In vitro induction of neoantigen-specific T cells in myelodysplastic syndrome,a disease with low mutational burden

Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34⁺) and normal (CD3⁺) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4⁺ response and 11 (34%) induced a CD8⁺ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients.     

Effect of amino acids and amines on the activity of the recombinant ι-carbonic anhydrase from the Gram-negative bacterium Burkholderia territorii

We here report a study on the activation of the ι-class bacterial CA from Burkholderia territorii (BteCAι). This protein was recently characterised as a zinc-dependent enzyme that shows a significant catalytic activity (k_cat 3.0 × 10⁵ s⁻¹) for the physiological reaction of CO₂ hydration to bicarbonate and protons. Some amino acids and amines, among which some proteinogenic derivatives as well as histamine, dopamine and serotonin, showed efficient activating properties towards BteCAι, with activation constants in the range 3.9–13.3 µM. L-Phe, L-Asn, L-Glu, and some pyridyl-alkylamines, showed a weaker activating effect towards BteCAι, with K_A values ranging between 18.4 µM and 45.6 µM. Nowadays, no information is available on active site architecture, metal ion coordination and catalytic mechanism of members of the ι-group of CAs, and this study represents another contribution towards a better understanding of this still uncharacterised class of enzymes.     

A method for 3D detection of symmetry line in asymmetric postures

The methods for symmetry line detection presented in the literature are typically suited to analyse symmetric upright postures, both standing and seated. The proposed method focuses on the symmetry line detection in subjects assuming asymmetric postures in which this line falls far outside the sagittal plane. The proposed approach evaluates the symmetry line by means of an autoregressive process in order to determine the set of planes suited to slice the back coherently with its geometric spatial configuration. The method is analysed assuming the cutaneous marking as reference and it is compared with a previous one, also developed by these authors. Results are analysed and critically discussed.     

Entomological surveillance,spatial distribution,and diversity of Culicidae (Diptera) immatures in a rural area of the Atlantic Forest biome,State of São Paulo,Brazil

Because of the high adaptive capacity of mosquitoes, studies that focus on transitional environments become very important, such as those in rural areas, which are considered as bridges between wild diseases and human populations of urban areas. In this study, a survey of the existing species of mosquitoes was performed in an Atlantic Forest area of the city of Santa Bárbara d'Oeste, São Paulo state, Brazil, using traps for immatures and analyzing the frequency and distribution of these insects over the sampling months. Five mosquito species were found: Aedes albopictus (the most frequent species), Aedes aegypti, Aedes fluviatilis, Culex quinquefasciatus, and Toxorhynchites theobaldi. The 4,524 eggs collected in ovitraps showed the presence of the tribe Aedini. Aedes aegypti and Ae. albopictus were identified after larval hatching in the laboratory, with different spatial distributions: the first of which coincides with the area of greatest diversity calculated using the Simpson index, while the second does not. The association of ecological analysis of spatial diversity with simple methods of data collection enables the identification of possible epidemiological risk situations and is a strategy that may be implemented to monitor ecological processes resulting from the interaction among different species of mosquitoes.     

The past,present and future of thermophilous Cyperus polystachyos Rottb. (Cyperaceae) on the island of Ischia (southern Italy)

Cyperus polystachyos is a hygrophilous, thermophilous and heliophilous plant with a punctiform distribution in southern Italy, where it is almost exclusively found on Ischia, an island in the Bay of Naples characterized by widespread volcanic hydrothermal activity. This species is a native of tropical and subtropical areas and there is evidence for ancient isolation events in the creation of its current distribution pattern. We have studied the historical literature available for this plant since 1800 and collected temporal and spatial presence data of this species in order to develop a habitat suitability map based on a GIS approach and using a multiple linear regression model. Moreover, we have used univariate and multivariate statistical analysis. The results show the importance of the environmental mosaic around fumaroles to preserve the species; urbanization and geothermal energy use of fumaroles in the past and the combination of abandonment of the typical agricultural system and the natural occurrence of reforestation in the present are the main causes of the decline in the number of populations.     

Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling

Wnt/β-catenin signalling is central to development and its regulation is essential in preventing cancer. Using phosphorylation of Dishevelled as readout of pathway activation, we identified Drosophila Wnk kinase as a new regulator of canonical Wnt/β-catenin signalling. WNK kinases are known for regulating ion co-transporters associated with hypertension disorders. We demonstrate that wnk loss-of-function phenotypes resemble canonical Wnt pathway mutants, while Wnk overexpression causes gain-of-function canonical Wnt-signalling phenotypes. Importantly, knockdown of human WNK1 and WNK2 also results in decreased Wnt signalling in mammalian cell culture, suggesting that Wnk kinases have a conserved function in ensuring peak levels of canonical Wnt signalling.     

Microvesicles as promising biological tools for diagnosis and therapy

ABSTRACT

Introduction: Shed by most cells, in response to a myriad of stimuli, extracellular vesicles (EVs) carry proteins, lipids, and various nucleic acids. EVs encompass diverse subpopulations differing for biogenesis and content. Among these, microvesicles (MVs) derived from plasma membrane, are key regulators of physiopathological cellular processes including cancer, inflammation and infection. This review is unique in that it focuses specifically on the MVs as a mediator of information transfer. In fact, few proteomic studies have rigorously distinguished MVs from exosomes.

Areas covered: Aim of this review is to discuss the proteomic analyses of the MVs. Many studies have examined mixed populations containing both exosomes and MVs. We discuss MVs’ role in cell-specific interactions. We also show their emerging roles in therapy and diagnosis.

Expert commentary: We see MVs as therapeutic tools for potential use in precision medicine. They may also have potential for allowing the identification of new biomarkers. MVs represent an invaluable tool for studying the cell of origin, which they closely represent, but it is critical to build a repository with data from MVs to deepen our understanding of their molecular repertoire and biological functions.