Clinical survey of neurosensory side-effects of mandibular parasymphyseal bone harvesting

The aim of the present survey was to assess neurosensory disturbances and/or tooth-pulp sensitivity losses after mandibular parasymphyseal bone-harvesting procedures. Twenty-eight harvesting areas in 16 patients were surveyed. Mucosal and skin sensitivity of the chin/lower lip, divided into four regions, were determined via Pointed-Blunt and Two-Point-Discrimination Tests. Pulp sensitivity of the mandibular teeth from the left second bicuspid to the right second bicuspid was tested by cold vitality preoperatively and 12 months postoperatively. Teeth were grouped according to sensitivity alterations and distance from the harvesting defects, as measured on CT scans, and statistically significant differences sought. At 12 months, 29% of preoperatively vital cuspids overlying the harvesting defects revealed pulp-sensitivity losses; no patient reported anaesthesia or analgesia; hypoaesthesia was present in 4% (8 sites; 2 patients), hypoalgesia was present in 3% (5 sites; 2 patients) and Two-Point-Discrimination Tests yielded pathologic responses in 5% of tested areas (10 sites; 4 patients). Teeth with and without pulp sensitivity changes were statistically indistinguishable regarding distances between root apices or mental foramen and the harvesting defect. The loss of pulp sensitivity in any tooth cannot be predicted simply on the basis of the distance between its apex and the harvesting osteotomy line.     

Epigenetic alterations in cervical carcinogenesis

During cervical carcinogenesis, the major etiologic factor, the persistent oncogenic HPV infection itself is not sufficient to immortalize and transform the epithelial host cells. Together with further genetic and epigenetic alterations disrupting the cell cycle control, the host cell acquires immortal phenotype and progresses further to an overt malignant and invasive phenotype. Here, we discuss how cancer-associated epigenetic alterations can affect the expression of papillomaviral as well as host genes in relation to stages representing the multistep process of carcinogenesis. Biomarker roles in clinical diagnosis and prognosis might be assigned to the epigenetic pattern of the involved genes.     

Relationships amongst age,language and related skills in adults with Down syndrome

Studies into the effects of ageing on language in adults with Down syndrome (DS) have tended to rely on measures that lack sensitivity to change because they fail to explore across linguistic domains or rely on proxy reports. The study aim was to use measures of receptive and expressive language from studies of younger individuals with DS in exploring relationships across linguistic and associated skills, and age in young to older adults. Fifty-five adults (aged 19–58 years), 10 with a diagnosis of or signs of early stage Alzheimer's Disease (AD), provided data on measures of functioning associated with AD, non-verbal cognition, receptive language (which provided a measure of mental age), receptive and expressive language, and short term auditory and visual memory. The first order correlation between the measure of AD and CA was significant; but not when the 10 participants with AD were removed from the analysis. Significant negative correlations were obtained between CA and all other measures; small to large significant positive correlations were found amongst the other measures. Partial correlations were conducted to remove the potential effects of AD and IQ (the latter measured by a test of non-verbal cognition). Remaining significant correlations were between auditory short term memory and all other included measures, expressive language and all other included measures, and CA and auditory short term memory and expressive language. The results indicate that deterioration with age in this cross-sectional study was accounted for largely by the presence of AD. The exceptions were for auditory short term memory and expressive language. The findings may reflect an underlying deficit in auditory short term memory for adults with DS, as has been found in previous research of children and adolescents. The implications are discussed in terms of the importance of including comprehensive measures of receptive and expressive language and the need to account for the presence of AD in studies of cognitive decline associated with ageing in DS.     

Homodimerization of UDP-glucuronosyltransferase 2B7 (UGT2B7) and identification of a putative dimerization domain by protein homology modeling

Although homodimerization of UGT1A proteins is well established, direct evidence for dimerization of UGT2B7, which is arguably the most important enzyme involved in human drug glucuronidation, is currently lacking. This study characterized UGT2B7 homodimerization by co-immunopreciptation and generated a UGT2B7 homology model that identified the dimerization domain. It was demonstrated that co-expressed, solubilized UGT2B7 proteins differentially tagged with hemagglutinin (UGT2B7-HA) and c-MYC (UGT2B7-cMYC) co-immunoprecipitated as active homodimers that catalyzed 4-methylumbelliferone glucuronidation. Substrate binding affinities (assessed as S₅₀ values) of the tagged and co-expressed tagged proteins were essentially identical to that of native UGT2B7. Co-association was not observed in a ‘mixed’ UGT2B7-HA and UGT2B7-cMYC protein preparation. Generation of a UGT2B7 homology model established from plant and human templates was achieved using SYBYLX1.2 with all residues energy minimized using the Tripos Force Field. The UGT2B7 model allowed elucidation of a putative protein dimerization domain within the B′–C loop of each UGT2B7 monomer. The eighteen amino acid dimerization domain is present in all UGT2B enzymes and comprises a proposed dimerization signature motif (FPPSYVPVVMS). Stabilization of the dimer interface is maintained by the formation of two salt bridges, aromatic π–π stacking interactions, two S-aromatic (face) interactions, and the presence of ‘proline brackets’. The homology model further provides important insights into structure–function relationships of this enzyme and the mechanism responsible for the atypical glucuronidation kinetics for substrates of UGT2B7 and other human UGT enzymes.     

Full automation of 68Ga labelling of DOTA-peptides including cation exchange prepurification

Here we describe a fully automated approach for the synthesis of ⁶⁸Ga-labelled DOTA-peptides based on pre-concentration and purification of the generator eluate by using a cation exchange-cartridge and its comparison with fully automated direct labelling applying fractionated elution. Pre-concentration of the eluate on a cation exchange cartridge both using a resin-based and a disposable cation-exchange cartridge efficiently removed ⁶⁸Ge as well as major metal contaminations with Fe and Zn. This resulted in a high labelling efficiency of DOTA-peptides at high specific activity (SA) with short synthesis times.     

Sporulation patterning and invasive growth in wild and domesticated yeast colonies

Different cell types can form patterns within fungal communities; for example, colonies of Saccharomyces cerevisiae form two sharply defined layers of sporulating cells separated by an intervening layer of unsporulated cells. Because colony sporulation patterns have only been investigated in a single laboratory strain background (W303), in this report we examined these patterns in other strain backgrounds. Two other laboratory strain backgrounds (SK1 and Σ1278b) that differ from W303 with respect to colony morphology, invasive growth, and sporulation efficiency nevertheless displayed the same colony sporulation pattern as W303. This pattern was also observed in colonies of wild isolates of S. cerevisiae and Saccharomyces paradoxus. The wild yeast colonies sporulated on a much wider range of carbon sources than did the lab yeast and displayed a similar layered sporulation pattern when grown on either acetate or glucose medium and on either rich or synthetic medium. SK1, Σ1278b and wild yeast colonies invaded the agar surface. The region of invasion varied between strains with respect to the organization and appearance of cells, but this invasion was always accompanied by sporulation. Thus, sporulation patterns are a general property of S. cerevisiae, and sporulation in colonies can be coordinated with invasive growth.