Moving Toward Continuous Therapy in Multiple Myeloma

The introduction of novel agents, characterized by favorable toxicity profiles and higher manageability compared to conventional drugs employed in the past, has considerably changed the treatment paradigm for multiple myeloma. Continuous therapy currently represents the standard approach for myeloma patients both at diagnosis and at relapse. In younger patients, long-term maintenance after autologous transplantation significantly improved progression-free survival and overall survival compared to observation. Also in transplant-ineligible patients, continuous treatment with combinations of newer agents and maintenance treatment following a more intense induction phase proved to be superior as compared to fixed-duration therapy. Maintenance and continuous therapy at diagnosis have shown to deepen responses and suppress minimal residual disease. At relapse, continuous therapy allowed better disease control over time. This review covers the main evidence supporting the use of continuous therapy in multiple myeloma as well as the open issues, such as the optimal agents to be used and the optimal candidates for receiving them

Linking monoterpenes and abiotic stress resistance in grapevines

Rising temperatures and ozone levels are among the most striking stressful phenomena of global climate changes, and they threaten plants that are unable to react rapidly and efficiently. Generic responses of plants to stresses include the production of excess reactive oxygen species (ROS). Excessive ROS accumulation can lead to extensive oxidation of important components such as nucleic acids, proteins and lipids which can further exacerbate ROS accumulation leading to programmed cell death. Although most studies on plant antioxidants have focused on non-volatile compounds, volatiles belonging to the isoprenoid family have been implicated in the protection against abiotic stresses, in particular thermal and oxidative stress whose frequency and extent is being exacerbated by ongoing global change and anthropogenic pollution. Historically, research has focused on isoprene, demonstrating that isoprene-emitting plants are more tolerant to ozone exposure and heat stress, reducing ROS accumulation. Yet, evidence is being compiled that shows other volatile isoprenoids may be involved in plant responses against abiotic stresses. Grapevines are not isoprene emitters but some varieties produce other volatile isoprenoids such as monoterpenes. We investigated photosynthesis and emission of volatile organic compounds upon heat stress in two Vitis vinifera cv. ‘Chardonnay’ clones differing only for a mutation in the DXS gene (2-C-methyl-D-erythritol 4-phosphate (MEP) pathway), regulating volatile isoprenoid biosynthesis. We showed that the mutation led to a strong increase in monoterpene emission upon heat stress. At the same time, maximum photochemical quantum yield (Fv/Fm ratio) of PSII was affected by the stress in the non-emitting clone while the monoterpene emitter showed a significant resilience, thus indicating a possible antioxidant role of monoterpenes in grapevine. Future mechanistic studies should focus on unveiling the actual mechanism responsible for such findings

Molecular biology and pathogenicity of phytoplasmas

Phytoplasmas are a large group of plant-pathogenic wall-less, non-helical, bacteria associated with diseases, collectively referred to as yellows diseases, in more than a thousand plant species worldwide. Many of these diseases are of great economic importance. Phytoplasmas are difficult to study, in particular because all attempts at culturing these plant pathogens under axenic conditions have failed. With the introduction of molecular methods into phytoplasmology about two decades ago, the genetic diversity of phytoplasmas could be elucidated and a system for their taxonomic classification based on phylogenetic traits established. In addition, a wealth of information was generated on phytoplasma ecology and genomics, phytoplasma–plant host interactions and phytoplasma–insect vector relationships. Taxonomically, phytoplasmas are placed in the class Mollicutes, closely related to acholeplasmas, and are currently classified within the provisional genus ‘Candidatus Phytoplasma’ based primarily on 16S rDNA sequence analysis. Phytoplasmas are characterised by a small genome. The sizes vary considerably, ranging from 530 to 1350 kilobases (kb), with overlapping values between the various taxonomic groups and subgroups, resembling in this respect the culturable mollicutes. The smallest chromosome, about 530 kb, is known to occur in the Bermuda grass white leaf agent ‘Ca. Phytoplasma cynodontis’. This value represents the smallest mollicute chromosome reported to date. In diseased plants, phytoplasmas reside almost exclusively in the phloem sieve tube elements and are transmitted from plant to plant by phloem-feeding homopteran insects, mainly leafhoppers and planthoppers, and less frequently psyllids. Most of the phytoplasma host plants are angiosperms in which a wide range of specific and non-specific symptoms are induced. Phytoplasmas have a unique and complex life cycle that involves colonisation of different environments, the plant phloem and various organs of the insect vectors. Furthermore, many phytoplasmas have an extremely wide plant host range. The dynamic architecture of phytoplasma genomes, due to the occurrence of repetitive elements of various types, may account for variation in their genome size and adaptation of phytoplasmas to the diverse environments of their plant and insect hosts. The availability of five complete phytoplasma genome sequences has made it possible to identify a considerable number of genes that are likely to play major roles in phytoplasma–host interactions. Among these, there are genes encoding surface membrane proteins and effector proteins. Also, it has been shown that phytoplasmas dramatically alter their gene expression upon switching between plant and insect hosts

Dataset online data collection (Experiment I)

Dataset from the online data collection

Investigation of the formation of an amorphous film at the ZrO2-Y2O3/NiCoCrAlY interface of thermal barrier coatings produced by plasma spraying

The interface between metallic bonding layers (NiCoCrAlY) and ceramic coatings of 8% yttria partially stabilized zirconia (YPSZ), produced by air plasma spraying (APS) at different deposition temperatures, was investigated by scanning electron microscopy (SEM) and analytical transmission electron microscopy (ATEM) on transverse thin foils. The presence of an Al-rich amorphous film was ascertained, probably originating during the deposition of the bond coat as a crystalline alumina surface layer. This layer successively remelts, grows and solidifies in the amorphous stare due to the rapid heat extraction during plasma spraying. The thickness of this interlayer is a function of the deposition temperature: the higher the substrate temperature during spraying, the thinner the interfacial amorphous film. Columnar YPSZ grains, elongated in the direction perpendicular to the surface and having typical dimensions of 50 nm x 500 nm, are superimposed on the amorphous layer. Equiaxed grains of comparable size extend above the columnar structure. Both columnar and equiaxed grains consist of a metastable tetragonal phase t', characterized by a higher toughness than the face-centred cubic equilibrium phase. The negative influence of this brittle interlayer, in particular on the adhesion strength of the thermal barrier coating (TBC), was also evaluated by means of four-point bending tests. Results confirm a low adhesion strength between the ceramic and the bond coat in the case of TBCs produced at low deposition temperatures

Dataset laboratory data collection (experiment II)

Dataset laboratory data collection (experiment II)