PolyACO+: a multi-level polygon-based ant colony optimisation classifier

Ant colony optimisation (ACO) for classification has mostly been limited to rule-based approaches where artificial ants walk on datasets in order to extract rules from the trends in the data, and hybrid approaches which attempt to boost the performance of existing classifiers through guided feature reductions or parameter optimisations. A recent notable example that is distinct from the mainstream approaches is PolyACO, which is a proof-of-concept polygon-based classifier that resorts to ACO as a technique to create multi-edged polygons as class separators. Despite possessing some promise, PolyACO has some significant limitations, most notably, the fact of supporting classification of only two classes, including two features per class. This paper introduces PolyACO+, which is an extension of PolyACO in three significant ways: (1) PolyACO+ supports classifying multiple classes, (2) PolyACO+ supports polygons in multiple dimensions enabling classification with more than two features, and (3) PolyACO+ substantially reduces the training time compared to PolyACO by using the concept of multi-levelling. This paper empirically demonstrates that these updates improve the algorithm to such a degree that it becomes comparable to state-of-the-art techniques such as SVM, neural networks, and AntMiner+.     

Novel target genes and a valid biomarker panel identified for cholangiocarcinoma

Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored.     

The effects of exogenous histamine in isolated rat hearts

The role of histamine in cardiac physiology and pathophysiology is not clarified, but is dependent on species. The effects of exogenous histamine in Langendorff-perfused rat hearts were investigated. 1 mM, 100, 10, 1 and 0.1 M of histamine (n=7 each) as 15 min infusions were employed in a dose-response study, and compared to control perfused hearts (n=7). In another experimental series, 100 M histamine (n=15) was added during reperfusion after 25 min global ischemia, and compared to control ischemia-reperfusion (n=15). The maximal response to histamine in the dose-response study (100 M) was an increase of left ventricular developed pressure to 126±8% of initial value (mean±SEM, p<0.04), and increase of coronary flow to 152+6% (p<0.02) after 5 min infusion. 100 M histamine did not significantly influence heart rate or rhythm. The lowest concentration (0.1 M) did not have effects cardiac performance. Reperfusion with histamine for 2 min after ischemia reduced left ventricular developed pressure to 68±10% of initial value versus 116+17% in ischemic controls (p<0.05), and increased left ventricular end-diastolic pressure to 24±8 mmHg compared to 6±2 mmHg in controls (p<0.04). Left ventricular pressures were similar in hearts reperfused with histamine and in ischemic controls for the rest of the observation. Coronary flow increased during reperfusion in hearts given histamine. Histamine had a dose-dependent positive inotropic and vasodilatory effect in isolated rat hearts. Exogenous histamine had only minor effects on post-ischemic cardiac function.     

A mouse model for in vivo tracking of the major dust mite allergen Der p 2 after inhalation

Inhaled environmental antigens, i.e. allergens, cause allergic symptoms in millions of patients worldwide. As little is known about the fate of an allergen upon inhalation, we addressed this issue for a major dust mite allergen, Der p 2. First, a model for Der p 2-sensitization was established in C57BL/6 J mice, in which sensitized mice mounted a Der p 2-specific IgE-response with eosinophilic lung inflammation after allergen challenge in the airways. In this model, we applied recombinant Der p 2 carrying a novel C-terminal tetrapeptide Sel-tag enabling labelling with the gamma-emitting radionuclide 75Se at a single selenocysteine residue ([75Se]Der p 2). In vivo tracking of intratracheally administered [75Se]Der p 2 using whole-body autoradiography revealed that [75Se]Der p 2-derived radioactivity persisted in the lungs of sensitized mice as long as 48 h. Radioactivity was also detected in kidneys, liver and in enlarged lung-associated lymph nodes. Interestingly, a larger proportion of radioactivity was found in the lungs of sensitized compared with nonsensitized mice 24 h after intratracheal instillation of [75Se]Der p 2. A radioactive protein corresponding to intact Der p 2 could only be detected in the lungs, whereas [75Se]Der p 2-derived radioactivity was recovered in known selenoproteins both in lung and other organs. Hence, using the recently developed Sel-tag method in a mouse model for Der p 2-sensitization, we could track the fate of an inhaled allergen in vivo. Based upon our findings, we conclude that the inflammatory state of the lung influences the rate of metabolism and clearance of Der p 2. Thus, an allergic response to the inhaled allergen may lead to prolonged retention of Der p 2 in the lung.     

Expression of bone morphogenetic protein 4 and its receptors in the remodeling heart

Aims

Heart failure is associated with activation of fetal gene programs. Bone morphogenetic proteins (BMPs) regulate embryonic development through interaction with BMP receptors (BMPRs) on the cell surface. We investigated if the expression of BMP4 and its receptors BMPR1a and BMPR2 were activated in post-infarction remodeling and heart failure.

Main methods

Left ventricular biopsies were taken from explanted hearts of patients with end-stage heart failure due to dilated cardiomyopathy (CMP; n = 15) or ischemic heart disease (CAD; n = 9), and compared with homograft control preparations from organ donors deceased due to non-cardiac causes (n = 7). Other samples were taken from patients undergoing coronary artery bypass grafting (CABG; n = 11). Mice were subjected to induced infarction by permanent coronary artery ligation or sham operation, and hearts were sampled serially thereafter (n = 7 at each time point).

Key findings

Human and mouse hearts expressed BMP4 and both receptor subtypes. CABG and CMP patients had increased expression of mRNA encoding for BMP4, but unchanged protein. Mouse hearts had increased BMP4 precursor protein 24 h after infarction. BMPR1a protein decreased in CAD patients and initially in postinfarcted mouse hearts, but increased again in the latter after two weeks. Human recombinant BMP4 promoted survival after H₂O₂ injury in HL-1 cells, and also protected adult mouse cardiomyocytes against hypoxia–reoxygenation injury.

Significance

Adult hearts express BMP4, the mRNA increasingly so in patients with coronary artery disease with good cardiac function. BMPRs are downregulated in cardiac remodeling and failure. Recombinant BMP4 has protective effects on cultured cardiomyocytes.     

Transient hyperosmolality modulates expression of cardiac aquaporins

Angiotensin-I converting enzyme (ACE) is a zinc dependent peptidase with a major role in regulating vasoactive peptide metabolism. ACE, a transmembrane protein, undergoes proteolysis, or shedding, by an as yet unidentified proteinase to release a catalytically active soluble form of the enzyme. Physiologically, soluble ACE in plasma is derived primarily from endothelial cells. We demonstrate that ACE shedding from confluent endothelial cells is increased in response to bacterial lipopolysaccharide, but not phorbol esters. Characterisation of lipopolysaccharide stimulated shedding showed that there is a lag phase before soluble ACE can be detected which is sensitive to inhibitors of translation, NF-κB, TNFα and TNFR-I/II. The shedding phase is less sensitive to these inhibitors, but is ablated by BB-94, a Matrix Metalloproteinase (MMP)/A Disintegrin and Metalloproteinase (ADAM) inhibitor. Tissue Inhibitor of Metalloproteinase (TIMP) profiling suggested a requirement for ADAM9 in lipopolysaccharide induced ACE shedding, which was confirmed by depletion with siRNA. Transient transfection of ADAM9 and ACE cDNAs into HEK293 cells demonstrated that ADAM9 requires both membrane anchorage and its catalytic domain to shed ACE.     

Effects of environmental enrichment on activity and lameness in commercial broiler production

The aim of this pilot study was to investigate the effects of commercially applied environmental enrichments on behavior and lameness in broilers. Two consecutive flocks of broilers were observed at 16 days and 30 days of age to investigate differences between enriched (peat, bales of lucerne hay, and elevated platforms) and control birds with regards to behavioral activities and lameness. More running (p < .001), worm running (p = .006), play fighting (p = .015), dust bathing (p = .009), and ground pecking while standing (p < .001) were observed at 16 days than at 30 days. Across both ages, enriched birds showed more wing flapping (p = .016), wing stretching (p = .002), body shaking (p = .002), ground scratching (p < .001), and ground pecking while standing (p < .001) and lying (p = .003) compared with control birds. Even when no enrichments were close, enriched birds showed more body shaking (p = .008) and ground pecking while standing (p < 0.001) and lying (p = .010) than birds in comparable locations in control pens. There was a tendency for a lower gait score (i.e., reduced lameness) with the enriched treatment (p = .077). In conclusion, enriched birds showed higher levels of several activities compared with control birds, and demonstrated higher levels in areas where no enrichments were present.