Exploring mobility in Italian Neolithic and Copper Age communities

As a means for investigating human mobility during late the Neolithic to the Copper Age in central and southern Italy, this study presents a novel dataset of enamel oxygen and carbon isotope values (δ18Oca and δ13Cca) from the carbonate fraction of biogenic apatite for one hundred and twenty-six individual teeth coming from two Neolithic and eight Copper Age communities. The measured δ18Oca values suggest a significant role of local sources in the water inputs to the body water, whereas δ13Cca values indicate food resources, principally based on C3 plants. Both δ13Cca and δ18Oca ranges vary substantially when samples are broken down into local populations. Statistically defined thresholds, accounting for intra-site variability, allow the identification of only a few outliers in the eight Copper Age communities, suggesting that sedentary lifestyle rather than extensive mobility characterized the investigated populations. This seems to be also typical of the two studied Neolithic communities. Overall, this research shows that the investigated periods in peninsular Italy differed in mobility pattern from the following Bronze Age communities from more northern areas

p53 Gene Mutational Rate, Gleason Score, and BK Virus Infection in Prostate Adenocarcinoma: Is There a Correlation?

Prostate cancer represents the second leading cause of cancer deaths in Western countries. Viral infections could play a role in prostate carcinogenesis. Human polyomavirus BK (BKV) is a possible candidate because of its transforming properties. In this study, BKV sequences in urine, blood, fresh, and paraffin-em bedded prostate cancer samples from 26 patients were searched using Q-PCR analysis. T antigen (TAg) and p53 localization in neoplastic cells were evaluated by immunohistochemical analysis. Also, the presence of mutations in 5-9 exons of p53 gene was analyzed. Results showed that BKV-DNA was found in urine (54%), plasma (31%), and in fresh prostate cancer specimens (85%). The analysis of p53 gene evidenced several mutations in high Gleason patients, according to tumor advanced stage. Immunohistochemical analysis results evidenced the localization of p53 and TAg into cytoplasm, whereas in TAg-negative tumors, p53 was nuclear. This study suggests that BKV acts as cofactor in the pathogenesis of prostate cancer. These observations emphasize previous studies regarding the cellular pathways that may be deregulated by BKV. J. Med. Virol. 80:2100-2107,2008. (C) 2008 Wiley-Liss, Inc

Inferring biallelism of two FSH receptor mutations associated with spontaneous ovarian hyperstimulation syndrome by evaluating FSH, LH and HCG cross-activity

International audienceResearch question: What is the cumulative effect of two follicle-stimulating hormone receptor (FSHR) mutations in spontaneous ovarian hyperstimulation syndrome (sOHSS) pathogenesis? Are these mutations in the mono- or biallelic state? Design: Two FSHR mutations were found in a pregnant patient affected by sOHSS with no predisposing conditions. While the p.Asn106His mutation is novel, the p.Ser128Tyr mutation has been associated with sOHSS previously. The patient's FSHR gene was analysed by Sanger sequencing, and FSHR cDNAs carrying a single or both point mutations were created by mutagenesis in vitro. cAMP activation by recombinant FSH, luteinizing hormone (LH), human chorionic gonadotropin (HCG) and thyroid-stimulating hormone (TSH) was evaluated in transfected HEK293 cells by bioluminescence resonance energy transfer. Results: All mutations decreased the 50% effective concentration of FSH calculated for cAMP (P < 0.05, n = 6), resulting in two- to 10-fold lower ligand potency. TSH failed to induce an FSHR-mediated increase in intracellular cAMP, while LH was approximately four-fold more potent than HCG in p.Ser128Tyr FSHR-expressing HEK293 cells despite lower cAMP plateau levels (P < 0.05, n = 5). The p.Ser128Tyr FSHR mutation was found to be responsible for an LH-/HCG-induced increase in cAMP when it was in the biallelic heterozygous state with p.Asn106His, but no increase in cAMP was induced in the monoallelic state. Conclusion: In-vitro data support that, in pregnant patients with sOHSS, the two FSHR mutations have an opposing effect on the pathogenesis of sOHSS and are in the biallelic heterozygous form, allowing HCG to induce a p.Ser128Tyr FSHR-mediated increase in cAMP

Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival

International audienceClassically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio,which negatively impacts follicle maturation and strongly correlates with preferential Gas protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromer striggered anti-apoptotic/proliferative FSH signaling delivered via the Gbgdimer, where as impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferatio

Search for leptonic decays of the dark photon at NA62

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of $1.4 \times 10^{17}$ protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% CL, improving on previous experimental limits for dark photon mass values between 50 and 600 MeV/$c^2$ and coupling values in the range $10^{−6}$ to $4 \times 10^{−5}$. An interpretation of the $e^+ e^−$ search result in terms of the emission and decay of an axion-like particle is also presented.The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of $1.4\times 10^{17}$ protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% CL, improving on previous experimental limits for dark photon mass values between 50 and 600 MeV$/c^2$ and coupling values in the range $10^{-6}$ to $4\times10^{-5}$. An interpretation of the $e^+ e^-$ search result in terms of the emission and decay of an axion-like particle is also presented

Search for leptonic decays of the dark photon at NA62

International audienceThe NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of $1.4\times 10^{17}$ protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% CL, improving on previous experimental limits for dark photon mass values between 50 and 600 MeV$/c^2$ and coupling values in the range $10^{-6}$ to $4\times10^{-5}$. An interpretation of the $e^+ e^-$ search result in terms of the emission and decay of an axion-like particle is also presented

Search for dark photon decays to μ+μ−\mu^+\mu^- at NA62

International audienceThe NA62 experiment at CERN, designed to study the ultra-rare decay $K^+ \to \pi^+\nu\overline{\nu}$, has also collected data in beam-dump mode. In this configuration, dark photons may be produced by protons dumped on an absorber and reach a decay volume beginning 80 m downstream. A search for dark photons decaying in flight to $\mu^+\mu^-$ pairs is reported, based on a sample of $1.4 \times 10^{17}$ protons on dump collected in 2021. No evidence for a dark photon signal is observed. A region of the parameter space is excluded at 90% CL, improving on previous experimental limits for dark photon masses between 215 and 550 MeV$/c^2$