CLINICAL AND CYTOGENETICAL STUDY OF A PATIENT WITH SYNDROME OF NO NN Е —MILRO V—-M ЕIGE COMBINED WITH SYNDROME OF LAURENCE—MOON—BARDET—BIEDL

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Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways

The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3â -/- intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states

Of Humans and Gerbils— Independent Diversification of Neuroligin-4 Into X- and Y-Specific Genes in Primates and Rodents

The neural cell adhesion protein neuroligin-4 has puzzled neuroscientists and geneticist alike for almost two decades. Its clinical association with autism spectrum disorders (ASD) is well established, however, its diversification into sex chromosome-specific copies, NLGN4X and NLGN4Y, remains uncharted territory. Just recently, the presence of substantial neuroligin-4 sequence differences between humans and laboratory mice, in which Nlgn4 is a pseudoautosomal gene, could be explained as a consequence of dramatic changes affecting the pseudoautosomal region on both sex chromosomes in a subset of rodents, the clade eumuroida. In this study, we describe the presence of sex chromosome-specific copies of neuroligin-4 genes in the Mongolian gerbil (Meriones unguiculatus) marking the first encounter of its kind in rodents. Gerbils are members of the family Muridae and are closely related to mice and rats. Our results have been incorporated into an extended evolutionary analysis covering primates, rodents, lagomorphs, treeshrews and culogos comprising together the mammalian superorder euarchontoglires. We gathered evidence that substantial changes in neuroligin-4 genes have also occurred outside eumuroida in other rodent species as well as in lagomorphs. These changes feature, e.g., a general reduction of its gene size, an increase in its average GC-content as well as in the third position (GC3) of synonymous codons, and the accumulation of repetitive sequences in line with previous observations. We further show conclusively that the diversification of neuroligin-4 in sex chromosome-specific copies has happened multiple times independently during mammal evolution proving that Y-chromosomal NLGN4Y genes do not originate from a single common NLGN4Y ancestor

Modulation of Biofilm Growth by Sub‐Inhibitory Amounts of Antibacterial Substances

It is generally accepted that bacteria in biofilm are more resistant to antibacterials than their planktonic counterparts. For numerous antibiotics, it has been shown that minimal inhibitory concentrations (MICs) for bacteria grown in broth are much lower than the minimal biofilm inhibition concentrations. While sub‐inhibitory concentrations, that is, amounts of antibacterials below the MIC, do not either influence or suppress to some extent or other the bacterial growth in liquid media, these same amounts of drugs, natural substances, etc., may have diverse effects on bacterial biofilms, ranging from suppression to stimulation of the sessile growth and varying with regard to the bacterial species and strains. This is a source of additional risks for both biofilm infection of host tissues and contamination indwelling devices. When considering the data for biofilm modulation, differences in experimental protocols should be taken into account, as well as the strain‐specific mechanisms of biofilm formation

ON THE INCIDENCE OF THE DIFFERENT FORMS OF PRIMARY GLAUCOMA

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Antiproliferative Activity of Natural Flavonoid Fustin Isolated from the Heartwood of Cotinus Coggygria Scop. Against Breast and Colon Cancer Cell Lines

Background and objective: Cotinus coggygria Scop. is a valuable medicinal plant species with pronounced pharmacological potential due to its numerous biological activities. The herb is characterized by a high content of polyphenols among which is fustin. The anticancer activities of fustin, however, are extremely weakly studied. The aim of the present study was to investigate the in vitro antiproliferative potential of fustin isolated from the heartwood of C. coggygria against cell lines originating from two of the most common cancer types – breast (MDA-MB-231 and MCF7), and colon cancer (Colon 26). Materials and methods: Cell growth inhibitory properties of fustin were examined by MTT assay. Subsequently, phase-contrast and fl uorescence microscopy analysis as well as colonyforming assay were carried out on the most sensitive to the cytostatic action of the fustin cell line. Results: The obtained results showed that fustin reduced the proliferation of all studied cell lines. The highest cytostatic eff ect was registered towards breast cancer MDA-MB-231 cells with a half maximal inhibitory concentration (IC50) value of 56.02 μg/ ml followed by colon cancer cells with an IC50 of 78.07 μg/ml. MCF7 cell proliferation was least aff ected with a calculated IC50 of 187.8 μg/ml. Further investigations on breast cancer MDA-MB-231 cells indicated decreased density of cell monolayer and some morphological alterations, signifi cant attenuation in the number of viable cells, and diminished clonogenic ability of cells after fustin exposure. Conclusion: It could be concluded that fustin isolated from the heartwood of medicinal plant C. coggygria possesses marked antiproliferative properties against breast cancer cell line MDA-MB-231 which will be a subject of our more detailed future investigations

Empirical Investigation on Agile Methods Usage: Issues Identified from Early Adopters in Malaysia

Agile Methods are a set of software practices that can help to produce products faster and at the same time deliver what customers want. Despite the benefits that Agile methods can deliver, however, we found few studies from the Southeast Asia region, particularly Malaysia. As a result, less empirical evidence can be obtained in the country making its implementation harder. To use a new method, experience from other practitioners is critical, which describes what is important, what is possible and what is not possible concerning Agile. We conducted a qualitative study to understand the issues faced by early adopters in Malaysia where Agile methods are still relatively new. The initial study involves 13 participants including project managers, CEOs, founders and software developers from seven organisations. Our study has shown that social and human aspects are important when using Agile methods. While technical aspects have always been considered to exist in software development, we found these factors to be less important when using Agile methods. The results obtained can serve as guidelines to practitioners in the country and the neighbouring regions

Comparing HBV Viral Load in Serum, Cerumen, and Saliva and Correlation With HBeAg Serum Status in Patients With Chronic Hepatitis B Infection

Background: Hepatitis B is a disease that is prevalent worldwide and is responsible for 10 of the deaths that occur every year. The virus persists in 5 of infected adults and 90 of infected children and can cause chronic hepatitis. In addition to blood, the virus may also be present in other secretions. Transmission through saliva, sexual fluids, and urine has also been confirmed. Objectives: The main aim of this study was to compare viral DNA copies in the serum, cerumen, and saliva of patients with HBeAg levels in their sera. Patients and Methods: This was a cross-sectional study and subjects were selected by non-randomized methods. Serum, cerumen, and saliva samples were collected from 50 patients who were diagnosed with chronic hepatitis B about a year prior to the study. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the presence of HBsAg and HBeAg in the gathered specimens. Viral DNA was extracted from specimens by using a Qiagen kit. The number of viral DNA copies was determined using a real-time polymerase chain reaction (PCR) assay. The study was performed in Ilam province in western Iran. Results: Twenty-eight percent of the patients were HBeAg positive. The average number of viral copies in serum, cerumen, and saliva was higher in women than in men, and a significant correlation was observed between the gender and average viral copies. However, no significant correlation was observed between viral copies present in the serum and cerumen with the age and gender of patients. In addition, no correlation was observed between serum HBeAg and viral copies present in serum, cerumen, and saliva. The correlation analysis confirmed a direct and definite correlation between viral DNA loads in the patients' serum and cerumen. Conclusions: A significant direct correlation was observed between the viral DNA copies present in patients' cerumen and serum. However, the correlation between saliva viral load with serum and cerumen viral load was very low and inverse. These findings suggest that the presence of the hepatitis B virus (HBV) in non-invasive specimens (such as cerumen and saliva) should also be evaluated when monitoring patients to determine the course of infection and disease