Weak Coupling Among Barrier Loci and Waves of Neutral and Adaptive Introgression Across an Expanding Hybrid Zone

Hybridization can serve as an evolutionary stimulus, but we have little understanding of introgression at early stages of hybrid zone formation. We analyze reproductive isolation and introgression between a range-limited and a widespread species. Reproductive barriers are estimated based on differences in flowering time, ecogeographic distributions, and seed set from crosses. We find an asymmetrical mating barrier due to cytonuclear incompatibility that is consistent with observed clusters of coincident and concordant tension zone clines (barrier loci) for mtDNA haplotypes and nuclear SNPs. These groups of concordant clines are spread across the hybrid zone, resulting in weak coupling among barrier loci and extensive introgression. Neutral clines had nearly equal introgression into both species’ ranges, whereas putative cases of adaptive introgression had exceptionally wide clines with centers shifted toward one species. Analyses of cline shape indicate that secondary contact was initiated within the last 800 generations with the per-generation dispersal between 200 and 400 m, and provide some of the first estimates of the strength of selection required to account for observed levels of adaptive introgression. The weak species boundary between these species appears to be in early stages of dissolution, and ultimately will precipitate genetic swamping of the range-limited species

Importance of low-relief nursery habitat for reef fishes

Coastal restoration projects to mitigate environmental impacts have increased global demand for sand resources. Unfortunately, these resources are often extracted from sand/shell banks on the inner continental shelf, resulting in significant alteration or loss of low-relief reefs in coastal oceans. Experimental reefs (oyster shell, limestone rubble, composite) were deployed in the western Gulf of Mexico to assess their potential value as nurseries for newly settled reef fishes. Occurrence, abundance, and species richness of juvenile fishes were significantly higher on all three types of low-relief reefs compared with unconsolidated sediment. Moreover, reefs served as nursery habitat for a range of reef fish taxa (angelfishes, grunts, sea basses, snappers, and triggerfishes). Red snapper (Lutjanus campechanus) was the dominant species present on all experimental reefs (100% occurrence), and mean density of this species was markedly higher on each of the three low-relief reefs (\u3e40.0 individuals/reef) relative to comparable areas over unconsolidated sediment (0.2 individuals). Our results suggest creation or restoration of structurally complex habitat on the inner shelf has the potential to markedly increase early life survival and expedite the recovery of exploited reef fish populations, and therefore may represent a critical conservation tool for increasing recruitment and maintaining reef fish diversity

Evaluation of the pulmonary embolism rule out criteria (PERC rule) in children evaluated for suspected pulmonary embolism

Background The pulmonary embolism rule out criteria (PERC) reliably predicts a low probability of PE in adults. We examine the diagnostic accuracy of the objective components of the PERC rule in children previously tested for PE. Methods Children aged 5–17 who had a D-dimer or pulmonary vascular imaging ordered from 2004 to 2014 in a large multicenter hospital network were identified by query of administrative databases. Using explicit, predefined methods, trained abstracters selected charts of children clearly tested for PE, collected the 8 objective variables for PERC, and determined PE criterion standard status (image or autopsy confirmed PE or deep vein thrombosis within 30 days by query of the Indiana Network for Patient Care (INPC)). Results We identified 543 patients, including 56 (10.3%, 95% CI: 7.8–13.1%) who were PE+, with a mean and median age of 15 years. All 8 objective criteria from PERC were negative in 170 patients (31%), including one with PE (false negative rate 0.6%, 0–3.2%). Diagnostic sensitivity and specificity were 98.2% (90.5–100%), and 34.7 (30.5–39.1%), respectively, leading to a likelihood ratio negative = 0.05 (0.1–0.27). When treated as a diagnostic test based upon sum of criteria positive, PERC had good discrimination between PE+ vs PE− with an area under receiver operating characteristic curve 0.81 (0.75–0.86). Conclusions In this sample of children and teenagers with suspected PE, the PERC rule was negative in 31%, and demonstrated good overall diagnostic accuracy, including a low false negative rate. These data support the need for a large, prospective diagnostic validation study of PERC in children

Relationship of DAG1 and SERPINA5 Sperm Proteins With Bull Fertility

Study Description: Semen from 22 dairy bulls was used to evaluate the presence, localization, and quantification of DAG1 and SERPINA5 on sperm. Sperm motility parameters and viability was also evaluated for semen from each bull. Semen from 19 out of the 22 dairy bulls was used for in vitro embryo production (two Low-SCR and one High-SCR were not available for in vitro embryo production). Bulls were classified based on their sire conception rates (SCR) values as High-SCR (SCR \u3e 1.0) or Low-SCR fertility (SCR \u3c -4.0). Low fertility bulls were subdivided based on their blastocyst rate (BL) as High-BL (Low-SCR/High-BL BL ≥ 31%) or Low-BL (Low-SCR/Low-BL BL ≤ 26%), and High-SCR bulls were not subdivided. The GLM procedure in SAS was used with bull as a fixed effect to determine if variance was greater between bulls compared to within bull. Correlations were determined among DAG1 and SERPINA5 concentrations, percentage of tail labeled for SERPINA5, SCR, sperm total motility, progressive motility, and viability, and in vitro embryo produced cleavage rate (CL) and BL. The GLIMMIX procedure of SAS was used to evaluate the relationship of bull field fertility (High- and Low-SCR), and field and in vitro fertility (High-SCR, Low-SCR/High-BL, Low-SCR/Low-BL) classifications with sperm total (TMOT) and progressive (PROG) motility, viability, CL, BL, DAG1 and SERPINA5 relative concentration, and proportion of sperm tail labeled for SERPINA5. Both SERPINA5 and DAG1 were localized on the sperm head; however, SERPINA5 was also localized on the sperm tail. There was greater variance in concentration among bulls compared to within bull for both DAG1 (P \u3c 0.01; 69.4 vs 49.1, respectively) and SERPINA5 (P \u3c 0.01; 325.8 vs 285.4, respectively). There was a positive correlation between concentration of DAG1 and SERPINA5 (P = 0.01; r = 0.54). Concentrations of SERPINA5 were also correlated with CL (P = 0.04; r = 0.48), and percentage of sperm tail labeled for SERPINA5 was correlated with viability (P = 0.05; r = 0.44) and tended to be correlated with CL (P = 0.10; r = 0.39). There was no relationship between SCR or BL rate classifications and DAG1 (P ≥ 0.66), SERPINA5 (P ≥ 0.54), or percentage of sperm tail labeled for SERPINA5 (P ≥ 0.48)

Nanoemulsion Adjuvant Augments Retinaldehyde Dehydrogenase Activity in Dendritic Cells via MyD88 Pathway

Mucosal surfaces are the primary point of entry for many infectious agents and mucosal immune responses serve as the primary defense to these pathogens. In order to mount an effective mucosal immune response, it is important to induce T cell homing to mucosal surfaces. Conventional vaccine adjuvants induce strong systemic immunity but often fail to produce mucosal immunity. We have developed an oil-in-water nanoemulsion (NE) adjuvant that provides mucosal immunity and efficient protection against mucosal pathogens when administered as part of an intranasal vaccine. In the present study, we demonstrate that intranasal immunization with NE indirectly activates the retinaldehyde dehydrogenase (RALDH) activity in dendritic cells through epithelial cell activity leading to SIgA as well as potent cellular responses and expression of α4β7 and CCR9 gut homing receptors on T cells. Confirming these findings, ex-vivo stimulation of splenocytes from NE nasally immunized animals showed increase in Th1/Th17 cytokines while suppressing Th2 responses. In examining mechanisms underlying this activation NE activated RALDH via MyD88 dependent pathways in DCs but did not activate the retinoic acid receptor directly. These results suggest that RALDH immune activities can be achieved by epithelial activation without direct RAR activation, which has significant implications for understanding mucosal immunity and the design of mucosal vaccines

PATH-38. ROSETTE-FORMING GLIONEURONAL TUMOR IS DEFINED BY FGFR1 ACTIVATING ALTERATIONS WITH FREQUENT ACCOMPANYING PI3K AND MAPK PATHWAY MUTATIONS

Abstract BACKGROUND Rosette-forming glioneuronal tumor (RGNT) is an uncommon CNS tumor originally described in the fourth ventricle characterized by a low-grade glial neoplasm admixed with a rosette-forming neurocytic component. METHODS We reviewed clinicopathologic features of 42 patients with RGNT. Targeted next-generation sequencing was performed, and genome-wide methylation profiling is underway. RESULTS The 20 male and 22 female patients had a mean age of 25 years (range 3–47) at time of diagnosis. Tumors were located within or adjacent to the lateral ventricle (n=16), fourth ventricle (15), third ventricle (9), and spinal cord (2). All 31 tumors assessed to date contained FGFR1 activating alterations, either in-frame gene fusion, kinase domain tandem duplication, or hotspot missense mutation in the kinase domain (p.N546 or p.K656). While 7 of these 31 tumors harbored FGFR1 alterations as the solitary pathogenic event, 24 contained additional pathogenic alterations within PI3-kinase or MAP kinase pathway genes: 5 with additional PIK3CA and NF1 mutations, 4 with PIK3CA mutation, 3 with PIK3R1 mutation (one of which also contained focal RAF1 amplification), 5 with PTPN11 mutation (one with additional PIK3R1 mutation), and 2 with NF1 deletion. The other 5 cases demonstrated anaplastic features including hypercellularity and increased mitotic activity. Among these anaplastic cases, 3 harbored inactivating ATRX mutations and two harbored CDKN2A homozygous deletion, in addition to the FGFR1 alterations plus other PI3-kinase and MAP kinase gene mutations seen in those RGNT without anaplasia. CONCLUSION Independent of ventricular location, RGNT is defined by FGFR1 activating mutations or rearrangements, which are frequently accompanied by mutations involving PIK3CA, PIK3R1, PTPN11, NF1, and KRAS. Whereas pilocytic astrocytoma and ganglioglioma are characterized by solitary activating MAP kinase pathway alterations (e.g. BRAF fusion or mutation), RGNT are genetically more complex with dual PI3K-Akt-mTOR and Ras-Raf-MAPK pathway activation. Rare anaplastic examples may show additional ATRX and/or CDKN2A inactivation

Vitality, Language Use, and Life Satisfaction : A Study of Bilingual Hungarian Adolescents Living in Romania

This study examined the relationship between objective and subjective vitality, in-group language use, and life satisfaction among two groups of bilingual Hungarians adolescents living in Romania: a low objective vitality group from Cluj-Napoca/Kolozsvar, where Hungarians are the demographic minority, and a high objective vitality group from Sfantu Gheorghe/Sepsiszentgyorgy, where Hungarians are the demographic majority. Consistent with predictions, the high objective vitality group reported higher subjective Hungarian vitality, lower subjective Romanian vitality, more frequent use of the Hungarian language, and higher life satisfaction, compared with the low objective vitality group. The effects of objective vitality on language use were partially mediated by subjective Romanian (but not Hungarian) vitality. Conversely, the effects of objective vitality on life satisfaction were fully mediated by subjective Hungarian (but not Romanian) vitality.Peer reviewe