Disruption of movement patterns due to alterations in habitat connectivity is a pervasive effect of humans on animal populations. In many terrestrial and aquatic systems, there is increasing tension ...between the need to simultaneously allow passage of some species while blocking the passage of other species. We explore the ecological basis for selective fragmentation of riverine systems where the need to restrict movements of invasive species conflicts with the need to allow passage of species of commercial, recreational, or conservation concern. We develop a trait-based framework for selective fish passage based on understanding the types of movements displayed by fishes and the role of ecological filters in determining the spatial distributions of fishes. We then synthesize information on trait-based mechanisms involved with these filters to create a multidimensional niche space based on attributes such as physical capabilities, body morphology, sensory capabilities, behavior, and movement phenology. Following this, we review how these mechanisms have been applied to achieve selective fish passage across anthropogenic barriers. To date, trap-and-sort or capture-translocation efforts provide the best options for movement filters that are completely species selective, but these methods are hampered by the continual, high cost of manual sorting. Other less effective methods of selective passage risk collateral damage in the form of lower or higher than desired levels of passage. Fruitful areas for future work include using combinations of ecological and behavioral traits to passively segregate species; using taxon-specific chemical or auditory cues to direct unwanted species away from passageways and into physical or ecological traps while attracting desirable species to passageways; and developing automated sorting mechanisms based on fish recognition systems. The trait-based approach proposed for fish could serve as a template for selective fragmentation in other ecological systems.
The American theater was not ignorant of the developments brought on by World War II, and actively addressed and debated timely, controversial topics for the duration of the war, including neutrality ...and isolationism, racism and genocide, and heroism and battle fatigue. Productions such as Watch on the Rhine (1941), The Moon is Down (1942), Tomorrow the World (1943), and A Bell for Adano (1944) encouraged public discussion of the war's impact on daily life and raised critical questions about the conflict well before other forms of popular media. American drama of the 1940s is frequently overlooked, but the plays performed during this eventful decade provide a picture of the rich and complex experience of living in the United States during the war years. McLaughlin and Parry's work fills a significant gap in the history of theater and popular culture, showing that American society was more divided and less idealistic than the received histories of the WWII home front and the entertainment industry recognize.
Extracts of paw paw ( Asimina triloba, Annonaceae) are among the most potent of the 3500 species of higher plants screened for bioactive compounds in our laboratories at Purdue University. The paw ...paw is a small tree native to eastern North America; its edible fruits (sometimes referred to as "Indiana Bananas") have nurtured mankind for centuries. Activity-directed fractionation of the paw paw extracts, using the brine shrimp lethality bioassay, led to the isolation and molecular characterization of over 50 unique annonaceous acetogenins. Fractionation of extracts from related species resulted in the identification of over 150 additional acetogenins. The annonaceous acetogenins are derivatives of long-chain (C32 or C34) fatty acids. They are potent inhibitors of mitochondrial (complex I) as well as cytoplasmic (anaerobic) production of adenosine triphosphate (ATP) and the related nucleotides. The powerful cytotoxicity, in vivo antitumor, pesticidal, antimalarial, anthelmintic, piscicidal, antiviral, and antimicrobial effects indicated a myriad of potentially useful applications. Commercial development of these compounds uses natural mixtures of active components, incorporated into pesticidal, topical, and dietary supplement products. Successful applications and commercial products include a shampoo, highly effective in treating infestations of head lice, fleas, and ticks; a series of pesticidal sprays, which protects host plants against a diversity of pests; and an ointment for treatment of oral herpes (HSV-1) and other skin afflictions. The extract (in capsule form) enhances a mixture of natural anthelmintics. In addition, an encapsulated extract has been effectively used by certain cancer patients as a botanical supplement product.
Cancer stem cells (CSCs) are a promising target for cancer therapy, particularly for metastatic lung cancers, but how CSCs are regulated is largely unknown. We identify two proteins, SLUG (encoded by ...SNAI2 gene) and SOX9, which are associated with advanced stage lung cancers and are implicated in the regulation of CSCs. Inhibition of either SLUG or SOX9 sufficiently inhibits CSCs in human lung cancer cells and attenuates experimental lung metastasis in a xenograft mouse model. Correlation between SLUG and SOX9 levels was observed remarkably, we therefore sought to explore their mechanistic relationship and regulation. SLUG, beyond its known function as an epithelial-mesenchymal transition transcription factor, was found to regulate SOX9 by controlling its stability via a post-translational modification process. SLUG interacts directly with SOX9 and prevents it from ubiquitin-mediated proteasomal degradation. SLUG expression and binding are necessary for SOX9 promotion of lung CSCs and metastasis in a mouse model. Together, our findings provide a novel mechanistic insight into the regulation of CSCs via SLUG-SOX9 regulatory axis, which represents a potential novel target for CSC therapy that may overcome cancer chemoresistance and relapse.
Wetlands provide numerous ecosystem services, from habitat provision to pollutant removal, floodwater storage, and microclimate regulation. Delivery of particular services relies on specific ...ecological functions, and thus to varying degree on wetland ecological condition, commonly quantified as departure from minimally impacted reference sites. Condition assessments are widely adopted as regulatory indicators of ecosystem function, and for some services (e.g., habitat) links between condition and function are often direct. For others, however, links are more tenuous, and using condition alone to enumerate ecosystem value (e.g., for compensatory mitigation) may underestimate important services. Hydrologic function affects many services cited in support of wetland protection both directly (floodwater retention, microclimate regulation) and indirectly (biogeochemical cycling, pollutant removal). We investigated links between condition and hydrologic function to test the hypothesis, embedded in regulatory assessment of wetland value, that condition predicts function. Condition was assessed using rapid and intensive approaches, including Florida's official wetland assessment tool, in 11 isolated forested wetlands in north Florida (USA) spanning a land use intensity gradient. Hydrologic function was assessed using hydrologic regime (mean, variance, and rates of change of water depth), and measurements of groundwater exchange and evapotranspiration (ET). Despite a wide range in condition, no systematic variation in hydrologic regime was observed; indeed reference sites spanned the full range of variation. In contrast, ET was affected by land use, with higher rates in intensive (agriculture and urban) landscapes in response to higher leaf area. ET determines latent heat exchange, which regulates microclimate, a valuable service in urban heat islands. Higher ET also indicates higher productivity and thus carbon cycling. Groundwater exchange regularly reversed flow direction at all sites in response to rainfall. This buffering effect on regional aquifer levels, an underappreciated service of isolated wetlands, was provided regardless of condition. Intensive landscapes may benefit most from the hydrologic services that wetlands provide because that is where certain services (floodwater storage, microclimate regulation) are realized. While the portfolio of wetland services clearly changes with disturbance, our results support a revised approach to wetland valuation that recognizes the services that accrue from sustained or enhanced functions in these "working wetlands."
The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving ...consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (~22 × ) and seven to ~1 × coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence.
All wetland ecosystems are controlled by water table and soil saturation dynamics, so any local-scale deviation in soil elevation and thus water table position represents variability in this primary ...control. Wetland microtopography is the structured variability in soil elevation and is typically categorized into a binary classification of local high points (hummocks) and local low points (hollows). Although the influence of microtopography on vegetation composition and biogeochemical processes in wetlands has received attention around the globe, its role in forested wetlands is still less understood. We studied relationships among microtopography and understory vegetation communities, tree biomass, and soil chemistry in 10 black ash (Fraxinus nigra Marshall) wetlands in northern Minnesota, USA. To do so, we combined a 1 cm resolution surface elevation model generated from terrestrial laser scanning (TLS) with colocated water table, vegetation, and soil measurements. We observed that microtopography was an important structural element across sites, where hummocks were loci of greater species richness; greater midstory and canopy basal area; and higher soil concentrations of chloride, phosphorus, and base cations. In contrast, hollows were associated with higher soil nitrate and sulfate concentrations. We also found that the effect of microtopography on vegetation and soils was greater at wetter sites than at drier sites, suggesting that the distance-to-mean water table is a primary determinant of wetland biogeochemistry. These findings highlight clear controls of microtopography on vegetation and soil distributions while also supporting the notion that microtopography arises from feedbacks that concentrate biomass, soil nutrients, and productivity on microsite highs, especially in otherwise wet conditions. We therefore conclude that microtopography is a fundamental organizing structure in black ash wetlands.
Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape ...functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.
Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules ...that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date.
Previous studies of the genetic landscape of Ireland have suggested homogeneity, with population substructure undetectable using single-marker methods. Here we have harnessed the haplotype-based ...method fineSTRUCTURE in an Irish genome-wide SNP dataset, identifying 23 discrete genetic clusters which segregate with geographical provenance. Cluster diversity is pronounced in the west of Ireland but reduced in the east where older structure has been eroded by historical migrations. Accordingly, when populations from the neighbouring island of Britain are included, a west-east cline of Celtic-British ancestry is revealed along with a particularly striking correlation between haplotypes and geography across both islands. A strong relationship is revealed between subsets of Northern Irish and Scottish populations, where discordant genetic and geographic affinities reflect major migrations in recent centuries. Additionally, Irish genetic proximity of all Scottish samples likely reflects older strata of communication across the narrowest inter-island crossing. Using GLOBETROTTER we detected Irish admixture signals from Britain and Europe and estimated dates for events consistent with the historical migrations of the Norse-Vikings, the Anglo-Normans and the British Plantations. The influence of the former is greater than previously estimated from Y chromosome haplotypes. In all, we paint a new picture of the genetic landscape of Ireland, revealing structure which should be considered in the design of studies examining rare genetic variation and its association with traits.
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