Structural heterozygosity in Scilla hyacinthoides L. and Scilla amoena L. (Liliaceae). Karyological analysis

Abstract

A karyological analysis carried out in Scilla hyacinthoides L. and Scilla amoena L. on material collected in the Botanical Garden of Cagliari (Sardinia), has shown the presence of heterozygous karyotypes in the two species. The chromosome number of S. hyacinthoides was found to be 2n = 20, while the chromosome number of S. amoena was 2n = 12, in accordance with the data found in the literature. Both the observed karyotypes show clear structural alterations, especially evident in one pair of clearly heteromorphic chromosomes. The analysis of the karyotypes seem to exclude a hybrid origin of the material examined and it is probable that such karyotypes may be the result of various structural re-arrangements, still evolving and aiming at a cytogenetic stabilization of the genus Scilla.     

Genetic variation in eggplant for Nitrogen Use Efficiency under contrasting NO3‐ supply

Eggplant (Solanum melongena L.) yield is highly sensitive to N fertilization, the excessive use of which is responsible for environmental and human health damage. Lowering N input together with the selection of improved Nitrogen‐Use‐Efficiency (NUE) genotypes, more able to uptake, utilize, and remobilize N available in soils, can be challenging to maintain high crop yields in a sustainable agriculture. The aim of this study was to explore the natural variation among eggplant accessions from different origins, in response to Low (LN) and High (HN) Nitrate (NO₃^‐) supply, to identify NUE‐contrasting genotypes and their NUE‐related traits, in hydroponic and greenhouse pot experiments. Two eggplants, AM222 and AM22, were identified as N‐use efficient and inefficient, respectively, in hydroponic, and these results were confirmed in a pot experiment, when crop yield was also evaluated. Overall, our results indicated the key role of N‐utilization component (NUtE) to confer high NUE. The remobilization of N from leaves to fruits may be a strategy to enhance NUtE, suggesting glutamate synthase as a key enzyme. Further, omics technologies will be used for focusing on C‐N metabolism interacting networks. The availability of RILs from two other selected NUE‐contrasting genotypes will allow us to detect major genes/quantitative trait loci related to NUE.     

Plant natural fragments,an innovative approach for drug discovery

Plant natural products (PNP) (e.g., secondary vegetal metabolites and their derivatives) have been a productive source of active ingredients for the pharmaceutical industry. The High Throughput Screening of Plant Natural Products (PNP-HTS) with extracts or isolated compounds has shown to be time consuming, expensive, and not as successful as expected. Recently building upon the innovative fragment-based drug discovery (FBDD) a disruptive approach was developed based on PNP. The fragment approach involves elaboration and/or isolation of weakly binding small molecules with molecular weights between 150 and 250 Da. This method is fundamentally different from HTS in almost every aspect (i.e., size of the compound library, screening methods, and optimization steps from hit to lead). Due to their nature, vegetal natural fragments have unique three-dimensional (3D) properties, high Fsp³, low aromaticity, and large chemo-diversities which represent potential opportunities for developing novel drugs. Preliminary results using vegetal natural fragments appear to be a promising and emerging field which offers valuable prospects for developing new drugs.

     

Inhibition of bromodomain and extra‐terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia

The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19⁺ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones.     

The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.     

NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice

While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3‐inflammasome protected mice from age‐related increased insulin sensitivity, reduced IGF‐1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age‐dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt‐mediated NAD⁺ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age‐associated changes in the heart, preserved cardiac function of aged mice and increased lifespan.