SIRT2 directs the replication stress response through CDK9 deacetylation

Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acetylome signaling, protects genome integrity, and is a murine tumor suppressor. We show that SIRT2 directs replication stress responses by regulating the activity of cyclin-dependent kinase 9 (CDK9), a protein required for recovery from replication arrest. SIRT2 deficiency results in replication stress sensitivity, impairment in recovery from replication arrest, spontaneous accumulation of replication protein A to foci and chromatin, and a G2/M checkpoint deficit. SIRT2 interacts with and deacetylates CDK9 at lysine 48 in response to replication stress in a manner that is partially dependent on ataxia telangiectasia and Rad3 related (ATR) but not cyclin T or K, thereby stimulating CDK9 kinase activity and promoting recovery from replication arrest. Moreover, wild-type, but not acetylated CDK9, alleviates the replication stress response impairment of SIRT2 deficiency. Collectively, our results define a function for SIRT2 in regulating checkpoint pathways that respond to replication stress through deacetylation of CDK9, providing insight into how SIRT2 maintains genome integrity and a unique mechanism by which SIRT2 may function, at least in part, as a tumor suppressor protein.     

Nimesil effectiveness in rheumatoid arthritis

Clinical efficiency and safety of nimesil were studied in the multicenter open clinical trial of 52 patients with verified rheumatoid arthritis. Nimesil was given for 12 weeks in a daily dose 200-400 mg in addition to basic therapy. Clinical and laboratory parameters were assessed after 4 and 8 weeks of the treatment and after its end. The treatment produced a significant positive response of the articular syndrome. Marked improvement was registered in 11 (23.4%) patients, improvement--in 33 (79.2%) patients. Side effects were reversible and occurred in 8 (15.3%) patients. In 5 patients the drug was withdrawn. The conclusion is made on high efficiency and good tolerance of nimesil in rheumatoid arthritis patients.     

Epilepsy and the dental management of the epileptic patient

AIM: The aim of this article is to educate oral healthcare providers on the diagnosis and treatment of epilepsy and seizure disorders. It also shows the impact of epilepsy on the oral cavity and provides suggestions on the dental management of epileptic patients. REVIEW: Epilepsy and seizure disorders affect 1.5 million Americans. The disease is caused by a number of genetic, physiologic, and infectious disorders as well as trauma. Treatment is primarily pharmaceutical but can also be surgical. The disease itself and the pharmaceutical management often have an impact on the oral cavity. Primary management considerations are the provision of good periodontal care and the restoration of the teeth with stable, strong restorations. CONCLUSIONS: With proper understanding of patients with epilepsy and seizure disorders and their medical treatment, the dental care team can safely and effectively render dental care that will benefit the patient and minimize the risk of oral health problems in the future.     

The Effect of Dopa on the Spinal Cord. 8. Presynaptic and “Remote” Inhibition of Transmission from Ia Afferents to Alpha Motoneurones

In unanesthetized spinal cats, injected with l-DOPA, intra-axonal recording was used to investigate the primary afferent depolarization (PAD) evoked in different species of afferents by volleys in the flexor reflex afferents (FRA). It was confirmed that a late PAD is evoked in la afferents and usually not in Ib or cutaneous afferents. Some late PAD was observed in a few group II muscle afferents. Intracellular recording from motoneurones revealed a considerable depression of the Ia EPSP during the late PAD evoked from the FRA after DOPA, but it was diffkult to attribute this entirely to the PAD in Ia afferents since there was also a late postsynaptic conductance increase in the motoneurones. A further analysis was made on acute spinal cats not injected with DOPA, in which a late P.4D sometimes is evoked by FR24 volleys, without the late postsynaptic soma effects in motoneurones. The marked depression of the Ia EPSP evoked from the FRA under these conditions has a longer duration than the PAD in la afferent terminals. It is postulated that two mechanisms contribute to the Ia EPSP depression, presynaptic inhibition and “remote inhibition”; the latter action persisting after the repolarization of Ia afferents. The results are discussed in relation to reflex regulation of stepping.     

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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In vitro assessment of MR relaxation properties of pituitary adenomas

Proton magnetic relaxation times (T1 and T2) and bound water content were measured in vitro in pituitary adenomas from 15 patients using 90 MHz radiofrequency excitation. These data were compared with those measured in normal pituitary glands obtained from four cats and seven fresh human cadavers. The T1 and T2 measured at 24 degrees C in the tumors (mean +/- SD: 1,170 +/- 80 and 123 +/- 35 ms, respectively) were significantly higher than those of cadaver pituitary (830 +/- 200 and 76 +/- 12 ms) and cat pituitary gland (790 +/- 120 and 69 +/- 10 ms). Although the absolute values were lower, similar differences were present in T1 measured at 4 degrees C. Two-dimensional T2 versus T1 plot was particularly helpful in distinguishing tumor from the normal gland. When tumors were grouped according to density on CT, histology or previous treatment (e.g., irradiation or bromocriptine), there were no significant differences in T1 values between the groups. Bound water content was not found to correlate with T1 or T2 values. We concluded that pituitary adenomas can be distinguished from normal pituitary glands by their different relaxation properties when measured at high frequency in vitro MR.     

Cyber bullying in ADHD and Asperger Syndrome populations

Cyber bullying or electronic bullying refers to bullying that occurs through the Internet or cellular phones. With the rise of technology, researchers have shown a keen interest in the topic of cyber bullying. However, that interest has not extended to individuals with special needs. To address this gap in the literature, the current study examined the prevalence of both “traditional” bullying and cyber bullying in youth with ADHD and/or Asperger's Syndrome, and assessed the social, psychological, and health effects of bullying on participants. In addition, the study addressed the disconnect between parents’ understanding of their child's online experiences and their child's actual experiences in the virtual world. Forty-two children and youth reported high rates of bullying victimization through both traditional and electronic means. Individuals not involved with bullying showed greater levels of physical and psychological health relative to those involved with bullying. Parents and children disagreed on a number of issues related to use of the Internet, indicating the need for more clear communication between parents and their children. The results are discussed in terms of theory of mind, both for self and for others.     

Synthesis and Anti-Chlamydial Activity of Substituted N-Benzylanilines

Pharmaceutical Chemistry Journal - Eleven substituted N-benzylanilines were synthesized. Their anti-chlamydial activity was studied. A water-soluble hydrochloride was prepared from one of the lead...