Connectivity, neutral theories and the assessment of species vulnerability to global change in temperate estuaries

One of the main adaptation strategies to global change scenarios, aiming to preserve ecosystem functioning and biodiversity, is to maximise ecosystem resilience. The resilience of a species metapopulation can be improved by facilitating connectivity between local populations, which will prevent demographic stochasticity and inbreeding. The objective of this investigation is to estimate the degree of connectivity among estuarine species along the north-eastern Iberian coast, in order to assess community vulnerability to global change scenarios. To address this objective, two connectivity proxy types have been used based upon genetic and ecological drift processes: 1) DNA markers for the bivalve cockle (Cerastoderma edule) and seagrass Zostera noltei, and 2) the decrease in the number of species shared between two sites with geographic distance; neutral biodiversity theory predicts that dispersal limitation modulates this decrease, and this has been explored in estuarine plants and macroinvertebrates. Results indicate dispersal limitation for both saltmarsh plants and seagrass beds community and Z. noltei populations; this suggests they are especially vulnerable to expected climate changes on their habitats. In contrast, unstructured spatial pattern found in macroinvertebrate communities and in C. edule genetic populations in the area suggests that estuarine soft-bottom macroinvertebrates with planktonic larval dispersal strategies may have a high resilience capacity to moderate changes within their habitats. Our findings can help environmental managers to prioritise the most vulnerable species and habitats to be restored

Postcranial morphology of the middle Pleistocene humans from Sima de los Huesos, Spain

Current knowledge of the evolution of the postcranial skeleton in the genus Homo is hampered by a geographically and chronologically scattered fossil record. Here we present a complete characterization of the postcranium of the middle Pleistocene paleodeme from the Sima de los Huesos (SH) and its paleobiological implications. The SH hominins show the following: (i) wide bodies, a plesiomorphic char- acter in the genus Homo inherited from their early hominin ancestors; (ii) statures that can be found in modern human middle-latitude pop- ulations that first appeared 1.6–1.5 Mya; and (iii) large femoral heads in some individuals, a trait that first appeared during the middle Pleistocene in Africa and Europe. The intrapopulational size variation in SH shows that the level of dimorphism was similar to modern humans (MH), but the SH hominins were less encephalized than Ne- andertals. SH shares many postcranial anatomical features with Ne- andertals. Although most of these features appear to be either plesiomorphic retentions or are of uncertain phylogenetic polarity, a few represent Neandertal apomorphies. Nevertheless, the full suite of Neandertal-derived features is not yet present in the SH popula- tion. The postcranial evidence is consistent with the hypothesis based on the cranial morphology that the SH hominins are a sister group to the later Neandertals. Comparison of the SH postcranial skeleton to other hominins suggests that the evolution of the postcranium oc- curred in a mosaic mode, both at a general and at a detailed level

The dynamic use of EGFR mutation analysis in cell-free DNA as a follow-up biomarker during different treatment lines in non-small-cell lung cancer patients

Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median = 11, IQR = 9 5-13) to the best response (median = 0, IQR = 0-0, p < 0 01), followed by a significant increase at progression (median = 11, IQR = 11-15, p < 0 01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received

Measurement of the Xe 136 two-neutrino double -decay half-life via direct background subtraction in NEXT

[EN] We report a measurement of the half-life of the 136Xe two-neutrino double-ß decay performed with a novel direct-background-subtraction technique. The analysis relies on the data collected with the NEXT-White detector operated with 136Xe-enriched and 136Xe-depleted xenon, as well as on the topology of double-electron tracks. With a fiducial mass of only 3.5 kg of Xe, a half-life of 2.34+0.80(stat)+0.30(sys)×1021 yr is derived from ¿0.46 ¿0.17 the background-subtracted energy spectrum. The presented technique demonstrates the feasibility of unique background-model-independent neutrinoless double-ß-decay searches.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under Grant No. 951281-BOLD; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under Grant No. 957202-HIDDEN; the MCIN/AEI/10.13039/501100011033 of Spain and ERDF "A way of making Europe" under Grant No. RTI2018-095979, the Severo Ochoa Program Grant No. CEX2018-000867-S, and the Maria de Maeztu Program Grant No. MDM-2016-0692; the Generalitat Valenciana of Spain under Grants No. PROMETEO/2021/087 and No. CIDEGENT/2019/049; the Portuguese FCT under Project No. UID/FIS/04559/2020 to fund the activities of LIBPhys-UC; the Pazy Foundation (Israel) under Grants No. 877040 and No. 877041; the U.S. Department of Energy under Contracts No. DE-AC02-06CH11357 (Argonne National Laboratory), No. DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), No. DE-FG02-13ER42020 (Texas A&M), No. DE-SC0019054 (Texas Arlington), and No. DE-SC0019223 (Arlington, TX); the U.S. National Science Foundation under Grant No. CHE 2004111; and the Robert A. Welch Foundation under Grant No. Y-203120200401. D.G.D. acknowledges support from the Ramon y Cajal program (Spain) under Contract No. RYC-2015-18820. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Novella, P.; Sorel, M.; Usón, A.; Adams, C.; Almazán, H.; Álvarez-Puerta, V.; Aparicio, B.... (2022). Measurement of the Xe 136 two-neutrino double -decay half-life via direct background subtraction in NEXT. Physical Review C (Online). 105(5):055501-1-055501-8. https://doi.org/10.1103/PhysRevC.105.055501055501-1055501-8105

NEXT-CRAB-0: A High Pressure Gaseous Xenon Time Projection Chamber with a Direct VUV Camera Based Readout

The search for neutrinoless double beta decay ($0\nu\beta\beta$) remains one of the most compelling experimental avenues for the discovery in the neutrino sector. Electroluminescent gas-phase time projection chambers are well suited to $0\nu\beta\beta$ searches due to their intrinsically precise energy resolution and topological event identification capabilities. Scalability to ton- and multi-ton masses requires readout of large-area electroluminescent regions with fine spatial resolution, low radiogenic backgrounds, and a scalable data acquisition system. This paper presents a detector prototype that records event topology in an electroluminescent xenon gas TPC via VUV image-intensified cameras. This enables an extendable readout of large tracking planes with commercial devices that reside almost entirely outside of the active medium.Following further development in intermediate scale demonstrators, this technique may represent a novel and enlargeable method for topological event imaging in $0\nu\beta\beta$.Comment: 32 Pages, 22 figure

Boosting background suppression in the NEXT experiment through Richardson-Lucy deconvolution

Next-generation neutrinoless double beta decay experiments aim for half-life sensitivities of ~$10^{27}$ yr, requiring suppressing backgrounds to <1 count/tonne/yr. For this, any extra background rejection handle, beyond excellent energy resolution and the use of extremely radiopure materials, is of utmost importance. The NEXT experiment exploits differences in the spatial ionization patterns of double beta decay and single-electron events to discriminate signal from background. While the former display two Bragg peak dense ionization regions at the opposite ends of the track, the latter typically have only one such feature. Thus, comparing the energies at the track extremes provides an additional rejection tool. The unique combination of the topology-based background discrimination and excellent energy resolution (1% FWHM at the Q-value of the decay) is the distinguishing feature of NEXT. Previous studies demonstrated a topological background rejection factor of ~5 when reconstructing electron-positron pairs in the $^{208}$Tl 1.6 MeV double escape peak (with Compton events as background), recorded in the NEXT-White demonstrator at the Laboratorio Subterr\'aneo de Canfranc, with 72% signal efficiency. This was recently improved through the use of a deep convolutional neural network to yield a background rejection factor of ~10 with 65% signal efficiency. Here, we present a new reconstruction method, based on the Richardson-Lucy deconvolution algorithm, which allows reversing the blurring induced by electron diffusion and electroluminescence light production in the NEXT TPC. The new method yields highly refined 3D images of reconstructed events, and, as a result, significantly improves the topological background discrimination. When applied to real-data 1.6 MeV $e^-e^+$ pairs, it leads to a background rejection factor of 27 at 57% signal efficiency.Comment: Submitted to JHE

Ba+2 ion trapping using organic submonolayer for ultra-low background neutrinoless double beta detector

If neutrinos are their own antiparticles the otherwise-forbidden nuclear reaction known as neutrinoless double beta decay can occur. The very long lifetime expected for these exceptional events makes its detection a daunting task. In order to conduct an almost background-free experiment, the NEXT collaboration is investigating novel synthetic molecular sensors that may capture the Ba dication produced in the decay of certain Xe isotopes in a high-pressure gas experiment. The use of such molecular detectors immobilized on surfaces must be explored in the ultra-dry environment of a xenon gas chamber. Here, using a combination of highly sensitive surface science techniques in ultra-high vacuum, we demonstrate the possibility of employing the so-called Fluorescent Bicolor Indicator as the molecular component of the sensor. We unravel the ion capture process for these molecular indicators immobilized on a surface and explain the origin of the emission fluorescence shift associated to the ion trapping

IgM memory B cells: a mouse/human paradox

Humoral memory is maintained by two types of persistent cells, memory B cells and plasma cells, which have different phenotypes and functions. Long-lived plasma cells can survive for a lifespan within a complex niche in the bone marrow and provide continuous protective serum antibody levels. Memory B cells reside in secondary lymphoid organs, where they can be rapidly mobilized upon a new antigenic encounter. Surface IgG has long been taken as a surrogate marker for memory in the mouse. Recently, however, we have brought evidence for a long-lived IgM memory B cell population in the mouse, while we have also argued that, in humans, these same cells are not classical memory B cells but marginal zone (MZ) B cells which, as opposed to their mouse MZ counterpart, recirculate and carry a mutated B cell receptor. In this review, we will discuss these apparently paradoxical results

Down-Regulation of AP-4 Inhibits Proliferation, Induces Cell Cycle Arrest and Promotes Apoptosis in Human Gastric Cancer Cells

BACKGROUND: AP-4 belongs to the basic helix-loop-helix leucine-zipper subgroup; it controls target gene expression, regulates growth, development and cell apoptosis and has been implicated in tumorigenesis. Our previous studies indicated that AP-4 was frequently overexpressed in gastric cancers and may be associated with the poor prognosis. The purpose of this study is to examine whether silencing of AP-4 can alter biological characteristics of gastric cancer cells. METHODS: Two specific siRNAs targeting AP-4 were designed, synthesized, and transfected into gastric cancer cell lines and human normal mucosa cells. AP-4 expression was measured with real-time quantitative PCR and Western blot. Cell proliferation and chemo-sensitivity were detected by CCK-8 assay. Cell cycle assay and apoptosis assay were performed by flow cytometer, and relative expression of cell cycle regulators were detected by real-time quantitative PCR and Western blot, expression of the factors involved in the apoptosis pathway were examined in mRNA and protein level. RESULTS: The expression of AP-4 was silenced by the siRNAs transfection and the effects of AP-4 knockdown lasted 24 to 96 hrs. The siRNA-mediated silencing of AP-4 suppressed the cellular proliferation, induced apoptosis and sensitized cancer cells to anticancer drugs. In addition, the expression level of p21, p53 and Caspase-9 were increased when AP-4 was knockdown, but the expression of cyclin D1, Bcl-2 and Bcl-x(L) was inhibited. It didn't induce cell cycle arrest when AP-4 was knockdown in p53 defect gastric cancer cell line Kato-III. CONCLUSIONS: These results illustrated that gene silencing of AP-4 can efficiently inhibited cell proliferation, triggered apoptosis and sensitized cancer cells to anticancer drugs in vitro, suggesting that AP-4 siRNAs mediated silencing has a potential value in the treatment of human gastric cancer