A reference-quality,fully annotated genome from a Puerto Rican individual

Until 2019, the human genome was available in only one fully annotated version, GRCh38, which was the result of 18 years of continuous improvement and revision. Despite dramatic improvements in sequencing technology, no other genome was available as an annotated reference until 2019, when the genome of an Ashkenazi individual, Ash1, was released. In this study, we describe the assembly and annotation of a second individual genome, from a Puerto Rican individual whose DNA was collected as part of the Human Pangenome project. The new genome, called PR1, is the first true reference genome created from an individual of African descent. Due to recent improvements in both sequencing and assembly technology, and particularly to the use of the recently completed CHM13 human genome as a guide to assembly, PR1 is more complete and more contiguous than either GRCh38 or Ash1. Annotation revealed 37,755 genes (of which 19,999 are protein coding), including 12 additional gene copies that are present in PR1 and missing from CHM13. Fifty-seven genes have fewer copies in PR1 than in CHM13, 9 map only partially, and 3 genes (all noncoding) from CHM13 are entirely missing from PR1.     

Reversible binding of multivalent antigen in the control of B lymphocyte activation.

A model is proposed describing multiple binding of multivalent antigen to specific receptors of immunocompetent cells. The rate at which these multiple bonds can dissociate and the effective valence of the antigen appear to be of the greatest importance in determining the degree of receptor occupancy at equilibrium. In particular, as antigen concentration decreases, only antigens with high number of determinants per molecule maintain the ability to form multiple bonds even if the dissociation rate is relatively high. Assuming that multiple binding is directly linked to lymphocyte activation, this may result in an inverse relation between antigen valence and ability to induce selection of clones with higher affinities.     

The Process-inducing Activity of Transmembrane Agrin Requires Follistatin-like Domains

Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system.     

Mutagenic effects of short term action of N-methyl-N’-nitro-N-nitrosoguanidine onChlamydomonas geitleri

A possible method of finding the best concentration of a chemical mutagen or a shortterm action is demonstrated by the results obtained withChlamydomonas geitleri. Mostly two cases occur. We must either use the shortest time of the mutagen action with a sufficiently high effect or utilize the whole limited time for this action using a suitable concentration with a similar effect. It is possible to choose such a structure of the doae of the chemical mutagen which in the mutation spectrum ensures either the optimal frequencies of all components or of only some of them chosen beforehand.     

The mode of action of Aescin and the release of prostaglandins

The horse-chestnut saponin Aescin, an anti-exudative compound, induces contraction of isolated portal vein of rat and rabbit. This effect appears to be mediated by Prostaglandins of F_α type.The ability of Aescin to stimulate generation and release of Prostaglandins has been demonstrated in isolated lung of the rat. Mass-fragmentographic analysis of the lung effluent indicate that when Aescin is perfused through this organ the release of PGF_2α is increased. The capability of Aescin to generate Prostaglandins is discussed in connection with its anti-exudative activity.     

Guild‐level responses by mammalian predators to afforestation and subsequent restoration in a formerly treeless peatland landscape

Afforestation of formerly open landscapes can transform mammalian predator communities, potentially impacting prey species like ground‐nesting birds. In Scotland's Flow Country, a globally important peatland containing many forestry plantations, earlier studies found reduced densities of breeding waders on open bogs, when forestry plantations were present within 700 m. One plausible explanation for this pattern is mammalian predation. We tested whether mammalian predator indices, based on scats (feces), differed between (1) open bog, forestry plantations, and former plantations being restored as bog (“restoration” habitats); (2) restoration habitats of different ages; and (3) open bogs with differing amounts of nearby forestry. We measured summer scat density and size over 14 years in 26 transects 0.6–4.5 km in length, collecting data during 93, 96, and 79 transect‐years in bog, forestry, and restoration habitats respectively. In forestry, scat density increased eightfold, reaching values ~6 times higher than those of bogs. On open bogs with over 10% forestry within 700 m, scat densities were 2.9 times higher than on open bogs with less forestry nearby. Results support the hypothesis that mammalian predators might be responsible for the low densities of breeding waders close to forests, on adjacent open bogs. In restoration habitats, scat densities rose 6–10 years after felling but fell to levels similar to open bogs in older restoration habitats, supporting restoration management as a means of reducing mammalian predator activity/abundance. We urge caution around decisions to establish forestry plantations in open landscapes of high biodiversity importance.     

Revisiting the coupling of fatty acid to phospholipid synthesis in bacteria with FapR regulation

A key aspect in membrane biogenesis is the coordination of fatty acid to phospholipid synthesis rates. In most bacteria, PlsX is the first enzyme of the phosphatidic acid synthesis pathway, the common precursor of all phospholipids. Previously, we proposed that PlsX is a key regulatory point that synchronizes the fatty acid synthase II with phospholipid synthesis in Bacillus subtilis. However, understanding the basis of such coordination mechanism remained a challenge in Gram-positive bacteria. Here, we show that the inhibition of fatty acid and phospholipid synthesis caused by PlsX depletion leads to the accumulation of long-chain acyl-ACPs, the end products of the fatty acid synthase II. Hydrolysis of the acyl-ACP pool by heterologous expression of a cytosolic thioesterase relieves the inhibition of fatty acid synthesis, indicating that acyl-ACPs are feedback inhibitors of this metabolic route. Unexpectedly, inactivation of PlsX triggers a large increase of malonyl-CoA leading to induction of the fap regulon. This finding discards the hypothesis, proposed for B. subtilis and extended to other Gram-positive bacteria, that acyl-ACPs are feedback inhibitors of the acetyl-CoA carboxylase. Finally, we propose that the continuous production of malonyl-CoA during phospholipid synthesis inhibition provides an additional mechanism for fine-tuning the coupling between phospholipid and fatty acid production in bacteria with FapR regulation.     

Regulation of ovule initiation by gibberellins and brassinosteroids in tomato and Arabidopsis: two plant species,two molecular mechanisms

Ovule primordia formation is a complex developmental process with a strong impact on the production of seeds. In Arabidopsis this process is controlled by a gene network, including components of the signalling pathways of auxin, brassinosteroids (BRs) and cytokinins. Recently, we have shown that gibberellins (GAs) also play an important role in ovule primordia initiation, inhibiting ovule formation in both Arabidopsis and tomato. Here we reveal that BRs also participate in the control of ovule initiation in tomato, by promoting an increase on ovule primordia formation. Moreover, molecular and genetic analyses of the co‐regulation by GAs and BRs of the control of ovule initiation indicate that two different mechanisms occur in tomato and Arabidopsis. In tomato, GAs act downstream of BRs. BRs regulate ovule number through the downregulation of GA biosynthesis, which provokes stabilization of DELLA proteins that will finally promote ovule primordia initiation. In contrast, in Arabidopsis both GAs and BRs regulate ovule number independently of the activity levels of the other hormone. Taken together, our data strongly suggest that different molecular mechanisms could operate in different plant species to regulate identical developmental processes even, as for ovule primordia initiation, if the same set of hormones trigger similar responses, adding a new level of complexity.