NNLS software was used for sample analysis. The zeta potential was measured by Laser Doppler Velocimetry (LDV) coupled with Photon Correlation Spectroscopy using a Zetasizer Nano ZS (Malvern Instruments, Malvern). The experiments were conducted at 25 °C and a scattering angle of 17°. The Zetapotential was calculated out of the electrophoretic mobility by applying the Henry equation. Although Photon Correlation Spectroscopy has its limitations for the assessment of fibrous particles it is an accepted technique to describe physicochemical parameters of CNTs in solvents (Ito et al., 2004 and Lee et al., 2005). Hence, this

method has also been used by several other groups for the characterization of CNTs for biological experiments (e.g., (Bhirde et al., 2010, Wang et al., 2011 and Yang et al., 2012)). To verify this data by another independent method, CNTs were also characterized Ivacaftor ic50 by transmission electron microscopy. The DAPT chemical structure CNTs were dispersed in DMEM + 10% FBS at 1 mg/ml and treated with ultrasound for 20 min. Five Microlitre of this solution were placed on a carbon coated copper grid that had previously been treated with a Pelco EasyGlow glow discharge device (Ted Pella, Inc., Redding, CA). After 1 min incubation, the solution was withdrawn using non hardened microscopic filter paper (Whatman, VWR International). Images were taken using a FEI Tecnai G2 20 transmission electron microscope (FEI Eindhoven)

with a Gatan ultrascan 1000 ccd camera. Acceleration voltage was 80 kV. Sizes of CNTs were measured from the TEM images. A549 human lung adenocarcinoma cells (ATCC) were cultured in DMEM + 10% fetal bovine serum in 6-well multiwell plates with polycarbonate membrane transwells (ThinCerts, Greiner bio-one, Frickenhausen). Cells were seeded with 500,000 cells/well. Cells in transwells were cultured in both liquid, submersed culture (LCC, cell culture medium in apical and basal compartment) and air–liquid interface (ALI) (apical compartment

air and basal compartment cell culture medium) at 37° C in a 95% air/5% CO2 atmosphere. For the exposures in the VITROCELL/PARI BOY and in the MicroSprayer, cells were seeded, medium was removed after 24 h and cells were cultured for an additional 7–8 days prior to the exposures. The expression of tight junction proteins in cells was studied Chlormezanone by the immunocytochemical localization of zona occludens protein-1 (ZO-1) and claudin-1. E-cadherin was chosen as a representative protein that is present in adherent junctions. Cells were fixed by incubation in 100% ethanol for 20 min, in 100% methanol for 2.5 min and in 1:1 ethanol/acetone 10 min at −20 °C. Thereafter, first antibodies and negative controls were added for 30 min at RT, followed by incubation with the secondary antibodies for 30 min at RT and counterstained with Hoechst 33342 for 15 min. Between all incubations, cells were rinsed three times for 5 min in PBS.

, 1997) could thereby be exacerbated, decreasing reproductive output in affected males. Conversely, reduced sperm swimming under acidified conditions could increase sperm longevity due to lowered consumption of limited endogenous energy provisioning ( Mita and Nakamura, 1998). Greater sperm longevity may increase chances of successful fertilization if sperm–egg-encounter rates remain sufficient over see more prolonged periods of time ( Levitan, 2000 and Marshall, 2002). Impacts of CO2-driven ocean acidification on

sperm swimming behavior of G. caespitosa may interact with other acidification impacts on fertilization variables such as male–female compatibility, egg competition or polyspermy block efficiency ( Evans and Marshall, 2005, Evans and Marshall, 2005 and Marshall and Bolton, 2007). Metabolism inhibitor Negative impacts of CO2-induced ocean acidification have also been

reported for later life-history stages of serpulid tubeworms, such as weaker calcareous tubes ( Chan et al., 2012 and Smith et al., 2013). Resultant cumulative effects on reproductive success and survivorship are likely to exacerbate the rate or intensity of selection pressure of climate change. Patterns of sperm swimming responses of G. caespitosa to CO2-induced acidification observed here were similar to those of Arenicola marina sperm in lowered seawater pH ( Pacey et al., 1994). Sperm activation in A. marina was delayed and sperm speed was reduced in HCl-acidified seawater (pH < 7.6). Interestingly, our findings are very different to those from Cediranib (AZD2171) a study on the related serpulid species Pomatoceros lamarckii ( Lewis et al., 2012). Sperm speeds of P. lamarckii were robust to CO2-induced pH reductions, percent motility was significantly reduced, but responses were non-linear. These findings may be explained by differences in experiment design and sample

size (5 pooled assays ( Lewis et al., 2012) vs 23 single individuals in this study). As outlined earlier, conducting adequately replicated studies will help to clarify whether these differences are caused by high inter-individual variability or differences in average responses between species. In conclusion, the substantial inter-individual variation in sperm responses observed here may ameliorate effects of future climate change, if the traits that drive phenotype robustness are heritable. Sperm from some G. caespitosa will be better equipped to cope with acidification than others, creating ‘winners’ and ‘losers’ in a future acidified ocean ( Schlegel et al., (2012). This observed resilience to near-future conditions could increase the potential for adaptation to far-future conditions, if gathering of advantageous alleles can occur quickly enough. Likewise, rapid selection against phenotypes susceptible to acidification may quickly reduce genetic diversity and lead to severe flow-on consequences for fitness and competitive ability downstream. Very few studies to date have investigated climate change impacts on polychaete species ( Chan et al.

In the current study, we used a tumor model that is known to be very sensitive to the MTD of cisplatin. Further studies in animal models with drug-resistant tumors are needed to explore the differences

in optical parameters in these settings. Moreover, it is likely that the changes in tumor tissue vary on the basis of the specific treatment given. To provide find more a more complete understanding of the relationship between optical spectroscopy parameters and pathologic response, the effect of other drugs on spectroscopy parameters needs to be investigated further. Conventional anatomic imaging alone lacks the sensitivity for early-response monitoring or assessing the effect of new targeted therapies that do not necessarily result in a change in tumor size. For these purposes, functional information, such as that obtained by 18F-FDG PET [7], [8] and [9] http://www.selleckchem.com/products/VX-765.html and contrast-enhanced magnetic resonance imaging [50] is more suitable. Optical spectroscopy is a relatively new functional imaging technique that may contribute to fast-response evaluation and timely shifting of systemic

treatment. This could be of great clinical benefit, even when it requires (minimal) invasive optical spectroscopy measurements in the tumor. In a time of personalized medicine, repeated tumor core biopsy is increasingly used during the course of treatment to generate a genetic or epigenetic profile allowing selection of the best possible treatment. Repeated biopsies may, however, be confounded by intratumor heterogeneity [51]. By performing optical spectroscopy along the needle path, an “optical tumor

profile” can be recorded covering a relatively large volume of tumor tissue. For example, Nachabe et al. [52] showed that optical spectroscopy measurements at the tip of a needle allowed real-time tissue characterization during percutaneous interventions. As such, optical spectroscopy offers the potential to measure real time alterations in the optical profile during systemic treatment. In this way, it may help to personalize cancer treatments Dichloromethane dehalogenase and may improve cost effectiveness of systemic treatment in cancer. In summary, this study shows that dual-modality DRS–AFS provides quantitative functional information that corresponds well with the degree of pathologic response of systemic treatment. This could be of considerable value for the monitoring and prediction of cancer therapy efficacy on the basis of individual patient response. Further studies including resistant tumor models and various therapeutic drugs are needed to verify the initial findings of this work.

, 2004), peptidoglycan ( Verbrugh et al., 1981) and lipoteichoic acid ( Wergeland et al., 1984), are also known to be immunogenic. In future studies we will include the analysis of the host response against these cell-wall components as well. Moreover, next to IgG levels, other immunoglobulins and their subclasses will be investigated. The authors do not have a commercial or other association that might pose a conflict of interest. We thank D.G.A.M. Koedijk for purification of Nuc, LytM, and IsaA. We thank G. Buist, T. Bosma, T. Foster, J.I. Epigenetic inhibitor solubility dmso Flock,

S. Rooijkakkers, S. Holtfreter, D. Grumann, and J.D. Fraser for kindly supplying the S. aureus proteins. S.v.d.B., T.B., G.B., J.M.v.D., A.v.B. and I.B.-W. were in part supported financially by the Top Institute Pharma project

T4-213. ”
“Salmonella enterica causes a spectrum of diseases, including typhoid and paratyphoid fever, and gastroenteritis ( Everest et al., 2001, Hohmann, 2001 and Boyle et al., 2007), and is a major threat to public health. S. enterica PARP inhibitors clinical trials serovar Typhi is the causative agent of typhoid fever. Paratyphoid fever, a clinically-similar disease with less prevalence, is caused by S. enterica serovar Paratyphi A, B and C. In developed countries, nontyphoidal isolates of Salmonella (NTS) usually cause gastroenteritis. In Africa, NTS, especially S. enterica serovar Typhimurium, are a common cause of invasive disease, in particular bacteremia. NTS bacteremia in sub-Saharan Africa primarily occurs in children under 2 years of age and HIV-infected individuals ( Graham et al., 2000, Graham, 2002, Graham, 2010, Brent et al., 2006 and Bronzan et al., 2007). The estimated minimum incidence of NTS bacteremia is 175 per 100,000 in Kenyan children under 5 years of age

per year ( Berkley et al., 2005). The lack of specific clinical presentation of NTS bacteremia makes diagnosis difficult. In addition, increased drug resistance and the emergence of new multi-drug resistant isolates ( Hohmann, 2001 and Mirza et al., 1996) have added to the burden of this often fatal disease. These findings emphasize the need for an effective vaccine against NTS. Currently, none is available for use in humans. The role of antibody in protection against Cepharanthine Salmonella has been well established. Adoptive transfer of antibodies confers protection against virulent Salmonella challenge ( Mastroeni et al., 1993 and McSorley and Jenkins, 2000). The importance of antibodies has also been emphasized by studies on Vi polysaccharide, which elicit T cell-independent antibody production and confer protection ( Acharya et al., 1987). A key assessment of most vaccines is their ability to induce specific antibody production. However, high antibody levels alone are insufficient, since vaccine-induced antibodies need to be protective.

For the analysis of total amount of biofilm formation (topography analysis), material groups (MPT, CPT and Zc) and regions (anterior and posterior) were used as categorical variables. When the total area of formed biofilm was evaluated between groups considering or not different regions, samples were assumed to be dependents and the Friedman test with post hoc Dunn test was applied. When the total area was evaluated between regions not considering different materials, Wilcoxon Selleck GSK1120212 matched-pair signed-rank test was carried out. By comparing the chemiluminescent intensity signals found in biofilm

samples and control lanes provided by the DNA checkerboard analysis, the number of micro-organisms colonising each substrate surface could be expressed in terms of counts. Percentages of colonised specimens

(incidence) for each target species were also provided. In order to compare the counts and the incidence of each microbial species at each material, the data were averaged within material groups and then averaged across different experimental regions (anterior and posterior). Significance of differences between groups Protein Tyrosine Kinase inhibitor for each species and total microbial count was sought using the Friedman test with post hoc Dunn test or Wilcoxon matched-pair test. Differences were considered significant when p < 0.05. All the statistical analyses were conducted using GraphPad InStat statistical software (GraphPad Software Inc., San Diego, CA, USA). The mean roughness surface (Ra, ±SD, ±standard error selleck chemicals llc of mean (SEM)) of the different tested substrates are summarised in Table

1. The Kruskal–Wallis analysis of variance showed extremely significant differences between tested materials (p < 0.0001). Dunn’s multiple comparison test showed higher mean roughness values for Zc when compared with titanium specimens (MPT and CPT; p < 0.001). MPT and CPT presented no differences between them (p > 0.05). Roughness values for titanium specimens ranged from 0.2 (minimum) to 0.46 μm (maximum), indicating a similar smooth structure of substrates. By contrast, the range for Zc specimens was 0.35–0.85 μm. The mean values of the total area (mm2) of formed biofilm for each material substrate are displayed in Fig. 1. Friedman test showed no significant differences in the total area of biofilm formation between evaluated substrates (p = 0.0724), neither after interaction with anterior or posterior region of disc placement (p = 0.2971). No significant differences were also observed when the biofilm area was compared only among regions (anterior and posterior) without interaction with material substrates (Wilcoxon matched-pair signed-rank test; p = 0.4546). The minimum value of the biofilm total area was recorded for an anterior Zc specimen (38.9 mm2), while the maximum values was recorded for anterior/posterior Zc and anterior MPT specimens (111.75 mm2, 111.64 mm2 and 111.

211 Support for this notion also comes from patients with β-thalassemia, who have low serum hepcidin levels despite iron overload.212 Growth differentiation factor 15 (GDF-15) and twisted gastrulation homolog 1 (TWSG1) have been identified as candidate erythrokines, although not erythroblast-specific, that have the potential to suppress hepcidin under conditions of increased

erythropoietic activity.[213], [214] and [215] GDF15 is an iron- and O2-regulated (HIF-independent) member of the TGF-β superfamily, which is secreted from maturing erythroblasts and has been shown to suppress BMS 754807 hepcidin transcription in primary human hepatocytes and hepatoma cells (Fig. 3).[213] and [216] While increased GDF15 serum levels associate with syndromes of ineffective erythropoiesis, for example α- and β-thalassemia, its role in hepcidin regulation under physiologic conditions and in other forms of anemia remains unclear.[213], [215], [217], [218] and [219] Therefore, it was proposed that GDF15 may be a marker of bone marrow stress or erythroblast apoptosis.215 selleckchem Elevated serum GDF15

level have also been found in patients with heart failure,220 which adds complexity to this model. We found that recombinant murine GDF15 suppressed hepcidin in Hep3B cells at a concentration of 750 pg/ml.207 This is in contrast to previous reports where higher doses of GDF15 were needed to achieve hepcidin suppression in human HuH-7 hepatoma cells and in primary hepatocytes, while low dose GDF15 treatment increased hepcidin.213 While demonstrated in mice, studies in humans receiving recombinant EPO have not yet shown a significant inverse relationship between serum hepcidin and GDF15 levels, which may

relate to the EPO doses administered, study size, complexity Enzalutamide clinical trial of regulation and species-dependent differences.[207] and [221] In the context of iron-deficiency anemia, Tanno and colleagues found that GDF15 serum levels were not elevated,222 while Lakhal and colleagues reported that patients with low serum iron had elevated GDF15 levels compared to iron-replete controls (mean of 1048 pg/ml vs. 542 pg/ml).216 Similarly, increased serum GDF15 levels were found following DFO treatment, suggesting iron-dependent regulation.216 Furthermore, temporary increases in serum GDF15 levels associated with increased serum EPO following ascent to high altitude.211 In addition to regulating iron metabolism, hypoxia has direct effects on the bone marrow. It promotes erythropoiesis by modulating erythroid progenitor maturation and proliferation.[223] and [224] Hypoxia stimulates EPOR expression and regulates components of the hemoglobin synthesis pathway.[52], [53], [54], [225] and [226] Hypoxia also modulates the interaction of erythroid progenitors with other cell types and thereby regulates stem cell maintenance, lineage differentiation and maturation.

, 2013 and Pellissier et al., 2013). These processes have been exacerbated as a consequence of the abandonment of agricultural and pastoral activities (Piussi and Farrell, 2000, Chauchard et al., 2007 and Zimmermann et al., 2010) and changes in traditional fire uses (Borghesio, 2009, Ascoli and Bovio, 2010, Conedera and Krebs, 2010 and Pellissier Tenofovir order et al., 2013), combined with intensified tourism pressure (Arndt et al., 2013). Many studies show how land-use abandonment and the following tree and shrub encroachment have negative consequences on biodiversity maintenance in the Alps, e.g., Laiolo et al. (2004), Fischer et al. (2008), Cocca et al. (2012), Dainese and Poldini (2012).

Under the second fire regime conditions, landscape opening favoured the creation of new habitats and niches with an increase in plant species richness (Carcaillet, 1998, Tinner et al., 1999, Colombaroli et al., 2010 and Berthel et al., 2012) and evenness, e.g., less dominant taxa (Colombaroli

et al., 2013). Such positive effects of fire on taxonomic and functional diversity are usually highest at intermediate fire disturbance level for both the plant (Delarze et al., 1992, Tinner et al., 2000, Beghin et al., 2010, Ascoli et al., 2013a and Vacchiano et al., 2014a) and invertebrate community (Moretti et al., 2004, Querner et al., 2010 and Wohlgemuth et al., 2010). In some cases fire favours the maintenance of habitats suitable for endangered INK 128 research buy Bay 11-7085 communities (Borghesio, 2009) or rare species (Moretti et al., 2006, Wohlgemuth et al., 2010 and Lonati et al., 2013). However, prolonged and frequent fire disturbance can lead to floristic impoverishment.

On the fire-prone southern slopes of the Alps the high frequency of anthropogenic ignitions during the second fire epoch (see also Fig. 2 and Fig. 3 for details) caused a strong decrease or even the local extinction at low altitudes of several forest taxa such as Abies alba, Tilia spp, Fraxinus excelsior and Ulmus spp. ( Tinner et al., 1999, Favilli et al., 2010 and Kaltenrieder et al., 2010) and animal communities, e.g., Blant et al. (2010). In recent times however, opening through fire results also in an increased susceptibility of the burnt ecosystems towards the colonization of invasive alien species ( Grund et al., 2005, Lonati et al., 2009 and Maringer et al., 2012) or animal communities, e.g., Lyet et al. (2009) and Blant et al. (2010). Similar to what is reported for the Mediterranean ( Arianoutsou and Vilà, 2012) or other fire prone ecosystems ( Franklin, 2010 and Monty et al., 2013), also in the Alpine environments fire may represent an unrequested spread channel for alien invasive species with pioneer character, what reinforce the selective pressure of fire in favour of disturbance adapted species of both native ( Delarze et al., 1992; Tinner et al., 2000 and Moser et al., 2010) and alien origin ( Lonati et al., 2009 and Maringer et al., 2012) ( Fig. 7).

As our landslide frequency-magnitude analysis is based on data that were obtained during a 50-year period, they do not necessarily reflect the long-term change in denudation rate after human disturbances. More research is needed to get a comprehensive understanding of the impact of human activities on landslide-induced sediment fluxes on longer time-scales. Data collection and logistic support for this project was provided through the Belgian Science Policy, Research Program for Earth Observation Stereo II, contract SR/00/133, as part of the FOMO project (remote sensing of the forest transition and its ecosystem impacts in mountain

environments). M. Guns was funded through a PhD fellowship from the Fonds National de la Recherche Scientifique (FRS-FNRS, Belgium), and the Prize for Tropical AUY-922 manufacturer Geography Yola Verhasselt of the Royal Academy for Overseas Sciences (Belgium). learn more The authors would like to thank Dr. A. Molina (University of Goettingen, Germany) and Dr. Vincent Balthazar for their precious help during fieldwork and Dr. Alain Demoulin for its advices. ”
“Human modification of the surface of the Earth is now extensive. Clear and obvious

changes to the landscape, soils and biota are accompanied by pervasive and important changes to the atmosphere and oceans. These have led to the concept of the Anthropocene (Crutzen and Stoermer, 2000 and Crutzen, 2002), which is now undergoing examination as a potential addition to the Geological Time Scale (Zalasiewicz et al., 2008, Williams et al., 2011 and Waters et al., 2014). These changes are significant geologically, and have attracted wide interest because of the potential consequences, for human populations, of living in a world changed geologically by humans themselves. Humans have also had an impact on the

underlying rock structure of the Earth, for up to several kilometres below the planetary surface. Indirect effects of this activity, such as the carbon transfer from rock to atmosphere, are cumulatively of considerable importance. However, the extent and geological significance Teicoplanin of subsurface crustal modifications are commonly neglected: out of sight, out of mind. It is a realm that ranges from difficult to impossible to gain access to or to experience directly. However, any deep subsurface changes, being well beyond the reach of erosion, are permanent on any kind of human timescale, and of long duration even geologically. Hence, in imprinting signals on to the geological record, they are significant as regards the human impact on the geology of the Earth, and therefore as regards the stratigraphic characterization of the Anthropocene.

Moving to the south, we encounter the palaeochannels CL1 and CL2, described in the last section. Between the Vittorio Emanuele III Channel and the Contorta S. Angelo Channel there are a few palaeochannels meandering mainly in the west–east direction. These palaeochannels probably belong to another Holocene path of the Brenta river close to Fusina (depicted in Fig. 4. 68, p. 321, in Bondesan and Meneghel, 2004). In

the lower right hand side of the PERK inhibitor map, we can see the pattern of a large tidal meander that existed already in 2300 BC that is still present today under the name Fasiol Channel. Comparison with the 1691 map shows that the palaeochannels close to the S. Secondo Channel disappeared, and so did the palaeochannel CL1 (Fig. 4b). The palaeochannel CL2 is no longer present in our reconstruction, but it may still exist under the Tronchetto Island, as we observed in the last section. The acoustic areal reconstruction of CL3 overlaps well with the path of the “coa de Botenigo” from the 1691 map that was flowing into the Giudecca Channel. This channel is clearly visible also

in Fig. 4c and www.selleckchem.com/products/crenolanib-cp-868596.html d. On the other hand, the palaeochannels close to the Fusina Channel of Fig. 4a have now disappeared. This may be related to the fact that in 1438 the Fusina mouth of the Brenta river was closed (p. 320 of Bondesan and Meneghel, 2004). To the lower right, the large meander of the Fasiol Channel is still present and one can see its ancient position and continuation. In 1811, the most relevant changes are the disappearance of the “Canal Novo de Botenigo” and of the “Canal de Burchi” (in Fig. 4c), that were immediately to the north and to the south of the Coa de Botenigo in Fig. 4b, respectively. The map in Fig. 4d has more details with small creeks developing perpendicular to the main channel. Moreover, the edification of the S. Marta area has started, so the last part of the “Coa de Botenigo”

was Oxymatrine rectified. Finally, the meander close to the Fasiol Channel is now directly connected to the Contorta S. Angelo Channel. In the current configuration of the channels, the morphological complexity is considerably reduced (Fig. 4e). The meanders of the palaochannel CL3 (“Coa de Botenigo”) and their ramification completely disappeared as a consequence of the dredging of the Vittorio Emanuele III Channel. The rectification of the palaochannel CL3 resulted in its rapid filling (Fig. 2d). This filling was a consequence of the higher energetic regime caused by the dredging of the new deep navigation channels in the area. The old Fusina Channel was partially filled and so it was the southern part of the Fasiol Channel meander. The creeks developing perpendicular to the main palaeochannels in 1901 (Fig. 4d) completely disappeared. A more detailed reconstruction of the different 20th century anthropogenic changes in the area can be found in Bondesan et al.

The weak form of methodological uniformitarianism might be viewed as suggesting that present process measurements GABA inhibitor drugs might inform

thinking in regard to the humanly disturbed conditions of the Anthropocene. In this way G.K. Gilbert’s classical studies of the effects of 19th century mining debris on streams draining the Sierra Nevada can inform thinking (though not to generate exact “predictions”) about future effects of accelerated disturbance of streams in mountain areas by mining, which is a definite feature of the Anthropocene. This reasoning is analogical. It is not uniformitarian in the classical sense, but it is using understanding of present-day or past (for Gilbert it was both) processes to apply to what one might causally hypothesize about (not “predict”) in regard to future processes. Knight and Harrison (2014) conclude that “post-normal science” will be impacted by the Anthropocene because of nonlinear systems that will be Crizotinib chemical structure less predictable, with increasing irrelevance for tradition systems properties such as equilibrium and equifinality. The lack of a characteristic state for these systems will prevent,

“…their easy monitoring, modeling and management. Post-normal science” is an extension of the broader theme of postmodernity, relying upon one of the many threads of that movement, specifically the social constructivist view of scientific knowledge (something of much more concern to sociologists than to working scientists). The idea of “post-normal Idelalisib science,” as defined by Funtowicz and Ravetz (1993), relies upon the view that “normal science” consists of what was described in one of many conflicting philosophical conceptions of scientific progress, specifically that proposed by Thomas Kuhn in his influential book Structure of Scientific Revolutions. Funtowicz and Ravetz (1993) make

a rather narrow interpretation of Kuhn’s concept of “normal science”, characterizing it as “…the unexciting, indeed anti-intellectual routine puzzle solving by which science advances steadily between its conceptual revolutions.” This is most definitely one of the many interpretations of his work that would (and did!) meet with total disapproval by Kuhn himself. In contrast to this misrepresented (at least as Kuhn would see it) view of Kuhnian “normal science,” Funtowicz and Ravetz (1993) advocate a new “post-normal science” that embraces uncertainty, interactive dialog, etc. This all seems to be motivated by genuine concerns about the limitations of the conventional science/policy interface in which facts are highly uncertain, values are being disputed, and decisions are urgent (Baker, 2007). Classical uniformitarianism was developed in the early 19th century to deal with problems of interpretation as to what the complex, messy signs (evidence, traces, etc.) of Earth’s actual past are saying to the scientists (mostly geologists) that were investigating them (i.e., what the Earth is saying to geologists), e.g.