Late Holocene expansion of ponderosa pine (\u3ci\u3ePinus ponderosa\u3c/i\u3e) in the Central Rocky Mountains, USA

Aim: Ponderosa pine (Pinus ponderosa) experienced one of the most extensive and rapid post-glacial plant migrations in western North America. We used plant macrofossils from woodrat (Neotoma) middens to reconstruct its spread in the Central Rocky Mountains, identify other vegetation changes coinciding with P. ponderosa expansion at the same sites, and relate P. ponderosa migrational history to both its modern phylogeography and to a parallel expansion by Utah juniper (Juniperus osteosperma). Location: Central Rocky Mountains, Wyoming and Montana, and Black Hills, Wyoming and South Dakota, USA. Methods: Plant macrofossils were analysed in 90 middens collected at 14 widely separated sites in the northern part of the range of P. ponderosa var. scopulorum. Middens with and without P. ponderosa were 14C dated to pinpoint time of appearance at each site. Sensitivity experiments using a bioclimatic model were used to evaluate potential climatic drivers of late Holocene expansion. Results: Pinus ponderosa colonized the Black Hills region by at least 3850 yr bp (all ages given in calendar years before present). It expanded into the eastern Bighorn Mountains of northern Wyoming by 2630 yr bp, quickly spreading north in the western Bighorns from 1400 to 1000 yr bp. Concurrent with the latter expansion, P. ponderosa spread c. 350 km to the Little Belt and Big Belt Mountains in western Montana, establishing its northern limit and the modern introgression zone between var. scopulorum and var. ponderosa. Expansion in the Central Rockies of P. ponderosa involved two known haplotypes

Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacity

Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear.; Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels.; There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss.; There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household

Late Holocene expansion of ponderosa pine (\u3ci\u3ePinus ponderosa\u3c/i\u3e) in the Central Rocky Mountains, USA

Aim: Ponderosa pine (Pinus ponderosa) experienced one of the most extensive and rapid post-glacial plant migrations in western North America. We used plant macrofossils from woodrat (Neotoma) middens to reconstruct its spread in the Central Rocky Mountains, identify other vegetation changes coinciding with P. ponderosa expansion at the same sites, and relate P. ponderosa migrational history to both its modern phylogeography and to a parallel expansion by Utah juniper (Juniperus osteosperma). Location: Central Rocky Mountains, Wyoming and Montana, and Black Hills, Wyoming and South Dakota, USA. Methods: Plant macrofossils were analysed in 90 middens collected at 14 widely separated sites in the northern part of the range of P. ponderosa var. scopulorum. Middens with and without P. ponderosa were 14C dated to pinpoint time of appearance at each site. Sensitivity experiments using a bioclimatic model were used to evaluate potential climatic drivers of late Holocene expansion. Results: Pinus ponderosa colonized the Black Hills region by at least 3850 yr bp (all ages given in calendar years before present). It expanded into the eastern Bighorn Mountains of northern Wyoming by 2630 yr bp, quickly spreading north in the western Bighorns from 1400 to 1000 yr bp. Concurrent with the latter expansion, P. ponderosa spread c. 350 km to the Little Belt and Big Belt Mountains in western Montana, establishing its northern limit and the modern introgression zone between var. scopulorum and var. ponderosa. Expansion in the Central Rockies of P. ponderosa involved two known haplotypes

Occurrence of fecal coliform bacteria in selected streams in Wyoming, 1990-99 /

Shipping list no.: 2001-0080-P.Caption title.Includes bibliographical references (p. 8).Mode of access: Internet

Expression of Ror2 mediates invasive phenotypes in renal cell carcinoma.

Ror2 is a Wnt ligand receptor that is overexpressed in a variety of tumors including clear cell renal cell carcinoma (ccRCC). Here we demonstrate that expression of wild type Ror2 results in increased tumorigenic properties in in vitro cell culture and in vivo xenograft models. In addition, Ror2 expression produced positive changes in both cell migration and invasion, which were dependent on matrix metalloprotease 2 (MMP2) activity. Mutations in key regions of the kinase domain of Ror2 resulted in the abrogation of increased tumor growth, cell migration, and cell invasion observed with expression of wild-type Ror2. Finally, we examined Ror2 expression as a prognostic biomarker for ccRCC utilizing the TCGA ccRCC dataset. High expression of Ror2 showed a significant correlation with higher clinical stage, nuclear grade, and tumor stage. Furthermore, high expression of Ror2 in ccRCC patients correlated with significant lower overall survival, cancer specific survival, and recurrence free survival. Together, these findings suggest that Ror2 plays a central role in influencing the ccRCC phenotype, and can be considered as a negative prognostic biomarker and potential therapeutic target in this cancer

Ror2 expression regulates cell invasion in RCC cells.

<p>Analysis of invasive potential using Boyden matrigel coated chamber assays under normal culture conditions with <b>A</b>) 786-0 cells show a significant reduction in invasion in both independent shRNA Ror2 knockdowns in comparison with parental 786-0 and vector control cells (representative images shown below). Additionally, <b>B</b>) 786-0 & <b>C</b>) HEK293T cells under normal culture conditions show a significant increase in cell invasion with overexpression of wild-type Ror2 that is reduced with expression of Ror2-DM (representative images shown below). The percentage of area covered was quantitated from random fields using ImageJ. <i>P</i>-values were calculated using an Anova one-way analysis with error bars representing stdev shown (*<.05, **<.001).</p

Ror2 regulation of MMP2 expression in RCC cells is dependent upon an intact kinase domain.

<p>Quantitative RT-PCR for 786-0 cells shows a significant correlated decrease in <b>A</b>) Ror2 and <b>B</b>) MMP2 mRNA levels in both shRNA knockdown cell lines relative to control. <b>C</b>) Additionally, induction of wildtype Ror2 and Ror2-DM is evident following treatment with doxycycline (500 ng/ml). <b>D</b>) But a matching increase in MMP2 is only seen with overexpression of wildtype Ror2. For all quantitative RT-PCR assays, transcript values were normalized to β-actin RNA internal standard with fold change calculated in reference to either 786-0 control or unstimulated GFP expressing cells. Error bars represent SEM across triplicates of a representative duplicated experiment. Gelatin Zymography shows increased levels of both the precursor pro-MMP2 and its cleaved active form with overexpression of wildtype Ror2 relative to GFP vector control in both <b>E</b>) 786-0 and <b>F</b>) HEK293T cells. Quantification of the levels of active MMP2 normalized to the media only control (Con) is shown below each gel. <b>G</b>) Invasion of 786-0 cells seeded in Boyden matrigel coated chambers under normal culture conditions show a significant decrease upon treatment with MMP2 inhibitor (OA-Hy - 60 uM) in both independent shRNA knockdowns and Ror2 overexpression in comparison with vehicle control. The percentage of area covered was quantitated from random fields using ImageJ. Error bars represent stdev across duplicates of a representative duplicated experiment. <i>P</i>-values were calculated using an Anova one-way analysis (*<.05, **<.001).</p

Summary of clinical characteristics of patients in the TCGA ccRCC dataset.

<p>Summary of clinical characteristics of patients in the TCGA ccRCC dataset.</p

High Ror2 expression correlates with increased tumor growth and stage in primary human RCC tumors.

<p>Tumor percentage breakdowns of TCGA ccRCC cases (468) stratified by Ror2-High and Ror2-Low expression show Ror2-High tumors exhibiting significant increases in <b>A</b>) tumor size, <b>B</b>) higher nuclear grade, <b>C</b>) clinical stage, and <b>D</b>) tumor stage. <i>P</i>-values were calculated using either an Anova one-way analysis or Fisher's exact test (*<.05, **<.001).</p

Expression of Ror2 promotes <i>in vivo</i> tumor growth and invasion.

<p><b>A&C</b>) Tabulated rates of successful injection and growth of all 786-0 xenograft tumors are shown. <b>B</b>) Average tumor size (cm) with error bars showing stdev for resulting xenograft tumors following paired orthotropic injections of 786-0 cells containing either the control empty vector, pcDNA6 or hRor2 exhibited a trend to increased <i>in vivo</i> tumor growth with Ror2 overexpression. <b>D</b>) Average tumor size (mm) with error bars showing stdev for resulting xenograft tumors following subcutaneous injection of 786-0 cells containing either the control empty vector, GFP, wild-type Ror2, or Ror2-DM showed a significant increase in <i>in vivo</i> tumor growth with wild-type Ror2 overexpression. <i>P</i>-values were calculated using an Anova one-way analysis (*<.05 **<.01). <b>E</b>) Representative image of an orthotopic xenograft consisting of 786-0 vector control cells. <b>F</b>) Increased invasion of local tissues was evident with Ror2 expression, with arrows highlighting areas of continued invasion into the spleen.</p