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Статті в журналах з теми "Initiation to landscape"

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Автор: Grafiati

Опубліковано: 19 квітня 2023

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1

Sherstyuk, Vladimir V., Alexander I. Shevchenko, and Suren M. Zakian. "Epigenetic landscape for initiation of DNA replication." Chromosoma 123, no. 3 (December 17, 2013): 183–99. http://dx.doi.org/10.1007/s00412-013-0448-3.

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2

MONTGOMERY, D. R., and W. E. DIETRICH. "Channel Initiation and the Problem of Landscape Scale." Science 255, no. 5046 (February 14, 1992): 826–30. http://dx.doi.org/10.1126/science.255.5046.826.

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3

Robbins-Pianka, A., M. D. Rice, and M. P. Weir. "The mRNA landscape at yeast translation initiation sites." Bioinformatics 26, no. 21 (September 6, 2010): 2651–55. http://dx.doi.org/10.1093/bioinformatics/btq509.

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4

Kameda, Takeru, Katsura Asano, and Yuichi Togashi. "Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex." PLOS Computational Biology 17, no. 6 (June 14, 2021): e1009068. http://dx.doi.org/10.1371/journal.pcbi.1009068.

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Specific interaction between the start codon, 5’-AUG-3’, and the anticodon, 5’-CAU-3’, ensures accurate initiation of translation. Recent studies show that several near-cognate start codons (e.g. GUG and CUG) can play a role in initiating translation in eukaryotes. However, the mechanism allowing initiation through mismatched base-pairs at the ribosomal decoding site is still unclear at an atomic level. In this work, we propose an extended simulation-based method to evaluate free energy profiles, through computing the distance between each base-pair of the triplet interactions involved in recognition of start codons in eukaryotic translation pre-initiation complex. Our method provides not only the free energy penalty for mismatched start codons relative to the AUG start codon, but also the preferred pathways of transitions between bound and unbound states, which has not been described by previous studies. To verify the method, the binding dynamics of cognate (AUG) and near-cognate start codons (CUG and GUG) were simulated. Evaluated free energy profiles agree with experimentally observed changes in initiation frequencies from respective codons. This work proposes for the first time how a G:U mismatch at the first position of codon (GUG)-anticodon base-pairs destabilizes the accommodation in the initiating eukaryotic ribosome and how initiation at a CUG codon is nearly as strong as, or sometimes stronger than, that at a GUG codon. Our method is expected to be applied to study the affinity changes for various mismatched base-pairs.

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5

Brac de la Perrière, Bénédicte. "Initiations in the Burmese Ritual Landscape." Journal of Ethnology and Folkloristics 11, no. 1 (June 27, 2017): 65–82. http://dx.doi.org/10.1515/jef-2017-0005.

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Abstract In Buddhist Burma, a variety of ritual has been found pertaining to quite differentiated aspects of religion. This rich ritual landscape remains under-examined due partly to the Buddhist-studies bias of most of the scholars looking at religion in Burma. In this paper, I develop comparative analysis of a class of ritual, namely that of initiation, in three components of Burmese religion: Buddhist monasticism, Buddhist esotericism, and spirit worship. At least from the present analytic perspective, the three components considered could be taken as encompassing the entire Buddhist religious sphere in Burma. Looking at initiation rituals in these three ‘paths’ is a means of understanding how they frame contrasting kinds of differently valued religious practice, and of showing that, although not often discussed, rituals do matter in Burma because they help to distinguish categories of action according to their relative religiosity. By doing so, I aim to give a sense of the real diversity of the Burmese ritual landscape, which until recently was rarely taken into account, and to contribute to the on-going debate in the field of Buddhist studies on what could be encapsulated as the question of Buddhism and spirit cults in Southeast Asian Theravada.

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6

Lam, I., and S. Keeney. "Nonparadoxical evolutionary stability of the recombination initiation landscape in yeast." Science 350, no. 6263 (November 19, 2015): 932–37. http://dx.doi.org/10.1126/science.aad0814.

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7

Milón, Pohl, Cristina Maracci, Liudmila Filonava, Claudio O. Gualerzi, and Marina V. Rodnina. "Real-time assembly landscape of bacterial 30S translation initiation complex." Nature Structural & Molecular Biology 19, no. 6 (May 6, 2012): 609–15. http://dx.doi.org/10.1038/nsmb.2285.

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8

Prorok, Paulina, Faezeh Forouzanfar, Nerea Murugarren, Isabelle Peiffer, Romain Charton, Ildem Akerman, and Marcel Méchali. "Loss of Ezh2 function remodels the DNA replication initiation landscape." Cell Reports 42, no. 4 (April 2023): 112280. http://dx.doi.org/10.1016/j.celrep.2023.112280.

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9

Gelsinger, Diego Rivera, Emma Dallon, Rahul Reddy, Fuad Mohammad, Allen R. Buskirk, and Jocelyne DiRuggiero. "Ribosome profiling in archaea reveals leaderless translation, novel translational initiation sites, and ribosome pausing at single codon resolution." Nucleic Acids Research 48, no. 10 (May 8, 2020): 5201–16. http://dx.doi.org/10.1093/nar/gkaa304.

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Abstract High-throughput methods, such as ribosome profiling, have revealed the complexity of translation regulation in Bacteria and Eukarya with large-scale effects on cellular functions. In contrast, the translational landscape in Archaea remains mostly unexplored. Here, we developed ribosome profiling in a model archaeon, Haloferax volcanii, elucidating, for the first time, the translational landscape of a representative of the third domain of life. We determined the ribosome footprint of H. volcanii to be comparable in size to that of the Eukarya. We linked footprint lengths to initiating and elongating states of the ribosome on leadered transcripts, operons, and on leaderless transcripts, the latter representing 70% of H. volcanii transcriptome. We manipulated ribosome activity with translation inhibitors to reveal ribosome pausing at specific codons. Lastly, we found that the drug harringtonine arrested ribosomes at initiation sites in this archaeon. This drug treatment allowed us to confirm known translation initiation sites and also reveal putative novel initiation sites in intergenic regions and within genes. Ribosome profiling revealed an uncharacterized complexity of translation in this archaeon with bacteria-like, eukarya-like, and potentially novel translation mechanisms. These mechanisms are likely to be functionally essential and to contribute to an expanded proteome with regulatory roles in gene expression.

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10

Gilman, Edward F., and Thomas H. Yeager. "Root Initiation in Root-pruned Hardwoods." HortScience 23, no. 4 (August 1988): 775. http://dx.doi.org/10.21273/hortsci.23.4.775.

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Abstract Lateral root pruning and rootstock undercutting is practiced in field tree production. The timing, frequency, pruning distance from the trunk, and depth of pruning vary within the industry. Lateral roots formed in response to pruning usually originate close to the cut surface (1, 2, 5). Two recent studies indicated that root pruning field-grown landscape-sized trees increased root density within the root ball (3, 4). This research was conducted to determine the effect of root pruning on the location of regenerated roots and growth of existing unpruned lateral roots.

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11

Hennrich, Dirk Michael. "Tragische Dispositionen der Moderne. Stimmung und Aura im Wandel des Landschaftsbegriffs." Philosophica: International Journal for the History of Philosophy 23, no. 46 (2015): 19–30. http://dx.doi.org/10.5840/philosophica2015234618.

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The present text deals with the relation between the consolidation and the development of landscape-painting and the concept of landscape during the 19th century and the catabasis of a certain economy of disposition until our days. The process of the transformation and overcoming of landscape-painting reflects the decadence of an entire epoch, influencing the introduction of the dispositions into philosophy, as well the initiation of a new philosophical discipline, the Philosophy of Landscape.

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12

Hsieh, Andrew C., Yi Liu, Merritt P. Edlind, Nicholas T. Ingolia, Matthew R. Janes, Annie Sher, Evan Y. Shi, et al. "The translational landscape of mTOR signalling steers cancer initiation and metastasis." Nature 485, no. 7396 (February 22, 2012): 55–61. http://dx.doi.org/10.1038/nature10912.

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13

Ye, Xiang, Yang Zhao, and John Karijolich. "The landscape of transcription initiation across latent and lytic KSHV genomes." PLOS Pathogens 15, no. 6 (June 12, 2019): e1007852. http://dx.doi.org/10.1371/journal.ppat.1007852.

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14

Koch, A., and A. Schwab. "Cutaneous pH landscape as a facilitator of melanoma initiation and progression." Acta Physiologica 225, no. 1 (June 17, 2018): e13105. http://dx.doi.org/10.1111/apha.13105.

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15

Riehl, Lara M., Johannes H. Schulte, Medhanie A. Mulaw, Meike Dahlhaus, Matthias Fischer, Alexander Schramm, Angelika Eggert, Klaus-Michael Debatin, and Christian Beltinger. "The mitochondrial genetic landscape in neuroblastoma from tumor initiation to relapse." Oncotarget 7, no. 6 (December 28, 2015): 6620–25. http://dx.doi.org/10.18632/oncotarget.6776.

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16

Quik, Cindy, Ype van der Velde, Jasper H. J. Candel, Luc Steinbuch, Roy van Beek, and Jakob Wallinga. "Faded landscape: unravelling peat initiation and lateral expansion at one of northwest Europe's largest bog remnants." Biogeosciences 20, no. 3 (February 15, 2023): 695–718. http://dx.doi.org/10.5194/bg-20-695-2023.

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Abstract. On the mainland of northwest Europe generally only remnants of former peat landscapes subsist. Due to the poor preservation of these landscapes, alternative approaches to reconstruct peat initiation and lateral expansion are needed compared to regions with intact peat cover. Here we aim (1) to find explanatory variables within a digital soil mapping approach that allow us to reconstruct the pattern of peat initiation and lateral expansion within (and potentially beyond) peat remnants, and (2) to reconstruct peat initiation ages and lateral expansion for one of the largest bog remnants of the northwest European mainland, Fochteloërveen. Basal radiocarbon dates were obtained from the peat remnant, which formed the basis for subsequent analyses. We investigated the relationship between peat initiation age and three potential covariates: (1) total thickness of organic deposits, (2) elevation of the Pleistocene mineral surface that underlies the organic deposits, and (3) a constructed variable representing groundwater-fed wetness based on elevation of the mineral surface and current hydraulic head. Significant relationships were found with covariates (1) and (3), which were then used for subsequent modelling. Our results indicate simultaneous peat initiation at several loci in Fochteloërveen during the Early Holocene and continuous lateral expansion until 900 cal BP. Lateral expansion accelerated between 5500–3500 cal BP. Our approach is spatially explicit (i.e. results in a map of peat initiation ages), and it allows for a quantitative evaluation of the prediction using the standard deviation and comparison of predictions with validation points. The applied method based on covariate (1) is only useful where remnant peat survived, whereas covariate (3) may ultimately be applied to reconstruct peat initiation ages and lateral peatland expansion beyond the limits of peat remnants.

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17

Friedmann-Morvinski, Dinorah, Prerna Magod, Lilach Agemy, and Liat Rousso-Noori. "Immune microenvironment landscape and the role of neutrophils in glioblastoma." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 135.23. http://dx.doi.org/10.4049/jimmunol.202.supp.135.23.

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Abstract Glioblastoma (GBM) is an aggressive, highly invasive primary brain tumor with near total fatality. Using a Cre-inducible lentiviral GBM mouse model we previously showed that gliomas can originate from terminally differentiated neurons and astrocytes, which can dedifferentiate to a stem cell-like state upon transformation. We believe that the tumor microenvironment (TME) may contribute to the process of tumor reprogramming. Although the majority of infiltrating cells in the tumor are peripheral macrophages and microglia, recent appreciation of the effects of neutrophils in cancer directed our efforts in understanding their role in GBM. Flow cytometry analysis revealed differences in the brain TME of both the innate and adaptive immune populations compared to healthy brain tissue, changes were also seen in spleen and bone marrow even at early stages of GBM development. The neutrophils population varies not only at different time-points but also between tumor subtypes. We believe neutrophils switch from anti-tumor to pro-tumor phenotype. Depletion of neutrophils right before tumor initiation accelerated the onset of the disease while co-transplantation of equal ratio of glioma cells and naïve neutrophils delayed the initiation of tumors lesions. In-vitro assays showed higher migration and formation of neutrophils extracellular traps (NETs) on exposure to glioma cells condition media or glioma derived exosomes. Our findings suggest neutrophils play a role in tumor initiation and progression, and further understanding the transition of neutrophils from anti-tumor to pro-tumor phenotype will shed light into new strategies to treat GBM.

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18

Adjalley, Sophie H., Christophe D. Chabbert, Bernd Klaus, Vicent Pelechano, and Lars M. Steinmetz. "Landscape and Dynamics of Transcription Initiation in the Malaria Parasite Plasmodium falciparum." Cell Reports 14, no. 10 (March 2016): 2463–75. http://dx.doi.org/10.1016/j.celrep.2016.02.025.

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19

Mentes, Ahmet, Ana Maria Florescu, Elizabeth Brunk, Jeff Wereszczynski, Marc Joyeux, and Ioan Andricioaei. "Free-Energy Landscape and Characteristic Forces for the Initiation of DNA Unzipping." Biophysical Journal 108, no. 7 (April 2015): 1727–38. http://dx.doi.org/10.1016/j.bpj.2015.01.025.

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20

Palucis, Marisa C., Thomas P. Ulizio, and Michael P. Lamb. "Debris flow initiation from ravel-filled channel bed failure following wildfire in a bedrock landscape with limited sediment supply." GSA Bulletin 133, no. 9-10 (February 1, 2021): 2079–96. http://dx.doi.org/10.1130/b35822.1.

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Abstract Steep, rocky landscapes often produce large sediment yields and debris flows following wildfire. Debris flows can initiate from landsliding or rilling in soil-mantled portions of the landscape, but there have been few direct observations of debris flow initiation in steep, rocky portions of the landscape that lacdk a thick, continuous soil mantle. We monitored a steep, first-order catchment that burned in the San Gabriel Mountains, California, USA. Following fire, but prior to rainfall, much of the hillslope soil mantle was removed by dry ravel, exposing bedrock and depositing ∼0.5 m of sandy sediment in the channel network. During a one-year recurrence rainstorm, debris flows initiated in the channel network, evacuating the accumulated dry ravel and underlying cobble bed, and scouring the channel to bedrock. The channel abuts a plowed terrace, which allowed a complete sediment budget, confirming that ∼95% of sediment deposited in a debris flow fan matched that evacuated from the channel, with a minor rainfall-driven hillslope contribution. Subsequent larger storms produced debris flows in higher-order channels but not in the first-order channel because of a sediment supply limitation. These observations are consistent with a model for post-fire ravel routing in steep, rocky landscapes where sediment was sourced by incineration of vegetation dams—following ∼30 years of hillslope soil production since the last fire—and transported downslope by dry processes, leading to a hillslope sediment-supply limitation and infilling of low-order channels with relatively fine sediment. Our observations of debris flow initiation are consistent with failure of the channel bed alluvium due to grain size reduction from dry ravel deposits that allowed high Shields numbers and mass failure even for moderate intensity rainstorms.

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21

Romme, William, and Daniel Kashian. "Long Term Development of Forest Stand Structure Following Catastrophic Fire in Yellowstone National Park: Do Landscape Legacies Persist?" UW National Parks Service Research Station Annual Reports 24 (January 1, 2000): 160–64. http://dx.doi.org/10.13001/uwnpsrc.2000.3439.

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The importance of large, infrequent natural disturbances, particularly as they influence postÂdisturbance succession, is well recognized. The conceptualization of ecological systems and landscapes as mosaics of patches generated by disturbance emphasizes successional change, which in turn is a major component of ecologists' understanding of disturbance in a landscape context. However, paradigms of succession largely evolved for small-scale dynamics. Subsequently, these paradigms do not adequately predict the spatial variability that occurs within the perimeter of large, infrequent disturbances, nor do they adequately consider the effects of heterogeneity on recovery of the system. Understanding the nature of the disturbance mosaic and the factors controlling landscape patterns are crucial for predicting ecosystem dynamics and vegetation development in disturbance-prone landscapes, and research that addresses these questions remains a priority. Landscape heterogeneity following large, mfrequent fires is represented by a patchwork of burned and unburned vegetation as well as by a mosaic of burn severities (Turner et al. 1997, Romme et al. 1998), so that the mosaic of stand structure and function produced by fire is a legacy of the disturbance itself as well as that of the pre-fire forest. In this sense, large, infrequent fires are thought to impose a persistent influence on landscape pattern. Landscape pattern has large implications for biodiversity, determines the connectivity of habitat, affects the spread of disturbances such as insect outbreaks, and may influence the initiation and spread of small, frequent surface fires by affecting the spatial distribution of fuels. Similarly, spatial heterogeneity in stand structure that exists across a landscape may influence the propagation of crown fires (Van Wagner 1977, Turner and Romme 1994). Clearly, understanding the changes that occur in landscape pattern provides the key to understanding the dynamics of many ecological processes. Our study examines the natural changes that occur in landscape pattern with succession in Yellowstone National Park (YNP) between large, infrequent wildfires. The 1988 fires in YNP created a mosaic of burn severities that produced tremendous variation in density of lodgepole pine (Pinus contorta var. latifolia) seedlings across the landscape (Turner et al. 1994). Because the Yellowstone mosaic of post-fire seedling densities varies from high-density stands (>50,000 trees/ha), which will inevitably be subject to self-thinning, to low-density stands (

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22

Pietrych, Krystyna. "Włoskie inicjacje Aleksandra Wata." Poznańskie Studia Polonistyczne. Seria Literacka, no. 38 (October 15, 2020): 157–79. http://dx.doi.org/10.14746/pspsl.2020.38.7.

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The article presents the stages of Aleksander Wat’s first journey to Italy in 1949 – starting from Venice, through Florence and Rome, finishing in Naples and Capri. Most of all, the article interprets the poetic records of the places visited by the poet and his impressions written down in letters. As a result, what the journey to Italy becomes for Wat is not only a discovery of the beauty of landscape and the plenty of art, but, most importantly, an experience of physical contact with the Mediterranean land, an initiation into the fascinating witnessing of the incarnation of cultural tradition into a visible landscape, a sensual initiation into the legacy of the Mediterranean. The coda of the text is his unexpected reminiscence from the first journey to Italy recorded in a social realist drama.

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23

Seth Nanda, Chandan, Sharavan Vishaan Venkateswaran, Neill Patani, and Mariia Yuneva. "Defining a metabolic landscape of tumours: genome meets metabolism." British Journal of Cancer 122, no. 2 (December 10, 2019): 136–49. http://dx.doi.org/10.1038/s41416-019-0663-7.

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AbstractCancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have long been acknowledged and considered a plausible therapeutic target, the crosstalk between genetic and metabolic alterations throughout cancer types is not clearly defined. In this review, we summarise the present understanding of the interactions between genetic drivers of cellular transformation and cancer-associated metabolic changes, and how these interactions contribute to metabolic heterogeneity of tumours. We discuss the essential question of whether changes in metabolism are a cause or a consequence in the formation of cancer. We highlight two modes of how metabolism contributes to tumour formation. One is when metabolic reprogramming occurs downstream of oncogenic mutations in signalling pathways and supports tumorigenesis. The other is where metabolic reprogramming initiates transformation being either downstream of mutations in oncometabolite genes or induced by chronic wounding, inflammation, oxygen stress or metabolic diseases. Finally, we focus on the factors that can contribute to metabolic heterogeneity in tumours, including genetic heterogeneity, immunomodulatory factors and tissue architecture. We believe that an in-depth understanding of cancer metabolic reprogramming, and the role of metabolic dysregulation in tumour initiation and progression, can help identify cellular vulnerabilities that can be exploited for therapeutic use.

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24

Alavi, Niloofar, and Douglas King. "Evaluating the Relationships of Inter-Annual Farmland Vegetation Dynamics with Biodiversity Using Multi-Spatial and Multi-Temporal Remote Sensing Data." Remote Sensing 12, no. 9 (May 6, 2020): 1479. http://dx.doi.org/10.3390/rs12091479.

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Agricultural landscapes are highly dynamic ecosystems, but the effects of temporal farmland vegetation dynamics on species diversity have not been widely studied. In 93 sample farm landscapes in eastern Ontario, Canada, biodiversity data for seven taxa were collected in 2011 and 2012, prior to the initiation of this study. The goal of this study was to determine if trends and variability in vegetation productivity detected in these sample landscapes using long-term archived moderate and coarse resolution remote sensing time series data are related to the measured biodiversity. Mid-summer Moderate Resolution Imaging Spectroradiometer (MODIS) (2000–2011) and Landsat 5 (1985–2011) Normalized Difference Vegetation Index (NDVI) data were used with the Thiel–Sen slope and Contextual Mann–Kendall trend analysis to identify pixels showing significant trends. NDVI temporal metrics included 1) the percentage of pixels in each landscape with a significant negative or positive trend, and 2) the temporal coefficient of variation (CV) of both the mean and spatial CV of landscape NDVI. Larger areas of significant positive NDVI trends were found in the sample landscapes than negative trends, the former being associated with agricultural intensification or crop changes and the latter with smaller areas of natural vegetation removal. Landsat better-detected changes in individual fields or small areas of natural vegetation due to its much smaller pixel size. In addition, the longer Landsat time series showed a change in the NDVI trend from positive (1985–2000) to negative or a leveling off (2000–2011) for many pixels. In biodiversity modeling, the Landsat temporal CV of NDVI was negatively correlated with 2011–2012 plant and beetle diversity, while plant biodiversity was positively correlated with the percentage of pixels in a sample landscape showing a significantly positive NDVI trend. No significant relationships were found using the MODIS data. This study shows that temporal trends and variability in farmland vegetation density derived from Landsat data are related to biodiversity for certain taxa and that such relationships should be considered along with the more commonly studied spatial landscape attributes in evaluating landscape-level impacts of farming on biodiversity.

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25

Ni, Ting, David L. Corcoran, Elizabeth A. Rach, Shen Song, Eric P. Spana, Yuan Gao, Uwe Ohler, and Jun Zhu. "A paired-end sequencing strategy to map the complex landscape of transcription initiation." Nature Methods 7, no. 7 (May 23, 2010): 521–27. http://dx.doi.org/10.1038/nmeth.1464.

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26

Bohm, Alexandra, Jessica DePetro, Carmen Binding, Cameron Grisdale, Matthaeus Ware, Sam Lawn, Nick Chahley, et al. "TMOD-02. A MODEL OF THE INITIATION AND GENOMIC LANDSCAPE OF GLIOBLASTOMA (GBM)." Neuro-Oncology 21, Supplement_6 (November 2019): vi262—vi263. http://dx.doi.org/10.1093/neuonc/noz175.1101.

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Abstract IDH-wildtype GBM is the most common variant of this cancer and occurs in older adults. Unfortunately patients’ tumors are either inherently resistant to standard treatment, which includes radio- and chemo-therapy, or acquire resistance during the therapeutic process. Additionally, although effective in other cancers, targeted therapies have yielded disappointing results in GBM, perhaps because the fully developed disease has significant cellular and molecular heterogeneity, allowing the tumour to adapt to treatments. Better insight into managing GBM might result from a detailed knowledge of its initiating events, which have not yet been elucidated. With this in mind, we developed a mouse model of GBM in which the earliest stages can be studied. This ex vivo model recreates GBM by culturing subventricular zone (SVZ) cells, the putative ‘cell of origin’ of GBM in platelet-derived growth factor A (PDGFA). Under this condition SVZ cells from p53 null mice transform, becoming exogenous growth factor independent and tumorigenic in immune-competent mice. In contrast, wildtype SVZ cells do not proliferate in PDGFA and null cells in EGF/FGF do not transform. To discover why p53 null SVZ cells uniquely transform in PDGFA, we performed array comparative genomic hybridization (aCGH) on cells before and after transformation in PDGFA and whole genome sequencing (WGS) on transformed cells and tumours generated from PDGFA-transformed cells. aCGH and WGS revealed that the genomic landscape of transformed cells displayed a striking similarity to that observed in primary human GBM. Specifically, these studies showed that chromosomal alterations are a hallmark of culturing SVZ cells in PDGFA, an intriguing finding considering GBM is also characterized by a specific landscape of copy number alterations. This model may resemble the pathogenesis of human GBM and be leveraged to investigate the early stages of tumorigenesis, further leading to the development of preventative strategies and novel therapeutics.

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27

Ben-Yehezkel, Tuval, Hadas Zur, Tzipy Marx, Ehud Shapiro, and Tamir Tuller. "Mapping the translation initiation landscape of an S. cerevisiae gene using fluorescent proteins." Genomics 102, no. 4 (October 2013): 419–29. http://dx.doi.org/10.1016/j.ygeno.2013.05.003.

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28

Dzialak, Matthew R., Michael J. Lacki, Jeffery L. Larkin, Kristina M. Carter, and Shawchyi Vorisek. "Corridors affect dispersal initiation in reintroduced peregrine falcons." Animal Conservation 8, no. 4 (November 2005): 421–30. http://dx.doi.org/10.1017/s1367943005002441.

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29

Dietze, Michael, Rainer Bell, Ugur Ozturk, Kristen L. Cook, Christoff Andermann, Alexander R. Beer, Bodo Damm, et al. "More than heavy rain turning into fast-flowing water – a landscape perspective on the 2021 Eifel floods." Natural Hazards and Earth System Sciences 22, no. 6 (June 2, 2022): 1845–56. http://dx.doi.org/10.5194/nhess-22-1845-2022.

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Abstract. Rapidly evolving floods are rare but powerful drivers of landscape reorganisation that have severe and long-lasting impacts on both the functions of a landscape’s subsystems and the affected society. The July 2021 flood that particularly hit several river catchments of the Eifel region in western Germany and Belgium was a drastic example. While media and scientists highlighted the meteorological and hydrological aspects of this flood, it was not just the rising water levels in the main valleys that posed a hazard, caused damage, and drove environmental reorganisation. Instead, the concurrent coupling of landscape elements and the wood, sediment, and debris carried by the fast-flowing water made this flood so devastating and difficult to predict. Because more intense floods are able to interact with more landscape components, they at times reveal rare non-linear feedbacks, which may be hidden during smaller events due to their high thresholds of initiation. Here, we briefly review the boundary conditions of the 14–15 July 2021 flood and discuss the emerging features that made this event different from previous floods. We identify hillslope processes, aspects of debris mobilisation, the legacy of sustained human land use, and emerging process connections and feedbacks as critical non-hydrological dimensions of the flood. With this landscape scale perspective, we develop requirements for improved future event anticipation, mitigation, and fundamental system understanding.

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Griffin, Matthew, and Terence K. Trow. "The evolving landscape of combination therapy for pulmonary arterial hypertension." Therapeutic Advances in Respiratory Disease 11, no. 2 (November 21, 2016): 91–95. http://dx.doi.org/10.1177/1753465816677485.

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Pulmonary arterial hypertension (PAH) is a progressively fatal disease, and the goal in treatment is to prevent disease progression. The standard of care often involves medications from multiple therapeutic classes, and there has been significant interest both in the choice of agent as well as the timing of initiation. There is a growing body of support for starting multiple medications at the time of diagnosis, or ‘upfront ’, rather than using sequential addition to prevent clinical deterioration.

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Aiderus, Aziz, Justin Y. Newberg, Liliana Guzman-Rojas, Ana M. Contreras-Sandoval, Amanda L. Meshey, Devin J. Jones, Felipe Amaya-Manzanares, et al. "Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression." PLOS Genetics 17, no. 8 (August 16, 2021): e1009094. http://dx.doi.org/10.1371/journal.pgen.1009094.

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The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.

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Qomariah, Umi Kulsum Nur, and Anggun Wulandari. "Inventarisasi Tumbuhan Berkhasiat Obat Sebagai Kandidat Elemen lansekap di Area Terdampak Inisiasi Bandara Kediri di Desa Bulusari." Exact Papers in Compilation (EPiC) 4, no. 3 (August 11, 2022): 579–84. http://dx.doi.org/10.32764/epic.v4i3.781.

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The initiation of the Kediri airport has had a direct impact on the availability of space in Bulusari village. Bulusari Village has a variety of medicinal plants which are still widely used by the community in their daily lives. However, the initiation of Kediri Airport has reduced the ecosystem space for medicinal plants. Conservation efforts need to be made to protect endemic species that can be synergized with the existence of Kediri Airport through the cultivation of medicinal plants as landscape elements. Inventory is the first step in conserving the diversity of medicinal plants in Bulusari village. The purpose of this study to conduct an inventory of medicinal plants that can be used as landscape elements in areas affected by the initiation of Kediri Airport in Bulusari Village. The method used is literature study, survey, observation and identification of medicinal plant names. Determination of the research location was done by purposive random sampling. Observations were made at three types of locations, namely telajakan, gardens and fields. Each sampling plot has an area of 10 x 10 m2. The inventory is focused on medicinal plants that just grow in nature or are not directly cultivated by humans. The results showed that there are 45 species of medicinal plants that have the potential as landscape elements with details of the functions as follows; 1) sunscreen, 2) pollutant absorber 3) privacy barrier, 4) wall, 5) space builder, 6) animal habitat, 7) erosion control, 8) aesthetic value, 9) physical barrier to movement of organisms and 10) ground cover.

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Hard, Gregory, Abenaa Jones, Abhery Das, and Julie Johnson. "Medical Cannabis Laws and Adolescent Alcohol Use Initiation." Cannabis 5, no. 3 (November 21, 2022): 1–10. http://dx.doi.org/10.26828/cannabis/2022.03.001.

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Background. The effects of medical cannabis laws (MCLs) on adolescent alcohol use remains unclear. Previous literature investigates alcohol consumption rather than alcohol initiation among adolescents, and does not examine the effect by sociodemographic characteristics and state-level dispensary status. We used population representative, state-level data to examine the relationship between MCLs and adolescent alcohol initiation. Methods. Data for this study were derived from the Youth Risk Behavior Survey (YRBS), a nationally representative, cross-sectional school-based survey administered by the Centers for Disease Control (CDC) in odd-numbered years from 1991 to 2015. We used a difference-in-difference model to assess pre and post effects of state MCL enactment on adolescent alcohol use initiation. Logistic regression analyses assessed associations between MCLs and varying ages of initiation. We further stratified our results by race/ethnicity, gender, and dispensary status. Results. Results from adjusted logistic regression models showed higher odds of initiating alcohol among adolescents in states without MCLs when compared to adolescents in states with MCLs (OR 1.37, [95% CI = 1.29, 1.44]). This effect was consistent across age, race/ethnicity, and gender groups. Reductions in self-report of alcohol initiation were also consistently found in multiple age strata (9-10, 11-12, and 13-14), though this finding did not reach conventional levels of statistical detection in all race/ethnicities. Conclusions. Our findings support a substitutive effect, suggesting that adolescents in states with MCLs, as opposed to states without MCLs, may substitute cannabis for alcohol. Considering the evolving landscape of medical cannabis laws and the proliferation of state-level legalization laws, further research into the effects of such policies, such as adult-use cannabis laws, is warranted to further elucidate their effects on adolescent substance use.

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Willems, Patrick, Elvis Ndah, Veronique Jonckheere, Simon Stael, Adriaan Sticker, Lennart Martens, Frank Van Breusegem, Kris Gevaert, and Petra Van Damme. "N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana." Molecular & Cellular Proteomics 16, no. 6 (April 21, 2017): 1064–80. http://dx.doi.org/10.1074/mcp.m116.066662.

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Nordell, Cameron J., Troy I. Wellicome, and Erin M. Bayne. "Flight initiation by Ferruginous Hawks depends on disturbance type, experience, and the anthropogenic landscape." PLOS ONE 12, no. 5 (May 18, 2017): e0177584. http://dx.doi.org/10.1371/journal.pone.0177584.

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36

Nepal, Chirag, Yavor Hadzhiev, Christopher Previti, Vanja Haberle, Nan Li, Hazuki Takahashi, Ana Maria M. Suzuki, et al. "Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis." Genome Research 23, no. 11 (September 3, 2013): 1938–50. http://dx.doi.org/10.1101/gr.153692.112.

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37

Chomette, D. "Krox20 hindbrain cis-regulatory landscape: interplay between multiple long-range initiation and autoregulatory elements." Development 133, no. 7 (April 1, 2006): 1253–62. http://dx.doi.org/10.1242/dev.02289.

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38

Tripathi, Subhash K., Tommi Välikangas, Ankitha Shetty, Mohd Moin Khan, Robert Moulder, Santosh D. Bhosale, Elina Komsi, et al. "Quantitative Proteomics Reveals the Dynamic Protein Landscape during Initiation of Human Th17 Cell Polarization." iScience 11 (January 2019): 334–55. http://dx.doi.org/10.1016/j.isci.2018.12.020.

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39

Strauch, Ronda, Erkan Istanbulluoglu, Sai Siddhartha Nudurupati, Christina Bandaragoda, Nicole M. Gasparini, and Gregory E. Tucker. "A hydroclimatological approach to predicting regional landslide probability using Landlab." Earth Surface Dynamics 6, no. 1 (February 7, 2018): 49–75. http://dx.doi.org/10.5194/esurf-6-49-2018.

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Abstract. We develop a hydroclimatological approach to the modeling of regional shallow landslide initiation that integrates spatial and temporal dimensions of parameter uncertainty to estimate an annual probability of landslide initiation based on Monte Carlo simulations. The physically based model couples the infinite-slope stability model with a steady-state subsurface flow representation and operates in a digital elevation model. Spatially distributed gridded data for soil properties and vegetation classification are used for parameter estimation of probability distributions that characterize model input uncertainty. Hydrologic forcing to the model is through annual maximum daily recharge to subsurface flow obtained from a macroscale hydrologic model. We demonstrate the model in a steep mountainous region in northern Washington, USA, over 2700 km2. The influence of soil depth on the probability of landslide initiation is investigated through comparisons among model output produced using three different soil depth scenarios reflecting the uncertainty of soil depth and its potential long-term variability. We found elevation-dependent patterns in probability of landslide initiation that showed the stabilizing effects of forests at low elevations, an increased landslide probability with forest decline at mid-elevations (1400 to 2400 m), and soil limitation and steep topographic controls at high alpine elevations and in post-glacial landscapes. These dominant controls manifest themselves in a bimodal distribution of spatial annual landslide probability. Model testing with limited observations revealed similarly moderate model confidence for the three hazard maps, suggesting suitable use as relative hazard products. The model is available as a component in Landlab, an open-source, Python-based landscape earth systems modeling environment, and is designed to be easily reproduced utilizing HydroShare cyberinfrastructure.

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40

Eskander, Ramez N. "The Epigenetic Landscape in the Treatment of Gynecologic Malignancies." American Society of Clinical Oncology Educational Book, no. 38 (May 2018): 480–87. http://dx.doi.org/10.1200/edbk_200203.

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The care of patients with advanced-stage or recurrent endometrial, ovarian, and cervical cancer remains clinically challenging. Despite the identification of novel therapeutics and advancements in supportive care, survival outcomes have been relatively unchanged over the past decade. In addition to established genomic alterations and the contributions of the tumor microenvironment to cancer progression, epigenetic mechanisms have emerged as important contributors to gynecologic cancer progression. DNA methylation, histone modification, and noncoding RNA expression may be important contributors to disease initiation and progression and may represent novel therapeutic targets. This article reviews the epigenetic landscape of endometrial, ovarian, and cervical cancer, describing the state of the science and discussing potential clinical applications. To date, the role of epigenetic drugs in the treatment of gynecologic cancers remains unclear, although continued progress may inform future treatment modalities.

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41

Palik, Brian J., and Kurt S. Pregitzer. "The repeatability of stem exclusion during even-aged development of bigtooth aspen dominated forests." Canadian Journal of Forest Research 23, no. 6 (June 1, 1993): 1156–68. http://dx.doi.org/10.1139/x93-147.

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Forest development following major disturbance is thought to follow a fairly repeatable temporal pattern. An initial cohort of trees establishes relatively rapidly (stand initiation), new establishment is precluded for an extended period (stem exclusion), and finally, new individuals again begin to establish, creating new age-classes in the forest understory (understory reinitiation), eventually leading to an uneven-aged condition. The current study was designed to assess the generality of this developmental pattern at the landscape level and gain insight into the possible mechanisms controlling stem exclusion and understory reinitiation in even-aged forests. Research was conducted within two bigtooth aspen (Populusgrandidentata Michx.) dominated landscapes in northern Lower Michigan having similar physical site characteristics, overstory compositions, and disturbance histories. The objectives for the study included (i) assessing the repeatability of development patterns within and between the two landscapes and (ii) exploring relationships between the timing of understory reinitiation and overstory growth characteristics and seed availability. Stem analysis was used to reconstruct establishment and growth histories of surviving stems in mature forest on replicate plots within each landscape. The age distributions of surviving individuals of all tree species in both forests reflected a developmental pattern characterized by rapid initial cohort establishment lasting 5–15 years, stem exclusion lasting 25–35 years, and understory reinitiation. The duration and timing of the developmental stages on the replicate plots were similar both within and between the two landscapes. There were, however, a small number of plots in landscape 2 that had substantially reduced stem exclusion lengths, relative to the remaining plots in both forests. Variation in the timing of understory reinitiation in landscape 2 was related to characteristics of remnant eastern white pine (Pinusstrobus L.) seed trees. The stem exclusion period was shorter, or almost nonexistent, on plots close to several large seed trees because of early, low-frequency establishment of white pine in the understory. Substantial increases in the frequency of understory establishment on all plots in landscape 2, as well as all new understory establishment on plots in landscape 1, were often associated with radial growth increases in overstory stems. The radial growth increases presumably reflected an increase in resource availability, possibly occurring in response to a concentrated wave of natural thinning within the bigtooth aspen dominated overstory. These results suggests that the timing of understory reinitiation may have been influenced by variation in seed availability interacting with changes in resource availability in the forest understory. A limited amount of new establishment occurred relatively early in forest development on plots that experienced abundant early seed rain, yet the bulk of new establishment occurred only after an increase in resource availability in the understory. The general patterns of forest development described in this study were similar both within and between landscapes. Similar descriptive studies are needed to address the repeatability of development patterns at the landscape level within other forest types. Additionally, experimental studies are needed to unequivocally identify the mechanisms controlling stem exclusion and understory reinitiation in even-aged forests.

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42

Clubb, Fiona J., Simon M. Mudd, David T. Milodowski, Declan A. Valters, Louise J. Slater, Martin D. Hurst, and Ajay B. Limaye. "Geomorphometric delineation of floodplains and terraces from objectively defined topographic thresholds." Earth Surface Dynamics 5, no. 3 (July 10, 2017): 369–85. http://dx.doi.org/10.5194/esurf-5-369-2017.

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Abstract. Floodplain and terrace features can provide information about current and past fluvial processes, including channel response to varying discharge and sediment flux, sediment storage, and the climatic or tectonic history of a catchment. Previous methods of identifying floodplain and terraces from digital elevation models (DEMs) tend to be semi-automated, requiring the input of independent datasets or manual editing by the user. In this study we present a new method of identifying floodplain and terrace features based on two thresholds: local gradient, and elevation compared to the nearest channel. These thresholds are calculated statistically from the DEM using quantile–quantile plots and do not need to be set manually for each landscape in question. We test our method against field-mapped floodplain initiation points, published flood hazard maps, and digitised terrace surfaces from seven field sites from the US and one field site from the UK. For each site, we use high-resolution DEMs derived from light detection and ranging (lidar) where available, as well as coarser resolution national datasets to test the sensitivity of our method to grid resolution. We find that our method is successful in extracting floodplain and terrace features compared to the field-mapped data from the range of landscapes and grid resolutions tested. The method is most accurate in areas where there is a contrast in slope and elevation between the feature of interest and the surrounding landscape, such as confined valley settings. Our method provides a new tool for rapidly and objectively identifying floodplain and terrace features on a landscape scale, with applications including flood risk mapping, reconstruction of landscape evolution, and quantification of sediment storage and routing.

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Gilliam, Charles H., D. Joseph Eakes, and John W. Olive. "Herbicide Use During Propagation Affects Root Initiation and Development." Journal of Environmental Horticulture 11, no. 4 (December 1, 1993): 157–59. http://dx.doi.org/10.24266/0738-2898-11.4.157.

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Abstract Two studies were conducted to evaluate the influence of herbicides on root initiation and development from stem cuttings of three woody landscape species. In the first experiment, Rhododendron obtusum ‘Hino Crimson’ rooting percentage was suppressed with Rout 3G (oxyfluorfen + oryzalin). Both root quality ratings and root lengths were lower for stem cuttings when herbicides were applied compared to untreated controls. Rooting percentages of Rhododendron × ‘Trouper’ and Gardenia jasminoides ‘August Beauty’ were not affected by herbicide application. Root quality ratings and root lengths were generally lower with Rout 3G, OH-2 3G (oxyfluorfen + pendimethlin), Snapshot 2.5TG (trifluralin + isoxaben), and Southern Weed Grass Control 2.68G (pendimethlin) when compared to untreated controls. In the second experiment, depth of sticking Gardenia jasminoides ‘August Beauty’ cuttings and herbicide treatments were evaluated. Cuttings in Rout 3G and Snapshot 2.5 TG treatments had improved root quality ratings when stuck to a depth of 2.5 cm (1.0 in) compared to 1.3 cm (0.5 in); however, all other herbicide treatments had similar root quality ratings to the untreated controls, regardless of depth of sticking.

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44

Tafangenyasha, Clifford, and Bruce Campbell. "Initiation and maintenance of degraded landscape in the Sinamatella area of Hwange National Park, Zimbabwe." Journal of Environmental Management 52, no. 1 (January 1998): 69–78. http://dx.doi.org/10.1006/jema.1997.0158.

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45

Hyrien, Olivier. "Peaks cloaked in the mist: The landscape of mammalian replication origins." Journal of Cell Biology 208, no. 2 (January 19, 2015): 147–60. http://dx.doi.org/10.1083/jcb.201407004.

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Replication of mammalian genomes starts at sites termed replication origins, which historically have been difficult to locate as a result of large genome sizes, limited power of genetic identification schemes, and rareness and fragility of initiation intermediates. However, origins are now mapped by the thousands using microarrays and sequencing techniques. Independent studies show modest concordance, suggesting that mammalian origins can form at any DNA sequence but are suppressed by read-through transcription or that they can overlap the 5′ end or even the entire gene. These results require a critical reevaluation of whether origins form at specific DNA elements and/or epigenetic signals or require no such determinants.

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46

de Lavaissière, Léopold, Stéphane Bonnet, Anne Guyez, and Philippe Davy. "Autogenic knickpoints in laboratory landscape experiments." Earth Surface Dynamics 10, no. 2 (March 15, 2022): 229–46. http://dx.doi.org/10.5194/esurf-10-229-2022.

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Abstract. The upstream propagation of knickpoints in river longitudinal profiles is commonly assumed to be related to discrete changes in tectonics, climate or base level. However, the recognition that some knickpoints may form autogenically, independent of any external perturbation, may challenge these assumptions. We investigate here the genesis and dynamics of such autogenic knickpoints in laboratory experiments at the drainage basin scale, where landscapes evolved in response to constant rates of base level fall and precipitation. Despite these constant forcings, we observe that knickpoints regularly initiate in rivers at the catchments' outlet throughout the duration of experiments. The upstream knickpoint propagation rate does not decrease monotonically in relationship with the decrease in drainage area, as predicted by stream-power-based models, instead the propagation rate first increases until the mid-part of catchments before decreasing. To investigate the dynamics of the knickpoints, we calculated hydraulic information (water depth, river width, discharge and shear stress) using a hydrodynamic model. We show that knickpoint initiation at the outlet coincides with a fairly abrupt river narrowing entailing an increase in their shear stress. Then, once knickpoints have propagated upward, rivers widen causing a decrease in shear stress and incision rate, and making the river incision less than the base level fall rate. This creates an unstable situation which drives the formation of a new knickpoint. The experiments suggest a new autocyclic model of knickpoint generation controlled by river width dynamics independent of variations in climate or tectonics. This questions an interpretation of landscape records focusing only on climate and tectonic changes without considering autogenic processes.

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Keramidas, Natacha L., John E. Queener, and Paul J. Hartung. "Forming mentoring relationships in graduate education: The role of personality." Australian Journal of Career Development 31, no. 2 (July 2022): 118–29. http://dx.doi.org/10.1177/10384162221107972.

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This study investigated mentoring relationships between doctoral students and faculty members. We examined initiation of mentoring as a mediator between key personality facets and mentoring received among 162 doctoral students (females = 77%, 77% psychology programs). Results confirmed that initiation of mentoring relationships by doctoral students significantly predicted mentoring received. Furthermore, mentoring initiation also mediated relationships between several personality facets (friendliness, assertiveness, achievement-striving, self-efficacy, and self-consciousness) and mentoring received. By demonstrating the significance of student-initiated mentoring and the influence of specific personality facets on this proactive behavior, our study underscores the importance of providing an environment supportive of mentoring and setting expectations for students early on in their doctoral studies if they are to benefit from mentoring. Future research on the impact of age could also help advance understanding of mentoring among older students as the career landscape continues to change.

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48

Rengers, Francis K., Luke A. McGuire, Nina S. Oakley, Jason W. Kean, Dennis M. Staley, and Hui Tang. "Landslides after wildfire: initiation, magnitude, and mobility." Landslides 17, no. 11 (August 11, 2020): 2631–41. http://dx.doi.org/10.1007/s10346-020-01506-3.

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Abstract In the semiarid Southwestern USA, wildfires are commonly followed by runoff-generated debris flows because wildfires remove vegetation and ground cover, which reduces soil infiltration capacity and increases soil erodibility. At a study site in Southern California, we initially observed runoff-generated debris flows in the first year following fire. However, at the same site three years after the fire, the mass-wasting response to a long-duration rainstorm with high rainfall intensity peaks was shallow landsliding rather than runoff-generated debris flows. Moreover, the same storm caused landslides on unburned hillslopes as well as on slopes burned 5 years prior to the storm and areas burned by successive wildfires, 10 years and 3 years before the rainstorm. The landslide density was the highest on the hillslopes that had burned 3 years beforehand, and the hillslopes burned 5 years prior to the storm had low landslide densities, similar to unburned areas. We also found that reburning (i.e., two wildfires within the past 10 years) had little influence on landslide density. Our results indicate that landscape susceptibility to shallow landslides might return to that of unburned conditions after as little as 5 years of vegetation recovery. Moreover, most of the landslide activity was on steep, equatorial-facing slopes that receive higher solar radiation and had slower rates of vegetation regrowth, which further implicates vegetation as a controlling factor on post-fire landslide susceptibility. Finally, the total volume of sediment mobilized by the year 3 landslides was much smaller than the year 1 runoff-generated debris flows, and the landslides were orders of magnitude less mobile than the runoff-generated debris flows.

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Nasiyev, Beybit, Aleksandr Bushnev, Nurbolat Zhanatalapov, Askhat Bekkaliyev, Ainur Zhylkybay, Tursunay Vassilina, Vladimir Shibaikin, and Renat Tuktarov. "Initiation of safflower sowings in the organic farming system of Western Kazakhstan." OCL 29 (2022): 21. http://dx.doi.org/10.1051/ocl/2022015.

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We carried out the research in 2020–2021 in Western Kazakhstan on medium-loamy dark chestnut soils. The purpose of the research is to identify changes in physico-chemical, biological parameters of soil cover, productivity, and quality of safflower (Carthamus tincforius L.) under the influence of different technologies of agrarian landscape shaping, for rational management of organic agrocenoses. The field experiments showed that in the conditions of Western Kazakhstan, the use of the biologized technology of organic farming increases the yield of safflower in comparison with the traditional technology by 26.66–35.38%, with a high oil content of 30.0–39.95%. The phytoameliorative role of safflower in improving agrophysical, agrochemical, and biological parameters of dark chestnut soils is proved.

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Koletsky, Alan J. "The Changing Therapeutic Landscape in Metastatic Prostate Cancer." Oncology & Hematology Review (US) 13, no. 02 (2017): 112. http://dx.doi.org/10.17925/ohr.2017.13.02.112.

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Over the past several years a number of novel and diverse agents have provided a significant clinical benefit for patients with metastatic castration-resistant prostate cancer including abiraterone, enzalutamide, sipuleucel-T, cabazitaxel, and radium-223. The early use of docetaxel or abiraterone at initiation of standard androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer has also led to substantial improvements in overall survival. The identification of a truncating mutation in the androgen receptor (ARV7), a biomarker of resistance, may help clarify a more optimal sequencing of hormonal and chemotherapy-based therapies for patients with metastatic disease. The genomic landscape of both primary and metastatic prostate cancer has been an important focal point of translational research. The most widely studied pathways that affect tumorigenesis are the phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) and poly ADP ribose polymerase (PARP) and DNA repair pathways. This review will highlight recent clinical trials which have had a major impact on the management of patients with metastatic disease with an emphasis on treatments driven by common genomic aberrations present in advanced prostate cancer.

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