Comparative Genomic Analysis Reveals a Critical Role of De Novo Nucleotide Biosynthesis for Saccharomyces cerevisiae Virulence

In recent years, the number of human infection cases produced by the food related species Saccharomyces cerevisiae has increased. Whereas many strains of this species are considered safe, other ‘opportunistic’ strains show a high degree of potential virulence attributes and can cause infections in immunocompromised patients. Here we studied the genetic characteristics of selected opportunistic strains isolated from dietary supplements and also from patients by array comparative genomic hybridization. Our results show increased copy numbers of IMD genes in opportunistic strains, which are implicated in the de novo biosynthesis of the purine nucleotides pathway. The importance of this pathway for virulence of S. cerevisiae was confirmed by infections in immunodeficient murine models using a GUA1 mutant, a key gene of this pathway. We show that exogenous guanine, an end product of this pathway in its triphosphorylated form, increases the survival of yeast strains in ex vivo blood infections. Finally, we show the importance of the DNA damage response that activates dNTP biosynthesis in yeast cells during ex vivo blood infections. We conclude that opportunistic yeasts may use an enhanced de novo biosynthesis of the purine nucleotides pathway to increase survival and favor infections in the host.     

Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status

Introduction

Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations.

Patients and Methods

We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number – defined as mean of 3 to 5 fusion signals in ≥10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease.

Results

No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885).

Conclusion

Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.     

Flower and fruit structure of the endangered species Petagnaea gussonei (Sprengel) Rauschert (Saniculoideae,Apiaceae) and implications for its reproductive biology

Petagnaea gussonei (Apiaceae) is an endangered species endemic to the Nebrodi mountains (north-eastern Sicily). Although an increasing number of studies have been performed on this species, its reproductive biology remains poorly understood. The aim of this study was to investigate in detail the structure of the flower and the fruit of Petagnaea, and the possible implications for its breeding system and seed dispersal mechanism. Results from fieldwork, light microscopy and scanning electron microscopy suggest (1) the presence of protandrous hermaphrodite flowers; (2) geitonogamy, autogamy, and allogamy as breeding system mechanisms of P. gussonei, even if asexual reproduction is preferred by the plant; and (3) epizoochory and hydrochory as possible modalities of fruit dispersal.     

Insights on the Use of Hybrid Life Cycle Assessment for Environmental Footprinting

Establishing a comprehensive environmental footprint that indicates resource use and environmental release hotspots in both direct and indirect operations can help companies formulate impact reduction strategies as part of overall sustainability efforts. Life cycle assessment (LCA) is a useful approach for achieving these objectives. For most companies, financial data are more readily available than material and energy quantities, which suggests a hybrid LCA approach that emphasizes use of economic input‐output (EIO) LCA and process‐based energy and material flow models to frame and develop life cycle emission inventories resulting from company activities. We apply a hybrid LCA framework to an inland marine transportation company that transports bulk commodities within the United States. The analysis focuses on global warming potential, acidification, particulate matter emissions, eutrophication, ozone depletion, and water use. The results show that emissions of greenhouse gases, sulfur, and particulate matter are mainly from direct activities but that supply chain impacts are also significant, particularly in terms of water use. Hotspots were identified in the production, distribution, and use of fuel; the manufacturing, maintenance, and repair of boats and barges; food production; personnel air transport; and solid waste disposal. Results from the case study demonstrate that the aforementioned footprinting framework can provide a sufficiently reliable and comprehensive baseline for a company to formulate, measure, and monitor its efforts to reduce environmental impacts from internal and supply chain operations.     

Adult neural stem cells: an endogenous tool to repair brain injury?

Research on stem cells has developed as one of the most promising areas of neurobiology. In the beginning of the 1990s, neurogenesis in the adult brain was indisputably accepted, eliciting great research efforts. Neural stem cells in the adult mammalian brain are located in the ‘neurogenic’ areas of the subventricular and subgranular zones. Nevertheless, many reports indicate that they subsist in other regions of the adult brain. Adult neural stem cells have arisen considerable interest as these studies can be useful to develop new methods to replace damaged neurons and treat severe neurological diseases such as neurodegeneration, stroke or spinal cord lesions. In particular, a promising field is aimed at stimulating or trigger a self‐repair system in the diseased brain driven by its own stem cell population. Here, we will revise the latest findings on the characterization of active and quiescent adult neural stem cells in the main regions of neurogenesis and the factors necessary to maintain their active and resting states, stimulate migration and homing in diseased areas, hoping to outline the emerging knowledge for the promotion of regeneration in the brain based on endogenous stem cells.     

Short-term effects of soil solarization in suppressing Calonectria microsclerotia

Background and aims

Calonectria species have been reported as devastating pathogens mostly on horticultural and forest crops worldwide. Since these pathogens represent a serious threat for the nursery production, the aim of this study was to investigate on the short-term potential of soil solarization for eradicating Calonectria microsclerotia.

Methods

Twenty Calonectria isolates collected in Italy from different hosts and locations were identified by using DNA sequencing of β-tubulin. The effect of thermal regimes and innovative solarizing films on the soil survival of Calonectria microsclerotia was evaluated through time at different sampling periods in growth chamber and greenhouse experiments.

Results

Eleven and nine isolates were identified as Calonectria pauciramosa and Calonectria polizzii, respectively. No viable Calonectria inoculum was recovered after 12 days from all solarized plots inside ethylene-tetrafluoroethylene (ETFE) greenhouse and at 15-cm depth from solarized plots inside ethylene-vinyl-acetate (EVA) greenhouse. Under EVA cover, solarization killed C. pauciramosa microsclerotia within 9 and 17 d at 15- and 30-cm depths in soil, respectively, whereas no viable inoculum was retrieved within 6 and 12 days from solarized plots inside ETFE greenhouse.

Conclusions

This paper demonstrates that short-term soil solarization is effective for Calonectria microsclerotia suppression in nurseries, and shows that ETFE film as well as other innovative materials could improve this technique.