bluuebunny/crossref_metadata_2025 huggingface dataset:
No broad decline of breeding monarch butterflies in North America: implications for conservation efforts
Authors: Davis Andrew K. , Crossley Michael S. , Moran Matthew D. , Glassberg Jeffrey , Snyder William E.
Published: August 2021

Many insects are in clear decline, with monarch butterflies (Danaus plexippus) drawing particular attention as a flagship species. Falling numbers of overwintering monarchs are well documented, but there has been debate regarding population trends of summer breeding populations. Here, we compile a series of long-term monarch monitoring datasets, some which are analyzed here for the first time, that reveal highly variable responses across the migratory geographic range, but no broad net decline in numbers of breeding monarchs. We also did not find evidence that sampling biased towards natural sites was masking declines at disturbed sites. Overall, our results suggest a robust resiliency in summer populations that thus far has allowed recovery from losses during the winter. Thus, monarchs may not require as much breeding habitat restoration as once thought, and focus should be on conserving the fall and spring migration.
Natural killer cell division regulates FcεRIγ expression downstream of mTOR activity
Authors: Shemesh Avishai , Calabrese Daniel R. , Arakawa-Hoyt Janice , Greenland John R. , Lanier Lewis L.
Published: August 2021

The expansion of human FcεRIγ-/low(FcRγ-/low) natural killer (NK) cells accrues during viral infections; however, the molecular mechanisms regulating FcRγ expression is not well defined and can have implication for host protection and NK cell immunotherapy. Our analysis of NK cell subsets in lung transplant patients during rapamycin treatment revealed significantly lower FcRγ levels in the NK cell population. Moreover, lower FcRγ levels in healthy donors were associated with low mTORC1/C2 activity and low T-bet expression. Cell division suppression by rapamycin or TGFβ suppressed FcRγ upregulation during IL-2 receptor stimulation, whereas promoting NK cell division by co-inhibiting FOXO1 activity restored FcRγ upregulation. These results suggest that the human FcRγ-/lowNK cell phenotype is associated with cell division suppression and reduced mTOR activity.
A new approach to integrate phylogenetic structure and partner availability to study biotic specialization in ecological networks
Authors: Pardo-De la Hoz Carlos J. , Medeiros Ian D. , Gibert Jean P. , Chagnon Pierre-Luc , Magain Nicolas , Miadlikowska Jolanta , Lutzoni François
Published: August 2021

Biotic specialization holds information about the assembly, evolution and stability of biological communities. Phylogenetic diversity metrics have been used to quantify biotic specialization, but their current implementations do not adequately account for the availability of the interacting partners. Also, the overdispersed pattern of phylogenetic specialization has been misinterpreted as an attribute of generalists. We developed an approach that resolves these issues by accounting for partner availability to quantify the phylogenetic structure of specialization (i.e., clustered, overdispersed, or random) in ecological networks. We showed that our approach avoids biases of previous methods. We also implemented it on empirical networks of host–parasite, avian seed-dispersal, lichenized fungi– cyanobacteria and coral–dinoflagellate interactions. We found a large proportion of taxa that interact with phylogenetically random partners, in some cases to a larger extent than detected with an existing method that does not account for partner availability. We also found many taxa that interact with phylogenetically clustered partners, while taxa with overdispersed partners were rare. Our results highlight the important role of randomness in shaping interaction networks, even in highly intimate symbioses, and provide a much-needed quantitative framework to assess the role that evolutionary history and symbiotic specialization play in shaping patterns of biodiversity.
Mites alight! Sunflower crop area and pollen supplementation enhance honey bee resistance to Varroa destructor
Authors: Palmer-Young Evan C , Malfi Rosemary , Zhou Yujun , Joyce Bryanna , Whitehead Hannah , Van Wyk Jennifer I , Baylis Kathy , Grubbs Kyle , Lopez Dawn , Evans Jay D , Irwin Rebecca E , Adler Lynn S
Published: August 2021

Anthropogenic landscape changes can affect parasite epidemiology in wild and agricultural animals. Honey bees are agricultural animals whose services are threatened by loss of floral resources and by parasites, most notably the invasive mite Varroa destructor. Existing mite control strategies rely heavily on chemical treatments that can adversely affect bees. Alternative, pesticide-free control methods are urgently needed to maintain effective pollination services. Many flowering plants provide nectar and pollen that enhance resistance to parasites in animals. Enrichment of landscapes with antiparasitic floral resources could therefore provide a sustainable means of parasite control in pollinators.

Floral rewards of Asteraceae plants have been shown to reduce parasitic infection in diverse bee species, including honey and bumble bees. Here, we tested the effects of sunflower (Helianthus annuus) cropland and pollen supplementation on honey bee resistance to macro- and microparasites. Our results show that each doubling of sunflower crop area is associated with a 28% reduction in mite infestation intensity. Late-summer supplementation of colonies with sunflower pollen reduced mite infestation by 2.75-fold relative to an artificial pollen. Our findings suggest the potential for sunflower plantings or pollen supplements to counteract a main driver of honey bee losses worldwide.
Near-Zero Phase-Lag Hyperscanning in a Novel Wireless EEG System
Authors: Chuang Chun-Hsiang , Lu Shao-Wei , Chao Yi-Ping , Peng Po-Hsun , Hsu Hao-Che , Jung Tzyy-Ping
Published: August 2021

Hyperscanning is an emerging technology that concurrently scans the neural dynamics of multiple individuals to study interpersonal interactions. In particular, hyperscanning with wireless electroencephalography (EEG) is increasingly popular owing to its mobility and ability to decipher social interactions in natural settings at the millisecond scale. To align multiple EEG time series with sophisticated event markers in a single time domain, a precise and unified timestamp is required for stream synchronization. This study proposed a clock-synchronized method using a custom-made RJ45 cable to coordinate the sampling between wireless EEG amplifiers to prevent incorrect estimation of interbrain connectivity due to asynchronous sampling. In this method, analog-to-digital converters are driven by the same sampling clock. Additionally, two clock-synchronized amplifiers leverage additional RF channels to keep the counter of their receiving dongles updated, guaranteeing that binding event markers received by the dongle with the EEG time series have the correct timestamp. The results of two simulation experiments and one video gaming experiment revealed that the proposed method ensures synchronous sampling in a system with multiple EEG devices, achieving near-zero phase-lag and negligible amplitude difference between signals. According to all of the signal-similarity metrics, the suggested method is a promising option for wireless EEG hyperscanning and can be utilized to precisely assess the interbrain couplings underlying social-interaction behaviors.
Assembling an illustrated family-level tree of life for exploration in mobile devices
Authors: Del Risco Andrés A. , Chacón Diego A. , Ángel Lucia , García David A.
Published: August 2021

Since the concept of the tree of life was introduced by Darwin about a century and a half ago, a considerable fraction of the scientific community has focused its efforts on its reconstruction, with remarkable progress during the last two decades with the advent of DNA sequences. However, the assemblage of a comprehensive tree of life for its exploration has been a difficult task to achieve due to two main obstacles: i) information is scattered into a plethora of individual sources and ii) practical visualization tools for exceptionally large trees are lacking. To overcome both challenges, we aimed to synthetize a family-level tree of life by compiling over 1400 published phylogenetic studies, ensuring that the source trees represent the best phylogenetic hypotheses to date based on a set of objective criteria. Moreover, we dated the synthetic tree by employing over 550 secondary-calibration points, using publicly available sequences for more than 5000 taxa, and by incorporating age ranges from the fossil record for over 2800 taxa. Additionally, we developed a mobile app (Tree of Life) for smartphones in order to facilitate the visualization and interactive exploration of the resulting tree. Interactive features include an easy exploration by zooming and panning gestures of touch screens, collapsing branches, visualizing specific clades as subtrees, a search engine, a timescale to determine extinction and divergence dates, and quick links to Wikipedia. Small illustrations of organisms are displayed at the tips of the branches, to better visualize the morphological diversity of life on earth. Our assembled Tree of Life currently includes over 7000 taxonomic families (about half of the total family-level diversity) and its content will be gradually expanded through regular updates to cover all life on earth at family-level.
Evaluating the efficacy of a consumer-centric method for ecological sampling: Using bonobo (Pan paniscus) feeding patterns as an instrument for tropical forest characterization
Authors: Wessling Erin G. , Samuni Liran , Mundry Roger , Pascual Miguel Adan , Lucchesi Stefano , Kambale Bienfait , Surbeck Martin
Published: August 2021

Characteristics of food availability and distribution are a key component of a species ecology. Objective measurement of food resources, such as vegetation plot sampling, do not consider aspects of selection by the consumer and therefore may produce imprecise measures of availability. Further, in most animal ecology research, traditional ecological surveying often is time-intensive and supplementary to ongoing behavioral observation. We propose a method to integrate ecological sampling of an animal’s environment into existing behavioral data collection systems by using the consumer as the surveyor. Here, we introduce the consumer-centric method (CCM) of assessing resource availability for its ability to measure food resource abundance, distribution, and dispersion. This method catalogues feeding locations observed during behavioral observation and uses aggregated data to characterize these ecological metrics.

We evaluated the CCM relative to traditional vegetation plot surveying using accumulated feeding locations across three years visited by a tropical frugivore, the bonobo (Pan paniscus), and compared it with data derived from over 200 vegetation plots across their 50km2+ home range.

We demonstrate that food species abundance estimates derived from the CCM are comparable to those derived from traditional vegetation plot sampling after approximately 600 observation days or 60 spatially explicit feeding locations. The agreement between the methods further improved when accounting for aspects of consumer selectivity in objective vegetation plot sampling (e.g., size minima). Estimates of density from CCM correlated with plot-derived estimates and were relatively insensitive to home range inclusion and other species characteristics, but were sensitive to sampling frequency (e.g., consumption frequency). Agreement between the methods in relative distribution of resources performed better across species than expected by chance, although measures of dispersion correlated poorly.

We demonstrate that while providing a robust measure to quantify local food availability, the CCM has an advantage over traditional sampling methods as it incorporates sampling biases relevant to the consumer. Therefore, as this method can be incorporated into existing observational data collection and does not require additional ecological surveying, it serves as a promising method for behavioral ecological data collection for animal species who re-use space and consume immobile food items.
A spatio-temporal model to reveal oscillator phenotypes in molecular clocks: Parameter estimation elucidates circadian gene transcription dynamics in single-cells
Authors: Unosson Måns , Brancaccio Marco , Hastings Michael , Johansen Adam M. , Finkenstädt Bärbel
Published: August 2021

We propose a stochastic distributed delay model together with a Markov random field prior and a measurement model for bioluminescence-reporting to analyse spatiotemporal gene expression in intact networks of cells. The model describes the oscillating time evolution of molecular mRNA counts through a negative transcriptional-translational feedback loop encoded in a chemical Langevin equation with a probabilistic delay distribution. The model is extended spatially by means of a multiplicative random effects model with a first order Markov random field prior distribution. Our methodology effectively separates intrinsic molecular noise, measurement noise, and extrinsic noise and phenotypic variation driving cell heterogeneity, while being amenable to parameter identification and inference. Based on the single-cell model we propose a novel computational stability analysis that allows us to infer two key characteristics, namely the robustness of the oscillations, i.e. whether the reaction network exhibits sustained or damped oscillations, and the profile of the regulation, i.e. whether the inhibition occurs over time in a more distributed versus a more direct manner, which affects the cells’ ability to phase-shift to new schedules. We show how insight into the spatio-temporal characteristics of the circadian feedback loop in the suprachiasmatic nucleus (SCN) can be gained by applying the methodology to bioluminescence-reported expression of the circadian core clock geneCry1across mouse SCN tissue. We find that while (almost) all SCN neurons exhibit robust cell-autonomous oscillations, the parameters that are associated with the regulatory transcription profile give rise to a spatial division of the tissue between the central region whose oscillations are resilient to perturbation in the sense that they maintain a high degree of synchronicity, and the dorsal region which appears to phase shift in a more diversified way as a response to large perturbations and thus could be more amenable to entrainment.
Canine oral melanoma genomic and transcriptomic study defines two molecular subgroups with different therapeutical targets
Authors: Prouteau Anais , Mottier Stephanie , Primot Aline , Cadieu Edouard , Bachelot Laura , Botherel Nadine , Cabillic Florian , Houel Armel , Cornevin Laurence , Kergal Camille , Corre Sebastien , Abadie Jerome , Hitte Christophe , Gilot David , Lindblad-Toh Kerstin , Andre Catherine , Derrien Thomas , Hedan Benoit
Published: August 2021

Mucosal melanoma (MM) is a rare and aggressive clinical cancer that occurs mostly in the head, neck, and anogenital regions. Despite recent advances in genetics and the development of revolutionary treatments, such as immunotherapy, the prognosis for MM remains poor. Canine MM shares several clinical, histological, and genetic features with its human counterpart, offering a relevant spontaneous and immunocompetent model to decipher the genetic bases and explore treatment options for human MM. We performed an integrative genomic and transcriptomic analysis of 32 canine MM samples, which allowed us to identify two molecular subgroups differing in microenvironment and structural variant (SV) content. The overexpression of genes related to the microenvironment and T-cell response was associated with tumors harboring a lower content of structural variants, whereas the overexpression of pigmentation-related pathways and oncogenes such as TERT were associated with a high SV burden. To detail the SVs, especially those with focal amplifications, whole-genome sequencing was performed on four canine MM cell lines. We showed that focal amplifications characterized complex chromosomal rearrangements targeting oncogenes such as MDM2 or CDK4 and a recurrently amplified region on canine chromosome 30, comprising the genes TRPM7, GABPB1, USP8, and SPPL2A, were candidate oncogenes for MM. We showed that the copy numbers of these genes were significantly correlated with their expression levels. Finally, we demonstrated that the genes TRPM7, GABPB1, and SPPL2A play a role in cell proliferation; thus, these may be considered new candidate oncogenes for human MM. Our findings suggest the existence of two MM molecular subgroups that may benefit from dedicated therapies, such as immune checkpoint inhibitors or targeted therapies. These results illustrate the relevance of dog models for deciphering genetic mechanisms in spontaneous MM, along with the potential to screen for efficient targeted therapies for rare and aggressive cancers in humans.
RPnet: A Reverse Projection Based Neural Network for Coarse-graining Metastable Conformational States for Protein Dynamics
Authors: Gu Hanlin , Wang Wei , Cao Siqin , Unarta Ilona Christy , Yao Yuan , Sheong Fu Kit , Huang Xuhui
Published: August 2021

Markov State Model (MSM) is a powerful tool for modeling the long timescale dynamics based on numerous short molecular dynamics (MD) simulation trajectories, which makes it a useful tool for elucidating the conformational changes of biological macromolecules. By partitioning the phase space into discretized states and estimate the probabilities of inter-state transitions based on short MD trajectories, one can construct a kinetic network model that could be used to extrapolate long time kinetics if the Markovian condition is met. However, meeting the Markovian condition often requires hundreds or even thousands of states (microstates), which greatly hinders the comprehension of conformational dynamics of complex biomolecules. Kinetic lumping algorithms can coarse grain numerous microstates into a handful of metastable states (macrostates), which would greatly facilitate the elucidation of biological mechanisms. In this work, we have developed a reverse projection based neural network (RPnet) method to lump microstates into macrostates, by making use of a physics-based loss function based on the projection operator framework of conformational dynamics. By recognizing that microstate and macrostate transition modes can be related through a projection process, we have developed a reverse projection scheme to directly compare the microstate and macrostate dynamics. Based on this reverse projection scheme, we designed a loss function that allows effectively assess the quality of a given kinetic lumping. We then make use of a neural network to efficiently minimize this loss function to obtain an optimized set of macrostates. We have demonstrated the power of our RPnet in analyzing the dynamics of a numerical 2D potential, alanine dipeptide, and the clamp opening of an RNA polymerase. In all these systems, we have illustrated that our method could yield comparable or better results than competing methods in terms of state partitioning and reproduction of slow dynamics. We expect that our RPnet holds promise in analyzing conformational dynamics of biological macromolecules.
The Arabidopsis HOP2 Gene Has a Role in Preventing illegitimate Exchanges between Nonhomologous Chromosomes
Authors: Farahani-Tafreshi Yisell , Wei Chun , Gan Peilu , Daradur Jenya , Riggs C. Daniel , Hasenkampf Clare A.
Published: August 2021

Meiotic homologous chromosomes pair up and undergo crossing over. In many eukaryotes both intimate pairing and crossing over require the induction of double stranded breaks (DSBs) and subsequent repair via Homologous Recombination (HR). In these organisms, two key proteins are the recombinases RAD51 and DMC1. Recombinase-modulators HOP2 and MND1 have been identified as proteins that assist RAD51 and DMC1 and are needed to promote stabilized pairing. We have probed the nature of the genetic lesions seen in hop2 mutants and looked at the role of HOP2 in the fidelity of genetic exchanges. Using γH2Ax as a marker for unrepaired DSBs we found that hop2-1 and mnd1 mutants have different appearance/disappearance for DSBs than wild type, but all DSBs are repaired by mid-late pachytene. Therefore, the bridges and fragments seen from metaphase I onward are due to mis-repaired DSBs, not unrepaired ones. Studying Arabidopsis haploid meiocytes we found that wild type haploids produced the expected five univalents, but hop2-1 haploids suffered many illegitimate exchanges that were stable enough to produce bridged chromosomes during segregation. Our results suggest that HOP2 has a significant active role in preventing nonhomologous associations. We also found evidence that HOP2 plays a role in preventing illegitimate exchanges during repair of radiation-induced DSBs in rapidly dividing petal cells. Thus, HOP2 plays both a positive role in promoting homologous chromosome synapsis and a separable role in preventing nonhomologous chromosome exchanges. Possible mechanisms for this second important role are discussed.

SIGNIFICANCE STATEMENT

The fidelity of Homologous Recombination (HR) during meiosis is essential to the production of viable gametes and for maintaining genome integrity in vegetative cells. HOP2 is an important protein for accurate meiotic HR in plants. We find high levels of illegitimate repairs between nonhomologous chromosomes during meiosis and in irradiated petal cells in HOP2 mutants. We consider mechanisms of how this second role might be accomplished.
The ethanol tolerance in Saccharomyces cerevisiae under a phenomics perspective
Authors: Wolf Ivan Rodrigo , Marques Lucas Farinazzo , de Almeida Lauana Fogaça , Lázari Lucas Cardoso , de Moraes Leonardo Nazário , Cardoso Luiz Henrique , de Oliveira Alves Camila Cristina , Nakajima Rafael Takahiro , Schnepper Amanda Piveta , de Assis Golim Marjorie , Cataldi Thais Regiani , Nijland Jeroen G. , Pinto Camila Moreira , Fioretto Matheus Naia , Almeida Rodrigo Oliveira , Driessen Arnold J. M. , Simōes Rafael Plana , Labate Mônica Veneziano , Grotto Rejane Maria Tommasini , Labate Carlos Alberto , Junior Ary Fernandes , Justulin Luís Antonio , Coan Rafael Luiz Buogo , Ramos Érica , Furtado Fabiana Barcelos , Martins Cesar , Valente Guilherme Targino
Published: August 2021

Ethanol (EtOH) is a substantial stressor for Saccharomyces cerevisiae. Data integration from strains with different phenotypes, including EtOH stress-responsive lncRNAs, are still not available. We covered these issues seeking systems modifications that drive the divergences between higher (HT) and lower (LT) EtOH tolerant strains under their highest stress conditions. We showed that these phenotypes are neither related to high viability nor faster population rebound after stress relief. LncRNAs work on many stress-responsive systems in a strain-specific manner promoting the EtOH tolerance. Cells use membraneless RNA/protein storage and degradation systems to endure the stress harming, and lncRNAs jointly promote EtOH tolerance. CTA1 and longevity are primer systems promoting phenotype-specific gene expression. The lower cell viability and growth under stress is a byproduct of sphingolipids and inositol phosphorylceramide dampening, acerbated in HTs by sphinganine, ERG9, and squalene overloads; LTs diminish this harm by accumulating inositol 1-phosphate. The diauxic shift drives an EtOH buffering by promoting an energy burst under stress, mainly in HTs. Analysis of mutants showed genes and lncRNAs in three strains critical for their EtOH tolerance. Finally, longevity, peroxisome, energy and lipid metabolisms, RNA/protein degradation and storage systems are the main pathways driving the EtOH tolerance phenotypes.
The genetic etiology of longitudinal measures of predicted brain ageing in a population-based sample of mid to late-age males
Authors: Gillespie Nathan A , Hatton Sean N , Hagler Donald H , Dale Anders M , Elman Jeremy A , McEvoy Linda K , Elyer Lisa T , Fennema-Notestine Christine , Logue Mark W , McKenzie Ruth E , Puckett Olivia K , Tu Xin M , Whitsel Nathan , Xian Hong , Reynolds Chandra A , Panizzon Matthew S , Lyons Michael J , Neale Michael C , Kremen William S , Franz Carol
Published: August 2021

Despite their increasing application, the genetic and environmental etiology of global predicted brain ageing (PBA) indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 52 to 72 years. Biometrical genetic analyses revealed significant and highly correlated estimates of additive genetic heritability ranging from 59% to 75%. Multivariate longitudinal modelling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences.
The lesser Pacific striped octopus, Octopus chierchiae: an emerging laboratory model for the study of octopuses
Authors: Grearson Anik G. , Dugan Alison , Sakmar Taylor , Dölen Gül , Gire David H. , Sivitilli Dominic M. , Niell Cristopher M. , Caldwell Roy L. , Wang Z. Yan , Grasse Bret
Published: August 2021

Cephalopods have the potential to become useful experimental models in various fields of science, particularly in neuroscience, physiology, and behavior. Their complex nervous systems, intricate color- and texture-changing body patterns, and problem-solving abilities have attracted the attention of the biological research community, while the high growth rates and short life cycles of some species render them suitable for laboratory culture. Octopus chierchiae is a small octopus native to the central Pacific coast of North America whose predictable reproduction, short time to maturity, small adult size, and ability to lay multiple egg clutches (iteroparity) make this species ideally suited to laboratory culture. Here we describe novel methods for culture of O. chierchiae, with emphasis on enclosure designs, feeding regimes, and breeding management. Our results demonstrate the feasibility of multigenerational culture of O. chierchiae. Specifically, O. chierchiae bred in the laboratory grows from a 3.5-millimeter mantle length at hatching to an adult mantle length of approximately 20-30 millimeters in 250-300 days, with 14-15% survivorship to over 400 days of age in first and second generations. O. chierchiae sexually matures at around an estimated six months of age and, unlike most octopus species, can lay multiple clutches of eggs, approximately every 30-90 days. Eggs are large and hatchlings emerge as direct developing octopuses. Based on these results, we propose that O. chierchiae possesses both the practical and biological features needed for a model octopus that can be cultured repeatedly to address a wide range of fundamental biological questions.
Mucin-mimetic action of capsaicin improves high fat diet-induced gut barrier dysfunction in mice colon
Authors: Kumar Vijay , Kumar Vibhu , Mahajan Neha , Kaur Jasleen , Devi Kirti , Dharavath Ravinder Naik , Singh Ravindra Pal , Kondepudi Kanthi Kiran , Bishnoi Mahendra
Published: August 2021

The gut barrier – including tight junction proteins and mucus layers, is the first line of defense against physical, chemical, or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While its mode of action is well established to enhance energy expenditure, metabolism and prevent dysbiosis, the more local effects on the host gut – particularly the gut barrier and mucus system remain elusive.

We employed a diet-induced obesity model to investigate the effect of capsaicin on the gut barrier and mucus production and to understand the involvement of mucus, bacteria, and TRPV1 in these phenomena. Mucin feeding reflected most of the effects produced by capsaicin, indicating that mucus modulation by capsaicin plays a crucial role in its anti-obesity effects. Capsaicin, bacteria and the host mucus system seem to act in a cyclic cascade involving TRPV1, which can be activated by capsaicin and various bacteria. These findings provide new insight into the role of TRPV1 in maintaining a healthy gut environment.

HIGHLIGHTS

Exogenous mucin feeding produced anti-obesity effects similar to capsaicin in mice.

Mucin and capsaicin improved TJP expression, intestinal permeability and gut microbial diversity.

Capsaicin modulated bacterial diversity in vitro, independently of the host.

Probiotic bacteria and butyrate activated TRPV1 in transfected HEK cells.

Anti-obesity action of capsaicin is not exclusive to TRPV1 agonism.

Capsaicin’s action as colonic mucus secretagogue – plays a crucial part in its anti-obesity benefits.
Functional multi-omics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma
Authors: Choudhry Priya , Kasap Corynn , Patiño-Escobar Bonell , Gugliemini Olivia , Geng Huimin , Sarin Vishesh , Kang Amrik , Kishishita Audrey , Rampersaud Sham , Sarah Letitia , Lin Yu-Hsiu T. , Paranjape Neha , Ramkumar Poornima , Patton Jonathan C. , Marcoulis Makeba , Wang Donghui , Phojanakong Paul , Steri Veronica , Hann Byron , Barwick Benjamin G. , Kampmann Martin , Wiita Arun P.
Published: August 2021

CD38 is a surface ectoenzyme expressed at high levels on myeloma plasma cells and is the target for the monoclonal antibodies (mAbs) daratumumab and isatuximab. Pre-treatment CD38 density on tumor cells is an important determinant of mAb efficacy. Several small molecules have been found to increase tumor surface CD38, with the goal of boosting mAb efficacy in a co-treatment strategy. Numerous other CD38-targeting therapeutics are currently in preclinical or clinical development. Here we sought to extend our currently limited insight into CD38 surface expression by using a multi-omics approach. Genome-wide CRISPR-interference screens integrated with patient-centered epigenetic analysis confirmed known regulators of CD38, such as RARA, while revealing XBP1 and SPI1 as other key transcription factors governing surface CD38 levels. CD38 knockdown followed by cell surface proteomics demonstrated no significant remodeling of the myeloma “surfaceome” after genetically-induced loss of this antigen. Integrated transcriptome and surface proteome data confirmed high specificity of all-trans retinoic acid in upregulating CD38 in contrast to broader effects of azacytidine and panobinostat. Finally, unbiased phosphoproteomics identified inhibition of MAP kinase pathway signaling in tumor cells after daratumumab treatment. Our work provides a resource to design strategies to enhance efficacy of CD38-targeting immunotherapies in myeloma.
Protist.guru: a comparative transcriptomics database for the protist kingdom
Authors: Villanueva Erielle Marie Fajardo , Lim Peng Ken , Lim Jolyn Jia Jia , Lim Shan Chun , Lau Pei Yi , Koh Kenny Ting Sween , Tan Emmanuel , Kairon Ryanjit Singh , See Wei An , Liao Jian Xiang , Hee Ker Min , Vijay Varsheni , Maitra Ishani , Boon Chong Jun , Fo Kevin , Wang Yee Tat , Jaya Ryan , Hew Li Anne , Lim Yong Yee , Lee Wei Quan , Lee Zhi Qi , Foo Herman , Lopes dos Santos Adriana , Mutwil Marek
Published: August 2021

During the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still neglected. To address this gap, we used gene expression data from 15 distinct protist species to create protist.guru: an online database equipped with tools for identifying functional co-expression networks, gene families, and enriched gene clusters. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes.

Availability

The database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.
NO-stressed Y. pseudotuberculosis have decreased cell division rates in the mouse spleen
Authors: Liu Bessie , Braza Rezia Era D. , Cotten Katherine L. , Davidson Robert K. , Davis Kimberly M.
Published: August 2021

Fluorescence dilution approaches can detect bacterial cell division events, and can detect if there are differential rates of cell division across individual cells within a population. This approach typically involves inducing expression of a fluorescent protein, and then tracking partitioning of fluorescence into daughter cells. However, fluorescence can be diluted very quickly within a rapidly replicating population, such as pathogenic bacterial populations replicating within host tissues. To overcome this limitation, we have generated two revTetR reporter constructs, where either mCherry or yellow fluorescent protein (YFP) is constitutively expressed, and repressed by addition of tetracyclines, resulting in fluorescence dilution within defined timeframes. We show that fluorescent signals are diluted in replicating populations, and that signal accumulates in growth-inhibited populations, including during nitric oxide exposure. Furthermore, we show that tetracyclines can be delivered to the mouse spleen during Yersinia pseudotuberculosis infection, and defined a drug concentration that results in even exposure of cells to tetracyclines. We then used this system to visualize bacterial cell division within defined timeframes post-inoculation. We detected growth attenuation of the revTetR-mCherry strains within mouse tissues, however data suggested heightened NO exposure correlated with heightened mCherry signal. We were able to restore normal bacterial growth with revTetR-YFP, and use this strain to show that heightened NO exposure correlated with heightened YFP signal, indicating decreased cell division rates within this subpopulation in vivo. This revTetR reporter will provide a critical tool for future studies to identify and isolate slowly replicating bacterial subpopulations from host tissues.
Evidence for a ‘trap-and-flip’ mechanism in a proton-dependent lipid transporter
Authors: Lambert Elisabeth , Mehdipour Ahmad Reza , Schmidt Alexander , Hummer Gerhard , Perez Camilo
Published: August 2021

Transport of lipids across membranes is fundamental for diverse biological pathways in cells. Multiple ion-coupled transporters participate in lipid translocation, but their mechanisms remain largely unknown. Major facilitator superfamily (MFS) lipid transporters play central roles in cell wall synthesis, brain development and function, lipids recycling, and cell signaling. Recent structures of MFS lipid transporters revealed overlapping architectural features pointing towards a common mechanism. Here we used cysteine disulfide trapping, molecular dynamics simulations, mutagenesis analysis, and transport assays in vitro and in vivo, to investigate the mechanism of LtaA, a proton-dependent MFS lipid transporter essential for lipoteichoic acids synthesis in the pathogen Staphylococcus aureus. We reveal that LtaA displays asymmetric lateral openings with distinct functional relevance and that cycling through outward- and inward-facing conformations is essential for transport activity. We demonstrate that while the entire amphipathic central cavity of LtaA contributes to lipid binding, its hydrophilic pocket dictates substrate specificity. We propose that LtaA catalyzes lipid translocation by a ‘trap-and-flip’ mechanism that might be shared among MFS lipid transporters.
Optical nanoscopy reveals SARS-CoV-2-induced remodeling of human airway cells
Authors: Nijenhuis Wilco , Damstra Hugo G.J. , van Grinsven Emma J. , Iwanski Malina K. , Praest Patrique , Soltani Zahra E. , van Grinsven Mariëlle M.P. , Brunsveld Jesse E. , de Kort Theun , Rodenburg Lisa W. , de Jong Dorien C.M. , Raeven Henriette H.M. , Spelier Sacha , Amatngalim Gimano D. , Akhmanova Anna , Nijhuis Monique , Lebbink Robert Jan , Beekman Jeffrey M. , Kapitein Lukas C.
Published: August 2021

A better understanding of host cell remodeling by the coronavirus SARS-CoV-2 is urgently needed to understand viral pathogenesis and guide drug development. Expression profiling and electron microscopy have frequently been used to study virus-host interactions, but these techniques do not readily enable spatial, sub-cellular and molecular analysis of specific cellular compartments. Here, we use diffraction-unlimited fluorescence microscopy to analyze how SARS-CoV-2 infection exploits and repurposes the subcellular architecture of primary human airway cells. Using STED nanoscopy, we detect viral entry factors along the motile cilia of ciliated cells and visualize key aspects of the viral life cycle. Using Tenfold Robust Expansion (TREx) microscopy, we analyze the extensively remodeled three-dimensional ultrastructure of SARS-CoV-2-infected ciliated cells and uncover Golgi fragmentation, emergence of large and atypical multivesicular bodies enclosing viral proteins, ciliary clustering, and remodeling of the apical surface. These results demonstrate a broadly applicable strategy to study how viruses reorganize host cells with spatial and molecular specificity and provide new insights into SARS-CoV-2 infection in primary human cell models.
A TIR-1/SARM1 phase transition underlies p38 immune pathway activation in theC. elegansintestine
Authors: Peterson Nicholas D. , Icso Janneke D. , Salisbury J. Elizabeth , Rodríguez Tomás , Thompson Paul R. , Pukkila-Worley Read
Published: August 2021

Intracellular signaling regulators can be concentrated into membrane-free, higher-ordered protein assemblies to initiate protective responses during stress — a process known as phase transition. Here, we show that a phase transition of theCaenorhabditis elegansToll/interleukin-1 receptor domain protein (TIR-1), an NAD+glycohydrolase homologous to mammalian sterile alpha and TIR motif-containing 1 (SARM1), underlies p38 PMK-1 immune pathway activation inC. elegansintestinal epithelial cells. Through visualization of fluorescently labeled TIR-1/SARM1 protein, we demonstrate for the first time that physiologic stresses, both pathogen and non-pathogen, induce multimerization of TIR-1/SARM1 into visible puncta within intestinal epithelial cells.In vitroenzyme kinetic analyses revealed that, like mammalian SARM1, the NAD+glycohydrolase activity ofC. elegansTIR-1 is dramatically potentiated by protein oligomerization and a phase transition. Accordingly,C. eleganswith genetic mutations that specifically block either multimerization or the NAD+glycohydrolase activity of TIR-1/SARM1 fail to induce p38 PMK phosphorylation, are unable to increase immune effector expression, and are dramatically susceptible to bacterial infection. Finally, we demonstrate that the TIR-1/SARM1 phase transition is modified by dietary cholesterol, revealing a new adaptive response that allows a metazoan host to anticipate pathogen threats during micronutrient deprivation, a time of relative susceptibility to infection. When cholesterol is limited, TIR-1/SARM1 oligomerizes into puncta in intestinal epithelial cells and engages its NAD+glycohydrolase activity, which increases p38 PMK-1 phosphorylation, and primes immune effector induction in a manner that promotes pathogen clearance from the intestine during a subsequent infection. Thus, a phase transition of TIR-1/SARM1 as a prerequisite for its NAD+glycohydrolase activity is strongly conserved across millions of years of evolution and is essential for diverse physiological processes in multiple cell types.
Balancing conservation priorities for grassland and forest specialist bird communities in agriculturally dominated landscapes
Authors: de Zwaan Devin R. , Alavi Niloofar , Mitchell Greg W. , Lapen David R. , Duffe Jason , Wilson Scott
Published: August 2021

Effective conservation planning often requires difficult decisions when at-risk species inhabit economically valuable landscapes or if the needs of multiple threatened species do not align. In the agriculture-dominated landscape of eastern Ontario and southwestern Quebec, Canada, conflicting habitat requirements exist between threatened grassland birds benefiting from certain agriculture practices and those of a diverse woodland bird community dependent on forest recovery. Using multi-scale species distribution models with Breeding Bird Survey (BBS) data, we assessed habitat suitability for 8 threatened grassland and forest specialists within this region. We also identified landscapes that jointly maximize occurrence of the 8 focal species and diversity of the overall grassland and forest communities. Influential habitat associations differed among species at the territory (200m radius) and landscape level (1km), highlighting the importance of considering multiple spatial scales. Species diversity was maximized when forest or grassland/pasture cover approached 40–50%, indicating a positive response to land cover heterogeneity. We identified species diversity hotspots near Lake Huron, as well as along the shore and southeast of the St. Lawrence River. These areas represent mosaic landscapes, balancing forest patches, wetland, grassland/pasture, and row crops such as corn, soybean, and cereals. Despite drastic landscape changes associated with agroecosystems, we demonstrate that targeted habitat protection and enhancement that prioritizes land cover diversity can maximize protection of bird communities with directly contrasting needs. We highlight multiple pathways to achieve this balance, including forest retention or separating row crops with hedgerows and wooded fence-lines, improving flexibility in conservation approaches.
A Cell Culture Model of BK Polyomavirus Persistence, Genome Recombination, and Reactivation
Authors: Zhao Linbo , Imperiale Michael J.
Published: August 2021

BK Polyomavirus (BKPyV) is a small non-enveloped DNA virus that establishes a ubiquitous, asymptomatic, and lifelong persistent infection in at least 80% of the world’s population. In some immunosuppressed transplant recipients, BKPyV reactivation causes polyomavirus-associated nephropathy and hemorrhagic cystitis. We report a novel in vitro model of BKPyV persistence and reactivation using a BKPyV natural host cell line. In this system, viral genome loads remain constant for various times post-establishment of persistent infection, during which BKPyV undergoes extensive random genome recombination. Certain recombination events result in viral DNA amplification and protein expression, resulting in production of viruses with enhanced replication ability.

Importance

BK polyomavirus (BKPyV) generally establishes a persistent subclinical infection in healthy individuals but can cause severe disease in transplant recipients. While an in vitro model to study acute replication exists, no practical model with which to study BKPyV persistence is currently available. We established a BKPyV persistence model in cell culture. Our model reveals that the virus can persist for varying periods of time before random recombination of the viral genome leads to enhanced replication.
Seipin forms a flexible cage at lipid droplet formation sites
Authors: Arlt Henning , Sui Xuewu , Folger Brayden , Adams Carson , Chen Xiao , Remme Roman , Hamprecht Fred A. , DiMaio Frank , Liao Maofu , Goodman Joel M. , Farese Robert V. , Walther Tobias C.
Published: August 2021

Lipid droplets (LDs) form in the endoplasmic reticulum by phase separation of neutral lipids. This process is facilitated by the seipin protein complex, which consists of a ring of seipin monomers, with yet unclear function. Here, we report a structure of yeast seipin based on cryo-electron microscopy and structural modeling data. Seipin forms a decameric, cage-like structure with the lumenal domains forming a stable ring at the cage floor and transmembrane segments forming the cage sides and top. The transmembrane segments interact with adjacent monomers in two distinct, alternating conformations. These conformations result from changes in switch regions, located between the lumenal domains and the transmembrane segments, that are required for seipin function. Our data suggest a model for LD formation in which a closed seipin cage enables TG phase separation and subsequently switches to an open conformation to allow LD growth and budding.
The challenge of delimiting cryptic species, and a supervised machine learning solution
Authors: Derkarabetian Shahan , Starrett James , Hedin Marshal
Published: August 2021

Abstract

The diversity of biological and ecological characteristics of organisms, and the underlying genetic patterns and processes of speciation, makes the development of universally applicable genetic species delimitation methods challenging. Many approaches, like those incorporating the multispecies coalescent, sometimes delimit populations and overestimate species numbers. This issue is exacerbated in taxa with inherently high population structure due to low dispersal ability, and in cryptic species resulting from nonecological speciation. These taxa present a conundrum when delimiting species: analyses rely heavily, if not entirely, on genetic data which over split species, while other lines of evidence lump. We showcase this conundrum in the harvester Theromaster brunneus, a low dispersal taxon with a wide geographic distribution and high potential for cryptic species. Integrating morphology, mitochondrial, and sub-genomic (double-digest RADSeq and ultraconserved elements) data, we find high discordance across analyses and data types in the number of inferred species, with further evidence that multispecies coalescent approaches over split. We demonstrate the power of a supervised machine learning approach in effectively delimiting cryptic species by creating a “custom” training dataset derived from a well-studied lineage with similar biological characteristics as Theromaster. This novel approach uses known taxa with particular biological characteristics to inform unknown taxa with similar characteristics, and uses modern computational tools ideally suited for species delimitation while also considering the biology and natural history of organisms to make more biologically informed species delimitation decisions. In principle, this approach is universally applicable for species delimitation of any taxon with genetic data, particularly for cryptic species.