In the world of insects, beetles rule. Evolutionary and palaeoecological interpretations using fossil beetles from Cretaceous ambers have become increasingly frequent in recent years, consequently ...leading to the discovery of an increasing number of new coleopteran species. By the end of 2019, a total of 364 new species from 81 families (some of them only known as fossils) were compiled, which are presented in this article. Beetles are currently among the most important pollinators of basal flowering plants and are thought to have been so since the origin of angiosperms. Some recent studies on specimens from Cretaceous amber support this idea, indicating the existence of a pre-existing guild of beetles that pollinated gymnosperms during the Early Cretaceous, with some groups moving from older gymnosperm to more recent angiosperm hosts. The effect of wood-boring beetle pests on resiniferous ancient forests has been widely cited in the literature, but there is no direct evidence in Cretaceous ambers. The current abundance of Lymexylidae beetles in Kachin amber (Myanmar) suggests that together with abiotic factors such as wildfires, storms, hurricanes and volcanos, fungal infections should also be thoroughly analysed as a cause of resin release in the past. In this review, we show how beetles from Cretaceous ambers are a useful tool for studying community and trophic structures as well as evolutionary implications for the ecosystem.
•Studies of fossil beetles from Cretaceous ambers have become frequent in recent years.•By the end of 2019, a total of 364 new species from 81 families were compiled.•The study of beetles from amber show evolutionary implications for the ecosystem.•Beetles were about the earliest pollinators of angiosperms during the Cretaceous.•Fungal infections should be analysed as a cause of resin release in the past.
Interactions with angiosperms have been hypothesised to play a crucial role in driving diversification among insects, with a particular emphasis on pollinator insects. However, support for ...coevolutionary diversification in insect-plant interactions is weak. Macroevolutionary studies of insect and plant diversities support the hypothesis that angiosperms diversified after a peak in insect diversity in the Early Cretaceous. Here, we used the family-level fossil record of insects as a whole, and insect pollinator families in particular, to estimate diversification rates and the role of angiosperms on insect macroevolutionary history using a Bayesian process-based approach. We found that angiosperms played a dual role that changed through time, mitigating insect extinction in the Cretaceous and promoting insect origination in the Cenozoic, which is also recovered for insect pollinator families only. Although insects pollinated gymnosperms before the angiosperm radiation, a radiation of new pollinator lineages began as angiosperm lineages increased, particularly significant after 50 Ma. We also found that global temperature, increases in insect diversity, and spore plants were strongly correlated with origination and extinction rates, suggesting that multiple drivers influenced insect diversification and arguing for the investigation of different explanatory variables in further studies.
Copper complexes are of medicinal and biological interest, including as anticancer drugs designed to cleave intracellular biomolecules by O2 activation. To exhibit such activity, the copper complex ...must be redox active and resistant to dissociation. Metallothioneins (MTs) and glutathione (GSH) are abundant in the cytosol and nucleus. Because they are thiol‐rich reducing molecules with high CuI affinity, they are potential competitors for a copper ion bound in a copper drug. Herein, we report the investigation of a panel of CuI/CuII complexes often used as drugs, with diverse coordination chemistries and redox potentials. We evaluated their catalytic activity in ascorbate oxidation based on redox cycling between CuI and CuII, as well as their resistance to dissociation or inactivation under cytosolically relevant concentrations of GSH and MT. O2‐activating CuI/CuII complexes for cytosolic/nuclear targets are generally not stable against the GSH/MT system, which creates a challenge for their future design.
Copper complexes are of medicinal and biological interest, including as anticancer drugs. O2‐activating CuI/CuII complexes for cytosolic/nuclear targets are generally not stable against glutathione and metallothioneins, which are abundant in the nucleus and cytosol. This should be considered when designing CuI/CuII complexes for biological and medicinal applications.
Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed cancer in the world. Its epidemiology depends not only on tobacco exposition but also air quality. While the global ...trends in NSCLC incidence have started to decline, we can observe region-dependent differences related to the education and the economic level of the patients. Due to an increasing understanding of NSCLC biology, new diagnostic and therapeutic strategies have been developed, such as the reorganization of histopathological classification or tumor genotyping. Precision medicine is focused on the recognition of a genetic mutation in lung cancer cells called “driver mutation” to provide a variety of specific inhibitors of improperly functioning proteins. A rapidly growing group of approved drugs for targeted therapy in NSCLC currently allows the following mutated proteins to be treated: EGFR family (ERBB-1, ERBB-2), ALK, ROS1, MET, RET, NTRK, and RAF. Nevertheless, one of the most frequent NSCLC molecular sub-types remains without successful treatment: the K-Ras protein. In this review, we discuss the current NSCLC landscape treatment focusing on targeted therapy and immunotherapy, including first- and second-line monotherapies, immune checkpoint inhibitors with chemotherapy treatment, and approved predictive biomarkers.
ABSTRACT
Insect–fungus mutualism is one of the better‐studied symbiotic interactions in nature. Ambrosia fungi are an ecological assemblage of unrelated fungi that are cultivated by ambrosia beetles ...in their galleries as obligate food for larvae. Despite recently increased research interest, it remains unclear which ecological factors facilitated the origin of fungus farming, and how it transformed into a symbiotic relationship with obligate dependency. It is clear from phylogenetic analyses that this symbiosis evolved independently many times in several beetle and fungus lineages. However, there is a mismatch between palaeontological and phylogenetic data. Herein we review, for the first time, the ambrosia system from a palaeontological perspective. Although largely ignored, families such as Lymexylidae and Bostrichidae should be included in the list of ambrosia beetles because some of their species cultivate ambrosia fungi. The estimated origin for some groups of ambrosia fungi during the Cretaceous concurs with a known high diversity of Lymexylidae and Bostrichidae at that time. Although potentially older, the greatest radiation of various ambrosia beetle lineages occurred in the weevil subfamilies Scolytinae and Platypodinae during the Eocene. In this review we explore the evolutionary relationship between ambrosia beetles, fungi and their host trees, which is likely to have persisted for longer than previously supposed.
Evidence of behavior is rarely found in fossil record. Here we describe two new species in Coleoptera tentatively described in Kateretidae based on two syninclusions (co-occurrences of multiple ...individuals) from mid-Cretaceous Kachin amber (Myanmar). Cretaretes minimus gen. et sp. nov. is described based on 41 fossil beetle specimens together in one piece of fossil resin and Eoceniretes antiquus sp. nov. is also described based on 41 fossil beetle specimens together in another piece of fossil resin from the same deposit. Eoceniretes Kirejtshuk and Nel, 2008 was first described from a fossil embedded in the lower Eocene Oise amber (France). This new species, Eoceniretes antiquus sp. nov., exhibits sexual dimorphism; males have a long and modified scapes. Although male mechanical modifications are usually understood to play a role in intrasexual competition, in this case the modified scapes is hypothesized to fulfill some function for sexual communication rather than for fighting. The syninclusions of many specimens from the same species demonstrate that this group of beetles, which today form large aggregations as larval and adult stages to feed on angiosperm flowers, had this aggregation behavior as early as the mid-Cretaceous. Kachin Myanmar amber (98.79 ± 0.62 Ma) was deposited during an intense diversification of angiosperms (also called Cretaceous Terrestrial Revolution), and so we postulate that Kateretidae were a possible pollinators for the basal angiosperms, an inference based upon their aggregative and pollination behavior in the extant species.
•Two syninclusions of Coleoptera in amber are described in two different new species.•They provide from mid-Cretaceous Kachin amber (Myanmar).•Eoceniretes antiquus shows modified scapes with function in sexual communication.•Kateretidae were possible pollinators for the basal angiosperms.
The ability of
to produce volatile sulfur compounds from sulfur amino acids and the metabolic pathway involved have been studied in seven strains from different food origins. Our results proved that ...l-methionine is the main precursor for sulfur compound generation. Crucial differences in the sulfur compound profile and amino acid consumption among
strains isolated from different food sources were observed. Strains isolated from dry pork sausages displayed the most complex sulfur compound profiles. Sulfur compound production, such as that of methional, could result from chemical reactions or yeast metabolism, while according to this study, thioester methyl thioacetate appeared to be generated by yeast metabolism. No relationship between sulfur compounds production by
strains and the expression of genes involved in sulfur amino acid metabolism was found, except for the
gene in the L1 strain for production of methyl thioacetate. Our results suggest a complex scenario during sulfur compound production by
.
Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS‐based lipidomics has become a powerful tool for the ...comprehensive determination of lipids. LC‐MS lipid profiling of HepG2 cells is proposed as an in vitro assay to study and anticipate phospholipidosis and steatosis. Cells with and without preincubation with a mixture of free fatty acids (FFA; i.e. oleic and palmitic) were exposed to a set of well‐known steatogenic and phospholipidogenic compounds. The use of FFA preloading accelerated the accumulation of phospholipids, thus leading to a better discrimination of phospholipidosis, and magnified the lipidomic alterations induced by steatogenic drugs. Phospholipidosis was characterized by increased levels of phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, and phosphatidylinositols, while steatosis induced alterations in FA oxidation and triacylglyceride (TG) synthesis pathways (with changes in the levels of FFA, acylcarnitines, monoacylglycerides, diacylglycerides, and TG). Interestingly, palmitic and oleic acids incorporation into lipids differed. A characteristic pattern was observed in the fold of change of particular TG species in the case of steatosis (TG(54:3) > TG(52:2) > TG(50:1) > TG(48:0)). Based on the levels of those lipids containing only palmitic and/or oleic acid moieties a partial least squares‐discriminant analysis model was built, which showed good discrimination among nontoxic, phospholipidogenic and steatogenic compounds. In conclusion, it has been shown that the use of FFA preincubation together with intracellular LC‐MS based lipid profiling could be a useful approach to identify the potential of drug candidates to induce phospholipidosis and/or steatosis.
Raman spectroscopy coupled to partial least squares (PLS) was used for the classification of amber samples according to their provenance and geological age. Spectral data were from samples from Czech ...Republic, Baltic region, and objects dated back from Upper Cretaceous and Cenozoic ages. Intensity ratio of two wavenumbers has been used as indicator of both geological age and provenance amber so far.
In this work, an alternative chemometric approach was proposed to select additional intervals of the spectra where discrimination relies. Several metrics (number of misclassifications and permutation test) evaluated the capability of the alternative PLS models to predict future measurements.
Results achieved indicated the possibility to assess the geological age and provenance of amber considering an interval of wavenumbers instead of single wavenumbers that could be disturbed by physical effects. Furthermore, differences in the Raman spectra were highlighted by using Variable Importance Projection methodology over PLS model. The proposed methodology clearly distinguished Baltic from Czech Republic amber and resins from Cenozoic period and Upper Cretaceous. This research could represent a breakthrough for amber cultural heritage studies.
Succinite and Valchovite amber were discriminated by Raman spectroscopy coupled to chemometrics. Variable importance projection characterized Baltic and Czech Republic fossil resins. Spectral wavenumbers from variable importance projection analysis revealed provenance and geological age of fossil resins.
Balancing selection, an evolutionary force that retains genetic diversity, has been detected in multiple genes and organisms, such as the sexual mating loci in fungi. However, to quantify the ...strength of balancing selection and define the mating-related genes require a large number of strains. In tetrapolar basidiomycete fungi, sexual type is determined by two unlinked loci, MATA and MATB. Genes in both loci define mating type identity, control successful mating and completion of the life cycle. These loci are usually highly diverse. Previous studies have speculated, based on culture crosses, that species of the non-model genus Trichaptum (Hymenochaetales, Basidiomycota) possess a tetrapolar mating system, with multiple alleles. Here, we sequenced a hundred and eighty strains of three Trichaptum species. We characterized the chromosomal location of MATA and MATB, the molecular structure of MAT regions and their allelic richness. The sequencing effort was sufficient to molecularly characterize multiple MAT alleles segregating before the speciation event of Trichaptum species. Analyses suggested that long-term balancing selection has generated trans-species polymorphisms. Mating sequences were classified in different allelic classes based on an amino acid identity (AAI) threshold supported by phylogenetics. 17,550 mating types were predicted based on the allelic classes. In vitro crosses allowed us to support the degree of allelic divergence needed for successful mating. Even with the high amount of divergence, key amino acids in functional domains are conserved. We conclude that the genetic diversity of mating loci in Trichaptum is due to long-term balancing selection, with limited recombination and duplication activity. The large number of sequenced strains highlighted the importance of sequencing multiple individuals from different species to detect the mating-related genes, the mechanisms generating diversity and the evolutionary forces maintaining them.
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