bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking habitat and population dynamics to inform conservation benchmarks for data-limited salmon stocks
Authors: Atlas William I. , Holt Carrie A. , Selbie Daniel T. , Connors Brendan M. , Cox-Rogers Steve , Carr-Harris Charmaine , Hertz Eric , Moore Jonathan W.
Published: March 2021

Management of data-limited populations is a key challenge to the sustainability of fisheries around the world. For example, sockeye salmon (Oncorhynchus nerka) spawn and rear in many remote coastal watersheds of British Columbia (BC), Canada, making population assessment a challenge. Estimating conservation and management targets for these populations is particularly relevant given their importance to First Nations and commercial fisheries. Most sockeye salmon have obligate lake-rearing as juveniles, and total abundance is typically limited by production in rearing lakes. Although methods have been developed to estimate population capacity based on nursery lake photosynthetic rate (PR) and lake area or volume, they have not yet been widely incorporated into stock-recruit analyses. We tested the value of combining lake-based capacity estimates with traditional stock-recruit based approaches to assess population status using a hierarchical-Bayesian stock-recruit model for 70 populations across coastal BC. This analysis revealed regional variation in sockeye population productivity (Ricker α), with coastal stocks exhibiting lower mean productivity than those in interior watersheds. Using moderately-informative PR estimates of capacity as priors reduced model uncertainty, with a more than five-fold reduction in credible interval width for estimates of conservation benchmarks (e.g. SMAX- spawner abundance at carrying capacity). We estimated that almost half of these remote sockeye stocks are below one commonly applied conservation benchmarks (SMSY), despite substantial reductions in fishing pressure in recent decades. Thus, habitat-based capacity estimates can dramatically reduce scientific uncertainty in model estimates of management targets that underpin sustainable sockeye fisheries. More generally, our analysis reveals opportunities to integrate spatial analyses of habitat characteristics with population models to inform conservation and management of exploited species where population data are limited.
Within- and transgenerational plasticity of a temperate salmonid in response to thermal acclimation and acute temperature stress
Authors: Penney Chantelle M. , Tabh Joshua K. R. , Wilson Chris C. , Burness Gary
Published: March 2021

Environmental temperatures associated with climate change are rising too rapidly for many species to adapt, threatening the persistence of taxa with limited capacities for thermal acclimation. We investigated the capacity for within- and transgenerational responses to increasing environmental temperatures in brook trout (Salvelinus fontinalis), a cold-adapted salmonid. Adult fish were acclimated to temperatures within (10□) and above (21□) their thermal optimum for six months before spawning, then mated in a full factorial breeding design to produce offspring from cold- and warm-acclimated parents as well as bidirectional crosses between parents from both temperature treatments. Offspring families were subdivided and reared at two acclimation temperatures (15□ and 19□) representing their current environment and a projected climate change scenario. Offspring thermal physiology was measured as the rate of oxygen consumption (MO2) during an acute change in temperature (+2□ h-1) to observe their MO2-temperature relationship. We also recorded resting MO2, the highest achieved (peak) MO2, and critical thermal maximum (CTM) as performance metrics. Within-generation plasticity was greater than transgenerational plasticity, with offspring acclimation temperature having demonstrable effects on peak MO2and CTM. Transgenerational plasticity was evident as an elevated resting MO2and the MO2-temperature relationship in offspring from warm-acclimated parents. Both parents contributed to offspring thermal responses, although the paternal effect was stronger. Although brook trout exhibit both within- and transgenerational plasticity for thermal physiology, it is unlikely that these will be sufficient for coping with long-term changes to environmental temperatures resulting from climate change.

Brook trout (Salvelinus fontinalis) exhibit within-generation and transgenerational plasticity for thermal performance, although neither response appears sufficient to cope with long-term climate change effects.
Vibrio choleraeParE2 toxin modulates its operon transcription by stabilization of an antitoxin DNA ruler
Authors: Garcia-Rodriguez Gabriela , Girardin Yana , Singh Ranjan Kumar , Volkov Alexander N. , Konijnenberg Albert , Sobott Frank , Charlier Daniel , Loris Remy
Published: March 2021

TheparDE2operon ofVibrio choleraeencodes a type II TA system, which is one of three loci in the superintegron of small chromosome II that show modest similarity to theparDEoperon of plasmid RK2. ParE2, like plasmid RK2-encoded ParE, inhibits DNA gyrase, an essential topoisomerase that is also the target of quinolone antibacterial agents. Mechanistic understanding on ParE2 toxin inhibition by direct interaction with its cognate antitoxin and transcriptional autoregulation of the TA system are currently lacking. ParD2, the ribbon-helix-helix (RHH) antitoxin, auto-represses theparDE2promoter. This repression is enhanced by ParE2, which therefore functions as a transcriptional co-repressor. Here we present protein-DNA interaction studies and high-resolution X-ray structures of the ParD2:ParE2 complex and isolated ParD2 antitoxin, revealing the basis of toxin inhibition and autoregulation of the TA operon by conditional cooperativity. Native mass spectrometry, SAXS and MALS studies confirm the presence of different oligomerization states of ParD2 in solution and the role of the DNA-binding hexameric ParD26:ParE22assembly in transcriptional repression.
Proteome plasticity in response to persistent environmental change
Authors: Domnauer Matthew , Zheng Fan , Li Liying , Zhang Yanxiao , Chang Catherine E. , Unruh Jay R. , Conkright-Fincham Julie , McCroskey Scott , Florens Laurence , Zhang Ying , Seidel Christopher , Fong Benjamin , Schilling Birgit , Sharma Rishi , Ramanathan Arvind , Si Kausik , Zhou Chuankai
Published: March 2021

Temperature is a variable component of the environment and all organisms must deal with or adapt to temperature change. Acute temperature change activates cellular stress responses resulting in the refolding or removal of damaged proteins. However, how organisms adapt to long-term temperature change remains largely unexplored. Here, we report that budding yeast responds to long-term high temperature challenge by switching from chaperone induction to the reduction of temperature sensitive proteins and re-localizing a portion of its proteome. Surprisingly, we also find many proteins adopt an alternative conformation. Using Fet3p as an example, we find that the temperature-dependent conformational difference is accompanied by distinct thermostability, subcellular localization, and importantly, cellular functions. We postulate that in addition to the known mechanisms of adaptation, conformational plasticity allows some polypeptides to acquire new biophysical properties and functions when environmental change endures.
Deep neural network analysis employing diffusion basis spectrum imaging metrics as classifiers improves prostate cancer detection and grading
Authors: Ye Zezhong , Yang Qingsong , Lin Joshua , Sun Peng , Shao Chengwei , Yu Yongwei , Chen Luguang , Zhu Yasheng , Wu Anthony T. , George Ajit , Song Chunyu , Yang Ruimeng , Zhan Jie , Gary Sam E. , Viox Jeffrey D. , Wang Zhen , Wang Minjie , Chen Yukun , Kim Eric H. , Ippolito Joseph E. , Lu Jianping , Song Sheng-Kwei
Published: March 2021

Structural and cellular complexity of prostatic histopathology limits the accuracy of noninvasive detection and grading of prostate cancer (PCa). We addressed this limitation by employing a novel diffusion basis spectrum imaging (DBSI) to derive structurally-specific diffusion fingerprints reflecting various underlying prostatic structural and cellular components. We further developed diffusion histology imaging (DHI) by combining DBSI-derived structural fingerprints with a deep neural network (DNN) algorithm to more accurately classify different histopathological features and predict tumor grade in PCa. We examined 243 patients suspected with PCa usingin vivoDBSI. Thein vivoDBSI-derived diffusion metrics detected coexisting prostatic pathologies distinguishing inflammation, PCa, and benign prostatic hyperplasia. DHI distinguished PCa from benign peripheral and transition zone tissues with over 95% sensitivity and specificity. DHI also demonstrated over 90% sensitivity and specificity for Gleason score noninvasively. We present DHI as a novel diagnostic tool capable of noninvasive detection and grading of PCa.

One sentence summary

Diffusion histology imaging noninvasively and accurately detects and grades prostate cancer.
A non-invasive brain-machine interface via independent control of individual motor units
Authors: Formento Emanuele , Botros Paul , Carmena Jose M.
Published: March 2021

Brain-machine interfaces (BMIs) have the potential to augment human functions and restore independence in people with disabilities, yet a compromise between non-invasiveness and performance limits their relevance. Here, we demonstrate a BMI controlled by individual motor units non-invasively recorded from the biceps brachii. Through real-time auditory and visual neurofeedback of motor unit activity, 8 participants learned to skillfully and independently control three motor units in order to complete a two-dimensional center-out task, with marked improvements in control over 6 days of training. Concomitantly, dimensionality of the motor unit population increased significantly relative to naturalistic behaviors, largely violating recruitment orders displayed during stereotyped, isometric muscle contractions. Finally, participants demonstrated the potential of a motor unit BMI to power general applications by navigating a virtual keyboard in a spelling task, achieving performances comparable to spelling-tailored non-invasive BMIs that leverage less flexible control strategies to improve performance. These results highlight a largely unexplored level of flexibility of the sensorimotor system and show that this can be exploited to create a versatile, skillfully-controllable non-invasive BMI that has great potential to both provide translational benefit and augment motor functions.
A Kalirin Missense Mutation Enhances Dendritic RhoA Signaling and Leads to Regression of Cortical Dendritic Arbors Across Development
Authors: Grubisha MJ , Sun T , Erickson SL , Eisenman L , Chou S , Helmer CD , Trudgen MT , Ding Y , Homanics GE , Penzes P , Wills ZP , Sweet RA
Published: March 2021

Normally, dendritic size is established prior to adolescence then remains relatively constant into adulthood due to a homeostatic balance between growth and retraction pathways. However, schizophrenia is characterized by accelerated reductions of cerebral cortex gray matter volume and onset of clinical symptoms during adolescence, with reductions in layer 3 pyramidal neuron dendritic length, complexity, and spine density identified in multiple cortical regions postmortem. Nogo receptor 1 (NGR1) activation of the GTPase RhoA is a major pathway restricting dendritic growth in the cerebral cortex. We show that the NGR1 pathway is stimulated by OMGp and requires the Rho guanine nucleotide exchange factor, Kalirin-9 (KAL9). Using a genetically encoded RhoA sensor, we demonstrate that a naturally occurring missense mutation inKalrn, KAL-PT, that was identified in a schizophrenia cohort, confers enhanced RhoA activitation in neuronal dendrites compared to wildtype KAL. In mice containing this missense mutation at the endogenous locus there is an adolescent-onset reduction in dendritic length and complexity of layer 3 pyramidal neurons in the primary auditory cortex. Tissue density of dendritic spines was also reduced. Early adult mice with these structural deficts exhibited impaired detection of short gap durations. These findings provide a neuropsychiatric model of disease capturing how a mild genetic vulnerability may interact with normal developmental processes such that pathology only emerges around adolescence. This interplay between genetic susceptibility and normal adolescent development, both of which possess inherent individual variability, may contribute to heterogeneity seen in phenotypes in human neuropsychiatric disease.

SIGNIFICANCE STATEMENT

Dendrites are long branching processes on neurons that contain small processes called spines that are the site of connections with other neurons, establishing cortical circuitry. Dendrites have long been considered stable structures, with rapid growth prior to adolescence followed by maintenance of size into adulthood. However, schizophrenia is characterized by accelerated reductions of cortical gray matter volume and onset of clinical symptoms during adolescence, with reductions in dendritic length present when examined after death. We show that dendrites retain the capacity for regression, and that a mild genetic vulnerability in a regression pathway leads to onset of structural impairments in previously formed dendrites across adolescence. This suggests that targeting specific regression pathways could potentially lead to new therapeutics for schizophrenia.
Catalase Activity is Critical forProteus mirabilisBiofilm Development, EPS Composition, and Dissemination During Catheter-Associated Urinary Tract Infection
Authors: White Ashley N. , Learman Brian S. , Brauer Aimee L. , Armbruster Chelsie E.
Published: March 2021

Proteus mirabilisis a leading uropathogen of catheter-associated urinary tract infections (CAUTIs), which are among the most common healthcare-associated infections worldwide. A key factor that contributes toP. mirabilispathogenesis and persistence during CAUTI is the formation of catheter biofilms, which provide increased resistance to antibiotic treatment and host defense mechanisms. Another factor that is important for bacterial persistence during CAUTI is the ability to resist reactive oxygen species (ROS), such as through the action of the catalase enzyme. Potent catalase activity is one of the defining biochemical characteristics ofP. mirabilis,and its single catalase gene (katA) was recently identified as a candidate fitness factor for UTI, CAUTI, and bacteremia. Here we show that disruption ofkatAresults in increased ROS levels, increased sensitivity to peroxide, and decreased biofilm biomass. The biomass defect was due to a decrease in extracellular polymeric substances (EPS) production by the ΔkatAmutant, and specifically due to reduced carbohydrate content. Importantly, the biofilm defect resulted in decreased antibiotic resistancein vitroand a colonization defect during experimental CAUTI. The ΔkatAmutant also exhibited decreased fitness in a bacteremia model, supporting a dual role for catalase inP. mirabilisbiofilm development and immune evasion.
Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation
Authors: Dewey Marley J. , Kolliopoulos Vasiliki , Ngo Mai T. , Harley Brendan A.C.
Published: March 2021

Effective design of biomaterials to aid regenerative repair of craniomaxillofacial (CMF) bone defects requires approaches that modulate the complex interplay between exogenously added progenitor cells and cells in the wound microenvironment, such as osteoblasts, osteoclasts, endothelial cells, and immune cells. We are exploring the role of the glycosaminoglycan (GAG) content in a class of mineralized collagen scaffolds recently shown to promote osteogenesis and healing of craniofacial bone defects. We previously showed that incorporating chondroitin-6-sulfate or heparin improved mineral deposition by seeded human mesenchymal stem cells (hMSCs). Here, we examine the effect of varying scaffold GAG content on hMSC behavior, and their ability to modulate osteoclastogenesis, vasculogenesis, and the immune response. We report the role of hMSC-conditioned media produced in scaffolds containing chondroitin-6-sulfate (CS6), chondroitin-4-sulfate (CS4), or heparin (Heparin) GAGs on endothelial tube formation and monocyte differentiation. Notably, endogenous production by hMSCs within Heparin scaffolds most significantly inhibits osteoclastogenesis via secreted osteoprotegerin (OPG), while the secretome generated by CS6 scaffolds reduced pro-inflammatory immune response and increased endothelial tube formation. All conditioned media down-regulated many pro- and anti-inflammatory cytokines, such as IL6, IL-1β, and CCL18 and CCL17 respectively. Together, these findings demonstrate that modifying mineralized collagen scaffold GAG content can both directly (hMSC activity) and indirectly (production of secreted factors) influence overall osteogenic potential and mineral biosynthesis as well as angiogenic potential and monocyte differentiation towards osteoclastic and macrophage lineages. Scaffold GAG content is therefore a powerful stimulus to modulate reciprocal signaling between multiple cell populations within the bone healing microenvironment.
Serotonin and dopamine modulate aging in response to food perception and availability
Authors: Miller Hillary A. , Huang Shijiao , Schaller Megan L. , Dean Elizabeth S. , Tuckowski Angela M. , Munneke Allyson S. , Beydoun Safa , Pletcher Scott D. , Leiser Scott F.
Published: March 2021

An organism’s ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction (DR), acts in-part through a cell non-autonomous signaling pathway that is inhibited by the perception of attractive smells. Using an intestinal reporter for a key gene induced by DR but suppressed by attractive smells, we identify three compounds that block food perception inC. elegans, thereby increasing longevity as DR mimetics. These compounds clearly implicate serotonin and dopamine in limiting lifespan in response to food perception. We further identify an enteric neuron in this pathway that signals through the serotonin receptor 5-HT1A/ser-4 and dopamine receptor DRD2/dop-3. Aspects of this pathway are conserved in D. melanogaster and mammalian cells. Thus, blocking food perception through antagonism of serotonin or dopamine receptors is a plausible approach to mimic the benefits of dietary restriction.
The architecture of Cidec-mediated interfaces between lipid droplets
Authors: Ganeva Iva , Lim Koini , Boulanger Jerome , Hoffmann Patrick C. , Savage David B. , Kukulski Wanda
Published: March 2021

Lipid droplets (LDs) are intracellular organelles responsible for storing surplus energy as neutral lipids. Their size and number vary enormously (1). In white adipocytes, they reach up to 100µm in size, occupying >90% of the cell. Cidec, which is strictly required for the formation of such large LDs, is concentrated at interfaces between adjacent LDs and facilitates the directional flux of neutral lipids from the smaller to the larger LD (2-7). However, the mechanism of lipid transfer is unclear, in part because the architecture of interfaces between LDs has remained elusive. Here we visualised interfaces between LDs by electron cryo-tomography (cryo-ET) and analysed the kinetics of lipid transfer by quantitative live fluorescence microscopy (FM). We show that transfer occurs through closely apposed intact monolayers, is slowed down by increasing the distance between the monolayers and follows exponential kinetics suggesting a pressure-driven mechanism. We thus propose that unique architectural features of LD-LD interfaces are mechanistic determinants of neutral lipid transfer.
Protein-primed RNA synthesis in SARS-CoVs and structural basis for inhibition by AT-527
Authors: Shannon Ashleigh , Fattorini Véronique , Sama Bhawna , Selisko Barbara , Feracci Mikael , Falcou Camille , Gauffre Pierre , Kazzi Priscila El , Decroly Etienne , Rabah Nadia , Alvarez Karine , Eydoux Cécilia , Guillemot Jean-Claude , Debart Françoise , Vasseur Jean-Jacques , Noel Mathieu , Moussa Adel , Good Steven , Lin Kai , Sommadossi Jean-Pierre , Zhu Yingxiao , Yan Xiaodong , Shi Hui , Ferron François , Canard Bruno
Published: March 2021

How viruses from theCoronaviridaefamily initiate viral RNA synthesis is unknown. Here we show that the SARS-CoV-1 and −2NidovirusRdRp-AssociatedNucleotidyltransferase (NiRAN) domain on nsp12 uridylates the viral cofactor nsp8, forming a UMP-Nsp8 covalent intermediate that subsequently primes RNA synthesis from a poly(A) template; a protein-priming mechanism reminiscent ofPicornaviridaeenzymes. In parallel, the RdRp active site of nsp12 synthesizes a pppGpU primer, which primes (-)ssRNA synthesis at the precise genome-poly(A) junction. The guanosine analogue 5’-triphosphate AT-9010 (prodrug: AT-527) tightly binds to the NiRAN and inhibits both nsp8-labeling and the initiation of RNA synthesis. A 2.98 Å resolution Cryo-EM structure of the SARS-CoV-2 nsp12-nsp7-(nsp8)2/RNA/NTP quaternary complex shows AT-9010 simultaneously binds to both NiRAN and RdRp active site of nsp12, blocking their respective activities. AT-527 is currently in phase II clinical trials, and is a potent inhibitor of SARS-CoV-1 and −2, representing a promising drug for COVID-19 treatment.
The fern CYPome: Fern-specific cytochrome P450 family involved in convergent evolution of chemical defense
Authors: Thodberg Sara , Hansen Cecilie Cetti , Takos Adam M. , Pičmanová Martina , Møller Birger Lindberg , Nelson David R. , Neilson Elizabeth H. Jakobsen
Published: March 2021

Plant natural products encompass an enormous chemical diversity bearing witness to great molecular innovation that occured throughout land plant evolution. Cytochrome P450 monooxygenases (CYPs) catalyze a wide variety of monooxygenation reactions essential to the metabolic repertoire of plants natural products. Ferns constitute the second largest group of vascular plants and hold a significant phylogenetic position in land evolution, lying sister to seed plants. To date, CYP diversity has not been described for this taxon and pathway discovery in ferns in general is scarce, despite possessing a rich diversity of natural products. We analysed over 8000 available fern CYPs, classifing and characterizing the landscape of this super-enzyme group. Fern CYPs are dominated by fern-specific families (∼60%), with the largest family – CYP981 – constituting approximately 15% of all predicted fern CYPs in the dataset. The abundancy and dynamics of the CYP981 family suggest a position equivalent to the CYP71 family present in seed plants, with potential roles in natural product biosynthesis. Ferns are the evolutionary oldest group to biosynthesize cyanogenic glycosides; amino acid-derived defense compounds. We show that CYP981F5 from the highly cyanogenic fernPhlebodium aureumcatalyzes the conversion of phenylacetonitrile to mandelonitrile, an intermediate step in cyanogenic glycoside biosynthesis. The fern CYPome provides an important platform to further understand evolution of metabolite biosynthesis throughout the plant kingdom, and in ferns specifically.
Membrane insertion mechanism of the caveolae coat protein Cavin1
Authors: Liu Kang-cheng , Pace Hudson , Larsson Elin , Hossain Shakhawath , Kabedev Aleksei , Shukla Ankita , Jerschabek Vanessa , Mohan Jagan , Bergström Christel A. S. , Bally Marta , Schwieger Christian , Hubert Madlen , Lundmark Richard
Published: March 2021

Caveolae are small plasma membrane invaginations, important for control of membrane tension, signaling cascades and lipid sorting. The caveolae coat protein Cavin1 is essential for shaping such high curvature membrane structures. Yet, a mechanistic understanding of how Cavin1 assembles at the membrane interface is lacking. Here, we used model membranes combined with biophysical dissection and computational modelling to show that Cavin1 inserts into membranes. We establish that initial PI(4,5)P2-dependent membrane adsorption of the trimeric helical region 1 (HR1) of Cavin1 mediates the subsequent partial separation and membrane insertion of the individual helices. Insertion kinetics of the HR1 is further enhanced by the presence of flanking negatively charged disordered regions, which was found important for the co-assembly of Cavin1 with Caveolin1 in living cells. We propose that this intricate mechanism potentiates membrane curvature generation and facilitates dynamic rounds of assembly and disassembly of Cavin1 at the membrane.

Significance statement

Caveolae are cholesterol enriched membrane invaginations coupled to severe muscle and lipid disorders. Their formation is dependent on assembly of the protein Cavin1 at the lipid membrane interface driving membrane curvature. In this work, we dissect the mechanism for how Cavin1 binds and inserts into membranes using a combination of biochemical and biophysical characterization as well as computational modelling. The proposed model for membrane assembly potentiates dynamic switching between shielded and exposed hydrophobic helices used for membrane insertion and clarifies how Cavin1 can drive membrane curvature and the formation of caveolae.
Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients
Authors: Zheng Qingliang , Xu XiangHong , Yang Fenglian , Gan Haili , Zhao Yongbo , Wan Xiaoping , Jin Liping
Published: March 2021

Due to the heterogeneity and different polarization state of decidual macrophages (dMΦ), they play an important role during the pregnancy, but their definition and exact function remain elusive. We isolated CD14+CD45+dMΦ from the normal or RSA decidua by flow cytometry, followed by single cell RNA sequencing (scRNA-seq). In total, 23,062 single-cell transcriptomes of macrophage were profiled (12,470 Normal and 10,592 RSA), which were divided into 13 major clusters via T-distributed stochastic neighbor embedding (t-SNE) visualization. We observed that there is higher percentage composition of M1 cells (70.6%) in the normal decidua, and higher percentage composition of M2 cells (68.3%) in the RSA decidua. We identified new markers (M1: S100A8, S100A9, M2: SELENOP, FOLR2, RNASE1) and secreted cytokines (M1: IL1β, TNFSF13B and MMP9; M2: CCL3, CCL4) of the dMΦ. We found that cluster 10 as the specific cluster of dMΦ highly expressing BAG3 in normal group and cluster 7 specific highly expressing CXCL9/10/11 chemokine. After pseudo-time trajectory analysis, we found that the dMΦ formed a continuous “V-shaped” trajectory, with M1 and M2 type cells mainly occupying the two heads. We found that NFκB1, MYC and TCF12 acted as the key transcription factors of dMΦ. Our study redefined the polarization state and physiological characteristic of dMΦ in early normal and RSA pregnancy, which suggests a novel view and therapeutic target for spontaneous abortion prevention.
Insight into Lipopolysaccharide Translocation by Cryo-EM structures of a LptDE Transporter in Complex with Pro-Macrobodies
Authors: Botte Mathieu , Ni Dongchun , Schenck Stephan , Zimmermann Iwan , Chami Mohamed , Bocquet Nicolas , Egloff Pascal , Bucher Denis , Trabuco Matilde , Cheng Robert K.Y. , Brunner Janine D. , Seeger Markus A. , Stahlberg Henning , Hennig Michael
Published: March 2021

Lipopolysaccharides (LPS) are major constituents of the extracellular leaflet in the bacterial outer membrane and form an effective physical barrier for environmental threats and for antibiotics in Gram-negative bacteria1. The last step of LPS insertion via the Lpt pathway is mediated by the LptD/E protein complex2. Despite detailed insights from X-ray crystallography into the architecture of LptDE transporter complexes3–5, no structure of a laterally open LptD transporter has been described, a transient state that occurs during LPS release6. To facilitate the acquisition of hitherto unknown conformations we subjected LptDE ofN. gonorrhoeaeto cryo-EM analyses. In complex with newly designed rigid chaperones derived from nanobodies (Pro-Macrobodies, PMbs) we obtained a map of a partially opened LptDE transporter at 3.4 Å resolution and in addition we captured a laterally fully opened LptDE complex from a subset of particles. Our work offers new insights into the mechanism of LPS insertion, provides a structural framework for the development of antibiotics targeting LptD and describes a novel, highly rigid and widely applicable chaperone scaffold to enable structural biology of challenging protein targets.
Distinct domains of Me31B interact with different eIF4E isoforms in the male germ line ofDrosophila melanogaster
Authors: Layana Carla , Vilardo Emiliano Salvador , Corujo Gonzalo , Hernández Greco , Rivera-Pomar Rolando
Published: March 2021

Eukaryotic translation initiation factor 4E (eIF4E) is a key factor involved in different aspects of mRNA metabolism.Drosophila melanogastergenome encodes eight eIF4E isoforms, and the canonical isoform eIF4E-1 is a ubiquitous protein that plays a key role in mRNA translation. eIF4E-3 is specifically expressed in testis and controls translation during spermatogenesis. In eukaryotic cells, translational control and mRNA decay is highly regulated in different cytoplasmic ribonucleoprotein foci, which include the processing bodies (PBs). In this study, we show thatDrosophilaeIF4E-1 and eIF4E-3 occur in PBs where might play a role in mRNA storage and translational repression. We also demonstrate that the DEAD-box RNA helicase Me31B, a component of PBs, physically interacts with eIF4E-1 and eIF4E-3 both in the yeast two-hybrid system and FRET inDrosophilaS2 cells.

Moreover, truncated and point mutated Me31B proteins indicate that the binding sites of Me31B for eIF4E-1 and eIF4E-3 are located in different domains. Residues Y401-L407 (at the carboxy-terminal) are essential for interaction with eIF4E-1, whereas residues F63-L70 (at the amino-terminal) are critical for interaction with eIF4E-3. Thus, Me31B represents a novel type of eIF4E-interacting protein. Our observations suggest that Me31B might recognize different eIF4E isoforms in different tissues, which could be the key to silencing specific messengers. They provide further evidence that alternative forms of eIF4E and their interactions with various partners add complexity to the control of gene expression in eukaryotes.
Rapid thermophilization of understorey plant communities in a 9 year‐long temperate forest experiment
Authors: Govaert Sanne , Vangansbeke Pieter , Blondeel Haben , Steppe Kathy , Verheyen Kris , De Frenne Pieter
Published: March 2021

The vast majority of plant biodiversity associated with temperate forests is harboured by the understorey layer. This layer also plays crucial roles in ecosystem functions such as tree regeneration, nutrient cycling and carbon dynamics. Research using space‐for‐time substitutions and resurveys of vegetation plots has shown that climate warming, changes in forest management and resource availability are key determinants of forest understorey biodiversity change and functioning. However, long‐term experiments are needed to better unravel their complex interactive effects.

Here we study the influence of nearly a decade of experimental warming, light addition using fluorescent tubes (as a proxy for management‐driven changes in forest‐floor light levels) and nitrogen input on understorey plant communities of temperate broadleaved forest.

Plant communities shifted towards a higher dominance of warm‐adapted species, a process referred to as thermophilization. We detected a marked community shift in all treatments including the control plots, reflecting ongoing ambient environmental changes. This reordering over time was greater than the shift induced by the treatments. Thermophilization was, however, greatest when temperature and/or light availability were enhanced. Communities were also taller in response to warming and increased light availability.

Synthesis. Our experiment provides important insights into 9 years of vegetation changes in a temperate forest and how canopy density and forest management can be adapted to limit thermophilization of forest understorey biodiversity under climate change. [Correction added on 27 April 2021, after first online publication: The Synthesis section in the abstract has been updated to reflect the original text supplied.]
Can it be all more simple? Manufacturing aflatoxin biocontrol products using dry spores of atoxigenic isolates of Aspergillus flavus as active ingredients
Authors: Ortega‐Beltran Alejandro , Kaptoge Lawrence , Senghor Amadou L. , Aikore Morounranti O. S. , Jarju Patrick , Momanyi Henry , Konlambigue Matieyedou , Falade Titilayo D. O. , Bandyopadhyay Ranajit
Published: March 2021

Aflatoxin contamination of staple crops, commonly occurring in warm areas, negatively impacts human and animal health, and hampers trade and economic development. The fungus Aspergillus flavus is the major aflatoxin producer. However, not all A. flavus genotypes produce aflatoxins. Effective aflatoxin control is achieved using biocontrol products containing spores of atoxigenic A. flavus. In Africa, various biocontrol products under the tradename Aflasafe are available. Private and public sector licensees manufacture Aflasafe using spores freshly produced in laboratories adjacent to their factories. BAMTAARE, the licensee in Senegal, had difficulties to obtain laboratory equipment during its first year of production. To overcome this, a process was developed in Ibadan, Nigeria, for producing high‐quality dry spores. Viability and stability of the dry spores were tested and conformed to set standards. In 2019, BAMTAARE manufactured Aflasafe SN01 using dry spores produced in Ibadan and sent via courier and 19 000 ha of groundnut and maize in Senegal and The Gambia were treated. Biocontrol manufactured with dry spores was as effective as biocontrol manufactured with freshly produced spores. Treated crops contained safe and significantly (P < 0.05) less aflatoxin than untreated crops. The dry spore innovation will make biocontrol manufacturing cost‐efficient in several African countries.
The affective and conversational benefits of a walk in nature among mother–daughter dyads
Authors: Izenstark Dina , Ravindran Niyantri , Rodriguez Sarah , Devine Natalee
Published: March 2021

The emotional benefits of nature among children and adults are well documented. However, little is known regarding how nature exposure influences a parent and child walking together (Journal of Planning Literature, 2015, 30, 433). We examine how both environmental setting and social context influence affect and conversational content among mother–daughter dyads. Twenty‐eight mother–daughter (aged 10–12) dyads participated in a within‐subjects experimental design that included two counterbalanced conditions—a 20 minute walk outdoors and a 20 minute walk indoors. Self‐reported positive affect and negative affect were collected before and after each condition, and audio‐recorded observations were utilized to code expressed positivity, negativity, and conversational content during each condition. Results showed that 1) daughters self‐reported positive affect increased after the outdoor walk and mothers and daughters reported decreased negative affect after both conditions, 2) mothers and daughters expressed less negativity during the nature walk and were more likely to influence each other's negative affect indoors, and 3) mothers and daughters talked more about the surrounding environment during the indoor walk and engaged in more neutral conversations during the outdoor walk. Findings from the study demonstrate the benefits of mother–daughter dyads walking together outdoors and highlight the importance of spending time outside as a way to promote positive family interactions.
The Hammer vs Mitigation—A comparative retrospective register study of the Swedish and Danish national responses to the COVID‐19 pandemic in 2020
Authors: Mens Helene , Koch Anders , Chaine Manon , Bengaard Andersen Aase
Published: March 2021

In the efforts to dampen the COVID‐19 pandemic, governments are compelled to outweigh disease control efforts to the possible negative consequences of closing large parts of society. Although Denmark and Sweden are alike in political organization and health care, national responses to the 2020 COVID‐19 epidemic differed noticeably. Denmark initiated a hard lock down followed by an outbreak control strategy (the so‐called “hammer and dance” strategy), while Sweden’s strategy was based on advising on social distancing, while keeping society open (a so‐called mitigative strategy). The objective of this study is to describe national epidemic control strategies in Denmark and Sweden in 2020, and compare the epidemic dynamics in the two countries, with respect to number of COVID‐19 cases, admissions to intensive care and mortality. Data on epidemic control efforts and COVID‐associated morbidity/mortality were downloaded from official government and epidemic surveillance webpages and comparatively described using basic statistics. Overall, we found “the hammer” resulted in better epidemic control during 2020 with less COVID‐19‐associated admissions to intensive care and lower mortality.
Deficient mitophagy pathways in sickle cell disease
Authors: Martino Suella , Arlet Jean‐Benoit , Odièvre Marie‐Hélène , Jullien Vincent , Moras Martina , Hattab Claude , Lefebvre Thibaud , Gouya Laurent , Ostuni Mariano A. , Lefevre Sophie D. , Le Van Kim Caroline
Published: March 2021

Sickle cell disease (SCD) is characterised by chronic haemolysis and oxidative stress. Herein, we investigated 30 SCD patients and found 40% with elevated mitochondria levels (SS‐mito+) in their mature red blood cells, while 60% exhibit similar mitochondria levels compared to the AA group (SS‐mito−). The SS‐mito+ patients are characterised by higher reticulocytosis and total bilirubin levels, lower foetal haemoglobin, and non‐functional mitochondria. Interestingly, we demonstrated decreased levels of mitophagy inducers, PINK1 and NIX, and higher levels of HSP90 chaperone in their red cells. Our results highlighted for the first time an abnormal retention of mitochondria in SCD linked with mitophagy‐related proteins.
Ashmole's hypothesis and the latitudinal gradient in clutch size
Authors: Lundblad Carl G. , Conway Courtney J.
Published: March 2021

One enduring priority for ecologists has been to understand the cause(s) of variation in reproductive effort among species and localities. Avian clutch size generally increases with increasing latitude, both within and across species, but the mechanism(s) driving that pattern continue to generate hypotheses and debate. In 1961, a Ph.D. student at Oxford University, N. Philip Ashmole, proposed the influential hypothesis that clutch size varies in direct proportion to the seasonality of resources available to a population. Ashmole's hypothesis has been widely cited and discussed in the ecological literature. However, misinterpretation and confusion has been common regarding the mechanism that underlies Ashmole's hypothesis and the testable predictions it generates. We review the development of well‐known hypotheses to explain clutch size variation with an emphasis on Ashmole's hypothesis. We then discuss and clarify sources of confusion about Ashmole's hypothesis in the literature, summarise existing evidence in support and refutation of the hypothesis, and suggest some under‐utilised and novel approaches to test Ashmole's hypothesis and gain an improved understanding of the mechanisms responsible for variation in avian clutch size and fecundity, and life‐history evolution in general.
Eco‐genetics of desiccation resistance in Drosophila
Authors: Wang Yiwen , Ferveur Jean‐François , Moussian Bernard
Published: March 2021

Climate change globally perturbs water circulation thereby influencing ecosystems including cultivated land. Both harmful and beneficial species of insects are likely to be vulnerable to such changes in climate. As small animals with a disadvantageous surface area to body mass ratio, they face a risk of desiccation. A number of behavioural, physiological and genetic strategies are deployed to solve these problems during adaptation in various Drosophila species. Over 100 desiccation‐related genes have been identified in laboratory and wild populations of the cosmopolitan fruit fly Drosophila melanogaster and its sister species in large‐scale and single‐gene approaches. These genes are involved in water sensing and homeostasis, and barrier formation and function via the production and composition of surface lipids and via pigmentation. Interestingly, the genetic strategy implemented in a given population appears to be unpredictable. In part, this may be due to different experimental approaches in different studies. The observed variability may also reflect a rich standing genetic variation in Drosophila allowing a quasi‐random choice of response strategies through soft‐sweep events, although further studies are needed to unravel any underlying principles. These findings underline that D. melanogaster is a robust species well adapted to resist climate change‐related desiccation. The rich data obtained in Drosophila research provide a framework to address and understand desiccation resistance in other insects. Through the application of powerful genetic tools in the model organism D. melanogaster, the functions of desiccation‐related genes revealed by correlative studies can be tested and the underlying molecular mechanisms of desiccation tolerance understood. The combination of the wealth of available data and its genetic accessibility makes Drosophila an ideal bioindicator. Accumulation of data on desiccation resistance in Drosophila may allow us to create a world map of genetic evolution in response to climate change in an insect genome. Ultimately these efforts may provide guidelines for dealing with the effects of climate‐related perturbations on insect population dynamics in the future.
Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study
Authors: Ameratunga R , Jordan A , Cavadino A , Ameratunga S , Hills T , Steele R , Hurst M , McGettigan B , Chua I , Brewerton M , Kennedy N , Koopmans W , Ahn Y , Barker R , Allan C , Storey P , Slade C , Baker A , Huang L , Woon S-T
Published: March 2021

Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Māori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.
Zinc finger protein 91 accelerates tumour progression by activating β‐catenin signalling in pancreatic cancer
Authors: Tang Neng , Xu Shanshan , Song Taiyu , Qiu Yudong , He Jian , Fu Xiao
Published: March 2021

Objectives

ZFP91, an E3 ligase, has been reported to possess cancer‐promoting functions. This study aimed to elucidate the exact role of ZFP91 in tumour progression of pancreatic cancer and underlying mechanisms.

Materials and Methods

We analysed the correlation between ZFP91 expression and pancreatic cancer through TCGA and GEO data sets. Growth curve, colony formation, wound healing and transwell invasion assays were conducted to evaluate proliferation, migration and invasion of lentivirus transfected pancreatic cancer cells. GSEA and Western blot analysis were performed to validate the regulatory effect of ZFP91 on β‐catenin. Drug response curve and orthotopic implantation model reflected the sensitivity of chemotherapies.

Results

ZFP91 overexpression is prevalent in pancreatic cancer and negatively correlated with overall survival. ZFP91 knock‐down attenuated proliferation, migration and invasion of pancreatic cancer cells. β‐catenin was a downstream gene of ZFP91, and its agonist could reverse the phenotype. ZFP91 promoted EMT and chemoresistance in pancreatic cancer.

Conclusions

We demonstrated that ZFP91 promoted pancreatic cancer proliferation, migration and invasion through activating β‐catenin signalling. EMT and chemoresistance were also regulated by ZFP91. ZFP91 might be a potential therapeutic target for pancreatic cancer.
Avoiding a conservation pitfall: Considering the risks of unsuitably hot bat boxes
Authors: Crawford Reed D. , O'Keefe Joy M.
Published: March 2021

Bat boxes are commonly deployed to mitigate the loss of bat roosting habitat. Due to a dearth of microclimate research, numerous untested commercially available bat boxes, and the uncertain impacts of a rapidly changing climate, the overheating risk presented to bats by bat boxes is largely unquantified. Based on limited research, we know many boxes overheat (i.e., temperatures >40°C). A lack of standardized protocols to evaluate microclimate and misleading information available to the public leads to a murky understanding of risks involved with deploying bat boxes. Herein, we evaluate the thermal tolerance of temperate‐zone bats, delineate areas of concern regarding the risks to temperate‐zone bats when bat boxes are deployed, identify strategies for reducing overheating risk, suggest methods for assessing microclimate, and provide a visual framework to assess overheating risk. Identifying suitable design and placement combinations is crucial to developing region‐specific strategies to mitigate against overheating. We urge consideration of the risks involved with using bat boxes, advocate for rigorous testing before deployment, and suggest using alternatives when possible.