From camps to communities: Neets'ąįį Gwich'in planning and development in a pre- and post-settlement context

Thesis (Ph.D.) University of Alaska Fairbanks, 2018This study focuses on the Neets'aii Gwich'in, whose traditional territory is located in the northeastern interior of Alaska, and their experiences with planning and development. Prior to settling into permanent villages, the Neets'ąįį lived in widely scattered camps moving in relation to seasonal subsistence resources. Equipped with extensive knowledge of their country, Neets'ąįį people knew at any given time where the best places for certain animals and resources were and thus would camp closer to those areas. According to Neets'ąįį oral history, life in the "those days" was preoccupied with basic survival. Planning ahead, being prepared, and adapting to changing conditions were some of the key strategies that enabled the Neets'ąįį to survive from one generation to the next in one of the harshest climates in the world. The past 170 years has brought unprecedented change to the Neets'ąįį. The socio-economic and political context which historically defined the experience of the Neets'ąįį shifted dramatically as a result of colonization, the establishment of permanent settlements and the ensuing need for community infrastructure. Today, the Neets'ąįį are centralized in two villages, Vashrąįį K'ǫǫ (Arctic Village) and Vįįhtąįį (Venetie), located within the boundaries of the 1.8 million-acre Venetie Indian Reserve. The transition from Neets'ąįį camps to permanent communities has introduced many new needs including landfills, roads, power generation, etc. Whereas Neets'ąįį ancestors traditionally used planning as a survival strategy, their descendants today use planning to attract external investment for much needed infrastructure. This dissertation explores the ways in which the Neets'ąįį Gwich'in have engaged in planning and development in a pre- and post-settlement context

A genome-wide in situ hybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain

BACKGROUND: In eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized. RESULTS: Here we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Using in situ hybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i) that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii) that a far larger subset (221) shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues. CONCLUSION: Our data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs that exhibit neural-specific expression as well as novel RBPs that show expression in non-neural tissues. The data presented here and in an online database provide a visual filter for the functional analysis of individual RBPs

Moons Are Planets: Scientific Usefulness Versus Cultural Teleology in the Taxonomy of Planetary Science

We argue that taxonomical concept development is vital for planetary science as in all branches of science, but its importance has been obscured by unique historical developments. The literature shows that the concept of planet developed by scientists during the Copernican Revolution was theory-laden and pragmatic for science. It included both primaries and satellites as planets due to their common intrinsic, geological characteristics. About two centuries later the non-scientific public had just adopted heliocentrism and was motivated to preserve elements of geocentrism including teleology and the assumptions of astrology. This motivated development of a folk concept of planet that contradicted the scientific view. The folk taxonomy was based on what an object orbits, making satellites out to be non-planets and ignoring most asteroids. Astronomers continued to keep primaries and moons classed together as planets and continued teaching that taxonomy until the 1920s. The astronomical community lost interest in planets ca. 1910 to 1955 and during that period complacently accepted the folk concept. Enough time has now elapsed so that modern astronomers forgot this history and rewrote it to claim that the folk taxonomy is the one that was created by the Copernican scientists. Starting ca. 1960 when spacecraft missions were developed to send back detailed new data, there was an explosion of publishing about planets including the satellites, leading to revival of the Copernican planet concept. We present evidence that taxonomical alignment with geological complexity is the most useful scientific taxonomy for planets. It is this complexity of both primary and secondary planets that is a key part of the chain of origins for life in the cosmos.Comment: 68 pages, 16 figures. For supplemental data files, see https://www.philipmetzger.com/moons_are_planets

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