Foot Bone in Vivo: Its Center of Mass and Centroid of Shape

This paper studies foot bone geometrical shape and its mass distribution and establishes an assessment method of bone strength. Using spiral CT scanning, with an accuracy of sub-millimeter, we analyze the data of 384 pieces of foot bones in vivo and investigate the relationship between the bone's external shape and internal structure. This analysis is explored on the bases of the bone's center of mass and its centroid of shape. We observe the phenomenon of superposition of center of mass and centroid of shape fairly precisely, indicating a possible appearance of biomechanical organism. We investigate two aspects of the geometrical shape, (i) distance between compact bone's centroid of shape and that of the bone and (ii) the mean radius of the same density bone issue relative to the bone's centroid of shape. These quantities are used to interpret the influence of different physical exercises imposed on bone strength, thereby contributing to an alternate assessment technique to bone strength.Comment: 9 pages, 4 figure

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Two-Loop Soft Corrections and Resummation of the Thrust Distribution in the Dijet Region

The thrust distribution in electron-positron annihilation is a classical precision QCD observable. Using renormalization group (RG) evolution in Laplace space, we perform the resummation of logarithmically enhanced corrections in the dijet limit, $T\to 1$ to next-to-next-to-leading logarithmic (NNLL) accuracy. We independently derive the two-loop soft function for the thrust distribution and extract an analytical expression for the NNLL resummation coefficient $g_3$. To combine the resummed expressions with the fixed-order results, we derive the $\log(R)$-matching and $R$-matching of the NNLL approximation to the fixed-order NNLO distribution.Comment: 50 pages, 12 figures, 1 table. Few minor changes. Version accepted for publication in JHE

Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable pre-clinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer. Mesenchymal cells which line the cochlear perilymphatic compartment can be selectively transfected with (naked) plasmid DNA using array - based gene electrotransfer, termed ‘close-field electroporation’. This technology is able to drive expression of brain derived neurotrophic factor (BDNF) in the deafened guinea pig model, causing re-growth of the spiral ganglion peripheral neurites towards the mesenchymla cells, and hence into close proximity with cochlear implant electrodes within scala tympani. This was associated with functional enhancement of the cochlear implant neural interface (lower neural recruitment thresholds and expanded dynamic range, measured using electrically - evoked auditory brainstem responses). The basis for the efficiency of close-field electroporation arises from the compression of the electric field in proximity to the ganged cochlear implant electrodes. The regions close to the array with highest field strength corresponded closely to the distribution of bioreporter cells (adherent human embryonic kidney (HEK293)) expressing green fluorescent reporter protein (GFP) following gene electrotransfer. The optimization of the gene electrotransfer parameters using this cell-based model correlated closely with in vitro and in vivo cochlear gene delivery outcomes. The migration of the cochlear implant electrode array-based gene electrotransfer platform towards a clinical trial for neurotrophin-based enhancement of cochlear implants is supported by availability of a novel regulatory compliant mini-plasmid DNA backbone (pFAR4; plasmid Free of Antibiotic Resistance v.4) which could be used to package a ‘humanized’ neurotrophin expression cassette. A reporter cassette packaged into pFAR4 produced prominent GFP expression in the guinea pig basal turn perilymphatic scalae. More broadly, close-field gene electrotransfer may lend itself to a spectrum of potential DNA therapeutics applications benefitting from titratable, localised, delivery of naked DNA, for gene augmentation, targeted gene regulation, or gene substitution strategies

Absence of an association of human polyomavirus and papillomavirus infection with lung cancer in China: a nested case–control study

BACKGROUND: Studies of human polyomavirus (HPyV) infection and lung cancer are limited and those regarding the association of human papillomavirus (HPV) infection and lung cancer have produced inconsistent results. METHODS: We conducted a nested case–control study to assess the association between incident lung cancer of various histologies and evidence of prior infection with HPyVs and HPVs. We selected serum from 183 cases and 217 frequency matched controls from the Yunnan Tin Miner’s Cohort study, which was designed to identify biomarkers for early detection of lung cancer. Using multiplex liquid bead microarray (LBMA) antibody assays, we tested for antibodies to the VP1 structural protein and small T antigen (ST-Ag) of Merkel cell, KI, and WU HPyVs. We also tested for antibodies against HPV L1 structural proteins (high-risk types 16, 18, 31, 33, 52, and 58 and low-risk types 6 and 11) and E6 and E7 oncoproteins (high risk types 16 and 18). Measures of antibody reactivity were log transformed and analyzed using logistic regression. RESULTS: We found no association between KIV, WUV, and MCV antibody levels and incident lung cancer (P-corrected for multiple comparisons >0.10 for all trend tests). We also found no association with HPV-16, 18, 31, 33, 52, and 58 seropositivity (P-corrected for multiple comparisons >0.05 for all). CONCLUSIONS: Future studies of infectious etiologies of lung cancer should look beyond HPyVs and HPVs as candidate infectious agents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2381-3) contains supplementary material, which is available to authorized users

Predicting disease-associated substitution of a single amino acid by analyzing residue interactions

<p>Abstract</p> <p>Background</p> <p>The rapid accumulation of data on non-synonymous single nucleotide polymorphisms (nsSNPs, also called SAPs) should allow us to further our understanding of the underlying disease-associated mechanisms. Here, we use complex networks to study the role of an amino acid in both local and global structures and determine the extent to which disease-associated and polymorphic SAPs differ in terms of their interactions to other residues.</p> <p>Results</p> <p>We found that SAPs can be well characterized by network topological features. Mutations are probably disease-associated when they occur at a site with a high centrality value and/or high degree value in a protein structure network. We also discovered that study of the neighboring residues around a mutation site can help to determine whether the mutation is disease-related or not. We compiled a dataset from the Swiss-Prot variant pages and constructed a model to predict disease-associated SAPs based on the random forest algorithm. The values of total accuracy and MCC were 83.0% and 0.64, respectively, as determined by 5-fold cross-validation. With an independent dataset, our model achieved a total accuracy of 80.8% and MCC of 0.59, respectively.</p> <p>Conclusions</p> <p>The satisfactory performance suggests that network topological features can be used as quantification measures to determine the importance of a site on a protein, and this approach can complement existing methods for prediction of disease-associated SAPs. Moreover, the use of this method in SAP studies would help to determine the underlying linkage between SAPs and diseases through extensive investigation of mutual interactions between residues.</p

Quantitative real-time RT-PCR of CD24 mRNA in the detection of prostate cancer

BACKGROUND: Gene expression profiling has recently shown that the mRNA for CD24 is overexpressed in prostate carcinomas (Pca) compared to benign or normal prostate epithelial tissues. Immunohistochemical studies have reported the usefulness of anti-CD24 for detecting prostate cancer over the full range of prostate specimens encountered in surgical pathology, e.g. needle biopsies, transurethral resection of prostate chips, or prostatectomies. It is a small mucin-like cell surface protein and thus promises to become at least a standard adjunctive stain for atypical prostate biopsies. We tested the usefulness of real-time RT-PCR for specific and sensitive detection of CD24 transcripts as a supplementary measure for discriminating between malignant and benign lesions in prostatic tissues. METHODS: Total RNA was isolated from snap-frozen chips in 55 cases of benign prostatic hyperplasia (BPH) and from frozen sections in 59 prostatectomy cases. The latter contain at least 50% malignant epithelia. Relative quantification of CD24 transcripts was performed on the LightCycler instrument using hybridization probes for detection and porphobilinogen deaminase transcripts (PBGD) for normalization. RESULTS: Normalized CD24 transcript levels showed an average 2.69-fold increase in 59 Pca-cases (mean 0.21) when compared to 55 cases of BPH (mean 0.08). This difference was highly significant (p < 0.0001). The method has a moderate specificity (47.3%) but a high sensitivity (86.4%) if the cutoff is set at 0.0498. CD24 expression levels among Pca cases were not statistically associated with the tumor and lymph-node stage, the grading (WHO), the surgical margins, or the Gleason score. CONCLUSION: The present study demonstrates the feasibility of quantitative CD24 RNA transcript detection in prostatic tissues even without previous laser microdissection

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Positive correlation between Merkel cell polyomavirus viral load and capsid-specific antibody titer

Merkel cell polyomavirus (MCPyV or MCV) is the first polyomavirus to be clearly implicated as a causal agent underlying a human cancer, Merkel cell carcinoma (MCC). Infection with MCPyV is common in the general population, and a majority of adults shed MCPyV from the surface of their skin. In this study, we quantitated MCPyV DNA in skin swab specimens from healthy volunteers sampled at different anatomical sites over time periods ranging from 3 months to 4 years. The volunteers were also tested using a serological assay that detects antibodies specific for the MCPyV virion. There was a positive correlation between MCPyV virion-specific antibody titers and viral load at all anatomical sites tested (dorsal portion of the hands, forehead, and buttocks) (Spearman’s r 0.644, P < 0.0001). The study results are consistent with previous findings suggesting that the skin is primary site of chronic MCPyV infection in healthy adults and suggest that the magnitude of an individual’s seroresponsiveness against the MCPyV virion generally reflects the overall MCPyV DNA load across wide areas of the skin. In light of previous reports indicating a correlation between MCC and strong MCPyV-specific seroresponsiveness, this model suggests that poorly controlled chronic MCPyV infection might be a risk factor in the development of MCC

SNP assay to detect the ‘Hyuuga’ red-brown lesion resistance gene for Asian soybean rust

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi Syd., has the potential to become a serious threat to soybean, Glycine max L. Merr., production in the USA. A novel rust resistance gene, Rpp?(Hyuuga), from the Japanese soybean cultivar Hyuuga has been identified and mapped to soybean chromosome 6 (Gm06). Our objectives were to fine-map the Rpp?(Hyuuga) gene and develop a high-throughput single nucleotide polymorphism (SNP) assay to detect this ASR resistance gene. The integration of recombination events from two different soybean populations and the ASR reaction data indicates that the Rpp?(Hyuuga) locus is located in a region of approximately 371 kb between STS70887 and STS70923 on chromosome Gm06. A set of 32 ancestral genotypes which is predicted to contain 95% of the alleles present in current elite North American breeding populations and the sources of the previously reported ASR resistance genes (Rpp1, Rpp2, Rpp3, Rpp4, Rpp5, and rpp5) were genotyped with five SNP markers. We developed a SimpleProbe assay based on melting curve analysis for SNP06-44058 which is tighly linked to the Rpp?(Hyuuga) gene. This SNP assay can differentiate plants/lines that are homozygous/homogeneous or heterozygous/heterogeneous for the resistant and susceptible alleles at the Rpp?(Hyuuga) locus