Investigation of p16(INK4a) as a prognostic biomarker in oral epithelial dysplasia.

Background: Human papilloma virus is a risk factor for oropharyngeal cancer. Evidence for a similar aetiological role in the development of oral dysplasia or its transformation to oral cancer is not as clear. Meta-analyses estimate the prevalence of high-risk human papilloma virus (HPV) serotypes to be three times higher in pre-malignant lesions and cancer than in normal oral mucosa.

Aberrant spindle dynamics and cytokinesis in Dictyostelium discoideum cells that lack glycogen synthase kinase 3.

Eukaryotic cell division requires the co-ordinated assembly and disassembly of the mitotic spindle, accurate chromosome segregation and temporal control of cytokinesis to generate two daughter cells. While the absolute details of these processes differ between organisms, there are evolutionarily conserved core components common to all eukaryotic cells, whose identification will reveal the key processes that control cell division. Glycogen synthase kinase 3 (GSK-3) is a major protein kinase found throughout the eukaryotes and regulates many processes, including cell differentiation, growth, motility and apoptosis.

Characterization of Anopheles gambiae transglutaminase 3 (AgTG3) and its native substrate Plugin.

Male Anopheles mosquitoes coagulate their seminal fluids via cross-linking of a substrate, called Plugin, by the seminal transglutaminase AgTG3. Formation of the "mating plug" by cross-linking Plugin is necessary for efficient sperm storage by females. AgTG3 has a similar degree of sequence identity (~30%) to both human Factor XIII (FXIII) and tissue transglutaminase 2 (hTG2).

The binary oral dysplasia grading system: validity testing and suggested improvement.

Objectives: A binary system is reputed to be superior to the World Health Organization (WHO) system in grading oral dysplasia. We aimed to validate its reproducibility and prognostic ability and examine whether it could be improved.

Study Design: Three pathologists graded 141 oral epithelial dysplasia biopsies with the use of both systems.

Prognostic biomarkers of survival in oropharyngeal squamous cell carcinoma: systematic review and meta-analysis.

Background: Human papillomavirus (HPV) positivity improves prognosis in patients with oropharyngeal squamous cell carcinoma (OPSCC). Combining HPV status with other biomarkers may improve its prognostic power.

Methods: The approach was a literature search for longitudinal studies of biomarkers in OPSCC, with systematic review and meta-analysis.

Validation of tissue microarrays in oral epithelial dysplasia using a novel virtual-array technique.

Background: Malignant transformation risk in oral epithelial dysplasia (OED) is currently determined by histological assessment. The subjectivity of this approach has led to interest in identifying prognostic biomarkers. Tissue microarrays (TMA) can reduce the utilization of the finite resources of a pathological archive.

Squamous cell carcinoma of the oral cavity rarely harbours oncogenic human papillomavirus.

Although it is now well established that a significant proportion of oropharyngeal squamous cell carcinomas (SCC) harbour oncogenic human papillomavirus (HPV) sequences, the frequency with which these sequences are detected in oral SCC (excluding oropharyngeal subsites) is highly variable. In an attempt to establish the true prevalence of HPV-16 and HPV-18 subtypes in oral SCC, we screened 142 consecutive cases from a UK cohort using both conventional PCR with consensus primers and type-specific quantitative PCR (Q-PCR), while at the same time employing a rigorous protocol to avoid sample contamination. Q-PCR revealed HPV sequences in five cases; two contained HPV-16 alone, two HPV-18 alone, and one sample carried both genotypes.

Mutant glycyl-tRNA synthetase (Gars) ameliorates SOD1(G93A) motor neuron degeneration phenotype but has little affect on Loa dynein heavy chain mutant mice.

Background: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system, and clinical phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions in addition to its canonical role in protein synthesis through catalyzing the addition of glycine to cognate tRNAs.

Methodology/principal Findings: We have recently described a new mouse model with a point mutation in the Gars gene resulting in a cysteine to arginine change at residue 201.

An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.

Mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system in humans, described clinically as Charcot-Marie-Tooth type 2D or distal spinal muscular atrophy type V. Here, we characterise a new mouse mutant, Gars(C201R), with a point mutation that leads to a non-conservative substitution within GARS. Heterozygous mice with a C3H genetic background have loss of grip strength, decreased motor flexibility and disruption of fine motor control; this relatively mild phenotype is more severe on a C57BL/6 background.

GSK3 is a multifunctional regulator of Dictyostelium development.

Glycogen synthase kinase 3 (GSK3) is a central regulator of metazoan development and the Dictyostelium GSK3 homologue, GskA, also controls cellular differentiation. The originally derived gskA-null mutant exhibits a severe pattern formation defect. It forms very large numbers of pre-basal disc cells at the expense of the prespore population.

Cell polarity and Dictyostelium development.

Cell polarity is essential for unicellular and multicellular stages of Dictyostelium development. Chemotaxis during early development requires each cell to rapidly reorganize its cytoskeleton to point towards a source of cAMP. This involves a balance between local induction of F-actin polymerization and suppression of pseudopods that point in other directions.

Identification of the functional domains of yeast sorting nexins Vps5p and Vps17p.

Sorting nexins (Snxs) are a recently discovered family of conserved hydrophilic cytoplasmic proteins that have been found associated with membranes of the endocytic system and that are implicated in the trafficking of many endosomal membrane proteins, including the epidermal growth factor receptor and transferrin receptor. Snx proteins are partly defined by the presence of a p40 phox homology domain that has recently been shown to bind phosphatidylinositol 3-phosphate. Most Snx proteins also contain a predicted coiled-coils domain in the carboxyl-terminal half of the protein and have been shown to form dimers with other members of the Snx family.