Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

Anticholinergic and antiglutamatergic agents protect against soman-induced brain damage and cognitive dysfunction.

Soman, a powerful inhibitor of acetylcholinesterase, causes an array of toxic effects in the central nervous system including convulsions, learning and memory impairments, and, ultimately, death. We report on the protection afforded by postexposure antidotal treatments, combined with pyridostigmine (0.1 mg/kg) pretreatment, against these consequences associated with soman poisoning. Scopolamine (0.1 mg/kg) or caramiphen (10 mg/kg) were administered 5 min after soman (1.2 LD50), whereas TAB (i.e., TMB4, atropine, and benactyzine, 7.5, 3, and 1 mg/kg, respectively) was injected in rats concomitant with the development of toxic signs. Atropine (4 mg/kg) was given to the two former groups at the onset of toxic symptoms. Caramiphen and TAB completely abolished electrographic seizure activity while scopolamine treatment exhibited only partial protection. Additionally, no significant alteration in the density of peripheral benzodiazepine receptors was noted following caramiphen or TAB administration, while scopolamine application resulted in a complex outcome: a portion of the animals demonstrated no change in the number of these sites whereas the others exhibited markedly higher densities. Cognitive functions (i.e., learning and memory processes) evaluated using the Morris water maze improved considerably by the three treatments when compared to soman-injected animals; the following rank order was observed: caramiphen > TAB > scopolamine. Additionally, statistically significant correlations (r = 0.72, r = 0.73) were demonstrated between two learning parameters and [3H]Ro5-4864 binding to brain membrane. These results show that drugs with a pharmacological profile consisting of anticholinergic and antiglutamatergic properties such as caramiphen and TAB, have a substantial potential as postexposure therapies against intoxication by organophosphates.     

Post-traumatic stress disorder and sleep-what a nightmare!

According to DSM IV criteria, sleep disturbances are incorporated in the definition of post-traumatic stress disorder (PTSD). These include the re-experiencing symptoms (nightmares, criteria B) and a hyperarousal state (difficulty initiating and maintaining sleep, criteria D). PTSD patients commonly complain of sleep disturbances. Moreover, insomnia, restless sleep and trauma-related dreams might be the primary complaint of some patients. However, although subjective sleep disturbances are considered characteristic of PTSD, sleep laboratory studies have provided inconsistent evidence of objective sleep disorders. A variety of sleep architectures and sleep patterns has been reported in PTSD. However, only a few studies have controlled for comorbidities. Thus, uncertainty exists to what extent the sustained complaints of sleep disturbances in chronic PTSD are specifically related to the impact of exposure to traumatic stress, or rather are a consequence of comorbid disorders. Specific changes in REM sleep suggest a pathophysiologic role of REM sleep abnormality in PTSD (e.g. anxiety dreams, increased REM density, exaggerated startle response, decreased dream recall and elevated awakening thresholds from REM sleep). However, again, studies have failed to show consistent changes in percentage of REM sleep or in REM latency. There might be a coexistence of pressure to REM along with inhibitory forces of REM that result in high variability of REM parameters across patients. Alternatively, changes in REM sleep might reflect the effect of comorbid psychiatric disorders that results in inconsistent findings between patients. The current review tries to address these issues based on recent studies carried out in this field.     

Complex robotic‐enhanced percutaneous coronary intervention

A remote‐controlled, robotic system was developed to address procedural challenges and occupational hazards associated with traditional percutaneous coronary intervention (PCI). The PRECISE (Percutaneous Robotically Enhanced Coronary Intervention) Study demonstrated the safety and feasibility of the robotic system. We report four cases of complex coronary interventions demonstrating the capabilities of robotic‐enhanced PCI to treat multilesion, multivessel coronary disease, saphenous venous graft disease, and an ST‐elevation myocardial infarction. The robotic system offers enhanced visibility, precise measurement, accurate stent positioning, improved ergonomics, and superior operator protection from radiation. © 2013 Wiley Periodicals, Inc.     

Serum amyloid type a may be a predictor of restenosis

Background: Elevation of acute phase proteins [C-reactive protein (CRP) and serum amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse clinical prognosis. Hypothesis: The study was undertaken to determine the effect of angioplasty on the levels of SAA and the correlation with postangioplasty restenosis. Methods: In a university-affiliated tertiary medical center, a prospective case study was undertaken in 55 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion for angina pectoris. Three groups of patients were clinically characterized according to Braunwald's classification of anginal syndrome: Group A: class III; Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an ELISA method before PICA and after 24 h, 1, and 3 months. Patients were followed clinically for 12 months. A thallium stress perfusion scan was performed 3 months after PTCA and coronary angiography was repeated in patients with an abnormal thallium perfusion scan. Results: Serum amyloid type A levels >100 m?/ml could identify Group A patients with a high sensitivity and specificity (r = 0.85 and 0.86, respectively). Of the patients studied. 75% increased their SAA level 24 h after angioplasty. An increase of SAA by >100% was associated with an increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). Conclusion: Increased levels of SAA characterize patients with unstable angina pectoris with a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after angioplasty may serve as a marker of restenosis.