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Spatial cell organization and biofabrication of microcapillary networks in vitro has a great potential in tissue engineering and regenerative medicine. This study explores the impact of local cell density enhancement achieved through an innovative sound-based patterning on microcapillary networks formation and their proteomic profile. Human umbilical vein endothelial cells (HUVEC) and human pericytes from placenta (hPC-PL) were mixed in a fibrin suspension. The mild effect of sound-induced hydrodynamic forces condensed cells into architected geometries showing good fidelity to the numerical simulation of the physical process. Local cell density increased significantly within the patterned areas and the capillary-like structures formed following the cell density gradient. Over five days, these patterns were well-maintained, resulting in concentric circles and honeycomb-like structures.Proteomic analysis of the pre-condensed cells cultured for 5 days, revealed over 900 differentially expressed proteins when cells were preassembled through mild-hydrodynamic forces. Gene ontology (GO) enrichment analysis identified cellular components, molecular functions, and biological processes that were up- and down-regulated, providing insights regarding molecular processes influenced by the local density enhancement. Furthermore, we employed Ingenuity Pathway Analysis (IPA) to identify altered pathways and predict upstream regulators. Notably, VEGF-A emerged as one of the most prominent upstream regulators.Accordingly, this study initiates the unraveling of the changes in microcapillary networks at both molecular and proteins level induced by cell condensation obtained through sound patterning. The findings provide valuable insights for further investigation into sound patterning as a biofabrication technique for creating more complex microcapillary networks and advancing in vitro models.

Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in T. brucei by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program.

Amphibian populations are increasingly threatened by global change and the study of their genetic diversity is a major conservation priority. Western palearctic tree frog species of the Hyla arborea group are commonly distributed across Europe and the Middle East and many have declining populations. We performed a PRISMA systematic review to gain insight into the genetic diversity of H. arborea group. Sixteen published studies were included in the final qualitative analysis. While the genetic diversity of H. arborea group species was widely variable, it could often be explained by phylogeographic history. Populations in Western and Northern Europe had lower genetic diversity, with some populations also affected by habitat fragmentation. However, important regions of high genetic diversity were found in the Balkan peninsula for H. arborea sensu stricto and around the Black Sea for H. orientalis. Genetic diversity of H. molleri, H. savignyi, H. meridionalis, H. felixarabica, H. intermedia, H. sarda has been investigated only across extensive phylogeographical studies, while data regarding their genetic diversity at the local level are missing. Through our review, we identify knowledge gaps about the genetic diversity of the H. arborea group that require further investigation, of and illustrate how filling these gaps might translate into future conservation efforts.

Background: Although rare, sinonasal cancers (SNCs) have a high occupational attributable fraction. Methods: We applied gender-based approaches to descriptive analyses, incidence, and patterns of exposures using the Italian National Sinonasal Cancer Registry (ReNaTuNS: Registro Nazionale Tumori Naso-Sinusali). Results: The study included 2851 SNC patients. SNC was diagnosed more often in men (73%) than in women (27%). The most frequent morphology in men was intestinal-type adenocarcinoma (33%), whereas in women, it was squamous cell carcinoma (49%). Nasal cavities were predominant in both genders (50%), ethmoidal sinus in men (24%), and maxillary in women (24%). Incidence rates were 0.76 (per 100,000 person-years) in men and 0.24 in women and increased by age, more evidently in men, peaking over 75 years in both. Occupational exposures to wood and leather dusts were the most frequent (41% for men, 33% for women). Few exposures were extra-occupational or domestic. Unlikely exposure was relevant in women (57%). Conclusions: The surveillance of SNC cases through a registry that allows for the identification of and compensation for this occupational disease is important in Italy, where numerous workers are exposed to carcinogens for SNC, without even being aware. Considering the rarity of the disease, particularly among women, the ReNaTuNS can provide a method to analyze gender differences.

A phylogeographic study on the chloroplast DNA of natural white oak forests (Quercus subgen. Quercus, sect. Quercus) was carried out to identify possible haplotype-structured distribution within the Italian Peninsula, Sicily, and Sardinia. Sixty white oak populations belonging to Q. frainetto, Q. robur and the collective groups Q. petraea and Q. pubescens were considered and analyzed by combining five Chloroplast Simple Sequence Repeat (cpSSR) markers. A total of 28 haplotypes were detected. Central and southern Italy displayed the highest variability (14 and 10 haplotypes, respectively), followed by northern Italy (7), Sardinia (7), and Sicily (5). A complex geographical structure of the haplotype distribution emerged, highlighting (i) a high number of low-frequency haplotypes; (ii) the marked isolation of Sardinia; (iii) the occurrence of haplotypes widely distributed throughout the Italian Peninsula; (iv) the idiosyncrasy of Sicily, which exhibits exclusive haplotypes, and haplotypes shared with Sardinia and the rest of the Italian Peninsula. The haplotype distribution was also found to be partially related to the taxonomic identity of the specimens, with the following features emerging: a geographic separation between the central Italy and southern Italy Q. frainetto populations, an unexpected discontinuity between the Calabrian and Sicilian Q. petraea subsp. austrotyrrhenica populations, and the absence of the most common haplotype among the Q. pubescens populations of central and southern Italy.

The relevant growth of the wood pellet market in Europe in the last decade led to an increased focus on solid biofuel as a necessary and available renewable resource for energy production. Among biofuels, wooden pellets are among the most widespread for domestic heating. Therefore, monitoring the qualitative properties of commercialized pellets is crucial in order to minimize the amount of harmful emissions in residential areas. Standard ISO 17225 sets threshold values for the chemical and physical properties that commercialized biofuels must fulfil. Specifically, ISO 17225-2 defines that pellets for residential use must be produced from virgin wood, but no method is proposed to assess the actual origin of the material, leading to the risk of the commercialization of pellets made up from chemically treated materials. This study proposes a model obtained via near infrared spectroscopy analyses and chemometrics methods, such as classification, to rapidly assess whether pellets are made up of virgin or chemically treated wood. The result suggests the effectiveness of NIRs for the detection of non-virgin pellets with an accuracy greater than 99%. Furthermore, the model appeared to be accurate in the assessment of both milled and intact pellets, making it a potential in-line instrument for assessments of pellets’ quality.

Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.Design Case–control study.Setting Cases from the National Mesothelioma Registry (2000–2018), controls from three previous case–control studies.Methods We selected male PM incident cases diagnosed in 2000–2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002–2004 and 2012–2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.Results The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.Conclusions We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Background and Objectives. A relatively small number of studies have investigated the characteristics, comorbidities and laboratory measures associated with prognosis in patients with COVID-19, admitted to Internal Medicine Units (IMU) in Italy. Therefore, we performed a retrospective multicentre study to identify baseline features, predisposing to severe disease and poor outcomes, in adult individuals with SARS-CoV-2 infection, hospitalized in 5 IMUs in the Emilia-Romagna region (Italy). Materials and Methods. We included 129 consecutive patients (male 75, median age 68 years) from 1st March 2020 to 31st October 2021. Patients’ baseline characteristics, comorbidities, laboratory measures, and outcomes were collected. Results. At admission, the factors significantly associated with a higher risk of in-hospital mortality included: age (median 68 vs. 83 years in survived vs. dead patients, P=0.000), diabetes [Odds Ratio (OR) 4.00, P=0.016], chronic obstructive pulmonary disease (OR 4.60, P=0.022), cancer (OR 5.81, P=0.021), acute- (OR 9.88, P=0.000) and chronic-renal failure (OR 6.76, P=0.004). During the study period, 16 individuals died (12.4%), all over 70 years old. In deceased vs. non-deceased patients were detected: i) more elevated white blood cells and neutrophils-counts and lower lymphocytes count; ii) higher levels of total/direct bilirubin, creatinine, C-reactive-protein, lactate-dehydrogenase, ferritin, but only a slight Interleukin-6 increase; iii) a trend of lower vitamin D values. Conclusions. We proposed a new I index, a modified form of the Age-Adjusted Charlson Comorbidity Index, by considering pO2/FiO2 ratio, to better characterize the severity of COVID-19. Furthermore, we critically discuss our results with the current assumption which considers COVID-19 as a pathological condition associated with cytokine storm.

Successful treatments for acute and chronic skin wounds remain challenging. The goal of this proof-of-concept study was to assess the technical feasibility and safety of a novel wound treatment solution, FastSkin®, in a pig model. FastSkin® was prepared from skin micrografts patterned in blood using acoustic waves. Upon coagulation, the graft was transferred on a silicone sheet and placed on wounds. Six full-thickness wounds were created at the back of two pigs and treated with either FastSkin®, split-thickness skin graft (positive control), a gauze coverage (negative control, NC1), or blood patterned without micrografts (negative control, NC2). Silicone sheets were removed after 7, 14, and 21 days. Wound healing was monitored for six weeks and evaluated macroscopically for re-epithelialization and morphometrically for residual wound area and wound contraction. Tissue regeneration was assessed with histology after six weeks. Re-epithelialization was faster in wounds covered with FastSkin® treatments compared to NC2 and in NC2 compared to NC1. Importantly, an enhanced collagen organization was observed in FastSkin® in contrast to NC treatments. In summary, two clinically approved skin wound treatments, namely micrografting and blood clot graft, were successfully merged with sound-induced patterning of micrografts to produce an autologous, simple, and biologically active wound treatment concept.

This study deals with the analysis of seedling fitness in three Quercus cerris wood stands, namely Selva di Castiglione (SC), Bosco della Ficora (BF) and Bosco di San Leo (BSL), developed in different lithological and physiographic conditions and subjected to different forestry practices. A phytosociological study was carried out for analysing the coenological features of the forest stands and to classify these latter from a syntaxonomic point of view. The Pignatti-Ellenberg index (PEi) was calculated on the matrix composed of the phytosociological relevés in order to highlight possible ecological differences or gradients among stands. The phenotypic parameters considered were the stem and root length and the leaf area, whereas the plant functional traits (PFTs) were specific leaf area (SLA), leaf dry matter content (LDMC), leaf thickness (Lth) and chlorophyll content (CHL). The results showed that seedlings coming from different sampling sites exhibited similar values in all the phenotypic parameters. Instead, statistically significant differences were observed in the PFTs. The results suggested that the different adaptation strategies implemented by the seedlings are to be related to the physical environment of the sampling sites and to the different forest structures. The Selva di Castiglione forest stand (SC) exhibited better growth conditions for seedlings testified by higher values of SLA and CHL and lower values of LDMC and Lth. These were interpreted as greater investment in carbon production aimed at rapid development and renewal of the seedling rather than carbon storage aimed at ensuring leaf longevity.

Skin aging is a dynamic process that determines structural alterations in ECM and reduction in dermal fibroblasts. The recent availability on the market of an innovative polycomponent formulation (KARISMA Rh Collagen® FACE, K) containing noncrosslinked high-molecular-weight hyaluronic acid (HMW-HA), a human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose (CMC), attracted our scientific interest in evaluating its biomolecular effects on human dermal adult and aged fibroblasts. After treatment with increasing K concentrations, cell proliferation, collagen I, prolyl 4-hydroxylase (P4HA1), an essential protein in collagen biosynthesis, and α-SMA levels were assessed. The fibroblast contractility, TGF-β1 levels, and oxidative stress markers were also evaluated. K formulation exposure led to a significant and dose-dependent increase in the proliferation and migration of adult fibroblasts. Of note, the K exposure counteracted the H2O2-induced aging by promoting cell proliferation, reducing β-galactosidase activity, and neutralizing the aging-associated oxidative damage. Moreover, an increase in collagen I, P4HA1, α-SMA, TGF-β1 levels, and improved contractility of adult and aged fibroblasts were observed after treatment. Overall, our results show evidence that the K treatment is efficacious in improving biological functions in adult fibroblasts and suppressing the biomolecular events associated with H2O2-induced cellular aging, thus supporting the regenerative and bio-revitalizing action of the K formulation helpful in preventing or treating skin aging.

The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME can trigger the vascular response and influence the therapeutic outcome of the treatment. To identify and develop new therapeutic strategies, 3D in vitro models that recapitulate the complexity of the TME are urgently needed. Among them, vascularized tumor models are a promising approach, allowing to target tumor angiogenesis and reduce tumor growth. By using sound patterning, cells can be condensed locally into highly reproducible patterns through the action of mild hydrodynamic forces. Here, we use a soundwave-driven cell assembly approach to create a ring-shaped microcapillary network in fibrin hydrogel. Then, we generate a 3D vascularized tumor model by combining a tumor heterotypic spheroid, consisting of fibroblasts and Malignant Pleural Mesothelioma (MPM) cells, with the surrounding vascular ring. Based on its shape, we name it Saturn-like vascularized Tumor Model (STM). The growth of the microcapillary network is monitored over time by fluorescence imaging. The area covered by the microcapillary network, and its continuous increase in presence of the heterotypic tumor spheroid was monitored. Interestingly, this effect is enhanced when treating the STM with the anticancer agent Cisplatin. Overall, we show the use of sound patterning as a fast and cell-friendly approach to spatially organize and condense cells, to generate a 3D in vitro platform from which simple readouts of drug tests can be extracted by image analysis, with the potential to provide a model system for tailored tumor therapy.

Typically, coniferous sawdust from debarked stems is used to make pellets. Given the high lignin content, which ensures strong binding and high calorific values, this feedstock provides the best quality available. However, finding alternative feedstocks for pellet production is crucial if small-scale pellet production is to be developed and used to support the economy and energy independence of rural communities. These communities have to be able to create pellets devoid of additives and without biomass pre-processing so that the feedstock price remains low. The features of pellets made from other sources of forest biomass, such as different types of waste, broadleaf species, and pruning biomass, have attracted some attention in this context. This review sought to provide an overview of the most recent (2019–2023) knowledge on the subject and to bring into consideration potential feedstocks for the growth of small-scale pellet production. Findings from the literature show that poor bulk density and mechanical durability are the most frequent issues when making pellets from different feedstocks. All of the tested alternative biomass typologies have these shortcomings, which are also a result of the use of low-performance pelletizers in small-scale production, preventing the achievement of adequate mechanical qualities. Pellets made from pruning biomass, coniferous residues, and wood from short-rotation coppice plants all have significant flaws in terms of ash content and, in some cases, nitrogen, sulfur, and chlorine content as well. All things considered, research suggests that broadleaf wood from beech and oak trees, collected through routine forest management activities, makes the best feasible feedstock for small-scale pellet production. Despite having poor mechanical qualities, these feedstocks can provide pellets with a low ash level. High ash content is a significant disadvantage when considering pellet manufacture and use on a small scale since it can significantly raise maintenance costs, compromising the supply chain’s ability to operate cost-effectively. Pellets with low bulk density and low mechanical durability can be successfully used in a small-scale supply chain with the advantages of reducing travel distance from the production site and storage time.

Antibodies against the SARS-CoV-2 nucleocapsid protein are produced by the immune system in response to SARS-CoV-2 infection, but most available vaccines developed to fight the pandemic spread target the SARS-CoV-2 spike protein. The aim of this study was to improve the detection of antibodies against the SARS-CoV-2 nucleocapsid by providing a simple and robust method applicable to a large population. For this purpose, we developed a DELFIA immunoassay on dried blood spots (DBSs) by converting a commercially available IVD ELISA assay. A total of forty-seven paired plasma and dried blood spots were collected from vaccinated and/or previously SARS-CoV-2-infected subjects. The DBS-DELFIA resulted in a wider dynamic range and higher sensitivity for detecting antibodies against the SARS-CoV-2 nucleocapsid. Moreover, the DBS-DELFIA showed a good total intra-assay coefficient of variability of 14.6%. Finally, a strong correlation was found between SARS-CoV-2 nucleocapsid antibodies detected by the DBS-DELFIA and ELISA immunoassays (r = 0.9). Therefore, the association of dried blood sampling with DELFIA technology may provide an easier, minimally invasive, and accurate measurement of SARS-CoV-2 nucleocapsid antibodies in previously SARS-CoV-2-infected subjects. In conclusion, these results justify further research to develop a certified IVD DBS-DELFIA assay for detecting SARS-CoV-2 nucleocapsid antibodies useful for diagnostics as well as for serosurveillance studies.

Background: Corifollitropin alfa (CFA) is a long-acting recombinant follicle-stimulating hormone (rFSH) used for controlled ovarian stimulation (COS). Several studies analyzing the clinical efficacy and safety of CFA compared to daily rFSH during COS have been carried out. The present study offers a meta-analysis of the randomized controlled trials (RCTs) on this topic. Methods: A computerized search of the published literature was carried out using PubMed, MEDLINE, Science direct and Google Scholar databases. The comparison between CFA and daily rFSH treatments during COS were investigated only in RCTs. The primary endpoint of the study is represented by the number of total oocytes retrieved at ovum pick-up. The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) or the mean difference (MD) along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and Chi-square tests. Results: The study examined a total of twelve RCTs published from 2004 to date and included a total of 4980 patients, with 2664 receiving CFA and 2316 patients receiving daily rFSH for COS. Women treated with CFA had higher number of total oocytes retrieved at ovum pick-up (MD 0.91, 95% CI [0.34, 1.49], p = 0.001), and higher number of metaphase II (MII) oocytes (MD 1.00, 95% CI [0.37, 1.62], p = 0.002) compared to those receiving daily rFSH. There were no significant differences between the two study groups regarding the other outcomes analyzed. The subgroup analysis performed comparing “normal” versus “poor” responders revealed that normal responders receiving CFA showed an higher cancellation rate, with respect to those receiving rFSH. Conclusions: This study shows that COS with CFA results in a higher number of oocytes retrieved at ovum pick-up in comparison with daily rFSH.

Six Amaranthus species (A. cruentus, A. hybridus, A. hypochondriacus, A. muricatus, A. tuberculatus, and A. viridis) were collected in Italy (wild habitats) from crops and roadsides. Amaranth seed oil was extracted to obtain fractions rich in squalene. Squalene, free fatty acid, tocopherol, and sterol composition and content were investigated in detail. An analysis of variance and principal components was performed. The oil content in the seed ranged from 5.17% (A. muricatus) to 12.20% (A. tuberculatus). The quantity of squalene in the oil varied from 3.43% (A. muricatus) to 6.09% (A. hypochondriacus). The primary sterols were beta-sitosterol, brassicasterol, campesterol, and stigmasterol. The main tocopherols in all the samples were alfa-tocopherol, beta-tocopherol, and delta-tocopherol. Our results exhibited that the smallest seeds (A. tuberculatus) have the highest percentages of oil and squalene, whereas the largest seeds size (A. muricatus) show the lowest percentages. There is also evidence that the samples growing at lower altitudes show the highest concentration of fatty acids. According to our results, the six wild Amaranthus species exhibited similar characteristics to commercial species. This study confirms that the site of the collection has an impact on the oil and squalene content of the Amaranthus species.

Simple Summary: Sinonasal cancer (SNC) is strongly associated with occupational exposure to several carcinogens involved in SNC's etiology, which vary by gender. Gender differences in SNC cases were examined through the Italian sinonasal cancer registry. Male-to-female incidence differences are neglectable in the youngest age classes but increase in older age classes, probably as a result of more men being diagnosed with SNC due to their greater occupational exposure to carcinogens (mostly wood and leather dusts) compared with women. Occupational exposures to carcinogens were the most frequent in both genders. A high percentage of women had unlikely exposures. Gender differences deserve more deep investigation, starting with a review of diagnostic processes and occupational history taking. Background: Although rare, sinonasal cancers (SNCs) have a high occupational attributable fraction. Methods: We applied gender-based approaches to descriptive analyses, incidence, and patterns of exposures using the Italian National Sinonasal Cancer Registry (ReNaTuNS: Registro Nazionale Tumori Naso-Sinusali). Results: The study included 2851 SNC patients. SNC was diagnosed more often in men (73%) than in women (27%). The most frequent morphology in men was intestinal-type adenocarcinoma (33%), whereas in women, it was squamous cell carcinoma (49%). Nasal cavities were predominant in both genders (50%), ethmoidal sinus in men (24%), and maxillary in women (24%). Incidence rates were 0.76 (per 100,000 person-years) in men and 0.24 in women and increased by age, more evidently in men, peaking over 75 years in both. Occupational exposures to wood and leather dusts were the most frequent (41% for men, 33% for women). Few exposures were extra-occupational or domestic. Unlikely exposure was relevant in women (57%). Conclusions: The surveillance of SNC cases through a registry that allows for the identification of and compensation for this occupational disease is important in Italy, where numerous workers are exposed to carcinogens for SNC, without even being aware. Considering the rarity of the disease, particularly among women, the ReNaTuNS can provide a method to analyze gender differences. [ABSTRACT FROM AUTHOR]

Given the recognized carcinogenicity of cadmium, several regulatory interventions have been carried out over the years to protect exposed workers. The aim of the study is to investigate the prevalence and extent of exposure to cadmium among Italian workers. Data was collected from a nation-wide occupational exposure registry (SIREP, 1996-2022). Gender-specific statistical analysis was carried out for some exposure-related variables (cadmium compound, activity sector, occupational group, firm size). Potentially exposed workers were estimated for some industrial sectors. Concurrent exposures were investigated using cluster analysis. Overall 4,264 measurements were analyzed. Four industrial sectors were found to be most involved by cadmium exposure: base metal manufacturing, fabricated metal products, machinery and equipment, and other transport equipment (55% of measurements). Jewellery/precious-metal workers, and glass/ceramic plant operators were found to be most at exposure risk. A total of 26,470 workers potentially exposed was estimated (69% men). Concurrent exposures to other occupational carcinogens were detected quite frequently (52% of workers). Several situations of exposure and co-exposure to cadmium deserve attention and awareness in order to minimize the risks associated with workers' health. Recognition of potentially hazardous exposure conditions is an important step in prevention strategies to better protect workers against cancer-causing agents. [ABSTRACT FROM AUTHOR]

A phylogeographic study on the chloroplast DNA of natural white oak forests (Quercus subgen. Quercus, sect. Quercus) was carried out to identify possible haplotype-structured distribution within the Italian Peninsula, Sicily, and Sardinia. Sixty white oak populations belonging to Q. frainetto, Q. robur and the collective groups Q. petraea and Q. pubescens were considered and analyzed by combining five Chloroplast Simple Sequence Repeat (cpSSR) markers. A total of 28 haplotypes were detected. Central and southern Italy displayed the highest variability (14 and 10 haplotypes, respectively), followed by northern Italy (7), Sardinia (7), and Sicily (5). A complex geographical structure of the haplotype distribution emerged, highlighting (i) a high number of low-frequency haplotypes; (ii) the marked isolation of Sardinia; (iii) the occurrence of haplotypes widely distributed throughout the Italian Peninsula; (iv) the idiosyncrasy of Sicily, which exhibits exclusive haplotypes, and haplotypes shared with Sardinia and the rest of the Italian Peninsula. The haplotype distribution was also found to be partially related to the taxonomic identity of the specimens, with the following features emerging: a geographic separation between the central Italy and southern Italy Q. frainetto populations, an unexpected discontinuity between the Calabrian and Sicilian Q. petraea subsp. austrotyrrhenica populations, and the absence of the most common haplotype among the Q. pubescens populations of central and southern Italy. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in T. brucei by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program. Author summary: SUMOylation is a reversible posttranslational modification found across eukaryotic organisms. It involves attaching a small ubiquitin-like modifier (SUMO) to specific lysine residues within proteins. This modification can happen at one lysine (monoSUMOylation), multiple lysines (multiSUMOylation), or through lysine-linked SUMO chains (polySUMOylation). By altering the interaction surface of proteins, SUMOylation acts like a switch, regulating their functions. This process is crucial for various cellular pathways, especially those involved in chromatin organization and function, such as transcription, replication, DNA damage repair, nucleocytoplasmic transport and chromosome segregation. SUMO chains, in particular, play a significant role during cellular stress. In our study, we explored the role of SUMO chains in Trypanosoma brucei, an early branching pathogenic eukaryote. We discovered that parasites capable of attaching only SUMO monomers are primed for differentiation from the slender replicative form to the stumpy non-replicative form. Our findings suggest that polySUMOylation of specific proteins helps maintain the replicative form of T. brucei, while reducing SUMO chain complexity may trigger the stress-induced transition to dormancy. This unveils a new function of polySUMOylation in controlling dormancy and, consequently, pathogenicity. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. METHODS: Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993–2015, incidence rates, survival median period and prognostic factors have been evaluated. A case–control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. RESULTS: Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85–7.31 and OR 3.42, 95% CI 1.93–6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. CONCLUSIONS: For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.

Marianecci C, Rinaldi F, Di Marzio L, et al. Int J Nanomedicine. 2014;9(1):635–651. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of TEM images in Figure 1. Specifically, Figure 1A, F1, appears to have been duplicated with the same image for Figure 1C, F3 and Figure 1D, F3AG. The authors did respond to our queries but were unable to explain how the duplication of images occurred, nor were they able to provide the original TEM images from the reported study. The decision was made to retract the article and the authors were notified of this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.