Marine turtles use geomagnetic cues during open-sea homing

Marine turtles are renowned long-distance navigators, able to reach remote targets in the oceanic environment; yet the sensory cues and navigational mechanisms they employ remain unclear [1, 3]. Recent arena experiments indicated an involvement of magnetic cues in juvenile turtles' homing ability after simulated displacements [4, 5], but the actual role of geomagnetic information in guiding turtles navigating in their natural environment has remained beyond the reach of experimental investigations. In the present experiment, twenty satellite-tracked green turtles (Chelonia mydas) were transported to four open-sea release sites 100-120 km from their nesting beach on Mayotte island in the Mozambique Channel; 13 of them had magnets attached to their head either during the outward journey or during the homing trip. All but one turtle safely returned to Mayotte to complete their egg-laying cycle, albeit with indirect routes, and showed a general inability to take into account the deflecting action of ocean currents as estimated through remote-sensing oceanographic measurements [7]. Magnetically treated turtles displayed a significant lengthening of their homing paths with respect to controls, either when treated during transportation or when treated during homing. These findings represent the first field evidence for the involvement of geomagnetic cues in sea-turtle navigation.     

Phenology and synchrony of roe deer breeding in northern Italy

The timing and synchrony of births of roe deerCapreolus capreolus Linnaeus, 1758 population were examined for 7 consecutive years in northern Italy. From 1997 to 2003, 136 fawns, 65 females and 71 males, from 117 litters were captured. The average date of fawning (30th of May) was constant among years and between sexes. The onset of parturition was 19th of May while the total length of the parturition season was 25 days (from 19th of May to 13th of June). Births were highly synchronous, with 80% of births occurring in 17 days. Synchrony of birth did not exhibit any significant interannual or intersexual variation. The stability of the birth pattern was confirmed by the parturition date of 13 radiocollared females who all gave birth within 4 days in consecutive fawning seasons. In agreement with previous findings, our data support the hypothesis that the roe deer is constrained at both ends of the fawning season by the short time between the fawning season and rut and by the need to match optimal climate conditions and forage quality to face late gestation and lactation. All these factors result in a relatively stable and synchronous birth season.     

Investigation of fungal biomolecules after Low Earth Orbit exposure: a testbed for the next Moon missions

The Moon is characterized by extremely harsh conditions due to ultraviolet irradiation, wide temperature extremes, vacuum resulting from the absence of an atmosphere and high ionizing radiation. Therefore, its surface may provide a unique platform to investigate the effects of such conditions. For lunar exploration with the Lunar Gateway platform, exposure experiments in Low Earth Orbit are useful testbeds to prepare for lunar space experiments and to understand how and if potential biomarkers are influenced by extra-terrestrial conditions. During the BIOMEX (BIOlogy and Mars EXperiment) project, dried colonies of the fungus Cryomyces antarcticus grown on Lunar Regolith Analogue (LRA) were exposed to space conditions for 16 months aboard the EXPOSE-R2 payload outside the International Space Station. In this study, we investigated the stability/degradation of fungal biomarkers in LRA after exposure to (i) simulated space and (ii) real space conditions, using Raman spectroscopy, gas chromatography–mass spectrometry and DNA amplification. The results demonstrated that fungal biomarkers were detectable after 16 months of real space exposure. This work will contribute to the interpretation of data from future biological experiments in the Cislunar orbit with the Lunar Gateway platform and/or on the lunar surface, in preparation for the next step of human exploration.     

Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma

Background

Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be ‘major’, characterized by a single tumor showing two different histologic types, and ‘minor’, due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas.

Methods

590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR.

Results

10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components.

Conclusion

Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes.     

A regulatory network comprising let-7 miRNA and SMUG1 is associated with good prognosis in ER+ breast tumours

Single-strand selective uracil–DNA glycosylase 1 (SMUG1) initiates base excision repair (BER) of uracil and oxidized pyrimidines. SMUG1 status has been associated with cancer risk and therapeutic response in breast carcinomas and other cancer types. However, SMUG1 is a multifunctional protein involved, not only, in BER but also in RNA quality control, and its function in cancer cells is unclear. Here we identify several novel SMUG1 interaction partners that functions in many biological processes relevant for cancer development and treatment response. Based on this, we hypothesized that the dominating function of SMUG1 in cancer might be ascribed to functions other than BER. We define a bad prognosis signature for SMUG1 by mapping out the SMUG1 interaction network and found that high expression of genes in the bad prognosis network correlated with lower survival probability in ER⁺ breast cancer. Interestingly, we identified hsa-let-7b-5p microRNA as an upstream regulator of the SMUG1 interactome. Expression of SMUG1 and hsa-let-7b-5p were negatively correlated in breast cancer and we found an inhibitory auto-regulatory loop between SMUG1 and hsa-let-7b-5p in the MCF7 breast cancer cells. We conclude that SMUG1 functions in a gene regulatory network that influence the survival and treatment response in several cancers.     

Cutting edge: differential chemokine production by myeloid and plasmacytoid dendritic cells

To examine the different roles of myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) in the induction and regulation of immune response, we have studied chemokine secretion by freshly isolated DC subsets in response to bacterial, viral, and T cell-derived stimuli. M-DCs selectively produced very high levels of the homeostatic chemokines CC chemokine ligand (CCL)17 and CCL22, while P-DCs produced very little if any. In contrast, the proinflammatory chemokine CCL3 was secreted mostly by P-DCs, whereas CCL4 and CXC chemokine ligand 8 were produced by both subsets. The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections. The high production of CCR4 ligands by M-DCs suggests their capacity to selectively recruit at sites of inflammation T cells with regulatory properties or with a Th2 phenotype, whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells.     

Gliadin-mediated proliferation and innate immune activation in celiac disease are due to alterations in vesicular trafficking

Background and Objectives

Damage to intestinal mucosa in celiac disease (CD) is mediated both by inflammation due to adaptive and innate immune responses, with IL-15 as a major mediator of the innate immune response, and by proliferation of crypt enterocytes as an early alteration of CD mucosa causing crypts hyperplasia. We have previously shown that gliadin peptide P31-43 induces proliferation of cell lines and celiac enterocytes by delaying degradation of the active epidermal growth factor receptor (EGFR) due to delayed maturation of endocytic vesicles. IL-15 is increased in the intestine of patients affected by CD and has pleiotropic activity that ultimately results in immunoregulatory cross-talk between cells belonging to the innate and adaptive branches of the immune response. Aims of this study were to investigate the role of P31-43 in the induction of cellular proliferation and innate immune activation.

Methods/Principal Findings

Cell proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation both in CaCo-2 cells and in biopsies from active CD cases and controls. We used real-time PCR to evaluate IL-15 mRNA levels and FACS as well as ELISA and Western Blot (WB) analysis to measure protein levels and distribution in CaCo-2 cells.Gliadin and P31-43 induce a proliferation of both CaCo-2 cells and CD crypt enterocytes that is dependent on both EGFR and IL-15 activity. In CaCo-2 cells, P31-43 increased IL-15 levels on the cell surface by altering intracellular trafficking. The increased IL-15 protein was bound to IL15 receptor (IL-15R) alpha, did not require new protein synthesis and functioned as a growth factor.

Conclusion

In this study, we have shown that P31-43 induces both increase of the trans-presented IL-15/IL5R alpha complex on cell surfaces by altering the trafficking of the vesicular compartments as well as proliferation of crypt enterocytes with consequent remodelling of CD mucosa due to a cooperation of IL-15 and EGFR.     

Towards a footwear design tool: Influence of shoe midsole properties and ground stiffness on the impact force during running

Several spring–damper–mass models of the human body have been developed in order to reproduce the measured ground vertical reaction forces during human running (McMahon and Cheng, 1990; Ferris et al., 1999; Liu and Nigg, 2000). In particular, Liu and Nigg introduced at the lower level of their model, i.e. at the interface between the human body and the ground, a nonlinear element representing simultaneously the shoe midsoles and the ground flexibility. The ground reaction force is modelled as the force supported by this nonlinear element, whose parameters are identified from several sets of experimental data. This approach proved to be robust and quite accurate. However, it does not explicitly take into account the shoe and the ground properties. It turns out to be impossible to study the influence of shoe materials on the impact force, for instance for footwear design purposes. In this paper, a modification of the Liu and Nigg's model is suggested, where the original nonlinear element is replaced with a bi-layered spring–damper–mass model: the first layer represents the shoe midsole and the second layer is associated with the ground.Ground is modelled as an infinite elastic half-space. We have assumed a viscoelastic behaviour of the shoe material, so the damping of shoe material is taken into account. A methodology for the shoe-soles characterization is proposed and used together with the proposed model. A parametric study is then conducted and the influence of the shoe properties on the impact force is quantified. Moreover, it is shown that impact forces are strongly affected by the ground stiffness, which should therefore be considered as an essential parameter in the footwear design.     

Intra- and inter-cores fungal diversity suggests interconnection of different habitats in an Antarctic frozen lake (Boulder Clay,Northern Victoria Land)

A perennially frozen lake at Boulder Clay site (Victoria Land, Antarctica), characterized by the presence of frost mounds, have been selected as an in situ model for ecological studies. Different samples of permafrost, glacier ice and brines have been studied as a unique habitat system. An additional sample of brines (collected in another frozen lake close to the previous one) was also considered. Alpha- and beta-diversity of fungal communities showed both intra- and inter-cores significant (p < 0.05) differences, which suggest the presence of interconnection among the habitats. Therefore, the layers of frost mound and the deep glacier could be interconnected while the brines could probably be considered as an open habitat system not interconnected with each other. Moreover, the absence of similarity between the lake ice and the underlying permafrost suggested that the lake is perennially frozen based. The predominance of positive significant (p < 0.05) co-occurrences among some fungal taxa allowed to postulate the existence of an ecological equilibrium in the habitats systems. The positive significant (p < 0.05) correlation between salt concentration, total organic carbon and pH, and some fungal taxa suggests that a few abiotic parameters could drive fungal diversity inside these ecological niches.