bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Three Medically Important Mosquito Species Using Raman Spectroscopy
Authors: Omucheni Dickson L , Kaduki Kenneth A , Mukabana Wolfgang R
Published: May 2022

Accurate identification of disease vector insects is crucial when collecting epidemiological data. Traditionally, mosquitoes that transmit diseases like malaria, yellow fever, chikungunya, and dengue fever have been identified by looking at their external morphological features at different life cycle stages. This process is tedious and labour intensive.

In this paper, the potential of Raman spectroscopy in combination with Linear and Quadratic Discriminant Analysis to classify three mosquito species, namely:Aedes aegypti, Anopheles gambiaeandCulex quinquefasciatus, was explored. The classification was based on the mosquitoes’ cuticular melanin. The three mosquito species represented two subfamilies of medically important mosquitoes, i.e. the Anophelinae and the Culicinae. The housefly (Musca domestica) was included as a ‘control’ group to assess the discrimination ability of the classifiers. This study is the first to use Raman spectroscopy to classify mosquitoes. Fresh mosquitoes were anaesthetized with chloroform, and a dispersive Raman microscope was used to capture spectra from their legs. Broad melanin peaks centred around 1400 cm-1, 1590 cm-1, and 2060 cm-1dominated the spectra. Variance Threshold (VT) and Principal Component Analysis (PCA) were used for feature selection and feature extraction respectively from the preprocessed data. The extracted features were then used to train and test Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA) classifiers.

The VT/PCA/QDA classification model performed better than VT/PCA/LDA. VT/PCA/QDA achieved an overall accuracy of 94%, sensitivity of 87% and specificity of 96%, whereas VT/PCA/LDA attained an accuracy of 85%, a sensitivity of 69% and a specificity of 90%. The success of these relatively simple classification models on Raman spectroscopy data lays the groundwork for future development of models for discriminating morphologically indistinguishable insect species.
Long-term adaptation to galactose as a sole carbon source selects for mutations in nutrient signaling pathways
Authors: Martínez Artemiza A. , Conboy Andrew , Buskirk Sean W. , Marad Daniel A. , Lang Gregory I.
Published: May 2022

Galactose is a secondary fermentable sugar that requires specific regulatory and structural genes for its assimilation, which are under catabolite repression by glucose. When glucose is absent, the catabolic repression is attenuated, and the structuralGALgenes are fully activated. InSaccharomyces cerevisiae, theGALpathway is under selection in environments where galactose is present. However, it is unclear the adaptive strategies in response to long-term propagation in galactose as a sole carbon source in laboratory evolution experiments. Here, we performed a 4,000-generation evolution experiment using 48 diploidSaccharomyces cerevisiaepopulations to study adaptation in galactose. We show that fitness gains were greater in the galactose-evolved population than in identically evolved populations with glucose as a sole carbon source. Whole-genome sequencing of 96 evolved clones revealed recurrentde novosingle nucleotide mutations in candidate targets of selection, copy number variations, and ploidy changes. We find that most mutations that improve fitness in galactose lie outside of the canonicalGALpathway and are involved in nutrient signaling. Reconstruction of specific evolved alleles in candidate target of selection,SEC23andIRA1, showed a significant increase in fitness in galactose compared to glucose. In addition, most of our evolved populations (28/46; 61%) fixed aneuploidies on Chromosome VIII, suggesting a parallel adaptive amplification. Finally, we show greater loss of extrachromosomal elements in our glucose-evolved lineages compared with previous glucose evolution. Broadly, these data further our understanding of the evolutionary pressures that drive adaptation to less-preferred carbon sources.
Predictability shifts from local to global rules during bacterial adaptation
Authors: Couce Alejandro , Magnan Melanie , Lenski Richard E. , Tenaillon Olivier
Published: May 2022

The distribution of fitness effects of new mutations is central to predicting adaptive evolution, but observing how it changes as organisms adapt is challenging. Here we use saturated, genome-wide insertion libraries to quantify how the fitness effects of new mutations changed in twoE. colipopulations that adapted to a constant environment for 15,000 generations. The proportions of neutral and deleterious mutations remained constant, despite large fitness gains. In contrast, the beneficial fraction declined rapidly, approximating an exponential distribution, with strong epistasis profoundly changing the genetic identity of adaptive mutations. Despite this volatility, many important targets of selection were predictable from the ancestral distribution. This predictability occurs because genetic target size contributed to the fixation of beneficial mutations as much as or more than their effect sizes. Overall, our results demonstrate that short-term adaptation can be idiosyncratic but empirically predictable, and that long-term dynamics can be described by simple statistical principles.

One-Sentence Summary

Couce et al. demonstrate that short-term bacterial adaptation is predictable at the scale of individual genes, while long-term adaptation is predictable at a global scale.
Improvement of sensory deficits in Fragile X mice by increasing cortical interneuron activity after the critical period
Authors: Kourdougli Nazim , Suresh Anand , Liu Benjamin , Juarez Pablo , Lin Ashley , Chung David T. , Graven Sams Anette , Gandal Michael , Martínez-Cerdeño Verónica , Buonomano Dean V. , Hall Benjamin J. , Mombereau Cédric , Portera-Cailliau Carlos
Published: May 2022

Changes in the function of inhibitory interneurons (INs) during cortical development could contribute to the pathophysiology of neurodevelopmental disorders. Using all-optical in vivo approaches in postnatal mouse somatosensory cortex (S1), we find that parvalbumin (PV) IN precursors are hypoactive and decoupled from excitatory neurons in Fmr1−/− mice, a model of Fragile X Syndrome (FXS). This leads to a loss of PV-INs in both mice and humans with FXS. Increasing the activity of future PV-INs in neonatal Fmr1−/− mice restores PV density and ameliorates transcriptional dysregulation in S1, but not circuit dysfunction. Critically, administering a novel allosteric modulator of Kv3.1 channels after the S1 critical period does rescue circuit dynamics and tactile defensiveness. Symptoms in FXS and related disorders could be mitigated by targeting PV-INs.
Skewness in bee and flower phenological distributions
Authors: Stemkovski Michael , Dickson Rachel G. , Griffin Sean R. , Inouye Brian D. , Inouye David W. , Pardee Gabriella L. , Underwood Nora , Irwin Rebecca E.
Published: May 2022

Phenological distributions are characterized by their central tendency, breadth, and shape, and all three determine the extent to which interacting species overlap in time. Pollination mutualisms rely on temporal co-occurrence of pollinators and their floral resources, and while much work has been done to characterize the shapes of flower phenological distributions, similar studies including pollinators are lacking. Here, we provide the first broad assessment of skewness, a component of distribution shape, for a bee community. We compare skewness in bees to that in flowers, related bee and flower skewness to other properties of their phenology, and quantify the potential consequences of differences in skewness between bees and flowers. Both bee and flower phenologies tend to be right-skewed, with a more exaggerated asymmetry in bees. Early-season species tend to be the most skewed, and this relationship is also stronger in bees than in flowers. Based on a simulation experiment, differences in bee and flower skewness could account for up to 14% of pair-wise overlap differences. Given the potential for interaction loss, we argue that difference in skewness of interacting species is an under-appreciated property of phenological change.
The Necrosis- and Ethylene-inducing peptide 1-like protein (NLP) gene family of the plant pathogen Corynespora cassiicola
Authors: Dal’Sasso Thaís Carolina da Silva , da Rocha Vinícius Delgado , Rody Hugo Vianna Silva , Costa Maximiller Dal-Bianco Lamas , de Oliveira Luiz Orlando
Published: May 2022

Effectors are secreted by plant-associated microorganisms in order to modify the host cell physiology. As effectors, the Necrosis- and Ethylene-inducing peptide 1-like proteins (NLPs) are involded in the early phases of plant infection and may trigger host immune responses. Corynespora cassiicola is a polyphagous plant-pathogen that causes target spot on many agriculturally important crops. Using genome assembly, gene prediction, and proteome annotation tools, we retrieved 135 NLP-encoding genes from proteomes of 44 isolates. We explored the evolutionary history of NLPs using Bayesian phylogeny, gene genealogies, and selection analyses. We accessed the expression profiles of the NLP genes during the early phase of C. cassiicola–soybean interaction. Three NLP effector genes (Cc_NLP1.1, Cc_NLP1.2A, and Cc_NLP1.2B) were maintained in the genomes of all isolates tested. A non-effector NLP gene (Cc_NLP1.3) was found in three isolates that had been originally obtained from soybean. NLP effectors were under different selective constraints: Cc_NLP1.1 was under stronger selective pressure, while Cc_NLP1.2A was under a more relaxed constraint. Meanwhile, Cc_NLP1.2B likely evolved under either positive or balancing selection. Despite highly divergent, the effector NLPs maintain conserved the residues necessary to trigger plant immune responses, suggesting they are potentially functional. Only the Cc_NLP1.1 effector gene was significantly expressed at the early hours of soybean colonization, while Cc_NLP1.2A and Cc_NLP1.2B showed much lower levels of gene expression.
Simulations of Pathogenic E1α Variants: Allostery and Impact on Pyruvate Dehydrogenase Complex-E1 Structure and Function
Authors: Gokcan Hatice , Bedoyan Jirair K. , Isayev Olexandr
Published: May 2022

Pyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidemia resulting in high morbidity and mortality, with limited therapeutic options. The E1 component of the mitochondrial multienzyme PDC (PDC-E1) is a symmetric dimer of heterodimers (αβ/α’β’) encoded by the PDHA1 and PDHB genes, with two symmetric active sites each consisting of highly conserved phosphorylation loops A and B. PDHA1 mutations are responsible for 82-88% of cases. Greater than 85% of E1α residues with disease-causing missense mutations (DMMs) are solvent inaccessible, with ~30% among those involved in subunit-subunit interface contact (SSIC). We performed molecular dynamics simulations of wild-type (WT) PDC-E1 and E1 variants with E1α DMMs at R349 and W185 (residues involved in SSIC), to investigate their impact on human PDC-E1 structure. We evaluated the change in E1 structure and dynamics and examined their implications on E1 function with the specific DMMs. We found that the dynamics of phosphorylation Loop A which is crucial for E1 biological activity, changes with DMMs that are at least about 15 Å away. Because communication is essential for PDC-E1 activity (with alternating active sites), we also investigated the possible communication network within WT PDC-E1 via centrality analysis. We observed that DMMs altered/disrupted the communication network of PDC-E1. Collectively, these results indicate allosteric effect in PDC-E1, with implications for development of novel small molecule therapeutics for specific recurrent E1α DMMs such as replacements of R349 responsible for ~10% of PDC deficiency due to E1α DMMs.
COVID-19 lockdown reveals fish density may be much higher in marine reserves
Authors: Olán-González Manuel , Reyes-Bonilla Héctor , Arreola-Alarcon Isabel Montserrat , Uribe Regina Valdovinos , Olivier Damien
Published: May 2022

Marine reserves generally allow ecotourism to offer an alternative income to fishing. However, we need to assess its impact on wildlife to make this activity sustainable. The COVID-19 lockdown provided a unique opportunity to evaluate wildlife diversity in the absence of human activity. In a Mexican reserve, we monitored fish assemblages before, during, and just after the lockdown. We show that ecotourism activities alter the behavior of fishes by finding a 2.5-fold density rise during the lockdown. We suggest that the noise pollution generated by the numerous recreational vessels is a significant factor of perturbation. In the absence of noise pollution, some fishes may be bolder (less hidden) and others can come back to the reserve from usually quieter areas (e.g., deeper waters). Our results represent a great worldwide incentive to improve the health of marine reserves by establishing concrete measures in managing plans to mitigate noise pollution.

Open Research statement

All data and code necessary to reproduce the results of the paper are enclosed in the submission for review purposes, and will be published on Zenodo following the acceptance of the paper.
Voltage-Dependent Ca2+ Release Is Impaired in Hypokalemic Periodic Paralysis Caused by CaV1.1-R528H but not by NaV1.4-R669H
Authors: DiFranco Marino , Cannon Stephen C.
Published: May 2022

Hypokalemic periodic paralysis (HypoPP) is a channelopathy of skeletal muscle caused by missense mutations in the voltage sensor domains (usually at an arginine of the S4 segment) of the CaV1.1 calcium channel or of the NaV1.4 sodium channel. The primary clinical manifestation is recurrent attacks of weakness, resulting from impaired excitability of anomalously depolarized fibers containing leaky mutant channels. While the ictal loss of fiber excitability is sufficient to explain the acute episodes of weakness, a deleterious change in voltage sensor function for CaV1.1 mutant channels may also compromise excitation-contraction coupling (EC-coupling).

We used the low-affinity Ca2+ indicator OGN-5 to assess voltage-dependent Ca2+-release as a measure of EC-coupling for our knock-in mutant mouse models of HypoPP. The peak ΔF/F0 in fibers isolated from CaV1.1-R528H mice was about two-thirds of the amplitude observed in WT mice; whereas in HypoPP fibers from NaV1.4-R669H mice the ΔF/F0 was indistinguishable from WT. No difference in the voltage dependence of ΔF/F0 from WT was observed for fibers from either HypoPP mouse model. Because late-onset permanent muscle weakness is more severe for CaV1.1-associated HypoPP than for NaV1.4, we propose the reduced Ca2+-release for CaV1.1-R528H mutant channels may increase the susceptibility to fixed myopathic weakness. In contrast the episodes of transient weakness are similar for CaV1.1- and NaV1.4-associated HypoPP, consistent with the notion that acute attacks of weakness are primarily caused by leaky channels and are not a consequence of reduced Ca2+-release.
Comparative genomics of five Valsa species gives insights on their pathogenicity evolution
Authors: Sun Guangchao , Xie Shichang , Tang Lin , Zhao Chao , Zhang Mian , Huang Lili
Published: May 2022

Valsa is a genus of ascomycetes fungi within the family Valsaceae that includes many wood destructive pathogens. The species such as Valsa mali and Valsa pyri that colonize fruit trees are threatening the global fruit production. Rapid host adaptation and fungicide resistance emergence are the main characteristics that make them devastating and hard to control. Efficient disease management can be achieved from early infection diagnosis and fungicide application, but lack of understandings of their genetic diversity and genomic features that underpin their pathogenicity evolution and drug resistance is essentially impeding the progress of effective and sustainable disease control. Here, we report genome assemblies of Valsa malicola, Valsa persoonii and Valsa sordida which represents close relatives of the two well known Valsa mali and Valsa pyri that cause canker disease with different host preferences. Comparative genomics analysis revealed that segmental rearrangements, inversions and translocations frequently occurred among Valsa spp. genomes. Genes identified in highly active regions exhibited high sequence differentiation and are enriched in membrane transporter proteins involved in anti-drug and nutrient transportation activities. Consistently, we also found membrane transporter gene families have been undergoing significant expansions in Valsa clade. Furthermore, unique genes that possessed or retained by each of the five Valsa species are more likely part of the secondary metabolic (SM) gene clusters which suggests SM one of the critical components that diverge along with the evolution of Valsa species. Repeat sequence content contributes significantly to genome size variation across the five species. The wide spread AT-rich regions resulted from repeat induced point C to T mutation (RIP) exhibited a specific proximity to secondary metabolic gene clusters and this positional proximity is correlated with the diversification of SM clusters suggesting a potential companion evolution between repeat sequence and secondary metabolism cluster. Lastly, we show that LaeA, the global regulator of secondary metabolic gene cluster, exhibiting diverged manner of regulation on the expression of clusters in vegetative and invasive mycelia of the devastating V. mali indicating the complexity of secondary metabolism in fungal species.
Jak2V617F Reversible Activation Shows an Essential Requirement for Jak2V617F in Myeloproliferative Neoplasms
Authors: Dunbar Andrew , Bowman Robert L. , Park Young , Izzo Franco , Myers Robert M. , Karzai Abdul , Kim Won Jun , Maestre Inés Fernández , Waarts Michael R. , Nazir Abbas , Xiao Wenbin , Brodsky Max , Farina Mirko , Cai Louise , Cai Sheng F. , Wang Benjamin , An Wenbin , Yang Julie L , Mowla Shoron , Eisman Shira E. , Mishra Tanmay , Houston Remie , Guzzardi Emily , Martinez Benitez Anthony R. , Viny Aaron , Koche Richard , Landau Dan A. , Levine Ross L.
Published: May 2022

Janus kinases (JAKs) mediate cytokine signaling, cell growth and hematopoietic differentiation.1 Gain-of-function mutations activating JAK2 signaling are seen in the majority of myeloproliferative neoplasm (MPN) patients, most commonly due to the JAK2V617F driver allele.2 While clinically-approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic JAK inhibitor therapy in most patients.3, 4 This has been postulated to be due to incomplete dependence on constitutive JAK/STAT signaling, alternative signaling pathways, and/or the presence of cooperating disease alleles;5 however we hypothesize this is due to the inability of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a Dre-rox/Cre-lox dual orthogonal recombinase system. Deletion of oncogenic Jak2V617Fabrogates the MPN disease phenotype, induces mutant-specific cell loss including in hematopoietic stem/progenitor cells, and extends overall survival to an extent not observed with pharmacologic JAK inhibition. Furthermore, reversal of Jak2V617F in MPN cells with antecedent loss of Tet26, 7 abrogates the MPN phenotype and inhibits mutant stem cell persistence suggesting cooperating epigenetic-modifying alleles do not alter dependence on mutant JAK/STAT signaling. Our results suggest that mutant-specific inhibition of JAK2V617F represents the best therapeutic approach for JAK2V617F-mutant MPN and demonstrate the therapeutic relevance of a dual-recombinase system to assess mutant-specific oncogenic dependencies in vivo.
The acute phase response in bats (Carollia perspicillata) varied with the time and dose of the immune-challenge
Authors: Viola Matheus F. , Herrera M. L. Gerardo , da Cruz-Neto Ariovaldo P.
Published: May 2022

The acute phase response (APR) is a core component of the innate immune response and represents the first line of immune defense used in response to infections. Although several studies with vertebrates reported fever, decrease in food intake and body mass, as well as increase in neutrophil/lymphocyte ratio and total white blood cell count after lipopolysaccharide (LPS) inoculation there was great variability in the magnitude of these responses. Some of these differences might reflect, to some extent, differences in time of endotoxin inoculation (during activity or resting periods) and dose; however, no study in the literature has evaluated the synergistic effect of these two factors in vertebrates. Therefore, our study tested the interplay between LPS dose and time of injection on selected physiological (fever and increase in total white blood cell count and neutrophil/lymphocyte ratio), and behavioral (food intake) components of APR using a Neotropical fruit-eating bat (Carollia perspicillata) as a model organism. We predicted that LPS would trigger a dose- and time-dependent response on APR components. APR components were assessed in resting and activity periods after injection of three doses of LPS (5, 10 and 15 mg/kg LPS). The results showed that LPS-evoked changes in skin temperature, food intake, neutrophil lymphocyte ratio depend markedly on the LPS dose and/or time that LPS is administered.
C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer’s disease
Authors: Gomez-Arboledas Angela , Carvalho Klebea , Balderrama-Gutierrez Gabriela , Chu Shu-Hui , Liang Heidi Yahan , Schartz Nicole D. , Selvan Purnika , Petrisko Tiffany J. , Pan Miranda A. , Mortazavi Ali , Tenner Andrea J.
Published: May 2022

Multiple studies have recognized the involvement of the complement cascade during Alzheimer’s disease pathogenesis; however, the specific role of C5a-C5aR1 signaling in the progression of this neurodegenerative disease is still not clear. Furthermore, its potential as a therapeutic target to treat AD still remains to be elucidated. Canonically, generation of the anaphylatoxin C5a as the result of complement activation and interaction with its receptor C5aR1 triggers a potent inflammatory response. Previously, genetic ablation of C5aR1 in a mouse model of Alzheimer’s disease exerted a protective effect by preventing cognitive deficits. Here, using PMX205, a potent, specific C5aR1 antagonist, in the Tg2576 mouse model of Alzheimer’s disease we show a striking reduction in dystrophic neurites in parallel with the reduced amyloid load, rescue of the excessive pre-synaptic loss associated with AD cognitive impairment and the polarization of microglial gene expression towards a DAM-like phenotype that are consistent with the neuroprotective effects seen. These data support the beneficial effect of a pharmacological inhibition of C5aR1 as a promising therapeutic approach to treat Alzheimer’s disease. Supportive of the safety of this treatment is the recent FDA-approval of another other C5a receptor 1 antagonist, Avacopan, as a treatment for autoimmune inflammatory diseases.

One Sentence Summary

C5aR1 antagonist shifts microglial gene expression toward neuroprotection.
Profiles of secoiridoids and alkaloids in tissue of susceptible and resistant green ash progeny reveal patterns of induced responses to emerald ash borer inFraxinus pennsylvanica
Authors: Stanley Robert K. , Carey David W. , Mason Mary E. , Poland Therese M. , Koch Jennifer L. , Jones A. Daniel , Romero-Severson Jeanne
Published: May 2022

The emerald ash borer (Agrilus planipennis, EAB) invasion in North America threatens most North AmericanFraxinusspecies, including green ash (F. pennsylvanica), the mostly widely distributed species (1, 2). A small number of green ash (“lingering ash”, 0.1-1%) survive years of heavy EAB attack (3) and kill more EAB larvae when challenged in greenhouse studies than susceptible controls (4). We combined untargeted metabolomics with intensive phenotyping of segregating F1progeny from susceptible or lingering ash parents to detect chemotypes associated with defensive responses to EAB. We examined three contrasting groups: low larval kill (0-25% of larvae killed), high larval kill (55-95% of larvae killed) and uninfested. Contrasting the chemotypes of these groups revealed evidence of an induced response to EAB. Infested trees deployed significantly higher levels of select secoiridoids than uninfested trees. Within the infested group, the low larval kill (LLK) individuals deployed significantly higher levels of select secoiridoids than the high larval kill (HLK) individuals. The HLK individuals deployed significantly higher concentrations of three metabolites annotated as aromatic alkaloids compared to the LLK and uninfested individuals. We propose a two-part model for the North AmericanFraxinusresponse to EAB wherein every individual has the capacity to detect and respond to EAB, but only certain trees mount an effective defense, killing enough EAB larvae to prevent or minimize lethal damage to the vascular system. Integration of intensive phenotyping of structured populations with metabolomics reveals the multi-faceted nature of the defenses deployed in naïve host populations against invasive species.

Significance

Long-lived forest trees employ evolutionarily conserved templates to synthesize an array of defensive metabolites. The regulation of these metabolites, honed against native pests and pathogens, may be ineffective against novel species, as illustrated by the high mortality (>99%) in green ash infested by the invasive emerald ash borer (EAB). However, high standing genetic variation may produce a few individuals capable of an effective defense, as seen in the rare surviving green ash. In an investigation of this plant-insect interaction, we annotated metabolites associated with generalized but ineffective responses to EAB, and others associated with successful defensive responses. Untargeted metabolomics combined with intensive phenotyping of structured populations provides a framework for understanding resistance to invasive species in naïve host populations.
Using NAMs to characterize chemical bioactivity at the transcriptomic, proteomic and phosphoproteomic levels
Authors: Li Yuan , Zhang Zhenpeng , Jiang Songhao , Xu Feng , Tulum Liz , Li Kaixuan , Liu Shu , Li Suzhen , Chang Lei , Liddell Mark , Tu Fengjuan , Gu Xuelan , Carmichael Paul Lawford , White Andrew , Peng Shuangqing , Zhang Qiang , Li Jin , Zuo Tao , Kukic Predrag , Xu Ping
Published: May 2022

Omic-based technologies are of particular interest and importance for non-animal chemical hazard and risk characterization based on the premise that any apical endpoint change must be underpinned by some alterations measured at the omic levels. In this work we studied cellular responses to caffeine and coumarin by generating and integrating multi-omic data from transcriptomic, proteomic and phosphoproteomic experiments. We have shown that the methodology presented here is able to capture the complete chain of events from the first compound-induced changes at the phosphoproteome level to changes in gene expression induced by transcription factors and lastly to changes in protein abundance that further influence changes at the cellular level. In HepG2 cells we found the metabolism of lipids and general cellular stress to be dominant biological processes in response to caffeine and coumarin exposure, respectively. The phosphoproteomic changes were detected early in time, at very low concentrations and provided a fast adaptive cellular response to chemical exposure. Changes in protein abundance were found much less frequently than the transcriptomic changes and can be used, together with the transcriptomic changes, to facilitate a more complete understanding of pathway responses to chemical exposure.

GRAPHIC ABSTRACT
Maize immune signalling peptide ZIP1 evolved de novo from a retrotransposon
Authors: Depotter Jasper R.L. , Misas Villamil Johana C. , Doehlemann Gunther
Published: May 2022

Plants are subjected to different types of threats that require appropriate physiological responses to counteract them. Signalling peptides are produced under specific conditions and elicit physiological changes.PROZIP1encodes such a signalling peptide, Zip1, that induces salicylic acid defence responses in maize (Zea mays) leading to a better protection against biotrophic pathogens. Despite salicylic acid pathway being conserved amongst plants, we observed that Zip1 only occurs in theZeagenus.PROZIP1’s evolution is associated with transposons, as it resides in the terminal repeat of a retrotransposon from the Gyma family. We traced back the mutations that were encountered by this transposon and found thatPROZIP1emergedde novoinZea. This emergence likely occurred less than 728,000 years ago. In conclusion, we describe the evolution of a recently emerged plant immune signalling peptide from a transposon sequence.
pastclim: an R package to easily access and use paleoclimatic reconstructions
Authors: Leonardi Michela , Hallett Emily Y. , Beyer Robert , Krapp Mario , Manica Andrea
Published: May 2022

The recent development of continuous paleoclimatic reconstructions covering hundreds of thousands of years paved the way to a large number of studies from disciplines ranging from paleoecology to linguistics, from archaeology to conservation and from population genetics to human evolution. Unfortunately, such climatic data can be challenging to extract and analyze for scholars unfamiliar with such specific climatic file formats.

Here we presentpastclim, an R package facilitating the access and use of two sets of paleoclimatic reconstructions covering respectively the last 120,000 and 800,000 years. The package contains a set of functions allowing to quickly and easily recover the climate for the whole world or specific areas for time periods of interest, extract data from locations scattered in space and/or time, retrieve time series from individual sites, and easily manage the ice or land coverage.

The package can easily be adapted to paleoclimatic reconstructions different from the ones already included, offering a handy platform to include the climate of the past into existing analyses and pipelines.
Serial depletion of Baltic herring since the Viking Age revealed by ancient DNA and population genomics
Authors: Atmore Lane M. , Martínez-García Lourdes , Makowiecki Daniel , André Carl , Lõugas Lembi , Barrett James H. , Star Bastiaan
Published: May 2022

Marine resource consumption has been a key component in European diet and culture since the Middle Ages, when fish consumption increased dramatically. Yet, the early origins of marine industries and the long-term ecological consequences of historical and contemporary fisheries remain debated. The Baltic Sea was home to the first “industrial” fishery ∼800 years ago targeting the Baltic herring, a species that is still economically and culturally important today. We combine modern whole genome data with ancient DNA (aDNA) to identify the first known long-distance herring trade in the region, illustrating that large-scale fish trade began during the Viking Age. We resolve population structure within the Baltic and observe demographic independence for four local herring stocks over at least 200 generations. It has been suggested that overfishing at Øresund in the 16thcentury resulted in a demographic shift from autumn-spawning to spring-spawning herring dominance in the Baltic. We show that while the Øresund fishery had a negative impact on the western Baltic herring stock, the existence of autumn-spawning refugia in other regions of the Baltic delayed the demographic shift to spring spawning dominance until the 20thcentury. Importantly, modelling demographic trajectories over time, we identify a consistent pattern of serial depletion within the Baltic that is associated with changes in fishing pressure and climate, and conclude that herring exploitation at both historical and recent intensities is not sustainable. Our results highlight the complex and enduring impacts humans have had on the marine environment well before the industrial era.
DCAlign v1.0: Aligning biological sequences using co-evolution models and informative priors
Authors: Muntoni Anna Paola , Pagnani Andrea
Published: May 2022

DCAlign is a new alignment method able to cope with the conservation and the co-evolution signals that characterize the columns of a multiple sequence alignment of homologous sequences. However, the pre-processing steps required to align a candidate sequence are computationally demanding. We show in v1.0 how to dramatically reduce the overall computing time by including an empirical prior over an informative set of variables mirroring the presence of insertions and deletions.

Availability and implementation

DCAlign v1.0 is implemented in Julia and it is fully available at https://github.com/infernet-h2020/DCAlign

Contact

anna.muntoni@polito.it
PGC-1β maintains mitochondrial metabolism and restrains inflammatory gene expression
Authors: Guak Hannah , Sheldon Ryan D. , Beddows Ian , Ark Alexandra Vander , Shen Hui , Jones Russell G. , St-Pierre Julie , Ma Eric H. , Krawczyk Connie M.
Published: May 2022

Metabolic programming of the innate immune cells known as dendritic cells (DCs) changes in response to different stimuli, influencing their function. While the mechanisms behind increased glycolytic metabolism in response to inflammatory stimuli are well-studied, less is known about the programming of mitochondrial metabolism in DCs. We used lipopolysaccharide (LPS) and interferon-β (IFN-β), which differentially stimulate the use of glycolysis and oxidative phosphorylation (OXPHOS), respectively, to identify factors important for mitochondrial metabolism. We found that the expression of peroxisome proliferator-activated receptor gamma coactivator 1β (PGC-1β), a transcriptional co-activator and known regulator of mitochondrial metabolism, decreases when DCs are activated with LPS, when OXPHOS is diminished, but not with IFN-β, when OXPHOS is maintained. We examined the role of PGC-1β in bioenergetic metabolism of DCs and found that PGC-1β deficiency in DCs indeed impairs mitochondrial respiration. PGC-1β-deficient DCs are more glycolytic compared to controls, likely to compensate for reduced OXPHOS. PGC-1β deficiency also causes decreased capacity for ATP production at steady state and in response to IFN-β treatment. Loss of PGC-1β in DCs leads to increased expression of genes in inflammatory pathways, and reduced expression of genes encoding proteins important for mitochondrial metabolism and function. Collectively, these results demonstrate that PGC-1β is a key positive regulator of mitochondrial metabolism in DCs.
Discovery and pre-clinical evaluation of antibodies to the NKG2A inhibitory receptor
Authors: Baek Du-San , Kim Ye-Jin , Li Wei , Macatangay Bernard JC , Cyktor Joshua C. , Hines Margaret G. , Mellors John W. , Dimitrov Dimiter S.
Published: May 2022

NK and CD8+ T cells are important cells for cytolysis of cancer cells. The tumor microenvironment can upregulate surface expression on these cells of NKG2A, an inhibitory receptor that can dampen immune responses to cancer leading to immune evasion. To block NKG2A-mediated inhibition, we discovered and characterized two fully human antibodies using phage and yeast display that bind to NKG2A. These antibodies are highly specific for human CD94/NKG2A heterodimer complex, displaying no binding to the activating NKG2C receptor. A mutagenesis study revealed that the serine residue at 170 position (S170) of NKG2A is critical for the selectivity of anti-NKG2A antibodies. In vitro cytotoxic assays showed that NKG2A antibody inhibitors activated primary NK cells and promoted ADCC function of specific antibodies that bind to antigens expressed on cancer cells.

Summary heading

Fully human antibodies to the NKG2A inhibitory receptor
Ancestral state reconstruction suggests repeated losses of recruitment communication during ant evolution (Hymenoptera: Formicidae)
Authors: Glaser Simone M , Grüter Christoph
Published: May 2022

Eusocial insects have evolved different strategies to share information about their environment and workers can recruit nestmates to food sources or new nest sites. Ants are the most species-rich social insect group and are known to use pheromones, visual and tactile signals to communicate and inform nestmates about resources. However, how these different strategies evolved and whether there was a predominant evolutionary sequence that led to present day recruitment strategies is not well understood. In our study we explored two competing hypotheses about the ancestral recruitment communication: (1) ant ancestors did not recruit nestmates and species evolved more complex recruitment strategies over time vs. (2) early ants used mass-recruitment, which was lost repeatedly in some lineages. We combined an extensive search of the scientific literature and ancestral state reconstruction to estimate the ancestral recruitment strategy, focusing on the categories (i) no recruitment, (ii) tandem running, (iii) group-recruitment and (iv) chemical mass-recruitment. Stochastic character mapping suggests that mass-recruitment was ancestral in ants (59-61%), whereas “no recruitment” was unlikely to be the ancestral condition (21%). Similarly, marginal ancestral state reconstruction suggests that mass-recruitment (44-81%) or group-recruitment (48-50%) represented the original state. Our results are consistent with the finding that early ants lived in colonies containing up to several thousand individuals, which are typically associated with mass-recruiting in ants. However, our ability to robustly identify patterns in the evolution of communication in ants remains hampered by a lack of natural history information for most ant species.
Diverse task-driven modeling of macaque V4 reveals functional specialization towards semantic tasks
Authors: Cadena Santiago A. , Willeke Konstantin F. , Restivo Kelli , Denfield George , Sinz Fabian H. , Bethge Matthias , Tolias Andreas S. , Ecker Alexander S.
Published: May 2022

Responses to natural stimuli in area V4 – a mid-level area of the visual ventral stream – are well predicted by features from convolutional neural networks (CNNs) trained on image classification. This result has been taken as evidence for the functional role of V4 in object classification. However, we currently do not know if and to what extent V4 plays a role in solvingothercomputational objectives. Here, we investigated normative accounts of V4 (and V1 for comparison) by predicting macaque single-neuron responses to natural images from the representations extracted by 23 CNNs trained on different computer vision tasks including semantic, geometric, 2D, and 3D types of tasks. We found that V4 was best predicted by semantic classification features and exhibited high task selectivity, while the choice of task was less consequential to V1 performance. Consistent with traditional characterizations of V4 function that show its high-dimensional tuning to various 2D and 3D stimulus directions, we found that diverse non-semantic tasks explained aspects of V4 function beyond those captured by individual semantic tasks. Nevertheless, jointly considering the features of a pair of semantic classification tasks was sufficient to yield one of our top V4 models, solidifying V4’s main functional role in semantic processing and suggesting that V4’s affinity to 2D or 3D stimulus properties found by electrophysiologists can result from semantic functional goals.
Disentangling the historical routes to community assembly in the global epicentre of biodiversity
Authors: Reijenga Bouwe Rutger , Freeman Benjamin G , Murrell David J , Pigot Alex L
Published: May 2022

Aim

The coexistence and turnover of species along elevation gradients makes tropical mountains hotspots of biodiversity. However, understanding the historical processes through which species arising in geographic isolation (i.e. allopatry) assemble along the same mountain slope (i.e. sympatry) remains a major challenge. Multiple models have been proposed including, (1) the sorting of already elevationally divergent species, (2) the displacement of elevation upon secondary contact, potentially followed by convergence, or (3) elevational conservatism, in which ancestral elevational ranges are retained. However, the relative contribution of these processes to generating patterns of elevational overlap and turnover is unknown.

Location

Tropical mountains of Central- and South-America.

Time period

The last 12 myr.

Major taxa studied

Birds.

Methods

We collate a dataset of 165 avian sister pairs containing estimates of phylogenetic age, geographical and regional elevational range overlap. We develop a framework based on continuous-time Markov models to infer the relative frequency of different historical pathways in explaining present day overlap and turnover of sympatric species along elevational gradients.

Results

We show that the turnover of closely related bird species across elevation can predominantly be explained by displacement of elevation ranges upon contact (81%) rather than elevational divergence in allopatry (19%). In contrast, overlap along elevation gradients is primarily (88%) explained by conservatism of elevational ranges rather than displacement followed by elevational expansion (12%).

Main conclusions

Bird communities across tropical elevation gradients are assembled through a mix of processes, including the sorting, displacement and conservatism of species elevation ranges. The dominant role of conservatism in explaining co-occurrence of species on mountain slopes rejects more complex scenarios requiring displacement followed by subsequent expansion. The ability of closely related species to coexist without elevational divergence provides a direct and thus faster pathway to sympatry and may help explain the exceptional species richness of tropical mountains.
A multi-domain connector links the outer membrane and cell wall in deep-branching bacteria
Authors: von Kügelgen Andriko , van Dorst Sofie , Alva Vikram , Bharat Tanmay A. M.
Published: May 2022

Deinococcus radiodurans is a deep-branching extremophilic bacterium that is remarkably tolerant to numerous environmental stresses, including large doses of ultraviolet radiation and extreme temperatures. It can even survive in outer space for several years. This endurance of D. radiodurans has been partly ascribed to its atypical cell envelope comprising an inner membrane, a large periplasmic space with a thick peptidoglycan (PG) layer, and an outer membrane (OM) covered by a surface layer (S-layer). Despite intense research, molecular principles governing envelope organization and OM stabilization are unclear in D. radiodurans and related bacteria. Here, we report an electron cryomicroscopy (cryo-EM) structure of the abundant D. radiodurans OM protein SlpA, showing how its C-terminal segment forms homotrimers of 30-stranded β-barrels in the OM, whereas its N-terminal segment forms long, homotrimeric coiled coils linking the OM to the PG layer via S-layer homology (SLH) domains. Using the power of structure prediction and sequence-based bioinformatics, we further show that SlpA-like proteins are widespread in deep-branching Gram-negative bacteria, plausibly constituting an ancestral superfamily of OM-PG connectors, important for organizing the cell envelopes of many bacteria. Finally, combining our atomic structures with tomography of cell envelopes, we report a model for the cell surface of D. radiodurans, with implications on understanding the cell surface organization and hyperstability of D. radiodurans and related bacteria. Furthermore, the widespread occurrence of SlpA-like OM-PG connectors in deep-branching bacteria will help in understanding the evolutionary transition between Gram-negative and Gram-positive bacteria.
ERK pathway activation inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangement
Authors: Dougherty Larissa L , Dutta Soumita , Avasthi Prachee
Published: May 2022

Mitogen-activated protein kinase (MAPK) pathways are well known regulators of the cell cycle but they have also been found to control ciliary length in a wide variety of organisms and cell types from Caenorhabditis elegans neurons to mammalian photoreceptors through unknown mechanisms. ERK1/2 is a MAP kinase in human cells that is predominantly phosphorylated by MEK1/2 and dephosphorylated by the phosphatase DUSP6. We have found that the ERK1/2 activator/DUSP6 inhibitor, (E)-2-benzylidine-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), inhibits ciliary maintenance in Chlamydomonas and hTERT-RPE1 cells and assembly in Chlamydomonas. These effects involve inhibition of total protein synthesis, microtubule organization, membrane trafficking, and partial kinesin-2 motor dynamics. Our data provide evidence for various avenues for BCI-induced ciliary shortening and impaired ciliogenesis that gives mechanistic insight into how MAP kinases can regulate ciliary length.
NON-TARGETED METABOLOMICS REVEAL DIFFERENCES IN THE METABOLIC PROFILE OF THE FALL ARMYWORM STRAINS WHEN FEEDING DIFFERENT FOOD SOURCES
Authors: Oliveira Nathalia C. , Phelan Larry , Labate Carlos A. , Cônsoli Fernando L.
Published: May 2022

Spodoptera frugiperda, the fall armyworm (FAW), is an important polyphagous agricultural pest feeding on nearly 350 host plants. FAW is undergoing incipient speciation with two well-characterized host-adapted strains, the “corn” (CS) and “rice” (RS) strains, which are morphologically identical but carry several genes under positive selection for host adaptation. We used non-targeted metabolomics based on gas chromatography/mass spectrometry to identify differences in metabolite profiles of the larval gut ofCSandRSfeeding on different host plants. Larvae were fed on artificial diet, maize, rice, or cotton leaves from eclosion to the sixth instar, when they had their midgut dissected for the analysis. This study revealed that the midgut metabolome of FAW varied due to larval diet and differed between the FAW host-adapted strains. Additionally, we identified several candidate metabolites that may be involved in the adaptation ofCSandRSto their host plants. Our findings provide clues toward the gut metabolic activities of the FAW strains.
Nucleotide resolution genetic mapping in pigs by publicly accessible whole genome imputation
Authors: Ding Rongrong , Savegnago Rodrigo , Liu Jinding , Long Nanye , Tan Cheng , Cai Gengyuan , Zhuang Zhanwei , Wu Jie , Yang Ming , Qiu Yibin , Ruan Donglin , Quan Jianping , Zheng Enqin , Hong Linjun , Li Zicong , Tan Suxu , Bedhane Mohammd , Schnabel Robert , Steibel Juan , Gondro Cedric , Yang Jie , Huang Wen , Wu Zhenfang
Published: May 2022

Genetic mapping to identify genes and alleles associated with or causing economically important quantitative trait variation in livestock animals such as pigs is a major goal in the genetic improvement animals. Despite recent advances in high throughput genotyping technologies, resolution of genetic mapping in pigs remains poor due in part to the low density of genotyped variant sites. In this study, we overcame this limitation by developing a reference haplotype panel for pigs based on 2,259 whole genome sequenced animals representing 44 pig breeds. We optimized the imputation procedure to achieve an average concordance rate in excess of 97%, non-reference concordance rate 91%, and r2 0.89. We demonstrated that genotype imputation using this resource can dramatically improve resolution of genetic mapping. Finally, we developed a public web server (swimgeno.org) to allow the pig genetics community to fully utilize this resource. We expect the resource and server to significantly facilitate genetic mapping and accelerate genetic improvement in pigs.