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Red raspberry cultivars that produce fruit on current season canes (primocanes) can produce additional fruit the following year on floricanes. The primocane-fruiting raspberries ‘Himbo Top’, ‘Joan J’, and ‘Polka’ were grown organically in high tunnels and pruned to different floricane densities to determine the effects on fruit yield (primocane, floricane, total) and harvest times. Floricane densities were 0, 2.4, or 4.8 canes per meter of row length in 2015, and 0, 4.9, or 9.8 canes per meter in 2016 and 2017. Total yield (floricane plus primocane) was significantly greater with low floricane density (17 t·ha−1) or high density (19 t·ha−1) compared with no floricanes (12 t·ha−1). Floricane density did not affect primocane yield or harvest times. Primocanes of ‘Polka’ were taller when floricanes were present, but primocanes of other cultivars were unaffected. Results indicate that producing fruit on both primocanes and floricanes (double cropping) can improve sustainable overall yields.

The importance of community relocation experiences for aboriginal land claims movements is well documented; the role played by successful land claims in prompting ongoing out-migration is not. Data collected in 2011 on the lives of migrants are used to test three hypotheses: H1, Inuit leaving the land claims area for a nearby nonaboriginal city show markedly different social outcomes based on the length of time since migration; H2, these social outcomes map onto patterns of intergroup boundaries in their new communities; and H3, both of these outcomes are better explained by migration patterns after the land claims than by the ethnic/racial exclusion that has been the focus of past research on inequality in the region. This analysis takes advantage of social network techniques used to study hard-to-reach populations, showing how these methods can be used to address broader questions of community structure and cohesion during rapid social change. Conclusions focus on the experiences of migrants on the marg...

Indigenous communities across the Alaskan Arctic have experienced profound revisions of livelihood, culture, and autonomy over the past century of colonization, creating radical discontinuities between the lives of young people and those of their parents and Elders. The disrupted processes of identity development, access to livelihoods, and cross-generational mentorship associated with colonialism have created complex challenges for youth as they envision and enact viable paths forward in the context of a rapidly changing Arctic home. In this study, we consider the meanings associated with different constructions of culture and selfhood, and the ways in which these identity narratives position Inupiaq Alaskan Native youth in relation to their personal and collective futures. Through an intergenerational and participatory inquiry process, this study explores how representations of shared heritage, present-day struggles, resilience, and hope can expand possibilities for youth and thus impact individual and community health.

Fibrosis is characterized by the excessive deposition of extracellular matrix and crosslinked proteins, in particular collagen and elastin, leading to tissue stiffening and disrupted organ function. Lysyl oxidases are key players during this process, as they initiate collagen crosslinking through the oxidation of the ε‐amino group of lysine or hydroxylysine on collagen side‐chains, which subsequently dimerize to form immature, or trimerize to form mature, collagen crosslinks. The role of LOXL2 in fibrosis and cancer is well documented, however the specific enzymatic function of LOXL2 and LOXL3 during disease is less clear. Herein, we describe the development of PXS‐5153A, a novel mechanism based, fast‐acting, dual LOXL2/LOXL3 inhibitor, which was used to interrogate the role of these enzymes in models of collagen crosslinking and fibrosis. PXS‐5153A dose‐dependently reduced LOXL2‐mediated collagen oxidation and collagen crosslinking in vitro. In two liver fibrosis models, carbon tetrachloride or streptozotocin/high fat diet‐induced, PXS‐5153A reduced disease severity and improved liver function by diminishing collagen content and collagen crosslinks. In myocardial infarction, PXS‐5153A improved cardiac output. Taken together these results demonstrate that, due to their crucial role in collagen crosslinking, inhibition of the enzymatic activities of LOXL2/LOXL3 represents an innovative therapeutic approach for the treatment of fibrosis.

In recent Inuit ethnography, a major concern has been how and to what extent contemporary Inuit participate in and depend on subsistence activities, particularly in the context of increasing wage employment and growing participation in the cash economy. This paper provides an analysis of these activities in the predominately Inuit community of Nain, Labrador. Using social network data and demographic information collected between January and June 2010, we examine the interconnections between subsistence activities—obtaining “country food” through activities such as hunting, fishing, and collecting—with access to the means of obtaining subsistence resources (such as snow mobiles, cabins, and boats), employment status, and income. Our data indicate that individuals with higher employment status and income tend to be more central to the network of subsistence food sharing, but not because they have greater access to hunting tools or equipment (they do not). We conclude that those individuals who play the most central role in the network are those who are financially able to do so, regardless of access to hunting tools/means.

Transcriptional gene silencing has been reported with siRNA targeting the promoter region of genes. We tested several siRNAs directed against the human VEGF promoter. Of these, siVFp(−992) exhibited ≥50% suppression of VEGF production in two human cell lines. To determine the specificity of this siRNA-mediated suppression, plasmids were prepared to express a luciferase reporter under the control of VEGF promoters featuring wild-type, mutated, or deleted target sequences. siRNA transfection assays established sequence-specific inhibition of luciferase from the reporter plasmid featuring the wild-type VEGF promoter. However, siVFp(−992) also suppressed the luciferase expression from the plasmids with mutated or deleted target sites, suggesting that silencing was due to a sequence-specific off-target phenomenon, and this was supported by subsequent microarray and bioinformatics analyses. To determine if our concerns regarding the specificity of promoter targeting siRNAs were relevant to other systems where RNA-mediated transcriptional silencing had been previously reported, we tested a published small RNA sequence directed to the HIVSF2-LTR promoter. siRNA transfection assays performed in human cells expressing a luciferase reporter gene under the control of the HIVSF2-LTR promoter revealed significant suppression whether the target sequence was intact or mutated, or when the entire HIVSF2-LTR was replaced by an irrelevant promoter. These data stress the need to examine target specificity when conducting investigations into transcriptional gene regulation with siRNA.

Cellular junctions are essential to the normal functioning of the endothelium and control angiogenesis, tissue leak, and inflammation. From a screen of micro RNAs (miRNAs) altered in in vitro angiogenesis, we selected a subset predicted to target junctional molecules. MiR-27a was rapidly downregulated upon stimulation of in vitro angiogenesis, and its level of expression is reduced in neovessels in vivo. The downregulation of miR-27a was essential for angiogenesis because ectopic expression of miR-27a blocked capillary tube formation and angiogenesis. MiR-27a targets the junctional, endothelial-specific cadherin, VE-cadherin. Consistent with this, vascular permeability to vascular endothelial growth factor in mice is reduced by administration of a general miR-27 inhibitor. To determine that VE-cadherin was the dominant target of miR-27a function, we used a novel technology with "Blockmirs," inhibitors that bind to the miR-27 binding site in VE-cadherin. The Blockmir CD5-2 demonstrated specificity for VE-cadherin and inhibited vascular leak in vitro and in vivo. Furthermore, CD5-2 reduced edema, increased capillary density, and potently enhanced recovery from ischemic limb injury in mice. The Blockmir technology offers a refinement in the use of miRNAs, especially for therapy. Further, targeting of endothelial junctional molecules by miRNAs has clinical potential, especially in diseases associated with vascular leak.