PEP A9, a new,unstable variant in the peptidase a system

Summary A rare peptidase A variant, tentatively designated PEP A⁹, was observed in six members of a German family, indicating autosomal codominant inheritance. The electrophoretic mobility is similar to that of PEP A 3-1, but it has very low in vivo stability. There is no apparent association with a disease state. A simple and sensitive staining reagent for PEP A was found in o-phthalaldehyde.     

Assessing conservation priorities of threatened medicinal plants in China: A new comprehensive phylogenetic scoring system

Over-harvesting, habitat loss and fragmentation, and biological invasions have led to a sharp decline in wild medicinal plants population in China, where they are an essential component of traditional medicine and used widely. The current national list of protected medicinal materials, the State Key-protected Wild Medicinal Species List (SKPWMSL), which has not been revised for 30 years, is in urgent need of an update. This study proposes a new scoring system with seven indicators that set the conservation priorities of threatened medicinal plants. The advantages of our approach include: (i) quantitative methods with high repeatability and comparability; and (ii) consideration of the evolutionary history of medicinal species. After assessing 911 threatened medicinal angiosperms in China, we identified 112 species as key medicinal plants for conservation priority (KMPCP). We suggest promoting the SKPWMSL with KMPCP as a supplement and update. Meanwhile, our scoring system will improve the future setting of conservation priority and can be extended to other countries or regions.     

Indications for admission to a coronary care unit in patients with unstable angina.

One hundred cases with an admission diagnosis of acute coronary insufficiency or unstable angina were reviewed to establish criteria for admission to a coronary care unit. Myocardial infarction was subsequently diagnosed in 20 of the patients. Ventricular tachycardia occurred in 16 patients and ventricular fibrillation in 1 patient. Clinical features found to predict an increased risk of myocardial infarction included chest pain for more than 30 minutes within 24 hours prior to admission, new nonspecific electrocardiographic abnormalities consistent with ischemia, and diaphoresis. All patients with ventricular tachydysrhythmias had presented with both prolonged chest pain prior to admission and new electrocardiographic changes. The sensitivity, specificity and predictive value of various clinical criteria for identifying patients likely to have a myocardial infarction were calculated, and criteria with very high (greater than 90%) sensitivity were identified. These could be used to establish which patients are at increased risk of myocardial infarction and therefore require admission to a coronary care unit.     

A new scoring function for top-down spectral deconvolution

Background

Top-down mass spectrometry plays an important role in intact protein identification and characterization. Top-down mass spectra are more complex than bottom-up mass spectra because they often contain many isotopomer envelopes from highly charged ions, which may overlap with one another. As a result, spectral deconvolution, which converts a complex top-down mass spectrum into a monoisotopic mass list, is a key step in top-down spectral interpretation.

Results

In this paper, we propose a new scoring function, L-score, for evaluating isotopomer envelopes. By combining L-score with MS-Deconv, a new software tool, MS-Deconv+, was developed for top-down spectral deconvolution. Experimental results showed that MS-Deconv+ outperformed existing software tools in top-down spectral deconvolution.

Conclusions

L-score shows high discriminative ability in identification of isotopomer envelopes. Using L-score, MS-Deconv+ reports many correct monoisotopic masses missed by other software tools, which are valuable for proteoform identification and characterization.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1140) contains supplementary material, which is available to authorized users.     

A new scoring system using multiple immunohistochemical markers for diagnosis of uterine smooth muscle tumors

The diagnosis of uterine smooth muscle neoplasms by light microscopy is difficult. Multiple classification schemes have been proposed based on mitotic rate, nuclear atypia, and the presence or absence of necrosis. None of these classification systems has been entirely successful. This study was undertaken to evaluate the use of selected immunohistochemical and histochemical markers in differentiating these tumors, in addition to accepted morphologic criteria. Ten cases of each of the following: leiomyosarcomas (LMS), atypical leiomyomas (AL), cellular leiomyomas (CL) and usual leiomyomas (UL), were classically evaluated for histological diagnosis and were stained for Ki-67 (MIB-1), bcl- 2 and p53 using monoclonal antibodies and the avidin-biotin peroxidase method, and argyrophilic nucleolar organizer region (AgNORs). The number of stained cells was counted in the most positively stained region in a 4 mm2 square cover glass mounted on each slide. The mean value was calculated for each group of tumors. The data for Ki-67 (MIB- 1), bcl-2, p53 and AgNOR staining respectively, were significantly higher in LMS by comparison to UL, CL or AL. Because many singular cases had superimposed data being difficult to diagnose, a new scoring system for pathological evaluation was created. The results obtained by this scoring system suggest that immunohistochemical markers Ki-67 (MIB-1), bcl-2, p53 together with the AgNOR staining could be useful, by the scoring system, as an adjunct to the current accepted morphologic criteria in differentiating smooth muscle tumors of the uterus.     

An update to MitoTool: Using a new scoring system for faster mtDNA haplogroup determination

The determination of human mitochondrial DNA (mtDNA) haplogroups is not only crucial in anthropological and forensic studies, but is also helpful in the medical field to prevent establishment of wrong disease associations. In recent years, high-throughput technologies and the huge amounts of data they create, as well as the regular updates to the mtDNA phylogenetic tree, mean that there is a need for an automated approach which can make a speedier determination of haplogroups than can be made by using the traditional manual method. Here, we update the MitoTool (www.mitotool.org) by incorporating a novel scoring system for the determination of mtDNA into haplogroups, which has advantages on speed, accuracy and ease of implementation. In order to make the access to MitoTool easier, we also provide a stand-alone version of the program that will run on a local computer and this version is freely available at the MitoTool website.     

Development of a risk scoring system for patients with papillary thyroid cancer

As the importance of personalized therapeutics in aggressive papillary thyroid cancer (PTC) increases, accurate risk stratification is required. To develop a novel prognostic scoring system for patients with PTC (n = 455), we used mRNA expression and clinical data from The Cancer Genome Atlas. We performed variable selection using Network‐Regularized high‐dimensional Cox‐regression with gene network from pathway databases. The risk score was calculated using a linear combination of regression coefficients and mRNA expressions. The risk score and clinical variables were assessed by several survival analyses. The risk score showed high discriminatory power for the prediction of event‐free survival as well as the presence of metastasis. In multivariate analysis, the risk score and presence of metastasis were significant risk factors among the clinical variables that were examined together. In the current study, we developed a risk scoring system that will help to identify suitable therapeutic options for PTC.     

A modified scoring system to describe gross pathology in the rabbit model of tuberculosis

Background  

The rabbit model is an ideal means to study the pathogenesis of tuberculosis due to its semblance to the disease in humans. We have previously described the results using a bronchoscopic route of infection with live bacilli as a reliable means of generating lung cavities in sensitized rabbits. The role of sensitization in the development of disease outcomes has been well established in several animal models. We have described here the varying gross pathology that result from lack of sensitization with heat-killed M. bovis prior to high-dose bronchoscopic infection with live bacilli.     

A bar code scoring system for behavioral research

A data collection method using lap-top computers and bar codes was developed and used in behavioral research. The studies involved several common sampling methods and a variety of study subjects. Advantages and restrictions of the system are discussed. Overall, we found bar code technology to increase both efficiency and accuracy of behavioral data collection.     

New scoring system to identify RNA G-quadruplex folding

G-quadruplexes (G4s) are non-canonical structures involved in many important cellular processes. To date, the prediction of potential G-quadruplex structures (PG4s) has been based almost exclusively on the sequence of interest agreeing with the algorithm G_x-N-_1–7-G_x-N_1–7-G_x-N_1–7-G_x (where x ≥ 3 and N = A, U, G or C). However, many sequences agreeing with this algorithm do not form G4s and are considered false-positive predictions. Here we show the RNA PG4 candidate in the 3′-untranslated region (UTR) of the TTYH1 gene to be one such false positive. Specifically, G4 folding was observed to be inhibited by the presence of multiple-cytosine tracks, located in the candidate’s genomic context, that adopted a Watson–Crick base-paired structure. Clearly, the neighbouring sequences of a PG4 may influence its folding. The secondary structure of 12 PG4 motifs along with either 15 or 50 nucleotides of their upstream and downstream genomic contexts were evaluated by in-line probing. Data permitted the development of a scoring system for the prediction of PG4s taking into account the effect of the neighbouring sequences. The accuracy of this scoring system was assessed by probing 14 other novel PG4 candidates retrieved in human 5′-UTRs. This new scoring system can be used, in combination with the standard algorithm, to better predict the folding of RNA G4s.     

A simple scoring system to differentiate between relapse and re-infection in patients with recurrent melioidosis

Background

Melioidosis is an important cause of morbidity and mortality in East Asia. Recurrent melioidosis occurs in around 10% of patients following treatment either because of relapse with the same strain or re-infection with a new strain of Burkholderia pseudomallei. Distinguishing between the two is important but requires bacterial genotyping. The aim of this study was to develop a simple scoring system to distinguish re-infection from relapse.

Methods

In a prospective study of 2,804 consecutive adult patients with melioidosis presenting to Sappasithiprasong Hospital, NE Thailand, between1986 and 2005, there were 141 patients with recurrent melioidosis with paired strains available for genotyping. Of these, 92 patients had relapse and 49 patients had re-infection. Variables associated with relapse or re-infection were identified by multivariable logistic regression and used to develop a predictive model. Performance of the scoring system was quantified with respect to discrimination (area under receiver operating characteristic curves, AUC) and categorization (graphically). Bootstrap resampling was used to internally validate the predictors and adjust for over-optimism.

Findings

Duration of oral antimicrobial treatment, interval between the primary episode and recurrence, season, and renal function at recurrence were independent predictors of relapse or re-infection. A score of <5 correctly identified relapse in 76 of 89 patients (85%), whereas a score ≥5 correctly identified re-infection in 36 of 52 patients (69%). The scoring index had good discriminative power, with a bootstrap bias-corrected AUC of 0.80 (95%CI: 0.73–0.87).

Conclusions

A simple scoring index to predict the cause of recurrent melioidosis has been developed to provide important bedside information where rapid bacterial genotyping is unavailable.     

T helper cell related interleukins and the angiographic morphology in unstable angina

Angiographically visible complex lesions, associated with disrupted plaques and intraluminal thrombus, are more common in unstable angina (UA). The aim of our study was to evaluate the relationship between the complex lesions and the T helper cells related Interleukins (IL). We analyzed the concentrations of IL-10, IL-12, IL-18 using ELISA and that of hsCRP using Latex particle enhanced Immunoturbidimetry in 50 patients of UA. Thirty-one of these patients had complex lesions and 19 had simple lesions as visible during coronary angiography. We further compared them with 30 control subjects having no evidence of coronary artery diseases. The levels of IL-12 in patients having complex lesions tended to be higher than in those having simple lesions and levels of IL-10 tended to be lower in the former than the latter, but the differences were not statistically significant. The patients with complex lesions showed significantly higher concentrations of IL-18 as compared to those having simple lesions. Furthermore, IL-18 was found to be independent predictor for the complex lesion morphology in UA patients. These findings suggest that disrupted plaques and intraluminal thrombus, angiographically visible as complex lesions are associated with increased concentrations of T helper 1 cell related interleukins, mainly IL-18, and IL-18 being a possible bio-marker for risk stratification in UA.     

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina

Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina (UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex- and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients: the adjusted odds ratios (ORs) per standard deviation increase in Shannon and Simpson indices were 1.30 (95% confidence interval, 1.01–1.70) and 1.36 (1.05–1.81), respectively. Two common species (depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis; P ≤ 0.002) and three rare species (depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45; P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of L-phenylalanine degradation (P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients (OR = 2.76 [1.17–8.16]). Moreover, Streptococcus parasanguinis was negatively correlated with fecal citrulline (Spearman's r_s = ?0.470, P = 0.009), a metabolite depleted in UA patients (OR = 0.26 [0.08–0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.