87 research outputs found
Understanding preferences for nature based and sustainable tourism. The role of personal values and general and specific environmental attitudes
This paper reports the results of a study which investigated the social psychological correlates of peopleâs preferences for sustainable and unsustainable tourism activities. Two-hundred-eighty-two participants from two Italian cities responded to a questionnaire which recorded their tourism preferences, their general pro-environmental attitudes and values, and their specific attitudes towards sustainable tourism. Results showed positive correlations among the constructs considered. Groups of participants differing in their tourism preferences were also identified and the paper discusses the way in which the social psychological variables considered here may be used to plan adequate strategies and management instruments able to address crucial issues of sustainability in tourism, including, for example, touristsâ ecological behaviors âon siteâ and their educational needs
Antennal Protein Profile in Honeybees: Caste and Task Matter More Than Age
Reproductive and task partitioning in large colonies of social insects suggest that colony members belonging to different castes or performing different tasks during their life (polyethism) may produce specific semiochemicals and be differently sensitive to the variety of pheromones involved in intraspecific chemical communication. The main peripheral olfactory organs are the antennal chemosensilla, where the early olfactory processes take place. At this stage, members of two different families of soluble chemosensory proteins [odorant-binding proteins (OBPs) and chemosensory proteins (CSPs)] show a remarkable affinity for different odorants and act as carriers while a further family, the Niemann-Pick type C2 proteins (NPC2) may have a similar function, although this has not been fully demonstrated. Sensillar lymph also contains Odorant degrading enzymes (ODEs) which are involved in inactivation through degradation of the chemical signals, once the message is conveyed. Despite their importance in chemical communication, little is known about how proteins involved in peripheral olfaction and, more generally antennal proteins, differ in honeybees of different caste, task and age. Here, we investigate for the first time, using a shotgun proteomic approach, the antennal profile of honeybees of different castes (queens and workers) and workers performing different tasks (nurses, guards, and foragers) by controlling for the potential confounding effect of age. Regarding olfactory proteins, major differences were observed between queens and workers, some of which were found to be more abundant in queens (OBP3, OBP18, and NPC2-1) and others to be more abundant in workers (OBP15, OBP21, CSP1, and CSP3); while between workers performing different tasks, OBP14 was more abundant in nurses with respect to guards and foragers. Apart from proteins involved in olfaction, we have found that the antennal proteomes are mainly characterized by castes and tasks, while age has no effect on antennal protein profile. Among the main differences, the strong decrease in vitellogenins found in guards and foragers is not associated with age
A pH-responsive crosslinker platform for antibody-drug conjugate (ADC) targeting delivery
We report a new 1-6 self-immolative, traceless crosslinker derived from the natural product gallic acid. The linker acts through a pH-dependent mechanism for drug release. This 5-(hydroxymethyl)pyrogallol orthoester derivative (HMPO) was stable for 24 hours at pH values of 7.4 and 6.6 and in plasma, releasing molecules bound to the hydroxymethyl moiety under acid-dependent stimuli at pH 5.5. The linker was non-toxic and was used for the conjugation of Doxorubicin (Doxo) or Combretastatin A4 with Cetuximab. The ADCs formed showed their pH responsivity reducing cell viability of A431 and A549 cancer cells better than Cetuximab alone. © 2022 The Royal Society of Chemistry
Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity
<p>Abstract</p> <p>Background</p> <p>Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinase-positive amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5 oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the trans-membrane Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this interaction has functional consequences on cell metabolism and phenotype.</p> <p>Methods</p> <p>The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14) by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored.</p> <p>Results</p> <p>We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs.</p> <p>Conclusion</p> <p>Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these effects can modulate the cell phenotype and can induce a higher sensitivity to tyrosine related anti-blastic drugs.</p
La lutte des ouvriers de GKN Florence, entre auto-organisation ouvriĂšre et mobilisation sociale
Cette chronique dĂ©crit la lutte des travailleurs de lâusine GKN de Florence contre sa fermeture et sa dĂ©localisation. AprĂšs avoir rendu compte des principales Ă©tapes du conflit, lâarticle se penche sur trois aspects fondamentaux : lâorganisation syndicale interne Ă lâusine et sa capacitĂ© Ă renforcer les ressources militantes autonomes des travailleurs, lâhabiletĂ© de ces derniers Ă mobiliser le tissu social environnant et Ă nouer des alliances avec dâautres mouvements sociaux et, enfin, la contribution apportĂ©e par le monde de lâuniversitĂ© et de la recherche dans lâĂ©laboration dâun plan de reconversion du site
Antibody drug conjugates with hydroxamic acid cargos for histone deacetylase (HDAC) inhibition.
The bioconjugation of hydroxamic acids to antibodies has been made possible through a non-cleavable linker based on the p-mercaptobenzyl alcohol structure that releases hydroxamates in the cells
The isolated Erebia pandrose Apennine population is genetically unique and endangered by climate change
1. Climate change is causing shifts in the distribution of many species and populations inhabiting mountain tops are particularly vulnerable to these threats because they are constrained in altitudinal shifts. Apennines are a relatively narrow and low mountain chain located in Southern Europe, which hosts many isolated populations of mountain species. The butterfly Erebia pandrose was recorded for the last time in the Apennines in 1977, on the top of a single massif (Monti della Laga).
2. We confirmed the presence of a small, isolated population of E. pandrose in the Apennines, at a distance of more than 400Âżkm to any other known populations. Then, we examined the cytochrome c oxidase subunit 1 mitochondrial DNA marker of this species across the Palaearctic area and estimated the potential decline over the Alps and the Apennines due to future climatic changes.
3. The Apennine population represents an endemic lineage characterised by eight mutations over the 658Âżbp analysed (1.2%). In the Alps and Apennines, this species has shifted uphill more than 3 m per year since the end of the 19th century and more than 22 m per year since 1995. Species distribution models suggested that these mountain populations will experience a generalised loss of climatic suitability, which, according to our projections, could lead to the extinction of the Apennine population in a few decades.
4. Erebia pandrose has the potential to become a flagship species for advertising the risk of losing unique fractions of genetic diversity for mountain species.funded by the project: âRicerca e conservazione sui lepidotteri diurni di sei Parchi Nazionali dell'Appennino centro-settentrionaleâ. Support for this research was also provided by âLa Caixaâ Foundation (ID 100010434) to M.M. (grant LCF/BQ/DR20/11790020), by the Academy of Finland to V.D. (Academy Research Fellow, decision no. 328895) and by project PID2019-107078GB-I00/AEI/10.13039/501100011033 to R.V.1 Introduction
2 Materials and methods
2.1 Data collection
2.2 COI analyses
2.3 Species distribution modelling
2.4 Elevational shifts of E. pandrose records through time
3 Results
3.1 COI structure
3.2 Climate change effects
4 Discussion
4.1 The population of Monte Gorzano
4.2 What is the future for E. pandrose on the Apennines?
4.3 Erebia pandrose in the context of preserving Apennine butterflies
5 Conclusions
Acknowledgements
Conflict of interes
Un viaggio nella Gestalt: come cambia il benessere durante il percorso gestaltico
Questo lavoro riporta alcuni risultati preliminari di un progetto di ricerca volto a indagare il rapporto tra il benessere percepito e il lavoro personale in psicoterapia della Gestalt. Nello specifico, presentiamo nel seguente articolo, i risultati relativi alla dinamica e ai cambiamenti che alcuni pazienti, che hanno liberamente partecipato alla ricerca, hanno mostrato riguardo al proprio senso di benessere, costrutto qui indagato attraverso lâuso di una scala autovalutativa nella sua versione adattata e standardizzata per la popolazione italiana.
METODOLOGIA. Si tratta di un disegno sperimentale longitudinale qualitativo che ha coinvolto cinque pazienti per tre mesi, tutti presi in carico da psicologi psicoterapeuti di approccio Gestalt fenomenologico-esistenziale. I dati sono stati raccolti ogni quattro sedute individuali
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe
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