Utility of Three-Protein Panels in the Separation of Aggressive Prostate Cancer from Non-Aggressive Tumors

Background Prostate cancer (PCa) is a heterogeneous group of tumors, including non-aggressive (NAG) and aggressive (AG) subtypes, with variable clinical outcomes. We assessed the diagnostic utility of selected protein markers to identify AG tumors. Methods The TMA was constructed, including NAG and AG. 12 protein markers were evaluated using the TMA by IHC stains. The makers were also evaluated for their potential utility as single or panels for distinguishing AG from NAG tumors. Results The higher expressions of four protein markers, including prostate specific membrane antigen (PSMA), phospho-EGFR, androgen receptor (AR), and P16, were identified in AG tumors of Gleason score 4 and 5. In contrast, Galectin-3, DPP4 and MAN1B1 revealed stronger staining patterns in NAG tumors. Sensitivity and specificity of individual marker varied widely. In tow-marker panels, especially in the panel of DPP4 and PSMA, the specificity was 38.46% at 95% sensitivity. To further improve the detection ability, we combined DPP4 and PSMA with either Galectin-3 or phospho-EGFR into three-marker panels. The specificity achieved >46% at 95% sensitivity and AUC was >0.85. Conclusions Our panels can be used to improve the separation of AG from NAG tumor and to add in the optimization of the treatment strategy for patients.

Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10−05, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10−05, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10−05, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10−05, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10−05, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10−02, p = 5.1 × 10−03, p = 1.2 × 10−02, respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.

Phylogenetic Revision of the Genus Aliivibrio: Intra- and Inter-Species Variance Among Clusters Suggest a Wider Diversity of Species

Genus Aliivibrio is known to harbor species exhibiting bioluminescence as well as pathogenic behavior affecting the fish farming industry. Current phylogenetic understanding of Aliivibrio has largely remained dormant after reclassification disentangled it from the Vibrio genus in 2007. There is growing evidence of wider diversity, but until now the lack of genomes and selective use of type strains have limited the ability to compare and classify strains firmly. In this study, a total of 143 bacterial strains, including 51 novel sequenced strains, were used to strengthen phylogenetic relationships in Aliivibrio by exploring intra-species and inter-species relations. Multilocus sequence analysis (MLSA), applying the six housekeeping genes 16S ribosomal RNA (rRNA), gapA, gyrB, pyrH, recA, and rpoA, inferred 12 clades and a singular branch in Aliivibrio. Along with four new phylogenetic clades, the MLSA resolved prior inconsistencies circumscribing Aliivibrio wodanis and formed a unique clade we propose as the novel species Aliivibrio sp. “friggae.” Furthermore, phylogenetic assessment of individual marker genes showed gyrB, pyrH, and recA superior to the 16S rRNA gene, resolving accurately for most species clades in Aliivibrio. In this study, we provide a robust phylogenetic groundwork for Aliivibrio as a reference point to classification of species.

GENETIC VARIABILITY OF SIRE BULLS IN THE ARKHANGELSK POPULATION OF THE KHOLMOGORY BREED WHEN OBSERVED OVER GENERATIONS

Проблема и цель. Целью настоящего исследования являлось изучение и анализ генетической структуры потомства у быков-производителей по поколениям (периодам наблюдений). Мониторинг генетической структуры холмогорской породы крупного рогатого скота позволяет провести исследования, дающие информацию во временной шкале по частотам генотипов групп крови для холмогорской породы; осуществлено наблюдение для интервалов наблюдений. Методология. Проведены исследования частот аллелей ЕАВ-локуса. Для холмогорской породы по быкам-производителям определена динамика формирования современной генетической структуры архангельской популяции. Определены частотные характеристики аллелей и анализ динамики их изменения. Результаты. Исследования показали, что аллелофонд холмогорской породы сбалансирован, но отмечена динамика убыли и возрастания частот отдельных аллелей-маркеров, которые свойственны только холмогорской породе крупного рогатого скота. Наблюдалась также достаточно высокая чувствительность и специфичность тестирования. Отмечено, что степень гомозиготности в разрезе анализируемых поколений быков-производителей имеет тенденцию к снижению с 11,4 % (1-й интервал наблюдений) до 5,7 % (9-й интервал). С другой стороны, количество эффективных аллелей – к росту – с 8,8 до 17,6 %. Наибольшее генетическое расстояние имеют чистокровные быки-производители холмогорской породы первого-второго интервалов наблюдений с голштинизированными восьмого-девятого интервалов (расстояния 0,25 и 0,23; 0,27 и 0,47 соответственно). Продолжающееся дистанцирование современных быков-производителей от предыдущих поколений подтверждает проведение поглотительного скрещивания и смещение породы в сторону голштинской с течением времени и в перспективе развития. Заключение. В результате работы проведена оценка генетической структуры холмогорской породы КРС Архангельской популяции и установлено, что в процессе проводимых селекционных мероприятий у быков холмогорской породы отмечается устойчивое увеличение числа аллелей, а чистопородные быки генетически дистанцируются от быков, межпородно гибридизованных с голштинской породой, в ряду поколений с течением времени. Выявлено, что наиболее генетически отдаленными являются чистопородные и голштинизированные быки-производители. Kholmogorskaya breed, Holsteinized stud bulls, allele pool, alleles of the EAB locus blood groups, homozygosity, genetic similarity, genetic distance Problems and purpose of investigation. The purpose of this research was to study and analyze the genetic structure of the bulls ofspring of stud bulls by generations (observation periods). Monitoring of the genetic structure of Kholmogorskaya breed made it possible to carry out studies that provide information on the time scale on the frequencies of genotypes of blood groups for Kholmogorskaya breed. The checkup of the observation intervals was carried out. Methodology. The studies of the allele frequencies of the EAB-locus were carried out. For Kholmogorskaya breed stud bulls, the dynamics of formation of the modern genetic structure of the Arkhangelsk population was determined. The frequency characteristics of the alleles and the analysis of the dynamics of their change were determined. Results. Studies showed that the allele pool of Kholmogorskaya breed was balanced, but the dynamics of the decrease and increase in the frequencies of individual marker alleles, which were characteristic only of Kholmogorskaya breed of cattle, were noted, and a sufciently high sensitivity and specifcs of testing wereobserved. It was noted that the degree of homozygosity in the context of the analyzed generations of stud bulls tended to decrease from 11.4 % (1st observation interval) to 5.7 % (9th interval). On the other hand, the number of efective alleles increased from 8.8 to 17.6 %. The maximal genetic distance was in purebred stud bulls of Kholmogorskaya breed of the frst and second observation intervals with Holsteinized bulls of the eighth to ninth generation intervals (distances 0.25 and 0.23; 0.27 and 0.47, respectively). The continuing distancing of modern stud bulls from previous generations confrmed accumulation cross breeding and the shift of the breed towards Holstein over time and in the future. Conclusion. As a result of the work, the assessment of the genetic structure of Kholmogorskaya breed of the Arkhangelsk population was carried out and it was found that in the process of breeding activities in the bulls of Kholmogorskaya breed there was a steady increase in the number of alleles, and purebred bulls genetically distance themselves from bulls interbreed hybridized with Holstein breed in a number of generations over time. It was revealed that the most genetically distant animals were purebred and Holsteinized stud bulls.

Plasma Matrilysins MMP-7 and MMP-26 Concentrations as Diagnostic Biomarkers for Breast Cancer Patients

Background: Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are the one of the group of MMPs that could represent potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the a diagnostic utility of studied matrilysins in BC patients. Methods: The study group consisted of 120 patients with BC, the control group consisted of 40 patients with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by Enzyme-Linked Immunosorbent Assay, CA 15-3 by Chemiluminescent Microparticle Immunoassay.Results: The plasma levels of MMP-7 were significantly higher in the entire BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were the highest in the III and IV stage of disease. The highest diagnostic sensitivity was observed in the III and IV stage of cancer for set of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters in all studied BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) set of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in III and IV stage. Also individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of disease. Conclusions: Data suggested that MMP-7 can be considered as additional marker improving diagnostic utility of CA 15-3 in early stages of BC patients. Therefore, combined analysis of MMP-7 and MMP-26 with CA 15-3 might be useful in detection of disease progression. Future investigation is needed to evaluate whether matrilysins might be a potential markers improving diagnosis of BC.

Stumbling over History: Stolpersteine and the Performance of Memory in Spain's Streets

The Stolpersteine (‘stumbling stones’) memorial project commemorates victims of Nazi violence and the Holocaust through an individual marker installed outside the last willing residence before deportation and execution. The Stolpersteine project has spread throughout Europe, providing an urban topography of sites where traumatic events occurred. Because Stolpersteine are placed in public streets, they create performance possibilities, inviting passing pedestrians to engage in past history and trauma. As the project grows throughout Europe, however, the universality of the stones abuts with the specificity of local history and memory. This article considers the Stolpersteine installed in the Catalan city of Manresa. These stones, representing twenty-eight Spanish Republicans who were interned at the Mauthausen-Gusen concentration camp, are framed by a Catalan-language audio guide that directly points to the collaboration of the Francisco Franco dictatorship with Nazi Germany. In so doing, the stones in Spain also stand for violence meted out during the Spanish Civil War and the Franco dictatorship.

Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion

Background: Tumour markers in pleural fluid and their diagnostic value are subject to debate. Although there are several studies on this topic, standardized cut-off values do not exist. In this study we investigated the potential of a ratio of carcinoembryonic antigen (CEA) in pleural fluid and serum, serving as an individual marker for pleural cancer manifestation. Methods: A total of 201 consecutive patients with unclear pleural effusion were included in the study; 98 were diagnosed with malignant pleural effusion and 103 had an effusion due to other, benign reasons. CEA levels in pleural fluid and serum were measured. Results: By using receiver operating characteristics analysis, at the cut-off of 1.0, the CEA ratio showed a specificity of 92% and sensitivity of 85%, with a positive predictive value of 91% and a negative predictive value of 87%. These results are higher than in previous investigations on different pleural tumour markers and their combination. Conclusions: The CEA ratio is a useful tool in predicting pleural carcinosis. Elevated results in cytology-negative patients should lead to further investigations, such as repeated cytological examination or thoracoscopy.

Genotype Fingerprints Enable Fast and Private Comparison of Genetic Testing Results for Research and Direct-to-Consumer Applications

Genetic testing has expanded out of the research laboratory into medical practice and the direct-to-consumer market. Rapid analysis of the resulting genotype data now has a significant impact. We present a method for summarizing personal genotypes as ‘genotype fingerprints’ that meets these needs. Genotype fingerprints can be derived from any single nucleotide polymorphism-based assay, and remain comparable as chip designs evolve to higher marker densities. We demonstrate that these fingerprints support distinguishing types of relationships among closely related individuals and closely related individuals from individuals from the same background population, as well as high-throughput identification of identical genotypes, individuals in known background populations, and de novo separation of subpopulations within a large cohort through extremely rapid comparisons. Although fingerprints do not preserve anonymity, they provide a useful degree of privacy by summarizing a genotype while preventing reconstruction of individual marker states. Genotype fingerprints are therefore well-suited as a format for public aggregation of genetic information to support ancestry and relatedness determination without revealing personal health risk status.

Genotype Fingerprints Enable Fast and Private Comparison of Genetic Testing Results for Research and Direct-to-Consumer Applications

Genetic testing has expanded out of the research laboratory into medical practice and the direct-to-consumer market, and rapid analysis of the resulting genotype data can now have significant impact. We present a method for summarizing personal genotypes as ‘genotype fingerprints’ that meet these needs. Genotype fingerprints can be derived from any single nucleotide polymorphism (SNP)-based assay, and remain comparable as chip designs evolve to higher marker densities. We demonstrate that they support distinguishing types of relationships among closely related individuals and closely related individuals from individuals from the same background population, as well as high-throughput identification of identical genotypes, individuals in known background populations, and de novo separation of subpopulations within a large cohort through extremely rapid comparisons. While fingerprints do not preserve anonymity, they provide a useful degree of privacy by summarizing a genotype in a way that prevents reconstruction of individual marker states. Genotype fingerprints are therefore well-suited as a format for public aggregation of genetic information to support ancestry and relatedness determination without revealing personal health risk status.