From Isotropic to Anisotropic Side Chain Representations: Comparison of Three Models for Residue Contact Estimation

The criterion to determine residue contact is a fundamental problem in deriving knowledge-based mean-force potential energy calculations for protein structures. A frequently used criterion is to require the side chain center-to-center distance or the -to- atom distance to be within a pre-determined cutoff distance. However, the spatially anisotropic nature of the side chain determines that it is challenging to identify the contact pairs. This study compares three side chain contact models: the Atom Distance criteria (ADC) model, the Isotropic Sphere Side chain (ISS) model and the Anisotropic Ellipsoid Side chain (AES) model using 424 high resolution protein structures in the Protein Data Bank. The results indicate that the ADC model is the most accurate and ISS is the worst. The AES model eliminates about 95% of the incorrectly counted contact-pairs in the ISS model. Algorithm analysis shows that AES model is the most computational intensive while ADC model has moderate computational cost. We derived a dataset of the mis-estimated contact pairs by AES model. The most misjudged pairs are Arg-Glu, Arg-Asp and Arg-Tyr. Such a dataset can be useful for developing the improved AES model by incorporating the pair-specific information for the cutoff distance

The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma – a retrospective analysis of 392 cases

Twenty per cent of sentinel lymph node (SLN)-positive melanoma patients have positive non-SLN lymph nodes in completion lymph node dissection (CLND). We investigated SLN tumour load, non-sentinel positivity and disease-free survival (DFS) to assess whether certain patients could be spared CLND. Sentinel lymph node biopsy was performed on 392 patients between 1999 and 2005. Median observation period was 38.8 months. Sentinel lymph node tumour load did not predict non-SLN positivity: 30.8% of patients with SLN macrometastases (⩾2 mm) and 16.4% with micrometastases (⩽2 mm) had non-SLN positivity (P=0.09). Tumour recurrences after positive SLNs were more than twice as frequent for SLN macrometastases (51.3%) than for micrometastases (24.6%) (P=0.005). For patients with SLN micrometastases, the DFS analysis was worse (P=0.003) when comparing those with positive non-SLNs (60% recurrences) to those without (17.6% recurrences). This difference did not translate into significant differences in DFS: patients with SLN micrometastasis, either with (P=0.022) or without additional positive non-SLNs (P<0.0001), fared worse than patients with tumour-free SLNs. The 2-mm cutoff for SLN tumour load accurately predicts differences in DFS. Non-SLN positivity in CLND, however, cannot be predicted. Therefore, contrary to other studies, no recommendations concerning discontinuation of CLND based on SLN tumour load can be deduced

PAX6 Haplotypes Are Associated with High Myopia in Han Chinese

Author name used in this publication: Maurice K. H. Yap2010-2011 > Academic research: refereed > Publication in refereed journalpublished_fina

Characterising the CI and CI-like carbonaceous chondrites using thermogravimetric analysis and infrared spectroscopy

The CI and CI-like chondrites provide a record of aqueous alteration in the early solar system. However, the CI-like chondrites differ in having also experienced a late stage period of thermal metamorphism. In order to constrain the nature and extent of the aqueous and thermal alteration, we have investigated the bulk mineralogy and abundance of H2O in the CI and CI-like chondrites using thermogravimetric analysis and infrared spectroscopy. The CI chondrites Ivuna and Orgueil show significant mass loss (28.5–31.8 wt.%) upon heating to 1000 °C due to dehydration and dehydroxylation of abundant phyllosilicates and Fe-(oxy)hydroxides and the decomposition of Fe-sulphides, carbonates and organics. Infrared spectra for Ivuna and Orgueil have a prominent 3-μm feature due to bound −OH/H2O in phyllosilicates and Fe-(oxy)hydroxides and only a minor 11-μm feature from anhydrous silicates. These characteristics are consistent with previous studies indicating that the CI chondrites underwent near-complete aqueous alteration. Similarities in the total abundance of H2O and 3 μm/11 μm ratio suggest that there is no difference in the relative degree of hydration experienced by Ivuna and Orgueil. In contrast, the CI-like chondrites Y-82162 and Y-980115 show lower mass loss (13.8–18.8 wt.%) and contain >50 % less H2O than the CI chondrites. The 3-μm feature is almost absent from spectra of Y-82162 and Y-980115 but the 11-μm feature is intense. The CI-like chondrites experienced thermal metamorphism at temperatures >500 °C that initially caused dehydration and dehydroxylation of phyllosilicates before partial recrystallization back into anhydrous silicates. The surfaces of many C-type asteroids were probably heated through impact metamorphism and/or solar radiation, so thermally altered carbonaceous chondrites are likely good analogues for samples that will be returned by the Hayabusa-2 and OSIRIS-REx missions

Biology of Streptococcus mutans-Derived Glucosyltransferases: Role in Extracellular Matrix Formation of Cariogenic Biofilms

The importance of Streptococcus mutans in the etiology and pathogenesis of dental caries is certainly controversial, in part because excessive attention is paid to the numbers of S. mutans and acid production while the matrix within dental plaque has been neglected. S. mutans does not always dominate within plaque; many organisms are equally acidogenic and aciduric. It is also recognized that glucosyltransferases from S. mutans (Gtfs) play critical roles in the development of virulent dental plaque. Gtfs adsorb to enamel synthesizing glucans in situ, providing sites for avid colonization by microorganisms and an insoluble matrix for plaque. Gtfs also adsorb to surfaces of other oral microorganisms converting them to glucan producers. S. mutans expresses 3 genetically distinct Gtfs; each appears to play a different but overlapping role in the formation of virulent plaque. GtfC is adsorbed to enamel within pellicle whereas GtfB binds avidly to bacteria promoting tight cell clustering, and enhancing cohesion of plaque. GtfD forms a soluble, readily metabolizable polysaccharide and acts as a primer for GtfB. The behavior of soluble Gtfs does not mirror that observed with surface-adsorbed enzymes. Furthermore, the structure of polysaccharide matrix changes over time as a result of the action of mutanases and dextranases within plaque. Gtfs at distinct loci offer chemotherapeutic targets to prevent caries. Nevertheless, agents that inhibit Gtfs in solution frequently have a reduced or no effect on adsorbed enzymes. Clearly, conformational changes and reactions of Gtfs on surfaces are complex and modulate the pathogenesis of dental caries in situ, deserving further investigation

Cohort profile: design and methods in the eye and vision consortium of UK Biobank

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life

Periodontitis and Outer Retinal Thickness: a Cross-Sectional Analysis of the United Kingdom Biobank Cohort

\ua9 2024 American Academy of OphthalmologyPurpose: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease. Design: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank. Participants: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging. Methods: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery. Main Outcome Measures: Photoreceptor layer (PRL) and retinal pigment epithelium–Bruch\u27s membrane (RPE–BM) thicknesses. Results: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P &lt; 0.001). On average, those with very severe periodontitis were hyperopic (0.05 \ub1 2.27 diopters) while those unaffected were myopic (−0.29 \ub1 2.40 diopters, P &lt; 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (−0.55 μm, 95% confidence interval [CI], −0.97 to −0.12; P = 0.022) but there was no difference in RPE–BM thickness (0.00 μm, 95% CI, −0.12 to 0.13; P = 0.97). The association between PRL thickness and very severe periodontitis was modified by age (P &lt; 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (−1.19 μm, 95% CI, −1.85 to −0.53; P &lt; 0.001) but not among those aged &lt; 60 years. Conclusions: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error : the CREAM consortium

Peer reviewe

Recent advances in studies of polymicrobial interactions in oral biofilms

The oral cavity supports a complex and finely balanced consortium of microbial species, many of which cooperate within structured biofilms. These communities develop through multitudinous synergistic and antagonistic interspecies relationships. Changes in the dynamics of oral microbial populations are associated with the transition from healthy teeth and gums to dental caries, gingivitis and periodontitis. Understanding the ecology of oral biofilm communities, and how different species communicate within a given host, will inform new strategies for treatment and prevention of oral diseases. Advances in sequencing technologies have fuelled an increasing trend towards global genomic and proteomic approaches to determine the key factors that initiate oral diseases. Whilst metabolic profiling seeks to identify phenotypic changes of whole microbial communities, transcriptomic studies are exploring their complex interactions with each other and the host. This review discusses the most recent in vitro and in vivo studies of interspecies interactions within polymicrobial oral biofilms