Pyrazinamide plays an important role in the treatment of tuberculosis. However, the microbiological test for pyrazinamide resistance is more complex and less reliable than testing of susceptibility ...to other anti-tuberculosis drugs due to the need to grow the pathogen at pH 5.5. Identification of mutations that cause resistance to anti-tuberculosis drugs can replace microbiological methods. Mutations in the
pncA
gene are responsible for the main mechanism of the resistance to pyrazinamide and are found in more than 90% of resistant strains. However, the genetic method for determining drug susceptibility is very complex, because mutations leading to pyrazinamide resistance are diverse and scattered throughout the gene. We have developed a software package for automatic data interpretation and prediction of the resistance to pyrazinamide based on Sanger sequencing results. The effectiveness of detection of pyrazinamide resistance in 16 clinical samples was compared using the BACTEC MGIT 960 automated system and
pncA
gene Sanger sequencing with automated analysis of the results. A significant advantage of the developed method over a single microbiological study was shown, due to greater reliability of the results irrespective of the purity of isolates.
Drug acetylation plays an important role in the medical practice. Modern methods of acetylation phenotype prediction are based on genotyping of polymorphisms in the second exon of the gene
NAT2
. ...Some disadvantages of these methods limit their application in the clinical practice. We developed a method of human genotyping based on identification of
NAT2
gene polymorphism
rs1495741
by real-time PCR. This method of genotype determination has a number of advantages: high sensitivity, simplicity, possibility of automated interpretation of the results, and feasibility in clinical laboratories.
This paper reports the olivine-group minerals from melilite–nepheline paralavas of two combustion metamorphic (CM) complexes of Mongolia. The paralavas formed by thermal alterations of sedimentary ...rocks due to multistage modern and ancient (since the Quaternary) wild coal fires. The decomposition products of the olivine solid solution into Ca-bearing fayalite and kirschsteinite have been found in paralavas of the Khamaryn–Khural–Khiid CM complex. Apart from these minerals, members of isomorphic series forsterite–fayalite, and monticellite–kirschsteinite, and simplectite-like intergrowths of kirschsteinite with nepheline were identified in the paralavas of the Nyalga CM complex. The studied minerals differ in structural features, Mg# value, and crystallization temperature as a consequence of local variations in formation conditions and composition of silica-undersaturated Ca-rich mafic melts initial for melilite–nepheline paralavas. The olivines of the monticellite–kirschsteinite series reaching 86 mol % of kirschsteinite end-member occur only in paralavas bearing xenoliths of thermally modified carbonate-silicate sedimentary rocks. The crystallization of these olivines together with gehlenitic melilite took place through interaction between mafic paralava melts and xenoliths of marly limestones with large variations in content of silicate (clay–feldspar) admixture.
The mineralogical and geochemical features of melted rocks of the Khamaryn–Khural–Khiid combustion metamorphic complex in Eastern Mongolia have been characterized for the first time and conditions of ...their formation have been estimated. Clinkers and paralavas were formed through partial melting of Early Cretaceous sedimentary sequence under the effect of wild coal fires, which have happened since at least 19th century. The studied area of the complex is dominated by pyrogenically modified pelitic rocks, while their melted varieties represented by clinkers of dacitic and rhyolitic compositions are restricted to the coal fire epicenters. Much less common are Ca-rich and Na-bearing silica-undersaturated mafic paralavas formed through melting of silicate minerals (newly formed and relict) in limestone. Pyrogenically modified mudstones and clinkers contain felsic silicate glass with melted grains of quartz, feldspar, monazite, and other minerals, as well as newly formed cordietite–sekaninaite, hercynite, magnetite, hematite, goethite, ferrosilite, cristobalite, barite-celestine, and accessory rutile, ilmenite, fluorapatite, and fayalite. The paralavas are fully crystallized rocks consisting of phenocryst assemblage (plagioclase, Al-clinopyroxene, melilite) and interstitial pleonast, K–Ba feldspar (celsian, hyalophane), minerals of the rhönite-kuratite series, Ca–Fe olivines (Ca-fayalite, kirschsteinite), pyrrhotite, barite, and fluorapatite. There are also barium Fe–Cu sulfides of the djerfisherite (zoharite, owensite) group and Fe phosphides (schreibersite, barringerite, and α-Fe + Fe
3
P eutectic). At the final stage, Ca-bearing nepheline-group mineral, supposedly, davidsmithite, crystallized in paralava matrix. The paralavas crystallized under high-temperature conditions (1365–945°C for Fe phosphides, near 1100°C for minerals of the rhönite-kuratite series, and 950–850°C for Fe–Ca olivines) at oxygen fugacity from IW to QFM buffers. Locally developed reducing conditions provided the formation of small drops of Fe phosphides and native iron. Some paralavas contain Fe
3+
-pleonast and rhönite-subgroup minerals with high dorrite end-member fraction, which were formed in oxidizing conditions likely corresponding to the HM buffer. Melilite–nepheline paralavas of combustion metamorphic complexes of Mongolia (Khamaryn–Khural–Khiid and Nyalga ones) have close mineralogical and geochemical features. Similar paralavas have not been described anywhere else in the world. The differences in the mineral–phase assemblages and geochemical composition of the clinkers and paralavas from these complexes can be related with composition variations of sedimentary protolith (pelitic and carbonate rocks) involved in the partial melting, as well as with local variations in the physicochemical conditions of their formation (temperature, fluid regime, oxygen fugacity, cooling–quenching rates of the pyrogenic melts, and other factors) during wild coal fires.
Obesity and type 2 diabetes mellitus (T2DM) are often combined and pathologically affect many tissues due to changes in circulating bioactive molecules. In this work, we evaluated the effect of blood ...plasma from obese (OB) patients or from obese patients comorbid with diabetes (OBD) on skeletal muscle function and metabolic state. We employed the mouse myoblasts C2C12 differentiation model to test the regulatory effect of plasma exposure at several levels: (1) cell morphology; (2) functional activity of mitochondria; (3) expression levels of several mitochondria regulators, i.e.,
,
, and miR-378a-3p. Existing databases were used to computationally predict and analyze mir-378a-3p potential targets. We show that short-term exposure to OB or OBD patients' plasma is sufficient to affect C2C12 properties. In fact, the expression of genes that regulate skeletal muscle differentiation and growth was downregulated in both OB- and OBD-treated cells, maximal mitochondrial respiration rate was downregulated in the OBD group, while in the OB group, a metabolic switch to glycolysis was detected. These alterations correlated with a decrease in
and
expression in the OB group and with an increase of miR-378a-3p levels in the OBD group.
Chrome spinels in carbonate veins of the Onguren Complex, East Siberia, Western Baikal region are predominantly ferrichromite and chrommagnetite (MgO ≤ 0.3 wt %, Mg# ≤ 0.04, Al
2
O
3
≤ 2.5 wt %; ...Cr# 0.91–1.00, Fe
2+
/Fe
3+
0.8–1.4) with a high ZnO content (0.9–4.6 wt %). In the calcite vein, titanian chrome-magnetite is transformed into Cr-bearing titanomagnetite, which decomposes into Ti-depleted magnetite and ilmenite at temperature of 970–1000°С and
approximately of +0.5…+0.7 QFM. In the dolomite vein, ferrichromite and chrome-magnetite grains contain relict cores of subferrialumochromite (Al
2
O
3
10.6–14.4 wt %, Cr# 0.63–0.73, Fe
2+
/Fe
3+
4.1–5.2, MgO ≤ 0.52 wt %) with elevated ZnO (3.7–5.1 wt %), TiO
2
(3.2–4.1 wt %), and MnO (0.6–1.1 wt %). Ferrichromite and chrome-magnetite are formed during the high-temperature (>600°C) metamorphism of the vein. Superimposed deformations under greenschist facies conditions lead to the formation of magnetite rims around chrome-magnetite grains.
The measurement of the level of mitochondrial DNA (mtDNA) in the blood is a difficult problem due to high variability of mitochondrial genes, deletions in the mitochondrial genome in some ...pathological conditions, different sources of mtDNA into the bloodstream (mtDNA from tissues, from blood cells,
etc
.). We designed primers and TaqMan probes for highly conserved regions of the
ND1
and
ND2
genes outside the mitochondrial deletions “hot zones”. For standardizing the technique, the true concentration of low-molecular-weight mtDNA was determined by real-time PCR for two targets: a fragment of the
ND2
gene (122 bp) and the
ND1
and
ND2
genes (1198 bp). The sensitivity and specificity of the developed approach were verified on a DNA pool isolated from the blood plasma of healthy donors of various nationalities. The concentration of low-molecular-weight mtDNA in the blood plasma of two patients with COVID-19 was monitored over two weeks of inpatient treatment. A significant increase in the content of low-molecular-weight mtDNA was observed during the first 5 days after hospitalization, followed by a drop to the level of healthy donors. The developed technique makes it possible to assess the blood level of low-molecular-weight mtDNA regardless of the quality of sampling and makes it possible to standardize this biological marker in a wide range of infectious and non-infectious pathologies.
The paper presents mineralogical and geochemical data on clinkers and paralavas and on conditions under which they were formed at the Nyalga combustion metamorphic complex, which was recently ...discovered in Central Mongolia. Mineral and phase assemblages of the CM rocks do not have analogues in the world. The clinkers contain pyrogenically modified mudstone relics, acid silicate glass, partly molten quartz and feldspar grains, and newly formed indialite microlites (phenocrysts) with a ferroindialite marginal zone. In the paralava melts, spinel microlites with broadly varying Fe concentrations and anorthite–bytownite were the first to crystallize, and were followed by phenocrysts of Al-clinopyroxene ± melilite and Mg–Fe olivine. The next minerals to crystallize were Ca-fayalite, kirschsteinite, pyrrhotite, minerals of the rhönite–kuratite series, K–Ba feldspars (celsian, hyalophane, and Ba-orthoclase, Fe
3+
-hercynite ± (native iron, wüstite, Al-magnetite, and fresnoite), nepheline ± (kalsilite), and later calcite, siderite, barite, celestine, and gypsum. The paralavas contain rare minerals of the rhönite–kuratite series, a new end-member of the rhönite subgroup Ca
4
Fe
8
2+
Fe
4
3+
O
4
Si
8
Al
4
O
36
, a tobermorite-like mineral Ca
5
Si
5
(Al,Fe)(OH)O
16
· 5H
2
O, and high- Ba F-rich mica (K,Ba)(Mg,Fe)
3
(Al,Si)
4
O
10
F
2
. The paralavas host quenched relics of microemulsions of immiscible residual silicate melts with broadly varying Si, Al, Fe, Ca, K, Ba, and Sr concentrations, sulfide and calcitic melts, and water-rich silicate–iron ± (Mn) fluid media. The clinkers were formed less than 2 Ma ago in various parts of the Choir–Nyalga basin by melting Early Cretaceous mudstones with bulk composition varies from dacitic to andesitic. The pyrogenic transformations of the mudstones were nearly isochemical, except only for volatile components. The CM melt rocks of basaltic andesitic composition were formed via melting carbonate–silicate sediments at temperatures above 1450°C. The Ca- and Fe-enriched and silicaundersaturated paralavas crystallized near the surface at temperatures higher than 900–1100°C and oxygen fugacity
f
O
2
between the IW and QFM buffers. In local melting domains of the carbonate–silicate sedimentary rocks and in isolations of the residual melts among the paralava matrix the fluid pressure was higher than the atmospheric one. The bulk composition, mineral and phase assemblages of CM rocks of the Nyalga complex are very diverse (dacitic, andesitic, basaltic andesitic, basaltic, and silica-undersaturated mafic) because the melts crystallized under unequilibrated conditions and were derived by the complete or partial melting of clayey and carbonate–silicate sediments during natural coal fires.
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