Lithics in the West: Using Lithic Analysis to Solve Archeological Problems in Western North America

Lithics in the West seeks to link the rich archaeological lithic data base from the western United States with some of the contemporary theoretical and analytical approaches used in global settings in stone tool and debitage analysis today. The book highlights the role that lithic analysis (in all its forms) plays in solving research problems in the prehistory of western North America. The book covers important archaeological sites and projects in Montana, Wyoming, Idaho, Colorado, and Washington. Contributors include William Andrefsky, Jr., Robert Kelly, Nicole Waguespack, Pei-Lin Yu, Doug MacDonald, Robert Brunswig, Scott Carpenter, Jackie Cook, David Diggs, Philip Fisher, Katie Harris, Brian Ostahowski, Mary Prasciunas, Ken Reid, and Todd Surovell.https://scholarworks.umt.edu/umpress-oabooks/1000/thumbnail.jp

FasL Gene–Deficient Mice Display a Limited Disruption in Spermatogenesis and Inhibition of Mono-(2-ethylhexyl) Phthalate–Induced Germ Cell Apoptosis

FasL (TNFSF6, CD95L) is hypothesized to trigger testicular germ cell apoptosis that normally occurs during a distinct peripubertal period as well as in response to toxicant-induced Sertoli cell injury. To test this hypothesis, we evaluated the testis of FasL gene–deficient mice (FasL−/−) at two distinct developmental ages (postnatal day [PND] 28 and 44) and after toxicant-induced Sertoli cell injury. Testicular cross sections from peripubertal (PND 28) FasL−/− mice showed significant increases in the basal germ cell apoptotic index (AI; 20.58 ± 4.59) as compared to the testis of C57BL/6J wild-type mice (5.16 ± 0.08) and closely correlated with increased expression of TRAIL protein in the testis of FasL−/− mice. A limited, but significant, number of seminiferous tubules in the testis of PND 28 FasL−/− mice showed a severe loss of germ cells with only Sertoli cells present. In contrast, no apparent gross histological changes were observed in the testis of adult (PND 44) FasL−/− mice. However, PND 44 FasL−/− mice did show a 51% reduction in homogenization-resistant elongate spermatids as compared to age-matched C57BL/6J mice. Exposure of PND 28 FasL−/− mice to mono-(2-ethylhexyl) phthalate (MEHP), a well-described Sertoli cell toxicant, unexpectedly caused a rapid decrease in the germ cell AI that paralleled increased levels of the CFLAR (c-FLIP) protein, a known inhibitor of death receptor signaling. In contrast, MEHP treatment did not decrease c-FLIP levels in PND 28 C57BL/6J mice. Taken together, these findings indicate that FasL protein expression is required during the peripubertal period for the proper regulation of germ cell apoptosis that occurs normally during this period. The influence of FasL on the cellular regulation of c-FLIP protein levels appears to be a unique mechanism for modulating germ cell apoptosis after toxicant-induced Sertoli cell injury

Production of polyploids from cultured shoot tips of Eucalyptus globulus Labill by treatment with colchicine

Polyploids from cultured shoot tips of Eucalyptus globulus were produced by treatment with colchicine. Results showed that the combination of 0.5% colchicine and treating multiple shoot clumps for 4 days was the most appropriate conditions for E. globulus polyploidy induction and the effect of the use of multiple shoot clumps for colchicine polyploidy-induced was better than single buds. By comparing the polyploidy plants with normal diploid ones in morphology, leaves of polyploid plants were thicker, larger, and darker green. The chromosome number of polyploidy plants that had been identified in morphology was 2n = 4x = 44, while that of diploids was 2n = 2x = 22

A quantitative comparison of in-line coating thickness distributions obtained from a pharmaceutical tablet mixing process using discrete element method and terahertz pulsed imaging

The application of terahertz pulsed imaging (TPI) in the in-line configuration to monitor the coating thickness distribution of pharmaceutical tablets has the potential to improve the performance and quality of the spray coating process. In this study, an in-line TPI method is used to measure coating thickness distributions on pre-coated tablets during mixing in a rotating pan, and compared with results obtained numerically using the discrete element method (DEM) combined with a ray-tracing technique. The hit rates (i.e. the number of successful coating thickness measurements per minute) obtained from both terahertz in-line experiments and the DEM/ray-tracing simulations are in good agreement, and both increase with the number of baffles in the mixing pan. We demonstrate that the coating thickness variability as determined from the ray-traced data and the terahertz in-line measurements represents mainly the intra-tablet variability due to relatively uniform mean coating thickness across tablets. The mean coating thickness of the ray-traced data from the numerical simulations agrees well with the mean coating thickness as determined by the off-line TPI measurements. The mean coating thickness of in-line TPI measurements is slightly higher than that of off-line measurements. This discrepancy can be corrected based on the cap-to-band surface area ratio of the tablet and the cap-to-band sampling ratio obtained from ray-tracing simulations: the corrected mean coating thickness of the in-line TPI measurements shows a better agreement with that of off-line measurements

Pathway analysis of kidney cancer using proteomics and metabolic profiling

BACKGROUND: Renal cell carcinoma (RCC) is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC). We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. RESULTS: Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values < 2.0 E-05) in glycolysis, propanoate metabolism, pyruvate metabolism, urea cycle and arginine/proline metabolism, as well as in the non-metabolic p53 and FAS pathways. In a pilot study using random urine samples from both ccRCC and control patients, we performed metabolic profiling and found that only sorbitol, a component of an alternative glycolysis pathway, is significantly elevated at 5.4-fold in RCC patients as compared to controls. CONCLUSION: Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy

Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats

Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance

BACKGROUND: The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC) is associated with frequent treatment failures (~90% in metastatic cases), and these tumors frequently contain PTEN abnormalities. RESULTS: Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis. CONCLUSION: Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories