Catalytically active holo Homo sapiens adenosine deaminase I adopts a closed conformation
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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.
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.
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.
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.
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.
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.
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.