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Phytochrome B (phyB) is an excellent light quality and quantity sensor that can detect subtle changes in the light environment. The relative amounts of the biologically active photoreceptor (phyB Pfr) are determined by the light conditions and light independent thermal relaxation of Pfr into the inactive phyB Pr, termed thermal reversion. Little is known about the regulation of thermal reversion and how it affects plants’ light sensitivity. In this study we identified several serine/threonine residues on the N-terminal extension (NTE) of Arabidopsis thaliana phyB that are differentially phosphorylated in response to light and temperature, and examined transgenic plants expressing nonphosphorylatable and phosphomimic phyB mutants. The NTE of phyB is essential for thermal stability of the Pfr form, and phosphorylation of S86 particularly enhances the thermal reversion rate of the phyB Pfr–Pr heterodimer in vivo. We demonstrate that S86 phosphorylation is especially critical for phyB signaling compared with phosphorylation of the more N-terminal residues. Interestingly, S86 phosphorylation is reduced in light, paralleled by a progressive Pfr stabilization under prolonged irradiation. By investigating other phytochromes (phyD and phyE) we provide evidence that acceleration of thermal reversion by phosphorylation represents a general mechanism for attenuating phytochrome signaling.

Living organisms detect changes in temperature using thermosensory molecules. However, these molecules and/or their mechanisms for sensing temperature differ among organisms. To identify thermosensory molecules in plants, we investigated chloroplast positioning in response to temperature changes and identified a blue-light photoreceptor, phototropin, that is an essential regulator of chloroplast positioning. Based on the biochemical properties of phototropin during the cellular response to light and temperature changes, we found that phototropin perceives temperature based on the temperature-dependent lifetime of the photoactivated chromophore. Our findings indicate that phototropin perceives both blue light and temperature and uses this information to arrange the chloroplasts for optimal photosynthesis. Because the photoactivated chromophore of many photoreceptors has a temperature-dependent lifetime, a similar temperature-sensing mechanism likely exists in other organisms. Thus, photoreceptors may have the potential to function as thermoreceptors.

Many aspects of photoperception by plants and microorganisms are initiated by the phytochrome (Phy) family of photoreceptors that detect light through interconversion between red light- (Pr) and far-red light-absorbing (Pfr) states. Plants synthesize a small family of Phy isoforms (PhyA to PhyE) that collectively regulate photomorphogenesis and temperature perception through redundant and unique actions. While the selective roles of these isoforms have been partially attributed to their differing abundances, expression patterns, affinities for downstream partners, and turnover rates, we show here from analysis of recombinant Arabidopsis chromoproteins that the Phy isoforms also display distinct biophysical properties. Included are a hypsochromic shift in the Pr absorption for PhyC and varying rates of Pfr to Pr thermal reversion, part of which can be attributed to the core photosensory module in each. Most strikingly, PhyB combines strong temperature dependence of thermal reversion with an order-of-magnitude faster rate to likely serve as the main physiological thermosensor, whereby thermal reversion competes with photoconversion. In addition, comparisons of Pfr occupancies for PhyA and PhyB under a range of red- and white-light fluence rates imply that low-light environments are effectively sensed by PhyA, while high-light environments, such as full sun, are effectively sensed by PhyB. Parallel analyses of the Phy isoforms from potato and maize showed that the unique features within the Arabidopsis family are conserved, thus indicating that the distinct biophysical properties among plant Phy isoforms emerged early in Phy evolution, likely to enable full interrogation of their light and temperature environments.

Reversion mosaicism has been reported in an increasing number of genetic disorders including primary immunodeficiency diseases. Several mechanisms can mediate somatic reversion of inherited mutations. Back mutations restore wild-type sequences, whereas second-site mutations result in compensatory changes. In addition, intragenic recombination, chromosomal deletions, and copy-neutral loss of heterozygosity have been demonstrated in mosaic individuals. Revertant cells that have regained wild-type function may be associated with milder disease phenotypes in some immunodeficient patients with reversion mosaicism. Revertant cells can also be responsible for immune dysregulation. Studies identifying a large variety of genetic changes in the same individual further support a frequent occurrence of reversion mosaicism in primary immunodeficiency diseases. This phenomenon also provides unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. In this paper, we review the recent findings of reversion mosaicism in primary immunodeficiency diseases and discuss its clinical implications.

Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rifampicin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, while exhibiting increased survival in blood and ability to invade host cells. Further genome analysis revealed chromosome structural variation uniquely associated with the SCV. These variations included an asymmetric inversion across half of the S. aureus chromosome via recombination between type I restriction modification system (T1RMS) genes, and the activation of a conserved prophage harboring the immune evasion cluster (IEC). Phenotypic reversion to the wild-type–like NCV state correlated with reversal of the chromosomal inversion (CI) and with prophage stabilization. Further analysis of 29 complete S. aureus genomes showed strong signatures of recombination between hsdMS genes, suggesting that analogous CI has repeatedly occurred during S. aureus evolution. Using qPCR and long-read amplicon deep sequencing, we detected subpopulations with T1RMS rearrangements causing CIs and prophage activation across major S. aureus lineages. Here, we have discovered a previously unrecognized and widespread mechanism of reversible genomic instability in S. aureus associated with SCV generation and persistent infections.

Literature is strongly contradictory about the molecular reasons for yellowing and brightness reversion of pure (lignin- and hemicellulose-free) celluloses, such as in highly bleached pulps, bacterial cellulose, or cotton linters. While oxidized groups—carbonyls (CO) and carboxyls (COOH)—have been recognized as the initiators of yellowing, they are generally always found together; thus, their effects are permanently superimposed in real-world cellulose. For this reason, their individual contributions could not be reliably determined. To tackle this conundrum, we have used a two-stage study: the employment of glucopyranose-derived model compounds and the use of special cellulosic pulps. Both substrates had either only carbonyl functions, only carboxyl functions, or defined ratios of both functionalities present at the same time. The model compounds alone already provided strong indications of the CO-related and COOH-related effects, and further confirmation was obtained by the pulp study. Here, in regard to the polymer case, the carbonyl groups are the minimum functional unit in cellulose responsible for chromophore generation (termed as the “CO effect”). The carbonyl groups are the precursors for the chromophores that are formed later upon yellowing/aging. Chromophore formation increases strictly linearly with the carbonyl content at a constant given carboxyl content. Carboxyl groups alone (i.e., in the absence of carbonyl groups) are fully innocent regarding the color generation. However, they have a strong promotive action when carbonyl groups are present (termed as the “COOH effect”), which includes acidic catalysis and an additional activation by electronic effects. The general roles of CO and COOH are the same for all aging types (e.g., thermal, acidic, or alkaline), while the respective rates of chromophore generation evidently depend on various parameters such as the temperature, medium, and pH value. Graphical abstract

Due to climate change, investors are increasingly interested in clean energy stocks attracting many investors due to clean energy prospects. This paper analyses investor overreactions to long-term prices in various clean energy stock indices, such as Clean Energy Fuels (CLNE), Global Clean Energy (GCEI), as well as the Dow Jones Industrials (DJI) stock index, over the period from 24 February 2022 to 23 May 2024. The results show that the Global Clean Energy (GCEI) clean energy stock index rejects H0 at the 16-day lag at a significance level of 1%; similarly, the Clean Energy Fuels (CLNE) index rejects the null hypothesis at lags 8, 9, 10, 11 and 12 days, both indices show negative serial autocorrelation, which means that price movements are not entirely random and are influenced by prior price movements. This evidence could mean that investors overreact to the information that reaches the market. On the other hand, the ETF (PWYF) and the Dow Jones Industrial Stock Index (DJI) show that the random walk hypothesis has not been rejected. In other words, these markets show that they are in equilibrium and that the existence of exaggerated reactions on the part of investors is not significant. The answer to the research question was partially accepted, so the Russian invasion of Ukraine in 2022 led to the partial presence of overreactions in these stock indices. In conclusion, investors operating in these markets should exercise caution and consider their risk tolerance before investing. Investors should, therefore, continue to monitor market trends and adjust their investment strategies accordingly.

How mammalian tissues maintain their architecture and tissue-specificity is poorly understood. Previously, we documented both the indispensable role of the extracellular matrix (ECM) protein, laminin-111 (LN1), in the formation of normal breast acini, and the phenotypic reversion of cancer cells to acini-like structures in 3-dimensional (3D) gels with inhibitors of oncogenic pathways. Here, we asked how laminin (LN) proteins integrate the signaling pathways necessary for morphogenesis. We report a surprising reciprocal circuitry comprising positive players: laminin-5 (LN5), nitric oxide (NO), p53, HOXD10 and three microRNAs (miRNAs) — that are involved in the formation of mammary acini in 3D. Significantly, cancer cells on either 2-dimensional (2D) or 3D and non-malignant cells on 2D plastic do not produce NO and upregulate negative players: NFκB, EIF5A2, SCA1 and MMP-9 — that disrupt the network. Introducing exogenous NO, LN5 or individual miRNAs to cancer cells reintegrates these pathways and induces phenotypic reversion in 3D. These findings uncover the essential elements of breast epithelial architecture, where the balance between positive- and negative-players leads to homeostasis. Most animal cells can secrete molecules into their surroundings to form a supportive meshwork of large proteins, called the extracellular matrix. This matrix is connected to the cell membrane through receptors that can transmit signals to the cell nucleus to change the levels of small RNA molecules called microRNAs. These, in turn, can switch genes on and off in the nucleus. In the laboratory, cells that build breast tissue and glands can be grown in gels containing extracellular matrix proteins called laminins. Under these conditions, ‘normal’ cells form organized clusters that resemble breast glands. However, if the communication between healthy cells and the extracellular matrix is interrupted, the cells can become disorganized and start to form clumps that resemble tumors, and if injected into mice, can form tumors. Conversely, if the interaction between the extracellular matrix and the cells is restored, each single cancer cell can – despite mutations – be turned into a healthy-looking cell. These cells form a normal-looking tissue through a process called reversion. Until now, it was not known which signals help normal breast tissue to form, and how cancerous cells revert into a ‘normal’ shape. To investigate this, Furuta et al. used a unique series of breast cells from a woman who underwent breast reduction. The cells taken from the discarded tissue had been previously grown by a different group of researchers in a specific way to ensure that both normal and eventual cancer cells were from the same individual. Furuta et al. then put these cells in the type of laminin found in extracellular matrix. The other set of cells used consisted of the same cancerous cells that had been reverted to normal-looking cells. Analysis of the three cell sets identified 60 genes that were turned down in reverted cancer cells to a level found in healthy cells, as well as 10 microRNAs that potentially target these 60 genes. A database search suggested that three of these microRNAs, which are absent in cancer cells, are necessary for healthy breast cells to form organized structures. Using this as a starting point, Furuta et al. discovered a signaling loop that was previously unknown and that organizes breast cells into healthy looking tissue. This showed that laminins help to produce nitric oxide, an important signaling molecule that activates several specific proteins inside the breast cells and restores the levels of the three microRNAs. These, in turn, switch off two genes that are responsible for activating an enzyme that can chop the laminins. Since the two genes are deactivated in the reverted cancer cells, the laminins remain intact and the cells can form organized structures. These findings suggest that if any of the components of the loop were missing, the cells would start to form cancerous clumps again. Reverting the cancer cells in the presence of laminins, however, could help cancer cells to form ‘normal’ structures again. These findings shed new light on how the extracellular matrix communicates with proteins in the nucleus to influence how single cells form breast tissues. It also shows that laminins are crucial for generating signals that regulate both form and function of specific tissues. A better understanding of how healthy and cancerous tissues form and re-form may in the future help to develop new cancer treatments.

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively 1 , 2 . These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain 3 . The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies. Findings from a systematic antigenic analysis of these surging Omicron subvariants that this lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.