Liver Disease Complicating Familial Mediterranean Fever: A Study on 66 Patients Out of 533 Adult From the JIR Cohort.

Background: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, associated with MEFV mutations. FMF patients can experience liver involvement, potentially leading to cirrhosis.

Objectives: This study aimed to evaluate liver involvement in FMF patients at a French tertiary centre for adult FMF.

Current and Future Costs of Intractable Conflicts-Can They Create Attitude Change?

Members of societies involved in an intractable conflict usually consider costs that stem from the continuation of the conflict as unavoidable and even justify for their collective existence. This perception is well-anchored in widely shared conflict-supporting narratives that motivate them to avoid information that challenges their views about the conflict. However, since providing information about such major costs as a method for moderating conflict-related views has not been receiving much attention, in this research, we explore this venue.

Exercise alone and exercise combined with education both prevent episodes of low back pain and related absenteeism: systematic review and network meta-analysis of randomised controlled trials (RCTs) aimed at preventing back pain.

Objectives: We aimed to investigate which prevention strategies for low back pain (LBP) are most effective.

Design: We completed a Bayesian network meta-analysis to summarise the comparative effectiveness of LBP prevention strategies. The primary outcomes were an episode of LBP and LBP-associated work absenteeism represented as ORs with associated 95% credibility intervals (CrIs).

Effects of 2-iodohexadecanal in the physiology of thyroid cells.

Iodide has direct effects on thyroid function. Several iodinated lipids are biosynthesized by the thyroid and they were postulated as intermediaries in the action of iodide. Among them, 2-iodohexadecanal (2-IHDA) has been identified and proposed to play a role in thyroid autoregulation.

Functional inactivation of thyroid transcription factor-1 in PCCl3 thyroid cells.

Thyroid transcription factor-1 (TTF-1) is a key regulator of thyroid development and function. In order to identify the genes whose expression depends on TTF-1 transcriptional activity within the thyrocyte we analyzed the consequence of the functional inactivation of this factor in PCCl3 cells. The expression of a fusion protein composed of the DNA binding domain of TTF-1 and of the strong repressive domain of the engrailed protein resulted in a dramatic loss of epithelial cell morphology and in proliferation arrest.

Delimitation and functional characterization of the bidirectional THOX-DUOXA promoter regions in thyrocytes.

The THOX and DUOXA genes encode components of the oxidative machinery involved in thyroid hormone biosynthesis. Both of these genes are duplicated in mammalian genomes and are positioned in a head-to-head configuration, THOX1 facing DUOXA1 and THOX2 facing DUOXA2, respectively. The intergenic regions in both couples of genes exhibit dissimilar compositions, being highly GC-rich in the case of THOX1-DUOXA1 but not in the other case.

Identification of a short basic peptide motif able to drive copy-number dependent nuclear accumulation of a linked protein.

The repetitive [RTRG](6) peptide was fortuitously identified as a potent nuclear localization signal when linked to the green fluorescent reporter protein. Replacing the arginines by lysines, or the threonines by glycines, both resulted in a decreased nuclear targeting ability of the peptide within this context. By contrast, the sequence [RT](12) proved able to drive nuclear accumulation of the linked protein as efficiently as the starting peptide.

Human Thyroid Oxidases genes promoter activity in thyrocytes does not appear to be functionally dependent on Thyroid Transcription Factor-1 or Pax8.

Thyroid Oxidases (ThOX/DUOX) genes encode proteins that are thought to play a crucial role in the biosynthesis of thyroid hormone by providing the oxidizing agent required to allow the organification of iodine. The expression of these genes is not restricted to the thyroid, but the corresponding mRNAs are found in the thyrocyte more abundantly than in several other cell types. It raises the question whether the same transcription factors, namely Thyroid Transcription Factor-1 (TTF-1) and Pax8, that control the expression of other genes involved in the differentiated thyroid function, also regulate ThOX/DUOX gene transcription in the thyrocyte.

Endoluminal occlusion of the inferior vena cava in renal cell carcinoma with retro- or suprahepatic caval thrombus.

Objective: To evaluate endoluminal occlusion of the inferior vena cava (IVC) during surgical treatment of renal cell carcinoma (RCC) with either retrohepatic (level II) or suprahepatic (level III) caval tumour thrombus.

Patients And Methods: From January 2000 to February 2005, 31 patients with renal vein/IVC involvement (T3b/c) of 278 who had a radical nephrectomy, were selected for review. Of these 31, 13 consecutive patients with RCC presenting a thrombus level II or III were prospectively treated with endoluminal occlusion of the free IVC cranial to the thrombus, to avoid dissection of the suprahepatic IVC or the subdiaphragmatic IVC.

Sequences downstream of the bHLH domain of the Xenopus hairy-related transcription factor-1 act as an extended dimerization domain that contributes to the selection of the partners.

XHRT1 is a member of the HRT/Hey protein subfamily that are known as Notch effectors. XHRT1 is expressed in the developing floor plate and encodes a basic helix-loop-helix (bHLH) transcription repressor. Here, we show that XHRT1 misexpression in the neural plate inhibits differentiation of neural precursor cells and thus may be important for floor plate cells to prevent them from adopting a neuronal fate.

Transcriptional repression by the bHLH-Orange factor XHRT1 does not involve the C-terminal YRPW motif.

Hairy-related transcription factors (HRTs) constitute a recently identified subfamily of basic-helix-loop-helix transcription factors containing an Orange domain (bHLH-O factors). As compared to the related HES proteins, HRTs exhibit distinct DNA-binding activities in vitro and the molecular mechanisms underlying their transcriptional activity remain poorly understood. We have identified here the sequence "ggCACGTGcc" as predominant binding site for Xenopus HRT1 (XHRT1).

The control of thyroid-specific gene expression: what exactly have we learned as yet?

The identification of transcription factors TTF 1 and Pax 8 and the demonstration of their pivotal role in thyroid development and in the control of thyroid-specific gene expression, although representing remarkable openings in our understanding of cell-specific transcription in the thyroid, still leave a lot of open questions. Recent work investigating the development of thyroid-specific gene expression in transgenic mouse models, now reveal that some basic assumptions have to be reconsidered also. Altogether, currently available data indicate that the regulatory machinery undergoes significant changes during thyroid organogenesis and confirm the existence of still unknown factors whose roles appear at least as critical as the ones played by TTF 1 and Pax 8 in the control of specific gene expression.

Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid.

Thyroid dysgenesis is the most common cause of congenital hypothyroidism, a relatively frequent disease affecting 1 in 3000-4000 newborns. Whereas most cases are sporadic, mutations in transcription factors implicated in thyroid development have been shown to cause a minority of cases transmitted as monogenic Mendelian diseases. PAX8 is one of these transcription factors, and so far, five mutations have been identified in its paired domain in patients with thyroid dysgenesis.

TM4SF10 gene sequencing in XLMR patients identifies common polymorphisms but no disease-associated mutation.

Background: The TM4SF10 gene encodes a putative four-transmembrane domains protein of unknown function termed Brain Cell Membrane Protein 1 (BCMP1), and is abundantly expressed in the brain. This gene is located on the short arm of human chromosome X at p21.1.

Structural and functional characterization of the two human ThOX/Duox genes and their 5'-flanking regions.

A crucial step in thyroid hormone synthesis is the oxidative coupling of iodide to thyroglobulin that is catalyzed by thyroperoxidase. The limiting factor of this reaction is the supply of hydrogen peroxide. The generation of hydrogen peroxide has been linked to an enzymatic system located at the apical pole of thyrocytes.

Identification of BOIP, a novel cDNA highly expressed during spermatogenesis that encodes a protein interacting with the orange domain of the hairy-related transcription factor HRT1/Hey1 in Xenopus and mouse.

Hairy-related transcription factor (HRT/Hey) genes encode a novel subfamily of basic helix-loop-helix (bHLH) transcription factors related to the Drosophila hairy and Enhancer-of-split (E(spl)) and the mammalian HES proteins that function as downstream mediators of Notch signaling. Using the yeast two-hybrid approach, a previously uncharacterized protein was identified in Xenopus that interacts with XHRT1 (originally referred to as bc8), one member of the HRT/Hey subclass. This protein is evolutionarily conserved in chordates.

XHRT-1, a hairy and Enhancer of split related gene with expression in floor plate and hypochord during early Xenopus embryogenesis.

We have isolated a Xenopus homologue of the mammalian hairy and Enhancer of split related gene HRT1. XHRT1 expression in late gastrula and early neurula embryos is restricted to two stripes of cells in the medial neural plate and in dorsal endodermal cells. At later stages, XHRT1 is expressed in the floor plate, in hypochord cells and in the somitogenic and anterior presomitic mesoderm.

Identification of the gene encoding Brain Cell Membrane Protein 1 (BCMP1), a putative four-transmembrane protein distantly related to the Peripheral Myelin Protein 22 / Epithelial Membrane Proteins and the Claudins.

Background: A partial cDNA clone from dog thyroid presenting a very significant similarity with an uncharacterized mouse EST sequence was isolated fortuitously. We report here the identification of the complete mRNA and of the gene, the product of which was termed "brain cell membrane protein 1" (BCMP1).

Results: The 4 kb-long mRNA sequence exhibited an open-reading frame of only 543 b followed by a 3.

Suboptimal enhancer sequences are required for efficient bovine leukemia virus propagation in vivo: implications for viral latency.

Repression of viral expression is a major strategy developed by retroviruses to escape from the host immune response. The absence of viral proteins (or derived peptides) at the surface of an infected cell does not permit the establishment of an efficient immune attack. Such a strategy appears to have been adopted by animal oncoviruses such as bovine leukemia virus (BLV) and human T-cell leukemia virus (HTLV).

A method for the large-scale cloning of nuclear proteins and nuclear targeting sequences on a functional basis.

We describe here a selection strategy allowing the cloning of sequences that contain a functional nuclear targeting signal. Our method relies on the use of green fluorescent protein fusion proteins to identify nuclear targeting sequences. Transfected cells expressing nuclear protein fusions were isolated on the basis of their nuclear fluorescence using flow cytometry and the transfected DNAs were recovered after bacterial transformation with total DNA from pools of sorted cells.

Nuclear targeting of proteins: how many different signals?

The nuclear import of proteins into the cell nucleus involves the recognition of a nuclear localization signal sequence, borne by the protein to be transported, by complex molecules called importins, that will subsequently mediate the crossing over of the nuclear envelope. The most frequently encountered signal sequence is made up of short stretches of basic amino acid residues and is recognized by importins alpha and/or beta. Other signal sequences have been described, and some have been shown to mediate the association with importins other than importin alpha or beta.

A canonical nerve growth factor-induced gene-B response element appears not to be involved in the cyclic adenosine monophosphate-dependent expression of differentiation in thyrocytes.

The expression of transcriptionally active nerve growth factor-induced gene-B (NGFI-B) is rapidly induced in thyroid follicular cells in response to cAMP stimulation. As the transcription of thyrocyte-specific genes is controlled by the cAMP cascade, we have investigated a possible involvement of NGFI-B in this control. Recombinant adenoviruses driving the expression of either the intact NGFI-B protein or a truncated form of it that lacks the capacity to transactivate a NBRE-dependent promoter, were used to infect dog thyrocytes maintained in primary culture.