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Breast Cancer (BC) is one of the most common and challenging cancers among females worldwide. Conventional treatments for oral cancer rely on the use of radiology and surgery accompanied by chemotherapy. Chemotherapy presents many side effects, and the cells often develop resistance to this chemotherapy. It will be urgent to adopt alternative or complementary treatment strategies that are new and more effective without these negative effects to improve the well-being of patients. A substantial number of epidemiological and experimental studies reported that many compounds are derived from natural products such as curcumin and their analogs, which have a great deal of beneficial anti-BC activity by inducing apoptosis, inhibiting cell proliferation, migration, and metastasis, modulating cancer-related pathways, and sensitizing cells to radiotherapy and chemotherapy. In the present study, we investigated the effect of the curcumin-analog PAC on DNA repair pathways in MCF-7 and MDA-MB-231 human breast-cancer cell lines. These pathways are crucial for genome maintenance and cancer prevention. MCF-7 and MDA-MB-231 cells were exposed to PAC at 10 µM. MTT and LDH assays were conducted to evaluate the effects of PAC on cell proliferation and cytotoxicity. Apoptosis was assessed in breast cancer cell lines using flow cytometry with annexin/Pi assay. The expression of proapoptotic and antiapoptotic genes was determined by RT-PCR to see if PAC is active in programming cell death. Additionally, DNA repair signaling pathways were analyzed by PCR arrays focusing on genes being related and confirmed by quantitative PCR. PAC significantly inhibited breast-cancer cell proliferation in a time-dependent manner, more on MDA-MB-231 triple-negative breast cancer cells. The flow cytometry results showed an increase in apoptotic activity. These data have been established by the gene expression and indicate that PAC-induced apoptosis by an increased Bax and decreased Bcl-2 expression. Moreover, PAC affected multiple genes involved in the DNA repair pathways occurring in both cell lines (MCF-7 and MDA-MB231). In addition, our results suggest that PAC upregulated more than twice 16 genes (ERCC1, ERCC2, PNKP, POLL, MPG, NEIL2, NTHL1, SMUG1, RAD51D, RAD54L, RFC1, TOP3A, XRCC3, XRCC6BP1, FEN1, and TREX1) in MDA-MB-231, 6 genes (ERCC1, LIG1, PNKP, UNG, MPG, and RAD54L) in MCF-7, and 4 genes (ERCC1, PNKP, MPG, and RAD54L) in the two cell lines. In silico analysis of gene–gene interaction shows that there are common genes between MCF-7 and MDA-MB-321 having direct and indirect effects, among them via coexpression, genetic interactions, pathways, predicted and physical interactions, and shared protein domains with predicted associated genes indicating they are more likely to be functionally related. Our data show that PAC increases involvement of multiple genes in a DNA repair pathway, this certainly can open a new perspective in breast-cancer treatment. [ABSTRACT FROM AUTHOR]

Arsenic (As) poses a significant environmental threat as a metalloid toxin, adversely affecting the health of both plants and animals. Strigolactones (SL) and nitric oxide (NO) are known to play crucial roles in plant physiology. Therefore, the present experiment was designed to investigate the potential cumulative role of SL (GR24–0.20 μM) and NO (100 μM) in mitigating the adverse effect of AsV (53 μM) by modulating physiological mechanisms in two genotypes of tomato (Riogrand and Super Strain 8). A sample randomized design with four replicates was used to arrange the experimental pots in the growth chamber. 45-d old both tomato cultivars under AsV toxicity exhibited reduced morphological attributes (root and shoot length, root and shoot fresh weight, and root and shoot dry weight) and physiological and biochemical characteristics [chlorophyll (Chl) a and b content, activity of δ -aminolevulinic acid dehydratase activity (an enzyme responsible for Chl biosynthesis), and carbonic anhydrase activity (an enzyme responsible for photosynthesis), and enhanced Chl degradation, overproduction of reactive oxygen species (ROS) and lipid peroxidation due to enhanced malondialdehyde (MDA) content. However, the combined application of SL and NO was more effective in enhancing the tolerance of both varieties to AsV toxicity compared to individual application. The combined application of SL and NO improved growth parameters, biosynthesis of Chls, NO and proline. However, the combined application significantly suppressed cellular damage by inhibiting MDA and overproduction of ROS in leaves and roots, as confirmed by the fluorescent microscopy study and markedly upregulated the antioxidant enzymes (catalase, peroxidase, superoxide dismutase, ascorbate dismutase and glutathione reductase) activity. This study provides clear evidence that the combined application of SL and NO supplementation significantly improves the resilience of tomato seedlings against AsV toxicity. The synergistic effect of SL and NO was confirmed by the application of cPTIO (an NO scavenger) with SL and NO. However, further molecular studies could be imperative to conclusively validate the simultaneous role of SL and NO in enhancing plant tolerance to abiotic stress. [Display omitted] • AsV toxicity impaired growth performance of tomato genotypes. • Combined SL and NO application promoted plant health by combating AsV toxicity. • SL plus NO suppressed cellular damage by inhibiting ROS overproduction and MDA accumulation in tomato seedlings. • Application of SL and NO together improved the biosynthesis of Chl, TSCs and proline. • SL Plus NO upregulated antioxidant enzyme activity and NO formation. [ABSTRACT FROM AUTHOR]

We investigated the rock art (petroglyphs) in the Al‐Quwaiyah Governorate (Saudi Arabia) with focus on the Musayqira site. Iconographic analysis showed a broad variety of human depictions, game animals (ibex, ass, ostrich, lion, etc.), domestic animals (cattle, camel, horse, dog, etc.), inscriptions and abstract symbols. Archaeometric measurements by pXRF provided the areal densities of Mn on petroglyphs and intact rock varnish. Varnish accumulation rates were derived from Mn density measurements on inscriptions of known approximate age. Applying these rates to varnish densities on the petroglyphs yielded age estimates. Some of the rock art was incised in fracture fill rather than true varnish, complicating the interpretation of the data. The combination of iconographic and archaeometric data indicated multiple phases of rock art creation, corresponding to the Late Neolithic, Bronze Age, Iron Age, and Islamic Period, with different artistic traditions, reflecting changing socioeconomic and ecological conditions. [ABSTRACT FROM AUTHOR]

Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent. [ABSTRACT FROM AUTHOR]

We conducted rock varnish measurements at four rock art sites in north‐western Saudi Arabia, including Kilwa and the Camel Site near Sakaka. We determined the areal densities of Mn and Fe in rock varnish that had accumulated on petroglyph surfaces since their creation, complemented by a detailed analysis of varnish samples. We inferred varnish accumulation rates by relating the Mn areal density on inscriptions to their ages estimated based on the type of script used. Applying these rates to the varnish densities on the rock art indicated that the art was produced during two distinct periods, corresponding to the Pre‐Pottery/Late Neolithic and the Bronze/Iron Age, respectively, with different artistic traditions, reflecting distinct socioeconomic and ecological conditions. Our dating approach, while admittedly burdened with substantial uncertainties, yields ages consistent with archaeological and historical evidence and it provides a unique quantitative tool to obtain at least rough ages for otherwise undatable rock art. [ABSTRACT FROM AUTHOR]

We investigated rock varnish, a thin, manganese- and iron-rich, dark surface crust, on basaltic lava flows and petroglyphs in the Owens and Rose Valleys (California) by portable X-ray fluorescence (pXRF) and femtosecond laser-ablation inductively-coupled-plasma mass spectrometry (fs-LA-ICPMS). The major element composition of the varnish was consistent with a mixture of Mn-Fe oxyhydroxides and clay minerals. As expected, it contained elevated concentrations of elements that are typically enriched in rock varnish, e.g., Mn, Pb, Ba, Ce, and Co, but also showed unusually high enrichments in U, Cu, and Th. The rare earth and yttrium (REY) enrichment pattern revealed a very strong positive cerium (Ce) anomaly and distinct negative europium (Eu) and Y anomalies. The light rare earth elements (REE) were much more strongly enriched than the heavy REY. These enrichment patterns are consistent with a formation mechanism by leaching of Mn and trace elements from aeolian dust, reprecipitation of Mn and Fe as oxyhydroxides, and scavenging of trace elements by these oxyhydroxides. We inferred accumulation rates of Mn and Fe in the varnish from their areal densities measured by pXRF and the known ages of some of the lava flow surfaces. The areal densities of Mn and Fe, as well as their accumulation rates, were comparable to our previous results from the desert of Saudi Arabia. There was a moderate dependence of the Mn areal density on the inclination of the rock surfaces, but no relationship to its cardinal orientation. We attempted to use the degree of varnish regrowth on the rock art surfaces as an estimate of their age. While an absolute dating of the petroglyphs was not possible because of the lack of suitable calibration surfaces and a considerable amount of variability, the measured degree of varnish regrowth on the various petroglyphs was consistent with chronologies based on archeological and other archaeometric techniques. In particular, our results suggest that rock art creation in the study area continued over an extended period of time, possibly starting around the Pleistocene/Holocene transition and extending into the last few centuries. [ABSTRACT FROM AUTHOR]

The present study presents the analysis of a moderate earthquake (Mw 4.0) and its largest aftershocks located along the Red Sea coast, southwestern Saudi Arabia, with the aim to understand the enigma of peculiar seismicity in the Arabian Shield. We analyzed a high-quality waveform dataset collected from ten well-recorded earthquakes of moment magnitude ranging from 2.0 to 4.0 in order to determine the hypocenter locations and focal mechanisms. The focal mechanisms were retrieved from the regional moment-tensor inversion for the mainshock and using the P-wave polarities for the corresponding aftershocks of Mw ≥ 2.0, respectively. The focal mechanism solutions were inverted to retrieve the seismogenic stress using the stress tensor inversion. The combination of the nearby fault trends and the obtained results from hypocentral relocations, focal mechanism solutions, and stress tensor inversion emphasizes that the NE fault trend is likely to be the causative fault resulting in the 2017 Namas earthquake sequence, implying that the local tectonic setting is incompatible with the large-scale regional tectonics of the Red Sea opening. On the contrary, estimates of low-stress drops exhibit typical values compatible with those reported for the shallow plate-boundary earthquakes that occurred in the Red Sea, suggesting that the existing weak zones in the southernmost part of the Arabian Shield may be attributed to the large-scale regional tectonics of the Red Sea opening. [ABSTRACT FROM AUTHOR]

Petroglyphs, engraved throughout the Holocene into rock varnish coatings on sandstone, were investigated in the Ha'il region of northwestern Saudi Arabia, at Jabal Yatib, Jubbah, and Shuwaymis. The rock art has been created by removing the black varnish coating and thereby exposing the light sandstone underneath. With time, the varnish, a natural manganese (Mn)-rich coating, grows back. To study the rate of regrowth, we made 234 measurements by portable X-ray fluorescence (pXRF) on intact varnish and engraved petroglyphs. Since many petroglyphs can be assigned to a specific time period, a relationship between their ages and the Mn surface densities (DMn) of the regrown material could be derived. This relationship was improved by normalizing the DMn in the petroglyphs with the DMn of adjacent intact varnish. In turn, we used this relationship to assign a chronologic context to petroglyphs of unknown ages. Following the removal of the varnish by the artist and prior to the beginning of Mn oxyhydroxide regrowth, a thin Fe-rich film forms on the underlying rock. This initial Fe oxyhydroxide deposit may act as catalyst for subsequent fast Mn oxidation. After a few decades of relatively rapid growth, the regrowth of the Mn-rich varnish slows down to about 0.017 μg cm-2 a-1 Mn, corresponding to about 0.012% a-1 Mn of the intact varnish density, or about 1.2 nm a-1, presumably due to a change of the catalytic process. Our results suggest that petroglyphs were engraved almost continuously since the pre-Neolithic period, and that rock varnish growth seems to proceed roughly linear, without detectable influences of the regional Holocene climatic changes. [ABSTRACT FROM AUTHOR]

Gemsa has been chosen as the site for one of a new generation of power stations along the south-western margin of the Gulf of Suez. This site has been affected by a number of destructive earthquakes (M> 5), in addition to large number of earthquakes with magnitudes of less than 5. In this study seismic activities in the region were collected and re-evaluated, and the main earthquake prone zones were identified. It is indicated that this site is affected by the southern Gulf of Suez, northern Red Sea and Gulf of Aqaba source zones. The southern Gulf of Suez source zone is the nearest to the proposed site. The stochastic simulation method has been applied to estimate the Peak GroundAcceleration at the site of the proposed Gemsa power plant. It was noticed that the pseudo-spectral acceleration (PSA) reaches 175 cm/sec2 resulting from the southern Gulf of Suez seismic source. In addition, the response spectrum was conducted with a damping value of 5% of the critical damping, and the predominant period reached 0.1sec at the site. These results should be taken into consideration by civil engineers and decision-makers for designing earthquake resistant structures. [ABSTRACT FROM AUTHOR]

The Arabian Gulf is adjacent to the Zagros Mountains, one of the most seismically active regions in the world. We observe that broadband seismic records of Zagros earthquakes recorded on the Arabian side of the Gulf display long-duration surface waves. While shorter periods (<1 s) are attenuated from crossing the deep sediments (>10 km) of the Gulf basin, the long-period energy is enhanced and transmitted efficiently. Consequently, large earthquakes in the Zagros could result in amplified ground motions at long periods (2-10 s) relative to average behavior. Such ground motions are of concern for large engineered structures, such as tall buildings and long bridges with resonant periods in the same period range. Here we present results of investigations of the characteristics of ground motions recorded on the western shore of the Gulf from selected earthquakes in the Zagros Mountains region. Exceptionally, long-duration seismic waves, as compared with standard models, are shown to occur with periods of 2-10 s. This may be due to waveguide effects in the deep sedimentary basin structure of the Arabian Platform. In addition to analyzing recorded ground motion we performed 3D wave propagation simulations using a finite difference method and experimental velocity models of the Gulf, with different shallow sedimentary layers structures. The simulation results confirm our hypothesis that long-period waves with extremely long duration and relatively large amplitudes are caused by the geometry of the basin sedimentary layers and, to some extent, by shallow earthquake depths. Combined effects of basin edge geometry with sharp velocity contrasts and shallow sources (<10 km) on the eastern side of the Arabian Gulf can cause large long-period ground motion on the western side of the Gulf. In contrast, the short-period content of ground motion (<2 s) at long distances is relatively weak. This is mainly due to wave propagation scattering and attenuation in the shallow sedimentary layers of the Gulf basin. [ABSTRACT FROM AUTHOR]

Jeddah-Makkah regionis have been suffering from earthquake crisis where some moderate to destructive earthquakes have been recorded. These earthquake activities are oriented along major faults or clustered in certain spots. Moreover, these earthquake events have annual recurrence periods, so the identification of these seismogenic source zones is of utmost importance for mapping the most hazardous localities which should be avoided in the future urban planning. Historical and instrumental earthquakes have been collected from national and international data centers and unified in catalogue. The existence of microearthquakes inland suggests that there is a significant level of tectonic activity at away from the axial trough of the Red Sea. Then, seismogenic source zones have been defined depending on the major tectonic trends; distribution of earthquake epicenters, seismicity rate (a & b-values) and fault plane solution of major earthquakes. It is concluded that Jeddah-Makkah region is affected by the outlined five seismogenic source zones; three of these zones aligned of the main Red Sea axial trough (southwestern Jeddah, western Jeddah, and northwestern Jeddah zones), while the other two zones are located in the land area of the region (Thewal-Rabegh and Jeddah-Makkah zones). These inland zones correlated well with the main trends of major tectonics which refleet the reactivation of tectonic movements along these fault trends. The Red Sea zones are in agreement with the main path of the axial trough. The range of b-value in these identified zones is 0.65 to 1.03 through these identified zones. The area characterized by higher b-values could be indicative of a relative low stress regime which was a result of resulting from the stress release by the earthquakes. Whereas, the areas of lower b-values can be considered as an evidence of a relatively higher stress regime associated with a dominantly extensional stresses. Based on aforementioned, the region is suffering from different stress level accumulations which, in turn, cause earthquakes with different magnitudes. Accordingly, deployment of local seismograph network through Jeddah-Makkah region is highly recommended. These results will support, to a great extent, seismic hazard assessment and risk mitigation of the region. [ABSTRACT FROM AUTHOR]

New velocity models of lithospheric thickness and velocity structure have been developed for the Arabian Shield by three tasks: 1) Computing P-Wave Receiver Functions (PRFs) and S-Wave Receiver Functions (SRFs) for all the broadband stations within the Saudi seismic networks. The number of receiver function waveforms depends on the recording time window and quality of the broadband station. 2) Computing ambient noise correlation Green's functions for all available station pairs within the Saudi seismic networks to image the shear velocity in the crust and uppermost mantle beneath the Arabian Peninsula. Together they provided hundreds of additional, unique paths exclusively sampling the region of interest. Both phase and group velocities for all the resulting empirical Green's functions have been measured and to be used in the joint inversion. 3) Jointly inverted the PRFs and SRFs obtained in task 1 with dispersion velocities measured on the Green's functions obtained in task 2 and with fundamental-mode, Rayleigh-wave, group and phase velocities borrowed from the tomographic studies to precisely determine 1D crustal velocity structure and upper mantle. The analysis of the PRFs revealed values of 25-45 km for crustal thickness, with the thin crust next to the Red Sea and Gulf of Aqaba and the thicker crust under the platform, and Vp/Vs ratios in the 1.70-1.80 range, suggesting a range of compositions (felsic to mafic) for the shield's crust. The migrated SRFs suggest lithospheric thicknesses in the 80-100 km range for portions of the shield close to the Red Sea and Gulf of Aqaba and near the Arabian Gulf. Generally, the novelty of the velocity models developed under this paper has consisted in the addition of SRF data to extend the velocity models down to lithospheric and sub-lithospheric depths. [ABSTRACT FROM AUTHOR]

The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs) are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4) and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR) and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer. [ABSTRACT FROM AUTHOR]

Metal toxicity in crop plants is a matter of scientific concern. Therefore, in recent years efforts have been made to minimize metal toxicity in crop plants. Out of various strategies, priming of seedlings with certain chemicals, like e.g. donors of signaling molecules, nutrients, metabolites or plant hormones has shown encouraging results. However, mechanisms related with the priming‐induced mitigation of metal toxicity are still poorly known. Hence, we have tested the potential of 2‐oxoglutarate (2‐OG) priming in enhancing the arsenate (AsV) toxicity tolerance in tomato seedlings along with deciphering the probable role of nitric oxide (NO) in accomplishing this task. Arsenate decreased growth, endogenous NO and nitric oxide synthase‐like activity but enhanced the accumulation of As, which collectively led to root cell death. Arsenate toxicity also decreased some photosynthetic characteristics (i.e. Fv/Fm, qP, Fv/F0 and Fm/F0, and total chlorophyll content) but enhanced NPQ. However, priming with 2‐OG alleviated the toxic effect of AsV on growth, endogenous NO, cell death and photosynthesis. Moreover, arsenate inhibited the activities of enzymes of nitrogen metabolism (i.e. nitrate reductase, nitrite reductase, glutamine synthetase and glutamine 2‐oxoglutarate aminotransferase) but increased the activity of glutamate dehydrogenase and NH4+ content. Superoxide radicals, hydrogen peroxide, lipid peroxidation, protein oxidation and membrane damage increased upon AsV exposure, but the antioxidant enzymes (i.e. superoxide dismutase, catalase and glutathione‐S‐transferase) showed differential responses. Overall, our results showed that 2‐OG is capable of alleviating AsV toxicity in tomato seedlings but the involvement of endogenous NO is probably required. [ABSTRACT FROM AUTHOR]

We investigated rock varnish formed on sandstone and petroglyphs in the Hima area, southwestern Saudi Arabia. To characterize the rock varnish, we made in-situ measurements by portable x-ray fluorescence (pXRF) and analyzed samples by femtosecond laser-ablation inductively coupled–plasma mass spectrometry (fs LA-ICP-MS). Detailed chemical analysis of the rock varnish samples and adjacent soil or aeolian dust yielded information about the varnish's geochemical context and formation mechanism. Untypically low positive Ce anomalies in the rock varnish samples correlated with negative Ce anomalies in the dust, supporting the hypothesis that the dust is the source of the varnish material. To study the varnish development, we made use of the fact that engraving the petroglyphs exposes a fresh bare sandstone surface without varnish, on which varnish regrows subsequently. We determined by pXRF the areal density of manganese (Mn) and iron (Fe) that had been deposited as rock varnish since the creation of the rock art. The rates of Mn deposition in the newly formed varnish were then estimated by correlating the areal density of Mn in Ancient Arabian and Old Arabic inscriptions with their known age ranges. The observed deposition rates showed substantial variability resulting from differences in exposure conditions of the rock surface, but were in a range comparable with that of our previous measurements in northwestern Arabia. This variability could be reduced significantly by referencing the measurements to the intact varnish adjacent to the individual petroglyphs. This normalization provided a much clearer relationship between varnish deposition and age, and enabled tentative ages to be assigned to rock art motifs without previously known ages. These tentative ages spanned most of the Holocene period and were consistent with the culturally or ecologically derived ages of the animal and human figures depicted in the rock art and the styles of scripts used in different periods. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Work of the Organisation of the Prohibition of Chemical Weapons (OPCW) is outlined. • Advice on assistance and protection from OPCW Scientific Advisory Board is provided. • Advice addresses medical care and treatment of longer term injuries from nerve agents. • Scientific literature on the topics is reviewed and over 130 references included. • This advice will better inform toxicologists, medics and emergency responders. Abstract The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice in relation to the Chemical Weapons Convention on assistance and protection. We present the SAB's response to a request from the OPCW Director-General in 2014 for information on the best practices for preventing and treating the health effects from acute, prolonged, and repeated organophosphorus nerve agent (NA) exposure. The report summarises pre- and post-exposure treatments, and developments in decontaminants and adsorbing materials, that at the time of the advice, were available for NAs. The updated information provided could assist medics and emergency responders unfamiliar with treatment and decontamination options related to exposure to NAs. The SAB recommended that developments in research on medical countermeasures and decontaminants for NAs should be monitored by the OPCW, and used in assistance and protection training courses and workshops organised through its capacity building programmes. [ABSTRACT FROM AUTHOR]

Objective: The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods: In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene's promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results: The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion: The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer. [ABSTRACT FROM AUTHOR]

In this study, we have explored the possible role of ascorbic acid (ASC) and glutathione (GSH) in alleviating arsenate (AsV) toxicity in brinjal roots. Moreover, we have also focused our attention on the possible involvement of endogenous nitric oxide (NO) in accomplishing this task. AsV treatment negatively impacts the length and fresh weight of roots and shoots as well as the dry weight and fitness of roots, and this was accompanied by greater As accumulation in roots and shoots of brinjal. AsV treatment also declined the endogenous NO level by inhibiting Nitric Oxide Synthase‐like (NOS‐like) activity. Furthermore, AsV stimulated oxidative stress markers, caused protein damage by their carbonylation due to downregulation in antioxidants [particularly ascorbate (AsA)‐GSH cycle], leading to disturbed cellular redox status. This, collectively, led to root cell death in brinjal. However, the addition of either ASC or GSH rescued brinjal roots from the toxic effects of AsV in. Interestingly, lycorine (an inhibitor of ASC biosynthesis) further increased AsV toxicity, while ASC rescued its effects. Moreover, buthionine sulphoximine (BSO, an inhibitor of GSH biosynthesis) interestingly increased further AsV toxicity, while GSH rescued the plant from the As toxic effects. An interesting notion of this study was that GSH rescued the toxic effect of lycorine, while ASC rescued the toxic effect of BSO, though the AsV toxicity mediated by either ASC or GSH was always accompanied by high endogenous NO level and NOS‐like activity. All together, these results suggest that ASC and GSH independently mitigate AsV toxicity in brinjal roots, but both might be dependent on endogenous NO for accomplishing the AsV toxicity alleviatory tasks. [ABSTRACT FROM AUTHOR]

Key message: Exogenous potassium (K+) and endogenous hydrogen sulfide (H2S) synergistically alleviate drought stress through regulating H+-ATPase activity, sugar metabolism and redox homoeostasis in tomato seedlings. Present work evaluates the role of K+ in the regulation of endogenous H2S signaling in modulating the tolerance of tomato (Solanum lycopersicum L. Mill.) seedlings to drought stress. The findings reveal that exposure of seedlings to 15% (w/v) polyethylene glycol 8000 (PEG) led to a substantial decrease in leaf K+ content which was associated with reduced H+-ATPase activity. Treatment with sodium orthovanadate (SOV, PM H+-ATPase inhibitor) and tetraethylammonium chloride (TEA, K+ channel blocker) suggests that exogenous K+ stimulated H+-ATPase activity that further regulated endogenous K+ content in tomato seedlings subjected to drought stress. Moreover, reduction in H+-ATPase activity by hypotaurine (HT; H2S scavenger) substantiates the role of endogenous H2S in the regulation of H+-ATPase activity. Elevation in endogenous K+ content enhanced the biosynthesis of H2S through enhancing the synthesis of cysteine, the H2S precursor. Synergistic action of H2S and K+ effectively neutralized drought stress by regulating sugar metabolism and redox homoeostasis that resulted in osmotic adjustment, as witnessed by reduced water loss, and improved hydration level of the stressed seedlings. The integrative role of endogenous H2S in K+ homeostasis was validated using HT and TEA which weakened the protection against drought stress induced impairments. In conclusion, exogenous K+ and endogenous H2S regulate H+-ATPase activity which plays a decisive role in the maintenance of endogenous K+ homeostasis. Thus, present work reveals that K+ and H2S crosstalk is essential for modulation of drought stress tolerance in tomato seedlings. [ABSTRACT FROM AUTHOR]

Present investigation reports the role of calcium (Ca2+) and hydrogen sulfide (H 2 S) crosstalk associated with Vigna radiata seedlings subjected to K+ deficient conditions under short-term (24 h) and long-term (72 h) NaCl stress. Perusal of the data reveals that under short-term NaCl stress an initial decline in K+ level led to the elevation in Ca2+ and H 2 S levels along with improvement in antioxidant system and reduction in reactive oxygen species (ROS) production. Under long-term NaCl stress a further decline in K+ content was deleterious that led to a lower K+/Na+ ratio. This was followed by reduction in antioxidant system along with excessive accumulation of ROS and methylglyoxal content, and increased membrane damage. However, supplementation of the seedling roots with Ca2+ enhanced biosynthesis of H 2 S through enhancing cysteine pool. The present findings suggest that synergistic action of Ca2+ and H 2 S induced the activity of H+-ATPase that created H+ gradient which in turn induced Na+/H+ antiport system that accelerated K+ influx and Na+ efflux. All of these together contributed to a higher K+/Na+ ratio, activation of antioxidative defense system, and maintenance of redox homeostasis and membrane integrity in Ca2+-supplemented stressed seedlings. Role of Ca2+ and H 2 S in the regulation of Na+/H+ antiport system was validated by the use of sodium orthovanadate (plasma membrane H+-ATPase inhibitor), tetraethylammonium chloride (K+ channel blocker), and amiloride (Na+/H+ antiporter inhibitor). Application of Ca2+-chelator EGTA (ethylene glycol-bis(b-aminoethylether)- N,N,Nʹ,Nʹ -tetraacetic acid) and H 2 S scavenger hypotaurine abolished the effect of Ca2+, suggesting the involvement of Ca2+ and H 2 S in the alleviation of NaCl stress. Moreover, use of EGTA and HT also substantiates the downstream functioning of H 2 S during Ca2+-mediated regulation of plant adaptive responses to NaCl stress. To sum up, present findings reveal the association of Ca2+ and H 2 S signaling in the regulation of ion homeostasis and antioxidant defense during K+-deficient NaCl stress. Image 1 • Short term NaCl-induced potassium (K+) deficiency regulates NaCl-induced impairments. • Under long term NaCl stress, further decline in K+ content was deleterious. • Calcium (Ca2+) regulates Na+/H+ antiport and defense system under NaCl stress. • Ca2+-dependent regulation of plant response to NaCl stress is mediated by hydrogen sulfide (H 2 S). • H 2 S functions downstream of Ca2+ during plant adaptive responses to NaCl stress. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) and nitric oxide (NO) have been known to affect vast number of processes in plants under abiotic stresses. Also, calcium (Ca) works as a second messenger in plants, which underpins the abiotic stress-induced damage. However, the sequence of action of these signaling molecules against cadmium (Cd)-induced cellular oxidative damage remains unidentified. Therefore, we studied the synergistic actions and/or relationship of signaling molecules and Ca-dependent activation of tolerance mechanisms in Vigna radiata seedlings under Cd stress. The present study shows that exogenous Ca supplemented to Cd-stressed V. radiata seedlings reduced Cd accumulation and improved the activity of nitrate reductase, and L/D-cysteine desulfhydrase (LCD/DCD) that resulted in improved synthesis of NO and H 2 S content. Application of Ca also elevated the level of cysteine (Cys) by upregulating the activity of Cys-synthesizing enzymes serine acetyltransferase and O -acetylserine(thiol)lyase in Cd-stressed seedlings. Maintenance of Cys pool under Cd stress contributed to improved H 2 S content which together with Ca and NO improved antioxidant enzymes and components of ascorbate-glutathione (AsA-GSH) cycle. All these collectively regulated the activity of NADPH oxidase and glycolate oxidase, resulting in the inhibition of Cd-induced generation of reactive oxygen species. The elevated level of Cys also assisted the Cd-stressed seedlings in maintaining GSH pool which retained normal functioning of AsA-GSH cycle and led to enhanced content of phytochelatins coupled with reduced Cd content. The positive effect of these events manifested in an enhanced rate of photosynthesis, carbohydrate accumulation, and growth attributes of the plants. On the contrary, addition of NO scavenger cPTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide], H 2 S scavenger HT (Hypotaurine) and Ca-chelator EGTA (Ethylene glycol-bis(b-aminoethylether)- N,N,Nʹ,Nʹ -tetraacetic acid) again developed a condition similar to stress and positive effect of the signaling molecules was abolished. The findings of the study postulate that Ca in association with NO and H 2 S mitigates Cd-induced impairment and enhances the tolerance of the V. radiata plants against Cd stress. The results of the study also substantiate that Ca acts both upstream as well as downstream of NO signals whereas, H 2 S acts downstream of Ca and NO during Cd-stress responses of the plants. Image 1 • Cadmium (Cd)-toxicity hampered photosynthesis and growth of Vigna radiata. • Application of calcium (Ca) induced the biosynthesis of nitric oxide (NO) and hydrogen sulfide (H 2 S). • Synergistic action of NO and H 2 S requires Ca for activation of defense system of the plants. • Interaction of Ca, NO and H 2 S maintain redox homeostasis. • Ca plays central role in the cross talk of NO and H 2 S under Cd toxicity. [ABSTRACT FROM AUTHOR]

Earthquake prediction is a popular topic among earth scientists; however, this task is challenging and exhibits uncertainty therefore, probability assessment is indispensable in the current period. During the last decades, the volume of seismic data has increased exponentially, adding scalability issues to probability assessment models. Several machine learning methods, such as deep learning, have been applied to large-scale images, video, and text processing; however, they have been rarely utilized in earthquake probability assessment. Therefore, the present research leveraged advances in deep learning techniques to generate scalable earthquake probability mapping. To achieve this objective, this research used a convolutional neural network (CNN). Nine indicators, namely, proximity to faults, fault density, lithology with an amplification factor value, slope angle, elevation, magnitude density, epicenter density, distance from the epicenter, and peak ground acceleration (PGA) density, served as inputs. Meanwhile, 0 and 1 were used as outputs corresponding to non-earthquake and earthquake parameters, respectively. The proposed classification model was tested at the country level on datasets gathered to update the probability map for the Indian subcontinent using statistical measures, such as overall accuracy (OA), F1 score, recall, and precision. The OA values of the model based on the training and testing datasets were 96% and 92%, respectively. The proposed model also achieved precision, recall, and F1 score values of 0.88, 0.99, and 0.93, respectively, for the positive (earthquake) class based on the testing dataset. The model predicted two classes and observed very-high (712,375 km2) and high probability (591,240.5 km2) areas consisting of 19.8% and 16.43% of the abovementioned zones, respectively. Results indicated that the proposed model is superior to the traditional methods for earthquake probability assessment in terms of accuracy. Aside from facilitating the prediction of the pixel values for probability assessment, the proposed model can also help urban-planners and disaster managers make appropriate decisions regarding future plans and earthquake management. [ABSTRACT FROM AUTHOR]

Abstract The present study is based on the use of Empirical Green's Function (EGF) deconvolution technique to retrieve the slip distribution of the 2014 M w 4.2 Jizan earthquake, Saudi Arabia. Two datasets of complex Source Time Functions (STFs) were retrieved using two appropriate EGF events. We inverted the STF datasets to recover the slip distribution over both nodal planes, using the Bayesian modeling followed by a linear least-squares method. The inversion was performed assuming both planes as the fault plane and examined the goodness of fit for each nodal plane. Based on a series of finite-source inversions using different rupture velocities, we resolved the rupture velocity at 2.7–2.8 km/s and the fault plane of NNW trending; paralleling the Red Sea rift. Using the estimated rupture velocities and the preferred fault plane, we imaged quite similar slip models, exhibiting two slip patches located to the updip and downdip directions from the hypocentre. The spatiotemporal slip distributions revealed a complex rupture history of such small-sized earthquake is likely to that reported for large-sized earthquakes. A seismic moment of 2.8–3.2E+15 NM and a corresponding moment magnitude of 4.2-4-3 are inferred. The stress drops obtained from the slip distribution models were 2.2–2.5 MPa; indicating a typical value that characterized the plate-boundary earthquakes. Highlights • Use EGF deconvolution technique to retrieve the STFs. • Invert STFS to obtain slip distribution model over the fault plane. • Two slip distribution models imaged two patches located to the up-dip and downdip directions from the hypocenter. • Low stress drops of 2.2–2.5 MPa indicated a typical value for plate-boundary earthquakes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Work of the Organisation of the Prohibition of Chemical Weapons (OPCW) is described. • Advice on assistance and protection from OPCW Scientific Advisory Board is presented. • The advice addresses medical care/treatment of injuries from nerve agents. • Scientific literature on the topics is reviewed and over 140 references highlighted. • This advice serves as a resource for toxicologists, medics and emergency responders. Abstract The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice on assistance and protection in relation to the Chemical Weapons Convention. In this, the first of several papers describing the SAB's work on this topic, we describe advice given in response to questions from the OPCW Director-General in 2013 and 2014 on the status of available medical countermeasures and treatments to organophosphorus nerve agents. This paper provides the evidence base for this advice which recommended to the OPCW pretreatments, emergency care, and long-term treatments that were available at the time of the request for this class of chemical warfare agent (CWA). It includes a bibliography of over 140 scientific references, which can be used as a platform for watching future medical countermeasure developments. The information provided in this paper should serve as a valuable reference for medical professionals and emergency responders who may have no knowledge of the symptoms and treatment options of exposure to nerve agents. [ABSTRACT FROM AUTHOR]

Herein, we evaluated the association of the Toll-like receptor 6 (TLR6) single nucleotide polymorphisms (SNPs) rs3796508 (Val327Met) and rs5743810 (Ser249Pro) with breast cancer (BC) susceptibility in Saudi Arabian women, using in silico analysis. We found no significant differences in genotypic and allelic frequencies for rs3796508 between the BC patients (n = 127) and healthy individuals (n = 116). However, 86% of the BC patients, versus 98% of the healthy controls, carried the rs5743810 Pro allele (OR = 0.103, CI = 0.036–0.293, P = 0.00001). Advanced analysis based on the comparison of the estrogen receptor (ER)-positive and -negative patients with the healthy controls indicated a significant association between rs5743810 allelic frequency and BC risk protection (OR = 0.100, CI = 0.034–0.297, P = 0.00001 for ER+ BC cases; OR = 0.102, CI = 0.033–0.318, P = 0.00001 for ER−BC cases). Furthermore, rs5743810 was associated with BC risk protection at either above or below 48 years of age at diagnosis (OR = 0.101, CI = 0.022–0.455, P = 0.00037 for age ≤48 years; OR = 0.120, CI = 0.028–0.519, P = 0.00087 for age >48 years). Such associations were not found for rs3796508. In silico analysis indicated that these SNPs had neutral effects within the TLR6 structure, confirming the protective role of rs5743810. Our findings therefore suggest a strong association between rs5743810 and protection against BC risk in Saudi Arabian women. Importantly, the rs5743810 Pro allele could be a potential BC diagnostic biomarker in this ethnic population. [ABSTRACT FROM AUTHOR]

The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice on the long-term storage and stability of samples collected in the context of chemical weapons investigations. The information they compiled and reviewed is beneficial to all laboratories that carry out analysis of samples related to chemical warfare agents and is described herein. The preparation of this report was undertaken on request from the OPCW Director-General. The main degradation products for chemicals on the Schedules in the Annex on Chemicals of the Chemical Weapons Convention are tabulated. The expertise of the 25 scientists comprising the SAB, a review of the scientific literature on environmental and biomedical sample analysis, and answers to a questionnaire from chemists of nine OPCW Designated Laboratories, were drawn upon to provide the advice. Ten recommendations to ensure the long-term storage and stability of samples collected in relation to the potential use of chemical weapons were provided and are repeated here for the consideration of all laboratories worldwide. [ABSTRACT FROM AUTHOR]

The Chemical Weapons Convention (CWC) is an international disarmament treaty that prohibits the development, stockpiling and use of chemical weapons. This treaty has 193 States Parties (nations for which the treaty is binding) and entered into force in 1997. The CWC contains schedules of chemicals that have been associated with chemical warfare programmes. These scheduled chemicals must be declared by the States that possess them and are subject to verification by the Organisation for the Prohibition of Chemical Weapons (OPCW, the implementing body of the CWC). Isotopically labelled and stereoisomeric variants of the scheduled chemicals have presented ambiguities for interpretation of the requirements of treaty implementation, and advice was sought from the OPCW's Scientific Advisory Board (SAB) in 2016. The SAB recommended that isotopically labelled compounds or stereoisomers related to the parent compound specified in a schedule should be interpreted as belonging to the same schedule. This advice should benefit scientists and diplomats from the CWC's State Parties to help ensure a consistent approach to their declarations of scheduled chemicals (which in turn supports both the correctness and completeness of declarations under the CWC). Herein, isotopically labelled and stereoisomeric variants of CWC-scheduled chemicals are reviewed, and the impact of the SAB advice in influencing a change to national licensing in one of the State Parties is discussed. This outcome, an update to national licensing governing compliance to an international treaty, serves as an example of the effectiveness of science diplomacy within an international disarmament treaty. [ABSTRACT FROM AUTHOR]

Chromium (Cr), a highly toxic redox-active metal cation in soil, seriously threatens global agriculture by affecting nutrient uptake and disturbing various physio-biochemical processes in plants, thereby reducing yields. Here, we examined the effects of different concentrations of Cr alone and in combination with hydrogen sulfide (H 2 S) application on the growth and physio-biochemical performance of two mungbeans (Vigna radiata L.) varieties, viz. Pusa Vishal (PV; Cr tolerant) and Pusa Ratna (PR; Cr sensitive), growing in a pot in hydroponics. Plants were grown in the pot experiment to examine their growth, enzymatic and non-enzymatic antioxidant levels, electrolyte balance, and plasma membrane (PM) H+-ATPase activity. Furthermore, root anatomy and cell death were analysed 15 days after sowing both varieties in hydroponic systems. The Cr-induced accumulation of reactive oxygen species caused cell death and affected the root anatomy and growth of both varieties. However, the extent of alteration in anatomical features was less in PV than in PR. Exogenous application of H 2 S promoted plant growth, thereby improving plant antioxidant activities and reducing cell death by suppressing Cr accumulation and translocation. Seedlings of both cultivars treated with H 2 S exhibited enhanced photosynthesis, ion uptake, glutathione, and proline levels and reduced oxidative stress. Interestingly, H 2 S restricted the translocation of Cr to aerial parts of plants by improving the nutrient profile and viability of root cells, thereby relieving plants from oxidative bursts by activating the antioxidant machinery through triggering the ascorbate-glutathione cycle. Overall, H 2 S application improved the nutrient profile and ionic homeostasis of Cr-stressed mungbean plants. These results highlight the importance of H 2 S application in protecting crops against Cr toxicity. Our findings can be utilised to develop management strategies to improve heavy metal tolerance among crops. [Display omitted] • Cr impairs growth, nutrient homeostasis and physiology of mungbean seedlings. • H 2 S enhanced photosynthetic pigments biosynthesis in mungbean genotypes. • H 2 S inhibits ROS production and increased nutrients accumulation. • H 2 S improves anatomical features, proline and antioxidant system of seedlings. • H 2 S application provides Cr stress tolerance in mungbean. [ABSTRACT FROM AUTHOR]

Summary: Desert varnishes are dark rock coatings observed in arid environments and might resemble Mn‐rich coatings found on Martian rocks. Their formation mechanism is not fully understood and the possible microbial involvement is under debate. In this study, we applied DNA metagenomic Shotgun sequencing of varnish and surrounding soil to evaluate the composition of the microbial community and its potential metabolic function. We found that the α diversity was lower in varnish compared to soil samples (p value < 0.05), suggesting distinct populations with significantly higher abundance of Actinobacteria, Proteobacteria and Cyanobacteria within the varnish. Additionally, we observed increased levels of transition metal metabolic processes in varnish compared to soil samples. Nevertheless, potentially relevant enzymes for varnish formation were detected at low to insignificant levels in both niches, indicating no current direct microbial involvement in Mn oxidation. This finding is supported by quantitative genomic analysis, elemental analysis, fluorescence imaging and scanning transmission X‐ray microscopy. We thus conclude that the distinct microbial communities detected in desert varnish originate from settled Aeolian microbes, which colonized this nutrient‐enriched niche, and discuss possible indirect contributions of microorganisms to the formation of desert varnish. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cause of cancer-related deaths among women in the Kingdom of Saudi Arabia. An association between the dysregulation of innate immunity, primarily the deregulation of Toll-like receptors (TLRs), and BC development was described a long time ago. Several studies have reported that BC risk factors appear to be related to the interaction between certain genes and exposure to various environmental factors. Here, we investigated the potential correlation of three TLR2 single-nucleotide polymorphisms (SNPs; rs3804100, rs4696480, and rs3804099) with the development of BC in female patients from Saudi Arabia. We collected 126 blood samples from women with BC and 146 blood samples from healthy women without any clinical signs of BC. The genotypic frequencies of TLR2 polymorphisms were assayed. Our results showed that the genotypic and allelic frequencies of TLR2 did not differ significantly between BC patients and healthy controls. However, the distributions of rs3804100 (1350 T/C) genotypes in BC groups were 1%, 19%, and 80% for CC, CT, and TT, respectively. In the control group, the rs3804100 (1350 T/C) genotype distributions were 3%, 18%, and 79% for CC, CT, and TT, respectively. The SNP rs3804100 homozygous "TT" genotype was not associated with the risk of developing BC in the BC patients compared with controls (odds ratio [OR], 4.5; confidence interval [CI], 0.49-41.02; P=0.145). The TLR2 rs4696480 AA genotype was observed in 23% of BC patients compared to 18% of control individuals, the AT genotype was seen in 40% of BC patients and 46% of control individuals, and the TT genotype was observed in 37% of BC patients and 36% of normal controls. Our results did not show any difference in genotypic frequency between BC patients and normal controls for the TLR2 rs3804099 SNP; however, the (C) phenotypic frequency was 49% in BC patients and 53% in controls. The (T) phenotypic frequency was 51% and 47% in BC patients and normal patients, respectively. These findings indicate that there is no association between the TLR2 polymorphisms tested and BC susceptibility in the female population from the Kingdom of Saudi Arabia. We suggest using other TLR2 SNPs to investigate the possible relationship between innate immunity deregulation by disruption of TLR2 and potential BC development. [ABSTRACT FROM AUTHOR]

Defects in the innate immune system, particularly in Toll-like receptors (TLRs), have been reported in several cigarette smoke-promoted diseases. The aim of this study was to examine the impact of tobacco smoke on allelic frequencies of TLR4 single-nucleotide polymorphisms (SNPs) and to compare the genotypic distribution of these SNPs in a Saudi Arabian population with that in previously studied populations. DNA was extracted from 303 saliva samples collected from smokers and nonsmokers. Two transitional SNPs in the promoter region of TLR4 were selected, rs2770150 (T/C) and rs10759931 (G/A). Genotype frequencies were determined using quantitative polymerase chain reaction. Our results showed a slight effect of smoking on the distribution of rs2770150 and rs10759931. However, the differences were not significant. Thus, we conclude that the SNPs selected for this study were independent of smoking and may not be related to smoking-induced diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)-, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism rs10759931 was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism rs2770150 was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism rs4986790 was also found to be associated with this malignancy in the ER- patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker. [ABSTRACT FROM AUTHOR]

Extensive volcanic fields on the western Arabian Plate have erupted intermittently over the last 30 Ma following emplacement of the Afar flood basalts in Ethiopia. In an effort to better understand the origin of this volcanism in western Saudi Arabia, we analyzed 3 He/ 4 He, and He, CO 2 and trace element concentrations in minerals separated from xenoliths and lava flows from Harrat Hutaymah, supplemented with reconnaissance He isotope data from several other volcanic fields (Harrat Al Birk, Harrat Al Kishb and Harrat Ithnayn). Harrat Hutaymah is young (< 850 ka) and the northeasternmost of the volcanic fields. There is a remarkable homogeneity of 3 He/ 4 He trapped within most xenoliths, with a weighted mean of 7.54 ± 0.03 R A (2σ, n = 20). This homogeneity occurs over at least eight different xenolith types (including spinel lherzolite, amphibole clinopyroxenite, olivine websterite, clinopyroxenite and garnet websterite), and encompasses ten different volcanic centers within an area of ~ 2500 km 2 . The homogeneity is caused by volatile equilibration between the xenoliths and fluids derived from their host magma, as fluid inclusions are annealed during the infiltration of vapor-saturated magmas along crystalline grain boundaries. The notable exceptions are the anhydrous spinel lherzolites, which have a lower weighted mean 3 He/ 4 He of 6.8 ± 0.3 R A (2σ, n = 2), contain lower concentrations of trapped He, and have a distinctly depleted light rare earth element signature. 3 He/ 4 He values of ~ 6.8 R A are also commonly found in spinel lherzolites from harrats Ithnayn, Al Birk, and from Zabargad Island in the Red Sea. Olivine from non-xenolith-bearing lava flows at Hutaymah spans the He isotope range of the xenoliths. The lower 3 He/ 4 He in the anhydrous spinel lherzolites appears to be tied to remnant Proterozoic lithosphere prior to metasomatic fluid overprinting. Elevated 3 He/ 4 He in the western harrats has been observed only at Rahat (up to 11.8 R A ; Murcia et al., 2013), a volcanic field situated above thinned lithosphere beneath the Makkah-Medinah-Nafud volcanic lineament. Previous work established that spinel lherzolites at Hutaymah are sourced near the lithosphere-asthenosphere boundary (LAB), while other xenolith types there are derived from shallower depths within the lithosphere itself (Thornber, 1992). Helium isotopes are consistent with melts originating near the LAB beneath many of the Arabian harrats, and any magma derived from the Afar mantle plume currently appears to be of minor importance. [ABSTRACT FROM AUTHOR]

Harrat Hutaymah is an alkali basalt volcanic field in north-central Saudi Arabia, at the eastern margin of a large Neogene continental, intraplate magmatic province. Lava flow, tephra and spatter cone compositions in the field include alkali olivine basalts and basanites. These compositions contrast with the predominantly tholeiitic, fissure-fed basalts found along the eastern margin of the Red Sea. The Hutaymah lava flows were erupted through Proterozoic arc-associated plutonic and meta-sedimentary rocks of the Arabian shield, and commonly contain a range of sub-continental lithospheric xenoliths, although the lavas themselves show little indication of crustal contamination. Previous radiometric dating of this volcanic field (a single published K–Ar age; 1.8 Ma) is suspiciously old given the field measurement of normal magnetic polarity only (i.e. Brunhes interval, ≤ 780 Ka). We report new age determinations on 14 lava flows by the 40 Ar– 39 Ar laser step heating method, all younger than ~ 850 Ka, to better constrain the time frame of volcanism, and major, trace and rare earth element compositions to describe the chemical variation of volcanic activity at Harrat Hutaymah. Crystal fractionation was dominated by olivine ± clinopyroxene at a range of upper mantle and crustal pressures. Rapid ascent and eruption of magma is indicated by the array of lower crustal and lithospheric xenoliths observed in lava flows and tephra. Modeling suggests 1–7% melting of an enriched asthenospheric mantle source occurred beneath Harrat Hutaymah under a relatively thick lithospheric cap (60–80 km). [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-κB pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infections by bacteria in the human colon and leads to induction of an acute secretion of inflammatory cytokines mediated by NF-κB. Also, we report here a clear evidence for an association between TLR4 rs10759931 polymorphism (OR = 0.086, CI: 0.04–0.18, P = <0.00001). This polymorphism affects the entire population without being specific to either gender or to any age group. In contrast, the rs2770150 is associated with colon cancer in women aged over 50 years and is closely linked with the decreased levels of female sex hormones during the post-menopausal period (OR = 0.188, CI: 0.074–0.48, P = <0.00084). rs10759932 and rs4986790 appear to have any association with colon cancer. Our data suggest that TLR4 SNPs could possibly serve as biomarkers for decision making in colon cancer treatment. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating the relationship between rs1801320 (G.C), rs1801321 (G.T), and rs2619681 (C.T) RAD51 gene polymorphisms and the risk of breast cancer development in Saudi females. The genotypes were analyzed using TaqMan genotyping assay and polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies were computed using chi-square or Fisher's exact test (two-tailed) by SPSS 21 software. The results showed that rs1801321G.T GG genotype and G allele frequency were strongly (P,0.0001) related to an elevated risk of breast cancer, while the mutant T allele appeared to provide protection against breast cancer development as observed from the significantly lower (P,0.0001) frequencies of the TT and GT genotypes in cancer patients compared to the healthy controls. The variant rs1801320G.C showed no significant differences in the frequencies of the genotypes and alleles in the patients and the control groups. The CC genotype and C allele frequency of rs2619681 (C.T) variant were significantly (P=0.012) higher in cancer patients, whereas the T allele showed a protective effect against cancer development. The frequencies of the three single-nucleotide polymorphisms did not differ in cancer patients with different tumor grades and human epidermal growth factor receptor 2 status (+ or -). However, the genotype frequency of rs1801320 (135G.C) differed in the patients with estrogen receptor (ER)+ and ER-, where CC genotype showed a significantly higher prevalence in the females with ER- who were suffering from breast cancer. In addition, the frequency of C allele of rs2619681 (C.T) was also significantly higher in the breast cancer patients who were ER+ and progesterone receptor (PR)+ compared to those with ER- and PR-. In the Saudi females, rs1801320 did not show an association with risk of breast cancer. Taken together, the results suggest that RAD51 rs1801321 polymorphism may be involved in the etiology of breast cancer in the Saudi females; however, further studies are necessary to confirm this relation. [ABSTRACT FROM AUTHOR]

Background: Cytochrome P450 (CYP)19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among women with breast cancer. The aim of this study was to analyze the genetic association of rs4646 (A > C) and rs700518 (Val > Val) in the CYP19A1 gene with the risk of breast cancer. Methods: These two single nucleotide polymorphisms (SNPs) were analyzed in a primary study group of breast cancer patients and healthy control subjects. Genotypes were determined by the TaqMan SNP analysis technique. The study data were analyzed using the chi-square or t-test and logistic regression analysis by Statistical Package for the Social Sciences version 16 software. Results: rs4646 and rs700518 had no association with susceptibility to breast cancer. There was no significant association for either of these SNPs overall in breast cancer samples when compared with healthy control samples. Our data do not support a relationship between the CYP19A1 rs4646 and rs700518 SNPs and risk of breast cancer. It may be that there are ethnic differences with regard to this relationship. Conclusion: This study demonstrated that CYP19A1 rs4646 and rs700518 SNPs may not be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of other ethnicities could provide evidence for the role of the CYP19A1 gene in breast carcinomas. [ABSTRACT FROM AUTHOR]

Use of untreated municipal wastewater (WW) contains toxic trace elements that pose a serious threat to the soil-plant-human continuum. The use of biochar (BC) is a promising approach to minimize trace element induced toxicity in the ecosystem. Therefore, the present study aims to evaluate the efficacy of BC derived from wheat straw and iron oxide nanoparticles doped biochar (IO-BC) to reduce trace element buildup in soil and plants that consequently affect tomato plant growth and physiological activity under WW irrigation. The BC and IO-BC were applied at four levels (0, 0.5, 1, and 1.5%) in WW irrigated soils. The results indicated that the addition of WW + BC and WW + IO-BC resulted in significant reduction in trace element mobility in soil. Interestingly, the application of WW + IO-BC (1.5%) was more effective in reducing trace element mobility and bioavailability in soil by 78% (As), 58% (Cr), 46% (Pb) and 50% (Cd) compared to WW irrigation, and thus reduced trace element accumulation and toxicity in plants. Results revealed that WW irrigation negatively affected tomato growth, fruit yield, physiology and antioxidative response. Addition of WW + BC and WW + IO-BC ameliorated the oxidative stress (up to 65% and 58% in H 2 O 2 and MDA) and increased plant tolerance (up to 49% in POD and APX activity). The risk indices also showed minimum human health risk (H1 < 1) from tomato after the addition of BC or IO-BC in WW irrigated soils. It is concluded that IO-BC addition in WW irrigated soil could assist in reducing trace elements accumulation and toxicity in tomato and associated human health risks. [Display omitted] • Trace elements accumulation impaired growth and physiology of tomato under wastewater (WW) irrigation. • Toxic ion accumulation resulted in limited uptake of essential nutrients and oxidative stress. • Iron oxide nanoparticles doped biochar (IO-BC) was more effective than biochar (BC). • IO-BC decreased oxidative stress by upregulating antioxidant enzymes. • Human health risk was greatly decreased in the presence of IO-BC [ABSTRACT FROM AUTHOR]

[Display omitted] • Work of the Organisation of the Prohibition of Chemical Weapons (OPCW) is described. • Advice on assistance and protection from OPCW Scientific Advisory Board is provided. • The advice addresses medical care/treatment of injuries from sulfur mustard. • Scientific literature on the topics is reviewed and 243 references are included. • This advice serves as a resource for toxicologists, medics and emergency responders. Blister agents damage the skin, eyes, mucous membranes and subcutaneous tissues. Other toxic effects may occur after absorption. The response of the Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) to a request from the OPCW Director-General in 2013 on the status of medical countermeasures and treatments to blister agents is updated through the incorporation of the latest information. The physical and toxicological properties of sulfur mustard and clinical effects and treatments are summarised. The information should assist medics and emergency responders who may be unfamiliar with the toxidrome of sulfur mustard and its treatment. [ABSTRACT FROM AUTHOR]

Wheat is one of the leading staple crops in many countries. Phosphorus (P) plays an important role for wheat growth and yield as it takes part in many metabolic pathways. Even for soluble phosphatic fertilizers, most of the Pakistani soils, being alkaline and calcareous in nature, show phosphorus use efficiency (PUE) not more than 10–25%. The major issue is the unavailability of P due to fixation and precipitation reactions with soil particles. Composting of rock-phosphate with animal and poultry manures supplied with bio-stimulated phosphate solubilizing bacteria (PSB) not only enhances the RP solubilization but also serves as a potent source of P for plants. Composted/bio-activated rock-phosphate (B-RP), prepared by group of three bacterial strains i.e., Pseudomonas sp. (E11), Bacillus sp. (MN54) and Enterobacter sp. (MN17) aided with molasses (5%) and urea (10%), was tested alone and in various combinations with di-ammonium phosphate (DAP). In this pot trial, the combined application of B-RP and DAP was found superior to the sole application of B-RP. Even the combination of B-RP and DAP sharing equal amount of recommended P showed better results as compared to the sole application of DAP, giving improved shoot biomass (25%), total P-uptake (67%), recovery efficiency of P (75%), dry matter (29%), crude protein (29%), and other yield, physiological and nutritional quality parameters of wheat. So, it could be concluded that integrated use of B-RP and DAP with equal proportion of recommended P could serve as a better management practice for not only improving quantity but also the quality of the wheat grain. [ABSTRACT FROM AUTHOR]

• Arsenic (As) impaired growth and development of Vicia faba plants. • Mel pus Ca2+ suppressed As-induced program cell death in guard cells, roots and leaves. • Mel and Ca2+ improved photosynthesis, and biosynthesis of chlorophyll, carbohydrates, and proline. • Mel and Ca2+ alleviated As-induced DNA damage, and reactive oxygen species formation. • Mel and Ca2+ regulated ascorbate-glutathione pathway and proteins expression under As stress. The interplay between melatonin (Mel) and calcium (Ca2+) in enhancing tolerance to metalloid toxicity and underlying physiological and biochemical mechanisms of this relationship still remains unknown. The present study reveals that the signaling molecules Mel and/or Ca2+ enhanced tolerance of Vicia faba (cv. Tara) plant to metalloid arsenic (As) toxicity. However, a combination of Mel and Ca2+ was more efficient than alone. Plants grew with As exhibited enhanced hydrogen peroxide, superoxide anion, electrolyte leakage, lipid peroxidation together with increased reactive oxygen species (ROS) producing enzymes, such as NADPH oxidase and glycolate oxidase (GOX). On the contrary, an inhibition in chlorophyll (Chl) biosynthesis and gas exchange parameters (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration) was observed. Under As toxicity conditions, the application of Mel and Ca2+ synergistically suppressed the plants' program cell death features (nucleus condensation and nucleus fragmentation) in guard cells of stomata, DNA damage, and formation of ROS in guard cells, leaves and roots. Moreover, it enhanced gas exchange parameters and activity of enzymes involved in photosynthesis process (carbonic anhydrase and RuBisco), Chl biosynthesis (δ -aminolevulinic acid dehydratase), and decreased activity of Chl degrading enzyme (chlorophyllase) under As toxicity conditions. Our investigation evidently established that expression of ATP synthase, Ca2+-ATPase, Ca2+-DPKase, Hsp17.6 and Hsp40 was found maximum in the plants treated with Mel + Ca2+, resulting in higher tolerance of plants to As stress. Also, increased total soluble carbohydrates, cysteine, and Pro accumulation with increased Pro synthesizing enzyme (Δ 1 -pyrroline-5-carboxylate synthetase (P5CS) and decreased Pro degrading enzyme (proline dehydrogenase) in Mel + Ca2+ treated plants conferred As toxicity tolerance. The obtained results postulate strong evidence that the application of Mel along with Ca2+ enhances resilience against As toxicity by upregulating the activity of plasma membrane H+-ATPase, enzymes involved in antioxidant system, and ascorbate-glutathione pathway. [ABSTRACT FROM AUTHOR]

Rock varnishes are μm-thin, dark, manganese(Mn)-rich crusts that accrete in the order of few μm/ka on weathering-resistant lithologies. Although these crusts can form in all climates, they are best known in arid to semi-arid settings. Aeolian dust is understood as a major contributor to the distinct trace metal and REE enrichments in rock varnish. However, the exact proportions of abiotic and biotic formation mechanisms that may explain the oxidation-reactions of Mn2+ to Mn4+, present as Mn oxyhydroxides in the varnish, are still a matter of ongoing debate. We present here the first systematic study of trace element enrichment processes between the uppermost layer of the varnish sequence and their adjacent <50 μm and >50 μm dust fractions across a selection of 41 major and trace elements. This approach is used to investigate samples from three fully arid deserts: the An Nafud in Saudi Arabia, the Negev in Israel, and the Mojave in the USA, which are compared to the significantly different environment of the semi-arid Knersvlakte in South Africa. A new in situ trace element analysis protocol was developed to perform femto- and nanosecond sector-field LA-ICP-MS microanalyses at high-spatial resolution, which allows us to measure the most recent varnish layers for their comparison with recent dust. In agreement with previous studies, all varnishes are enriched in Mn, Pb, Ce, Co, Ba, Zn, Ni, and the Rare-Earth Elements (REE). Here we demonstrate that fine (<50 μm) dust is characterized by similar trace element trends as the varnishes, at overall lower mass fractions. Dust >50 μm has low trace element mass fractions, and enrichment patterns plotting distinctly away from varnish and fine dust. Based on these geochemical patterns, our results indicate a general enrichment mechanism from fine dust to varnish. Previous studies suggested dust to play an integral role in providing the trace elements that are incorporated into the varnish by pH-Eh fluctuations in short-term rain and fog events. We amalgamate and refine previous growth models by providing direct evidence that leaching of about 10% of the Mn and other trace elements from clay minerals in rain or fog droplets at pH ~5 and subsequent scavenging on varnish surfaces at pH ~8 leads integrated over time to the distinct enrichment patterns of the varnish, while initial Mn oxyhydroxide formation is suggested to follow pathways of metal oxide mediated photo-catalysis. For the semi-arid occurrence in the Knersvlakte we present a distinct growth model as both environment, varnish, and dust composition differ significantly from the arid settings. Here, thick, metallic-looking varnish occurs mainly on the rim of quartz pebbles, lacks microlamination, and likely has upscaled growth processes. Among other aspects, we suggest a more complex interplay between photo-catalysis, nocturnal condensation events on quartz pebbles with subsequent water trapping at the rock-soil-atmosphere interface, due to a salic top-soil layer, to mainly account for these differences. Unlabelled Image • First systematic study comparing youngest varnish layers to different fractions of recent dust • Higher similarity of varnish and fine dust excludes coarse fractions from varnish growth process. • Airborne and soil dust are geochemically alike, explaining similarities in varnishes from different geomorphological niches. • Differences between varnishes arise from environmental aspects, geomorphological position, and dust mineral assemblage. • Mn accumulation via 10% leaching from clays and metal-oxide-mediated photooxidation explain subaerial varnish growth. [ABSTRACT FROM AUTHOR]

Background: Toll‐like receptors play a substantial role in innate immunity and the effects of TLR4 genetic variants on cardiovascular diseases are still largely unknown. Therefore, we aimed to investigate the effects of TLR4 polymorphisms on cardiovascular diseases risk in the Saudi population. Methods: Three tag single‐nucleotide polymorphisms (rs2770150, rs10759931, and rs4986790) in TLR4 were studied on 222 unrelated patients with cardiovascular diseases and 190 healthy volunteers. Results: We found that, in patients over 60 years old, the frequency of the TT genotype in rs2770150 and the variant allele G in rs10759931 were higher compared to the control group. Based on gender, the genotype frequency of rs2770150 increases the risk for cardiovascular diseases in female patients by 3.6‐fold. The allele frequency for the G allele of rs10759931 increased the risk for CVDs in male patients by more than 1.5‐fold. Furthermore, the genotype frequency of rs2770150 had a significant association with cardiovascular diseases in patients without hypertension and G allele of rs10759931 significantly increased the risk of cardiovascular diseases in patients that smoked. After Bonferroni correction only patients without hypertension showed significant risk of CVD with rs2770150. Conclusion: A deeper understanding of the genetic variability of TLR4 will enable us to better identification of biomarkers for early detection and prognosis, and also enhance the decision‐making process of treatments for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Thymic stromal Lymphopoeitin (TSLP) is a key cytokine involved in inflammation and cancer progression. TSLP gene polymorphisms have been associated with increased susceptibility to cancer progression in different organs. We performed a control case study to examine the correlation of expression and polymorphisms of three nucleotides in TSLP with breast cancer (BC) risk in Saudi Arabian females. Materials and methods: The study was conducted on 116 healthy control subjects and 127 female patients with BC for the purpose of genotyping. Ten matching tissues provided data on immunohistochemistry to evaluate TSLP expression. Three SNPs (rs10043985, rs2289276, and rs3806933) were genotyped with TaqMan allelic discrimination assay. The patients' ages and estrogen receptor statuses were used to investigate the potential correlations between the different variations of TSLP genotypes and BC risk. Results: BC tissues expressed positive immuno‐staining for TSLP at a high rate compared to normal matching breast tissues. Malignant breast tumors exhibited higher TSLP expression than benign breast tumors. We also found that the rs3806933 (T) allele frequency decreased the risk of developing BC in the study population (OR = 0.356, p = 0.00027) significantly (0.356 times). Interestingly, statistical analysis revealed that the genotype mutant (AC) and the allele mutant (C) of rs10043985 within TSLP were significantly correlated with an increased BC risk (odds ratio [OR] = 4.762, confidence interval [CI] = 1.000–22.666, p = 0.03244; OR = 4.762, CI = 1.000–22.666, p = 0.03244; and OR = 4.575, CI = 0.975–21.464, p = 0.03516, respectively). In addition, the AC and AC + CC genotypes of TSLP rs10043985 were confirmed to be associated with an increased risk of BC risk in women aged above 48 years, compared with the AA genotype (AC and AC + CC vs. AA: OR = 9.468, CI = 0.493–181.768, p = 0.04537). Conclusion: The results reveal significant correlation between SNPs in TSLP and BC progression in Saudi Arabian female patients. [ABSTRACT FROM AUTHOR]

Melatonin, a natural agent, has multiple functions in animals as well as in plants. However, its possible roles in plants under abiotic stress are not clear. Nowadays, soil salinity is a major threat to global agriculture because a high soil salt content causes multiple stresses (hyperosmotic, ionic, and oxidative). Therefore, the aim of the present study was to explore: (1) the involvement of melatonin in biosynthesis of photosynthetic pigments and in regulation of photosynthetic enzymes, such as carbonic anhydrase (CA) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco); (2) the role of melatonin in osmoregulation by proline and carbohydrate metabolism; and (3) the function of melatonin in the antioxidant defense system under salinity. Outcomes of the study reveal that under non-saline conditions, application of melatonin (20 and 50 µM) improved plant growth, viz. shoot length, root length, shoot fresh weight (FW), root FW, shoot dry weight (DW), root DW and leaf area and physio-biochemical parameters [chlorophyll (Chl) a and b, proline (Pro) and total soluble carbohydrates (TSC) content, and increased the activity of CA and Rubisco]. However, tomato seedlings treated with NaCl exhibited enhanced Chl degradation, electrolyte leakage (EL), malondialdehyde (MDA) and reactive oxygen species (ROS; superoxide and hydrogen peroxide). ROS were detected in leaf and root. Interestingly, application of melatonin improved plant growth and reduced EL, MDA and ROS levels through upregulation of photosynthesis enzymes (CA, Rubisco), antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase and ascorbate reductase) and levels of non-enzymatic antioxidants [ascorbate (ASC) and reduced glutathione (GSH)], as well as by affecting the ASC—GSH cycle. Additionally, exogenous melatonin also improved osmoregulation by increasing the content of TSC, Pro and Δ1-pyrroline-5-carboxylate synthetase activity. These results suggest that melatonin has beneficial effects on tomato seedlings growth under both stress and non-stress conditions. Melatonin's role in tolerance to salt stress may be associated with the regulation of enzymes involved in photosynthesis, the antioxidant system, metabolism of proline and carbohydrate, and the ASC—GSH cycle. Also, melatonin could be responsible for maintaining the high ratios of GSH/GSSG and ASC/DHA. [ABSTRACT FROM AUTHOR]