Unexpected role of sterol synthesis in RNA stability and translation in Leishmania

Leishmania parasites are trypanosomatid protozoans that cause leishmaniasis affecting millions of people worldwide. Sterols are important components of the plasma and organellar membranes. They also serve as precursors for the synthesis of signaling molecules. Unlike animals, Leishmania does not synthesize cholesterol but makes ergostane-based sterols instead. C-14-demethylase is a key enzyme involved in the biosynthesis of sterols and an important drug target. In Leishmania parasites, the inactivation of C-14-demethylase leads to multiple defects, including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C-14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis in Leishmania plays an unexpected role in global gene regulation

Observation of narrow baryon resonance decaying into pKs0pK^0_s in pA-interactions at 70GeV/c70 GeV/c with SVD-2 setup

SVD-2 experiment data have been analyzed to search for an exotic baryon state, the $\Theta^+$-baryon, in a $pK^0_s$ decay mode at $70 GeV/c$ on IHEP accelerator. The reaction $pA \to pK^0_s+X$ with a limited multiplicity was used in the analysis. The $pK^0_s$ invariant mass spectrum shows a resonant structure with $M=1526\pm3(stat.)\pm 3(syst.) MeV/c^2$ and $\Gamma < 24 MeV/c^2$. The statistical significance of this peak was estimated to be of $5.6 \sigma$. The mass and width of the resonance is compatible with the recently reported $\Theta^+$- baryon with positive strangeness which was predicted as an exotic pentaquark ($uudd\bar{s}$) baryon state. The total cross section for $\Theta^+$ production in pN-interactions for $X_F\ge 0$ was estimated to be $(30\div120) \mu b$ and no essential deviation from A-dependence for inelastic events $(\sim A^{0.7})$ was found.Comment: 8 pages, 7 figures, To be submitted to Yadernaya Fizika. v3-v5 - Some references added, minor typos correcte

Comparative morphological characteristics of the uteroplacental area in abnormal placentation

The aim. To carry out a comparative morphological characteristic of the uteroplacental area with abnormal placentation – pl. accreta, pl. increta, pl. percreta. Materials and methods. The study included 47 patients with atypical placentation; the comparison group included 10 healthy pregnant women with uterine scar after a previous caesarean section. A histological study of uteroplacental area samples was performed with hematoxylin and eosin, methylene blue staining. An immunohistochemical study with primary antibodies to cytokeratin 7 (CK7), Hif2a, vascular endothelial growth factor, α-SMA was carried out. The differences between the compared values were considered to be statistically significant at p &lt; 0.05. The results of the study. Pl. accreta was determined in 12 (25.5 %), pl. increta – in 30 (63.9 %), pl. percreta – in 5 (10.6 %) patients. In all patients of the main group, the decidua was completely or partially absent in the area of abnormal placentation or was replaced by an uneven layer of fetal fibrinoid. Cases when placental villi unevenly penetrated into the thickness of myometrium in the form of “tongues” or “coves” bordered by fetal fibrinoid and often located intermuscularly were defined as pl. increta (n = 26). Cases with the placental villi ingrowth to the serous membrane were considered as pl.  percreta (n  =  5). In cases with deep variants of  ingrowth (pl. increta and pl. percreta) (n = 31), the villi were visualized in the lumen of the vessels and the thinning of the lower uterine segment with the presence of stretched muscle bundles was revealed. Aseptic necrosis of  the myometrium was  found: in 2 (16.7 %) of 12 women with pl. accreta, in 26 (86.7 %) of 30 women with pl. increta and in 5 (100 %) women with pl. percreta. There were no areas of necrosis in the myometrium of the women of comparison group. Conclusion. The appearance and increase of myometrial necrosis zones in response to an increase in the depth of placental villus ingrowth were detected. Myometrial necrosis zones could be the cause of activation of angiogenic factors and an important stimulus for the development of abnormal vascularization in placenta accreta spectrum

On the Influence of Pulse Shapes on Ionization Probability

We investigate analytical expressions for the upper and lower bounds for the ionization probability through ultra-intense shortly pulsed laser radiation. We take several different pulse shapes into account, including in particular those with a smooth adiabatic turn-on and turn-off. For all situations for which our bounds are applicable we do not find any evidence for bound-state stabilization.Comment: 21 pages LateX, 10 figure

Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

BACKGROUND: The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron’s rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta. METHODS: We analyzed nasal swab PCR tests for samples collected between December 12 and 16, 2021, in Connecticut when the proportion of Delta and Omicron variants was relatively equal. We used the spike gene target failure (SGTF) to classify probable Delta and Omicron infections. We fitted an exponential curve to the estimated infections to determine the doubling times for each variant. We compared the test positivity rates for each variant by vaccination status, number of doses, and vaccine manufacturer. Generalized linear models were used to assess factors associated with odds of infection with each variant among persons testing positive for SARS-CoV-2. FINDINGS: For infections with high virus copies (Ct < 30) among vaccinated persons, we found higher odds that they were infected with Omicron compared to Delta, and that the odds increased with increased number of vaccine doses. Compared to unvaccinated persons, we found significant reduction in Delta positivity rates after two (43.4%–49.1%) and three vaccine doses (81.1%), while we only found a significant reduction in Omicron positivity rates after three doses (62.3%). CONCLUSION: The rapid rise in Omicron infections was likely driven by Omicron’s escape from vaccine-induced immunity. FUNDING: This work was supported by the Centers for Disease Control and Prevention (CDC)

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities

In-situ temperatures and thermal properties of the East Siberian Arctic shelf sediments: Key input for understanding the dynamics of subsea permafrost

Significant reserves of methane (CH4) are held in the Arctic shelf, but the release of CH4 to the overlying ocean and, subsequently, to the atmosphere has been believed to be restricted by impermeable subsea permafrost, which has sealed the upper sediment layers for thousands of years. Our studies demonstrate progressive degradation of subsea permafrost which controls the scales of CH4 release from the sediment into the water-atmospheric system. Thus, new knowledge about the thermal state of subsea permafrost is crucial for better understanding of the permafrost -hydrate system and associated CH4 release from the East Siberian Arctic Shelf (ESAS) – the broadest and shallowest shelf in the World Ocean, which contains about 80% of subsea permafrost and giant pools of hydrates. Meanwhile, the ESAS, still presents large knowledge gaps in many aspects, especially with respect to subsea permafrost distribution and physical properties of bottom sediments. New field data show that the ESAS has an unfrozen (ice-free) upper sediment layer, which in-situ temperature is −1.0 to −1.8 °C and 0.6оС above the freezing point. On one hand, these cold temperature patterns may be related to the presence of subsea permafrost, which currently primarily occurs in the part of the ESAS that is shallower than 100 m, while ice-bearing sediments may also exist locally under deeper water in the Laptev Sea. On the other hand, the negative bottom sediment temperatures of −1.8 °C measured on the Laptev Sea continental slope sediments underlying water columns as deep as down to 330 m may result from dissociation of gas hydrates or possibly from dense water cascading down from the shelf. In contrast, data collected on recent expeditions in the northern Laptev shelf, zones of warmer bottom temperatures are coinciding with methane seeps, likely induced by seismic and tectonic activity in the area. These warm temperatures are not seen in the East Siberian Sea area, not even in areas of methane seeps, yet with little seismic activity. The thermal conductivity and heat capacity of bottom sediments recorded in the database of thermal parameters for the ESAS areas mainly depend on their lithification degree (density or porosity), moisture content, and particle size distribution. The thermal conductivity and heat capacity average about 1.0 W/(m·K) and 2900 kJ/(m3·K), with ±20% and ±10% variance, respectively, in all sampled Arctic sediments to a sub-bottom interval of 0–0.5 m

Rapid ecological change in the coastal zone of Lake Baikal (East Siberia): Is the site of the world\u27s greatest freshwater biodiversity in danger?

Ecological degradation of the benthic littoral zone is an emerging, urgent problem at Lake Baikal (East Siberia), the most species-rich lake on Earth. Within the last five years, multiple changes have occurred in the nearshore benthos where most of the lake\u27s endemic species reside. These changes include proliferation of benthic algae, deaths of snails and endemic sponges, large coastal wash-ups of dead benthic algae and macrophytes, blooms of toxin-producing benthic cyanobacteria, and inputs of industrial contaminants into parts of the lake. Some changes, such as massive coastal accumulations of benthic algae, are currently shared with the Laurentian Great Lakes (LGLs); however, the drivers of these changes differ between Lake Baikal and the LGLs. Coastal eutrophication from inputs of untreated sewage is causing problems at multiple sites in Lake Baikal, whereas in the LGLs, invasive dreissenid mussels redirect pelagic nutrients to the littoral substrate. At other locations in Lake Baikal, ecological degradation may have different causes including water level fluctuations and the input of toxic industrial contaminants. Importantly, the recent deterioration of the benthic littoral zone in both Lake Baikal and the LGLs has occurred while little change has occurred offshore. This highlights the necessity of monitoring both the littoral and pelagic zones of large lakes for assessing ecosystem health, change and conservation