Case report: change of dominant strain during dual SARS-CoV-2 infection.

BACKGROUND: The dual infection with SARS-CoV-2 is poorly described and is currently under discussion. We present a study of two strains of SARS-CoV-2 detected in the same patient during the same disease presentation. CASE PRESENTATION: A patient in their 90 s was hospitalised with fever. Oropharyngeal swab obtained on the next day (sample 1) tested positive for SARS-CoV-2. Five days later, the patient was transferred to the ICU (intensive care unit) of the hospital specialising in the treatment of COVID-19 patients, where the patient's condition progressively worsened and continuous oxygen insufflation was required. Repeated oropharyngeal swab (sample 2), which was taken eight days after the first one, also tested positive for SARS-CoV-2. After 5 days of ICU treatment, the patient died. The cause of death was a coronavirus infection, which progressed unfavourably due to premorbid status. We have performed sequencing of full SARS-CoV-2 genomes from oropharyngeal swabs obtained eight days apart. Genomic analysis revealed the presence of two genetically distant SARS-CoV-2 strains in both swabs. Detected strains belong to different phylogenetic clades (GH and GR) and differ in seven nucleotide positions. The relative abundance of strains was 70% (GH) and 30% (GR) in the first swab, and 3% (GH) and 97% (GR) in the second swab. CONCLUSIONS: Our findings suggest that the patient was infected by two genetically distinct SARS-CoV-2 strains at the same time. One of the possible explanations is that the second infection was hospital-acquired. Change of the dominant strain ratio during disease manifestation could be explained by the advantage or higher virulence of the GR clade strain.

Long-Chain Polyunsaturated Fatty Acids in the Green Microalga Lobosphaera incisa Contribute to Tolerance to Abiotic Stresses.

Lobosphaera incisa is a green microalga that accumulates high levels of the valuable omega-6 long-chain polyunsaturated fatty acids (LC-PUFA) arachidonic acid (ARA, 20:4n-6) in triacylglycerols (TAG) under nitrogen (N) starvation. LC-PUFA accumulation is a rare trait in photosynthetic microalgae with insufficiently understood physiological significance. In this study, RNAi was attempted, for the first time in L. incisa, to produce knockdown lines for the Δ5 desaturase gene. Two lines, termed modified lines, which were isolated during screening for transgenic events, demonstrated alterations in their LC-PUFA profile, ARA-biosynthesis gene expression and lipid class distribution. In line M5-78, which appeared to carry a mutation in the Δ6 elongase gene, LC-PUFA were substituted by 18:3n-6 in all glycerolipids. Line M2-35, for which the exact genetic background has not been established, displayed a dramatic reduction in 20:4n-6, concomitant with an augmented proportion of 18:1n-9, in particular in the extraplastidial membrane lipids and TAG. The physiological responses of the modified lines to stressful conditions were compared with the wild type and the Δ5 desaturase mutant. In the N-replete cells of modified lines, the frequency of lipid droplets was reduced, while a number of starch grains increased, suggesting altered partitioning of assimilated carbon into reserve products. Furthermore, both lines exhibited reduced ability to accumulate TAG under N deprivation and recover from N starvation. Both lines demonstrated lower photosynthetic pigment contents, impairments in photosynthesis under a range of stressful conditions, and less efficient functioning of photoprotection under optimal conditions. Possible implications of fatty acids modifications in the stress response of L. incisa are addressed.

Modulation of photosynthetic activity and photoprotection in Haematococcus pluvialis cells during their conversion into haematocysts and back.

The engagement of different photoprotective mechanisms in the cells of the carotenogenic astaxanthin-accumulating chlorophyte Haematococcus pluvialis (i) under favorable conditions, (ii) in the course of stress-induced haematocyst formation and (iii) during recovery from the stress was studied. To this end, we followed the changes in primary photochemistry, electron flow at the acceptor side of photosystem II, and non-photochemical quenching (NPQ) using PAM chlorophyll fluorimetry. A general trend recorded in the stressed cells undergoing transition to haematocysts (and reversed during recovery from the stress) was a gradual reduction of the photosynthetic apparatus accompanied by down-regulation of energy-dependent photoprotective mechanisms such as NPQ, along with the accumulation of astaxanthin. On this background, a transient up-regulation of the photosynthetic activity was detected at the intermediated stages (20-50 h of the stress exposure) of haematocyst formation. This phenomenon was tentatively related with the peak of metabolic activity found earlier in the forming haematocysts. The role of secondary carotenogenesis coupled with a reversible transition from 'active' (energy-dependent) to 'passive' photoprotective mechanisms in the extremely high stress tolerance of carotenogenic phototrophs is discussed.

Exploring disorder correlations in superconducting systems: spectroscopic insights and matrix element effects.

Understanding the intricate interplay between disorder and superconductivity has become a key area of research in condensed matter physics, with profound implications for materials science. Recent studies have shown that spatial correlations of disorder potential can improve superconductivity, prompting a re-evaluation of some theoretical models. This paper explores the influence of disorder correlations on the fundamental properties of superconducting systems, going beyond the traditional assumption of spatially uncorrelated disorder. In particular, we investigate the influence of disorder correlations on key spectroscopic superconductor properties, including the density of states, as well as on the matrix elements of the superconducting coupling constant and their impact on the localization length. Our findings offer valuable insights into the role of disorder correlations in shaping the behavior of superconducting materials.

Nondestructive monitoring of carotenogenesis in Haematococcus pluvialis via whole-cell optical density spectra.

We investigated the feasibility of rapid, nondestructive assay of carotenoid-to-chlorophyll (Car/Chl) ratio and total carotenoids (Car) in cell suspensions of the carotenogenic chlorophyte Haematococcus pluvialis Flotow under stressful conditions. Whole-cell spectra are characterized by variable nonlinear contributions of Car and chlorophylls (Chl), with a strong influence of Car packaging and sieve effect inherent to stressed H. pluvialis cells. Nevertheless, nondestructive assay of Car/Chl in the range of 0.55-31.2 (Car content up to 188 mg L(-1); 5.4 % of the cell dry weight) turned to be achievable with a simple spectrophotometer lacking an integrating sphere upon deposition of the cells on glass fiber filters. The scattering-corrected optical density (OD) in the blue-green region of the whole-cell spectrum, normalized to that in the red maximum of Chl absorption (OD500/OD678), was tightly related (r (2) = 0.96) with the Car/Chl ratio found in extracts. Some features such as the amplitude and position of the minimum of the normalized first-derivative OD whole-cell spectra also exhibited a strong (r (2) > 0.90) nonlinear correlation with Car/Chl. These spectral indices were also tightly related with Car, but the slope of the relationship varied with the stressor intensity. The importance of calibration over the widest possible range of pigment contents and a correct choice of biomass load per filter are emphasized. The advantages and limitations of nondestructive monitoring of carotenogenesis in H. pluvialis are discussed in view of its possible application in optical sensors for laboratory cultivation and mass production systems of the algae.

Multiscale simulation of small peptides: consistent conformational sampling in atomistic and coarse-grained models.

A bottom-up coarse-graining procedure for peptides in aqueous solution is presented, where the interactions in the coarse-grained (CG) model are determined such that the CG peptide samples conformations according to a high-resolution (atomistic) model. It is shown that important aspects of conformational sampling, such as correlated degrees of freedom (DOF) which play an important role in secondary structure formation, can be reproduced in the CG description. In some cases, microscopic structural/conformational details are lost in the coarse-graining process. We show that these "lost" properties can be recovered in a backmapping procedure which reintroduces atomistic DOF into CG structures - as long as the overall conformational sampling of the molecule is correctly represented in the CG level of resolution. Thus, it is possible to link an existing all-atom model of a biomolecular system with a CG description such that after inverse mapping one can recover structures at high resolution with the correctly sampled (according to the atomistic model) conformational properties.

Long-term data on the proposed adalimumab biosimilar BCD-057 in patients with moderate to severe psoriasis: A randomized controlled trial.

INTRODUCTION: The objective of this study was to demonstrate that BCD-057 is similar to innovator adalimumab (iADA) in terms of efficacy, safety, and pharmacokinetics in steady state in the target population of patients with moderate to severe plaque psoriasis (NCT02762955). METHODS: Patients were randomized in 1:1 ratio to receive 80 mg of BCD-057 or iADA at week 0 and 40 mg thereafter every other week from week 1. At week 24 patients from iADA group were re-randomized (1:1) to continue iADA or to be switched to BCD-057. The primary efficacy endpoint was 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75), secondary endpoints included PASI percent improvement and relative change in affected Body Surface Area (BSA) from baseline at weeks 16, 24, 33, and 55. Safety was assessed through monitoring of adverse events (AEs) and antidrug antibodies. Pharmacokinetics was evaluated at steady state. RESULTS: Overall, 346 adult patients were included in the study (174/172 patients in BCD-057/iADA arms, respectively). At week 16 PASI 75 was achieved by 60.34% and 63.37% of patients in BCD-057 and iADA arms, respectively (p = 0.5622). Bounds of the calculated 95% confidence interval (CI) for the difference between PASI 75 responses in arms [-13.26%; 7.2%] fall within the equivalence margin [-15% to 15%] demonstrating equivalent efficacy of BCD-057 and iADA. At week 55 81.61%, 85.56%, and 80.49% of patients in BCD-057, iADA and iADA/BCD-057 arms achieved PASI 75. Comparison of the secondary endpoints did not show significant differences between arms. A comparable pharmacokinetics was shown at steady state. Safety profiles and proportions of patients with antidrug antibodies were similar between arms. The switch from the iADA to BCD-057 did not affect the immunogenicity profile. CONCLUSION: Obtained data demonstrate that BCD-057 and iADA are highly similar in clinical efficacy, pharmacokinetics, safety, and immunogenicity in patients with moderate to severe plaque psoriasis.

Exact solution for 1D spin-polarized fermions with resonant interactions.

Using the asymptotic Bethe ansatz, we obtain an exact solution of the many-body problem for 1D spin-polarized fermions with resonant p-wave interactions, taking into account the effects of both scattering volume and effective range. Under typical experimental conditions, accounting for the effective range, the properties of the system are significantly modified due to the existence of "shape" resonances. The excitation spectrum of the considered model has unexpected features, such as the inverted position of the particle- and holelike branches at small momenta, and rotonlike minima. We find that the frequency of the "breathing" mode in the harmonic trap provides an unambiguous signature of the effective range.

Immobilization of microalgae on the surface of new cross-linked polyethylenimine-based sorbents.

We report on the use of the polyethylenimine-based (PEI) sorbents for immobilization and harvesting of microalgae (MA) cells. Specific materials assessed were porous solid polymers from highly-branched PEI synthesized by cross-linking with epichlorohydrin (ECH) or diethylene glycol diglycidyl ether (DGDE). We estimated the effect of PEI/cross-linker ratio on the MA attachment and biocompatibility of the sorbents with the MA cells. A decrease in the cross-linker percentage resulted in the enhancement of the immobilization efficiency but impaired the cell viability as was manifested by inhibition of the photosynthetic activity of the MA cells. The rate of Chlorella vulgaris cell attachment to the sorbents with ECH was faster as compared to that of the PEI-DGDE-based polymers. The cells immobilized on the PEI-ECH sorbents showed a more profound decline in their viability (assessed via photosynthetic activity). The sorbents with 60% of DGDE were characterized by high immobilization efficiency. These sorbents supported a prolonged cultivation of the immobilized MA without impairing their viability and metabolic activity. We conclude that the sorbents with a lower percentage of DGDE (<30%) and sorbents with ECH are suitable for harvesting of the MA cells intended for immediate downstream processing, potentially without the cell desorption. To the best of our knowledge, this is the first report on successful application of PEI-based sorbents in microalgal biotechnology.

The enrichment of biomass of cyanobacteria with vanadium using the cation and anion forms of its compounds.

Compounds of the trace element vanadium have been shown to mimic insulin effects in in vitro and in vivo systems. Vanadium compounds have emerged as agents for potential use in diabetes therapy. In our work we show the possibility of obtaining enriched biomass of cyanobacteria genus Spirulina (S. platensis and S. maxima) with vanadium in organic form. We have investigated the accumulation of vanadium by the cells of cyanobacteria S. platensis and S. maxima by adding to cultural medium both the forms of vanadium in various concentrations and have defined the optimal concentrations of vanadium in the medium for maximum enrichment of the cells. We defined that S. maxima is more steady to increased concentration of vanadium(IV) and (V) in medium. Optimal concentration of vanadium(IV) in the medium for enrichment of S. platensis and S. maxima biomass was 1.5 g/L, at this vanadium concentration in medium the content of vanadium in the cells of S. platensis was 1245±105 µg/g and in the cells of S. maxima was 1550±75 µg/g. In the case of vanadium(V) addition, the optimal concentration for S. platensis enrichment was 1.5 g/L vanadium(V) in medium, and the intracellular concentration was 2855±254 µg/g. For S. maxima the optimal concentration was 1.0 g/L vanadium(V) in medium, at that concentration the content of vanadium in cells was 2650±206 µg/g. In addition, we revealed the alterations in macro- and microelemental compositions of both cultures caused by the increased concentration of vanadium compounds in cultural medium.

Microscopic Simulations of Charge Transport in Disordered Organic Semiconductors.

Charge carrier dynamics in an organic semiconductor can often be described in terms of charge hopping between localized states. The hopping rates depend on electronic coupling elements, reorganization energies, and driving forces, which vary as a function of position and orientation of the molecules. The exact evaluation of these contributions in a molecular assembly is computationally prohibitive. Various, often semiempirical, approximations are employed instead. In this work, we review some of these approaches and introduce a software toolkit which implements them. The purpose of the toolkit is to simplify the workflow for charge transport simulations, provide a uniform error control for the methods and a flexible platform for their development, and eventually allow in silico prescreening of organic semiconductors for specific applications. All implemented methods are illustrated by studying charge transport in amorphous films of tris-(8-hydroxyquinoline)aluminum, a common organic semiconductor.

Versatile Object-Oriented Toolkit for Coarse-Graining Applications.

Coarse-graining is a systematic way of reducing the number of degrees of freedom representing a system of interest. Several coarse-graining techniques have so far been developed, such as iterative Boltzmann inversion, force-matching, and inverse Monte Carlo. However, there is no unified framework that implements these methods and that allows their direct comparison. We present a versatile object-oriented toolkit for coarse-graining applications (VOTCA) that implements these techniques and that provides a flexible modular platform for the further development of coarse-graining techniques. All methods are illustrated and compared by coarse-graining the SPC/E water model, liquid methanol, liquid propane, and a single molecule of hexane.