François Gros: from antibiotics to messenger RNA.

François Gros was a prominent French Molecular Biologist who made a major contribution to the discovery of messenger RNA in 1961. He pursued outstanding research on bacterial mRNA and its translation into proteins followed by pioneering work on muscle differentiation. I was lucky to be among his graduate students and owe much of my success in science to him.

Patellar Instability in Young Athletes.

This article summarizes the latest research related to pediatric patellar instability. The epidemiology, patterns of patellar instability, and underlying pathoanatomy are unique in children and adolescents. Information related to the natural history and predictive factors of patellar instability in young patients would allow for better patient counseling and management decisions.

Translation, cross-cultural adaptation and reliability of the International Knee Documentation Committee (IKDC) subjective knee form and the tampa scale for kinesiophobia (TSK) into Hebrew.

Introduction: The International Knee Documentation Committee-Subjective Form (IKDC-SF) is one of the most used measures for evaluating the quality of life among people experiencing knee pain but is not yet available in Hebrew. Similarly, the Tampa Scale for Kinesiophobia (TSK), used to evaluate fear of movement, is not available in Hebrew. This study aimed to determine the reliability and construct validity of the Hebrew IKDC-SF and TSK among people experiencing chronic knee pain.

SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress.

Enduring behavioral changes upon stress exposure involve changes in gene expression sustained by epigenetic modifications in brain circuits, including the mesocorticolimbic pathway. Brahma (BRM) and Brahma Related Gene 1 (BRG1) are ATPase subunits of the SWI/SNF complexes involved in chromatin remodeling, a process essential to enduring plastic changes in gene expression. Here, we show that in mice, social defeat induces changes in BRG1 nuclear distribution.

3D-printed Cutting Guides for Lower Limb Deformity Correction in the Young Population.

Background: Three-dimensional (3D) virtual surgical planning technology has advanced applications in the correction of deformities of long bones by enabling the production of 3D stereolithographic models, patient-specific instruments and surgical-guiding templates. Herein, we describe the implementation of this technology in young patients who required a corrective osteotomy for a complex 3-plane (oblique plane) lower-limb deformity.

Patients And Methods: A total of 17 patients (9 males, average age 14.

Surgical Treatment of Congenital and Obligatory Dislocation of the Patella in Children.

Background: Congenital (fixed) dislocations and obligatory (habitual) patellar dislocations represent a complex clinical and surgical challenge. Numerous treatment options, offering different perspectives, and surgical solutions are reported in the literature.We implemented the surgical technique principles, originally described by Stanisavljevic, for congenital (fixed) and obligatory (habitual) patellar dislocations, with slight modifications.

Chromatin remodeling: from transcription to cancer.

In this short review article, I have tried to trace the path that led my laboratory from the early studies of the structure of papova minichromosomes and transcription control to the investigation of chromatin remodeling complexes of the SWI/SNF family. I discuss briefly the genetic and biochemical studies that lead to the discovery of the SWI/SNF complex in yeast and drosophila and summarize some of the studies on the developmental role of the murine complex. The discovery of the tumor suppressor function of the SNF5/INI1/SMARCB1 gene in humans and the identification of frequent mutations in other subunits of this complex in different human tumors opened a fascinating field of research on this epigenetic regulator.

The transcription factor JunD mediates transforming growth factor {beta}-induced fibroblast activation and fibrosis in systemic sclerosis.

Objectives: Transforming growth factor β (TGFβ) has been identified as a key player in fibrotic diseases. However, the molecular mechanisms by which TGFβ activates fibroblasts are incompletely understood. Here, the role of JunD, a member of the activator protein 1 (AP-1) family of transcription factors, as a downstream mediator of TGFβ signalling in systemic sclerosis (SSc), was investigated.

The 50th anniversary of the publication of the operon theory in the Journal of Molecular Biology: past, present and future.

A series of eight review articles that appear in the present issue of the Journal of Molecular Biology celebrates the 50th anniversary for the landmark publication of François Jacob and Jacques Monod entitled "Genetic Regulatory Mechanisms in the Synthesis of Proteins". In this publication, the authors presented a model for the regulation of gene expression deduced from genetic and biochemical studies. They proposed that a new class of genes, regulatory genes, would code for repressors that bind to operator sequences upstream of operons consisting of a group of catabolic or biosynthetic genes with related functions.

Human papillomavirus type 8 E2 protein unravels JunB/Fra-1 as an activator of the beta4-integrin gene in human keratinocytes.

The papillomavirus life cycle parallels keratinocyte differentiation in stratifying epithelia. We have previously shown that the human papillomavirus type 8 (HPV8) E2 protein downregulates beta4-integrin expression in normal human keratinocytes, which may trigger subsequent differentiation steps. Here, we demonstrate that the DNA binding domain of HPV8 E2 is sufficient to displace a cellular factor from the beta4-integrin promoter.

SWI/SNF deficiency results in aberrant chromatin organization, mitotic failure, and diminished proliferative capacity.

Switch (SWI)/sucrose nonfermentable (SNF) is an evolutionarily conserved complex with ATPase function, capable of regulating nucleosome position to alter transcriptional programs within the cell. It is known that the SWI/SNF complex is responsible for regulation of many genes involved in cell cycle control and proliferation, and it has recently been implicated in cancer development. The ATPase action of SWI/SNF is conferred through either the brahma-related gene 1 (Brg1) or brahma (Brm) subunit of the complex, and it is of central importance to the modification of nucleosome position.

Mitochondrial dysfunction contributes to impaired insulin secretion in INS-1 cells with dominant-negative mutations of HNF-1alpha and in HNF-1alpha-deficient islets.

Maturity Onset Diabetes of the Young-type 3 (MODY-3) has been linked to mutations in the transcription factor hepatic nuclear factor (HNF)-1alpha, resulting in deficiency in glucose-stimulated insulin secretion. In INS-1 cells overexpressing doxycycline-inducible HNF-1alpha dominant-negative (DN-) gene mutations, and islets from Hnf-1alpha knock-out mice, insulin secretion was impaired in response to glucose (15 mm) and other nutrient secretagogues. Decreased rates of insulin secretion in response to glutamine plus leucine and to methyl pyruvate, but not potassium depolarization, indicate defects specific to mitochondrial metabolism.

Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia.

Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 x 10(-5)) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.

The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer.

Factors that drive prostate cancer progression remain poorly defined, thus hindering the development of new therapeutic strategies. Disseminated tumors are treated through regimens that ablate androgen signaling, as prostate cancer cells require androgen for growth and survival. However, recurrent, incurable tumors that have bypassed the androgen requirement ultimately arise.

Small DNA tumour viruses and their contributions to our understanding of transcription control.

The study of small DNA tumour viruses like SV40 and polyoma was one of the major entry points for the study of eukaryotes. It opened fields like gene structure, transcription or replication control, chromatin structure and cell transformation. This review outlines the breakthroughs that occurred at the end of the 1970s and during the 1980s in our understanding of gene structure and the basic processes involved in control of gene expression starting with DNA tumour viruses and reaching their cellular hosts.

V osteotomy and Ilizarov technique for residual idiopathic or neurogenic clubfeet.

Purpose: To report the treatment outcomes of V osteotomy and Ilizarov technique for residual idiopathic or neurogenic clubfeet.

Methods: 13 patients (14 feet) aged 8 to 18 years underwent V osteotomy via the calcaneus and talus, followed by gradual distraction of soft tissue and bone for foot reconstruction. Eight of the clubfeet were idiopathic and had undergone previous surgeries.

JunD protects the liver from ischemia/reperfusion injury by dampening AP-1 transcriptional activation.

The AP-1 transcription factor modulates a wide range of cellular processes, including cellular proliferation, programmed cell death, and survival. JunD is a major component of the AP-1 complex following liver ischemia/reperfusion (I/R) injury; however, its precise function in this setting remains unclear. We investigated the functional significance of JunD in regulating AP-1 transcription following partial lobar I/R injury to the liver, as well as the downstream consequences for hepatocellular remodeling.

Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters.

Multi-gene families of transcription factors pose a formidable challenge to molecular and functional analysis. Dissecting distinct functions for individual family members requires a combination of approaches in different cellular and animal models. The AP-1 transcription factor complex serves as a paradigm for understanding the dynamics of transcriptional regulation.

Treatment of severe late-onset Perthes' disease with soft tissue release and articulated hip distraction: revisited at skeletal maturity.

Purpose: Late-onset Perthes' disease is diagnosed after 9 years of age. Conservative treatment and conventional surgical techniques have limited ability to reduce the pressure in the joint or change the shape of the femoral head. We used a combination of soft tissue release and joint distraction with a hinged mono-lateral external fixator for these patients.