Forecasting of epizootic Activity of the Central Caucasian natural High-Mountain Plague Focus

Central-Caucasian natural plague focus was permanently epizootically active since its discovering in 1971 till 2007. Inter-epizootic period has been in progress since 2008. It was not possible to isolate agent strains from field material. Therefore a forecast for focus activation is a relevant task, especially against the background of registered plague cases in humans in 2014–2016. Objective of the study was to create a forecasting model for quantitative prediction of possible activation or maintenance of inter-epizootic period. Materials and methods. We used archival data of Kabardino-Balkar Plague Control Station: journals of rodents’ autopsy, annual reports on epizootiological surveillance, meteorological data from meteostation “Kislovodsk” over the period of 1989–2017, and our epidemiological data for the period 2010 to 2017. We applied Spearman nonparametric correlation analysis, regression analysis, including principal component method, quarterly analysis, and inhomogeneous sequential pattern recognition procedures for statistical processing. Results and discussion. We have designed statistical model which provides for forecasting of plague focus epizootic activity proactively, a year in advance and 99 % probability or higher. The model was tested on retrospective data over the course of 7 years. All predictions were correct. The operational forecasts from 2015 to 2017 proved right too. However there is a possibility of fast changes in the ecology system conditions of the Central-Caucasian natural plague focus because of the global warming. Thereby the forecasting model will be annually checked for informative value of the predictors and, if necessary, adjusted accordingly

Peculiarities of Immunological Structure Formation in Plague Carriers of the Central-Caucasian High-Mountain Natural Plague Focus

Objective of the study is to analyze immunological structure of the mountain souslik, habitant in various zones of natural focality in the Central-Caucasian natural plague focus.Materials and methods. The data on serological investigations conducted on the mountain souslik, within the periods of 1974–1988 and 2001–2004 have been obtained from FGHI “Kabardino-Balkaria Plague Control Station” of the Rospotrebnadzor. Applying passive hemagglutination test and indirect hemagglutination test, with the help of Excel Microsoft Office 2010, evaluated have been 63147 blood survey results.Conclusions. It is established that the highest ratio of the souslik with low antibody titer in blood, which characterizes initial contact with plague infection, is observed at the peak of epizootic activity. In the mountain steppe of the eastern focal part, the apex coincides with June, in the western part, as well as in the Alpine and Subalpine zones of the eastern one – with August. Animals with high antibody titers, i.e. secondarily infected, emerge in vast numbers at the peak of mountain souslik lethality. In the mountain steppe this period falls upon June, i.e. simultaneously with the peak of epizootic activity. In the western part lethality apex is also observed in June, but maximum epizootic activity takes place in August. In Alpine and Subalpine zones of the eastern focal part, peaks of epizootic activity and lethality among the souslik populations concur and fall upon August. Isolation of plague microbe cultures alongside with positive serological tests is reasonably more often observed in the mountain steppe of the river Baksan, than in other areas of natural focality

Sp1 Expression Is Disrupted in Schizophrenia; A Possible Mechanism for the Abnormal Expression of Mitochondrial Complex I Genes, NDUFV1 and NDUFV2

The prevailing hypothesis regards schizophrenia as a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed in schizophrenia, and consequently can affect the expression of genes implicated in this disorder. promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin.These findings suggest that abnormality in Sp1, which can be the main activator/repressor or act in combination with additional transcription factors and is subjected to environmental stimuli, can contribute to the polygenic and clinically heterogeneous nature of schizophrenia

Mitochondrial ATP synthase: architecture, function and pathology

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions

Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression

BACKGROUND:Mitochondrial dysfunction was reported in schizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics. METHODOLOGY/PRINCIPAL FINDINGS:mRNA and protein levels of complex I subunits NDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients with schizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found. Schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed in schizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group. CONCLUSIONS/SIGNIFICANCE:These results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders

Crystal structure of bovine mitochondrial factor B at 0.96-Å resolution

Coupling factor B (FB) is a mitochondrial inner membrane polypeptide that facilitates the energy-driven catalysis of ATP synthesis in animal mitochondria by blocking a proton leak across the membrane. Here, we report the crystal structure of the bovine mitochondrial FB mutant with Gly-3–Glu substitution determined at a resolution of 0.96 Å and that of the WT polypeptide at a resolution of 2.9 Å. The structure reveals an oblong, oval-shaped molecule with a unique globular N-terminal domain that is proposed to be the membrane anchor domain and the capping region to the C-terminal leucine-rich repeats domain. A short N-terminal α-helix, which extends away from the molecule's body, is suggestive of functioning as an anchor for FB to the matrix side of the mitochondrial inner membrane. Identification of a bound Mg2+ ion reveals that FB is a metalloprotein. We also report the cocrystal structures of FB bound with phenylarsine oxide and Cd2+, two known inhibitors of the FB coupling activity