The apicomplexans are a group of obligate animal pathogens that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis) 1. They are an extremely diverse ...and specious group but are nevertheless united by a distinctive suite of cytoskeletal and secretory structures related to infection, called the apical complex, which is used to recognize and gain entry into animal host cells. The apicomplexans are also known to have evolved from free-living photosynthetic ancestors and retain a relict plastid (the apicoplast), which is non-photosynthetic but houses a number of other essential metabolic pathways 2. Their closest relatives include a mix of both photosynthetic algae (chromerids) and non-photosynthetic microbial predators (colpodellids) 3. Genomic analyses of these free-living relatives have revealed a great deal about how the alga-parasite transition may have taken place, as well as origins of parasitism more generally 4. Here, we show that, despite the surprisingly complex origin of apicomplexans from algae, this transition actually occurred at least three times independently. Using single-cell genomics and transcriptomics from diverse uncultivated parasites, we find that two genera previously classified within the Apicomplexa, Piridium and Platyproteum, form separately branching lineages in phylogenomic analyses. Both retain cryptic plastids with genomic and metabolic features convergent with apicomplexans. These findings suggest a predilection in this lineage for both the convergent loss of photosynthesis and transition to parasitism, resulting in multiple lineages of superficially similar animal parasites.
•The origin of apicomplexans from algae occurred at least three times independently•Piridium and Platyproteum form distinct lineages of obligate animal parasites•They both retain cryptic plastids that are highly convergent with apicomplexans
Apicomplexans are a major group of diverse animal parasites thought to have evolved once from free-living photosynthetic algae. Mathur et al. show, using single-cell genomics, that this complex evolutionary shift actually occurred at least three times independently, resulting in multiple lineages of highly convergent animal parasites.
Microreactor technology is increasingly applied in the chemical‐pharmaceutical industry for safer and more efficient drug production as compared to the traditional batch process. This technology is ...employed for the first time to study the production of 2‐methyl(pyridin‐2‐yl)aminoethanol, the first intermediate in rosiglitazone synthesis. Under the optimum operating conditions, a single microreactor chip at 160 °C allowed to produce the equivalent of more than five batch reactors at 120 °C. The kinetic study indicated that the reaction is second order. Thermodynamic parameters were determined by the Eyring equation and density functional theory (DFT) calculations with good agreement. DFT results suggested a concerted nucleophilic aromatic substitution reaction mechanism.
Formation of 2‐methyl(pyridin‐2‐yl)aminoethanol was followed vs. time. The use of microreactor technology led to a tenfold yield increase, and one capillary microreactor produced the equivalent of five batch reactors. Computed thermodynamic properties agree with those estimated by Eyring's equation, so the density functional theory energy estimation can serve as a starting basis for drug design.
We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped ...Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10−16, at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10−21). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10−16). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.
Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on ...between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10
), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7.5% per allele, P = 4.9 × 10
and 7.3% per allele, P = 7.5 × 10
, respectively). Variants that increase mean and between-subject variance in fasting glucose levels tend to increase T2D risk, whereas those that increase the mean but reduce variance do not (r
= 0.61). The variants that increase between-subject variance increase fasting glucose heritability estimates. Intuitively, our results show that increasing the mean and variance of glucose levels is more likely to cause pathologically high glucose levels than increase in the mean offset by a decrease in variance.
The eastern brown snake is the predominant cause of snakebites in mainland Australia. Its venom induces defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia. Cardiovascular ...collapse has been described as an early cause of death in patients, but, so far, the mechanisms involved have not been fully identified. In the present work, we analysed the venome of Pseudonaja textilis by combining high throughput proteomics and transcriptomics, aiming to further characterize the components of this venom. The combination of these techniques in the analysis and identification of toxins, venom proteins and putative toxins allowed the sequence description and the identification of the following: prothrombinase coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and “acidic PLA2”, three-finger toxins (3FTx) and the Kunitz-type protease inhibitor textilinin, venom metalloproteinase, C-type lectins, cysteine rich secretory proteins, calreticulin, dipeptidase 2, as well as evidences of Heloderma lizard peptides. Deep data-mining analysis revealed the secretion of a new transcript variant of venom coagulation factor 5a and the existence of a splicing variant of PLA2 modifying the UTR and signal peptide from a same mature protein. The transcriptome revealed the diversity of transcripts and mutations, and also indicates that splicing variants can be an important source of toxin variation.
•Pseudonaja textilis venome was analysed by combining transcriptome and proteome.•A novel coagulation factor 5a splicing variant was detected by both approaches.•A new long three finger toxin was detected by both approaches.•Two identical PLA2s with different UTRs and signal peptides were sequenced.
Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment ...response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects.
We performed genome-wide association studies of serum levels of AFP (
= 22,686), carcinoembryonic antigen (
= 22,309), cancer antigens 15.3 (
= 7,107), 19.9 (
= 9,945), and 125 (
= 9,824), and ALP (
= 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry.
We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels.
Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood.
Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers.
Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that ...have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as “Seshat: Global History Databank.” We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history.
We generated two polygenic scores, one capturing verbal and the other spatial aspects of cognitive ability, using UK Biobank data and studied their effects on various diseases and other traits in the ...Icelandic population. The score tagging spatial ability associated with higher body mass index (β = 0.032, p = 3.2 × 10−13), but lower risk of schizophrenia (OR = 0.82, p = 8.8 × 10−9) and other mental disorders. Furthermore, it associated with less openness, a personality trait reflecting curiosity and creativity (β = −0.023, p = 1.3 × 10−4). Conversely, the score tagging verbal ability associated with lower body mass index (β = −0.023, p = 1.6 × 10−7) and more openness (β = 0.045, p = 3.5 × 10−14), but did not associate with risk of schizophrenia (OR = 0.97, p = 0.42). Furthermore, applying genomic structural equation modeling, we observed that the genetic component of verbal ability associated positively with the genetic component of schizophrenia after conditioning on the g factor (bg = 0.193, p = 5.4 × 10−4). Thus, at the genetic level, verbal and spatial ability exhibit contrasting associations with indicators of mental and physical health, as well as with personality.
•Verbal and spatial ability exhibit contrasting associations with health.•Spatial ability shares sequence variants with greater body mass index.•After adjusting for g, verbal ability shares sequence variants with schizophrenia.
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