Successful treatment of severe passenger lymphocyte syndrome with efgartigimod synergy.

INTRODUCTION: This case describes passenger lymphocyte syndrome (PLS) generating human platelet antigen 1a (HPA-1a) alloantibodies against the recipient's platelets after liver transplant. Given the rarity of PLS, especially in liver transplant with HPA-1a alloantibodies, disease course and management options are poorly described. METHODS: The patient had cirrhosis secondary to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma, encephalopathy, and severe ascites. The model for end-stage liver disease (MELD) score was 15 at presentation. The patient developed hepatic artery thrombosis after an orthotopic liver transplant and was relisted for transplant with a MELD score of 40. The patient received a hepatitis C virus antibody positive, hepatitis C virus nucleic amplification test positive donor liver on postoperative day (POD) 7 after first transplant. On POD 7 after the second transplant, the patient developed profound thrombocytopenia refractory to platelet infusion. They were found to have serum antibody to HPA-1a based upon serum platelet alloantibody testing. The donor was later found to be negative for HPA-1a by genetic testing. However, the patient's native platelets were HPA-1a positive. The patient was diagnosed with PLS. RESULTS: The patient's treatment course included 57 units of platelets transfused, emergency splenectomy, rituximab, plasma exchange, intravenous immunoglobulin (IVIG), eltrombopag, romiplostim, and efgartigimod. DISCUSSION: The synergistic effect of efgartigimod with eltrombopag and romiplostim most likely resolved the patient's thrombocytopenia. This case represents a novel use of efgartigimod in the treatment of passenger lymphocyte syndrome following liver transplant.

Inferring protein fitness landscapes from laboratory evolution experiments.

Directed laboratory evolution applies iterative rounds of mutation and selection to explore the protein fitness landscape and provides rich information regarding the underlying relationships between protein sequence, structure, and function. Laboratory evolution data consist of protein sequences sampled from evolving populations over multiple generations and this data type does not fit into established supervised and unsupervised machine learning approaches. We develop a statistical learning framework that models the evolutionary process and can infer the protein fitness landscape from multiple snapshots along an evolutionary trajectory. We apply our modeling approach to dihydrofolate reductase (DHFR) laboratory evolution data and the resulting landscape parameters capture important aspects of DHFR structure and function. We use the resulting model to understand the structure of the fitness landscape and find numerous examples of epistasis but an overall global peak that is evolutionarily accessible from most starting sequences. Finally, we use the model to perform an in silico extrapolation of the DHFR laboratory evolution trajectory and computationally design proteins from future evolutionary rounds.

Persistent Opioid Use After Cardiac Implantable Electronic Device Procedures.

BACKGROUND: Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown. METHODS: This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of patients undergoing CIED procedures. Adult patients were included if they were opioid-naïve during the 180-day period before the procedure and did not undergo another procedure with anesthesia in the next 180 days. POU was defined by filling an additional opioid prescription >30 days after the CIED procedure. RESULTS: Of the 143 400 patients who met the inclusion criteria, 15 316 (11%) filled an opioid prescription within 14 days of surgery. Among these patients, POU occurred in 1901 (12.4%) patients 30 to 180 days after surgery. The likelihood of developing POU was increased for patients who had a history of drug abuse (odds ratio, 1.52; P=0.005), preoperative muscle relaxant (odds ratio, 1.52; P<0.001) or benzodiazepine (odds ratio, 1.23; P=0.001) use, or opioid use in the previous 5 years (OR, 1.76; P<0.0001). POU did not differ after subcutaneous implantable cardioverter defibrillator or other CIED procedures (11.1 versus 12.4%; P=0.5). In a sensitivity analysis excluding high-risk patients who were discharged to a facility or who had a history of drug abuse or previous opioid, benzodiazepine, or muscle relaxant use, 8.9% of the remaining cohort had POU. Patients prescribed >135 mg of oral morphine equivalents had a significantly increased risk of POU. CONCLUSIONS: POU is common after CIED procedures, and 12% of patients continued to use opioids >30 days after surgery. Higher initially prescribed oral morphine equivalent doses were associated with developing POU.

Comparative transcriptomics and eQTL mapping of response to Melampsora americana in selected Salix purpurea F2 progeny.

BACKGROUND: Melampsora spp. rusts are the greatest pathogen threat to shrub willow (Salix spp.) bioenergy crops. Genetic resistance is key to limit the effects of these foliar diseases on host response and biomass yield, however, the genetic basis of host resistance has not been characterized. The addition of new genomic resources for Salix provides greater power to investigate the interaction between S. purpurea and M. americana, species commonly found in the Northeast US. Here, we utilize 3' RNA-seq to investigate host-pathogen interactions following controlled inoculations of M. americana on resistant and susceptible F2 S. purpurea genotypes identified in a recent QTL mapping study. Differential gene expression, network analysis, and eQTL mapping were used to contrast the response to inoculation and to identify associated candidate genes. RESULTS: Controlled inoculation in a replicated greenhouse study identified 19 and 105 differentially expressed genes between resistant and susceptible genotypes at 42 and 66 HPI, respectively. Defense response gene networks were activated in both resistant and susceptible genotypes and enriched for many of the same defense response genes, yet the hub genes of these common response modules showed greater mean expression among the resistant plants. Further, eight and six eQTL hotspots were identified at 42 and 66 HPI, respectively. The combined results of three analyses highlight 124 candidate genes in the host for further analysis while analysis of pathogen RNA showed differential expression of 22 genes, two of which are candidate pathogen effectors. CONCLUSIONS: We identified two differentially expressed M. americana transcripts and 124 S. purpurea genes that are good candidates for future studies to confirm their role in conferring resistance.

Increasing myocardial edema is associated with greater microvascular obstruction in ST-segment elevation myocardial infarction.

Microvascular obstruction (MVO) frequently develops after ST-elevation myocardial infarction (STEMI) and is associated with increased mortality and adverse left ventricular remodeling. We hypothesized that increased extravascular compressive forces in the myocardium that arise from the development of myocardial edema because of ischemia-reperfusion injury would contribute to the development of MVO. We measured MVO, infarct size, and left ventricular mass in patients with STEMI (n = 385) using cardiac MRI 2 to 3 days following successful percutaneous coronary intervention and stenting. MVO was found in 57% of patients with STEMI. The average infarct size was 45 ± 29 g. Patients with MVO had significantly greater infarct size and reduced left ventricular (LV) function (P < 0.01) compared with patients without MVO. Patients with MVO had significantly greater LV mass than patients without MVO and there was a linear increase in MVO with increasing LV mass (P < 0.001). Myocardial edema by T2-weighted imaging increased with increasing LV mass and patients with MVO had significantly greater myocardial edema than patients without MVO (P < 0.01). Patients with MVO had significantly greater left ventricular end-diastolic pressure (LVEDP) than patients without MVO (P < 0.05). In a cohort of patients with STEMI who underwent primary percutaneous intervention, we observed that MVO increased linearly with increasing LV mass and was associated with increased myocardial edema and higher LVEDP. These observations support the concept that extravascular compressive forces in the left ventricle may increase with increasing ischemic injury and contribute to the development of MVO.NEW & NOTEWORTHY Patients with STEMI (n = 385) had cardiac MRIs 2 to 3 days following reperfusion with primary PCI to determine the relationship between myocardial edema, LV mass, and MVO. We observed that MVO increased linearly with LV mass and that myocardial edema measured by T2-imaging also increased linearly with LV mass. Patients with MVO had greater edema and LVEDP than subjects without MVO. These findings suggest that myocardial edema which arises from ischemia-reperfusion injury may result in extravascular compression of the microcirculation manifested as MVO on cardiac MRI.

Whole-Brain Dynamics in Aging: Disruptions in Functional Connectivity and the Role of the Rich Club.

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50-64 years versus older group (n = 310); age range, 65-91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

The Melampsora americana Population on Salix purpurea in the Great Lakes Region Is Highly Diverse with a Contributory Influence of Clonality.

Shrub willows (Salix spp.) are emerging as a viable lignocellulosic, second-generation bioenergy crop with many growth characteristics favorable for marginal lands in New York State and surrounding areas. Willow rust, caused by members of the genus Melampsora, is the most limiting disease of shrub willow in this region and remains extremely understudied. In this study, genetic diversity, genetic structure, and pathogen clonality were examined in Melampsora americana over two growing seasons via genotyping-by-sequencing to identify single-nucleotide polymorphism markers. In conjunction with this project, a reference genome of rust isolate R15-033-03 was generated to aid in variant discovery. Sampling between years allowed regional and site-specific investigation into population dynamics, in the context of both wild and cultivated hosts within high-density plantings. This work revealed that this pathogen is largely panmictic over the sampled areas, with few sites showing moderate genetic differentiation. These data support the hypothesis of sexual recombination between growing seasons because no genotype persisted across the two years of sampling. Additionally, clonality was determined as a driver of pathogen populations within cultivated fields and single shrubs; however, there is also evidence of high genetic diversity of rust isolates in all settings. This work provides a framework for M. americana population structure in the Great Lakes region, providing crucial information that can aid in future resistance breeding efforts.

Determination of anatomic level of myelomeningocele by prenatal ultrasound.

PURPOSE: Ultrasound is the primary method for prenatal identification of myelomeningocele and is critical to prognostication and treatment planning. No study has considered the degree of inaccuracy of prenatal US lesion level estimates and anatomic lesion level on postnatal imaging using the weighted kappa coefficient (κw), nor the impact of maternal BMI on agreement. We examined the accuracy of prenatal ultrasound lesion level estimation in a cohort of patients with myelomeningocele using κw and determined whether BMI influenced accuracy. METHODS: The study is a retrospective review including patients born 2011-2019 who had prenatal imaging and primary myelomeningocele closure at a single institution. Lesion levels from prenatal ultrasound and postnatal imaging studies were analyzed for agreement at exact level, within 1 level, and within 2 levels using κw. Maternal BMI was examined for correlation with accuracy. RESULTS: Fifty-seven patients met inclusion criteria. Mean BMI was 31.2. There was no association between maternal BMI and agreement at any level. Lesion level on prenatal ultrasound agreed with postnatal imaging to the exact level in 13 (22.8%) cases, within 1 level in 38 (66.7%) cases, and within 2 levels in 50 (87.7%) cases. Weighted kappa showed moderate agreement at exact level (κw = 0.494) and substantial agreement within 1 (κw = 0.761) and 2 levels (κw = 0.902). CONCLUSION: Weighted kappa adds confidence for clinical decision making by accounting for accuracy. Prenatal ultrasound is a reliable and accurate method of determining lesion level with near-perfect agreement to postnatal imaging within 2 spinal levels. Maternal BMI may not influence lesion level determination after initial diagnosis.

Anxiety and depression affect performance on the symbol digit modalities test over time in MS and other immune disorders.

BACKGROUND: Longitudinal studies assessing depression and anxiety effects on cognition in multiple sclerosis (MS) are limited. OBJECTIVE: We tested whether within-person fluctuations in symptoms of depression or anxiety over time affect cognition in persons with MS, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and a lifetime history of depression/anxiety disorders (DEP/ANX) but without an immune-mediated inflammatory diseases (IMID). METHODS: We followed participants (MS: 255, IBD: 247, RA: 154, and DEP/ANX: 306) for 3 years. Annually, they completed the hospital anxiety and depression scale (HADS) and cognitive tests including the symbol digit modalities test (SDMT). We evaluated associations of elevated symptoms (scores ⩾ 11) of anxiety (HADS-A) and depression (HADS-D) with SDMT z-scores using multivariable linear models-estimating between-person and within-person effects. RESULTS: Participants with MS performed worse on the SDMT than participants in the DEP/ANX cohort (ß = -0.68; 95% CI: -0.88, -0.48). Participants with elevated HADS-A scores performed worse on the SDMT than those without elevated scores (ß = -0.43; 95% CI: -0.65, -0.21), particularly those with RA. Time-varying within-person elevations in depressive symptoms were associated with worse SDMT performance (ß = -0.12; 95% CI: -0.21, -0.021). CONCLUSIONS: Across persons, elevated symptoms of anxiety adversely affected information processing. Elevated symptoms of depression within-persons over time were associated with declines in information processing speed.

Sexual dimorphism in the dioecious willow Salix purpurea.

PREMISE: The evolution of sex chromosomes is driven by sexual dimorphism, yet it can be challenging to document sexually dimorphic traits in dioecious plant species. At the genetic level, sexual dimorphism can be identified through sequence variation between females and males associated with sexually antagonistic traits and different fitness optima. This study aims to examine sexual dimorphism for 26 traits in three populations of Salix purpurea (a diversity panel and F1 and F2 populations) and determine the effect of the traits on biomass yield, a key trait in Salix bioenergy crops across multiple years, locations, and under manipulated growth conditions. METHODS: Sexual dimorphism was evaluated for morphological, phenological, physiological, and wood composition traits in a diversity panel of unrelated S. purpurea accessions and in full-sib F1 and F2 families produced through controlled cross pollinations and grown in replicated field trials. RESULTS: We observed sexual dimorphism in the timing of development for several traits that were highly predictive of biomass yield across three populations of S. purpurea. Across all populations and years surveyed, males had significantly shallower branching angle. Male plants highly predictive of biomass yield across three populations of S. purpurea also accumulated more nitrogen under fertilizer amendment as measured by SPAD in the diversity panel and had greater susceptibility to the rust fungus Melampsora americana in the F2 family. Allometric modelling of biomass yield showed an effect of sex and of location on the interaction between yield and stem height. CONCLUSIONS: These results provide evidence of sexual dimorphism for certain traits in S. purpurea that may be involved in sex chromosome evolution.

Does taxonomic and numerical resolution affect the assessment of invertebrate community structure in New World freshwater wetlands?

The efficiency of biodiversity assessments and biomonitoring studies is commonly challenged by limitations in taxonomic identification and quantification approaches. In this study, we assessed the effects of different taxonomic and numerical resolutions on a range of community structure metrics in invertebrate compositional data sets from six regions distributed across North and South America. We specifically assessed the degree of similarity in the metrics (richness, equitability, beta diversity, heterogeneity in community composition and congruence) for data sets identified to a coarse resolution (usually family level) and the finest taxonomic resolution practical (usually genus level, sometimes species or morphospecies) and by presence-absence and relative abundance numerical resolutions. Spearman correlations showed highly significant and positive associations between univariate metrics (richness and equitability) calculated for coarse- and finest-resolution datasets. Procrustes analysis detected significant congruence between composition datasets. Higher correlation coefficients were found for datasets with the same numerical resolutions regardless of the taxonomic level (about 90%), while the correlations for comparisons across numerical resolutions were consistently lower. Our findings indicate that family-level resolution can be used as a surrogate of finer taxonomic resolutions to calculate a range of biodiversity metrics commonly used to describe invertebrate community structure patterns in New World freshwater wetlands without significant loss of information. However, conclusions on biodiversity patterns derived from datasets with different numerical resolutions should be critically considered in studies on wetland invertebrates.

n→π* Interactions Modulate the Disulfide Reduction Potential of Epidithiodiketopiperazines.

Epithiodiketopiperazines (ETPs) are a structurally complex class of fungal natural products with potent anticancer activity. In ETPs, the diketopiperazine ring is spanned by a disulfide bond that is constrained in a high-energy eclipsed conformation. We employed computational, synthetic, and spectroscopic methods to investigate the physicochemical attributes of this atypical disulfide bond. We find that the disulfide bond is stabilized by two n→π* interactions, each with large energies (3-5 kcal/mol). The n→π* interactions in ETPs make disulfide reduction much more difficult, endowing stability in physiological environments in a manner that could impact their biological activity. These data reveal a previously unappreciated means to stabilize a disulfide bond and highlight the utility of the n→π* interaction in molecular design.

A sense of place: pink salmon use a magnetic map for orientation.

The use of 'map-like' information from the Earth's magnetic field for orientation has been shown in diverse taxa, but questions remain regarding the function of such maps. We used a 'magnetic displacement' experiment to demonstrate that juvenile pink salmon (Oncorhynchus gorbuscha) use magnetic cues to orient. The experiment was designed to simultaneously explore whether their magnetic map is used to direct fish (i) homeward, (ii) toward the center of their broad oceanic range or (iii) along their oceanic migratory route. The headings adopted by these navigationally naive fish coincided remarkably well with the direction of the juveniles' migration inferred from historical tagging and catch data. This suggests that the large-scale movements of pink salmon across the North Pacific may be driven largely by their innate use of geomagnetic map cues. Key aspects of the oceanic ecology of pink salmon and other marine migrants might therefore be predicted from magnetic displacement experiments.

Synthesis of Potent Cytotoxic Epidithiodiketopiperazines Designed for Derivatization.

We describe our design, synthesis, and chemical study of a set of functional epidithiodiketopiperazines (ETPs) and evaluation of their activity against five human cancer cell lines. Our structure-activity relationship-guided substitution of ETP alkaloids offers versatile derivatization while maintaining potent anticancer activity, offering exciting opportunity for their use as there are no examples of complex and potently anticancer (nM) ETPs being directly used as conjugatable probes or warheads. Our synthetic solutions to strategically designed ETPs with functional linkers required advances in stereoselective late-stage oxidation and thiolation chemistry in complex settings, including the application of novel reagents for dihydroxylation and cis-sulfidation of diketopiperazines. We demonstrate that complex ETPs equipped with a strategically substituted azide functional group are readily derivatized to the corresponding ETP-triazoles without compromising anticancer activity. Our chemical stability studies of ETPs along with cytotoxic evaluation of our designed ETPs against A549, DU 145, HeLa, HCT 116, and MCF7 human cancer cell lines provide insights into the impact of structural features on potency and chemical stability, informing future utility of ETPs in chemical and biological studies.

Association between Maternal Serum Hormones along the Maternal-Fetal Hypothalamic-Pituitary-Adrenal Axis and Successful Vaginal Delivery Measured Prior to Labor Induction.

OBJECTIVE: This study aimed to evaluate if maternal serum hormones along the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis, when drawn prior to labor induction, differed between women who delivered vaginally and those who underwent cesarean. STUDY DESIGN: This was a prospective observational study at a single perinatal center performed from August 2017 to May 2018. Nulliparous women with uncomplicated singleton pregnancies ≥39 weeks had maternal serum collected prior to induction. Corticotrophin-releasing hormone (CRH) was measured by ELISA; dehydroepiandrosterone sulfate (DHEA-S), cortisol, estriol (E3) estradiol (E2), and progesterone (P4) were measured by chemiluminescent reaction. Mean analyte concentrations as well as three ratios (E2/P4, E3/P4, and E2/E3) were compared between women who had a vaginal versus cesarean delivery. Logistic regression was used to model the relationship between CRH and the odds of vaginal birth. We estimated that a sample size of 66 would have 90% power to detect a 25% difference in mean CRH levels assuming a vaginal:cesarean ratio of 2:1 with a baseline CRH concentration of 140 (standard deviation = 36) pg/mL. RESULTS: Of the 88 women who had their serum analyzed, 27 (31%) underwent cesarean. Mean maternal serum CRH levels were similar between the vaginal delivery and cesarean groups (122.6 ± 95.2 vs. 112.3 ± 142.4, p = 0.73). Similarly, there were no significant differences in any other maternal serum analytes or ratios. Logistic regression showed a nonsignificant odds ratio for successful vaginal birth (p = 0.69) even when evaluating only the 16 women who had a cesarean for an arrest disorder (p = 0.08). CONCLUSION: In low-risk nulliparous women undergoing full-term labor induction, there were no differences noted in a broad array of other maternal-fetal HPA-axis hormones between women who had a vaginal or cesarean delivery.

Differential Susceptibility of Diverse Salix spp. to Melampsora americana and Melampsora paradoxa.

Melampsora spp. willow rust is the most serious disease of shrub willow bioenergy production in the northeastern United States. Recent phylogenetic studies have identified several Melampsora spp. present on willow in the Northeast; however, in-depth understanding of Melampsora spp. host susceptibility remain unresolved. In this study, a panel of 82 rust isolates collected from the northeastern United States were genotyped via ribosomal DNA sequencing and a subset of these isolates were assayed for host susceptibility. This work revealed that Melampsora americana is the most prevalent species in the sampled geographic region and that there is potential for rust resistance breeding using the Salix spp. taxa assayed. Additionally, leaf morphology traits of these Salix spp. hosts were quantified for correlation analysis, revealing that trichome density and stomata density are possible contributors to resistance. This work provides foundational rust pathology information, which is crucial for M. americana resistance breeding.

EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice.

BACKGROUND: EphrinA1-Fc abolishes acute I/R injury and attenuates nonreperfused cardiac injury 4 days after permanent occlusion in mice. The goal of this study was to assess the capacity of a single intramyocardial administration of ephrinA1-Fc at the time of coronary artery ligation, to determine the degree to which early salvage effects translate to reduced adverse remodeling after 4 weeks of nonreperfused myocardial infarction (MI) in wild-type B6 and EphA2-R-M (EphA2 receptor null) mice. METHODS: At 4 weeks post-MI, echocardiography, histologic and immunohistochemical analyses of B6 mouse hearts were performed. Primary mouse cardiac fibroblasts (FBs) isolated from B6 mice cultured in the presence of low and high dose ephrinA1-Fc, both with and without pro-fibrotic TGF-ß stimulation and Western blots, were probed for relative expression of remodeling proteins MMP-2, MMP-9 and TIMP-1, in addition to DDR2 and (p)SMAD2/3/totalSMAD2/3. RESULTS: EphrinA1-Fc preserved a significant degree of contractile function, decreased adverse left ventricular remodeling, attenuated excessive compensatory hypertrophy, and decreased interstitial fibrosis in wild-type (WT) B6 mouse hearts. In contrast, most of these parameters were poorer in ephrinA1-Fc-treated EphA2-R-M mice. Of note, fibrosis was proportionately decreased, implying that other EphA receptor(s) are more important in regulating the pro-fibrotic response. Primary FBs showed disparate alteration of MMP-2, MMP-9 and TIMP-1, as well as DDR2 and p-SMAD2/3/totalSMAD2/3, which indicates that matrix remodeling and cardiac fibrosis in the injured heart are influenced by ephrinA1-Fc. CONCLUSION: This study demonstrates the capacity of a single administration of ephrinA1-Fc at the onset of injury to attenuate long-term nonreperfused post-MI ventricular remodeling that results in progressive heart failure, and the important role of EphA2 in mitigating the deleterious effects.

Elevated CO2 impairs olfactory-mediated neural and behavioral responses and gene expression in ocean-phase coho salmon (Oncorhynchus kisutch).

Elevated concentrations of CO2 in seawater can disrupt numerous sensory systems in marine fish. This is of particular concern for Pacific salmon because they rely on olfaction during all aspects of their life including during their homing migrations from the ocean back to their natal streams. We investigated the effects of elevated seawater CO2 on coho salmon (Oncorhynchus kisutch) olfactory-mediated behavior, neural signaling, and gene expression within the peripheral and central olfactory system. Ocean-phase coho salmon were exposed to three levels of CO2 , ranging from those currently found in ambient marine water to projected future levels. Juvenile coho salmon exposed to elevated CO2 levels for 2 weeks no longer avoided a skin extract odor that elicited avoidance responses in coho salmon maintained in ambient CO2 seawater. Exposure to these elevated CO2 levels did not alter odor signaling in the olfactory epithelium, but did induce significant changes in signaling within the olfactory bulb. RNA-Seq analysis of olfactory tissues revealed extensive disruption in expression of genes involved in neuronal signaling within the olfactory bulb of salmon exposed to elevated CO2 , with lesser impacts on gene expression in the olfactory rosettes. The disruption in olfactory bulb gene pathways included genes associated with GABA signaling and maintenance of ion balance within bulbar neurons. Our results indicate that ocean-phase coho salmon exposed to elevated CO2 can experience significant behavioral impairments likely driven by alteration in higher-order neural signal processing within the olfactory bulb. Our study demonstrates that anadromous fish such as salmon may share a sensitivity to rising CO2 levels with obligate marine species suggesting a more wide-scale ecological impact of ocean acidification.

Joint linkage and association mapping of complex traits in shrub willow (Salix purpurea L.).

BACKGROUND AND AIMS: Increasing energy demands and the necessity to reduce greenhouse gas emissions are key motivating factors driving the development of lignocellulosic crops as an alternative to non-renewable energy sources. The effects of global climate change will require a better understanding of the genetic basis of complex adaptive traits to breed more resilient bioenergy feedstocks, like willow (Salix spp.). Shrub willow is a sustainable and dedicated bioenergy crop, bred to be fast-growing and high-yielding on marginal land without competing with food crops. In a rapidly changing climate, genomic advances will be vital for the sustained improvement of willow and other non-model bioenergy crops. Here, joint genetic mapping was used to exploit genetic variation garnered from both recent and historical recombination events in S. purpurea. METHODS: A panel of North American naturalized S. purpurea accessions and full-sib F2S. purpurea population were genotyped and phenotyped for a suite of morphological, physiological, pest and disease resistance, and wood chemical composition traits, collected from multi-environment and multi-year replicated field trials. Controlling for population stratification and kinship in the association panel and spatial variation in the F2, a comprehensive mixed model analysis was used to dissect the complex genetic architecture and plasticity of these important traits. KEY RESULTS: Individually, genome-wide association (GWAS) models differed in terms of power, but the combined approach, which corrects for yearly and environmental co-factors across datasets, improved the overall detection and resolution of associated loci. Although there were few significant GWAS hits located within support intervals of QTL for corresponding traits in the F2, many large-effect QTL were identified, as well as QTL hotspots. CONCLUSIONS: This study provides the first comparison of linkage analysis and linkage disequilibrium mapping approaches in Salix, and highlights the complementarity and limits of these two methods for elucidating the genetic architecture of complex bioenergy-related traits of a woody perennial breeding programme.