Hexavalent chromium, Cr(VI), is a known carcinogen and environmental health concern. It has been established that reactive oxygen species, genomic instability, and DNA damage repair deficiency are ...important contributors to the Cr(VI)-induced carcinogenesis mechanism. However, some hallmarks of cancer remain under-researched regarding the mechanism behind Cr(VI)-induced carcinogenesis. Increased lipogenesis is important to carcinogenesis and tumorigenesis in multiple types of cancers, yet the role increased lipogenesis has in Cr(VI) carcinogenesis is unclear. We report here that Cr(VI)-induced transformation of three human lung cell lines (BEAS-2B, BEP2D, and WTHBF-6) resulted in increased lipogenesis (palmitic acid levels), and Cr(VI)-transformed cells had an increased expression of key lipogenesis proteins (ATP citrate lyase ACLY, acetyl-CoA carboxylase ACC1, and fatty acid synthase FASN). We also determined that the Cr(VI)-transformed cells did not exhibit an increase in fatty acid oxidation or lipid droplets compared to their passage-matched control cells. Additionally, we observed increases in ACLY, ACC1, and FASN in lung tumor tissue compared with normal-adjacent lung tissue (in chromate workers that died of chromate-induced tumors). Next, using a known FASN inhibitor (C75), we treated Cr(VI)-transformed BEAS-2B with this inhibitor and measured cell growth, FASN protein expression, and growth in soft agar. We observed that FASN inhibition results in a decreased protein expression, decreased cell growth, and the inhibition of colony growth in soft agar. Next, using shRNA to knock down the FASN protein in Cr(VI)-transformed BEAS-2B cells, we saw a decrease in FASN protein expression and a loss of the xenograft tumor development of Cr(VI)-transformed BEAS-2B cells. These results demonstrate that FASN is important for Cr(VI)-transformed cell growth and cancer properties. In conclusion, these data show that Cr(VI)-transformation in vitro caused an increase in lipogenesis, and that this increase is vital for Cr(VI)-transformed cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Two experiments (Exp.) were conducted to validate a 3-point model for the regression method of determining ME, using canola meal (CM) and wheat as test ingredients (TI). Corn-soybean meal-based test ...diets (TD) contained 0, 100, 200, or 300 g/kg CM, added at the proportional expense of all energy contributing ingredients for Exp. 1, and 0, 150, 300, or 450 g/kg wheat for Exp. 2. For each Exp., 192 Cobb 500 male broiler chickens were weighed and allotted by BW to 1 of 4 treatments at d 21 post hatching in a randomized complete block design. Growth performance and metabolizability responses were evaluated for linear and quadratic effects using orthogonal contrasts, and ileal digestible energy (IDE), ME, and MEn of TI were determined by regressing the TI-associated energy against the dry matter intake of TI using a generalized linear model. Four data sets were used to determine ME, using all possible 3 and 4-point combinations of TD in each Exp. Increasing TI inclusion elicited linear decreases (P < 0.01) in the digestibility and metabolizability of DM and GE in the 2 studies. The ME of CM obtained from the 4 data sets ranged from 1,731 to 1,992 kcal/kg DM, however, excluding the highest concentration of CM produced the highest estimate of ME, whereas the other 3 sets ranged from 1,731 to 1,793 kcal/kg DM. The ME of wheat from the 4 data sets had a smaller range of 3,041 to 3,106 kcal/kg DM. Excluding the highest concentration of either TI produced higher standard errors for the estimate of ME compared to the other 3 sets (42 and 36% greater SE, respectively). Results for IDE and MEn were similar. These data indicate that there is no difference in the variation of estimates between the 3 and 4-point models, provided that the inclusion of the TI is adequate and both models represent the linearity and variability of responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
"This monograph weaves together fundamentals of Mikhail Leonidovich Gromov's hyperbolic groups with the theory of cube complexes dual to spaces with walls. Many fundamental new ideas and ...methodologies are presented here for the first time: A cubical small-cancellation theory generalizing ideas from the 1960's, a version of "Dehn Filling" that works in the category of special cube complexes, and a variety of new results about right-angled Artin groups. The book culminates by providing an unexpected new theorem about the nature of hyperbolic groups that are constructible as amalgams. Among the stunning applications, are the virtual fibering of cusped hyperbolic 3-manifolds and the resolution of R.J. Baumslag's conjecture on the residual finiteness of one-relator groups with torsion. Most importantly, the book outlines the author's program towards the resolution of the most important remaining conjectures of William Thurston, and achieves
Fragile X syndrome (FXS) is an inherited form of intellectual disability that is usually caused by expansion of a polymorphic CGG repeat in the 5′ untranslated region of the X‐linked FMR1 gene, which ...leads to hypermethylation and transcriptional silencing. Two non‐neurological phenotypes of FXS are enlarged testes and connective tissue dysplasia, which could be caused by alterations in a growth factor signaling pathway. FXS patients also frequently have autistic‐like symptoms, suggesting that the signaling pathways affected in FXS may overlap with those affected in autism. Identifying these pathways is important for both understanding the effects of FMR1 inactivation and developing treatments for both FXS and autism. Here we show that decreasing the levels of the insulin‐like growth factor (Igf) receptor 1 corrects a number of phenotypes in the mouse model of FXS, including macro‐orchidism, and that increasing the levels of IGF2 exacerbates the seizure susceptibility phenotype. These results suggest that the pathways altered by the loss of the FMR1‐encoded protein (FMRP) may overlap with the pathways affected by changes in Igf signaling or that one or more of the proteins that play a role in Igf signaling could interact with FMRP. They also indicate a new set of potential targets for drug treatment of FXS and autism spectrum disorders.
Genetic changes in the levels of Igf signaling proteins alter several phenotypes in Fragile X mice.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
•First study to measure chromosomal chemical dispersant toxicity in marine mammal cells.•Corexit 9500 is cytotoxic and genotoxic in sperm whale skin cells.•Corexit 9527 is cytotoxic and genotoxic in ...sperm whale skin cells.•Corexit 9527 was less cytotoxic, but more genotoxic than Corexit 9500.
The 2010 Deepwater Horizon oil rig explosion in the Gulf of Mexico drew attention to the need for toxicological studies of chemical dispersants. We are still learning the effects these spills had on wildlife. Little is known about the toxicity of these substances in marine mammals. The objective of this study was to determine the toxicity of the two dispersants (Corexit 9500 and 9527). Corexit 9500 and 9527 were both cytotoxic to sperm whale skin fibroblasts. Corexit 9527 was less cytotoxic than 9500. S9 mediated metabolism did not alter cytotoxicity of either dispersant. Both dispersants were genotoxic to sperm whale skin fibroblasts; S9 mediated metabolism increased Corexit 9527 genotoxicity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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Mixed 3-manifolds are virtually special PRZYTYCKI, PIOTR; WISE, DANIEL T.
Journal of the American Mathematical Society,
04/2018, Volume:
31, Issue:
2
Journal Article
Peer reviewed
Open access
Let M be a compact oriented irreducible 3-manifold which is neither a graph manifold nor a hyperbolic manifold. We prove that \pi _1M is virtually special.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
Major depression is associated with altered static functional connectivity in various brain networks, particularly the default mode network (DMN). Dynamic functional connectivity is a novel tool with ...little application in affective disorders to date, and holds the potential to unravel fluctuations in connectivity strength over time in major depression. We assessed stability of connectivity in major depression between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in ruminative cognitions. Functional connectivity stability between the mPFC and PCC over the course of a resting-state functional magnetic resonance imaging (fMRI) scan was compared between medication-free patients with major depression and healthy controls matched for age, sex and handedness. We tested replicability of the results in an independent sample using multi-echo resting-state fMRI. The primary sample included 20 patients and 19 controls, while the validation sample included 19 patients and 19 controls. Greater connectivity variability was detected in major depression between mPFC and PCC. This was demonstrated in both samples indicating that the results were reliable and were not influenced by the fMRI acquisition approach used. Our results demonstrate that alterations within the DMN in major depression go beyond changes in connectivity strength and extend to reduced connectivity stability within key DMN regions. Findings were robustly replicated across two independent samples. Further research is necessary to better understand the nature of these fluctuations in connectivity and their relationship to the aetiology of major depression.
The Coompana Province, located between the three cratonic blocks of Australia, is significant for understanding the Proterozoic assembly of the continent. However, the basement rocks are completely ...covered and poorly understood, and as a result reconstructions are poorly constrained. Recent collection of detailed geophysical data sets and a stratigraphic drilling campaign in the eastern Coompana Province is used to understand the crustal architecture and tectonomagmatic history of the region. A north to northeast trending grain represents a series of amalgamated 1618–1526 Ma tectonic belts between the Western and South Australian cratons. These belts are cut by a northeast trending, shear‐bounded corridor of thinned crust, intruded by voluminous circa 1150–1140 Ma granite plutons. The new data indicate two main stages of deformation between circa 1200 and 1140 Ma. Circa 1200–1170 Ma east‐west extension was pervasive, causing widespread partial melting, shallowly dipping layering, recumbent folding, and minor shoshonitic magmatism. Circa 1160–1140 Ma deformation was partitioned into the northeast trending corridor, which focused transfer and emplacement of voluminous A‐type magmas. The two stages represent a switch from pervasive to localized deformation, with accompanying changes in magmatic style. Early pervasive extension caused progressive melt extraction, producing small sheets. Subsequent shearing locally promoted melt reorganization in the lower and middle crust. This caused local changes in rock strength with the continued partitioning of deformation into the oblique corridor. The crustal‐scale structures disrupted the lower crustal MASH zones, mobilizing and focusing the voluminous magmatism.
Key Points
Crustal architecture and tectonomagmatism in the Proterozoic Coompana Province are examined using aeromagnetic, seismic, and drill hole data
The province records a switch from widespread to local extension during the Mesoproterozoic, indicating a change in crustal behavior
The switch was triggered by deformation locally reorganizing melt, leading to a feedback between anatexis, magmatism, and deformation
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Background Stress is an established important contributor to the development of mental illness and stress related disorders. The biology implicated in the homeostasis of pathological stress ...mechanisms is not fully established. One of the difficulties with current techniques is the limitation in capturing chronic levels of cortisol as an expression of stress levels in humans. Hair samples can be used to evaluate cortisol levels averaged over relatively long periods of time, therefore providing a more valid measure of chronic levels of this hormone. A highly replicable technique to measure long-term cortisol could prove pivotal in improving our understanding of the role of stress in psychiatric disorders. Methods This review synthesises all the published studies relating hair cortisol concentration (HCC) to stress and to psychiatric disorders. It describes and summarises their findings with the aim of providing a summary picture of the current state of this line of research. Results The strongest finding to date is the replicable increases in hair cortisol associated with stressful life events. Findings in psychiatric disorders are more sparse and inconsistent. There is some support for the presence of raised HCC in major depressive disorders, and for lowered HCC in posttraumatic stress disorder, suggesting chronic hypercortisolaemia and hypocortisolaemia respectively. Conclusions HCC is a promising methodology to study chronic cortisol levels with the potential to help characterise psychiatric and stress related disorders. The combination of chronic and acute cortisol measurements has the potential for more accurately determining different aspects of the stress response, and ultimately for the development of a biological marker to aid diagnosis and response to treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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