nils-herrmann/clean_scirepeval huggingface dataset:
Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution
Venue: PLoS biology

Although Plasmodium vivax is responsible for the majority of malaria infections outside Africa, little is known about its evolution and pathway to humans. Its closest genetic relative, P. vivax-like, was discovered in African great apes and is hypothesized to have given rise to P. vivax in humans. To unravel the evolutionary history and adaptation of P. vivax to different host environments, we generated using long- and short-read sequence technologies 2 new P. vivax-like reference genomes and 9 additional P. vivax-like genotypes. Analyses show that the genomes of P. vivax and P. vivax-like are highly similar and colinear within the core regions. Phylogenetic analyses clearly show that P. vivax-like parasites form a genetically distinct clade from P. vivax. Concerning the relative divergence dating, we show that the evolution of P. vivax in humans did not occur at the same time as the other agents of human malaria, thus suggesting that the transfer of Plasmodium parasites to humans happened several times independently over the history of the Homo genus. We further identify several key genes that exhibit signatures of positive selection exclusively in the human P. vivax parasites. Two of these genes have been identified to also be under positive selection in the other main human malaria agent, P. falciparum, thus suggesting their key role in the evolution of the ability of these parasites to infect humans or their anthropophilic vectors. Finally, we demonstrate that some gene families important for red blood cell (RBC) invasion (a key step of the life cycle of these parasites) have undergone lineage-specific evolution in the human parasite (e.g., reticulocyte-binding proteins [RBPs]).
Prd1 associates with the clathrin adaptor α-Adaptin and the kinesin-3 Imac/Unc-104 to govern dendrite pruning in Drosophila
Venue: PLoS biology

Refinement of the nervous system depends on selective removal of excessive axons/dendrites, a process known as pruning. Drosophila ddaC sensory neurons prune their larval dendrites via endo-lysosomal degradation of the L1-type cell adhesion molecule (L1-CAM), Neuroglian (Nrg). Here, we have identified a novel gene, pruning defect 1 (prd1), which governs dendrite pruning of ddaC neurons. We show that Prd1 colocalizes with the clathrin adaptor protein α-Adaptin (α-Ada) and the kinesin-3 immaculate connections (Imac)/Uncoordinated-104 (Unc-104) in dendrites. Moreover, Prd1 physically associates with α-Ada and Imac, which are both critical for dendrite pruning. Prd1, α-Ada, and Imac promote dendrite pruning via the regulation of endo-lysosomal degradation of Nrg. Importantly, genetic interactions among prd1, α-adaptin, and imac indicate that they act in the same pathway to promote dendrite pruning. Our findings indicate that Prd1, α-Ada, and Imac act together to regulate discrete distribution of α-Ada/clathrin puncta, facilitate endo-lysosomal degradation, and thereby promote dendrite pruning in sensory neurons.
The mammalian decidual cell evolved from a cellular stress response
Venue: PLoS biology

Among animal species, cell types vary greatly in terms of number and kind. The number of cell types found within an organism differs considerably between species, and cell type diversity is a significant contributor to differences in organismal structure and function. These observations suggest that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms that result in the evolution of novel cell types, however, are poorly understood. Here, we show that a novel cell type of eutherians mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESFs, the majority of decidual core regulatory genes respond to decidualizing signals but do not regulate decidual effector genes. Rather, in opossum ESFs, decidual transcription factors function in apoptotic and oxidative stress response. We propose that rewiring of cellular stress responses was an important mechanism for the evolution of the eutherian decidual cell type.
Resilient reefs may exist, but can larval dispersal models find them?
Venue: PLoS biology

The Great Barrier Reef (GBR) is an interconnected system of thousands of coral reefs and shoals spanning more than 2,000 km of the eastern Australian coastline. Anthropogenic pressures—principally climate change—pose an existential threat to this iconic marine ecosystem . Management actions are urgently required to halt and reverse the degradation, but the GBR’s enormous size creates logistical and budgetary challenges. In a recent research article, Hock and colleagues  offer a solution to this predicament: They argue that a tiny fraction of the GBR’s reefs—fewer than 1%—act as its ‘life-support system’ . The reefs are primarily identified by their larval connectivity, the movement of juvenile individuals between reefs on ocean currents. A dispersive larval stage is common to many species on coral reefs—notably fishes and reef-building corals—and is an essential source of new recruits following mortality and disturbance. Unfortunately, because larvae are difficult and expensive to follow during their pelagic dispersal phase, empirical data are not available at management-relevant scales . Instead, Hock and colleagues base their decisions on ‘biophysical models’—computer simulations that integrate individual-based models of larval behaviour with hydrodynamic ocean current models. In recent years, biophysical models have become a standard tool for investigating the effects of larval connectivity on marine ecology, evolution, and conservation [4–6]. Because their biophysical model predicts that a small number of reefs contribute disproportionately to the GBR’s persistence and resilience, Hock and colleagues claim that these reefs should be a primary focus of management resources. In this comment, we show that the identity of these reefs should be treated with caution, since different numerical models of larval connectivity select different reefs as priorities. More generally, we argue that the current generation of biophysical models should not be used to guide management actions at the scale of individual reefs. The last decade has seen rapid advances in the sophistication of biophysical models. Highperformance computing allows these models to simulate billions of larval releases across thousands of kilometres, while their biological components now incorporate experimentally measured sensory and swimming capabilities. However, despite these strengths, accurate numerical modelling of shallow coastal flow fields with highly variable bathymetry—conditions typical of coral reefs—remains an immense challenge. Critical near-reef hydrodynamics often vary at substantially smaller scales (1 m–1,000 m) than the resolution of biophysical models (100 m–10,000 m; ). Such difficulties are exacerbated by uncertainty about the parameters that describe larval development, behaviour, and mortality, as well as adult spawning behaviour [6]. These limitations have been debated extensively ; given this level of uncertainty, we have strong reservations about whether existing biophysical models are
Response to Bode and colleagues: ‘Resilient reefs may exist, but can larval dispersal models find them?’
Venue: PLoS biology

Bode and colleagues’ response to our paper posits that the identification of specific reefs that drive recovery is unsafe because models of larval dispersal (‘connectivity’) are insufficiently accurate or consistent to make useful predictions at this scale . They go on to argue that managers should not base decisions on reef-level predictions of connectivity. The evidence they provide for these assertions is that the results of their own modelling—with a different model but run with a ‘comparable parameterisation’—diverge considerably from ours. The legitimacy of Bode and colleagues’ concern rests on the apparent disparity in behaviour between connectivity models. Unfortunately, Bode and colleagues’ study differs from ours in many more ways than simply the modelling of oceanography. In short, (1) their representation of the Great Barrier Reef (GBR) excludes approximately half the reefs we recognise (2,175 versus 3,806), so the network metrics of those reefs ‘in common’ are incomparable; (2) they represent different species by ignoring larvae with short settlement times (<7–14 days) and allowing a continuous release of larvae, whereas we considered a wider range of competencies beginning at 12 hours and simulated punctuated spawning events that are more relevant to invertebrates; (3) their model was parameterised two decades ago (1996–2002), so their assessment makes the unlikely assumption that conditions had not changed by the recent period we represented (2008–2013); (4) their model is unable to capture an important dispersal process on the GBR because it takes a two-dimensional depth-integrated approach that ignores the shear flow captured in our 3D Connie model; and (5) they were unable to implement all of the connectivity criteria we applied. Specifically, their finding of a strongly connected network precluded use of graph theory to identify regionally connected sources as we did. The causes of such strong connections in Bode and colleagues’ analysis are unclear but likely include use of higher rates of larval release and a continuous release period of 156 days, though we consider this to be an inappropriate representation of coral spawning, and we elected to retain the temporal dynamics of multiple punctuated spawning events. Given these five fundamental differences, it is not surprising that their assessment of connectivity patterns differed from ours. However, this discrepancy does not imply that choice of hydrodynamic model alone is the cause. Nor does it constitute evidence that our identification of key source reefs is too uncertain to be useful. The eReefs/Connie hydrodynamic model we adopted has been calibrated against data from tide gauges, wave-rider buoys, an extensive array of moorings and temperature loggers across the GBR, and Argo floats  as well as formal assimilation of satellite data. An additional, and
Emerging plant disease epidemics: Biological research is key but not enough
Venue: PLoS biology

The effective management of plant diseases is of fundamental importance for food production, forestry, and other plant-derived products, as well as for the sustainability of natural environments. When considering the impact of a plant pathogen, the financial costs incurred by an outbreak usually receive the most focus, but there are other much less understood consequences for the affected society, culture, and environment due to disease. This poorly studied layer of complexity is particularly relevant for emerging outbreaks, of which often only limited knowledge is available to devise management strategies, but decisions and actions must be made quickly. The recent outbreak of a bacterial plant pathogen in Europe illustrates how understanding not only the biology of an emerging pathogen but also the cultural context is critical for effectively communicating and engaging with stakeholders and policy makers in order to implement successful disease control strategies.
Within-host competition can delay evolution of drug resistance in malaria
Venue: PLoS biology

In the malaria parasite P. falciparum, drug resistance generally evolves first in low-transmission settings, such as Southeast Asia and South America. Resistance takes noticeably longer to appear in the high-transmission settings of sub-Saharan Africa, although it may spread rapidly thereafter. Here, we test the hypothesis that competitive suppression of drug-resistant parasites by drug-sensitive parasites may inhibit evolution of resistance in high-transmission settings, where mixed-strain infections are common. We employ a cross-scale model, which simulates within-host (infection) dynamics and between-host (transmission) dynamics of sensitive and resistant parasites for a population of humans and mosquitoes. Using this model, we examine the effects of transmission intensity, selection pressure, fitness costs of resistance, and cross-reactivity between strains on the establishment and spread of resistant parasites. We find that resistant parasites, introduced into the population at a low frequency, are more likely to go extinct in high-transmission settings, where drug-sensitive competitors and high levels of acquired immunity reduce the absolute fitness of the resistant parasites. Under strong selection from antimalarial drug use, however, resistance spreads faster in high-transmission settings than low-transmission ones. These contrasting results highlight the distinction between establishment and spread of resistance and suggest that the former but not the latter may be inhibited in high-transmission settings. Our results suggest that within-host competition is a key factor shaping the evolution of drug resistance in P. falciparum.
HAP2/GCS1: Mounting evidence of our true biological EVE?
Venue: PLoS biology

Sex has consequences—indeed, where would we be without it? Yet for all its importance, remarkably little is known about how sex evolved, why it has persisted, or even what mechanisms allow sperm–egg fusion to occur. Fortunately, answers to these questions are beginning to emerge with studies of hapless 2/generative cell specific1 (HAP2/GCS1), a molecular machine that promotes gamete fusion in organisms ranging from protists to flowering plants and insects. In studies by Fedry and colleagues, key structural features of the HAP2 protein are revealed for the first time, lending new insights into its mode of action and reinforcing its relationship to viral proteins that accomplish a similar task and may be intimately linked to the origins of cell–cell fusion events (including sexual reproduction) across evolutionary time.
Timescales of influenza A/H3N2 antibody dynamics
Venue: PLoS biology

Human immunity influences the evolution and impact of influenza strains. Because individuals are infected with multiple influenza strains during their lifetime, and each virus can generate a cross-reactive antibody response, it is challenging to quantify the processes that shape observed immune responses or to reliably detect recent infection from serological samples. Using a Bayesian model of antibody dynamics at multiple timescales, we explain complex cross-reactive antibody landscapes by inferring participants’ histories of infection with serological data from cross-sectional and longitudinal studies of influenza A/H3N2 in southern China and Vietnam. We find that individual-level influenza antibody profiles can be explained by a short-lived, broadly cross-reactive response that decays within a year to leave a smaller long-term response acting against a narrower range of strains. We also demonstrate that accounting for dynamic immune responses alongside infection history can provide a more accurate alternative to traditional definitions of seroconversion for the estimation of infection attack rates. Our work provides a general model for quantifying aspects of influenza immunity acting at multiple timescales based on contemporary serological data and suggests a two-armed immune response to influenza infection consistent with competitive dynamics between B cell populations. This approach to analysing multiple timescales for antigenic responses could also be applied to other multistrain pathogens such as dengue and related flaviviruses.
Axonal sodium channel NaV1.2 drives granule cell dendritic GABA release and rapid odor discrimination
Venue: PLoS biology

Dendrodendritic synaptic interactions between olfactory bulb mitral and granule cells represent a key neuronal mechanism of odor discrimination. Dendritic release of gamma-aminobutyric acid (GABA) from granule cells contributes to stimulus-dependent, rapid, and accurate odor discrimination, yet the physiological mechanisms governing this release and its behavioral relevance are unknown. Here, we show that granule cells express the voltage-gated sodium channel α-subunit NaV1.2 in clusters distributed throughout the cell surface including dendritic spines. Deletion of NaV1.2 in granule cells abolished spiking and GABA release as well as inhibition of synaptically connected mitral cells (MCs). As a consequence, mice required more time to discriminate highly similar odorant mixtures, while odor discrimination learning remained unaffected. In conclusion, we show that expression of NaV1.2 in granule cells is crucial for physiological dendritic GABA release and rapid discrimination of similar odorants with high accuracy. Hence, our data indicate that neurotransmitter-releasing dendritic spines function just like axon terminals.
Leaky resistance and the conditions for the existence of lytic bacteriophage
Venue: PLoS biology

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIR is maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIR in these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”
Call combinations in birds and the evolution of compositional syntax
Venue: PLoS biology

Syntax is the set of rules for combining words into phrases, providing the basis for the generative power of linguistic expressions. In human language, the principle of compositionality governs how words are combined into a larger unit, the meaning of which depends on both the meanings of the words and the way in which they are combined. This linguistic capability, i.e., compositional syntax, has long been considered a trait unique to human language. Here, we review recent studies on call combinations in a passerine bird, the Japanese tit (Parus minor), that provide the first firm evidence for compositional syntax in a nonhuman animal. While it has been suggested that the findings of these studies fail to provide evidence for compositionality in Japanese tits, this criticism is based on misunderstanding of experimental design, misrepresentation of the importance of word order in human syntax, and necessitating linguistic capabilities beyond those given by the standard definition of compositionality. We argue that research on avian call combinations has provided the first steps in elucidating how compositional expressions could have emerged in animal communication systems.
Serial representation of items during working memory maintenance at letter-selective cortical sites
Venue: PLoS biology

A key component of working memory is the ability to remember multiple items simultaneously. To understand how the human brain maintains multiple items in memory, we examined direct brain recordings of neural oscillations from neurosurgical patients as they performed a working memory task. We analyzed the data to identify the neural representations of individual memory items by identifying recording sites with broadband gamma activity that varied according to the identity of the letter a subject viewed. Next, we tested a previously proposed model of working memory, which had hypothesized that the neural representations of individual memory items sequentially occurred at different phases of the theta/alpha cycle. Consistent with this model, the phase of the theta/alpha oscillation when stimulus-related gamma activity occurred during maintenance reflected the order of list presentation. These results suggest that working memory is organized by a cortical phase code coordinated by coupled theta/alpha and gamma oscillations and, more broadly, provide support for the serial representation of items in working memory.
Compositionality in animals and humans
Venue: PLoS biology

A key step in understanding the evolution of human language involves unravelling the origins of language’s syntactic structure. One approach seeks to reduce the core of syntax in humans to a single principle of recursive combination, merge, for which there is no evidence in other species. We argue for an alternative approach. We review evidence that beneath the staggering complexity of human syntax, there is an extensive layer of nonproductive, nonhierarchical syntax that can be fruitfully compared to animal call combinations. This is the essential groundwork that must be explored and integrated before we can elucidate, with sufficient precision, what exactly made it possible for human language to explode its syntactic capacity, transitioning from simple nonproductive combinations to the unrivalled complexity that we now have.
Evolutionary diversification of the HAP2 membrane insertion motifs to drive gamete fusion across eukaryotes
Venue: PLoS biology

HAPLESS2 (HAP2) is a broadly conserved, gamete-expressed transmembrane protein that was shown recently to be structurally homologous to viral class II fusion proteins, which initiate fusion with host cells via insertion of fusion loops into the host membrane. However, the functional conformation of the HAP2 fusion loops has remained unknown, as the reported X-ray structure of Chlamydomonas reinhardtii HAP2 lacked this critical region. Here, we report a structure-guided alignment that reveals diversification of the proposed HAP2 fusion loops. Representative crystal structures show that in flowering plants, HAP2 has a single prominent fusion loop projecting an amphipathic helix at its apex, while in trypanosomes, three small nonpolar loops of HAP2 are poised to interact with the target membrane. A detailed structure-function analysis of the Arabidopsis HAP2 amphipathic fusion helix defines key residues that are essential for membrane insertion and for gamete fusion. Our study suggests that HAP2 may have evolved multiple modes of membrane insertion to accommodate the diversity of membrane environments it has encountered during eukaryotic evolution.