Systems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we ...used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups, i.e., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxicity screening using THP-1 cells revealed a pronounced cytotoxicity for the ammonium-terminated Au-NPs, while no cell death was seen after exposure to the carboxylated or PEG-modified Au-NPs. Moreover, Au-NR3+ NPs, but not the Au-COOH NPs, were found to trigger dose-dependent lethality in vivo in the model organism, Caenorhabditis elegans. RNA sequencing combined with mass spectrometry-based proteomics predicted that the ammonium-modified Au-NPs elicited mitochondrial dysfunction. The latter results were validated by using an array of assays to monitor mitochondrial function. Au-NR3+ NPs were localized in mitochondria of THP-1 cells. Moreover, the cationic Au-NPs triggered autophagy in macrophage-like RFP-GFP-LC3 reporter cells, and cell death was aggravated upon inhibition of autophagy. Taken together, these studies have disclosed mitochondria-dependent effects of cationic Au-NPs resulting in the rapid demise of the cells.
Anisotropy of magnetic susceptibility (AMS) techniques are applied to Permo-Triassic red beds from the Castilian Branch (Iberian Range, NE Spain) that were deposited in an extensional basin inverted ...during Cenozoic times. The main goal of this work is to characterize the tectonic evolution of the basinal stage by differentiating synsedimentary to early diagenetic magnetic fabrics from the secondary tectonic fabrics related to compression, which are scarcely developed because no penetrative structures related to compression have been recognized. Oblate magnetic fabrics, with kmin axes perpendicular to bedding ,are observed in most cases. Magnetic lineations are variable, showing a dominant ENE-WSW maximum, which fits with a dextral transtensional regime acting on NW-SE master faults during the Triassic. We propose that variations in the orientation of the magnetic lineation are associated with transfer faults which fragment the basin and trigger strain partitioning in different areas. Magnetic fabrics are locally modified by Cenozoic compression, with intermediate and minimum axes distributed along girdles perpendicular to fold axes. Comparing all these results with macrostructures and mesostructural kinematic indicators, we conclude that the fine-grained hematite-bearing rocks carry a consistent magnetic fabric which can be used to reconstruct the basin history.
•Magnetic fabrics used to unravel the deformational history of an inverted basin.•Hematite (main) and phyllosilicates are the main contributors to the AMS.•kmin axes usually perpendicular to bedding, according to a sedimentary fabric.•kmax orientations (ENE-WSW) fit with a dextral transtensional regime.•Strain partitioning inferred from variations in magnetic lineation orientations.
The Guadalentín River, located in southeast Spain, is considered one of the most torrential rivers in Spain, as indicated by catastrophic events such as the 1879 flood that caused 777 fatalities in ...the Murcia region. In this paper, flood frequency and magnitude of the upper Guadalentín River were reconstructed using geomorphological evidence, combined with one-dimensional hydraulic modelling and supported by records from documentary sources at Lorca in the lower Guadalentín catchment. Palaeoflood studies were conducted along a 2.5-km reach located at the confluence of the Rambla Mayor (162
km
2) and Caramel River (210
km
2). These tributaries join at the entrance of a narrow bedrock canyon, carved in Cretaceous limestone, which is 15–30
m wide and 40
m deep. Six stratigraphic profiles were described, the thickest and most complete corresponding to flood benches deposited upstream of the canyon constriction. The stratigraphic and documentary records identify five main phases of increased flood frequency. Phase 1, based on sedimentary palaeoflood evidence alone, occurred at c. AD 950–1200 with at least ten floods with minimum discharge estimates of 15–580
m
3
s
−
1
. Phases 2–5, identified through combined sedimentary and documentary evidence occurred at: (a) AD 1648–1672, with eight documentary floods and two palaeofloods exceeding 580–680
m
3
s
−
1
(most probably the AD 1651 and 1653 events); (b) AD 1769–1802, comprising seven documentary floods, of which at least two events (>
250
m
3
s
−
1
) are preserved in the sedimentary record; (c) AD 1830–1840, with four documentary floods, and at least two events recorded in the stratigraphy (760–1035
m
3
s
−
1
); and finally (d) the AD 1877–1900 period that witnessed seven documentary floods, with three palaeofloods exceeding 880
m
3
s
−
1
. The palaeoflood and historical flood information indicate an anomalous increase in the frequency of large magnitude floods between AD 1830 and 1900, which can be attributed to climatic variability accentuated by intensive deforestation and land use practices during the first decades of the nineteenth century.
The p38 MAPK signaling pathway has been proposed as a critical mediator of the therapeutic effect of several antitumor agents, including cisplatin. Here, we found that sensitivity to cisplatin, in a ...system of 7 non-small cell lung carcinoma derived cell lines, correlated with high levels of MKK6 and marked activation of p38 MAPK. However, knockdown of MKK6 modified neither the response to cisplatin nor the activation of p38 MAPK. Deeper studies showed that resistant cell lines also displayed higher basal levels of MKK3. Interestingly, MKK3 knockdown significantly decreased p38 phosphorylation upon cisplatin exposure and consequently reduced the response to the drug. Indeed, cisplatin poorly activated MKK3 in resistant cells, while in sensitive cell lines MKK3 showed the opposite pattern in response to the drug. Our data also demonstrate that the low levels of MKK6 expressed in resistant cell lines are the consequence of high basal activity of p38 MAPK mediated by the elevated levels of MKK3. This finding supports the existence of a regulatory mechanism between both MAPK kinases through their MAPK. Furthermore, our results were also mirrored in head and neck carcinoma derived cell lines, suggesting our observations boast a potential universal characteristic in cancer resistance of cisplatin. Altogether, our work provides evidence that MKK3 is the major determinant of p38 MAPK activation in response to cisplatin and, hence, the resistance associated with this MAPK. Therefore, these data suggest that the balance between both MKK3 and MKK6 could be a novel mechanism which explains the cellular response to cisplatin.
The 5-year overall survival rate remains approximately 50% for head and neck (H&N) cancer patients, even though new cancer drugs have been approved for clinical use since 2016. Cancer drug studies ...are now moving toward the use of three-dimensional culture models for better emulating the unique tumor microenvironment (TME) and better predicting
in vivo
response to cancer treatments. Distinctive TME features, such as tumor geometry, heterogenous cellularity, and hypoxic cues, notably affect tissue aggressiveness and drug resistance. However, these features have not been fully incorporated into
in vitro
H&N cancer models. This review paper aims to provide a scholarly assessment of the designs, contributions, and limitations of
in vitro
models in H&N cancer drug research. We first review the TME features of H&N cancer that are most relevant to
in vitro
drug evaluation. We then evaluate a selection of advanced culture models, namely, spheroids, organotypic models, and microfluidic chips, in their applications for H&N cancer drug research. Lastly, we propose future opportunities of
in vitro
H&N cancer research in the prospects of high-throughput drug screening and patient-specific drug evaluation.
We present a pion photoproduction model on the free nucleon based on an Effective Lagrangian Approach (ELA) which includes the nucleon resonances (
Δ(1232),
N(1440),
N(1520),
N(1535),
Δ(1620),
...N(1650), and
Δ(1700)), in addition to Born and vector meson exchange terms. The model incorporates a new theoretical treatment of spin-3/2 resonances, first introduced by Pascalutsa, avoiding pathologies present in previous models. Other main features of the model are chiral symmetry, gauge invariance, and crossing symmetry. We use the model combined with modern optimization techniques to assess the parameters of the nucleon resonances on the basis of world data on electromagnetic multipoles. We present results for electromagnetic multipoles, differential cross-sections, asymmetries, and total cross-sections for all one pion photoproduction processes on free nucleons. We find overall agreement with data from threshold up to 1
GeV in laboratory frame.
The Chácobo are a Panoan speaking tribe of about 1000 members (300+ adults) in Beni, Bolivia. Originally nomadic, the Chácabo were relocated to their current main location in the 1960s. Researchers ...have visited the Chácabo since 1911. A first more detailed anthropological report exists from the late 1960s, and ecological-ethnobotanical studies were conducted in the 1980s and 1990s. The presented work represents a complete ethnobotanical inventory of the entire adult Chácobo population, with interviews and plant collection conducted directly by Chácobo counterparts.
Based on previous reports and our preliminary studies, we hypothesized that twenty-first century Chácobo plant use centered on income generation, and that traditional plant use related to household utensils, medicine and traditional crop varieties had almost disappeared. To test this hypothesis, we started the "Chácobo Ethnobotany Project," training 10 indigenous Chácobo participants in ethnobotanical interview and plant collection techniques, in order to more fully document Chácobo knowledge and avoid the influence of foreign interviewers.
Our study found 331 useful plant species in 241genera of 95 plant families, with leaves, roots and bark being the most commonly used plant parts The comprehensive documentation that these methods enabled completely nullified our initial hypothesis of knowledge loss. Traditional crop varieties are still widely grown and traditional knowledge is alive. Moreover, it is being actively recuperated in certain domains by the younger generation. Most Chácobo know, and can name, traditional utensils and tools, although only the older generation has still the skills to manufacture them. While many Chácobo still know the names and uses of medicinal species, the younger generation is however often unsure how to identify them.
In this paper we illustrate the complexity of perspectives on knowledge at different ages, and the persistence of knowledge over almost a century. We found that traditional knowledge was only partially affected by the processes of exposure to a market economy, and that different knowledge domains experienced different trends as a result of these changes. Overall knowledge was widely distributed, and we did not observe a directional knowledge loss. We stress the importance to not directly conclude processes of knowledge loss, cultural erosion or acculturation when comparing the knowledge of different age groups.
PDF
