White-tailed deer (Odocoileus virginianus) had substantial cumulative impacts on patterns of forest tree recruitment across most of northern Wisconsin between 1983 and 2013. The diagram shows the ...path model used to trace direct and cumulative effects of deer on patterns of sapling recruitment in Acer rubrum, Acer saccharum, and Populus tremuloides over this interval. Deer densities refer to 10-year average estimates from Wisconsin DNR’s Sex-Age-Kill model as customized for each of 48 Deer Management Units in northern Wisconsin. Saplings refers to the logged sums of 2.5–5cm DBH sapling numbers in these species as tallied over matching 10-year intervals from U.S. Forest Service FIA survey data on tree numbers and growth within 13,105 plots in this region. See Fig. 7 and Table 5. Image of deer used with permission by the Integration and Application Network, Univ. of Maryland Center for Environmental Science (ian.umces.edu/imagelibrary/). Display omitted
•Trees deer prefer to eat have failed to regenerate over the past 30years.•The mean, mode, and skew of sapling numbers in USFS FIA data reveal deer impacts.•Regeneration of less palatable trees declines in direct response to deer density.•Regeneration failures have already shifted forest composition and diversity.
Local, short- to medium-term studies make clear that white-tailed deer can greatly suppress tree growth and survival in palatable tree species. To assess how deer have broadly affected patterns of tree recruitment across northern Wisconsin, we analyzed recruitment success in 11 common trees species that vary in palatability across 13,105 USFS - FIA plots sampled between 1983 and 2013. We also examined how recruitment in these species covaried with estimated deer densities here. Saplings of five palatable species were scarce relative to less palatable species and showed highly skewed distributions. Scarcity and skew provide reliable signals of deer impacts even when deer have severely reduced recruitment and/or no reliable deer density data are available. Deer densities ranged from 2.3 to 23 deer per km2 over a 30year period. Sapling numbers in two maples (Acer) and aspen (Populus) with intermediate palatability declined sharply in apparent response to higher deer density. Path analysis also reveals that deer act to cumulatively depress sapling recruitment in these species over successive decades. Together, these approaches show that deer have strongly depressed sapling recruitment in all taxa except Abies and Picea. As these impacts are now propagating into larger sized trees, deer are also altering canopy composition and dynamics. The tools developed here provide efficient and reliable indicators for monitoring deer impacts on forest tree recruitment using consistent data collected by public agencies.
Alzheimer’s disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau ...(rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology.
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•Mice with human tau and amyloid mutations develop progressive neuropathology•We identify transcriptional changes associated with tau and amyloid pathology•Discrete co-expression networks are associated with the progression of tau pathology•These are enriched for genes and pathways implicated in the onset of human AD
Castanho et al. use transgenic mice harboring human tau and amyloid precursor protein mutations to identify transcriptional changes associated with the progression of Alzheimer’s disease (AD) pathology. Their data support an immune-response component in the accumulation of tau and reveal molecular pathways associated with AD neuropathology.
Combining the selective AKT inhibitor, capivasertib, and SERD, fulvestrant improved PFS in a Phase III clinical trial (CAPItello-291), treating HR+ breast cancer patients following aromatase ...inhibitors, with or without CDK4/6 inhibitors. However, clinical data suggests CDK4/6 treatment may reduce response to subsequent monotherapy endocrine treatment. To support understanding of trials such as CAPItello-291 and gain insight into this emerging population of patients, we explored how CDK4/6 inhibitor treatment influences ER+ breast tumour cell function and response to fulvestrant and capivasertib after CDK4/6 inhibitor treatment. In RB+, RB- T47D and MCF7 palbociclib-resistant cells ER pathway ER and Greb-1 expression were reduced versus naïve cells. PI3K-AKT pathway activation was also modified in RB+ cells, with capivasertib less effective at reducing pS6 in RB+ cells compared to parental cells. Expression profiling of parental versus palbociclib-resistant cells confirmed capivasertib, fulvestrant and the combination differentially impacted gene expression modulation in resistant cells, with different responses seen in T47D and MCF7 cells. Fulvestrant inhibition of ER-dependent genes was reduced. In resistant cells, the combination was less effective at reducing cell cycle genes, but a consistent reduction in cell fraction in S-phase was observed in naïve and resistant cells. Despite modified signalling responses, both RB+ and RB- resistant cells responded to combination treatment despite some reduction in relative efficacy and was effective in vivo in palbociclib-resistant PDX models. Collectively these findings demonstrate that simultaneous inhibition of AKT and ER signalling can be effective in models representing palbociclib resistance despite changes in pathway dependency.
Recent data suggest that the adhesion docking protein NEDD9/HEF1/Cas-L is a critical regulator of adhesion-dependent signalling pathways during mammary tumour development. Multiple phosphorylation ...modifications of NEDD9 regulate interaction with downstream protein partners, thus the regulation of NEDD9 phospho-forms is an important point of control for NEDD9 function. As estradiol (E2) plays a central role in the development and progression of breast cancer, we have investigated NEDD9 phospho-form regulation in MCF-7 estrogen receptor (ER)-positive breast cancer cells in response to estrogen. We find that levels of the 105-kDa NEDD9 phospho-form are significantly increased after 3
days of estrogen exposure, and this is suppressed by the anti-estrogen tamoxifen. Analysis of protein decay kinetics following treatment with the protein synthesis inhibitor cycloheximide indicates that increased 105-kDa levels are due to a slower rate of protein decay. Moreover, exogenous expression of NEDD9 failed to induce spreading in the presence of E2, and this was reversed by tamoxifen treatment. Finally, we show that the 105-kDa NEDD9 phospho-form appears to predominate in ER-positive versus ER-negative breast cancer cell lines. Taken together, our results suggest that estradiol may suppress phospho-form-specific functions of NEDD9.
► Estradiol regulates the stability of NEDD9 phospho-forms. ► NEDD9-mediated cell spreading is inhibited by estradiol. ► Estradiol suppresses phospho-form-specific functions of NEDD9.
Current literature suggests that seeing and bagging game, among other experiences, play a major role in overall satisfaction for hunters. In addition, research highlights relationships that harvest ...expectations may have with harvest success and in explaining satisfaction. We add to the multiple satisfactions concept that, despite other derived benefits, harvest success may be fundamental to sustain participation and duck (Anatidae) hunters themselves are agents of their own success. We used data from mail surveys conducted between 2007–2015 of Wisconsin, USA, waterfowl hunters to investigate the role of duck hunter behavior and expectations in explaining differences in season satisfaction ratings. We found that duck hunters who spent more days afield, scouted prior to hunting, were mobile during the season, and utilized public lands harvested substantially more ducks than those who did not put effort into these behaviors. Furthermore, we find evidence in support of previous work that by examining the effect of harvest success through the lens of harvest expectations, it better describes satisfaction than either measure did alone among this population of duck hunters. Based on past experiences, duck hunters may develop unrealistic expectations that doom them to dissatisfactory harvests. These results provide assistance to managers and conservationists in helping hunters understand and set realistic harvest expectations, achieve their harvest goals, and continue to be active hunters.
In the decades after the Civil War, Southerners wrote and published their own history textbooks for secondary schools. These “mint julep textbooks,” as the Southern all-white editions were called by ...the 1960s, reinforced a Lost Cause narrative of the war for Southern audiences while competing with Northern versions of events. In this study, we employ both historical narrative and content analysis of six textbooks’ portrayals of John Brown, John Wilkes Booth, and Nathan Bedford Forrest. The textbooks that are compared– three Southern and three Northern – were written from the 1870s through the 1910s. While subtle but important differences emerge between the Northern and Southern depiction of these three figures, an even more important trend developed when analyzing change over time. In this article we conclude that, as time progressed, Southern versions of events increasingly impacted Northern textbooks. By the 1930s, the mint julep version of these three figures became the national consensus, as reflected in the work of historian David Saville Muzzey. This consensus around events like the raid at Harpers Ferry, the assassination of Lincoln, and the massacre at Fort Pillow lasted for much of the 20th century. By the early 20th century, Northerners appeased Southern interests in the writing of history textbooks.
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