New and little known blattogryllidae (Insecta: Grylloblattida) from the Permian and Triassic of Russia,Kazakhstan, and Kyrgyzstan

New members of the family Blattogryllidae are described, including Permoblattogryllus praecox gen. et sp. nov. from the Middle Permian Soyana locality in Russia, Protoblattogryllus nedubrovensis from the Lower Triassic Nedubrovo locality in Russia, Madygenocephalus micropteron gen. et sp. nov. (the second known case of brachyptery in grylloblattids), and Costatoviblatta similis sp. nov. from the Middle Triassic Madygen locality in Kyrgyzstan. Protoblattogryllus zajsanicus Storozhenko, 1990 from the Upper Permian Karaungir II locality in Kazakhstan is redescribed. The genus Microblattogryllus Storozhenko, 1990 from Madygen is considered to be a synonym of Protoblattogryllus Storozhenko, 1990. Protoblattogryllus abruptus Storozhenko, 1990 from the Madygen locality is transferred to the genus Mesoblattogryllus Storozhenko, 1990.     

New and little known grylloblattida (Insecta) from intertrappean deposits of the Tunguska Basin of Sibiria

New grylloblattids from the Triassic of the Tunguska Basin (Evenkia, Russia) are described, including Chauliodites eskovi sp. nov. (Chaulioditidae) from the Nirungdakan-1 locality, Shurabia lukashevichae sp. nov. and Sh. bashkuevi sp. nov. (Geinitziidae) from the Lower Lyulyuikta-1 locality, Megakhosarodes shcherbakovi sp. nov. (Megakhosaridae) and Protoblattogryllus vittatus sp. nov. (Blattogryllidae) from the Anakit-3 locality. Chauliodites durus (Aristov, 2003) (Chaulioditidae) from the Anakit-1 locality is redescribed.     

Two Related RNA-editing Proteins Target the Same Sites in Mitochondria of Arabidopsis thaliana

The facilitators for specific cytosine-to-uridine RNA-editing events in plant mitochondria and plastids are pentatricopeptide repeat (PPR)-containing proteins with specific additional C-terminal domains. Here we report the related PPR proteins mitochondrial editing factor 8 (MEF8) and MEF8S with only five such repeats each to be both involved in RNA editing at the same two sites in mitochondria of Arabidopsis thaliana. Mutants of MEF8 show diminished editing in leaves but not in pollen, whereas mutants of the related protein MEF8S show reduced RNA editing in pollen but not in leaves. Overexpressed MEF8 or MEF8S both increase editing at the two target sites in a mef8 mutant. Double mutants of MEF8 and MEF8S are not viable although both identified target sites are in mRNAs for nonessential proteins. This suggests that MEF8 and MEF8S may have other essential functions beyond these two editing sites in complex I mRNAs.     

In vitro RNA editing in plant mitochondria does not require added energy

RNA editing in flowering plant mitochondria is investigated by in vitro assays. These cauliflower mitochondrial lysates require added NTP or dNTP. We have now resolved the reason for this requirement to be the inhibition of the RNA binding activity of the glutamate dehydrogenases (GDH). Both GDH1 and GDH2 were identified in RNA-protein cross-links. The inhibition of in vitro RNA editing by GDH is confirmed by the ability of the GDH-specific herbicide phosphinothricin to substitute for NTP. NADH and NADPH, but not NAD or NADP, can also replace NTP, suggesting that the NAD(P)H-binding-pocket configuration of the GDH contacts the RNA. RNA editing in plant mitochondria is thus intrinsically independent of added energy in the form of NTP.     

Replacing the phthalimide core in thalidomide with benzotriazole

The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4A^CRBN E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting “benzotriazolo thalidomide” has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture.     

Retention in Endoplasmic Reticulum 1 (RER1) Modulates Amyloid-β (Aβ) Production by Altering Trafficking of γ-Secretase and Amyloid Precursor Protein (APP)

The presence of neuritic plaques containing aggregated amyloid-β (Aβ) peptides in the brain parenchyma is a pathological hallmark of Alzheimer disease (AD). Aβ is generated by sequential cleavage of the amyloid β precursor protein (APP) by β- and γ-secretase, respectively. As APP processing to Aβ requires transport through the secretory pathway, trafficking of the substrate and access to the secretases are key factors that can influence Aβ production (Thinakaran, G., and Koo, E. H. (2008) Amyloid precursor protein trafficking, processing, and function. J. Biol. Chem. 283, 29615–29619). Here, we report that retention in endoplasmic reticulum 1 (RER1) associates with γ-secretase in early secretory compartments and regulates the intracellular trafficking of γ-secretase. RER1 overexpression decreases both γ-secretase localization on the cell surface and Aβ secretion and conversely RER1 knockdown increases the level of cell surface γ-secretase and increases Aβ secretion. Furthermore, we find that increased RER1 levels decrease mature APP and increase immature APP, resulting in less surface accumulation of APP. These data show that RER1 influences the trafficking and localization of both γ-secretase and APP, thereby regulating the production and secretion of Aβ peptides.     

A perspective of present approaches to EEG analyses performed with intention to find seizure predictors

In the late 90-s of the previous century the American Society of Epileptologists defined a priority for research as "possibilities to predict a seizure, early determinate and reduct". A method, which would allow the prediction of epileptical seizure's onset based on the EEG data registered with the patient with an epilepsy disease, would also allow implementing the new approach to treatment. If it became reliably possible to predict a moment of seizure, based on the EEG dynamics, one could create an automated closed loop system to prevent a seizure. In the article a number of works regarding this subject were reviewed. Also own results were discussed which were derived from analyses of brain electrical activity of rats with absence epilepsy and with the use of own developed software. Moreover specifics of absence initiation and course were discussed, as well as formation mechanism of thalamus-cortical loop, existing abilities of reduction not only absences, but also cognitive and emotional dissociations. Also described results of analyses of the EEG time series, that were derived by computation of correlation dimension with own developed software.     

Body composition in severe refractory asthma: comparison with COPD patients and healthy smokers

Background

Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated.

Methodology and Principal Findings

213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients) without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements) and spirometry were performed. Differences in fat free mass index (FFMI) between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3–18.3)–19.5(18.4–21.5), p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I–III COPD and comparable to those of stage IV COPD patients [18.0(17.3–18.3)–18.8(17.8–20.1), p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS) and daily use of oral corticosteroids (OCS). In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used.

Conclusions and Significance

SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.