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Surplus bread accounts for a significant proportion of food waste in many countries. The focus of this study was twofold: firstly, to investigate the use of carasau bread residue as a sourdough substrate, and secondly, to reuse this sourdough into a new carasau baking process. Selected lactic acid bacteria (Lactiplantibacillus plantarum) and yeast strains (Saccharomyces cerevisiae and Wickerhamomyces anomalus) were used to inoculate three substrates: bread residue (S1), bread residue supplemented with durum wheat middlings (S2), and semolina (S3). Sourdoughs were refreshed for five days by backslopping, and microbiological and physicochemical analyses were performed. Results indicated that incorporating wheat middlings into bread residue enhanced microbial performance, as evidence by a decrease in pH from 6.0 to around 4.5 compared to using bread residue alone as a substrate. Carasau bread produced with the sourdough derived from bread residue and wheat middlings exhibited comparable physicochemical properties to commercial baker’s yeast carasau bread, but had better sensory properties, scoring a mean acceptability of 7.0 versus 6.0 for baker’s yeast bread. These results show that bread residue supplemented with wheat middlings can serve as a sourdough substrate, allowing its reuse in the baking process to produce high-quality carasau bread and promote the circular economy.

The aim of this work was to test native microbial strains and fruits for brewing, with a multidisciplinary approach for a sustainable production linked to the territory. Pediococcus acidilactici B5 and Hanseniaspora uvarum L2 strains were isolated from apricot Bisucciu fruits, a Sardinian local variety (Prunus armeniaca L.), and P. acidilactici B5 was used to ferment a sterile apricot Bisucciu puree, which was then added to a malt wort. The H. uvarum L2 strain and the industrial yeast Saccharomyces cerevisiae US-05 were used sequentially to ferment a portion of this wort (M2); a control was carried out with an industrial yeast, S. cerevisiae T-58 (T58). Beer standard quality parameters were studied and a sensorial analysis performed in the beers obtained from the two fermentations. Intermediate and end molecular products were characterized by proton Nuclear Magnetic Resonance (1H NMR) for glucidic, organic acids and amino acids and by Gas Chromatography–Mass Spectrometry (SPME/GC/MS) for volatile profiles. M2 and T58 samples showed differences in color, foam stability and in the carbohydrates, acids and amino acids profiles. The highest concentrations of ethyl acetate were found in M2, whereas a high concentration of 3-methylbutan-1-ol characterized T58. Sensory analysis highlighted differences in flavor, astringency and balance between the two beers studied.

We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg) A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia.

Identification of susceptibility genes for essential hypertension in humans has been a challenge due to its multifactorial pathogenesis complicated by gene-gene and gene-environment interactions, developmental programing and sex specific differences. These concurrent features make identification of causal hypertension susceptibility genes with a single approach difficult, thus requiring multiple lines of evidence involving genetic, biochemical and biological experimentation to establish causal functional mutations. Here we report experimental evidence encompassing genetic, biochemical and in vivo modeling that altogether support ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1 encodes the α1Na,K-ATPase isoform, the sole sodium pump in vascular endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12-nucleotide long thymidine (12T) insertion(ins)/deletion(del) polymorphism within a poly-T sequence (38T vs 26T) in the ATP1A1 5'-regulatory region associated with hypertension in a male Sardinian population. The 12T-insertion allele confers decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28-0.93]) accounting for 12.1 mmHg decrease in systolic BP (P = 0.02) and 6.6 mmHg in diastolic BP (P = 0.046). The ATP1A1 promoter containing the 12T-insertion exhibited decreased transcriptional activity in in vitro reporter-assay systems, indicating decreased α1Na,K-ATPase expression with the 12T-insertion, compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased α1Na,K-ATPase expression on blood pressure, we measured blood pressure by radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/- male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/- mice showed significantly lower blood pressure (P < 0.03) than age-matched male wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected to lower Na-reabsorption in the kidney thereby decreasing sodium-associated risk for hypertension and sodium-induced endothelial stiffness and dysfunction. Altogether, data support ATP1A1 as a hypertension susceptibility gene in a male Sardinian population, and mandate further investigation of its involvement in hypertension in the general population.

Background The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. Methods We analyzed two population‐based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population‐based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. Results A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12–1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42–1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon–rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. Conclusions The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow‐up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies. This is the first study able to calculate population‐based risk of thyroid cancers as a first or second tumor separately for different thyroid cancer histological types (i.e., follicular, medullary, and poorly differentiated). In a context of a large proportion of thyroid cancer cases due to overdiagnosis, the findings of the present study may help to more focused primary prevention and surveillance for side effects of treatments, thus avoiding overtreatment, particularly among younger women.

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity.We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.

SQLE encodes squalene epoxidase, a key enzyme in cholesterol synthesis. SQLE has sporadically been reported among copy-number driven transcripts in multi-omics cancer projects. Yet, its functional relevance has never been subjected to systematic analyses. Here, we assessed the correlation of SQLE copy number (CN) and gene expression (GE) across multiple cancer types, focusing on the clinico-pathological associations in breast cancer (BC). We then investigated whether any biological effect of SQLE inhibition could be observed in BC cell line models. Breast, ovarian and colorectal cancers showed the highest CN driven GE among 8,783 cases from 22 cancer types, with BC presenting the strongest one. SQLE overexpression was more prevalent in aggressive BC and was an independent prognostic factor of unfavorable outcome. Through SQLE pharmacological inhibition and silencing in a panel of BC cell lines portraying the diversity of SQLE CN and GE, we demonstrated that SQLE inhibition resulted in a copy-dosage correlated decrease in cell viability and in a noticeable increase in replication time, only in lines with detectable SQLE transcript. Altogether, our results pinpoint SQLE as a bona fide metabolic oncogene by amplification and as a therapeutic target in BC. These findings could have implications in other cancer types.

Purpose Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. Methods Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. Results In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29–0.92, P  = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16–0.88; P  = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. Conclusion Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification.

Clinically relevant survival outcomes, including cure fraction estimates, and long-term survival outcomes of paediatric CNS tumours from large-scale databases have not been reported for Europe. Moreover, various biases hinder direct geographical comparisons, thereby limiting the effective translation of population-based findings into cancer care, surveillance, and research. We aimed to estimate these survival outcomes across Europe through the EUROCARE database. In this population-based study, we analysed survival data from the EUROCARE-6 database from children younger than 15 years with a CNS tumour across 31 European countries. For the period 2008–13, we estimated observed survival via the actuarial method, and 5-year observed survival was reported at the European level and national level for four major CNS tumour groups. For the period 1998–2013, cure fraction was estimated through a mixture cure model assuming constant long-term mortality from other causes. Additionally, model-based 10-year and 15-year survival were estimated. For observed survival analyses, 13 782 tumour cases were included. 5-year observed survival was 72% (95% CI 68 to 75) for ependymomas, 92% (91 to 93) for low-grade gliomas, 47% (45 to 49) for high-grade gliomas, 24% (21 to 27) for high-grade gliomas excluding glioma not otherwise specified, and 64% (62 to 67) for medulloblastomas. A total of 30 392 children were included in the cure fraction analysis. During the study period, the largest absolute increase in cure fraction was observed for ependymomas from 65% (57 to 73) in 1998–2001 to 79% (69 to 89) in 2010–13, whereas low-grade gliomas increased from from 89% (85 to 94) to 95% (89 to 100), high-grade gliomas had a 6 percentage point change increase (2 to 10), and medulloblastomas increased from 52% (49 to 55) to 56% (51 to 60). The estimated 10-year and 15-year survival rates were highest for low-grade gliomas at 90·6% (89·4 to 91·7) at 10 years and 88·5% (87·2 to 89·8) at 15 years, whereas the lowest survival rates were observed for high-grade gliomas excluding glioma not otherwise specified at 20·5% (17·0 to 24·1) and 19·0% (15·6 to 22·5). This study is the first to report a comprehensive evaluation of survival parameters for paediatric CNS tumour patients in Europe. These outcomes are important to evaluate advances in care for children with a CNS tumour. Princess Máxima Center for Pediatric Oncology and Associazione Italiana per la Ricerca sul Cancro.