bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection on visual opsin genes in diurnal Neotropical frogs and loss of theSWS2opsin in poison frogs
Authors: Wan YC , Navarrete MJ , O’Connell LA , Uricchio LH , Roland AB , Maan ME , Ron SR , Betancourth-Cundar M , Pie MR , Howell KA , Richards-Zawacki CL , Cummings ME , Cannatella DC , Santos JC , Tarvin RD
Published: October 2022

Amphibians are ideal for studying visual system evolution because their biphasic (aquatic and terrestrial) life history and ecological diversity expose them to a broad range of visual conditions. Here we evaluate signatures of selection on visual opsin genes across Neotropical anurans and focus on three diurnal clades that are well-known for the concurrence of conspicuous colors and chemical defense (i.e., aposematism): poison frogs (Dendrobatidae), Harlequin toads (Bufonidae:Atelopus), and pumpkin toadlets (Brachycephalidae:Brachycephalus). We found evidence of positive selection on 44 amino acid sites inLWS, SWS1, SWS2,andRH1opsin genes, of which one inLWSand two inRH1have been previously identified as spectral tuning sites in other vertebrates. Given that anurans have mostly nocturnal habits, the patterns of selection revealed new sites that might be important in spectral tuning for frogs, potentially for adaptation to diurnal habits and for color-based intraspecific communication. Furthermore, we provide evidence thatSWS2, normally expressed in rod cells in amphibians, has likely been lost in the ancestor of Dendrobatidae, suggesting that under low-light levels, dendrobatids have inferior wavelength discrimination compared to other frogs. This loss might follow the origin of diurnal activity in dendrobatids and could have implications for their chemical ecology, biodiversity, and behavior. Our analyses show that assessments of opsin diversification in understudied groups could expand our understanding of the role of sensory system evolution in ecological adaptation.
Species interactions and diversity: a unified framework using Hill numbers
Authors: Godsoe William , Murray Rua , Iritani Ryosuke
Published: October 2022

Biodiversity describes the variety of organisms on planet earth. Ecologists have long hoped for a synthesis between analyses of biodiversity and analyses of biotic interactions among species, such as predation, competition, and mutualism. However, it is often unclear how to connect details of these interactions with complex modern analyses of biodiversity. To resolve this gap, we propose a unification of models of biotic interactions and measurements of diversity. We show that analyses of biodiversity obscure details about biotic interactions. For example, identical changes in biodiversity can arise from predation, competition or mutualism. Our approach indicates that traditional models of community assembly miss key facets of diversity change. Instead, we suggest that analyses of diversity change should focus on partitions, which measure mechanisms that directly shape changes in diversity, notably species level selection and immigration, rather than traditional analyses of biotic interactions.

Speculations

Our paper proposes that observations of biodiversity cannot be used to distinguish different types of biotic interactions. For generations ecologists have been fascinated with the links between biodiversity and biotic interactions (i.e. competition, mutualism and predation). Many of us expect that observations of biodiversity provide vital clues about how biotic interactions operate in nature, but it is hard to tell when these clues are reliable.

Our work integrates models of biotic interactions and measurements of biodiversity diversity change. This highlights how an observed change in diversity can be compatible with any type of biotic interaction (i.e. competition, mutualism, predation etc.). So for example, the same increase in Shannon diversity could indicate the superior ability of a competitor the success of mutualists or a predator’s tendency to harvest dominant prey species. This is so because diversity measures are designed to be concerned with changes in relative abundances but not account for absolute abundance changes.

Observations of biodiversity change are unlikely to yield insights about biotic interactions per se because biodiversity itself obscures species’ absolute abundances. Therefore, models of diversity change should focus on mechanisms that are less influenced by changes in absolute abundances such as species-level selection.
Throat colour polymorphism in relation to sex and body size of the Litter skink,Lankascincus fallax
Authors: Jayamanna J.M.A. Ishara K. , de Silva Anslem , Ukuwela Kanishka D.B.
Published: October 2022

Colour polymorphism is a pervasive phenomenon in both animal and plant kingdoms and understanding its evolution and maintenance is of great interest. Among the lizards of Sri Lanka, the endemic skinkLankascincus fallaxshows throat colour polymorphism in which, the underlying basis is not clearly known. In this study, we examined the relationship of the three different throat colour morphs observed in this species with the sex, body size and the geographic location ofL. fallax. Live skinks were sampled from two locations in Sri Lanka and sex and the throat colour was categorized visually and the snout to vent length (SVL) was measured. Tail tips of some selected individuals from the two locations were taken and a fragment of the 12S rRNA gene was sequenced in representative individuals having the different throat colour morphs. Pairwise genetic distance of the three colour morphs ranged between 0.4–0.5% confirming that the three colour morphs were the same species. Three colour morphs (red, black and white) were observed in males in both locations, while only the white morph was observed in females, suggesting that the throat color polymorphism was confined to males. There was a significant difference between the mean SVL of males with red and black throat colours (39.35 mm) and males with white throat colours (30.31 mm). Thus, the study suggests that the throat colour in these skinks is highly associated with sex and the body size in males. The study further suggests thatL. fallaxis sexually dichromatic and that the males show throat colour polymorphism. However, future studies are necessary to understand the underlying drivers for the presence and maintenance of sexual dichromatism and throat colour polymorphism inL. fallax.
Regulation of interstitial fluid flow along adventitia of vasculature by heartbeat and respiration
Authors: Li Hongyi , Li Bei , Luo Wenqi , Qi Xi , Hao You , Yang Chaozhi , Li Wenqing , Li Jiazheng , Hua Zhen , Guo Tan , Zheng Zhijian , Yu Xue , Liu Lei , Zhao Jianping , Li Tiantian , Huang Dahai , Hu Jun , Li Zongmin , Wang Fang , Li Hua , Ma Chao , Ji Fusui
Published: October 2022

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows along adventitia of vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.
Temporal Application of Lysyl Oxidase during Hierarchical Collagen Fiber Formation Differentially Effects Mechanics in Engineered Tissues
Authors: Bates Madison , Troop Leia , Brown M. Ethan , Puetzer Jennifer L.
Published: October 2022

The primary source of strength in musculoskeletal menisci, tendons, and ligaments are hierarchical collagen fibers; however, these fibers are not regenerated after injury nor in engineered replacements, resulting in limited repair options. Collagen strength is reliant on fiber alignment, density, diameter, and crosslinking. Recently, we developed a culture system which guides cells in high-density collagen gels to develop native-like hierarchically organized collagen fibers, which match native alignment and fiber diameters by 6 weeks. However, tissue mechanics plateau at 1 MPa, suggesting crosslinking is lacking. Collagen crosslinking is regulated by lysyl oxidase (LOX) which forms immature crosslinks that condense into mature trivalent crosslinks. Trivalent crosslinks are thought to be the primarily source of strength in fibers, but its not well understood how they form. The objective of this study was to evaluate the effect of exogenous LOX treatment at different stages of hierarchical fiber formation in our culture system to produce functional engineered replacements and to better understand factors effecting collagen crosslink maturation. We found LOXL2 treatment did not restrict hierarchical fiber formation, with constructs still forming aligned collagen fibrils by 2 weeks, larger fibers by 4 weeks, and early fascicles by 6 weeks. However, LOXL2 treatment did significantly increase mature pyridinium crosslink accumulation and tissue mechanics, with timing of LOXL2 supplementation during fiber formation having a significant effect. Overall, we found one week of LOXL2 supplementation at 4 weeks produced constructs with native fiber organization, increased PYD accumulation, and increased mechanics, ultimately matching the tensile modulus of immature bovine menisci.

Statement of Significance

Collagen fibers are the primarily source of strength and function in connective tissues throughout the body, however it remains a challenge to develop these fibers in engineered replacements, greatly reducing treatment options. Here we demonstrate lysyl oxidase like 2 (LOXL2) can be used to significantly improve the mechanics of tissue engineered constructs, but timing of application is important and will most likely depend on degree of collagen organization or maturation. Currently there is limited understanding of how collagen crosslinking is regulated, and this system is a promising platform to further investigate cellular regulation of LOX crosslinking. Understanding the mechanism that regulates LOX production and activity is needed to ultimately regenerate functional repair or replacements for connective tissues throughout the body.
A germline-targeting chimpanzee SIV envelope glycoprotein elicits a new class of V2-apex directed cross-neutralizing antibodies
Authors: Bibollet-Ruche Frederic , Russell Ronnie M. , Ding Wenge , Liu Weimin , Li Yingying , Wagh Kshitij , Wrapp Daniel , Habib Rumi , Skelly Ashwin N. , Roark Ryan S. , Sherrill-Mix Scott , Wang Shuyi , Rando Juliette , Lindemuth Emily , Cruickshank Kendra , Park Younghoon , Baum Rachel , Connell Andrew Jesse , Li Hui , Giorgi Elena E. , Song Ge S. , Ding Shilei , Finzi Andrés , Newman Amanda , Hernandez Giovanna E. , Machiele Emily , Cain Derek W. , Mansouri Katayoun , Lewis Mark G. , Montefiori David C. , Wiehe Kevin J. , Alam S. Munir , Teng I-Ting , Kwong Peter D. , Andrabi Raiees , Verkoczy Laurent , Burton Dennis R. , Korber Bette T. , Saunders Kevin O. , Haynes Barton F. , Edwards Robert J. , Shaw George M. , Hahn Beatrice H.
Published: October 2022

HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germline-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, non-neutralizing antibodies revealed that SCIV-expressed Envs as well as some primary HIV-1 Envs adopted a more open conformation, thereby exposing a conserved V2 epitope that is occluded in closed SIVcpz and HIV-1 Env trimers. These results expand the spectrum of V2-apex targeted antibodies that can contribute to neutralization breadth and identify novel SIV Env platforms for further development as germline-targeting and immunofocusing immunogens.

One sentence summary

A cryptic V2 epitope in occluded-open HIV and SIV Env trimers is the target of a new class of V2-directed cross-neutralizing antibodies.
Automating microbial taxonomy workflows with PHANTASM: PHylogenomic ANalyses for the TAxonomy and Systematics of Microbes
Authors: Wirth Joseph S. , Bush Eliot C.
Published: October 2022

The nucleotide sequences of 16S ribosomal RNA (rRNA) genes have been used to inform the taxonomic placement of prokaryotes for several decades. Whole-genome approaches can better resolve evolutionary relationships of organisms, but these analyses often require computational proficiencies that are uncommon among microbiologists. PHANTASM is a new tool capable of automating these workflows. This tool was designed to work for a wide range of prokaryotes and is the first example of an automated reconciliation of NCBI’s Taxonomy database with that of the List of Prokaryotic names with Standing in Nomenclature (LPSN). In this study, we describe the workflow of PHANTASM and provide several examples of results generated by it. The source code is freely-available on GitHub. In order to facilitate the ease-of-access for researchers, PHANTASM is also available as a Docker image. While other tools exist to facilitate starting points for these analyses, PHANTASM provides users with a greater degree of control and produces outputs that can be used to make publication-quality figures.
A Chromosome-length Assembly of the Black Petaltail (Tanypteryx hageni) Dragonfly
Authors: Tolman Ethan R. , Beatty Christopher D. , Bush Jonas , Kohli Manpreet , Moreno Carlos M. , Ware Jessica L. , Weber K. Scott , Khan Ruqayya , Maheshwari Chirag , Weisz David , Dudchenko Olga , Aiden Erez Lieberman , Frandsen Paul B.
Published: October 2022

We present a chromosome-length genome assembly and annotation of the Black Petaltail dragonfly (Tanypteryx hageni). This habitat specialist diverged from its sister species over 70 million years ago, and separated from the most closely related Odonata with a reference genome 150 million years ago. Using PacBio HiFi reads and Hi-C data for scaffolding we produce one of the most high quality Odonata genomes to date. A scaffold N50 of 206.6 Mb and a BUSCO score of 96.8% indicate high contiguity and completeness.

Significance

We provide a chromosome-length assembly of the Black Petaltail dragonfly (Tanypteryx hageni), the first genome assembly for any non-libelluloid dragonfly. The Black Petaltail diverged from its sister species over 70 million years ago.T. hageni, like its confamilials, occupies fen habitats in its nymphal stage, a life history uncommon in the vast majority of dragonflies. We hope that the availability of this assembly will facilitate research onT. hageniand other petaltail species, to better understand their ecology and support conservation efforts.
Early life sleep disruption has long lasting, sex specific effects on later development of sleep in prairie voles
Authors: Jones-Tinsley Carolyn E. , Olson Randall J. , Mader Miranda , Wickham Peyton T. , Gutowsky Katelyn , Wong Claire , Chu Sung Sik , Milman Noah E. , Cao Hung , Lim Miranda M.
Published: October 2022

In mammals, sleep duration is highest in the early postnatal period of life and is critical for shaping neural circuits that control the development of complex behaviors. The prairie vole is a wild, highly social rodent that serves as a unique model for the study of complex, species-typical social behaviors. Previous work in our laboratory has found that early life sleep disruption (ELSD) in prairie voles during a sensitive window of postnatal development leads to long lasting changes in social and cognitive behaviors as well as structural changes in excitatory and inhibitory neural circuits in the brain. However, it is currently unknown how later sleep is impacted by ELSD, both shortly after ELSD and over the long term. Therefore, the aim of this study was to describe the effects of ELSD on later life sleep, compared to sleep in normally developing prairie voles. First, we conducted tethered electroencephalogram/electromyogram (EEG/EMG) recordings in juvenile prairie voles undergoing ELSD, compared to Control conditions. Second, we conducted 24 hours of home cage tethered EEG/EMG recordings in either adolescent or adult male and female prairie voles that had previously undergone ELSD or Control conditions as juveniles. We found that, as adults, male ELSD prairie voles showed persistently lower REM sleep duration and female ELSD prairie voles showed persistently higher NREM sleep duration compared to Controls, but no other sleep parameters differed. We concluded that 1) persistent effects of ELSD on sleep into adulthood may contribute to the social and cognitive deficits observed in adult voles, and 2) sleep disruption early in life can influence later sleep patterns in adulthood.
Indications of an Achaea sp. caterpillar outbreak disrupting fruiting of an ectomycorrhizal tropical tree in Central African rainforest
Authors: Norghauer Julian M. , Newbery David M. , Neba Godlove A.
Published: October 2022

Background and aims

Where one or several tree species come to dominate patches of tropical forest, as many masting ectomycorrhizal legumes do in central Africa, ecological theory predicts they may be prone to herbivory which might alter their reproductive output. This was indirectly investigated in lowland rainforest in Cameroon forTetraberlinia korupensis, whose crowns were attacked in 2008 by an outbreaking black caterpillar—identified as anAchaeasp., probablyA. catocaloides—in Korup National Park.

Material and methods

Field-collected data on tree-level seed and fruit (pod) production ofT. korupensisin its 2008 masting event were compared with that of its two co-dominant neighbours (T. bifoliolata, Microberlinia bisulcata) whose populations masted in 2007 (and 2010). To do this, bivariate regression models (linear, polynomial, ZiG [zero-inflated gamma model]), contingency table analysis, and non-parametric measures of dispersion were used.

Key results

AssumingT. korupensisis prone toAchaeacaterpillar attacks, empirical data support the hypothesized lower proportion of adults participating in its masting (54% in 2008) than for either masting population ofM. bisulcata(98% in 2007, 89% in 2010) orT. bifoliolata(96% in 2007, 78% in 2010). These fruitingT. korupensistrees were about one-third larger in stem diameter than conspecific non-fruiters and produced as many pods and seeds per capita asT. bifoliolata. But regressions only modestly support the hypothesis that the positive tree size–fecundity relationship forT. korupensiswas weaker (i.e., lower adj.R2) than forM. bisulcata(whose leaves are morphologically similar) orT. bifoliolata, with mostly similar dispersion about the median among these species.

Conclusion

Altogether, the findings suggest a role for tolerance in nutrient-poor forests. It is postulated that instead of conferring resistance to herbivores, the ectomycorrhizas associated with these trees may enable them to more quickly recover from potential yet unpredictable insect outbreaks.
Enhancing functionalized liposome avidity to cells via lipid phase separation
Authors: Vu Timothy Q. , Sant’Anna Lucas E. , Kamat Neha P.
Published: October 2022

The addition of both cell-targeting moieties and polyethylene glycol (PEG) to nanoparticle (NP) drug delivery systems is a standard approach to improve the biodistribution, specificity, and uptake of therapeutic cargo. The spatial presentation of these molecules affects avidity of the NP to target cells in part through an interplay between the local ligand concentration and the steric hindrance imposed by PEG molecules. Here, we show that lipid phase separation in nanoparticles can modulate liposome avidity by changing the proximity of PEG and targeting protein molecules on a nanoparticle surface. Using lipid-anchored nickelnitrilotriacetic acid (Ni-NTA) as a model ligand, we demonstrate that the attachment of lipid anchored Ni-NTA and PEG molecules to distinct lipid domains in nanoparticles can enhance liposome binding to cancer cells by increasing ligand clustering and reducing steric hindrance. We then use this technique to enhance the binding of RGD-modified liposomes, which can bind to integrins overexpressed on many cancer cells. These results demonstrate the potential of lipid phase separation to modulate the spatial presentation of targeting and shielding molecules on nanocarriers, offering a powerful tool to enhance the efficacy of NP drug delivery systems.
IL-6/STAT3 signaling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis
Authors: Arneson-Wissink Paige C. , Mendez Heike , Pelz Katherine , Dickie Jessica , Bartlett Alexandra Q. , Worley Beth L. , Krasnow Stephanie M. , Eil Robert , Grossberg Aaron J.
Published: October 2022

Cancer cachexia is highly prevalent in patients with pancreatic ductal adenocarcinoma (PDAC). Although advanced cachexia is associated with inflammatory signaling, the early events driving wasting are poorly defined. Using an orthotopic mouse model of PDAC, we find that early cachexia is defined by a pronounced vulnerability to undernutrition, characterized by increased skeletal muscle wasting. PDAC suppresses lipid beta oxidation and impairs ketogenesis in the liver, which coordinates the adaptive response to nutritional scarcity. When PDAC mice are fed ketogenic diet, this effect is reversed, and muscle mass is preserved. Furthermore, physiologic levels of ketones are sufficient to protect myotubes against PDAC-associated wasting. Interleukin-6 (IL-6) drives liver metabolic reprogramming, and hepatocyte-specific loss of Signal Transducer and Activator of Transcription 3 (STAT3) is sufficient to prevent PDAC-associated muscle loss. Together, these studies define a key role for the liver in cachexia development and directly link skeletal muscle homeostasis to hepatic lipid oxidation.
Thousandfold Cell-Specific Pharmacology of Neurotransmission
Authors: Shields Brenda C. , Yan Haidun , Lim Shaun S.X. , Burwell Sasha C. , Fleming Elizabeth A. , Cammarata Celine M. , Kahuno Elizabeth W. , Vagadia Purav P. , Loughran Marie H. , Zhiquan Lei , McDonnell Mark E. , Scalabrino Miranda L. , Thapa Mishek , Hawley Tammy M. , Reitz Allen B. , Schiltz Gary E. , Hull Court , Field Greg D. , Glickfeld Lindsey L. , Tadross Michael R.
Published: October 2022

Cell-specific pharmaceutical technologies promise mechanistic insight into clinical drugs―those that treat, and often define, human disease. In particular,DART(drug acutely restricted by tethering) achieves genetically programmable control of drug concentration over cellular dimensions. The method is compatible with clinical pharmaceuticals and amenable to studies in behaving animals. Here, we describeDART.2, comprising three advances. First, we improve the efficiency of chemical capture, enabling cell-specific accumulation of drug to ∼3,000-times the ambient concentration in 15 min. Second, we develop tracer reagents, providing a behavior-independent measure of cellular target engagement in each animal. Third, we extend the method to positive allosteric modulators and outline design principles for this clinically significant class. We showcase the platform with four pharmaceuticals―two that weaken excitatory (AMPAR) or inhibitory (GABAAR) chemical neurotransmission, and two that strengthen these forms of synaptic communication. Across four labs, we tested reagents in the mouse cerebellum, basal ganglia, visual cortex, and retina. Collectively, we demonstrate robust, bidirectional editing of chemical neurotransmission. We provide for distribution of validated reagents, community design principles, and synthetic building blocks for application to diverse pharmaceuticals.
Huntingtin expression influences spontaneous seizure disorder susceptibility in FVN/B mice
Authors: Van Raamsdonk Jeremy M. , Al-Shekeli Hilal , Wagner Laura , Bredy Tim W , Chan Laura , Pearson Jacqueline , Schwab Claudia , Murphy Zoe , Devon Rebecca S. , Lu Ge , Kobor Michael S. , Hayden Michael R. , Leavitt Blair R.
Published: October 2022

Huntington disease (HD) is an adult-onset neurodegenerative disorder that is caused by a trinucleotide CAG repeat expansion in the HTT gene that codes for the protein huntingtin (HTT or Htt in mice). HTT is a multi-functional, ubiquitously expressed protein that is essential for embryonic survival, normal neurodevelopment, and adult brain function. The ability of wild-type HTT to protect neurons against various forms of death raises the possibility that loss of normal HTT function may worsen disease progression in HD. Huntingtin-lowering therapeutics are being evaluated in clinical trials for HD, but concerns have been raised that decreasing wild-type HTT levels may have adverse effects. Here we show that Htt levels modulate the occurrence of an idiopathic seizure disorder that spontaneously occurs in FVB/N mice. These abnormal FVB/N mice demonstrate various cardinal features of mouse models of epilepsy including spontaneous seizures, astrocytosis, neuronal hypertrophy, upregulation of brain-derived neurotrophic factor (BDNF), and sudden seizure-related death. Interestingly, decreasing wild-type Htt levels increased the frequency of this disorder, while over-expression of HTT completely prevented it. Examination of the mechanism underlying huntingtin’s ability to modulate the frequency of this seizure disorder indicated that over-expression of full length HTT can promote neuronal survival following seizures. Overall, our results demonstrate a protective role for huntingtin in this form of epilepsy and provide a plausible explanation for the observation of seizures in the juvenile form of HD, Lopes-Maciel-Rodan syndrome, and Wolf-Hirschhorn syndrome. Adverse effects caused by altering huntingtin levels has ramifications related to Huntingtin-lowering therapies in development to treat HD.
A highly contiguous genome assembly reveals sources of genomic novelty in the symbiotic fungusRhizophagus irregularis
Authors: Manley Bethan F. , Lotharukpong Jaruwatana S. , Barrera-Redondo Josué , Yildirir Gokalp , Sperschneider Jana , Corradi Nicolas , Paszkowski Uta , Miska Eric A. , Dallaire Alexandra
Published: October 2022

The root systems of most plant species are aided by the soil foraging capacities of symbiotic Arbuscular Mycorrhizal (AM) fungi of the Glomeromycotina subphylum. Despite recent advances in our knowledge of the ecology and molecular biology of this mutualistic symbiosis, our understanding of the AM fungi genome biology is just emerging. Presented here are the most contiguous and highest-quality nuclear and mitochondrial genome assemblies of an arbuscular mycorrhizal fungus to date, achieved through Nanopore long-read DNA sequencing and Hi-C data. This haploid genome assembly ofRhizophagus irregularis, alongside short- and long-read RNA-Sequencing data, was used to produce a comprehensive annotation catalogue of gene models, repetitive elements, small RNA loci, and DNA cytosine methylome. A phylostratigraphic gene age inference framework revealed that the birth of genes associated with nutrient transporter activity and transmembrane ion transport systems predates the emergence of Glomeromycotina. While symbiotic nutrient cycling in AM fungi relies on genes that existed in ancestor lineages, a burst of Glomeromycotina-restricted genetic innovation is also detected. Analysis of the chromosomal distribution of genetic and epigenetic features highlights evolutionarily young genomic regions that produce abundant small RNAs, suggesting active RNA-based monitoring of genetic sequences surrounding recently evolved genes. This chromosome-scale view of the genome of an AM fungus genome reveals previously unexplored sources of genomic novelty in an organism evolving under an obligate symbiotic life cycle.

Highlights

Assembly of 32 highly contiguous chromosomal scaffolds forR. irregularis, with 23 complete and gapless

Gene annotation based on short- and long-read RNA-Seq data from different developmental stages

Complete annotation set including mitochondrial genes, DNA methylome, small RNAome, repetitive/transposable elements, functional annotation

Identification of a burst of lineage-restricted genetic innovation in the Glomeromycotina subphylum
Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses
Authors: Zapatero María Ramos , Tong Alexander , Sufi Jahangir , Vlckova Petra , Rodriguez Ferran Cardoso , Nattress Callum , Qin Xiao , Hochhauser Daniel , Krishnaswamy Smita , Tape Christopher J.
Published: October 2022

Patient-derived organoids (PDOs) can model personalized therapy responses, however current screening technologies cannot reveal drug response mechanisms or study how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly-multiplexed mass cytometry platform to measure post translational modification (PTM) signaling in >2,500 colorectal cancer (CRC) PDOs and cancer-associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developedTrellis— a highly-scalable, hierarchical tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is patient-specific. We found drug-induced apoptosis does not correlate with genotype or clinical staging but does align with cell-intrinsic PTM signaling in PDOs. CAFs protect chemosensitive PDOs by shifting cancer cells into a slow-cycling cell-state and CAF chemoprotection can be reversed by inhibiting YAP.

Highlights

>2,500 single-cell PTM signaling, DNA-damage, cell-cycle, and apoptosis responses from drug-treated PDOs and CAFs.

Trellis: hierarchical tree-based treatment effect method for single-cell screening analysis.

PDOs have patient-specific drug responses that align with cell-intrinsic PTM signaling states.

CAFs chemoprotect PDOs by altering PDO cell-state via YAP signaling.
Impact of neurons on patient derived-cardiomyocytes using organ-on-a-chip and iPSC biotechnologies
Authors: Bernardin Albin A. , Colombani Sarah , Rousselot Antoine , Andry Virginie , Goumon Yannick , Pasqualin Côme , Brugg Bernard , Jacotot Etienne , Pasquié Jean-Luc , Lacampagne Alain , Meli Albano C.
Published: October 2022

In the heart, cardiac function is regulated by the autonomic nervous system (ANS) that extends through the myocardium and establish junctions at the sinus node and ventricular levels. Thus, an increase or decrease of neuronal activity acutely affects myocardial function and chronically affects its structure through remodeling processes. The neuro-cardiac junction (NCJ), which is the major structure of this system, is poorly understood and only few cell models allow us to study it. Here we present an innovant neuro-cardiac organ-on-chip model to study this structure to better understand the mechanisms involved in the establishment of NCJ. To create such a system, we used microfluidic devices composed of two separate cells compartment interconnected by asymmetric microchannels. Rat PC12 cells, were differentiated to recapitulate the characteristics of sympathetic neurons, and cultivated with cardiomyocytes derived from human induced pluripotent stem cells (hiPSC). We confirmed the presence of specialized structure between the two cell types that allow neuromodulation and observed that the neuronal stimulation impacts the excitation-contraction coupling properties including the intracellular calcium handling. Finally, we also co-cultivated human neurons (hiPSC-NRs) with human cardiomyocytes (hiPSC-CMs) both obtained from the same hiPSC line. Hence, we have developed a neuro-cardiac compartmentalized in vitro model system that allows to recapitulate structural and functional properties of neuro-cardiac junction and that can be used to better understand interaction between heart and brain in humans, as well as to evaluate the impact of drugs on a reconstructed human neuro-cardiac system.
Strawberry additive increases nicotine vapor sampling and systemic exposure but does not enhance Pavlovian-based nicotine reward in mice
Authors: Patten Theresa , Johnson Natalie L. , Shaw Jessica K. , Dossat Amanda M. , Dreier Allison , Kimball Bruce A. , Wesson Daniel W. , De Biasi Mariella
Published: October 2022

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, due to the availability of electronic nicotine devices (i.e., “vaping”) and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Nevertheless, mice exposed to nicotine + strawberry additive vapor had higher plasma cotinine concentrations, which did not appear to reflect altered nicotine metabolism. Instead, by directly measuring vapor sampling through respiration monitoring, we uncovered an increase in the amount of sniffing toward strawberry-containing nicotine vapor compared to nicotine vapor alone. Together these data indicate that chemosensory-rich e-liquid additives may enhance the perceived sensory profile of nicotine vapors rather than the reward valueper se, which leads to overall increased nicotine exposure.

Significance Statement

With the rise in popularity of flavored e-cigarette products, many have considered the possibility that flavor volatiles will enhance nicotine reward; however, the possibility that flavor additives have chemosensory properties that can affect nicotine intake has been largely overlooked. Here, by delivering nicotine to adolescent mice as a vapor we were able to consider both possibilities. We found that mice had increased sniffing intensity and nicotine exposure when vapors contained a strawberry additive, despite the fact that the same additive was unable to enhance Pavlovian nicotine reward using a CPP paradigm. This research highlights the importance of considering the chemosensory properties of e-cigarette additives as a mechanism for their effect on nicotine use.
Unique and shared proteome responses of rice plants (Oryza sativa) to individual abiotic stresses
Authors: Habibpourmehraban Fatemeh , Atwell Brian J. , Haynes Paul A.
Published: October 2022

Food safety of staple crops such as rice is of global concern and is at the top of the policy agenda worldwide. Abiotic stresses are one of the main limitations to optimizing yields for sustainability, food security and food safety. We analyzed proteome changes inOryza sativassp. Nipponbare in response to three adverse abiotic treatments, including three levels of drought (mild, moderate, and severe), soil salinization, and non-optimal temperatures. All treatments had modest, negative effects on plant growth, enabling us to identify proteins that were common to all stresses, or unique to one. More than 75% of the total of differentially abundant proteins in response to abiotic stresses were specific to individual stresses, while fewer than 5% of stress-induced proteins were shared across all abiotic constraints. Stress-specific and non-specific stress-responsive proteins identified were categorized in terms of core biological processes, molecular functions, and cellular localization.

Data Access

All data have also been submitted to the PRIDE data repository, and will be available with project identifier PXD037280.
An evolutionary conserved division-of-labor between hippocampal and neocortical sharp-wave ripples organizes information transfer during sleep
Authors: van Schalkwijk Frank J. , Weber Jan , Hahn Michael A. , Lendner Janna D. , Inostroza Marion , Lin Jack J. , Helfrich Randolph F.
Published: October 2022

The hippocampal sharp-wave ripple (SW-R) is the key substrate of the hippocampal-neocortical dialogue underlying memory formation. Recently, it became evident that SW-R are not unique to archicortex, but constitute a wide-spread neocortical phenomenon. To date, little is known about morphological and functional similarities between archi- and neocortical SW-R. Leveraging intracranial recordings from the human hippocampus and prefrontal cortex during sleep, our results reveal region-specific functional specializations, albeit a near-uniform morphology. While hippocampal SW-R trigger directional hippocampal-to-neocortical information flow, neocortical SW-R reduce information flow to minimize interference. At the population level, hippocampal SW-R confined population dynamics to a low-dimensional subspace, while neocortical SW-R diversified the population response; functionally uncoupling the hippocampal-neocortical network. Critically, our replication in rodents demonstrated the same division-of-labor between archi-and neocortical SW-R. These results uncover an evolutionary preserved mechanism where coordinated interplay between hippocampal and neocortical SW-R temporally segregates hippocampal information transfer from neocortical processing.
Plant YTHDF proteins are direct effectors of antiviral immunity against an m6A-containing RNA virus
Authors: Martínez-Pérez Mireya , Aparicio Frederic , Arribas-Hernández Laura , Due Tankmar Mathias , Rennie Sarah , Brodersen Peter , Pallas Vicente
Published: October 2022

In virus-host interactions, nucleic acid-directed first lines of defense that allow viral clearance without compromising growth are of paramount importance. Plants use the RNA interference pathway as such a basal antiviral immune system, but additional RNA-based mechanisms of defense also exist. The infectivity of the plant positive strand RNA virus alfalfa mosaic virus (AMV) relies on demethylation of viral RNA by recruitment of the cellularN6-methyladenosine (m6A) demethylase ALKBH9B, but how demethylation of viral RNA promotes AMV replication remains unknown. Here, we show that inactivation of the cytoplasmic YT521-B homology domain (YTH)-containing m6A-binding proteins, ECT2, ECT3, and ECT5 is sufficient to restore AMV infectivity in partially resistantalkbh9bmutants. We also show that the antiviral function of ECT2 is distinct from its previously demonstrated function in promotion of proliferation of primordial cells, because an ECT2 mutant carrying a small deletion in its intrinsically disordered region is partially compromised for antiviral defense, but not for developmental functions. These results indicate that the m6A-YTH axis constitutes a novel branch of basal antiviral immunity in plants.
Metabolic evolution in response to interspecific competition in a eukaryote
Authors: Ghedini Giulia , Marshall Dustin J.
Published: October 2022

Competition can drive rapid evolution which, in turn, alters the trajectory of ecological communities. The role of eco-evolutionary dynamics in ecological communities is increasingly well-appreciated, but a mechanistic framework for identifying the types of traits that will evolve, and their trajectories, is required. Metabolic theory makes explicit predictions about how competition should shape the evolution of metabolism and size but these predictions have gone largely untested, particularly in eukaryotes. We use experimental evolution of a eukaryotic phototroph to examine how metabolism, size, and demography coevolve under both inter- and intra-specific competition. We find that the focal species evolves a smaller body size in response to competition, reducing density-dependence and maximizing carrying capacity. Metabolic theory successfully predicted most of these adaptations, but we also find important departures from theory. Longer-term evolution (70 generations) led to Pareto improvements in both population growth rate and carrying capacity, suggesting that classic r-K trade-offs observed among species can be evaded within species. The evasion of this trade-off appeared to arise due to the rapid evolution of enhanced metabolic plasticity: lineages exposed to competition evolved more labile metabolisms that tracked resource availability more effectively than lineages that were competition-free. We predict that rapid evolution in both size and metabolism may be a ubiquitous feature of adaptation to changing resource regimes that occurviaspecies invasions and environmental change.
Differential reduction of neuropathic pain symptoms by mGlu4-mediated neuromodulation of amygdala circuits
Authors: Pereira Vanessa , Arias Juri Aparicio , Llebaria Amadeu , Goudet Cyril
Published: October 2022

Neuropathic pain is a common health problem, resulting in exacerbated response to noxious and non noxious stimuli, as well as impaired emotional and cognitive responses. Unfortunately, neuropathic pain is also one of the most difficult pain syndromes to manage, highlighting the importance of better understanding of the brain regions and neuromodulatory mechanisms involved in its regulation. Among the many interconnected brain areas which process pain, the amygdala is known to play an important role in the integration of sensory and emotional pain signals. Here, we questioned the ability of a recently identified neuromodulatory mechanisms associated to the metabotropic glutamate receptors mGlu4in the amygdala to modulate neuropathic pain. In a murine model of peripheral mononeuropathy induced by a chronic constriction of the sciatic nerve, we demonstrate that pharmacological activation of amygdala mGlu4receptors efficiently alleviates sensory and depressive-like symptoms in both male and female mice. Moreover, we reveal a differential modulation of those symptoms, activating mGlu4receptors in the controlateral amygdala, relatively to the side of the mononeuropathy, is necessary and sufficient to relieve both sensory and depressive-like symptoms while ipsilateral activation solely reduces depressive-like symptoms. Furthermore, using photopharmacology, a recent strategy allowing a precise spatiotemporal photocontrol of deep brain endogenous targets, we further demonstrate the rapid and reversible action of mGlu4-mediated neuromodulation on neuropathic pain symptoms. Finally, coupling photopharmacology and analgesic conditioned place preference, we show an important pain-reducing effect of mGlu4 activation. Taken together, these data highlight the analgesic potential of enhancing amygdala mGlu4activity to counteract neuropathy in the hope of improving existing treatments.
Assisting walking balance using a bio-inspired exoskeleton controller
Authors: Afschrift M. , Van Asseldonk E. , Van Mierlo M. , Bayon C. , Keemink A. , van der Kooij H. , De Groote F.
Published: October 2022

Balance control is important for mobility, yet exoskeleton research has mainly focused on improving metabolic energy efficiency. Here we present a biomimetic exoskeleton controller that supports walking balance and reduces muscle activity. Humans restore balance after a perturbation by adjusting activity of the muscles actuating the ankle in proportion to deviations from steady-state center of mass kinematics. We designed a controller that mimics the neural control of steady-state walking and the balance recovery responses to perturbations. This controller uses both feedback from ankle kinematics in accordance with an existing model and feedback from the center of mass velocity. Control parameters were estimated by fitting the experimental relation between kinematics and ankle moments observed in humans that were walking while being perturbed by push and pull perturbations. This identified model was implemented on a bilateral ankle exoskeleton. The exoskeleton provided 30% of the estimated ankle moment during steady-state and perturbed walking. Across twelve subjects, exoskeleton support reduced calf muscle activity in steady-state walking by 19 % with respect to a minimal impedance controller. Proportional feedback of the center of mass velocity improved balance support after perturbation. Muscle activity is reduced in response to push and pull perturbations by 10 and 16 % and center of mass deviations by 9 and 18% with respect to the same controller without center of mass feedback. Our control approach implemented on bilateral ankle exoskeletons can thus effectively support steady-state walking and balance control and therefore has the potential to improve mobility in balance-impaired individuals.
Tumor infiltrating iNKT cells sustain neutrophil pro-tumorigenic functions influencing disease progression in human colorectal cancer
Authors: Lattanzi Georgia , Strati Francesco , Díaz-Basabe Angélica , Perillo Federica , Amoroso Chiara , Protti Giulia , Giuffrè Maria Rita , Baldari Ludovica , Cassinotti Elisa , Ghidini Michele , Galassi Barbara , Lopez Gianluca , Noviello Daniele , Porretti Laura , Trombetta Elena , Mazzarella Luca , Iezzi Giandomenica , Nicassio Francesco , Granucci Francesca , Caprioli Flavio , Facciotti Federica
Published: October 2022

iNKT cells account for a relevant fraction of effector T-cells in the intestine. Although iNKT cells are cytotoxic lymphocytes, their role in colorectal cancer (CRC) remains controversial. From the analysis of colonic LPMCs of human and murine CRC specimens we report that tumor-infiltrating iNKT cells are characterized by an IL17/GM-CSF pro-tumorigenic phenotype, while maintaining cytotoxic properties in the adjacent non-tumoral tissue. Exposure of iNKT cells to the tumor-associated pathobiontFusobacterium nucleatumblunted their cytotoxic capability and enhanced iNKT cell-mediated neutrophils chemotaxis, which upregulated PMN-MDSC gene signatures and functions. Importantly,in vivostimulation of iNKT cells with αGalCer restored their anti-tumorigenic functions. Survival analyses demonstrated that human CRC co-infiltration by iNKT cells and tumor-associated neutrophils correlates with negative outcomes.

Our results reveal a functional plasticity of human intestinal iNKT cells with pro- and anti-tumorigenic activities in CRC, suggesting an iNKT pivotal role in shaping the cancer developmental trajectory.