Decoding function through comparative genomics: from animal evolution to human disease

Deciphering the functionality encoded in the genome constitutes an essential first step to understanding the context through which mutations can cause human disease. In this dissertation, I present multiple studies based on the use or development of comparative genomics techniques to elucidate function (or lack of function) from the genomes of humans and other animal species. Collectively, these studies focus on two biological entities encoded in the human genome: genes related to human disease susceptibility and those that encode microRNAs - small RNAs that have important gene-regulatory roles in normal biological function and in human disease. Extending this work, I investigated the evolution of these biological entities within animals to shed light on how their underlying functions arose and how they can be modeled in non-human species. Additionally, I present a new tool that uses large-scale clinical genomic data to identify human mutations that may affect microRNA regulatory functions, thereby providing a method by which state-of-the-art genomic technologies can be fully utilized in the search for new disease mechanisms and potential drug targets. The scientific contributions made in this dissertation utilize current data sets generated using high-throughput sequencing technologies. For example, recent whole-genome sequencing studies of the most distant animal lineages have effectively restructured the animal tree of life as we understand it. The first two chapters utilize data from this new high-confidence animal phylogeny - in addition to data generated in the course of my work - to demonstrate that (1) certain classes of human disease have uncommonly large proportions of genes that evolved with the earliest animals and/or vertebrates, and (2) that canonical microRNA functionality - absent in at least two of the early branching animal lineages - likely evolved after the first animals. In the third chapter, I expand upon recent research in predicting microRNA target sites, describing a novel tool for predicting clinically significant microRNA target site variants and demonstrating its applicability to the analysis of clinical genomic data. Thus, the studies detailed in this dissertation represent significant advances in our understanding of the functions of disease genes and microRNAs from both an evolutionary and a clinical perspective

Rapid Expectation Setting for Learners in the Emergency Department

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163402/1/aet210433_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163402/2/aet210433.pd

From Primed Concepts to Action: A Meta-Analysis of the Behavioral Effects of Incidentally Presented Words

A meta-analysis assessed the behavioral impact of and psychological processes associated with presenting words connected to an action or a goal representation. The average and distribution of 352 effect sizes (analyzed using fixed-effects and random-effects models) was obtained from 133 studies (84 reports) in which word primes were incidentally presented to participants, with a nonopposite control group, before measuring a behavioral dependent variable. Findings revealed a small behavioral priming effect (dFE = 0.332, dRE = 0.352), which was robust across methodological procedures and only minimally biased by the publication of positive (vs. negative) results. Theory testing analyses indicated that more valued behavior or goal concepts (e.g., associated with important outcomes or values) were associated with stronger priming effects than were less valued behaviors. Furthermore, there was some evidence of persistence of goal effects over time. These results support the notion that goal activation contributes over and above perception-behavior in explaining priming effects. In summary, theorizing about the role of value and satisfaction in goal activation pointed to stronger effects of a behavior or goal concept on overt action. There was no evidence that expectancy (ease of achieving the goal) moderated priming effects

Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants.

BackgroundIndividuals with inactive alleles of the fucosyltransferase 2 gene (FUT2; termed the 'secretor' gene) are common in many populations. Some members of the genus Bifidobacterium, common infant gut commensals, are known to consume 2'-fucosylated glycans found in the breast milk of secretor mothers. We investigated the effects of maternal secretor status on the developing infant microbiota with a special emphasis on bifidobacterial species abundance.ResultsOn average, bifidobacteria were established earlier and more often in infants fed by secretor mothers than in infants fed by non-secretor mothers. In secretor-fed infants, the relative abundance of the Bifidobacterium longum group was most strongly correlated with high percentages of the order Bifidobacteriales. Conversely, in non-secretor-fed infants, Bifidobacterium breve was positively correlated with Bifidobacteriales, while the B. longum group was negatively correlated. A higher percentage of bifidobacteria isolated from secretor-fed infants consumed 2'-fucosyllactose. Infant feces with high levels of bifidobacteria had lower milk oligosaccharide levels in the feces and higher amounts of lactate. Furthermore, feces containing different bifidobacterial species possessed differing amounts of oligosaccharides, suggesting differential consumption in situ.ConclusionsInfants fed by non-secretor mothers are delayed in the establishment of a bifidobacteria-laden microbiota. This delay may be due to difficulties in the infant acquiring a species of bifidobacteria able to consume the specific milk oligosaccharides delivered by the mother. This work provides mechanistic insight into how milk glycans enrich specific beneficial bacterial populations in infants and reveals clues for enhancing enrichment of bifidobacterial populations in at risk populations - such as premature infants

The community structure of functional brain networks exhibits scale-specific patterns of inter- and intra-subject variability

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain\u27s modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time are surprisingly lacking. Here, we present a method that uses multi-layer networks to simultaneously discover the modular structure of many subjects at once. This method builds upon the well-known multi-layer modularity maximization technique, and provides a viable and principled tool for studying differences in network communities across individuals and within individuals across time. We test this method on two datasets and identify consistent patterns of inter-subject community variability, demonstrating that this variability - which would be undetectable using past approaches - is associated with measures of cognitive performance. In general, the multi-layer, multi-subject framework proposed here represents an advance over current approaches by straighforwardly mapping community assignments across subjects and holds promise for future investigations of inter-subject community variation in clinical populations or as a result of task constraints

The Grizzly, September 11, 2014

Ursinus Remembers Bobby Fong • Student Government Changes Executive Board • Wismer Adds Food Station • UC Professors Show Work at Berman • Do You Smell That? Wismer Gets a New Composting System • Bring on the Local Food Trucks • Opinion: Is Yik Yak All That?; Argument Against Wet Campus is a Slippery One • Gridiron Gang Primed for Solid Season in 2014 • Trying Hard: Men\u27s and Women\u27s Club Rugby Squads Looking Forward to the Fall Slatehttps://digitalcommons.ursinus.edu/grizzlynews/1908/thumbnail.jp

PELAKSANAAN POS PEMBINAAN TERPADU PENYAKIT TIDAK MENULAR (POSBINDU PTM) DI KOTA AMBON: SEBUAH STUDI KUALITATIF DI KELURAHAN PANDAN KASTURI DAN HATIVE KECIL

Posbindu PTM adalah salah satu bentuk pemberdayaan masyarakat yang dibentuk oleh pemerintah guna menanggulangi penyakit tidak menular. Walaupun demikian, dalam pelaksanaannya terdapat berbagai permasalahan yang dapat menghambat keefektifan Posbindu PTM. Penulisan merupakan hasil analisis penelitian kualitatif Fakultas Kedokteran Universitas Pattimura pada bulan November 2019 - Januari 2020. Tujuan analisis adalah mengetahui pelaksanaan Posbindu PTM. Data diperoleh hasil wawancara mendalam dan FGD informan yang berada di Posbindu PTM wilayah Puskesmas Rijali dan Puskesmas Hative Kecil serta Dinas Kesehatan Provinsi Maluku. Analisis dilakukan terhadap pelaksanaan, sumber pembiayaan, dan respon masyarakat pada masing-masing Posbindu PTM. Hasil analisis menunjukkan bahwa Posbindu PTM di Kelurahan Pandan Kasturi dan Negeri Hative Kecil telah berjalan. Terdapat beberapa hal yang perlu ditingkatkan seperti melibatkan pihak swasta dan pelatihan kader secara berkala

KESENJANGAN PEMAHAMAN KONSEP PELAKSANAAN POS PEMBINAAN TERPADU DENGAN PELAKSANAANNYA DARI SUDUT PANDANG PENGAMBIL KEBIJAKAN DI KOTA AMBON DAN PULAU SAPARUA

Penyakit tidak menular (PTM) telah telah mendorong dibentuknya strategi Pencegahan dan Pengendalian Penyakit Tidak Menular (P2PTM) sebagai prioritas pembangunan di setiap negara sesuai dengan Sustainable Development Goals 2030. Pos Pembinaan Terpadu Penyakit Tidak Menular (Posbindu PTM) merupakan peran serta masyarakat dalam melakukan kegiatan deteksi dini dan pemantauan faktor risiko PTM Utama yang dilaksanakan secara terpadu, rutin, dan periodik. Berbagai Posbindu PTM tidak berjalan secara optimal dengan salah satu penyebabnya karena pemahaman pelaksanaan dan persiapan Posbindu yang belum sesuai dengan konsep yang telah ditentukan oleh Kemenkes RI tentang petunjuk teknis Posbindu PTM. Penelitian ini bertujuan untuk menggali berbagai kesenjangan atau ketidaksesuaian pemahaman dalam pelaksanaan Posbindu PTM dengan konsep yang telah ditetapkan dan membahas upaya tindak lanjut yang sesuai dengan konsep Posbindu PTM sehingga diharapkan bisa mengurangi hambatan. Studi kualitatif ini dilakukan pada bulan November 2019-Januari 2020 di Kota Ambon dan Pulau Saparua dengan melakukan wawancara mendalam pada 12 informan di pihak Dinas Kesehatan Provinsi Maluku, Dinas Kesehatan Kota Ambon, Dinas Kesehatan Kabupaten Maluku Tengah, 2 Puskesmas di Kota Ambon (Puskesmas Hative Kecil dan Puskesmas Rijali), dan 3 Puskesmas di Pulau Saparua (Puskesmas Jazirah Tenggara, Puskesmas Porto-Haria dan Puskesmas Booi-Paperu). Dari penelitian ini didapatkan berbagai miskonsepsi atau kesenjangan antara teori konsep Posbindu PTM dengan pelaksanaannya dalam hal pemahaman tentang tujuan program, sumber anggaran, pelaksanaan kegiatan, anggapan masyarakat, pengintegrasian, serta monitoring dan evaluasi program, sehingga dilakukan pembahasan untuk saran tindak lanjut yang sesuai dengan konsep Posbindu PTM untuk mengurangi hambatan