.

Animals↗
PubMed1996

The immunodominant proteins of reticuloendotheliosis virus.

The antigenic profiles of three REV prototype strains, CSV, SNV and REV-T and eight Israeli isolates were analysed by SDS-PAGE and immunoblotting with convalescent chicken serum, three mAbs, 11A25, 11C237 and 11C100, a rabbit antiserum to REV-T whole virus (Cui et al., 1986) and a rabbit antiserum to REV-A p30 gag protein (Tsai et al., 1985). Under both reducing (+DTT) and non-reducing conditions of SDS-PAGE, a major immunodominant 75-100 kDa band was shared by all strains examined. In contrast to the chicken serum that recognized both continuous and discontinuous epitopes on the 75-100 kDa band of all the isolates, the mAbs and the two rabbit sera behaved otherwise. Only the DTT-resistant epitopes on the 75-100 kDa band of REV-T were recognized by the rabbit antisera and the mAb 11C237, and only the DTT-labile epitopes of REV-T 75-100 kDa antigen were detected by mAb 11C100. The two mAbs 11A25 and 11C237 detected discontinuous epitopes of all the strains except SNV, while the rabbit antisera recognized the discontinuous epitopes on the 75-100 kDa band of all the 11 strains. The rabbit antisera and mAb 11C237 detected additional lower molecular weight proteins and the mAb 11C237 also detected three proteins of high molecular weight under non-reducing conditions only. The p30 antiserum detected the low molecular weight proteins demonstrating their gag gene-encoded identity. From these results we conclude that the major immunogen of REV is the 75-100 kDa protein that contains both continuous and discontinuous epitopes. With this panel of antibodies the eight new isolates appeared to belong antigenically to REV subtype 3 (Chen et al., 1987).

Animals↗