The LSM1-7 Complex Differentially Regulates Arabidopsis Tolerance to Abiotic Stress Conditions by Promoting Selective mRNA Decapping

This work was supported by Grants BIO2010-17545 and BIO2013-47788-R from MINECO to J.S., GA14-34792S from CSFtoO.N., andMCB-1022435 fromtheNationalScience Foundation to L.S. R.C. is supported by a JAE-DOCcontract fromtheCSIC, andC.C.-L. is a recipient of a FPI fellowship from MINECO.International audienceIn eukaryotes, the decapping machinery is highly conserved and plays an essential role in controlling mRNA stability, a key step in the regulation of gene expression. Yet, the role of mRNA decapping in shaping gene expression profiles in response to environmental cues and the operating molecular mechanisms are poorly understood. Here, we provide genetic and molecular evidence that a component of the decapping machinery, the LSM1-7 complex, plays a critical role in plant tolerance to abiotic stresses. Our results demonstrate that, depending on the stress, the complex from Arabidopsis thaliana interacts with different selected stress-inducible transcripts targeting them for decapping and subsequent degradation. This interaction ensures the correct turnover of the target transcripts and, consequently, the appropriate patterns of downstream stress-responsive gene expression that are required for plant adaptation. Remarkably, among the selected target transcripts of the LSM1-7 complex are those encoding NCED3 and NCED5, two key enzymes in abscisic acid (ABA) biosynthesis. We demonstrate that the complex modulates ABA levels in Arabidopsis exposed to cold and high salt by differentially controlling NCED3 and NCED5 mRNA turnover, which represents a new layer of regulation in ABA biosynthesis in response to abiotic stress. Our findings uncover an unanticipated functional plasticity of the mRNA decapping machinery to modulate the relationship between plants and their environment

DISINTEGRANTS AND THEIR INFLUENCE ON THE DISSOLUTION OF SUBSTANCES OF BIOPHARMACEUTICAL CLASSIFICATION SYSTEM CLASSES

The characteristic of disintegrants used in technology of solid dosage forms is reviewed. The effect on release of substances of different classes from the tablets according to the biopharmaceutical classification system is presented. The characteristic of disintegrants used in technology of solid dosage forms is reviewed. The mechanisms of their action and methods of compounding into tablets, as well as factors that must be considered when choosing the optimal disintegrant, are given. The results of studies on the effectiveness of various disintegrants (crospovidone, croscarmellose sodium, sodium starch glycollate, etc.) on the release of active substances of different classes according to the biopharmaceutical classification system from tablets are discussed. A promising use of co-disintegrating agents in the technology of tablets of substances of class II BCS is highlighted. Examples of disintegrants of natural origin (mucus) used in tablets dispersed in the oral cavity are given

Lycopene β-cyclase expression influences plant physiology, development and metabolism in tobacco plants

Carotenoids are important isoprenoids produced in the plastids of photosynthetic organisms that play key roles in photoprotection and antioxidative processes. β-carotene is generated from lycopene by the lycopene β-cyclase (LCYB). Previously, we demonstrated that the introduction of the Daucus carota (carrot) DcLCYB1 gene into tobacco (cultivar Xanthi) resulted in increased levels of abscisic acid (ABA) and especially gibberellins (GAs), resulting in increased plant yield. In order to understand this phenomenon prior exporting this genetic strategy to crops, we generated tobacco (cultivar Petit Havana) mutants that exhibited a wide range of LCYB expression. Transplastomic plants expressing DcLCYB1 at high levels showed a wild-type-like growth, even though their pigment content was increased, and their leaf GA content was reduced. RNAi NtLCYB lines showed different reductions in NtLCYB transcript abundance, correlating with reduced pigment content and plant variegation. Photosynthesis (leaf absorptance, Fv/Fm, and ETRII) and plant growth were impaired. Remarkably, drastic changes in phytohormone content also occurred in the RNAi lines. However, external application of phytohormones was not sufficient to rescue their phenotypes, suggesting that altered photosynthetic efficiency might be another important factor explaining their reduced biomass. These results show that LCYB expression influences plant biomass by different mechanisms and suggests thresholds for LCYB expression levels that might be beneficial/detrimental for plant growth

Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice

Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-191,2. A bispecific IgG1-like molecule (CoV-X2) has been developed on the basis of C121 and C135, two antibodies derived from donors who had recovered from COVID-193. Here we show that CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable spike binding to the cellular receptor of the virus, angiotensin-converting enzyme 2 (ACE2). Furthermore, CoV-X2 neutralizes wild-type SARS-CoV-2 and its variants of concern, as well as escape mutants generated by the parental monoclonal antibodies. We also found that in a mouse model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, the simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, and combines the advantages of antibody cocktails with those of single-molecule approaches

Three-dimensional analysis of the early development of the dentition

Tooth development has attracted the attention of researchers since the 19th century. It became obvious even then that morphogenesis could not fully be appreciated from two-dimensional histological sections. Therefore, methods of three-dimensional (3D) reconstructions were employed to visualize the surface morphology of developing structures and to help appreciate the complexity of early tooth morphogenesis. The present review surveys the data provided by computer-aided 3D analyses to update classical knowledge of early odontogenesis in the laboratory mouse and in humans. 3D reconstructions have demonstrated that odontogenesis in the early stages is a complex process which also includes the development of rudimentary odontogenic structures with different fates. Their developmental, evolutionary, and pathological aspects are discussed. The combination of in situ hybridization and 3D reconstruction have demonstrated the temporo-spatial dynamics of the signalling centres that reflect transient existence of rudimentary tooth primordia at loci where teeth were present in ancestors. The rudiments can rescue their suppressed development and revitalize, and then their subsequent autonomous development can give rise to oral pathologies. This shows that tooth-forming potential in mammals can be greater than that observed from their functional dentitions. From this perspective, the mouse rudimentary tooth primordia represent a natural model to test possibilities of tooth regeneration