Microarray-based comparative genomic analyses of the human malaria parasite Plasmodium falciparum using Affymetrix arrays

Microarray-based comparative genomic hybridization (CGH) provides a powerful tool for whole genome analyses and the rapid detection of genomic variation that underlies virulence and disease. In the field of Plasmodium research, many of the parasite genomes that one might wish to study in a high throughput manner are not laboratory clones, but clinical isolates. One of the key limitations to the use of clinical samples in CGH, however, is the miniscule amounts of genomic DNA available. Here we describe the successful application of multiple displacement amplification (MDA), a non-PCR-based amplification method that exhibits clear advantages over all other currently available methods. Using MDA, CGH was performed on a panel of NF54 and IT/FCR3 clones, identifying previously published deletions on chromosomes 2 and 9 as well as polymorphism in genes associated with disease pathology.     

Pseudoaneurysm of the left ventricle following apical approach TAVI

News from the Society for Cardiovascular Magnetic Resonance     

Resistance of a vaccinia virus A34R deletion mutant to spontaneous rupture of the outer membrane of progeny virions on the surface of infected cells

The extracellular form of vaccinia virus is referred to as an enveloped virion (EV) because it contains an additional lipoprotein membrane surrounding the infectious mature virion (MV) that must be discarded prior to cell fusion and entry. Most EVs adhere to the surface of the parent cell and mediate spread of the infection to adjacent cells. Here we show that some attached EVs have ruptured envelopes. Rupture was detected by fluorescence microscopy of unfixed and unpermeabilized cells using antibodies to the F13 and L1 proteins, which line the inner side of the EV membrane and the outer side of the MV membrane, respectively. The presence of ruptured EV membranes was confirmed by immunogold transmission electron microscopy. EVs with broken membranes were present on several cell lines examined including one deficient in glycosaminoglycans, which are thought to play a role in breakage of the EV membrane prior to fusion of the MV. No correlation was found between EVs with ruptured membranes and actin tail formation. Studies with several mutant viruses indicated that EV membranes lacking the A34 protein were unbroken. This result was consistent with other properties of A34R deletion mutants including resistance of the EV membrane to polyanions, small plaque formation and low infectivity that can be increased by disruption of the EV membrane by freezing and thawing.     

Synthesis of novel pyrazolobenzothiazine 5,5-dioxide derivatives as potent anti-HIV-1 agents

A new series of pyrazolobenzothiazine-based carbohydrazides was prepared in a facile way, starting with commercially available sodium saccharine. The final products were sufficiently characterized by spectroscopic techniques. In addition, compound 5k was confirmed with X-ray crystallography as well. All the compounds were screened for anti-HIV-1 and cytotoxicity activities. Overall, out of 15 compounds, seven exhibited good activity with EC₅₀ values <20 μM. Compounds 5c, 5d, 5g, 5j and 5k appeared as the potent anti-HIV-1 agents with EC₅₀ values <5.0 μM. The structure–activity relationship would facilitate the discovery of new molecules with better profile of HIV inhibition activity.     

Are Infertile Men Less Healthy than Fertile Men? Results of a Prospective Case-Control Survey

Background

An association between either subfertility or infertility and an elevated risk of certain male cancers has been previously reported. Nothing is known about abnormalities in infertility and general health conditions.

Objective

To assess whether men with male factor infertility (MFI) are overall less healthy than fertile men, regardless of the reasons for infertility.

Design, setting, and participants

From September 2006 to September 2007, 344 consecutive European Caucasian men with MFI were enrolled in this prospective case-controlled study. Patients were compared with a control group of 293 consecutive age-comparable fertile men. Infertile men were consecutively attending the outpatient male reproductive clinic at a tertiary academic center. Fertile controls were consecutively recruited by use of advertisements posted within our hospital.

Measurements

Comorbidities of patients and fertile men were objectively scored with the Charlson Comorbidity Index (CCI) according to the International Classification of Diseases modified ninth version (ICD-9-CM) codes. Multivariate linear regression models tested the association between predictors and CCI score, as a proxy of general health status.

Results

According to the CCI scores, infertile men had a significantly higher rate of comorbidities compared with the fertile controls (CCI: 0.33 [0.8] vs 0.14 [0.5]; p < 0.001; 95% CI: 0.08–0.29). Linear regression analyses showed that although educational status did not have an impact on CCI (β: 0.035; p = 0.365), while CCI linearly increased with age (β: 0.196; p < 0.001) and body mass index (BMI; β: 0.161; p < 0.001). After adjusting for age, BMI, and educational status, a significantly lower CCI was calculated for fertile men and compared with MFI patients (β: −0.199; p < 0.001).

Conclusions

These results show that MFI accounts for a higher CCI, which may be considered a reliable proxy of a lower general health status.     

Are Caucasian-European men delaying fatherhood? Results of a 7 year observational study of infertile couples with male factor infertility

This study was aimed at assessing presence and predictors of a trend towards more advanced paternal age at presentation in a cohort of 1283 Caucasian-European infertile couples with male factor infertility (MFI) over a short time frame. Multivariate linear regression analysis tested the association between predictors [namely, partners' age, length of infertility at first presentation, patients' comorbidities as scored with the Charlson Comorbidity Index (CCI) and educational status] and patient's age at presentation. Using anova, patient's age at presentation (F ratio: 2.43; p = 0.024) and patients' educational status (χ(2) trend: 142.38; p < 0.001) significantly increased over time. In contrast, length of infertility at first presentation, CCI and partners' age did not significantly change over time (all p ≥ 0.05). Linear regression analyses showed that CCI, educational status and year of presentation were not correlated with patients' age at presentation (all p ≥ 0.05), whereas partners' age (β = 0.170; p < 0.001) and length of infertility (β = 0.123; p = 0.004) were independent predictors of delayed fatherhood. These results showed a significant shift towards advanced paternal age, but a non-significant increase of maternal age at first presentation among Caucasian-European infertile couples with MFI over a short time frame.