The authors would like to thank CNPQ (IC grant: Flávia C U Kata

The authors would like to thank CNPQ (IC grant: Flávia C. U. Katayama) and FAPESP for the financial support (process numbers 2009/02258-0, 2009/06364-9). “
“This article has been retracted at the request of the Editor. Please this website see Elsevier Policy on Article Withdrawal ( This article has been retracted as the authors have plagiarized part of a published PhD thesis entitled “Studies on the characterization

and purification of recombinant Bt-insecticidal proteins and development of polyclonal antibody based Elisa kit”, awarded to Dr. Abhishek Ojha (International Centre for Genetic Engineering and Biotechnology, New Delhi) ON-01910 concentration on 23rd September 2008 by the University of Lucknow, India. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such, this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and

apologies are offered to readers of the journal that this was not detected during the submission process. “
“The authors regret that the Highlights provided for this article were incorrect. The correct Highlights are reported below: The LC–MS/MS analysis accelerated the quantitative analysis. ► The concentration of (+)-catechin in the coconut water was 0.344 μg/mL. ► The concentration of (−)-epicatechin in the coconut water was 0.242 μg/mL. ► Results obtained in this study will serve as quality control. The authors would like to apologise for any inconvenience caused. “
“Reactive oxygen species (ROS) and reactive nitrogen species

(RNS) are products of normal cellular metabolism and they are well recognized for playing a dual role in living systems Erastin once their effects can be either harmful or beneficial. The term ROS includes oxygen-derived radicals such as superoxide radical (O2 −), peroxyl radical (ROO ), hydroxyl radical (HO ), and non-radical species, such as hydrogen peroxide (H2O2), singlet oxygen (1O2), and hypochlorous acid (HOCl) (Choe & Min, 2006), whilst RNS includes mainly the nitric oxide radical ( NO) and non-radical species, such as peroxynitrite anion (ONOO−) (Halliwell & Gutteridge, 2007, chap. 9). At moderate concentrations, ROS and RNS can be involved in cellular responses to injury, e.g. in the defense against infectious agents, and also in cellular signalling systems.

e , 50, 10, 1 0, and 0 5 mM for glucose and fructose, 10,

e., 50, 10, 1.0, and 0.5 mM for glucose and fructose, 10,

1.0, 0.5, and 0.1 mM for sucrose, and 10, 5.0, 1.0, and 0.5 mM for galactose), and used these solutions to construct standard curves for each sugar component. These standard curves were then used to estimate the concentrations of the different components in the JBOVS from the HSQC spectra using the same NMR measurement conditions. The following acquisition NMR parameters were used for the quantification HSQC measurements: the size of fid was 1024 data points in F2 (1H) and 240 data points in F1 (13C), with 40 scans and an interscan delay (D1) of 1.5 s with 16 dummy scans; the transmitter frequency offset was 4.708 ppm in F2

(1H) and 75.5 ppm in F1 PS-341 purchase (13C) with spectral widths of 14 and 59 ppm in F2 (1H) and F1 (13C), respectively. For the construction of the standard curves, only signals with a coefficient of determination (R2) greater than 0.999 HDAC inhibitor were selected for each sugar component. Using the resulting standard curves, the sugar concentration estimates were calculated by averaging each signal (excluding any overlapping signals) as well as the standard deviations. Bacterial cell pellets of the collected samples from in vitro experiments and the fecal samples from in vivo experiments were suspended in TE buffer (10 mM Tris–HCl, 1 mM EDTA, pH 8.0). Then, the samples were homogenised and disrupted with 0.1 mm Zirconia/Silica Beads (BioSpec Products, Inc., OK, USA) and extracted with 10% sodium dodecyl sulphate (SDS)/TE solutions. After centrifugation at 20,000g for 10 min at room temperature, the DNA was purified using a phenol/chloroform/isoamyl alcohol (25:24:1) solution and precipitated by adding ethanol and sodium acetate, and then stored at −20 °C. For PCR-DGGE analyses, PCR amplification

and DGGE analysis were performed according to previous studies (Date et al., 2010). The gels obtained from DGGE were stained using SYBR Green I (Lonza, Rockland, ME USA) and were acquired by GelDoc XR (Bio-Rad Laboratories Inc., Tokyo, Japan). For identification C-X-C chemokine receptor type 7 (CXCR-7) of the bacterial origin of DNA sequences in the gel, selected DGGE bands were excised from the original gels and their DNA fragments were reamplified with the corresponding primers. The obtained PCR product was sequenced using a DNA Sequencer (Applied Biosystems 3130xl Genetic Analyzer) with a BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems Japan Ltd., Tokyo, Japan). The sequences were submitted to BLAST search programs at the DNA Data Bank of Japan (DDBJ) to determine their closest relatives. The sequences determined in this study and those retrieved from the databases were aligned using CLUSTAL W, and then a phylogenetic tree was constructed with CLUSTAL W and Tree View by the neighbour-joining method.

5 and 1 5 kV, respectively The output voltage of the capillary w

5 and 1.5 kV, respectively. The output voltage of the capillary was 95.2 V for anthocyanins (ESI+) and 120 V for the other phenolic compounds (ESI+ and ESI−). The other conditions in both modes were: end plate offset −500 V, drying gas (N2) temperature of 325 °C and flow of 8 l/min, nebulizer at 30 psi. The MS/MS was acquired in automatic mode, applying fragmentation energy of 1.2 V. The scan range was from m/z 100 to 1000. The carotenoids were separated on C30 YMC column (5 μm, 250 × 4.6 mm Ribociclib cell line id) (Waters, Wilmington, USA), using the

APCI ionisation source, according to the method previously described by De Rosso and Mercadante (2007a). Carotenoids were quantified by HPLC-DAD based on calibration curves obtained for all-trans-lutein, all-trans-zeaxanthin, BGB324 mouse all-trans-β-cryptoxanthin, all-trans-α-carotene and all-trans-β-carotene. The cis isomers, when present, were estimated using the calibration curve of the corresponding all-trans isomer. The ascorbic acid was analysed by HPLC-DAD, using a C18 Shim-pack column described above and as mobile phase an aqueous solution of sulphuric acid at pH 2.5, in isocratic condition at a flow rate of 0.7 mL/min and a column temperature

set at 25 °C. The chromatograms were processed at 254 nm. The limit of detection (LOD) of 0.01 mg/100 g was calculated from Eq. (3), using the parameters obtained from the calibration curve for ascorbic acid (5–60 μg/mL). equation(3) LOD=3.3×SDCAwhere SD is the standard deviation of the response for peak area and CA is the slope of VAV2 the linear fit obtained for the calibration curve. The identification of all compounds was performed using the combined data of the following parameters: elution order on reversed-phase column, co-chromatography with standards, and characteristics from the UV–Vis and mass spectra, compared with standards analysed in same conditions and with data available in the literature (Britton et al., 2004, Cuyckens and Claeys, 2004, De Rosso and Mercadante, 2007a, De Rosso and Mercadante, 2007b,

De Rosso et al., 2008, Fabre et al., 2001, Lin and Harnly, 2007 and Wu and Prior, 2005). The ABTS + scavenging capacity test was carried out according to the method described by Re et al. (1999), under pH 1.0, 3.0, 5.0, 7.0 and 9.0 conditions, using the appropriate buffer for each pH. The FE was diluted in each buffer at a proportion of 0.7%v/v. The diluted extract was added to the ABTS + solution (1:1v/v proportion) to achieve an initial ABTS + absorbance (at 734 nm) of 0.80 ± 0.02, and absorbance was immediately monitored at 734 nm for 15 min. The results were calculated based on a calibration curve of Trolox (3–20 μM), obtained for each condition of pH, and TEAC (Trolox-equivalent antioxidant capacity) values were expressed as μmol Trolox/g fruit. The protection against 1O2 was only performed under pH 1.0 and 3.0, using DMA (0.

, in press) The levels of BPA in Sweden were among the lowest co

, in press). The levels of BPA in Sweden were among the lowest compared to the levels in the other five participating countries that analyzed BPA (Covaci et al., in press). When compared to studies of children and women of childbearing age outside the harmonization program, the urinary levels of phthalates and BPA in the current study were in the same magnitude as levels found in studies from US, Canada, Netherlands and Norway (CDC, 2009, CDC, 2013, Health Canada,

2013, Ye et al., 2008 and Ye et al., 2009). The levels of DEHP metabolites and MEP in the current study were generally among the lowest, whereas the levels of MnBP were among the highest compared to these studies. The levels of parabens in the current study were among the lowest and the levels of TCS were remarkably lower compared with studies from Spain, US and Denmark

(Calafat et al., 2010, Casas et al., 2011 and Frederiksen et al., 2013b). The analyses of determinants Protein Tyrosine Kinase inhibitor of exposure based on questionnaire data should be interpreted with caution and the results should be regarded as indications of potentially important exposure sources for these compounds. The number of participants was fairly low, thus the statistical power was limited and a few random high values may get unbalanced importance in subgroups containing few participants. The number of exposure sources covered by the questionnaire was limited and some questions may serve as dummies for other related source–exposure relationships than the ones covered here. Given the frequent use of products containing the studied compounds, recurrent exposure over time is likely to see more occur. A single urine sample may therefore reasonably represent an individual’s ongoing exposure (Christensen et al., 2012, Frederiksen et al., 2013a, Mouritsen et al., 2013 and Smith et al., 2012). In the current study, first morning urine sampling was applied, which has been shown to reasonably reflect the individual exposure (except for BPA). Adjustment for creatinine is used

to correct for dilution in individual urine samples. However, the creatinine excretion varies with factors such as age, gender and ethnicity (Barr et al., 2005). Therefore, direct comparisons of creatinine-adjusted levels between Dimethyl sulfoxide different groups of the population, e.g. mothers and children or children of various ages, should be interpreted with caution. To our knowledge this is the first study examining exposure determinants for phthalates, BPA, parabens and TCS in Swedish mother–child couples. Phthalates, BPA and parabens were significantly correlated to certain foods and personal care products which were expected to be relevant exposure sources for these contaminants. The levels were fairly well correlated between the mothers and their children. For both mothers and children, urinary levels of phthalates were generally associated with food consumption whereas the levels of parabens were associated with use of cosmetics and personal care products.

6, p   =  24, ηp2= 14, and no interaction of Condition and Outcom

6, p   = .24, ηp2=.14, and no interaction of Condition and Outcome Size, F(1,9)<1,ηp2<.01. Additional ANOVAs confirmed that, in each condition, the children searched longer for the 3rd puppet in the trials in which the transformation resulted in 3 puppets (puppet addition/subtraction condition: F  (1, 9) = 101.1, p   < .001, ηp2=.92; branch addition/subtraction condition: F  (1, 11) = 78.6, p   < .001, ηp2=.88). Furthermore, performance was significantly better with the small numbers of Experiment

3 compared to the large numbers of Experiment 2 (interaction between Experiment and Outcome Size for the puppet addition/subtraction condition: F  (1, 20) = 13.5, p   = .0015, Nutlin3 ηp2=.40; for the branch addition/subtraction condition: F  (1, 22) = 15.0, p   < .001, ηp2=.40). In the context of small numbers, children were able to remember and process addition and subtraction

transformations adeptly. They were equally able to do so whether the transformation affected a visible or an invisible set (branches or puppets). This finding converges with a host of research showing that children are able to infer and correct surreptitious transformations in small sets of objects (Gelman, 1972b and Gelman and Gallistel, 1986). The children’s success in Experiment 3 provided evidence that they were able to remember and understand the transformation events, thus excluding memory of the transformation events and other limits to processing the transformations as the reason for the children’s failure in Experiment 2. Three potential explanations for this failure remain. First, perhaps children were able to remember a transformation SCH727965 datasheet event while tracking a small set of objects, but remembering

both a transformation and a one-to-one mapping between branches and puppets exceeded their memory capacity. Indeed, in contrast to the conditions presenting large sets of puppets, it is possible that children SSR128129E did not use the branches to succeed with small sets, given that the set sizes did not exceed their object-tracking limit. Second, perhaps children remembered both the starting configuration and the transformation, but failed to combine these pieces of information so as to update their expectations for the final mapping between puppets and branches. In all the transformations used so far (additions and subtractions), the end configuration was different from the starting configuration, hence the need to update the mapping. Third, perhaps children of this age do not have a full understanding of whether transformations affect one-to-one mappings between sets; in other words, maybe children fail to recognize that relations established by one-to-one pairings follow the principle of Addition/Subtraction. Under this hypothesis, children in Experiment 2 were unsure whether the transformation events affected the one-to-one correspondence mapping between the branches and puppets, and thus they stopped attending to this mapping altogether.

Retirement from academia freed Dick’s time to dive into applied a

Retirement from academia freed Dick’s time to dive into applied aspects of

forest soils, which he supported by working as the director of research and development for Temple-Inland Forest Products Corporation in Dibol, Texas (1999–2006). Dick’s career included a wide and deep set of contributions to his profession, students, and colleagues. He was an instructor in the Organization for Tropical Studies field courses in Central America from 1970 through 1999. He served both the Soil Science Society of America (including chairing the Forest, Range and Wildland Soils Division) and the Society selleckchem of American Foresters (he was elected a Fellow of the SAF). Dick authored and coauthored over 100 refereed publications, co-authored

(together with Dan Binkley) three editions of the textbook Ecology and Management of Forest Soils. The publishers, editors, and readers of Forest Ecology and Management are particularly indebted to Dick for his 18 years of leadership BIBW2992 nmr as co-editor-in-chief of the Journal. Dick shepherded the Journal through more than half of its existence, overseeing the period of major growth with a 5-fold increase in annual production of the best research articles in the field. Forest Ecology and Management’s status as the top international journal in the field is just one of the hallmarks of Dick Fisher’s career; we thank him, and we miss him. “
“The Brazil nut (BN)1 tree (Bertholletia excelsa, Bonpland, 1808) is currently

classified as vulnerable to extinction ( IUCN, 2010). Its conservation status is attributed to extensive seed gathering, which is said to compromise the regeneration of the over-exploited populations, and to deforestation, which reduces the species’ biogeographical range. That harvest pressure may result in vulnerability is controversial. This issue continues to divide those who support ( Wadt et al., 2008 and Zuidema and Boot, 2002) the ecological sustainability of BN extraction from those who deny that such sustainability BCKDHB is possible ( Peres et al., 2003). In contrast, BN vulnerability due to habitat loss is clearly a direct consequence of the conversion of Amazon forests into agricultural fields ( Escobal and Aldana, 2003) and pastures ( Clay, 1997). Medium to large farms and cattle ranches are responsible for nearly 70% of total Amazon deforestation (Fearnside, 2005). Indigenous and extractive populations stand out as historical antagonists and as a force for political resistance against latifundium expansion (Allegretti, 1990 and Campos and Nepstadt, 2006).

A total of 21 root canals with pulp necrosis and apical periodont

A total of 21 root canals with pulp necrosis and apical periodontitis were analyzed by the three different LAL methods. All three LAL methods were effective in the recovery of endotoxin from root canal infection. Regardless of the method

tested, endotoxin was detected in 100% of the root canals investigated (21/21). The KQCL assay yielded a median value of endotoxin of 7.49 EU/mL, which selleck compound was close to and not significantly different from the turbidimetric test (9.19 EU/mL) (both kinetic methods) (p > 0.05). In contrast, the endpoint QCL showed a median value of 34.20 EU/mL (p < 0.05) ( Table 2). The percentage of PPC values revealed a good interaction between the root canal samples and LAL substrate regarding the turbidimetric method (% values ranging from 50 to 197) (Table 2). Product inhibition values were found in 2 of 21 root canal samples analyzed by the KQCL method (PPC value <50%). The endpoint QCL revealed product interference in 12 of 21 root canal samples (values lower than 0.4 EU/mL ± 25%)

(Table 2). The color interference assay performed for the endpoint-QCL method indicated color interference in 11 of 21 root canal samples, even after a dilution to the 10−4. The linearity of the standard curve was equally good for all methods (all r =1) ( Table 2). The coefficient of variance for endotoxin concentration was greater than 10% in 17 Selleck LBH589 of 21 root canal samples analyzed by the endpoint-QCL assay, indicating its low reproducibility ( Table

2). In contrast, the KQCL and turbidimetric kinetic assays revealed as high as 5.50% and 4.46% values of the coefficient of variance, respectively (both being precise and with best reproducibility) ( Table 2). The LAL tests use a serine protease catalytic coagulation cascade that is activated Ribonucleotide reductase by endotoxin (18). Factor C, the first component in the cascade, is a protease zymogen activated by endotoxin binding. Downstream, this pathway activates a proclotting enzyme into a clotting enzyme (coagulogen into coagulin) (18). The chromogenic LAL assay (QCL or KQCL) uses the synthetic peptide-pNA substrate, which is cleaved by the clotting enzyme, imparting a yellow color to the solution. The turbidimetric kinetic assay uses coagulogen by monitoring its conversion into coagulin, which begins to form a gel clot, increasing the turbidity. The strength of the yellow color (determined at an optical density [OD] = 405 nm) resulting from the chromogenic LAL substrate and the turbidity (determined at an OD = 340 nm) resulting from the coagulogen conversion are correlated with the endotoxin concentration. The progress of the LAL reaction leading to coagulogen conversion (as measured by OD) was monitored in two ways in the current study: using the endpoint and kinetic methods. In the first (QCL test), OD is recorded at single time (≈16 minutes), which compromises its sensitivity (0.1-1 EU/mL) (18).

The titers of virus produced

in infected cells (treated o

The titers of virus produced

in infected cells (treated or not treated with rAVLO) were determined by monitoring the cytopathic effect (CPE) in an endpoint dilution assay and the results were expressed as the highest dilution of virus able to induce CPE in 50% of cells. The protein responsible for the antiviral effect of L. obliqua hemolymph was isolated and purified by gel filtration chromatography using a Superdex 75 column ( Greco et al., 2009). Then, the semi-purified fraction containing the antiviral activity was applied onto an ion-exchange Resource-Q column. As previously demonstrated by our group ( Greco et al., 2009), the antiviral protein purified by this procedure decreased AZD2281 mouse the production of measles Bortezomib solubility dmso virus (from 3.3 ± 1.25 × 107 to 2.1 ± 1.5 × 105 TCID50/ml) by 157 times the production of poliovirus (2.8 ± 1.08 × 109 to 4.58 ± 1.42 × 107 TCID50/ml) by 61 times. These differences were significant at p < 0.05. The mass spectrometry

was used to determine the N-terminal of the protein. Further, the N-terminal sequence was analyzed against previously constructed L. obliqua cDNA libraries ( Veiga et al., 2005). RNA was extracted and the cDNA was generated as described in Section 2. The samples were analyzed on 1% agarose gels, in which a band of 587 bp was observed, confirming the amplification of the cDNA that codes for the antiviral protein (Fig. 1A). The sequences of the cDNA coding for the other proteins (LOH-19-AY829833, 663 pb, and 8-LOH, 963 pb) were also confirmed by agarose gel electrophoresis next (Fig. 1B). The amplified cDNA coding for the antiviral protein was cloned in the pFASTBac1™ donor plasmid. As observed by agarose gel electrophoresis in Fig. 1A,

the cloned cDNA had an expected size of 587 bp for the antiviral protein, 663 bp for LOH-19-AY829833 and 963 bp for 8-LOH (Fig. 1B). E. coli DH5α cells were transformed to the recombinant donor plasmid, plasmid-containing colonies were selected and the purified plasmid was subsequently used in the transformation of E. coli DH10Bac™ for the construction of the recombinant bacmids. These bacmids, containing the sequence of a protein with antiviral activity and other proteins, were further used for the expression of this protein in the baculovirus/Sf9 cells system (as shown below). After bacterial transformation with the recombinant plasmids rAVLO-pFastBac1™, LOH-19-pFastBac1™ and 8-LOH-pFastBac1™, white and blue colonies were observed in the plates. White colonies were indicative that successful transposition occurred, while blue colonies indicated that the bacmid remained unchanged. Colonies with recombinant bacmids were analyzed by PCR followed by 1% agarose gel electrophoresis, in which baculovirus transposition was confirmed by the appearance of DNA bands 2887 for antiviral protein (Fig. 2), 2963 for LOH-19 protein and 3263 for 8-LOH protein (data not shown). The recombinant plasmids were selected in E.

Geomorphologists increasingly focus on such interactions in the f

Geomorphologists increasingly focus on such interactions in the form of feedback loops between resource use, landscape stability, ecosystem processes, resource availability, and natural hazards (Chin et al., in press). An example comes from the sediment budget developed for the Colorado River in Grand Canyon (Wiele et al., 2007 and Melis, 2011). Much of the river sand within Grand Canyon comes from upstream and is now trapped by the dam, but sand also enters Grand Canyon via tributaries downstream from the dam. Sand present along the main river corridor at the time of dam

closure can also be redistributed between channel-bed and channel-margin storage sites. Alteration of water and sediment fluxes by Glen Canyon Dam has RG7420 manufacturer led to beach erosion and loss of fish habitat in Grand Canyon, affecting recreational river runners and endemic native fish Compound C populations. Resource managers respond to these landscape and ecosystem alterations by experimenting with different ways of operating the dam. The availability and distribution of sand-sized sediment drives decisions as to when managers will create experimental floods by releasing larger-than-average

volumes of water from the dam. Given the documented extent and intensity of human alteration of the critical zone, a vital question now is how can geomorphologists most PAK6 effectively respond to this state of affairs? More than one recently published paper notes the absence of a geomorphic perspective in discussions of global change and sustainability (e.g., Grimm and van der Pluijm, 2012, Knight and Harrison, 2012 and Lane, 2013). Geomorphologists certainly have important contributions to make to scholarly efforts to understand and predict diverse aspects of global change and sustainability, but thus far the community as a whole has not been very effective in communicating this to scholars in other disciplines or to society in general. Scientists as a group are

quite aware of existing and accelerating global change, but there may be less perception of the long history of human manipulation of surface and near-surface environments, or of the feedbacks through time between human actions and landscape configuration and process. Geomorphologists can particularly contribute to increasing awareness of human effects on the critical zone during past centuries. Geomorphologists can also identify how human-induced alterations in the critical zone propagate through ecosystems and human communities – that is, geomorphologists can contribute the recognition that landscapes are not static entities with simple or easily predictable responses to human manipulation, but are rather complex, nonlinear systems that commonly display unexpected responses to human alteration.

The study of terraces represents a challenge for our modern socie

The study of terraces represents a challenge for our modern society and deserves particular attention. The reasons are several: their economic, environmental and historical–cultural implications and their hydrological functions, such as erosion control, slope stabilization, lengthening SB431542 molecular weight of the rainfall concentration time, and the eventual reduction of the surface runoff. However, land abandonment and the different expectations of the young generation (people are moving from farmland to cities where job opportunities are plentiful) are seriously affecting terrace-dominated landscapes. The result is a progressive increase in soil erosion and landslide risk that can be a problem for society when these processes are

triggered in densely populated areas. Another result, less evident but in our opinion still important, is the fact that we are progressively losing and forgetting one of the historical and cultural roots that has characterized entire regions and cultures for centuries. Terraced landscapes need to be maintained, well managed (including the use of new remote sensing technologies such lidar), and protected. While these actions can help overcome the critical issues related to erosion risk and landslides, they can also offer another benefit, possibly more relevant because it is related to the economy. Terrace maintenance can improve tourism, leisure activities, and the commerce of products related to

agricultural production, and can offer new job opportunities Trichostatin A for the younger generations. Analysis resources and terrestrial laser scanner data were provided by the Interdepartmental Osimertinib ic50 Research Centre of Geomatics—CIRGEO, at the University of Padova. Aerial lidar data were provided by the Italian Ministry of the Environment and Protection of Land and Sea (Ministero dell’Ambiente

e della Tutela del Territorio e del Mare, MATTM), within the framework of the `Extraordinary Plan of Environmental Remote Sensing’ (Piano Straordinario di Telerilevamento Ambientale, PST-A). We thank the Fattoria di Lamole di Paolo Socci for granting us access to the Lamole study area for the field surveys. This study has been partly supported by the following projects: PRIN 20104ALME4_002 Rete nazionale per il monitoraggio, la modellazione e la gestione sostenibile dei processi erosivi nei territori agricoli, collinari e montani, funded by the Italian Ministry of Education, Universities and Research, and MONACO, funded by the Italian Ministry of Agricultural, Food and Forestry Policies (Ministero delle Politiche Agricole, Alimentari e Forestali, MiPAAF). “
“Welcome to the first issue of Anthropocene, a journal devoted to advancing research on human interactions with Earth systems. The scale and intensity of human interactions with Earth systems have accelerated in recent decades, even though humans have changed the face of Earth throughout history and pre-history. Virtually no place on Earth is left untouched now by human activity.