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Next-generation sequencing (NGS) assays can sensitively detect somatic variation, and increasingly can enable the identification of complex structural rearrangements. A subset of infantile spindle cell sarcomas, particularly congenital mesoblastic nephromas with classic or mixed histology, have structural rearrangement in the form of internal tandem duplications (ITD) involving EGFR. We performed prospective analysis to identify EGFR ITD through clinical or research studies, as well as retrospective analysis to quantify the frequency of EGFR ITD in pediatric sarcomas. Within our institution, three tumors with EGFR ITD were prospectively identified, all occurring in patients less than 1 year of age at diagnosis, including two renal tumors and one mediastinal soft tissue tumor. These three cases exhibited both cellular and mixed cellular and classic histology. All patients had no evidence of disease progression off therapy, despite incomplete resection. To extend our analysis and quantify the frequency of EGFR ITD in pediatric sarcomas, we retrospectively analyzed a cohort of tumors (n = 90) that were previously negative for clinical RT-PCR-based fusion testing. We identified EGFR ITD in three analyzed cases, all in patients less than 1 year of age (n = 18; 3/18, 17%). Here we expand the spectrum of tumors with EGFR ITD to congenital soft tissue tumors and report an unusual example of an EGFR ITD in a tumor with cellular congenital mesoblastic nephroma histology. We also highlight the importance of appropriate test selection and bioinformatic analysis for identification of this genomic alteration that is unexpectedly common in congenital and infantile spindle cell tumors.

Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified.We enrolled 50 children who were undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA sequencing to identify somatic variation and we confirmed our findings using high-depth targeted DNA sequencing.We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). In agreement with previous studies, we identified somatic variation affecting solute carrier family 35 member A2 (SLC35A2) and mechanistic target of rapamycin kinase (MTOR) pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) of patients with Type I focal cortical dysplasia (FCD)s. Somatic variation in mitogen-activated protein kinase (MAPK) pathway genes (i.e., fibroblast growth factor receptor 1 [FGFR1], FGFR2, B-raf proto-oncogene, serine/threonine kinase [BRAF], and KRAS proto-oncogene, GTPase [KRAS]) was associated with low-grade epilepsy-associated developmental tumors. RNA sequencing enabled the detection of somatic structural variation that would have otherwise been missed, and which accounted for more than one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes not yet associated with focal cortical dysplasia.These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

As global change shifts the species composition of forests, we need to understand which species characteristics affect soil organic matter cycling to predict future soil carbon (C) storage. Recently, whether a tree species forms a symbiosis with arbuscular (AM) versus ectomycorrhizal (EcM) fungi has been suggested as a strong predictor of soil carbon storage, but there is wide variability within EcM systems. In this study, we investigated how mycorrhizal associations and the species composition of canopy trees and mycorrhizal fungi relate to the proportion of soil C and nitrogen (N) in mineral-associations and soil C:N across four sites representing distinct climates and tree communities in the Eastern U.S. broadleaf forest biome. In two of our sites, we found the expected relationship of declining mineral-associated C and N and increasing soil C:N ratios as the basal area of EcM-associating trees increased. However, across all sites these soil properties strongly correlated with canopy tree and fungal species composition. Sites where the expected pattern with EcM basal area was observed were 1) dominated by trees with lower quality litter in the Pinaceae and Fagaceae families and 2) dominated by EcM fungi with medium distance exploration type hyphae, melanized tissues, and the potential to produce peroxidases. This observational study demonstrates that differences in soil organic matter between AM andEcM systems are dependent on the taxa of trees and EcM fungi involved. Important information is lost when the rich mycorrhizal symbiosis is reduced to two categories. This article is protected by copyright. All rights reserved.

Roads are a major driver of environmental stress, yet we know surprisingly little about how roads impact the movement of insect pollinators, and consequent pollination. We investigated the influence of roads on pollinator movement and pollination by examining patterns of pigment transfer between focal plants of two species, Coreopsis verticillata and Monarda fistulosa. We asked whether roads reduced pigment transfer, and what characteristics of roads were important in driving this reduction. We also evaluated whether pollinator assemblage differed between species, and if this mediated the effect of roads on pigment transfer. Plants across a road from a pigment‐added plant received significantly less pigment than plants on the same side of the road. This effect was stronger for coreopsis than for monarda. The mean body size of visitors to coreopsis was significantly smaller than that of visitors to monarda, suggesting that smaller bees are more limited by roads. Road width was the best predictor of pigment transfer, with a smaller effect of traffic volume; further research is needed to fully disentangle the effects of different road characteristics. Roadside habitat had little influence on pigment transfer, and roadside plants did not receive significantly less pigment than plants in contiguous habitat. Synthesis and applications. This study demonstrates that roads pose substantial barriers to bee movement, reducing pollen flow between plants located across roadways from one another. Road characteristics, particularly width and traffic volume, mediated this effect, as did bee size. Our results suggest that the effects of roads on pollinators and pollination can be mitigated by many of the same design strategies currently being implemented to reduce human traffic accidents, offering the opportunity for win–win scenarios.

Developmental dyslexia is a common neurodevelopmental disorder characterized by difficulties in reading and writing. Although underlying biological and genetic mechanisms remain unclear, anomalies in phonological processing and auditory processing have been associated with dyslexia. Several candidate risk genes have also been identified, with KIAA0319 as a main candidate. Animal models targeting the rodent homolog (Kiaa0319) have been used to explore putative behavioral and anatomic anomalies, with mixed results. For example after downregulation of Kiaa0319 expression in rats via shRNA, significant adult rapid auditory processing impairments were reported, along with cortical anomalies reflecting atypical neuronal migration. Conversely, Kiaa0319 knockout (KO) mice were reported to have typical adult auditory processing, and no visible cortical anomalies. To address these inconsistencies, we tested Kiaa0319 KO mice on auditory processing tasks similar to those used previously in rat shRNA knockdown studies. Subsequent neuroanatomic analyses on these same mice targeted medial geniculate nucleus (MGN), a receptive communication-related brain structure. Results confirm that Kiaa0319 KO mice exhibit significant auditory processing impairments specific to rapid/brief stimuli, and also show significant volumetric reductions and a shift toward fewer large and smaller neurons in the MGN. The latter finding is consistent with post mortem MGN data from human dyslexic brains. Combined evidence supports a role for KIAA0319 in the development of auditory CNS pathways subserving rapid auditory processing functions critical to the development of speech processing, language, and ultimately reading. Results affirm KIAA0319 variation as a possible risk factor for dyslexia specifically via anomalies in central acoustic processing pathways.

Chemical characterization of cryptotephra is critical for temporally linking archaeological sites. Here, we describe cryptotephra investigations of two Middle–Upper Paleolithic sites from north‐west Italy, Arma Veirana and Riparo Bombrini. Cryptotephra are present as small (75 wt.%) with low FeO ( 1 and P2 is also a high silica rhyolite (>75 wt.%) but with higher FeO (2.33–2.65 wt.%). Shards at Riparo Bombrini (P3) are of the same composition as P1 shards at Arma Veirana, providing a distinct link between deposits at both sites. Geochemical characteristics suggest three possible sources for P1 and P3: eruptions from Lipari Island (56–37.7 ka) in Italy, the Acigöl volcanic field (200–20 ka) in Turkey and the Miocene Kirka‐Phrigian caldera (18 Ma) in Turkey. Eruptions from Lipari Island are the most likely source for P1,3 cryptotephra. This study highlights how cryptotephra can benefit archaeology, by providing a direct link between Arma Veirana and Riparo Bombrini as well as other deposits throughout the Mediterranean.