Transport properties of the azimuthal magnetorotational instability

The magnetorotational instability (MRI) is thought to be a powerful source of turbulence in Keplerian accretion disks. Motivated by recent laboratory experiments, we study the MRI driven by an azimuthal magnetic field in an electrically conducting fluid sheared between two concentric rotating cylinders. By adjusting the rotation rates of the cylinders, we approximate angular velocity profiles ω ∝ r q . We perform direct numerical simulations of a steep profile close to the Rayleigh line q & −2 and a quasiKeplerian profile q ≈ −3/2 and cover wide ranges of Reynolds (Re ≤ 4 · 104 ) and magnetic Prandtl numbers (0 ≤ Pm ≤ 1). In the quasi-Keplerian case, the onset of instability depends on the magnetic Reynolds number, with Rmc ≈ 50, and angular momentum transport scales as √ PmRe2 in the turbulent regime. The ratio of Maxwell to Reynolds stresses is set by Rm. At the onset of instability both stresses have similar magnitude, whereas the Reynolds stress vanishes or becomes even negative as Rm increases. For the profile close to the Rayleigh line, the instability shares these properties as long as Pm & 0.1, but exhibits a markedly different character if Pm → 0, where the onset of instability is governed by the Reynolds number, with Rec ≈ 1250, transport is via Reynolds stresses and scales as Re2 . At intermediate Pm = 0.01 we observe a continuous transition from one regime to the other, with a crossover at Rm = O(100). Our results give a comprehensive picture of angular momentum transport of the MRI with an imposed azimuthal field

Interleukin-11 Drives Early Lung Inflammation during Mycobacterium tuberculosis Infection in Genetically Susceptible Mice

IL-11 is multifunctional cytokine whose physiological role in the lungs during pulmonary tuberculosis (TB) is poorly understood. Here, using in vivo administration of specific antibodies against IL-11, we demonstrate for the first time that blocking IL-11 diminishes histopathology and neutrophilic infiltration of the lung tissue in TB-infected genetically susceptible mice. Antibody treatment decreased the pulmonary levels of IL-11 and other key inflammatory cytokines not belonging to the Th1 axis, and down-regulated IL-11 mRNA expression. This suggests the existence of a positive feedback loop at the transcriptional level, which is further supported by up-regulation of IL-11 mRNA expression in the presence of rIL-11 in in vitro cultures of lung cells. These findings imply a pathogenic role for IL-11 during the early phase of Mycobacterium tuberculosis-triggered disease in a genetically susceptible host

Characteristics of antibiotic resistance of non-typhoidal Salmonella circulating in the Russian Federation in the period from 2019 to 2022

Introduction. Non-typhoidal Salmonella make a significant contribution to the incidence of enteric infections and are characterized by an increasing proportion of strains resistant to antimicrobial agents (AMA), including the first choice antibiotics (cephalosporins III and fluoroquinolones). The purpose of the study is to assess the phenotypic resistance of Salmonella to various classes of AMAs and determine the relationship between the phenotypic resistance, serotype, source of isolation and nature of incidence. Materials and methods. We studied 752 representative strains of Salmonella of 2494 strains isolated from various sources (clinical samples, food products, environment) received from 59 regions of Russia in the period from 2019 to 2022. The phenotypic resistance to 22 antibiotics of 11 CLSI classes of AMAs was assessed by broth microdilution method (minimum inhibitory concentration). The diversity of resistance profiles of Salmonella serotypes was compared using the Shannon index. Results. The dominant position in terms of isolation frequency is occupied by the serotypes Salmonella Enteritidis, S. Infantis, S. Muenchen, S. Typhimurium, S. Bovismorbificans, which accounted for 64.4% of the studied strains. 543 (72.2%) strains showed resistance to at least one of the tested antibiotics; 193 (25.7%) strains were characterized by multidrug resistance phenotype (MDR). Resistance to AMA classes was characterized by the following distribution: quinolones (61.3%), tetracyclines (28.1%), penicillins (19.1%), β-lactam combination agents (18.6%), folate pathway antagonists (16, 5%), phenicols (10.1%), aminoglycosides (5.6%), cephems (4.7%), monobactams (4.4%), lipopeptides (3.9%). No penem-resistant strains have been identified. The features of Salmonella resistance by AMA classes are shown to depend on the sources of isolation, the Salmonella serotype and the nature of the incidence (outbreak and sporadic). Conclusions. Monitoring of phenotypic antibiotic resistance is an important tool for epidemiological surveillance in order to prevent the spread of bacterial resistance to AMAs

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Treatment with anti-IL-11 antibodies significantly attenuates the severity of TB in I/St mice.

<p>(A) ∼3-fold decrease in lung CFU counts compared to control animals. (B and C) Lung pathology in individual animals. None of anti-IL-11-treated mice developed necrotic TB foci evident in control mice <i>a</i>, <i>d</i> and <i>g</i> (circled). (D) Statistical evaluation of the proportion of inflamed lung tissue. CFU counts and morphometry were performed in all mice included in 2 independent experiments (total N = 16 and 17 for experimental and control groups, respectively). Histology is displayed for individual mice analyzed in one experiment (N = 7 for each group).</p

Anti-IL-11 antibody therapy decreases levels of IL-11 and pro-inflammatory factors in the lung tissue without shifting the IL-12 – IFN-γ/IL-10 balance.

<p>Cytokine contents in lung homogenates were assessed by ELISA for 4 mice in each group. The results of one of two similar experiments are displayed as mean ± SEM.</p

Protein levels of IL-11 affect IL-11 mRNA expression.

<p>(A) <i>In vivo</i> administration of anti-IL-11 antibodies leads to a selective down-regulation of IL-11 mRNA. The level of expression was quantified in 5 individual mice per group, using qrt-PCR and normalization against the level of GAPDH expression. Results obtained in 1 of 2 similar experiments are expressed as mean ± SEM (for IL-11 expression <i>P</i> = 0.021, for other cytokines <i>P</i>>0.05). (B) Introduction of 100 ng/ml rIL-11 in cultures of lung cells up-regulates the expression of IL-11 mRNA. Results of two similar experiments are expressed as mean of 3 wells ± SEM (<i>P</i><0.01, ANOVA, compared to negative controls and cultures stimulated with 10 ng/ml IL-11).</p

Properties of anti-IL-11 polyclonal antibodies.

<p>(A) Reactivity of affinity purified rabbit globulin preparation against mIL-11 assessed in ELISA format. No reactivity was found in pre-immune globulin (diamonds); immunoglobulin from rabbits immunized thrice with rmIL-11 showed very strong reactivity (squares); after exhaustion on mycobacterial sonicate adsorbent, specific anti-IL-11 reactivity dropped but was readily detected (triangles). (B) Immune blotting with rmIL-11 with polyclonal rabbit anti-mIL-11 antibodies (preparation identical to one displayed as triangles in (A). Tracks: 1, 2 – immune rabbits 1 and 2; 3, 4 – pre-immune rabbits 1 and 2; 5 – conjugate-free control.</p

Two weeks after TB challenge the level of IL-11 mRNA increases ∼1 log in the lungs of TB-susceptible I/St but does not change in TB-resistant A/Sn mice.

<p>Mean ± SEM expression level plotted against that of GABDT in 4 individual mice per group is displayed (<i>P</i><0.01, ANOVA, between naïve and infected I/St mice).</p

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells