Catalytically active holo Homo sapiens adenosine deaminase I adopts a closed conformation
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Ma, Minh Thu↗
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An isotopic test of the seasonal migration hypothesis for large grazing ungulates inhabiting the Palaeo-Agulhas Plain
The Greater Cape Floristic Region of South Africa was critical to the evolution of early modern humans ( Homo sapiens ) during the Pleistocene. The now submerged continental shelf formed its own ecosystem, the Palaeo-Agulhas Plain (PAP), where early humans lived and foraged. Grazing animals living on the plain might have migrated east and west tracking seasonally varying rains—a hypothesis tested here by examining δ 13 C and δ 18 O of serially-drilled teeth from seven ungulate genera: Alcelaphus , Connochaetes , Antidorcus , Redunca , Damaliscus , and Hippotragus . Modern observations and paleoecological reconstructions indicate that summer rainfall areas to the east have more C 4 grasses while the winter rainfall areas to the west have more C 3 grasses, and that summer and winter rains differ in δ 18 O. Thus, we analyze δ 13 C and δ 18 O preserved in herbivore teeth from the site of PP30 (a hyena den dating to ~151 ka) to infer diet and water source throughout tooth formation. On a generic level, we report none of the samples exhibit δ 13 C or δ 18 O values that differ significantly from a taxon that likely foraged locally through the year (Southern reedbuck, Redunca arundium ). Overall, results indicate that the PAP could support herbivore populations year-round without substantial migration, providing an ecosystem ideal for human inhabitants.
59 BASIC BIOLOGICAL SCIENCES↗
Directionally supervised cellular automaton for the initial peopling of Sahul
Reconstructing the patterns of Homo sapiens expansion out of Africa and across the globe has been advanced using demographic and travel-cost models. However, modelled routes are ipso facto influenced by migration rates, and vice versa. We combined movement ‘superhighways’ with a demographic cellular automaton to predict one of the world's earliest peopling events — Sahul between 75000 and 50000 years ago. Novel outcomes from the superhighways-weighted model include (i) an approximate doubling of the predicted time to continental saturation (~10,000 years) compared to that based on the directionally unsupervised model (~5000 years), suggesting that rates of migration need to account for topographical constraints in addition to rate of saturation; (ii) a previously undetected movement corridor south through the centre of Sahul early in the expansion wave based on the scenarios assuming two dominant entry points into Sahul; and (iii) a better fit to the spatially de-biased, Signor-Lipps-corrected layer of initial arrival inferred from dated archaeological material. Our combined model infrastructure provides a data-driven means to examine how people initially moved through, settled, and abandoned different regions of the globe.
29 ENERGY PLANNING, POLICY, AND ECONOMY↗
Structure of the pre-mRNA leakage 39-kDa protein reveals a single domain of integrated zf-C3HC and Rsm1 modules
In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP repeat)-like super family, with key residues of the canonical BIR domain being conserved. Features unique to the Pml39 modules refer to the spacing between the Zn-coordinating residues, giving rise to a substantially tilted helix αC in the zf-C3HC and Rsm1 modules, and an extra helix αAB' in the Rsm1 module. Conservation of key residues responsible for its distinct features identifies S. pombe Rsm1 and Homo sapiens NIPA/ZC3HC1 as structural orthologs of ScPml39. Based on the recent functional characterization of NIPA/ZC3HC1 as a scaffold protein that stabilizes the nuclear basket of the NPC, our data suggest an analogous function of ScPml39 in S. cerevisiae.
59 BASIC BIOLOGICAL SCIENCES↗
Until the sun dies
This book gives a popular account of the forces that have shaped human beings into their present form and created the power of human intelligence, and considers the prospects for intelligent life on other planets in the solar system and elsewhere in the universe. The chain of events leading from the big bang to the origin of life on earth is reviewed together with the observations that established the expansion of the universe. Philosophical difficulties with the concept of a universe that has both a beginning and an end are pondered, steady-state cosmology is briefly explained, and the discovery of the relict microwave background is discussed. The formation of the solar system is recounted along with the scientific view of the origin of terrestrial life. Attention is given to the origin of cells and the evolution of oxygen-breathing life, multicelled creatures, armored animals, fishes, amphibians, early reptiles, dinosaurs, and mammals. The development of mammalian intelligence is traced from the early tree dwellers through monkeys, apes, ape men, humanoid tool makers, and primitive members of the genus Homo, to Homo sapiens. Possible evidence for the existence of life on Mars is evaluated together with prospects for communication or other contact with extraterrestrial intelligence.
Jastrow, R.↗
Isolation and characterization of a novel gene sfig in rat skeletal muscle up-regulated by spaceflight (STS-90)
We obtained the skeletal muscle of rats exposed to weightless conditions during a 16-day-spaceflight (STS-90). By using a differential display technique, we identified 6 up-regulated and 3 down-regulated genes in the gastrocnemius muscle of the spaceflight rats, as compared to the ground control. The up-regulated genes included those coding Casitas B-lineage lymphoma-b, insulin growth factor binding protein-1, titin and mitochondrial gene 16 S rRNA and two novel genes (function unknown). The down-regulated genes included those encoding RNA polymerase II elongation factor-like protein, NADH dehydrogenase and one novel gene (function unknown). In the present study, we isolated and characterized one of two novel muscle genes that were remarkably up-regulated by spaceflight. The deduced amino acid sequence of the spaceflight-induced gene (sfig) comprises 86 amino acid residues and is well conserved from Drosophila to Homo sapiens. A putative leucine-zipper structure located at the N-terminal region of sfig suggests that this gene may encode a transcription factor. The up-regulated expression of this gene, confirmed by Northern blot analysis, was observed not only in the muscles of spaceflight rats but also in the muscles of tail-suspended rats, especially in the early stage of tail-suspension when gastrocnemius muscle atrophy initiated. The gene was predominantly expressed in the kidney, liver, small intestine and heart. When rat myoblastic L6 cells were grown to 100% confluence in the cell culture system, the expression of sfig was detected regardless of the cell differentiation state. These results suggest that spaceflight has many genetic effects on rat skeletal muscle.
STS-90 Shuttle Project↗
Abundant raw material for cis-regulatory evolution in humans
Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.
NASA Discipline Evolutionary Biology↗
FOREWORD: Satellite Remote Sensing Beyond 2015
Satellite remote sensing has progressed tremendously since the first Landsat was launched on June 23, 1972. Since the 1970s, satellite remote sensing and associated airborne and in situ measurements have resulted in vital and indispensable observations for understanding our planet through time. These observations have also led to dramatic improvements in numerical simulation models of the coupled atmosphere-land-ocean systems at increasing accuracies and predictive capability. The same observations document the Earth's climate and are driving the consensus that Homo sapiens is changing our climate through greenhouse gas emissions. These accomplishments are the combined work of many scientists from many countries and a dedicated cadre of engineers who build the instruments and satellites that collect Earth observation data from satellites, all working toward the goal of improving our understanding of the Earth. This edition of the Remote Sensing Handbook (Vol. I, II, and III) is a compendium of information for many research areas of our Planet that have contributed to our substantial progress since the 1970s. Remote sensing community is now using multiple sources of satellite and in situ data to advance our studies, what ever they might be. In the following paragraphs, I will illustrate how valuable and pivotal role satellite remote sensing has played in climate system study over last five decades, The Chapters in the Remote Sensing Handbook (Vol. I, II, and III) provides many other specific studies on land, water, and other applications using EO data of last five decades, The Landsat system of Earth-observing satellites has led the way in pioneering sustained observations of our planet. From 1972 to the present, at least one and sometimes two Landsat satellites have been in operation. Starting with the launch of the first NOAA-NASA Polar Orbiting Environmental Satellites NOAA-6 in 1978, improved imaging of land, clouds, and oceans and atmospheric soundings of temperature were accomplished. The NOAA system of polar-orbiting meteorological satellites has continued uninterrupted since that time, providing vital observations for numerical weather prediction. These same satellites are also responsible for the remarkable records of sea surface temperature and land vegetation index from the Advanced Very High Resolution Radiometers (AVHRR) that now span more than 33 years, although no one anticipated these valuable climate records from this instrument before the launch of NOAA-7 in 1981. The success of data from the AVHRR led to the design of the MODIS instruments on NASA's Earth Observing System of satellite platforms that improved substantially upon the AVHRR. The first of the EOS platforms, Terra, was launched in 2000 and the second of these platforms, Aqua, was launched in 2002.
Tucker, Compton J.↗
Increasing the Statistical Rigor of Cross-Species Differential Expression Analysis
Microgravity inflicts substantial, but undercharacterized, pressure on organisms that induces metabolic responses such as increased microbial virulence and antibiotic resistance, altered organ weights in developing rats, and loss of bone tissue in astronauts. Numerous studies have analyzed the effects of microgravity on specific organisms, tissues, or test conditions, but these projects are necessarily limited by the small sample size of space research. Increasing the sample size of spaceflight studies is non-trivial; however, pooling data from numerous studies can greatly increase the statistical rigor of comparative analyses. The GeneLab houses datasets from 73 spaceflight studies that performed transcription profiling assays. These data encompass a diverse array of organisms ranging from Escherichia coli to Mus musculus to Homo sapiens and comprise studies analyzing ionizing radiation, mammalian pregnancy, etc. Collectively, the GeneLab database contains a large quantity of transcription assays and RNA sequence data analyzing Differential Gene Expression (DGE) between microand normogravity. Xspecies, a cross-species analysis method for DGE developed by Kristiansson, et al. in 2012, identifies homologous genes between species that are universally up- or downregulated in response to test conditions. Previous work by an intern at GeneLab applied Xspecies to 19 datasets containing seven different species and identified 14 homologous groups differentially expressed under spaceflight conditions including several heat shock proteins and cytoskeletal components. Unfortunately, these results may be biased by the disproportionate number of studies on Arabidopsis thaliana (5) and Mus musculus (6) and the results are not normalized by evolutionary distances. Here, we present modifications to the Xspecies algorithm that permits incorporation of multi-omic data and normalizes data for effect size, directionality, and evolutionary distances. We then apply this algorithm to all currently available GeneLab studies
Xspecies↗
Searching for Intelligent Life in the Universe: NASA's High Resolution Microwave Survey
The nature of the universe, the place of humans in it, and the question of life elsewhere have captured the interest and stimulated the imaginations of men and women since Homo sapiens first contemplated the cosmos. Today, the question of whether life, even intelligent life, exists beyond Earth remains one of the most intriguing questions confronting hunmankind. While ours is not the first generation to contemplate life beyond earth, we are the first to develop and apply the technical means required to conduct a scientific investigation of the question.
extraterrestial↗
Human Liver Epithelial Cells (HuH7) Response to HCoV-229E Infection Epigenomics (ATAC-Seq) (ACS-DP4)
The purpose of this experiment was to evaluate how wild-type Human coronavirus strain 229E (HCoV-299E) infection alters chromatin accessibility in infected cells. Sample data was obtained from mock-infected cells, UV-inactivated virus treated cells, and replication competent HCoV-229E infected immortalized human liver cells (HuH7) at 24 hours post infection. Samples were processed using ATAC-seq methods for reported bar coded libraries. Sample data was acquired using an Illumina Hi-Seq 2500 sequencer system and further processed for ATAC-Seq expression analysis.
59 BASIC BIOLOGICAL SCIENCES↗
Human Host Cellular Response to HCoV-229E Infection Transcriptomics (ACS-DP1)
The purpose of this experiment was to evaluate the human host cellular response to wild-type Human coronavirus strain 229E (HCoV-229E) infection. Sample data was obtained for mock and infected immortalized human lung epithelial cells (A549) (MOI 5), immortalized human lung fibroblasts cells (MRC5) (MOI5), and primary human airway epithelial (HAE) (MOI 3) cells from lung tissue. Sample data was acquired using an Illumina HiSeq 2000 sequencer system and processed for RNA sequencing (RNA-Seq) expression analysis.
59 BASIC BIOLOGICAL SCIENCES↗
Human Primary Airway Epithelium +/- Macrophages Response to HCoV-229E Infection Transcriptomics (ACS-DP3)
The purpose of this experiment was to evaluate the human host cellular response to wild-type Human coronavirus strain 229E (HCoV-299E) infection. Sample data was obtained for mock and infected (MOI 3) primary human airway epithelial cells with and without macrophages and grown in air-liquid interface conditions. Sample data was acquired using an Illumina Hi-Seq 4000 sequencer system and further processed for RNA sequencing (RNA-Seq) expression analysis.
59 BASIC BIOLOGICAL SCIENCES↗
Human Liver Epithelium Response to HCoV-229E Infection Epigenomics (ACS-DP4)
The purpose of this experiment was to evaluate how wild-type Human coronavirus strain 229E (HCoV-229E) infection alters chromatin accessibility in infected cells only. Sample data was obtained for mock and infected (standard and UV-inactivated) immortalized human liver cells (HuH-7) and collected 24 hrs. post infection. Samples were processed using assay for transposase-accessible chromatin using high-throughput sequencing (ATAC-Seq) and generated bar coded library samples were evaluated for RNA sequencing (RNA-Seq) expression analysis. Processed ATAC-Seq datasets are openly accessible from the download button and contain secondary processed RNA-Seq results files and supporting metadata materials. Data download includes a sample naming key, infection titer metadata, normalized counts, and relevant computational source code information supporting data transparency and reuse.
59 BASIC BIOLOGICAL SCIENCES↗