The Dilemma of Dredging and Dredged Material Disposal in the Aquatic Waters of Rhode Island and Its Impact on the Regional Marina Industry

Since the closures, in 1971, of the Prudence Island and Brenton Reef disposal sites, water-related industries have not had aquatic disposal of dredged sediments as a management option. The marina industry in Rhode Island has been especially impacted as natural sedimentation processes have reduced the water depths at many of these locations and have resulted in the loss of business as operators have been unable to operate their marinas to their fullest potential. The elimination of this option is based on political and environmental concerns over declines in local commercial fisheries which are alleged to be the result of the aquatic disposal of dredged sediments from the Providence River Channel deepening project. Politically, the dredging and disposal issue is very complex as authority to permit dredging resides in several state and federal agencies. Regulations result in long processing times and increased costs for applications, and claims of economic hardship are being by the marina industry. Finally, while acknowledging the need to define a long-term solution for dredging and disposal problems, there is steadfast opposition to these activities from commercial fishing and environmental interests

Simulating nutrient release from parental carcasses increases the growth, biomass and genetic diversity of juvenile Atlantic salmon

The net transport of nutrients by migratory fish from oceans to inland spawning areas has decreased due to population declines and migration barriers. Restoration of nutrients to increasingly oligotrophic upland streams (that were historically salmon spawning areas) have shown short‐term benefits for juvenile salmon, but the longer term consequences are little known. Here we simulated the deposition of a small number of adult Atlantic salmon Salmo salar carcasses at the end of the spawning period in five Scottish upland streams (‘high parental nutrient’ treatment), while leaving five reference streams without carcasses (‘low parental nutrient’ treatment). All streams received exactly the same number of salmon eggs (n = 3,000) drawn in equal number from the same 30 wild‐origin families, thereby controlling for initial egg density and genetic composition. We then monitored the resulting juvenile salmon and their macroinvertebrate prey, repeating the carcass addition treatment in the next spawning season. Macroinvertebrate biomass and abundance were five times higher in the high parental nutrient streams, even 1 year after the carcass addition, and led to faster growth of juvenile salmon over the next 2 years (but with no change in population density). This faster growth led to more fish exceeding the size threshold that would trigger emigration to sea at 2 rather than 3 years of age. There was also higher genetic diversity among surviving salmon in high parental nutrient streams; genotyping showed that these effects were not due to immigration but to differential survival. Synthesis and applications. This 2‐year field experiment shows that adding nutrients that simulate the presence of small numbers of adult salmon carcasses can have long‐term effects on the growth rate of juvenile salmon, likely increasing the number that will migrate to sea early and also increasing their genetic diversity. However, the feasibility of adding nutrients to spawning streams as a management tool to boost salmon populations will depend on whether the benefits at this stage are maintained over the entire life cycle

Simulating nutrient release from parental carcasses increases the growth, biomass and genetic diversity of juvenile Atlantic salmon

The net transport of nutrients by migratory fish from oceans to inland spawning areas has decreased due to population declines and migration barriers. Restoration of nutrients to increasingly oligotrophic upland streams (that were historically salmon spawning areas) have shown short‐term benefits for juvenile salmon, but the longer term consequences are little known. Here we simulated the deposition of a small number of adult Atlantic salmon Salmo salar carcasses at the end of the spawning period in five Scottish upland streams (‘high parental nutrient’ treatment), while leaving five reference streams without carcasses (‘low parental nutrient’ treatment). All streams received exactly the same number of salmon eggs (n = 3,000) drawn in equal number from the same 30 wild‐origin families, thereby controlling for initial egg density and genetic composition. We then monitored the resulting juvenile salmon and their macroinvertebrate prey, repeating the carcass addition treatment in the next spawning season. Macroinvertebrate biomass and abundance were five times higher in the high parental nutrient streams, even 1 year after the carcass addition, and led to faster growth of juvenile salmon over the next 2 years (but with no change in population density). This faster growth led to more fish exceeding the size threshold that would trigger emigration to sea at 2 rather than 3 years of age. There was also higher genetic diversity among surviving salmon in high parental nutrient streams; genotyping showed that these effects were not due to immigration but to differential survival. Synthesis and applications. This 2‐year field experiment shows that adding nutrients that simulate the presence of small numbers of adult salmon carcasses can have long‐term effects on the growth rate of juvenile salmon, likely increasing the number that will migrate to sea early and also increasing their genetic diversity. However, the feasibility of adding nutrients to spawning streams as a management tool to boost salmon populations will depend on whether the benefits at this stage are maintained over the entire life cycle

PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR.

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a Myc motif in their promoter. MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases MYC translation. In summary, our data suggest that PHAROH regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma

Providing a Framework for Seagrass Mapping in United States Coastal Ecosystems Using High Spatial Resolution Satellite Imagery

Seagrasses have been widely recognized for their ecosystem services, but traditional seagrass monitoring approaches emphasizing ground and aerial observations are costly, time-consuming, and lack standardization across datasets. This study leveraged satellite imagery from Maxar\u27s WorldView-2 and WorldView-3 high spatial resolution, commercial satellite platforms to provide a consistent classification approach for monitoring seagrass at eleven study areas across the continental United States, representing geographically, ecologically, and climatically diverse regions. A single satellite image was selected at each of the eleven study areas to correspond temporally to reference data representing seagrass coverage and was classified into four general classes: land, seagrass, no seagrass, and no data. Satellite-derived seagrass coverage was then compared to reference data using either balanced agreement, the Mann-Whitney U test, or the Kruskal-Wallis test, depending on the format of the reference data used for comparison. Balanced agreement ranged from 58% to 86%, with better agreement between reference- and satellite-indicated seagrass absence (specificity ranged from 88% to 100%) than between reference- and satellite-indicated seagrass presence (sensitivity ranged from 17% to 73%). Results of the Mann-Whitney U and Kruskal-Wallis tests demonstrated that satellite-indicated seagrass percentage cover had moderate to large correlations with reference-indicated seagrass percentage cover, indicative of moderate to strong agreement between datasets. Satellite classification performed best in areas of dense, continuous seagrass compared to areas of sparse, discontinuous seagrass and provided a suitable spatial representation of seagrass distribution within each study area. This study demonstrates that the same methods can be applied across scenes spanning varying seagrass bioregions, atmospheric conditions, and optical water types, which is a significant step toward developing a consistent, operational approach for mapping seagrass coverage at the national and global scales. Accompanying this manuscript are instructional videos describing the processing workflow, including data acquisition, data processing, and satellite image classification. These instructional videos may serve as a management tool to complement field- and aerial-based mapping efforts for monitoring seagrass ecosystems

Sub-micron moulding topological mass transport regimes in angled vortex fluidic flow

Shear stress in dynamic thin films, as in vortex fluidics, can be harnessed for generating non-equilibrium conditions, but the nature of the fluid flow is not understood. A rapidly rotating inclined tube in the vortex fluidic device (VFD) imparts shear stress (mechanical energy) into a thin film of liquid, depending on the physical characteristics of the liquid and rotational speed,ω, tilt angle,θ, and diameter of the tube. Through understanding that the fluid exhibits resonance behaviours from the confining boundaries of the glass surface and the meniscus that determines the liquid film thickness, we have established specific topological mass transport regimes. These topologies have been established through materials processing, as spinning top flow normal to the surface of the tube, double-helical flow across the thin film, and spicular flow, a transitional region where both effects contribute. The manifestation of mass transport patterns within the film have been observed by monitoring the mixing time, temperature profile, and film thickness against increasing rotational speed,ω. In addition, these flow patterns have unique signatures that enable the morphology of nanomaterials processed in the VFD to be predicted, for example in reversible scrolling and crumbling graphene oxide sheets. Shear-stress induced recrystallisation, crystallisation and polymerisation, at different rotational speeds, provide moulds of high-shear topologies, as ‘positive’ and ‘negative’ spicular flow behaviour. ‘Molecular drilling’ of holes in a thin film of polysulfone demonstrate spatial arrangement of double-helices. The grand sum of the different behavioural regimes is a general fluid flow model that accounts for all processing in the VFD at an optimal tilt angle of 45°, and provides a new concept in the fabrication of novel nanomaterials and controlling the organisation of matter

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are the predominant dependency present in >90% of PDAC patients, targeting KRAS mutants directly has been challenging in PDAC. Similarly, strategies targeting known KRAS downstream effectors have had limited clinical success due to feedback mechanisms, alternate pathways, and dose-limiting toxicities in normal tissues. Therefore, identifying additional functionally relevant KRAS interactions in PDAC may allow for a better understanding of feedback mechanisms and unveil potential therapeutic targets. Here, we used proximity labeling to identify protein interactors of active KRAS in PDAC cells. We expressed fusions of wild-type (WT) (BirA-KRAS4B), mutant (BirA-KRAS4BG12D), and nontransforming cytosolic double mutant (BirA-KRAS4BG12D/C185S) KRAS with the BirA biotin ligase in murine PDAC cells. Mass spectrometry analysis revealed that RSK1 selectively interacts with membrane-bound KRASG12D, and we demonstrate that this interaction requires NF1 and SPRED2. We find that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS. Our findings link NF1 to the membrane-localized functions of RSK1 and highlight a role for WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors in PDAC

Harnessing landrace diversity empowers wheat breeding

Harnessing genetic diversity in major staple crops through the development of new breeding capabilities is essential to ensure food security1. Here we examined the genetic and phenotypic diversity of the A.E. Watkins landrace collection2 of bread wheat (Triticum aestivum), a major global cereal, through whole-genome re-sequencing (827 Watkins landraces and 208 modern cultivars) and in-depth field evaluation spanning a decade. We discovered that modern cultivars are derived from just two of the seven ancestral groups of wheat and maintain very long-range haplotype integrity. The remaining five groups represent untapped genetic sources, providing access to landrace-specific alleles and haplotypes for breeding. Linkage disequilibrium (LD) based haplotypes and association genetics analyses link Watkins genomes to the thousands of high-resolution quantitative trait loci (QTL), and significant marker-trait associations identified. Using these structured germplasm, genotyping and informatics resources, we revealed many Watkins-unique beneficial haplotypes that can confer superior traits in modern wheat. Furthermore, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritised QTL in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilising genetic diversity in crop improvement to achieve sustainable food security.</p

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known