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Aiming at understanding the source of the fluids that mineralizing within seismically active fault zones, we investigate the noble gas isotopes (i.e., helium (He), neon (Ne), and argon (Ar)) in the fluid inclusions (FIs) trapped in the calcite veins sampled along high‐angle fault zones of the Contursi hydrothermal basin, southern Italy. The latter basin lies in close vicinity of the MW = 6.9, 1980 Irpinia earthquake and exposes numerous fault scarps dissecting Mesozoic shallow‐water carbonates. The analyses of noble gases (He, Ne, Ar) are conducted to identify the origin of the volatiles circulating along the faults at the time of calcite precipitation. Then, outcomes of this discussions are compared with currently outgassing of deep‐sourced CO2 coupled to mantle‐derived He in that area, whose output is larger than those from some volcanic areas worldwide. The results indicate that He in FIs is dominated by a crustal radiogenic component (4He), and by an up to 20% of a mantle‐derived component (3He), with a highest isotopic signature of 1.38 Ra. This value is consistent with the highest percentage of mantle‐derived He associated to high‐flux CO2 gas emission in the investigated area (1.41 Ra). We propose that the variability of the He isotopic signature measured in primary FIs can result from early trapping of fluid inclusions or post trapping processes and seismic activity that modify the pristine He isotopic signature (i.e., derived from the crust and/or mantle) in groundwater along the faults during periods of background seismicity. Such investigations are fundamental to understand fluid migration in fault systems and the role of fluids in processes of earthquake nucleation. Key Points: Paleofluids in the studied seismogenic fault derive from the mixing between crustal and mantle (∼20%) derived fluidsThe variability of the He isotopic signature registered in fluid inclusions results from either early trapping processes (due to past possible earthquakes events) or post trapping processes by addition of radiogenic 4He produced within fractured calcite veins over time (vein aging)The pristine mantle source has been active in the Irpinia area (southern Italy) for at least 1 Ma based on the post trapping process [ABSTRACT FROM AUTHOR]

Background: Diverticular disease (DD) is a common condition in Western countries. The role of microbiota in the pathogenesis of DD and its related symptoms has been frequently postulated since most complications of this disease are bacteria‐driven and most therapies rely on microbiota modulation. Preliminary data showed fecal microbial imbalance in patients with DD, particularly when symptomatic, with an increase of pro‐inflammatory and potentially pathogenetic bacteria. In addition, bacterial metabolic markers can mirror specific pathways of the disease and may be even used for monitoring treatment effects. All treatments currently suggested for DD can affect microbiota structure and metabolome compositions. Purpose: Sparse evidence is available linking gut microbiota perturbations, diverticular disease pathophysiology, and symptom development. We aimed to summarize the available knowledge on gut microbiota evaluation in diverticular disease, with a focus on symptomatic uncomplicated DD, and the relative treatment strategies. [ABSTRACT FROM AUTHOR]

Diurnal variations in the shallow and deep meridional overturning over West Africa during the premonsoon (April–May) and monsoon (July–September) seasons were analyzed using ECMWF Reanalysis 5th Generation (ERA5) reanalysis and Tropical Rainfall Measuring Mission (TRMM)/Global Precipitation Measurement (GPM) satellite radar data from 1998 to 2019. We found that a daytime sea breeze and two nocturnal low‐level jets have varying impacts on the diurnal cycle of convection and the meridional circulations over West Africa, depending on the season. During the premonsoon, the zonal rain belt is centered over the Gulf of Guinea and the sea breeze initiates intense deep convection (and thus deep overturning) over the coastal region in the afternoon that propagates northward into the early evening. The nocturnal Sahel/Sahara low‐level jet (SLLJ) then drives low‐level convergence into the West African heat low, producing a strong, dry shallow overturning over land at night. During the monsoon, the rain belt is centered over land (10∘$$ 1{0}^{\circ } $$N) and the sea breeze is forced by weaker temperature gradients, producing less intense convection that does not propagate as far inland as during the premonsoon. However, organized convection inland maintains deep daytime overturning. At night, a coastal low‐level jet strengthens northward moisture transport from the Gulf of Guinea into the active monsoon region after the sea breeze dissipates, helping maintain convective systems with large stratiform components and continued deep meridional overturning over land. The nocturnal SLLJ still drives low‐level convergence into the West African heat low, but the dry shallow meridional overturning is farther north and weaker than in the premonsoon. While ERA5 winds and moisture‐flux convergence are generally consistent with diurnal variations in the TRMM/GPM precipitation, ERA5 precipitation is not. The reanalysis indicates significant biases in the timing and magnitude of rainfall over the Gulf of Guinea and West Africa in each season, with the convective and large‐scale rain fields both contributing to the disparate precipitation patterns. [ABSTRACT FROM AUTHOR]

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The High Agri Valley (southern Italy) is one of the largest intermontane basin of the southern Apennines affected by intensive agricultural and industrial activities. The study of groundwater chemical features provides much important information useful in water resource management. In this study, hydrogeochemical investigations coupled with multivariate statistics, saturation indices, and stable isotope composition (δD and δ18O) were conducted in the High Agri Valley to determine the chemical composition of groundwater and to define the geogenic and anthropogenic influences on groundwater quality. Twenty-four sampling point (including well and spring waters) have been examined. The isotopic data revealed that groundwater has a meteoric origin. Well waters, located on recent alluvial-lacustrine deposits in shallow porous aquifers at the valley floor, are influenced by seasonal rainfall events and show shallow circuits; conversely, spring waters from fissured and/or karstified aquifers are probably associated to deeper and longer hydrogeological circuits. The R -mode factor analysis shows that three factors explain 94% of the total variance, and F1 represents the combined effect of dolomite and silicate dissolution to explain most water chemistry. In addition, very low contents of trace elements were detected, and their distribution was principally related to natural input. Only two well waters, used for irrigation use, show critical issue for NO3- concentrations, whose values are linked to agricultural activities. Groundwater quality strongly affects the management of water resources, as well as their suitability for domestic, agricultural, and industrial uses. Overall, our results were considered fulfilling the requirements for the inorganic component of the Water Framework Directive and Italian legislation for drinking purposes. The water quality for irrigation is from "good to permissible" to "excellent to good" although salinity and relatively high content of Mg2+ can occasionally be critical. [ABSTRACT FROM AUTHOR]

Melanomas are skin tumors that show a variety of biological behavior. Some develop very fast and some other grow extremely slow, with metastasis appearing, eventually, many years after the diagnosis. The number of mitoses in primary melanoma has been related to a more aggressive tumor and may have a potential as predictive factor for cutaneous melanoma survival. However, tumor mitotic rate is a static measure and in multivariate analysis on tumor survival, it has scored less than other tumor characteristics. We tried to evolve tumor mitotic rate from a static parameter to a time‐dependent one. Similar to the already described growth rate (GR), we propose the speed rate (SR). SR is defined as the ratio of tumor mitotic rate to time to melanoma development. A prospective series of 345 patients with melanoma was investigated for the role of SR as predictive factor for sentinel lymph node (SLN) positivity and tumor progression. We calculated the best threshold for SR and GR to predict the risk of recurrence. Melanoma clinical and histological characteristics as well as GR were correlated in a multivariated analysis with SR. SR values >0.2 mitoses/month were associated with negative prognostic factors such as ulceration (82.8%), SLN positivity (80%), progression (82.8%), and death (85.7%). The association of GR > 0.3 mm/months and SR > 0.2 mitoses/month had a significant predictive value in terms of SLN positivity, progression, and recurrence‐free survival. We propose SR as a new "dynamic" predictor of histological SLN positivity and melanoma recurrence risk. We think that he association with this new feature with GR may be helpful in improving the accuracy of predicted clinical outcome of patient especially with thin melanomas. [ABSTRACT FROM AUTHOR]

The process of "coming out" for a lesbian, gay, or bisexual (LGB) individual has been described in social sciences literature for almost 40 years. This review of the literature investigated whether sexual minority individuals continue to struggle with a coming‐out process in a more accepting society. Historically, the literature focused on the stages of acknowledging to oneself and others that one identifies with a minority sexual orientation. However, current literature offers new models for understanding sexual orientation and alternative paths to sexual identity that use more contextual and culturally relevant frameworks. Several other variables—including the internalization of sexual stigma, the intersection of sexual identity with other cultural variables, and the minority stress experienced by LGB individuals—have a major impact on the well‐being of LGB individuals and their families. This article also discusses the impact of the current sociopolitical climate on the coming‐out process. [ABSTRACT FROM AUTHOR]

Links between mother-infant affective matching and attachment security are well-documented, but research on other types of behavioral matching and attachment security are lacking, as are studies that examine these constructs later in children's development. We examine language style matching (LSM) between mothers and their school-aged children (N = 68), using interviews with each dyad member. As predicted, regressions revealed that higher mother-child relational LSM was associated with greater child attachment security (operationalized as high security, low dismissal), and that higher LSM predicted smaller increases in children's electrodermal response to a relational probe 1.5 years later. Further, mother-child relational LSM was a mediator in the indirect path between children's attachment security and children's reactivity. We discuss the potential utility of LSM as a measure of relationship quality and future studies that could refine our understanding of parent-child language matching. [ABSTRACT FROM AUTHOR]

The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagic activity. However, when the cells were treated with SAHA/PN combination, SAHA suppressed PN effect on Akt/mTOR/Nrf2 pathway, while PN reduced the prosurvival autophagic activity of SAHA. In addition SAHA/PN combination induced GSH depletion, fall in Δψm, release of cytochrome c, activation of caspase 3 and apoptosis. Finally we demonstrated that combined treatment maintained both hyperacetylation of histones H3 and H4 induced by SAHA and down-regulation of DNMT1 expression induced by PN. Inhibition of the DNA-binding activity of NF-kB, which is determined by PN, was also observed after combined treatment. In conclusion, combination of PN to SAHA inhibits the cytoprotective responses induced by the single compounds, but does not alter the mechanisms leading to the cytotoxic effects. Taken together our results suggest that this combination could be a candidate for TNBC therapy. J. Cell. Physiol. 230: 1276-1289, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company [ABSTRACT FROM AUTHOR]

Background: The Decapentaplegic (Dpp) signaling pathway is used in many developmental and homeostatic contexts, each time resulting in cellular responses particular to that biological niche. The flexibility of Dpp signaling is clearly evident in epithelial cells of the Drosophila wing imaginal disc. During larval stages of development, Dpp functions as a morphogen, patterning the wing developmental field and stimulating tissue growth. A short time later, however, as wing-epithelial cells exit the cell cycle and begin to differentiate, Dpp is a critical determinant of vein-cell fate. It is likely that the Dpp signaling pathway regulates different sets of target genes at these two developmental time points. Results: To identify mechanisms that temporally control the transcriptional output of Dpp signaling in this system, we have taken a gene expression profiling approach. We identified genes affected by Dpp signaling at late larval or early pupal developmental time points, thereby identifying patterning- and differentiation-specific downstream targets, respectively. Conclusions: Analysis of target genes and transcription factor binding sites associated with these groups of genes revealed potential mechanisms by which target-gene specificity of the Dpp signaling pathway is temporally regulated. In addition, this approach revealed novel mechanisms by which Dpp affects the cellular differentiation of wing-veins. Developmental Dynamics 243:818-832, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 ( IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 ( IDH1R132) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1R132 residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1R132 in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1R132 are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas. Hum Mutat 30, 7-11, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The neurotrophic tyrosine receptor kinase (NTRK) family is potentially implicated in tumorigenesis and progression of several neoplastic diseases, including lung cancer. We investigated a large number of pulmonary neuroendocrine tumors (PNETs) and non-small cell lung carcinomas (NSCLCs) without morphological evidence of neuroendocrine differentiation for mutations in the NTRK gene family. A total of 538 primary lung carcinomas, including 17 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 39 small cell lung carcinomas (SCLCs), 29 large cell neuroendocrine carcinomas (LCNECs), and 443 NSCLCs were evaluated by single-strand conformation polymorphism (SSCP) and sequencing of the tyrosine kinase domain (TKD) of NTRK1, NTRK2, and NTRK3. The NTRK1 gene was never found to be mutated. A total of 10 somatic mutations were detected in NTRK2 and NTRK3, mostly located in the activating and catalytic loops. NTRK mutations were seen in 9 (10%) out of 95 PNETs but in 0 out of 443 NSCLCs investigated. No mutations were observed in TCs, ACs, and SCLCs. Interestingly, all the mutations were restricted to the LCNEC histotype, in which they accounted for 31% of cases. A mutational analysis, performed after microdissection of LCNECs combined with adenocarcinoma (ADC), showed that only neuroendocrine areas were positive, suggesting that NTRK mutations are involved in the genesis of the neuroendocrine component of combined LCNECs. Our data indicate that somatic mutations in the TKD of NTRK genes are frequent in LCNECs. Such mutational events could represent an important step in the cancerogenesis of these tumors and may have potential implications for the selection of patients for targeted therapy. Hum Mutat 29(5), 609-616, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated ( p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Survivin is an inhibitor of apoptosis protein, overexpressed in most human malignancies and implicated in mitosis regulation and preservation of cell viability. In order to investigate the prevalence and clinical significance of survivin in early-stage non-small cell lung carcinoma (NSCLC), survivin mRNA levels and protein expression were evaluated, using quantitative real-time RT-PCR and immunohistochemistry, respectively, in a series of 83 patients with stage I (IA and IB) surgically resected NSCLC. Detectable survivin mRNA levels could be demonstrated in all non-neoplastic lung tissue samples and in the tumours analysed. Survivin mRNA levels were elevated in 80 carcinomas (96%) compared to normal lung (p = 0.008). Among all tumours, survivin transcripts were present at a higher level in squamous cell carcinomas (p = 0.0022). Cytoplasmic and nuclear immunoreactivity was found in 70% and 80% of tumours, respectively and both were present in 54%. Cytoplasmic immunoreactivity correlated with tumour stage (p = 0.019). Survivin expression levels did not correlate with patient survival. In one specimen, cytoplasmic and focal nuclear immunostaining was observed in dysplastic bronchial squamous metaplasia. These results document that survivin overexpression is almost always present in early-stage NSCLC, suggesting that this protein may play a role in lung tumourigenesis. This ubiquitous expression makes survivin an appealing new target for novel therapies in lung cancer. In addition, this study also documents that survivin overexpression could be exploited for diagnostic purposes and that quantitative real-time RT-PCR can be a useful tool for evaluating survivin activation in NSCLC. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]