Downfall of an empire: Unmasking the hidden diversity and distribution of the Amanita rubescens species complex.

Amanita is one of the most salient mushroom genera due to its cultural, economic, and medical importance. Recently, many new Amanita species have been described worldwide, increasing the genus richness. However, several clades have cryptic diversity, and many species complexes have not yet been resolved. This is the case of the rubescent species in the Validae section, which have been widely cited under the name Amanita rubescens s.l. We used a four-locus matrix (nuc rDNA internal transcribed spacer [ITS] and 28S regions and genes for RNA polymerase II subunit 2 [rpb2], translation elongation factor 1-α [tef1-α], and ß-tubulin [tub2]) to solve the phylogenetic relationships within the Amanita section Validae. To analyze the diversity and distribution patterns of species, we used an extensive ITS sequence sampling including environmental DNA databases. The phylogenetic analyses demonstrated that the Validae section is divided into three monophyletic and highly supported major clades: Mappae, Validae, and Rubescentes. At least 11 species-level clades within the Rubescentes clade were highly supported: A. cruentilemurum nom. prov. A. brunneolocularis, A. rubescens s.s. (European clade), A. rubescens s.s. (Asiatic clade), A. orsonii s.s. A. 'orsonii,' A. aureosubucula nom. prov., A. novinupta, A. flavorubens, and two undescribed North American species. We proved that A. rubescens s.s. has two segregated populations (European and Asiatic) and it is not naturally distributed in America. Furthermore, we found that America has more cryptic species within the Rubescentes clade than Eurasia.

Multiple domestication events explain the origin of Gossypium hirsutum landraces in Mexico.

Several Mesoamerican crops constitute wild-to-domesticated complexes generated by multiple initial domestication events, and continuous gene flow among crop populations and between these populations and their wild relatives. It has been suggested that the domestication of cotton (Gossypium hirsutum) started in the northwest of the Yucatán Peninsula, from where it spread to other regions inside and outside of Mexico. We tested this hypothesis by assembling chloroplast genomes of 23 wild, landraces, and breeding lines (transgene-introgressed and conventional). The phylogenetic analysis showed that the evolutionary history of cotton in Mexico involves multiple events of introgression and genetic divergence. From this, we conclude that Mexican landraces arose from multiple wild populations. Our results also revealed that their structural and functional chloroplast organizations had been preserved. However, genetic diversity decreases as a consequence of domestication, mainly in transgene-introgressed (TI) individuals (π = 0.00020, 0.00001, 0.00016, 0, and 0, of wild, TI-wild, landraces, TI-landraces, and breeding lines, respectively). We identified homologous regions that differentiate wild from domesticated plants and indicate a relationship among the samples. A decrease in genetic diversity associated with transgene introgression in cotton was identified for the first time, and our outcomes are therefore relevant to both biosecurity and agrobiodiversity conservation.

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.

Incorporating evolutionary and threat processes into crop wild relatives conservation.

Crop wild relatives (CWR) intra- and interspecific diversity is essential for crop breeding and food security. However, intraspecific genetic diversity, which is central given the idiosyncratic threats to species in landscapes, is usually not considered in planning frameworks. Here, we introduce an approach to develop proxies of genetic differentiation to identify conservation areas, applying systematic conservation planning tools that produce hierarchical prioritizations of the landscape. It accounts for: (i) evolutionary processes, including historical and environmental drivers of genetic diversity, and (ii) threat processes, considering taxa-specific tolerance to human-modified habitats, and their extinction risk status. Our analyses can be used as inputs for developing national action plans for the conservation and use of CWR. Our results also inform public policy to mitigate threat processes to CWR (like crops living modified organisms or agriculture subsidies), and could advise future research (e.g. for potential germplasm collecting). Although we focus on Mesoamerican CWR within Mexico, our methodology offers opportunities to effectively guide conservation and monitoring strategies to safeguard the evolutionary resilience of any taxa, including in regions of complex evolutionary histories and mosaic landscapes.