Estakhr Project - Third preliminary report of the joint Mission of the Iranian center for archaeological research, the Parsa-Pasargadae research foundation and the Sapienza University of Rome, Italy

This report presents the preliminary results of the study of the pottery collected during the excavation campaign carried out in 2012 in the framework of the joint Iranian-Italian Archaeological Mission in Estakhr. The ceramic finds relate to a time span ranging from the 9th to the 12th century, corresponding to the occupation phases identified within the stratigraphy. Moreover, the use of archaeometry made it possible to identify both imported and locally manufactured wares

The challenges of defining hormesis in epidemiological studies: The case of radiation hormesis

In the current radiation protection system, preventive measures and occupational exposure limits for controlling occupational exposure to ionizing radiation are based on the linear no-threshold extrapolation model. However, currently an increasing body of evidence indicates that this paradigm predicts very poorly biological responses in the low-dose exposure region. In addition, several in vitro and in vivo studies demonstrated the presence of hormetic dose response curves correlated to ionizing radiation low exposure. In this regard, it is noteworthy that also the findings of different epidemiological studies, conducted in different categories of occupationally exposed workers (e.g., healthcare, nuclear industrial and aircrew workers), observed lower rates of mortality and/or morbidity from cancer and/or other diseases in exposed workers than in unexposed ones or in the general population, then suggesting the possible occurrence of hormesis. Nevertheless, these results should be considered with caution since the identification of hormetic response in epidemiological studies is rather challenging because of a number of major limitations. In this regard, some of the most remarkable shortcomings found in epidemiological studies performed in workers exposed to ionizing radiation are represented by lack or inadequate definition of exposure doses, use of surrogates of exposure, narrow dose ranges, lack of proper control groups and poor evaluation of confounding factors. Therefore, considering the valuable role and contribution that epidemiological studies might provide to the complex risk assessment and management process, there is a clear and urgent need to overcome the aforementioned limits in order to achieve an adequate, useful and more real-life risk assessment that should also include the key concept of hormesis. Thus, in the present conceptual article we also discuss and provide possible approaches to improve the capacity of epidemiological studies to identify/define the hormetic response and consequently improve the complex process of risk assessment of ionizing radiation at low exposure doses

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

Purpose: To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). Methods: PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. Results: 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (a\u3b22GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 \ub1 6.4 nmol/min/ml vs. 19.5 \ub1 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG a\u3b22GPI disclosed higher PAF-AH than patients with only IgM a\u3b22GPI-positive antibodies (23.1 \ub1 7.2 nmol/min/ml vs. 20.1 \ub1 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 \ub1 3.8 nmol/min/ml; p = 0.003). Conclusions: PAF-AH plasmatic activity is particularly up-regulated in LAC+ and in a\u3b22GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patient

Introspección reflexiva del estudiante sobre su experiencia en másteres internacionales

Value co-creation is becoming a mainstream in higher education, as a progress within the ?Students as Customer? approach. Furthermore, the development of qualitative studies through reflective methods from students can help instructors and managers. The aim of this research is to explore with the aid of a CAQDAS, 30 students? reflective statements in two master programs. Findings are presented in terms of value dimensions: functional, emotional and social, and in terms of positive (benefits) and negative (cost) aspects of the experience. The usefulness of introspective methodologies from students is shown in the evaluation of the multidimensional and intercultural educational experience

Mitochondrial ROS drive resistance to chemotherapy and immune-killing in hypoxic non-small cell lung cancer

BACKGROUND: Solid tumors subjected to intermittent hypoxia are characterized by resistance to chemotherapy and immune-killing by effector T-lymphocytes, particularly tumor-infiltrating Vγ9Vδ2 T-lymphocytes. The molecular circuitries determining this double resistance are not known. METHODS: We analyzed a panel of 28 human non-small cell lung cancer (NSCLC) lines, using an in vitro system simulating continuous and intermittent hypoxia. Chemosensitivity to cisplatin and docetaxel was evaluated by chemiluminescence, ex vivo Vγ9Vδ2 T-lymphocyte expansion and immune-killing by flow cytometry. Targeted transcriptomics identified efflux transporters and nuclear factors involved in this chemo-immuno-resistance. The molecular mechanism linking Hypoxia-inducible factor-1α (HIF-1α), CCAAT/Enhancer Binding Protein-β (C/EBP-β) isoforms LAP and LIP, ABCB1, ABCC1 and ABCA1 transporters were evaluated by immunoblotting, RT-PCR, RNA-IP, ChIP. Oxidative phosphorylation, mitochondrial ATP, ROS, depolarization, O(2) consumption were monitored by spectrophotometer and electronic sensors. The role of ROS/HIF-1α/LAP axis was validated in knocked-out or overexpressing cells, and in humanized (Hu-CD34(+)NSG) mice bearing LAP-overexpressing tumors. The clinical meaning of LAP was assessed in 60 NSCLC patients prospectively enrolled, treated with chemotherapy. RESULTS: By up-regulating ABCB1 and ABCC1, and down-regulating ABCA1, intermittent hypoxia induced a stronger chemo-immuno-resistance than continuous hypoxia in NSCLC cells. Intermittent hypoxia impaired the electron transport chain and reduced O(2) consumption, increasing mitochondrial ROS that favor the stabilization of C/EBP-β mRNA mediated by HIF-1α. HIF-1α/C/EBP-β mRNA binding increases the splicing of C/EBP-β toward the production of LAP isoform that transcriptionally induces ABCB1 and ABCC1, promoting the efflux of cisplatin and docetaxel. LAP also decreases ABCA1, limiting the efflux of isopentenyl pyrophosphate, i.e. the endogenous activator of Vγ9Vδ2 T-cells, and reducing the immune-killing. In NSCLC patients subjected to cisplatin-based chemotherapy, C/EBP-β LAP was abundant in hypoxic tumors and was associated with lower response to treatment and survival. LAP-overexpressing tumors in Hu-CD34(+)NSG mice recapitulated the patients’ chemo-immuno-resistant phenotype. Interestingly, the ROS scavenger mitoquinol chemo-immuno-sensitized immuno-xenografts, by disrupting the ROS/HIF-1α/LAP cascade. CONCLUSIONS: The impairment of mitochondrial metabolism induced by intermittent hypoxia increases the ROS-dependent stabilization of HIF-1α/LAP complex in NSCLC, producing chemo-immuno-resistance. Clinically used mitochondrial ROS scavengers may counteract such double resistance. Moreover, we suggest C/EBP-β LAP as a new predictive and prognostic factor in NSCLC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02447-6

Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis

Background: Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles. Results: We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion. Conclusion: This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in-depth molecular CFTR analysis

El papel de la reflexión metodológica y la actualidad de la observación-participante en la antropología contemporánea: Entrevista a Cecilia Hidalgo

En este artículo presentamos un trabajo realizado durante la cursada del primer cuatrimestre de 2017 en la materia Metodología y Técnicas de la Investigación de Campo, en el cual los y las estudiantes nos organizamos grupalmente en torno a temáticas específicas, que en nuestro caso fue Perspectivas Etnográficas en los estudios de la ciencia, la tecnología y la innovación. Abordajes etnográficos en campos disciplinares y multidisciplinares. Para llevar a cabo dicho trabajo, decidimos como equipo entrevistar a la Dra. Cecilia Hidalgo, referente conocida en nuestra casa de estudios por su orientación en la Antropología de la Ciencia. Este trabajo de reflexión fue luego revisado con la colaboración de docentes de la materia, y comentado por ellos a modo de conclusión, para así reflexionar sobre algunos aspectos de la enseñanza de la metodología, en este caso especialmente sobre la OP.Fil: Liebling, Tamara. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Pérez, Amalia Margarita. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Porsella, Rodrigo Martín. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Villahoz, Martina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Perez Velilla, Alejandro. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Fontana, Dolores. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Padawer, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas; ArgentinaFil: Pico, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; Argentin

Designation of optimal reference strains representing the infant gut bifidobacterial species through a comprehensive multi-omics approach

The genomic era has resulted in the generation of a massive amount of genetic data concerning the genomic diversity of bacterial taxa. As a result, the microbiological community is increasingly looking for ways to define reference bacterial strains to perform experiments that are representative of the entire bacterial species. Despite this, there is currently no established approach allowing a reliable identification of reference strains based on a comprehensive genomic, ecological, and functional context. In the current study, we developed a comprehensive multi-omics approach that will allow the identification of the optimal reference strains using the Bifidobacterium genus as test case. Strain tracking analysis based on 1664 shotgun metagenomics datasets of healthy infant faecal samples were employed to identify bifidobacterial strains suitable for in silico and in vitro analyses. Subsequently, an ad hoc bioinformatic tool was developed to screen local strain collections for the most suitable species-representative strain alternative. The here presented approach was validated using in vitro trials followed by metagenomics and metatranscriptomics analyses. Altogether, these results demonstrated the validity of the proposed model for reference strain selection, thus allowing improved in silico and in vitro investigations both in terms of cross-laboratory reproducibility and relevance of research findings

Rapid SARS-CoV-2 intra-host and within-household emergence of novel haplotypes

In February 2020, the municipality of Vo’, a small town near Padua (Italy) was quarantined due to the first coronavirus disease 19 (COVID-19)-related death detected in Italy. To investigate the viral prevalence and clinical features, the entire population was swab tested in two sequential surveys. Here we report the analysis of 87 viral genomes, which revealed that the unique ancestor haplotype introduced in Vo’ belongs to lineage B, carrying the mutations G11083T and G26144T. The viral sequences allowed us to investigate the viral evolution while being transmitted within and across households and the effectiveness of the non-pharmaceutical interventions implemented in Vo’. We report, for the first time, evidence that novel viral haplotypes can naturally arise intra-host within an interval as short as two weeks, in approximately 30% of the infected individuals, regardless of symptom severity or immune system deficiencies. Moreover, both phylogenetic and minimum spanning network analyses converge on the hypothesis that the viral sequences evolved from a unique common ancestor haplotype that was carried by an index case. The lockdown extinguished both the viral spread and the emergence of new variant

Genetic strategies for sex-biased persistence of gut microbes across human life

Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation.We thank GenProbio Srl for the financial support of the Laboratory of Probiogenomics. Part of this research is conducted using the High- Performance Computing (HPC) facility of the University of Parma. This research has financially been supported by the Programme “FIL-Quota Incentivante” of University of Parma and co-sponsored by Fondazione Cariparma”. D.v.S. is a member of APC Microbiome Ireland funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (Grant no. SFI/12/RC/2273-P1 and SFI/12/RC/ 2273-P2). G.T. has been supported by “Fondazione Cariparma” in the framework of the project entitled “Parma Microbiota”. LMV has been supported by by “Programma Operativo Nazionale 2014–2020 of the Italian Ministry of University and Research. The funding from Project AGL2017-83653R (Spanish “Ministerio de Ciencia, Innovación y Universidades (MCIU)”, “Agencia Estatal de Investigación (AEI)” and FEDER) is also acknowledged