Antiviral and antimicrobial profiles of selected isoquinoline alkaloids from Fumaria and Corydalis species

In the current study, 33 isoquinoline alkaloids belonging to protopine-, benzylisoquinoline-, benzophenanthridine-, spirobenzylisoquinoline-, phthalideisoquinoline-, aporphine-, protoberberine-, cularine-, and isoquinolone-types as well as 7 derivatives of them obtained from some Fumaria and Corydalis species growing in Turkey have been evaluated for their in vitro antiviral and antimicrobial activities. Both DNA virus Herpes simplex (HSV) and RNA virus Parainfluenza (PI-3) were employed for antiviral assessment of the compounds using Madine-Darby bovine kidney and Vero cell lines and their maximum non-toxic concentrations (MNTC) and cytopathogenic effects (CPE) were determined using acyclovir and oseltamivir as the references. Antibacterial and antifungal activities of the alkaloids were tested against Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Bacillus subtilis, and Candida albicans by the microdilution method and compared to ampicilline, ofloxacine, and ketocanazole as the references. The alkaloids did not present any notable antibacterial effect, while they had significant antifungal activity at 8 microg/ml concentration. On the other hand, the alkaloids were found to have selective inhibition against the PI-3 virus ranging between 0.5 and 64 microg/ml as minimum and maximum CPE inhibitory concentrations, whereas they were completely inactive towards HSV.     

Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis

The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4‐dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo‐like kinase Cdc5. In parallel, upregulated CDK1 activity also targets Dbf4. An enhanced Dbf4‐Cdc5 interaction pronounced phosphorylation of Dbf4 and accelerated SC destruction, while reduced/abolished Dbf4 phosphorylation hampered destruction of SC proteins. SC destruction relieved meiotic inhibition of the ubiquitous recombinase Rad51, suggesting that the mitotic recombination machinery is reactivated following prophase I exit to repair any persisting meiotic DNA double‐strand breaks. Taken together, we propose that the concerted action of DDK, Polo‐like kinase, and CDK1 promotes efficient SC destruction at the end of prophase I to ensure faithful inheritance of the genome.     

The Turkish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery

Background

Cognitive impairment may be seen in as many as 43–70% of patients with multiple sclerosis (MS) and may be observed in all MS subtypes. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) battery may be used to evaluate cognition status. The purpose of the current study is to validate the BICAMS battery in Turkish.

Methods

Patients with MS attending our clinic between September 2014 and April 2015 were invited to participate. Healthy control participants were matched in terms of age, gender and years of education.

Results

One hundred seventy-three MS patients and 153 healthy control participants were enrolled in the study. MS patients performed significantly worse in all trials than the members of the healthy control group. In addition, cognitive dysfunction was identified in 78 of the 173 (45.1%) patients. In the MS with cognitive impairment group, 64 out of 151 (42.4%) subjects were RRMS patients, 12 out of 18 (66.7%) were secondary progressive MS patients, and 2 out of 4 (50%) were primer progressive MS patients.

Conclusions

The BICAMS has been proposed for assessing cognitive impairment in MS patients. This study shows that the battery is suitable for use in Turkey.

     

The Ecm11-Gmc2 Complex Promotes Synaptonemal Complex Formation through Assembly of Transverse Filaments in Budding Yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation.     

Surface dose measurements with GafChromic EBT film for 6 and 18 MV photon beams

The aim of this study was to determine the surface doses using GafChromic EBT films and compare them with plane-parallel ionization chamber measurements for 6 and 18 MV high energy photon beams. The measurements were made in a water equivalent solid phantom in the build-up region of the 6 and 18 MV photon beams at 100 cm SSD for various field sizes. Markus type plane-parallel ion chamber with fixed-separation between collecting electrodes was used to measure the percent depth doses. GafChromic EBT film measurements were performed both on the phantom surface and maximum dose depth at the same geometry with ion chamber measurements. The surface doses found using GafChromic EBT film were 15%, 20%, 29%and 39% ± 2% (1SD) for 6 MV photons, 6%, 11%, 23% and 32% ± 2% (1SD) for 18 MV photons at 5, 10, 20 and 30 cm² field sizes, respectively. GafChromic EBT film provides precise measurements for surface dose in the high energy photons. Agreement between film and plane-parallel chamber measurements was found to be within ±3% for 18 MV photon beams. There was 5% overestimate on the surface doses when compared with the plane-parallel chamber measurements for all field sizes in the 6 MV photon beams.