Step In Evolution Research Articles

The genomic and cellular basis of biosynthetic innovation in rove beetles

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation.

Morphological Evolution of an Intertidal Mudflat in Relation to Mangrove Growth: Implications for Future Erosion Control.

There is limited information regarding the influence of mangrove growth on the morphological evolution of intertidal mudflats. In this study, Tan Phu Dong district, Tien Giang Province, Vietnam, was selected for investigating how mangrove growth influenced the morphological evolution of an intertidal mudflat. The authors analyzed a series of satellite images (from 1995 and 2022), calculated the enhanced vegetation index (EVI), and documented field visits and observations in pursuit of the objective of the study. The findings revealed that fine-grained sediment accumulated as unconsolidated substratum (US) in the first step of the morphological evolution of the intertidal mudflat, with sediment accumulation of 910 ha in 1995. The US provided favorable conditions for mangroves to grow, while mangrove growth helped compact the US into a compact substratum (CS) in addition to promoting continuous sediment accumulation, increased the vegetation cover of the island, and elevated the substrate density of the remaining areas. As a result, the US and CS decreased steadily between 1995 and 2020, from 910 ha in 1995 to 401 ha in 2020 and from 433 ha in 2005 to 111 ha in 2020, respectively. Meanwhile, the low-vegetation area (LVA), medium-vegetation area (MVA), and high vegetation area (HVA) gradually increased between 1995 and 2015, from 0 ha in 1995 to 104 ha in 2015, from 0 ha in 1995 to 96 ha in 2015, and from 0 ha in 1995 to 114 ha in 2015, respectively. However, the LVA decreased slightly between 2015 and 2020 due to significant sand accumulation, which significantly killed the mangrove trees. In contrast, the MVA and HVA steadily increased between 2015 and 2020, from 96 ha in 2015 to 116 ha in 2020 and from 114 ha in 2015 to 221 ha in 2020, respectively. In 2022, there was a steady increase in HVA (298 ha in 2022), although the date of the 2022 satellite retrieval was 28 January 2022. This study recommends that the technical design of the existing coastal protection works should be revised or adapted to take account of sediment accumulation as the first step in the morphological evolution of the examined intertidal mudflat, rather than mangrove growth.

A short guide to the tight junction.

Tight junctions (TJs) are specialized regions of contact between cells of epithelial and endothelial tissues that form selective semipermeable paracellular barriers that establish and maintain body compartments with different fluid compositions. As such, the formation of TJs represents a critical step in metazoan evolution, allowing the formation of multicompartmental organisms and true, barrier-forming epithelia and endothelia. In the six decades that have passed since the first observations of TJs by transmission electron microscopy, much progress has been made in understanding the structure, function, molecular composition and regulation of TJs. The goal of this Perspective is to highlight the key concepts that have emerged through this research and the future challenges that lie ahead for the field.

Fault Structure Reconstruction From Magnetic Anomalies Using an Improved Backtracking Search Optimization Algorithm

AbstractFault structure reconstruction is an important aspect of magnetic prospecting as it contributes to understanding tectonic history, hazard assessment, and infrastructure planning. Metaheuristics have proven useful in estimating fault structure parameters from geophysical anomalies. Recently, a modified version of the Backtracking Search Optimization Algorithm (BSA), named mBSA, has been proposed that combines mutation steps of BSA and Differential Evolution (DE) algorithms to achieve a better balance between exploration and exploitation. Here, we present imBSA as an efficient approach that builds on the improvements of mBSA. It uses an adaptive amplitude control factor in the mutation step derived from a normally distributed random number obtained via an exponential function. The performances of these approaches were tested on some widely used benchmark functions such as Rosenbrock, Rastrigin, Griewank, and Himmelblau. Synthetic magnetic fault anomalies were evaluated with and without noise, as well as three real anomalies from the Dehri (India), Perth Basin, and Lachlan Fold Belt (Australia). Prior to the optimizations, the solvability of the model parameters was examined using some error topography images. The obtained solutions in the synthetic cases were evaluated using principal component analysis. In addition, a novel visualization option for high‐dimensional optimization problems was introduced. The experiments showed that imBSA has a faster convergence rate and better optimization statistics compared to BSA and mBSA. Therefore, it is believed to be an efficient and good alternative tool to widely used metaheuristics such as Particle Swarm Optimization and DE in explaining geophysical anomalies and optimization problems in other geoscientific disciplines.

From ‘dirty word’ to ‘critical enabler’: the evolution of peacekeeping-intelligence

ABSTRACT The article provides a historical analysis of the evolution of ‘Peacekeeping-Intelligence’ (PKI) as a UN intelligence system and tool of conflict management. It examines the processes leading to the development of the PKI Policy by analyzing the analytical entities that cumulatively contextualized these developments. It also examines the institutional mechanisms at the UNHQ, the underlying logic, and the challenges surrounding these processes. The article first traces the various iterations of information and analysis structures within the UN since the early 1960s. It then focuses on intelligence developments in the 1990s and the new millennium, where the lack of intelligence capabilities, particularly at the mission level, was identified as an underlining factor for the operational problems faced by the UN. It concludes with an examination of the PKI policy as an evolutionary step in UN peacekeeping. The paper argues that PKI offers a new pathway to effective peacekeeping and provides a foundation for enhanced decision-making through situational awareness, the safety and security of peacekeepers, and the protection of civilians.

Functional ecology and evolution of terrestrial and epiphytic species of Rhododendron section Schistanthe (Ericaceae)

Epiphytes are often characterized by small size, specifically adapted to a relatively dry and nutrient-poor habitat. However, this epiphyte syndrome is derived from studies on species-rich and habitat-dominating groups such as orchids and bromeliads. To better understand general trait syndromes of epiphytes, it is important to analyze plant groups that are more transitional in the evolution of epiphytism e.g., the Australasian vireyas (Rhododendron sect. Schistanthe; Ericaceae). Here, we studied the morphology, ecophysiology, and anatomy of 44 species of Rhododendron section Schistanthe from living collections and obtained data for 288 species related to their "life form" (holoepiphytes [= obligatory epiphytes], facultative epiphytes and terrestrial congeners) from the literature. For phylogeny and time-calibrated tree, we used the nuclear ITS (Internal Transcribed Spacers) region. Using different statistics and phylogenetic comparative methods, our results support the hypothesis that holoepiphytic vireyas are smaller in size than the terrestrial ones. Terrestrial vireyas are found at higher minimum and maximum elevation than either facultative or holoepiphytic congeners. We demonstrate that the diversification of tropical Rhododendron is not related to the evolution of the epiphytic life form. Regarding the evolution of traits that are important for water economy, holoepiphytic vireyas do not differ much from their terrestrial relatives indicating that evolutionary steps for specialization towards an holoepiphytic habit are in their initial stages in Rhododendron. Given the large species diversity of the group conclusions based on the subset used here must be considered preliminary. However, our results provide the basis for more detailed future studies.

Supporting meta-model-based language evolution and rapid prototyping with automated grammar transformation

In model-driven engineering, developing a textual domain-specific language (DSL) involves constructing a meta-model, which defines an underlying abstract syntax, and a grammar, which defines the concrete syntax for the DSL. We consider a scenario in which the meta-model is manually maintained, which is common in various contexts, such as blended modeling, in which several concrete syntaxes co-exist in parallel. Language workbenches such as Xtext support such a scenario, but require the grammar to be manually co-evolved, which is laborious and error-prone. In this paper, we present GrammarTransformer, an approach for transforming generated grammars in the context of meta-model-based language evolution. To reduce the effort for language engineers during rapid prototyping and language evolution, it offers a catalog of configurable grammar transformation rules. Once configured, these rules can be automatically applied and re-applied after future evolution steps, greatly reducing redundant manual effort. In addition, some of the supported transformations can globally change the style of concrete syntax elements, further significantly reducing the effort for manual transformations. The grammar transformation rules were extracted from a comparison of generated and existing, expert-created grammars, based on seven available DSLs. An evaluation based on the seven languages shows GrammarTransformer’s ability to modify Xtext-generated grammars in a way that agrees with manual changes performed by an expert and to support language evolution in an efficient way, with only a minimal need to change existing configurations over time.

Transposons Carrying the aacC2e Aminoglycoside and blaTEM Beta-Lactam Resistance Genes in Acinetobacter.

This study examines the genetic contexts and evolutionary steps responsible for the formation of the widely spread transposon Tn6925 carrying blaTEM and aacC2e, which confers resistance to beta-lactam and aminoglycoside antibiotics in Gram-negative bacteria. The blaTEM-1 and aacC2e genes were found in several transposons. They were first observed within an IS26 bounded 3.7 kb transposon (Tn6925) on several Acinetobacter baumannii plasmids located within a 4.7 kb dif module. Truncated and expanded variations of Tn6925 were found across other A. baumannii plasmids, as well as in other Gram-negative bacteria (including Vibrio cholerae). Moreover, blaTEM-1 and aacC2e were in much larger resistance-heavy transposons including the ISAba1-bounded 24.6 kb (here called Tn6927), found in an A. baumannii chromosome. A novel ISKpn12-bounded transposon was also observed to contain blaTEM and aacC2e which was found interrupting Tn5393 along with an IS26 pseudo-compound transposon to form a 24.9 kb resistance island in an Acinetobacter pittii plasmid. Multiple mobile genetic elements are involved in the formation of transposon structures that circulate blaTEM and aacC2e. Among these, IS26 and ISAba1 appear to have played a major role in the formation and spread of these elements in the Acinetobacter species.

Ways to increase the validity of group decision

The modern step of evolution of administrative activities is characterized the growing trend of growing group decision-making. A group does have an opportunity to process more information, correct each other’s mistakes, use one another’s habits, knowledge and competences. However, this does not mean that the more we make group decisions the better. Nevertheless, it’s better if we don’t use this method if it is not necessary. The necessity is determined by how sudden and unexpected is the situation, whether or not is the information enough to make a right decision. Make a decision with a group does have it’s disadvantages. One of those is considered to be the phenomenal of “group thinking”, Among the many ways to overcome this, we consider the most important to be the provision of diversity of members of the decision-making group and the encouragement of organizational learning, which will help to develop different ideas, will grow the wish of group members to lead the environment they work in. Key words: leading decision, group thinking, effectiveness of the meeting, organizational learning, choosing stuff.

Suppressing the damage of deposited Mn(II) ions to graphite anode in lithium‐ion batteries by electrolyte additive agent and positive material coating

AbstractSEM and EDS techniques are carried out to demonstrate the variation of morphology and chemical compound on the surface of graphite anode, which suggest a well‐accepted concept that the manganese ions have serious influence on the reversible capacity fade of graphite anode in lithium ion batteries. Based the main chemical compounds of the inorganic layer on the graphite surface, the evolution steps of graphite structure damaged by Mn ions are derived. Although the amount of deposited manganese ions is small, these play an important role in the catalytic decomposition of the electrolyte. Moreover, Raman analysis shows that the structure of the graphite anode becomes irregular at initial SEI formation cycles and tends to be stable at subsequent cycles. This structure variation is probably generated from the manganese ion deposition and the solid electrolyte interphase (SEI) film formation. According to the capacity tests, the cycling performance of NCM811/graphite lithium‐ion batteries could be improved 50% by FEC additive and B2O3 surface coating. FEC additive maybe benefit graphite forming a stable SEI film in the early stages of cycling to suppress the damage of Mn2+ ions, then improving the cycling performance.

A novel multiple sex chromosome system in Orthoptera, found in the tree cricket Oecanthus rubromaculatus Zefa, 2022 (Grylloidea, Oecanthidae).

The X0♂/XX♀ sex chromosome system prevails in most Orthopteran species. The X chromosome stands as one of the largest chromosomes within the complement, and is characterized by its heterochromatic nature. Variations of this model were found in some species of grasshoppers, crickets, and katydids, based on X/autosome rearrangements, giving rise to new sex chromosome systems, such as neo-XY♂/XX♀ and neo-X1X2Y♂/X1X1X2X2♀. The sex chromosome system neo-X1X20♂/X1X1X2X2♀ is rare in Orthoptera, and was observed only in two cricket species. In this study, we present the first multiple chiasmatic sex chromosome system in Orthoptera, found in the tree cricket Oecanthus rubromaculatus Zefa, 2022 from two distinct locations in the State of Rio Grande do Sul, Brazil. In one location, individuals exhibited a karyotype with 2n = 12, X1X2Y1Y2♂/X1X1X2X2♀, while in the other a karyotype of 2n = 12, X1X2X3Y1Y2Y3♂/X1X1X2X2X3X3♀ was observed. We proposed a model to explain the evolutionary steps in the formation of these karyotypes, based on chromosomal information of the Neotropical Oecanthus' species. In this context, we proposed a hypothesis to explain the chromosome reorganization in O. rubromaculatus, starting from an ancestral karyotype of 2n = 21, X0♂, like the karyotype found in Oecanthus pictus Milach & Zefa, 2015, resulting in a significant reduction to 2n = 12 in O. rubromaculatus. This reorganization has led to the emergence of the novel multiple sex chromosome system in Orthoptera.

Optical and thermo-plasmonic properties of spherical and hollow gold nanoparticles injected in cell organelles

The advent of nanotechnology has profoundly altered many traditional treatment approaches, due to the beneficial physicochemical and functional characteristics of gold nanoparticles (AuNPs). These gold nanostructures are attracting particular interest in a wide range of biomedical applications, such as thermotherapy, diagnostics, detection, and drug delivery. Due to their exceptional characteristics, AuNPs have long been considered as a potential means of combating cancer. These features include surface plasmon resonance (SPR), surface chemistry and multi-functionalization. In addition to targeting tissues and cancer cells, AuNPs with the ability to specifically target organelles are attracting growing interest and are seen as the next evolutionary step in nanomedicine, forming the third generation of this technology. Subcellular targeting offers unique advantages over free targeting, as it enables specific delivery of encapsulated NPs to the intracellular site of action. This translates into greater therapeutic efficacy with a reduced dose and, above all, the ability to overcome immune resistance. AuNPs act as small heat sources taking advantage of SPR phenomenon, enabling targeted heating of specific organelles. The thermoplasmonic effect disrupts organelle function in targeted cancer cells, leading to their destruction. In this work, we used the finite element method (FEM) to examine the properties associated with the SPR of both spherical and hollow AuNPs when they are embedded in the main cellular components, including the lysosome, cell membrane, mitochondria, nucleus, cytoplasm and extracellular medium. In order to predict the thermal destructive power of solid spheres (SAuNPs) and hollow (HAuNPs) gold nanoparticles embedded in these different organelles, we simulated their absorption capacity, field enhancement effect and temperature distribution. The results obtained show that the thermoplasmonic effect is very important for HAuNPs compared with SAuNPs. In addition, the optical and thermoplasmonic properties of SAuNPs and HAuNPs show differential behavior for different cell organelles.

The crisis of peer review: Part of the evolution of science

AbstractPeer review in journals is in crisis, and its current situation and sustainability are increasingly concerning for academics and scientific communities. We identify this crisis as part of an evolutionary step in the continuous development of science, arguing that peer review maintains a central role. We analyse the emergence and historical development of peer review, identifying its role as crucial to the legitimisation of global science, particularly in guaranteeing quality control in the scientific process of massification—despite its flaws. We then focus on the crisis as part of the recent second wave of massification stemming from ‘publish or perish’ dynamics, which overburden those involved in peer review management and activities. Based on this crisis and given that the alternative models to peer review rely on the same core ideals, we argue that the current scenario represents a golden opportunity for the peer‐review process to adapt by correcting some of its known biases, becoming more inclusive and relevant, and gaining recognition for its crucial role in career progression and in the training of the researchers of tomorrow.

Liquid‐Assisted Laser Nanotexturing of Silicon: Onset of Hydrodynamic Processes Regulated by Laser‐Induced Periodic Surface Structures

AbstractUpon systematic studies of femtosecond‐laser processing of monocrystalline Si in oxidation‐preventing methanol, it is shown that the electromagnetic processes dominating at initial steps of the progressive morphology evolution define the onset of the hydrodynamic processes and morphology upon subsequent multi‐pulse exposure. Under promoted exposure quasi‐regular subwavelength laser‐induced periodic surface structures (LIPSSs) are justified to evolve through the template‐assisted development of the Rayleigh‐Plateau hydrodynamic instability in the molten ridges forming quasi‐regular patterns with a supra‐wavelength periodicity and preferential alignment along polarization direction of the incident light. Subsequent exposure promotes fusion‐assisted morphology rearrangement resulting in a spiky surface with random orientation, yet constant inter‐structure distance correlated with initial LIPSS periodicity. Along with the insight onto the physical picture driving the morphology evolution and supra‐wavelength nanostructure formation, this experiments also demonstrated that resulting quasi‐regular and random spiky morphology can be tailored by the intensity/polarization distribution of incident laser beam allowing on‐demand surface nanotexturing with diverse hierarchical surface morphologies exhibiting reduced reflectivity at visible and shortwave‐IR wavelengths. Finally, the practical attractiveness of the suggested approach for improving near‐IR photoresponse and expanding operation spectral range of vertical p‐n junction Si photodetector operating under room temperature and zero‐bias conditions via single‐step annealing‐free nanopatterning is highlighted.

The Mystery of Homochirality on Earth.

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule, is a seemingly improbable event, on a closer look, it is almost inevitable that some homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic "ocean". Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. Furthermore, a concept of physical compartmentalization based on rock nanopores in analogy to nanocavities of digital immunoassays is introduced to suggest that complex cell walls or membranes were also not required for the first steps of chemical evolution. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.

Cation exchange to montmorillonite induces selective adsorption of amino acids

Concentrating simple organic molecules, such as amino acids, in the adsorbed phase could have been an early step in prebiotic evolution towards more complex bio-macromolecules on the early Earth. Smectite clay minerals represent potential selective sorbents for prebiotic molecules because of their negative structural charge and high surface area. This study evaluated the adsorption behavior of amino acids to montmorillonite, a well-characterized smectite, at varying pH and fluid compositions. At both pH 5 and 7 in a sodium chloride fluid, amino acids with basic sidechains (L-arginine and L-lysine), which are primarily cationic under these conditions, were selectively adsorbed to montmorillonite with Langmuir constants much greater than amino acids that were predominantly zwitterionic or anionic in solution. On average, the Langmuir constants for the cationic amino acids were 30 (pH 5) and 50 (pH 7) times greater than the constants for zwitterionic amino acids and 120 (pH 5) and 80 (pH 7) times greater than the constants for L-glutamic acid. Under the same pH conditions in a magnesium chloride solution, the adsorption of L-arginine and L-lysine was substantially inhibited with Langmuir constants ∼ 10 times smaller. These observations suggest that cation exchange is the dominant adsorption mechanism for amino acids on montmorillonite. X-ray diffraction and infrared spectroscopy indicate that L-arginine and L-lysine enter the smectite interlayer where the protonated amino sidechain has the strongest interactions with the mineral surface, further supporting adsorption driven primarily through electrostatic interactions. Therefore, smectites on the early Earth may have selectively concentrated cationic amino acids, providing a potential template for the polymerization of α-amine linked peptides.

Glow & Lovely: Purpose-driven Brand

The rebranding of Fair & Lovely (F&L), one of Hindustan Unilever Limited’s (HUL) flagship brands, to Glow & Lovely (G&L) in 2020 had hogged the limelight. HUL termed the rebranding as an important evolutionary step that moved away from the “regressive idea of beauty” and banished an undesirable social stereotype. Stakeholders had divergent opinions with the rebranding effort being termed from “path-breaking” to “too little”. Likewise, there was a divided house on the future sales of the repositioned brand. However, G&L, akin to its predecessor, maintained traction in the marketplace. The case provides an opportunity to understand the concepts of brand positioning and brand repositioning. It highlights how a corporate citizen can engage in responsible advertising and break an undesirable social stereotype. Attributes associated with fairness were identified to capture the extent of brand repositioning. Attributes associated with fairness were identified to capture the extent of brand repositioning. The primary data collected on such attributes was analysed with the help of Multi-Dimensional Scaling using alternating least-squares (ALSCAL) method. Discriminant analysis was used to understand which attributes differentiated various brands of fairness creams.

Stoichiometry for entry and binding properties of the Env protein of R5 T cell-tropic HIV-1 and its evolutionary variant of macrophage-tropic HIV-1.

Human immunodeficiency virus type 1 normally targets CD4+ T cells for viral replication. When T cells are limiting, the virus can evolve to infect myeloid cells. The evolutionary step involves a change from requiring a high surface density of CD4 for entry to being able to infect cells with a low density of CD4, as is found on myeloid lineage cells such as macrophage and microglia. Viruses able to infect macrophages efficiently are most often found in the CNS late in the disease course, and such viruses may contribute to neurocognitive impairment. Here, we examine the CD4 binding properties of the viral Env protein to explore these two different entry phenotypes.

Astronomically paced climate and carbon cycle feedbacks in the lead-up to the Late Devonian Kellwasser Crisis

Abstract. Repeated carbon isotope excursions and widespread organic-rich shale deposition mark the Middle and Upper Devonian series. Various explanations such as extensive volcanism and land plant evolution have been given for these perturbations and the general sensitivity of the Devonian oceans to the development of anoxia, but their repeated nature suggests that astronomical forcing may have controlled their timing. Here, a cyclostratigraphic study of the Kellwasser Crisis at the Frasnian–Famennian stage boundary (ca. 372 Ma) is carried out. The Kellwasser Crisis was one of the most ecologically impactful of the Devonian perturbations and is ranked among the “Big Five” Phanerozoic mass extinctions. The studied site is the Winsenberg roadcut section in the Rhenish Massif, Germany, which represents a quiet tropical shelf basin setting. Centimetre-scale elemental records, generated by portable X-ray scanning, allow for testing of the hypothesis that a 2.4 Myr eccentricity node preceded the Upper Kellwasser event. The study's results are supportive of this hypothesis. We find enhanced chemical weathering (K2O / Al2O3) during the period leading up to the Upper Kellwasser and a peak in distal detrital input (SiO2 / CaO) and riverine runoff (TiO2 / Al2O3) just prior to the start of the Upper Kellwasser event. We interpret this pattern as the long-term eccentricity minimum facilitating excessive regolith build-up in the absence of strong seasonal contrasts. The Earth's system coming out of this node would have rapidly intensified the hydrological cycle, causing these nutrient-rich regoliths to be eroded and washed away to the oceans, where they resulted in eutrophication and anoxia. An astronomical control on regional climate is observed beyond this single crisis. Wet–dry cycles were paced by 405 kyr eccentricity, with both the Lower and Upper Kellwasser events taking place during comparatively drier times. A precession-sensitive monsoonal climate system prevailed on shorter timescales. Intensification of this monsoonal system following the node may have caused the widespread regolith erosion. We estimate the total duration of the Kellwasser Crisis at ca. 900 kyr, with the individual events lasting for ca. 250 and 100 kyr, respectively. If astronomical control indeed operated via regolith development in monsoonal climates, then land plants may have played an important role. This would not have been through evolutionary steps directly triggering Kellwasser perturbations but by gradually strengthening the climatic response to orbital forcing via soil development – creating soils thick enough to meaningfully respond to orbital forcing – and intensifying the hydrological cycle.

CAR-T Therapy of Multiple Myeloma, Based on the Congresses ASH-2021 and ASCO-2022

Current treatment of multiple myeloma (ММ) based on proteasome inhibitors, immunomodulating drugs, and monoclonal antibodies has, to a certain extent, reached the limit of its potential. Despite considerable clinical advance, ММ still remains a chronic incurable disease. Tumor-specific T-cell therapy with chimeric antigen receptor (CAR) is a new evolution step towards achieving MM cure. Today, B-cell maturation antigen (BCMA) is regarded as the primary target of CAR-T treatment of MM. This receptor is mainly expressed on the surface of tumor plasma cells in ММ as well as in B-cells of late differentiation stages and normal plasma cells. In 2021–2022, two CAR-T drugs, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), were approved for clinical use in the USA and the European Union for patients with relapsed/refractory MM. The studies of these drugs yielded encouraging clinical results. Other antigen (GPRC5D, SLAMF7) cell-based drugs are now in early stages of development. The present review is concerned with latest advances in CAR-T therapy for MM reported at the recent congresses ASH-2021 and ASCO-2022. The review comprehensively discusses the results of the KarMMa (ide-cel, stage II) and CARTITUDE-1 (cilta-cel, stage IB/II) studies. It also provides historical background of CAR-Т cell generation as well as preclinical and on-going clinical trial data on MM. It outlines potential failure causes and prospects of further improvement of the new technology.of its potential. Despite considerable clinical advance, ММstill remains a chronic incurable disease. Tumor-specific T-cell therapy with chimeric antigen receptor (CAR) isa new evolution step towards achieving MM cure. Today,B-cell maturation antigen (BCMA) is regarded as the primary target of CAR-T treatment of MM. This receptor is mainlyexpressed on the surface of tumor plasma cells in ММ aswell as in B-cells of late differentiation stages and normalplasma cells. In 2021–2022, two CAR-T drugs, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel(cilta-cel), were approved for clinical use in the USA andthe European Union for patients with relapsed/refractoryMM. The studies of these drugs yielded encouraging clinical results. Other antigen (GPRC5D, SLAMF7) cell-baseddrugs are now in early stages of development. The presentreview is concerned with latest advances in CAR-T therapyfor MM reported at the recent congresses ASH-2021 andASCO-2022. The review comprehensively discusses theresults of the KarMMa (ide-cel, stage II) and CARTITUDE-1(cilta-cel, stage IB/II) studies. It also provides historicalbackground of CAR-Т cell generation as well as preclinicaland on-going clinical trial data on MM. It outlines potentialfailure causes and prospects of further improvement of thenew technology.