Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Biogeography and global flows of 100 major alien fungal and fungus‐like oomycete pathogens

Aim: Spreading infectious diseases associated with introduced pathogens can have devastating effects on native biota and human livelihoods. We analyse the global distribution of 100 major alien fungal and oomycete pathogens with substantial socio‐economic and environmental impacts and examine their taxonomy, ecological characteristics, temporal accumulation trajectories, regional hot‐ and coldspots of taxon richness and taxon flows between continents. Location: Global. Taxon: Alien/cryptogenic fungi and fungus‐like oomycetes, pathogenic to plants or animals. Methods: To identify over/underrepresented classes and phyla, we performed Chi2 tests of independence. To describe spatial patterns, we calculated the region‐wise richness and identified hot‐ and coldspots, defined as residuals after correcting taxon richness for region area and sampling effort via a quasi‐Poisson regression. We examined the relationship with environmental and socio‐economic drivers with a multiple linear regression and evaluated a potential island effect. Regional first records were pooled over 20‐year periods, and for global flows the links between the native range to the alien regions were mapped. Results: Peronosporomycetes (Oomycota) were overrepresented among taxa and regional taxon richness was positively correlated with area and sampling effort. While no island effect was found, likely due to host limitations, hotspots were correlated with human modification of terrestrial land, per capita gross domestic product, temperate and tropical forest biomes, and orobiomes. Regional first records have increased steeply in recent decades. While Europe and Northern America were major recipients, about half of the taxa originate from Asia. Main Conclusions: We highlight the putative importance of anthropogenic drivers, such as land use providing a conducive environment, contact opportunities and susceptible hosts, as well as economic wealth likely increasing colonisation pressure. While most taxa were associated with socio‐economic impacts, possibly partly due to a bias in research focus, about a third show substantial impacts to both socio‐economy and the environment, underscoring the importance of maintaining a wholescale perspective across natural and managed systems

The Role of Cargo Proteins in GGA Recruitment

Coat proteins are recruited onto membranes to form vesicles that transport cargo from one compartment to another, but the extent to which the cargo helps to recruit the coat proteins is still unclear. Here we have examined the role of cargo in the recruitment of Golgi-localized, γ-ear-containing, ADP ribosylation factor (ARF)-binding proteins (GGAs) onto membranes in HeLa cells. Moderate overexpression of CD8 chimeras with cytoplasmic tails containing DXXLL-sorting signals, which bind to GGAs, increased the localization of all three GGAs to perinuclear membranes, as observed by immunofluorescence. GGA2 was also expressed at approximately twofold higher levels in these cells because it was degraded more slowly. However, this difference only partially accounted for the increase in membrane localization because there was a approximately fivefold increase in GGA2 associated with crude membranes and a ∼12-fold increase in GGA2 associated with clathrin-coated vesicles (CCVs) in cells expressing CD8-DXXLL chimeras. The effect of cargo proteins on GGA recruitment was reconstituted in vitro using permeabilized control and CD8-DXXLL-expressing cells incubated with cytosol containing recombinant GGA2 constructs. Together, these results demonstrate that cargo proteins contribute to the recruitment of GGAs onto membranes and to the formation of GGA-positive CCVs

Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1 Mutant Myelodysplastic Syndromes With Ringed Sideroblasts

View full abstracthttps://openworks.mdanderson.org/leading-edge/1025/thumbnail.jp

CANDELS:Elevated Black Hole Growth in the Progenitors of Compact Quiescent Galaxies at z ∼ 2

We examine the fraction of massive (M M ∗ &gt; 1010) compact star-forming galaxies (cSFGs) that host an active galactic nucleus (AGN) at z ∼ 2. These cSFGs are likely the direct progenitors of the compact quiescent galaxies observed at this epoch, which are the first population of passive galaxies to appear in large numbers in the early Universe. We identify cSFGs that host an AGN using a combination of Hubble WFC3 imaging and Chandra X-ray observations in four fields: the Chandra Deep Fields, the Extended Groth Strip, and the UKIDSS Ultra Deep Survey field. We find that 39.2 % - +3.6 3.9 (65/166) of cSFGs at 1.4 3.0 &lt; z &lt; host an X-ray detected AGN. This fraction is 3.2 times higher than the incidence of AGN in extended star-forming galaxies with similar masses at these redshifts. This difference is significant at the 6.2s level. Our results are consistent with models in which cSFGs are formed through a dissipative contraction that triggers a compact starburst and concurrent growth of the central black hole. We also discuss our findings in the context of cosmological galaxy evolution simulations that require feedback energy to rapidly quench cSFGs. We show that the AGN fraction peaks precisely where energy injection is needed to reproduce the decline in the number density of cSFGs with redshift. Our results suggest that the first abundant population of massive quenched galaxies emerged directly following a phase of elevated supermassive black hole growth and further hints at a possible connection between AGN and the rapid quenching of star formation in these galaxies.</p

Major merging history in CANDELS. I. Evolution of the incidence of massive galaxy–galaxy pairs from z = 3 to z ∼ 0

The rate of major galaxy–galaxy merging is theoretically predicted to steadily increase with redshift during the peak epoch of massive galaxy development (1 ≤ z ≤ 3). We use close-pair statistics to objectively study the incidence of massive galaxies (stellar M1 > 2 × 1010 M⊙) hosting major companions (1 ≤ M1/M2 ≤ 4; i.e. 4:1) companions at z > 1. We show that these evolutionary trends are statistically robust to changes in companion proximity. We find disagreements between published results are resolved when selection criteria are closely matched. If we compute merger rates using constant fraction-to-rate conversion factors (Cmerg,pair = 0.6 and Tobs,pair = 0.65 Gyr), we find that MR rates disagree with theoretical predictions at z > 1.5. Instead, if we use an evolving Tobs,pair(z) ∝ (1 + z)−2 from Snyder et al., our MR-based rates agree with theory at 0 < z < 3. Our analysis underscores the need for detailed calibration of Cmerg,pair and Tobs,pair as a function of redshift, mass, and companion selection criteria to better constrain the empirical major merger history

Altered translation of GATA1 in Diamond-Blackfan anemia

Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA)[superscript 1, 2], congenital asplenia[superscript 3] and T cell leukemia[superscript 4]. Yet, how mutations in genes encoding ubiquitously expressed proteins such as these result in cell-type– and tissue-specific defects remains unknown[superscript 5]. Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce levels of full-length GATA1 protein and cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can lead to decreased GATA1 mRNA translation, possibly resulting from a higher threshold for initiation of translation of this mRNA in comparison with other mRNAs. In primary hematopoietic cells from patients with mutations in RPS19, encoding ribosomal protein S19, the amplitude of a transcriptional signature of GATA1 target genes was globally and specifically reduced, indicating that the activity, but not the mRNA level, of GATA1 is decreased in patients with DBA associated with mutations affecting ribosomal proteins. Moreover, the defective hematopoiesis observed in patients with DBA associated with ribosomal protein haploinsufficiency could be partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations affecting ubiquitous ribosomal proteins can result in human disease.National Institutes of Health (U.S.) (Grant P01 HL32262)National Institutes of Health (U.S.) (Grant U54 HG003067-09