Quantifying the Indirect Effect of Wolves on Aspen in Northern Yellowstone National Park: Evidence for a Trophic Cascade?

Yellowstone National Park is renowned for its incredible wildlife, and perhaps the most famous of these species is the gray wolf, which was reintroduced to the Park in the mid-1990s. After reintroduction, it was highly publicized by scientists, journalists, and environmentalists that the wolf both decreased elk density and changed elk behavior in a way that reduced elk effects on plants, a process known as a “trophic cascade.” Aspen, which is eaten by elk in winter, is one species at the forefront of Yellowstone trophic cascade research because it has been in decline across the Park for over a century. However, due to the challenges of measuring trophic cascades, there is continued uncertainty regarding the effects of wolves on aspen in northern Yellowstone. Thus, the purpose of my dissertation was to provide a comprehensive test of a trophic cascade in this system. Specifically, I used 20 years of data on aspen, elk, and wolves in Yellowstone to: 1) clarify annual trends in browsing and height of young aspen (a proxy for regeneration) after wolf reintroduction, 2) assess the influence of wolves scaring elk on aspen (“trait-mediated indirect effects”), and 3) evaluate the effect of wolves killing elk on aspen (“density-mediated indirect effects”). My research suggests that wolves indirectly contributed to increased aspen over story recruitment following their reintroduction by helping to reduce the elk population size, but elk response to the risk of wolf predation did not reduce elk foraging in a way that measurably increased aspen recruitment. Additionally, hunter harvest of elk north of the park was twice as important as wolf predation in causing increased aspen recruitment. However, despite wolves and hunters limiting elk abundance, it is still uncommon for young aspen to grow past peak browsing height (120-cm), indicating that many stands remain vulnerable to elk herbivory nearly 30 years after wolf reintroduction. These results highlight that the strength and mechanism of predator effects on plant communities are context-specific. Thus, using predator reintroduction as a tool for ecosystem restoration without considering the many factors that shape trophic cascades may result in different management and conservation outcomes than intended

Sampling Bias Exaggerates a Textbook Example of a Trophic Cascade

Understanding trophic cascades in terrestrial wildlife communities is a major challenge because these systems are difficult to sample properly. We show how a tradition of non-random sampling has confounded this understanding in a textbook system (Yellowstone National Park) where carnivore [Canis lupus (wolf)] recovery is associated with a trophic cascade involving changes in herbivore [Cervus canadensis (elk)] behaviour and density that promote plant regeneration. Long-term data indicate a practice of sampling only the tallest young plants overestimated regeneration of overstory aspen (Populus tremuloides) by a factor of 4–7 compared to random sampling because it favoured plants taller than the preferred browsing height of elk and overlooked non-regenerating aspen stands. Random sampling described a trophic cascade, but it was weaker than the one that non-random sampling described. Our findings highlight the critical importance of basic sampling principles (e.g. randomisation) for achieving an accurate understanding of trophic cascades in terrestrial wildlife systems

Non-Random Sampling Measures the Occurrence but not the Strength of a Textbook Trophic Cascade

Although sampling the five tallest young aspen in a stand is useful for detecting the occurrence of any aspen recruitment, this technique overestimates the population response of aspen to wolf reintroduction. Our original conclusion that random sampling described a trophic cascade that was weaker than the one described by non-random sampling is unchanged

Impacts of Climate Change on Multiple Use Management of Bureau of Land Management Land in the Intermountain West, USA

Although natural resource managers are concerned about climate change, many are unable to adequately incorporate climate change science into their adaptation strategies or management plans, and are not always aware of or do not employ the most current scientific knowledge. One of the most prominent natural resource management agencies in the United States is the Bureau of Land Management (BLM), which is tasked with managing over 248 million acres (\u3e1 million km2) of public lands for multiple, often conflicting, uses. Climate change will affect the sustainability of many of these land uses and could further increase conflicts between them. As such, the purpose of our study was to determine the extent to which climate change will affect public land uses, and whether the BLM is managing for such predicted effects. To do so, we first conducted a systematic review of peer-reviewed literature that discussed potential impacts of climate change on the multiple land uses the BLM manages in the Intermountain West, USA, and then expanded these results with a synthesis of projected vegetation changes. Finally, we conducted a content analysis of BLM Resource Management Plans in order to determine how climate change is explicitly addressed by BLM managers, and whether such plans reflect changes predicted by the scientific literature. We found that active resource use generally threatens intrinsic values such as conservation and ecosystem services on BLM land, and climate change is expected to exacerbate these threats in numerous ways. Additionally, our synthesis of vegetation modeling suggests substantial changes in vegetation due to climate change. However, BLM plans rarely referred to climate change explicitly and did not reflect the results of the literature review or vegetation model synthesis. Our results suggest there is a disconnect between management of BLM lands and the best available science on climate change. We recommend that the BLM actively integrates such research into on-the-ground management plans and activities, and that researchers studying the effects of climate change make a more robust effort to understand the practices and policies of public land management in order to effectively communicate the management significance of their findings

Pathways curriculum and family interventions to promote healthful eating and physical activity in American Indian schoolchildren

Pathways, a multisite school-based study aimed at promoting healthful eating and increasing physical activity, was a randomized field trial including 1704 American Indian third to fifth grade students from 41 schools (21 intervention, 20 controls) in seven American Indian communities

The 'Survivorship Passport' for childhood cancer survivors

Background: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. Method: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union–funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. Results: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. Conclusions: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts