Integrative functional genomics decodes herpes simplex virus 1

Funder: Alexander von Humboldt-Stiftung (Alexander von Humboldt Foundation); doi: https://doi.org/10.13039/100005156Abstract: The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

<scp>ReSurveyEurope</scp>: A database of resurveyed vegetation plots in Europe

AbstractAimsWe introduce ReSurveyEurope — a new data source of resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.ResultsReSurveyEurope includes resurveyed vegetation plots from all habitats. Version 1.0 of ReSurveyEurope contains 283,135 observations (i.e., individual surveys of each plot) from 79,190 plots sampled in 449 independent resurvey projects. Of these, 62,139 (78%) are permanent plots, that is, marked in situ, or located with GPS, which allow for high spatial accuracy in resurvey. The remaining 17,051 (22%) plots are from studies in which plots from the initial survey could not be exactly relocated. Four data sets, which together account for 28,470 (36%) plots, provide only presence/absence information on plant species, while the remaining 50,720 (64%) plots contain abundance information (e.g., percentage cover or cover–abundance classes such as variants of the Braun‐Blanquet scale). The oldest plots were sampled in 1911 in the Swiss Alps, while most plots were sampled between 1950 and 2020.ConclusionsReSurveyEurope is a new resource to address a wide range of research questions on fine‐scale changes in European vegetation. The initiative is devoted to an inclusive and transparent governance and data usage approach, based on slightly adapted rules of the well‐established European Vegetation Archive (EVA). ReSurveyEurope data are ready for use, and proposals for analyses of the data set can be submitted at any time to the coordinators. Still, further data contributions are highly welcome.</jats:sec

Rice Yield Gaps in Smallholder Systems of the Kilombero Floodplain in Tanzania

To meet the growing rice demand in Africa, gaps between actual and attainable yields have to be reduced. In Tanzania, this particularly concerns smallholder rain-fed production systems in the floodplains. After quantifying the existing yield gaps, key contributing factors need to be analyzed to improve site-specific management. Field experiments were conducted for three years and in three pedo-hydrological environments (fringe, middle, and center positions) of the Kilombero floodplain to evaluate: (1) The grain yield under farmers&rsquo; management (actual yield), (2) yield with the best-recommended management (attainable yield), and (3) the non-limited yield simulated by the APSIM model (potential yield). In the field, we additionally assessed incremental effects of (1) field bunding and soil levelling, (2 and 3) additionally applying of 60 kg N ha&minus;1, as urea or as farmyard manure (FYM), and (4 and 5) incorporating in-situ-grown leguminous green manures. Attainable yields were determined with mineral N application at 120 kg ha&minus;1, additional PK fertilizer and supplemental irrigation. On average across years and positions, the potential, the attainable, and farmers&rsquo; actual yields were 11.5, 8.5, and 2.8 t ha&minus;1 indicating a high total yield gap. About 16&ndash;38%, 11&ndash;20%, and 28&ndash;42% of this gap could be attributed to non-controllable yield-reducing (i.e., pest and diseases), yield-limiting (i.e., water and nutrient deficiencies), and yield-defining factors (i.e., poor soil and crop management), respectively. Results indicate a closure of the exploitable yield gap (differences between attainable and farmers&rsquo; actual yields) by up to 6.5 t ha&minus;1 (nearly 60% of the potential yield). This exploitable yield gap was larger in 2016 than in 2017. Also, the gap was larger in the water-limited fringe and middle than in the frequently submerged center positions. Simple field bunds combined with land levelling could close 15&ndash;35% of the exploitable yield gap, depending on field positions and year. FYM or green manures were less effective than mineral N; however, in 2017 and in the wetter middle and center positions, they reduced the yield gap by &gt;50%. We conclude that yield gaps in rainfed rice in Kilombero floodplain are large, but that a site- and system-specific adaptation of crop management can close much of the exploitable yield gap and increase grain yields by 0.7&ndash;4.8 t ha&minus;1. Similar benefits may be obtained in other hydrologically variable floodplain environments of the region and beyond

Site and Management Effects on Grain Yield and Yield Variability of Rainfed Lowland Rice in the Kilombero Floodplain of Tanzania

In East Africa, smallholder farmers produce rainfed lowland rice mainly in floodplains. Low nitrogen contents of the predominant Fluvisols and highly variable hydrological conditions result in low yields and large yield variations, and hence, result in high production risks for farmers. We investigated crop management strategies aimed at increasing yield and reducing yield variability. The field trials were carried out in the Kilombero floodplain near Ifakara in Tanzania, in three hydrological zones (potentially drought-prone fringe, favorable middle and submergence-prone center positions) over three years. The study compared farmers&rsquo; management practices (no field levelling and bunding, no fertilizer input), with the effect of bunding and levelling alone, or in combination with mineral N use at 0 (bunding), 60 (recommended rate) and 120 kg + 60 kg PK ha&minus;1 (attainable yield). Rice mean grain yields (averaged over the four treatments) were higher in the fringe (6.5 t ha&minus;1) and the middle (5.7 t ha&minus;1) than in the center positions (4.6 t ha&minus;1). Farmers&rsquo; practice resulted in lowest yield (3.0 t ha&minus;1) and highest yield variability, with an adjusted coefficient of variation (aCV) of up to 91% between fields, years and positions. Simple bunding of the plots and field levelling increased yields by 40% above farmers&rsquo; practice, particularly in the fringe and middle positions, while reducing yield variation (aCV of 36&ndash;61%). Mineral N application resulted in the highest yields (7.0 t ha&minus;1) and further reduced yield variation (aCV of 14&ndash;27%). However, only in bunded fields of the floodplain fringe rice could benefit from N application beyond 60 kg ha&minus;1, while mineral N use efficiency was lower in middle and center positions. Improved crop management options are most beneficial in floodplain fringe positions, where they can increase yields and reduce production risks. Due to low yield, high production risks and poor responsiveness to management interventions, the center may be taken out of rice production and could be considered for future use as protection zones

Role for ribosome-associated complex and stress-seventy subfamily B (RAC-Ssb) in integral membrane protein translation

Targeting of most integral membrane proteins to the endoplasmic reticulum is controlled by the signal recognition particle, which recognizes a hydrophobic signal sequence near the protein N terminus. Proper folding of these proteins is monitored by the unfolded protein response and involves protein degradation pathways to ensure quality control. Here, we identify a new pathway for quality control of major facilitator superfamily transporters that occurs before the first transmembrane helix, the signal sequence recognized by the signal recognition particle, is made by the ribosome. Increased rates of translation elongation of the N-terminal sequence of these integral membrane proteins can divert the nascent protein chains to the ribosome-associated complex and stress-seventy subfamily B chaperones. We also show that quality control of integral membrane proteins by ribosome-associated complex-stress-seventy subfamily B couples translation rate to the unfolded protein response, which has implications for understanding mechanisms underlying human disease and protein production in biotechnology

Structural analysis of a signal peptide inside the ribosome tunnel by DNP MAS NMR

Proteins are synthesized in cells by ribosomes and, in parallel, prepared for folding or targeting. While ribosomal protein synthesis is progressing, the nascent chain exposes amino-terminal signal sequences or transmembrane domains that mediate interactions with specific interaction partners, such as the signal recognition particle (SRP), the SecA–adenosine triphosphatase, or the trigger factor. These binding events can set the course for folding in the cytoplasm and translocation across or insertion into membranes. A distinction of the respective pathways depends largely on the hydrophobicity of the recognition sequence. Hydrophobic transmembrane domains stabilize SRP binding, whereas less hydrophobic signal sequences, typical for periplasmic and outer membrane proteins, stimulate SecA binding and disfavor SRP interactions. In this context, the formation of helical structures of signal peptides within the ribosome was considered to be an important factor. We applied dynamic nuclear polarization magic-angle spinning nuclear magnetic resonance to investigate the conformational states of the disulfide oxidoreductase A (DsbA) signal peptide stalled within the exit tunnel of the ribosome. Our results suggest that the nascent chain comprising the DsbA signal sequence adopts an extended structure in the ribosome with only minor populations of helical structure