Detection of genotoxic and non-genotoxic carcinogens in Xpc(-/-)p53(+/-) mice.

An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances.

IGFBP7's susceptibility to proteolysis is altered by A-to-I RNA editing of its transcript.

The selective deamination of adenosines (A) to inosines (I) in messenger RNAs (mRNAs) can alter the encoded protein's amino acid sequence, with often critical consequences on protein stability, localization, and/or function. Insulin-like growth factor-binding protein 7 (IGFBP7) supports cell-adhesion and stimulates fibroblast proliferation with IGF and insulin. It exists in both proteolytically processed and unprocessed forms with altered cell-extracellular matrix interactions.

FEBio: finite elements for biomechanics.

In the field of computational biomechanics, investigators have primarily used commercial software that is neither geared toward biological applications nor sufficiently flexible to follow the latest developments in the field. This lack of a tailored software environment has hampered research progress, as well as dissemination of models and results. To address these issues, we developed the FEBio software suite (http://mrl.

Cryopreservation of adenovirus-transfected dendritic cells (DCs) for clinical use.

In this study, we examined the effects of cryoprotectant, freezing and thawing, and adenovirus (Adv) transduction on the viability, transgene expression, phenotype, and function of human dendritic cells (DCs). DCs were differentiated from cultured peripheral blood (PB) monocytes following Elutra isolation using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 6 days and then transduced using an Adv vector with an IL-12 transgene. Fresh, cryopreserved, and thawed transduced immature DCs were examined for their: 1) cellular concentration and viability; 2) antigenicity using an allogeneic mixed lymphocyte reaction (MLR); 3) phenotype (HLA-DR and CD11c) and activation (CD83); and 4) transgene expression based on IL-12 secretion.

Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome.

Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available.

Solute transport across a contact interface in deformable porous media.

A finite element formulation of neutral solute transport across a contact interface between deformable porous media is implemented and validated against analytical solutions. By reducing the integral statements of external virtual work on the two contacting surfaces into a single contact integral, the algorithm automatically enforces continuity of solute molar flux across the contact interface, whereas continuity of the effective solute concentration (a measure of the solute mechano-chemical potential) is achieved using a penalty method. This novel formulation facilitates the analysis of problems in biomechanics where the transport of metabolites across contact interfaces of deformable tissues may be of interest.

Influence of individual characteristics on static rotational knee laxity using the Rotameter.

Purpose: The purpose of this study was to evaluate the influence of individual characteristics on rotational knee laxity in healthy participants. Our second aim was to verify whether the contralateral knee of patients with a non-contact ACL injury presents greater rotational knee laxity than a healthy control group.

Methods: Sixty healthy participants and 23 patients having sustained a non-contact ACL injury were tested with a new Rotameter prototype applying torques up to 10 Nm.

Posttranscriptional recoding by RNA editing.

The posttranscriptional recoding of nuclear RNA transcripts has emerged as an important regulatory mechanism during eukaryotic gene expression. In particular the deamination of adenosine to inosine (interpreted by the translational machinery as a guanosine) is a frequent event that can recode the meaning of amino acid codons in translated exons, lead to structural changes in the RNA fold, or may affect splice consensus or regulatory sequence sites in noncoding exons or introns and modulate the biogenesis of small RNAs. The molecular mechanism of how the RNA editing machinery and its substrates recognize and interact with each other is not understood well enough to allow for the ab initio delineation of bona fide RNA editing sites.

[Exosomes and cancer].

Exosomes are a subtype of vesicles released by cells of both healthy and neoplastic origin. Preclinical studies suggest a role for tumour-derived exosomes in tumour progression, mainly through the transfer of RNA and proteins from tumour cells to other cells. The transfer of RNA and proteins by tumour-derived exosomes seems to mediate stimulation of angiogenesis and suppression of immune cells; in contrast, exosomes from healthy cells of the immune system appear to have anti-tumour characteristics.

Surgical treatment of macroglossia in patients with Beckwith-Wiedemann syndrome: a 20-year experience and review of the literature.

Macroglossia is observed in the majority of paediatric patients diagnosed with Beckwith-Wiedemann syndrome and surgical treatment may be indicated. A 20-year retrospective study was performed to evaluate all patients with Beckwith-Wiedemann syndrome who underwent tongue reduction surgery at the authors' institution. A literature review was performed.

Finite element implementation of mechanochemical phenomena in neutral deformable porous media under finite deformation.

Biological soft tissues and cells may be subjected to mechanical as well as chemical (osmotic) loading under their natural physiological environment or various experimental conditions. The interaction of mechanical and chemical effects may be very significant under some of these conditions, yet the highly nonlinear nature of the set of governing equations describing these mechanisms poses a challenge for the modeling of such phenomena. This study formulated and implemented a finite element algorithm for analyzing mechanochemical events in neutral deformable porous media under finite deformation.

Genome-wide evaluation and discovery of vertebrate A-to-I RNA editing sites.

RNA editing by adenosine deamination, catalyzed by adenosine deaminases acting on RNA (ADAR), is a post-transcriptional modification that contributes to transcriptome and proteome diversity and is widespread in mammals. Here we administer a bioinformatics search strategy to the human and mouse genomes to explore the landscape of A-to-I RNA editing. In both organisms we find evidence for high excess of A/G-type discrepancies (inosine appears as a guanosine in cloned cDNA) at non-polymorphic, non-synonymous codon sites over other types of discrepancies, suggesting the existence of several thousand recoding editing sites in the human and mouse genomes.

Static rotational and sagittal knee laxity measurements after reconstruction of the anterior cruciate ligament.

Purpose: The goal of the present study was to evaluate static anteroposterior and rotational knee laxity after ACL reconstructions with two noninvasive measurement devices by comparing the measured results of the operated with the contralateral healthy knees of the patients.

Methods: Fifty-two consecutive patients were reviewed after isolated single-bundle transtibial ACL reconstruction using a BPTB graft. At a mean follow-up of 27 months, sagittal AP laxity was tested using a noninvasive knee measurement system (Genourob) with an applied pressure of 67 N, 89 N and 134 N.

In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1.

Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells.

Identification of spontaneous mutations within the long-range limb-specific Sonic hedgehog enhancer (ZRS) that alter Sonic hedgehog expression in the chicken limb mutants oligozeugodactyly and silkie breed.

The evolutionarily conserved, non-coding ~800-base-pair (bp) zone of polarizing activity (ZPA) regulatory sequence (ZRS) controls Shh expression in the posterior limb. We report that the chicken mutant oligozeugodactyly (ozd), which lacks limb Shh expression, has a large deletion within the ZRS. Furthermore, the preaxial polydactylous, Silkie Breed chicken, which develops ectopic anterior limb Shh expression, has a single bp change within the ZRS.

The atypical 16p11.2 deletion: a not so atypical microdeletion syndrome?

One of the recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome (593 kb; ∼29.5 Mb to ∼30.

Epithelial-to-mesenchymal transformation alters electrical conductivity of human epicardial cells.

The myocardium of the developing heart tube is covered by epicardium. These epicardial cells undergo a process of epithelial-to-mesenchymal transformation (EMT) and develop into epicardium-derived cells (EPDCs). The ingrowing EPDCs differentiate into several celltypes of which the cardiac fibroblasts form the main group.

Gene regulation through RNA editing.

RNA editing by adenosine deamination is a posttranscriptional mechanism for the regulation of gene expression and is particularly widespread in mammals. A-to-I RNA editing generates transcriptome and proteome diversity allowing organisms to produce many more gene products and functions than predicted based on the number of genes within their genome. Also, it regulates important functional properties of neurotransmitter receptor genes in the central nervous system by changing single codons in pre-mRNA.

The jumping SHOX gene--crossover in the pseudoautosomal region resulting in unusual inheritance of Leri-Weill dyschondrosteosis.

Context: During meiosis I, the recombination frequency in the pseudoautosomal region on Xp and Yp (PAR1) in males is very high. As a result, mutated genes located within the PAR1 region can be transferred from the Y-chromosome to the X-chromosome and vice versa.

Patients: Here we describe three families with SHOX abnormalities resulting in Leri-Weill dyschondrosteosis or Langer mesomelic dysplasia.

ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells.

Background: Unrepaired DNA double-stranded breaks (DSBs) cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ) pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability.

Finite element algorithm for frictionless contact of porous permeable media under finite deformation and sliding.

This study formulates and implements a finite element contact algorithm for solid-fluid (biphasic) mixtures, accommodating both finite deformation and sliding. The finite element source code is made available to the general public. The algorithm uses a penalty method regularized with an augmented Lagrangian method to enforce the continuity of contact traction and normal component of fluid flux across the contact interface.

MiRNA editing.

RNA editing by A-to-I modification is a widespread mechanism in complex organisms that leads to the posttranscriptional alteration of protein coding as well as noncoding sequences. MiRNA transcripts have been recognized as a major target for RNA editing enzymes, and single-nucleotide changes through editing can impact the biogenesis of mature miRNAs, as well as the target specificity of the regulatory RNA. Bona fide A-to-I RNA editing events are validated experimentally through parallel analysis of genomic DNA and transcribed sequences of miRNA genes isolated from the same specimen through gene-specific amplification and sequencing of endogenous transcripts.

Epicardium-derived cells enhance proliferation, cellular maturation and alignment of cardiomyocytes.

During heart development, cells from the proepicardial organ spread over the naked heart tube to form the epicardium. From here, epicardium-derived cells (EPDCs) migrate into the myocardium. EPDCs proved to be indispensable for the formation of the ventricular compact zone and myocardial maturation, by largely unknown mechanisms.

Enlarged nuchal translucency in chromosomally normal fetuses: strong association with orofacial clefts.

Objectives: The aim of this study was to investigate whether there is an association between enlarged nuchal translucency (NT) and orofacial clefts.

Methods: The pregnancy outcome of women who underwent an NT measurement between January 2000 and November 2008 was reviewed. All orofacial clefts detected prenatally and postnatally in karyotypically normal fetuses/infants were reviewed and a distinction was made between isolated defects and clefts as part of multiple congenital anomalies (associated).