Gel-Based Proteomics of Clinical Samples Identifies Potential Serological Biomarkers for Early Detection of Colorectal Cancer

The burden of colorectal cancer (CRC) is considerable—approximately 1.8 million people are diagnosed each year with CRC and of these about half will succumb to the disease. In the case of CRC, there is strong evidence that an early diagnosis leads to a better prognosis, with metastatic CRC having a 5-year survival that is only slightly greater than 10% compared with up to 90% for stage I CRC. Clearly, biomarkers for the early detection of CRC would have a major clinical impact. We implemented a coherent gel-based proteomics biomarker discovery platform for the identification of clinically useful biomarkers for the early detection of CRC. Potential protein biomarkers were identified by a 2D gel-based analysis of a cohort composed of 128 CRC and site-matched normal tissue biopsies. Potential biomarkers were prioritized and assays to quantitatively measure plasma expression of the candidate biomarkers were developed. Those biomarkers that fulfilled the preset criteria for technical validity were validated in a case-control set of plasma samples, including 70 patients with CRC, adenomas, or non-cancer diseases and healthy individuals in each group. We identified 63 consistently upregulated polypeptides (factor of four-fold or more) in our proteomics analysis. We selected 10 out of these 63 upregulated polypeptides, and established assays to measure the concentration of each one of the ten biomarkers in plasma samples. Biomarker levels were analyzed in plasma samples from healthy individuals, individuals with adenomas, CRC patients, and patients with non-cancer diseases and we identified one protein, tropomyosin 3 (Tpm3) that could discriminate CRC at a significant level (p = 0.0146). Our results suggest that at least one of the identified proteins, Tpm3, could be used as a biomarker in the early detection of CRC, and further studies should provide unequivocal evidence for the real-life clinical validity and usefulness of Tpm3

The price of a vote: Diseconomy in proportional elections

The increasing cost of electoral campaigns raises the need for effective campaign planning and a precise understanding of the return of such investment. Interestingly, despite the strong impact of elections on our daily lives, how this investment is translated into votes is still unknown. By performing data analysis and modeling, we show that top candidates spend more money per vote than the less successful and poorer candidates, a relation that discloses a diseconomy of scale. We demonstrate that such electoral diseconomy arises from the competition between candidates due to inefficient campaign expenditure. Our approach succeeds in two important tests. First, it reveals that the statistical pattern in the vote distribution of candidates can be explained in terms of the independently conceived, but similarly skewed distribution of money campaign. Second, using a heuristic argument, we are able to explain the observed turnout percentage for a given election of approximately 63% in average. This result is in good agreement with the average turnout rate obtained from real data. Due to its generality, we expect that our approach can be applied to a wide range of problems concerning the adoption process in marketing campaigns

Raman and infrared spectroscopy of Sr2B′UO6 (B′ = Ni; Co) double perovskites

Temperature dependent normal modes and lattice thermal expansion of Sr 2B′UO6 (B′ = Ni, Co) double perovskites were investigated by Raman/infrared spectroscopies and synchrotron X-ray diffraction, respectively. Monoclinic crystal structures with space group P21/n were confirmed for both compounds, with no clear structural phase transition between 10 and 400 K. As predicted for this structure, the first-order Raman and infrared spectra show a plethora of active modes. In addition, the Raman spectra reveal an enhancement of the integrated area of an oxygen stretching mode, which is also observed in higher-order Raman modes, and an anomalous softening of ∼1 cm-1 upon cooling below T* ∼ 300 K. In contrast, the infrared spectra show conventional temperature dependence. The band profile phonon anomalies are possibly related to an unspecified electronic property of Sr2B′UO6 (B′ = Ni, Co).Centro de Química Inorgánic

Raman and infrared spectroscopy of Sr2B′UO6 (B′ = Ni; Co) double perovskites

Temperature dependent normal modes and lattice thermal expansion of Sr 2B′UO6 (B′ = Ni, Co) double perovskites were investigated by Raman/infrared spectroscopies and synchrotron X-ray diffraction, respectively. Monoclinic crystal structures with space group P21/n were confirmed for both compounds, with no clear structural phase transition between 10 and 400 K. As predicted for this structure, the first-order Raman and infrared spectra show a plethora of active modes. In addition, the Raman spectra reveal an enhancement of the integrated area of an oxygen stretching mode, which is also observed in higher-order Raman modes, and an anomalous softening of ∼1 cm-1 upon cooling below T* ∼ 300 K. In contrast, the infrared spectra show conventional temperature dependence. The band profile phonon anomalies are possibly related to an unspecified electronic property of Sr2B′UO6 (B′ = Ni, Co).Centro de Química Inorgánic

Detection and identification of Xanthomonas pathotypes associated with citrus diseases using comparative genomics and multiplex PCR

Background. In Citrus cultures, three species of Xanthomonas are known to cause distinct diseases. X. citri subsp. citri patothype A, X. fuscans subsp. aurantifolii pathotypes B and C, and X. alfalfae subsp. citrumelonis, are the causative agents of cancrosis A, B, C, and citrus bacterial spots, respectively. Although these species exhibit different levels of virulence and aggressiveness, only limited alternatives are currently available for proper and early detection of these diseases in the fields. The present study aimed to develop a new molecular diagnostic method based on genomic sequences derived from the four species of Xanthomonas. Results. Using comparative genomics approaches, primers were synthesized for the identification of the four causative agents of citrus diseases. These primers were validated for their specificity to their target DNA by both conventional and multiplex PCR. Upon evaluation, their sensitivity was found to be 0.02 ng/mu l in vitro and 1.5 x 10(4) CFU ml(-1) in infected leaves. Additionally, none of the primers were able to generate amplicons in 19 other genomes of Xanthomonas not associated with Citrus and one species of Xylella, the causal agent of citrus variegated chlorosis (CVC). This denotes strong specificity of the primers for the different species of Xanthomonas investigated in this study. Conclusions. We demonstrated that these markers can be used as potential candidates for performing in vivo molecular diagnosis exclusively for citrus-associated Xanthomonas. The bioinformatics pipeline developed in this study to design specific genomic regions is capable of generating specific primers. It is freely available and can be utilized for any other model organism.7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIG481226/2013-3CFP 51/2013; 3385/2013APQ-02387-1

Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure

BACKGROUND AND AIMS: Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterise the cardiac complications of EMD variants. METHODS: Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidence in male and female variant-carriers was determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared to consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). RESULTS: Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers (mean [SD] ages 33.4 [13.3] and 43.3 [16.8] years, respectively). Nine (23.6%) males developed MVA and five (13.2%) developed ESHF during a median [IQR] follow-up of 65.0 [24.3, 109.5] months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median [IQR] age of 58.6 [53.2, 60.4] years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank p = 0.49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank p = 0.09). CONCLUSIONS: Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease

Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations

Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer’s disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (ρ = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD

Assessing the symptoms of Internet Gaming Disorder among college/university students: An international validation study of a self-report

The present study evaluated the psychometric properties of a self-report scale for assessing Internet Gaming Disorder (IGD) symptoms according to the DSM-5 and ICD-11 among 3270 college/university students (2095 [64.1%] females; age mean 21.6 [3.1] years) from different countries worldwide. Croatian, English, Polish, Portuguese, Serbian, Turkish, and Vietnamese versions of the scale were tested. The study showed that symptoms of IGD could be measured as a single underlying factor among college/university students. A nine item-symptom scale following DSM-5, and a short four-item scale representing the main ICD-11 symptoms, had sound internal consistency and construct validity. Three symptom-items were found non-invariant across the language samples (i.e., preoccupation with on-line gaming, loss of interests in previous hobbies and entertainment, and the use of gaming to relieve negative moods). This study provides initial evidence for assessing IGD symptoms among college/university students and will hopefully foster further research into gaming addiction in this population worldwide especially with taking into account language/cultural differences