bluuebunny/crossref_metadata_2025 huggingface dataset:
A general trait-based model for multiplex ecological networks
Authors: Hale Kayla R. S. , Thébault Elisa , Valdovinos Fernanda S.
Published: August 2023

Ecological networks can represent the structure of food webs, energy flow, and the many and diverse types of interactions between species in ecosystems. Despite its tremendous importance for understanding biodiversity, stability, ecosystem functioning, research on ecological networks has traditionally been restricted to subsets of the species or interactions in ecosystems, i.e., “subnetworks” such as pollination networks or food webs. As a result, the structure of “multiplex” networks that include multiple interaction types is mostly unknown and there is no robust, underlying theory to support their study. Some ecological traits, such as body size or length of mouth parts, are well-known as key predictors of different species interactions. These traits are often strongly related to each other due to evolutionary history, allometry, and selection, and this relatedness may constrain the structure of ecological multiplex networks. We use this idea to develop a model that simulates multiplex ecological networks by interconnecting subnetworks using correlated traits. Our model predicts how multiplex network structure, measured as the overlaps between species’ functional roles, is affected by neutral processes, interaction rules, and trait constraints, while the structure of individual subnetworks is independent of these trait correlations. Additionally, our model accurately predicts the structure of an observed multiplex network using existing knowledge on species trait correlations and basic features of known ecological subnetworks. This work will stimulate new studies of the structure and dynamics of complex ecosystems by providing a null expectation for how multiplex ecological networks are structured under different ecological conditions.
Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates
Authors: Yee Sook Wah , Ferrández-Peral Luis , Alentorn Pol , Fontsere Claudia , Ceylan Merve , Koleske Megan L. , Handin Niklas , Artegoitia Virginia M. , Lara Giovanni , Chien Huan-Chieh , Zhou Xujia , Dainat Jacques , Zalevsky Arthur , Sali Andrej , Brand Colin M. , Capra John A. , Artursson Per , Newman John W. , Marques-Bonet Tomas , Giacomini Kathleen M.
Published: August 2023

SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.
THE NEUROPROTECTIVE ROLE OF NICOTINE AND ASCORBIC ACID ON ALUMINIUM CHLORIDE (ALCL3)-INDUCED NEUROTOXICITY IN THE HIPPOCAMPUS OF ADULT MALE WISTER RATS
Authors: Akanbi Kareemat Adebanke , Ilesanmi Aramide
Published: August 2023

Objectives

Free radicals induced oxidative stress has been disrupted in the neurological functionality of the hippocampus in relation to aluminium chloride induced neurotoxicity. Ascorbic acid was been used as an antioxidants to prevent the oxidative damage induced by aluminium chloride. Therefore this present study was conducted to evaluate the antioxidant role Ascorbic acid and nicotine against the neurodegenerative consequences associated with aluminium chloride.

Materials and method

Thirty five (35) adult male Wister rats weighing 130-150g per body weight was used for this study. The rats were randomly grouped into five groups (A, B, C, D, and E) with each group having seven animals. Animals in group A(control group) were fed only water ad libitum for 21 days; animals in group B were administered Aluminium Chloride only with 100mg/kgBW for 21 days; animals in group C were administered aluminium chloride for the first 21 days with 100mg/kgBW, after which nicotine of 14mg/kgBW was administered. Animals in group D was administered with aluminium chloride of 100mg/kgBW for the first 21days after which Ascorbic acid was administered with 100mg/kgBW for the next 21days. Animals in group E were administered with Aluminium chloride, received 100mg/kgBW of Alcl3for the first 21days then 14mg/kgBW Nicotine for 21days follow by administration of 100mg/kgBW of Ascorbic acid for the next 21days, concomitantly.

Results

Oxidative stress was observed from the degeneration the antioxidants (catalase, glutathione peroxidase, superoxide dismutase) in animals that were exposed to aluminium chloride. Histological examination showed that the hippocampus microarchitecture of animals exposed to aluminium chloride have a neurodegenerative changes characterized fragmentation, chromatolytic changes as well as some pyknotic changes in the purkinje and granule cell layers with a gross reduction in the cytoplasmic Nissl proteins. Administration of Ascorbic acid and nicotine was said to revert close to all the cytoarchitectural, biochemical, neurochemical, and immunohistochemical alterations induced by aluminium chloride neurotoxicity.

Conclusion

The results suggests that the administration of Ascorbic acid and nicotine may have caused a significant ameliorative effect against the neurotoxicity of aluminium chloride.
Modelled impact of Tiny Targets on the distribution and abundance of riverine tsetse
Authors: Vale Glyn A , Hargrove John W , Hope Andrew , Torr Steve J
Published: August 2023

Background

The insecticide-treated baits known as Tiny Targets are one of the cheapest means of controlling riverine species of tsetse flies, the vectors of the trypanosomes that cause sleeping sickness in humans. Models of the efficacy of these targets deployed near rivers are potentially useful in planning control campaigns and highlighting the principals involved.

Methods and principal findings

We produced a simple non-seasonal model of the births, deaths, mobility and aging of tsetse, and we programmed it to simulate the impact of seven years of target use against the tsetse,Glossina fuscipes fuscipes, in the riverine habitats of NW Uganda. The model’s outputs matched reality in showing that: (i) good control can be achieved despite the degradation of targets, (ii) local elimination of tsetse is impossible if invasion sources are not tackled, and (iii) with invasion and target degradation it is difficult to detect any effect of control on the age structure of the tsetse population.

Conclusions

Despite its simplifications, the model can assist planning and teaching, but allowance should be made for any complications due to seasonality and management challenges associated with greater scale.

Author summary

We produced a simple model of the population dynamics of the riverine tsetse fly,Glossina fuscipes fuscipes, to simulate the field results of controlling this insect for seven years using Tiny Targets, i.e., artificial insecticide-treated baits, in NW Uganda. The model is potentially useful in planning tsetse control and illustrating the principles involved. Thus, it confirmed that targets can give good control, even if the targets degrade so much that they need replacement after six months. It showed that reinvasion can limit severely the efficacy of control campaigns and mask the changes in the age structure of the population. We stress the need to consider the possibility of seasonal complications and problems of managing large scale operations.
Assessing the global prevalence of wild birds in trade
Authors: Donald Paul F. , Fernando Eresha , Brown Lauren , Busana Michela , Butchart Stuart H.M. , Chng Serene , de la Colina Alicia , Ferreira Juliana Machado , Jain Anuj , Jones Victoria R. , Lapido Rocio , Malsch Kelly , McDougall Amy , Muccio Colum , Nguyen Dao , Outhwaite Willow , Petrovan Silviu O. , Stafford Ciara , Sutherland William J. , Tallowin Oliver , Safford Roger
Published: August 2023

Trade represents a significant threat to many wild species and is often clandestine and poorly monitored. Information on which species are most prevalent in trade, and potentially threatened by it, therefore remains fragmentary. We mobilised seven global datasets on birds in trade to identify the species or groups of species that might be at particular risk. These datasets sample different parts of the broad trade spectrum but we nevertheless find a statistically strong congruence between them in which species are recorded in trade. Furthermore, the frequency with which species are recorded within datasets is positively correlated with their occurrence across datasets. This allows us to propose a trade prevalence score that can be applied to all bird species globally. This score discriminates well between species known from semi-independent assessments to be heavily or unsustainably traded and all other species. Globally, 45.1% of all bird species, and 36.7% of globally threatened bird species, were recorded in at least one of the seven datasets. Species listed in Appendices I or II of CITES, species with large geographical distributions and non-songbirds had higher trade prevalence scores. Speciose orders with high mean trade prevalence scores include the Falconiformes, Psittaciformes, Accipitriformes, Anseriformes, Bucerotiformes and Strigiformes. Despite their low mean prevalence score, Passeriformes accounted for the highest overall number of traded species of any order but had low representation in CITES Appendices. Geographical hotspots where large numbers of traded species co-occur differed between songbirds (South-East Asia and Eurasia) and non-songbirds (central South America, sub-Saharan Africa and India). This first attempt to quantify and map the relative prevalence in trade of all bird species globally can be used to identify species and groups of species which may be at particular risk of harm from trade and can inform conservation and policy interventions to reduce its adverse impacts.

Article impact statement

The first metric to estimate the prevalence in trade of all the world’s bird species is presented.
Innate sleep apnoea in spontaneously hypertensive rats is associated with microvascular rarefaction and neuronal loss in the preBötzinger Complex
Authors: Roberts Reno , Huckstepp Robert T. R.
Published: August 2023

Sleep apnoea is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. Sleep apnoea holds a bidirectional relationship with hypertension which drives atherosclerosis, ultimately culminating in vascular dementia. To enable a better understanding of this sequalae of events, we investigated innate sleep apnoea in spontaneously hypertensive rats (SHRs), which have a range of cardiovascular disorders. SHRs displayed a higher degree of sleep disordered breathing, which emanates from poor vascular health leading to a loss of preBötC neurons. This model also displays small vessel white matter disease, a form of vascular dementia, likely associated with neuroinflammation in the hippocampus and the related deficits in both long- and short-term memory. Therefore, hypertension induces sleep apnoea through vascular damage in the respiratory column, culminating in neuronal loss in the inspiratory oscillator. This induction of sleep apnoea which in turn will independently exacerbate hypertension and neural inflammation, increasing the rate of vascular dementia.
Mapping of Facial and Vocal Processing in Common Marmosets with ultra-high field fMRI
Authors: Dureux Audrey , Zanini Alessandro , Everling Stefan
Published: August 2023

Primate communication relies on multimodal cues, such as vision and audition, to facilitate the exchange of intentions, enable social interactions, avoid predators, and foster group cohesion during daily activities. Understanding the integration of facial and vocal signals is pivotal to comprehend social interaction. In this study, we acquired whole-brain ultra-high field (9.4T) fMRI data from awake marmosets (Callithrix jacchus) to explore brain responses to unimodal and combined facial and vocal stimuli. Our findings reveal that the multisensory condition not only intensified activations in the occipito-temporal ‘face patches’ and auditory ‘voice patches’ but also engaged a more extensive network that included additional parietal, prefrontal and cingulate areas, compared to the summed responses of the unimodal conditions. By uncovering the neural network underlying multisensory audiovisual integration in marmosets, this study highlights the efficiency and adaptability of the marmoset brain in processing facial and vocal social signals, providing significant insights into primate social communication.
Evolutionary formation of a humande novoopen reading frame from a non-primate non-coding genomic region that proceeds via biased random mutations
Authors: Delihas Nicholas
Published: August 2023

Two open reading frames (ORFs) of evolutionary interest stem from the human geneSMIM45. An investigation shows that one consists of an ultra-conserved 68 amino acid (aa) sequence that dates back to the amphibians, ∼192 MYA. In contrast, the other, an ORF of 107 aa develops slowly during primate evolution. An early developmental stage of the 107 aa ORF has been detected in non-primate genomes. In the mouse, it consists of a small sequence homologous to a segment of the human 107 aa ORF, the aa sequence SGLE*VTVYGGGVQKGKT. This suggests the evolutionary root of the 107 aa ORF dates to an ancestor of the mouse; root species have been proposed based on the presence or absence of the early developmental sequence in ancestors. The formation of the complete 107 aa ORF during primate evolution is also outlined. Found is growth of the 107 aa ORF by biased random mutations. The delineation of mutations occurring during development of the 107 aa ORF can provide a model for the evolutionary formation of ORFs ofde novoprotein genes.
Structural Remodeling of Fungal Cell Wall Promotes Resistance to Echinocandins
Authors: Widanage Malitha C. Dickwella , Gautam Isha , Sarkar Daipayan , Mentink-Vigier Frederic , Vermaas Josh V. , Fontaine Thierry , Latgé Jean-Paul , Wang Ping , Wang Tuo
Published: August 2023

The insufficient efficacy of existing antifungal drugs and the rise in resistance necessitate the development of new therapeutic agents with novel functional mechanisms1,2. Echinocandins are an important class of antifungals that inhibit β-1,3-glucan biosynthesis to interfere with cell wall structure and function3,4. However, their efficacy is limited by the fungistatic activity againstAspergillusspecies and the trailing effect during clinical application. Here, we describe how echinocandins remodel the supramolecular assembly of carbohydrate polymers in the fungal cell wall in an unexpected manner, possibly resulting in a subsequent inhibition of the activity of these drugs. Solid-state nuclear magnetic resonance (ssNMR) analysis of intact cells from the human pathogenic fungusAspergillus fumigatusshowed that the loss of β-1,3-glucan and the increase of chitin content led to a decrease in cell wall mobility and water-permeability, thus enhancing resistance to environmental stresses. Chitosan and α-1,3-glucan were found to be important buffering molecules whose physical association with chitin maintained the wall integrity. These new findings revealed the difficult-to-understand structural principles governing fungal pathogens’ response to echinocandins and opened new avenues for designing novel antifungal agents with improved efficacy.
Visualizing a two-state conformational ensemble in stem-loop 3 of the transcriptional regulator 7SK RNA
Authors: Camara Momodou B. , Lange Bret , Yesselman Joseph D. , Eichhorn Catherine D.
Published: August 2023

Structural plasticity is integral to RNA function; however, there are currently few methods to quantitatively resolve RNAs that have multiple structural states. NMR spectroscopy is a powerful approach for resolving conformational ensembles but is size-limited. Chemical probing is well-suited for large RNAs but provides limited structural and no kinetics information. Here, we integrate the two approaches to visualize a two-state conformational ensemble for the central stem-loop 3 (SL3) of 7SK RNA, a critical element for 7SK RNA function in transcription regulation. We find that the SL3 distal end exchanges between two equally populated yet structurally distinct states in both isolated SL3 constructs and full-length 7SK RNA. We rationally designed constructs that lock SL3 into a single state and demonstrate that both chemical probing and NMR data fit to a linear combination of the two states. Comparison of vertebrate 7SK RNA sequences shows conservation of both states, suggesting functional importance. These results provide new insights into 7SK RNA structural dynamics and demonstrate the utility of integrating chemical probing with NMR spectroscopy to gain quantitative insights into RNA conformational ensembles.
Local interneurons in the murine visual thalamus have diverse receptive fields and can provide feature selective inhibition to relay cells
Authors: Gorin Alexis S. , Miao Yizhan , Ahn Seohee , Suresh Vandana , Su Yinan , Ciftcioglu Ulas M. , Sommer Friedrich T. , Hirsch Judith A.
Published: August 2023

By influencing the type and quality of information that relay cells transmit, local interneurons in thalamus have a powerful impact on cortex. To define the sensory features that these inhibitory neurons encode, we mapped receptive fields of optogenetically identified cells in the murine dorsolateral geniculate nucleus. Although few in number, local interneurons had diverse types of receptive fields, like their counterpart relay cells. This result differs markedly from visual cortex, where inhibitory cells are typically less selective than excitatory cells. To explore how thalamic interneurons might converge on relay cells, we took a computational approach. Using an evolutionary algorithm to search through a library of interneuron models generated from our results, we show that aggregated output from different groups of local interneurons can simulate the inhibitory component of the relay cell’s receptive field. Thus, our work provides proof-of-concept that groups of diverse interneurons can supply feature-specific inhibition to relay cells.
A leaky gut dysregulates gene networks in the brain associated with immune activation, oxidative stress, and myelination in a mouse model of colitis
Authors: Boles Jake Sondag , Krueger Maeve E. , Jernigan Janna E. , Cole Cassandra L. , Neighbarger Noelle K. , Huarte Oihane Uriarte , Tansey Malú Gámez
Published: August 2023

The gut and brain are increasingly linked in human disease, with neuropsychiatric conditions classically attributed to the brain showing an involvement of the intestine and inflammatory bowel diseases (IBDs) displaying an ever-expanding list of neurological comorbidities. To identify molecular systems that underpin this gut-brain connection and thus discover therapeutic targets, experimental models of gut dysfunction must be evaluated for brain effects. In the present study, we examine disturbances along the gut-brain axis in a widely used murine model of colitis, the dextran sodium sulfate (DSS) model, using high-throughput transcriptomics and an unbiased network analysis strategy coupled with standard biochemical outcome measures to achieve a comprehensive approach to identify key disease processes in both colon and brain. We examine the reproducibility of colitis induction with this model and its resulting genetic programs during different phases of disease, finding that DSS-induced colitis is largely reproducible with a few site-specific molecular features. We focus on the circulating immune system as the intermediary between the gut and brain, which exhibits an activation of pro-inflammatory innate immunity during colitis. Our unbiased transcriptomics analysis provides supporting evidence for immune activation in the brain during colitis, suggests that myelination may be a process vulnerable to increased intestinal permeability, and identifies a possible role for oxidative stress and brain oxygenation. Overall, we provide a comprehensive evaluation of multiple systems in a prevalent experimental model of intestinal permeability, which will inform future studies using this model and others, assist in the identification of druggable targets in the gut-brain axis, and contribute to our understanding of the concomitance of intestinal and neuropsychiatric dysfunction.
Effect of Aqueous Garlic Extract on Hyperlipidaemia in Rats: A Randomised Case-Control Study
Authors: Sankarl Gamel , Akyeampong Enoch , Sarhene Micheal , Anai Rexford Kporvie
Published: August 2023

This study aimed to determine the effect of garlic extract on hyperlipidemia in rats. This was a randomised case-control study in 42 rats comprising seven groups with six animals per group. Group I consisted of rats fed with 100% Normal rat chow serving as control, Group II: Butter diet, Group III: Butter diet + Atorvastatin, Group IV: Butter diet + Garlic extract, Group V: rats injected with dexamethasone, Group VI: Dexamethasone + Atorvastatin, Group VII: Dexamethasone + Garlic extract. Blood was collected from all the animals and the separated serum was subjected to the estimations of lipoproteins levels and coronary risk. There was a significant increase in the concentration of TC in the butter control group (BCG) compared to the concentration of the LDL-C (p=0.028) of the normal control group (NCG). The concentration of TG was significantly higher in DCG when compared with TG concentration in NCG (p<0.0001) and BCG (p=0.0002). Total Cholesterol level was significantly higher in BCG when compared to BGG (p<0.0001), BAG (p=0.0001) and NCG (p=0.023) which typifies hypercholesterolemia. Hyperlipidemia was induced by the long-term high-fat diet but lipid levels were reduced after the administration of aqueous garlic extract and atorvastatin.
The aryl hydrocarbon receptor in β-cells mediates the effects of TCDD on glucose homeostasis in mice
Authors: Hoyeck Myriam P , Ching Ma. Enrica Angela , Basu Lahari , Van Allen Kyle , Palaniyandi Jana , Perera Ineli , Poleo-Giorgani Emilia , Hanson Antonio A , Bruin Jennifer E
Published: August 2023

Chronic exposure to persistent organic pollutants (POPs) is associated with increased incidence of type 2 diabetes, hyperglycemia, and poor insulin secretion in humans. Dioxins and dioxin-like compounds are a broad class of POPs that exert cellular toxicity through activation of the aryl hydrocarbon receptor (AhR). We previously showed that a single high-dose injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, aka dioxin; 20 µg/kg)in vivoreduced fasting and glucose-stimulated plasma insulin levels for up to 6 weeks in male and female mice. TCDD-exposed male mice were also modestly hypoglycemic and had increased insulin sensitivity, whereas TCDD-exposed females were transiently glucose intolerant; whether these effects are driven by AhR activation in β-cells requires investigation. Here we exposed female and male β-cell specific AhR knockout (βAhrKO) mice and littermate Ins1-Cre genotype controls (βAhrWT) to a single high dose of 20 µg/kg TCDD and tracked the mice for 6 weeks. We found that deleting AhR from β-cells increased insulin secretionex vivoin female mouse islets and promoted modest weight gain in male mice under baseline conditions. Importantly, high-dose TCDD exposure impaired glucose homeostasis and β-cell function in βAhrWTmice, but these phenotypes were largely abolished in TCDD-exposed βAhrKOmice. Our study demonstrates that AhR signaling in β-cell is important for regulating baseline β-cell function in female mice and energy homeostasis in male mice. We also show that β-cell AhR signaling largely mediates the effects of TCDD on glucose homeostasis in both female and male mice, suggesting that the effects of TCDD on β-cell function/health are driving metabolic phenotypes in peripheral tissues.
Assessing Inter-Individual Genetic Variability in Peach Sugar Metabolism through Reliable Parameter Estimation of a Kinetic Model
Authors: Kanso Hussein , Memah Mohamed-Mahmoud , Baldazzi Valentina , Quilot-Turion Bénédicte , Baey Charlotte
Published: August 2023

Integrating genetic information into dynamical models is key to understand variations among genotypes and improve crop performances face to current agronomic and ecological constraints. A first and necessary step in building gene-to-phenotype models is the calibration of a large number of genotypes. We compared here two different strategies for the calibration of an Ordinary Differential Equations (ODE) kinetic model simulating the accumulation of different sugars during peach fruit development. First, the model was calibrated for each genotype independently using a Genotype-Based (GB) strategy. Two formulations of the problem have been tested, either as a Single-Objective Optimization (GBS) problem or as a Multi-Objective Optimization (GBM) problem. Second, the model was calibrated for all genotypes simultaneously using a Population-Based (PB) strategy. The two strategies were first applied to a set of simulated data and then to a real dataset derived from an interspecific population of 106 peach genotypes. Results showed that the GB strategy allowed for a high goodness of fit for most genotypes, especially in the GBS formulation. However, the estimated parameters suffered from a lack of practical identifiability as independent repetitions of the estimation algorithm did not always converge to the same value for most genotypes. The PB calibration strategy overcame this issue showing a good identifiability of the population parameter values, a goodness of fit comparable to the one obtained with the GB strategy and a good characterisation of parameter variations within the progeny, which is a key to assess the inter-individual genetic variability. These results are an important step towards the development of reliable gene-to-phenotype models.
VelosGT: Edge-Computing for Human Variant Analysis
Authors: Flygare Josh , Born Alex
Published: August 2023

VelosGTis a MacOS application to analyze human genomes for genetic mutation and rare disease. It consumes raw read files (fasta/fastq) and returns annotated, functionally prioritized variants in a single step, while significantly out-performing standard pipelines. VelosGTingests short-read data in all common formats (fastq, fasta, fastq.gz, and fasta.gz) as well as paired data. It can perform analyses on single genomes (proband) or trios. The underlying algorithms have been optimized to the extent that it can run directly on a personal computer, with no additional hardware required. This increases convenience and speed because no large uploads or downloads are required. All discovered variants are immediately displayed and searchable within the app. On an average*Mac laptop, VelosGTwill return the results of a high-coverage 30GB read file in under an hour, and a 5GB read file in ten minutes or less. Trios can be computed using the completed child-parent analyses in a few minutes.
Predicting species distributions in the open ocean with convolutional neural networks
Authors: Morand Gaétan , Joly Alexis , Rouyer Tristan , Lorieul Titouan , Barde Julien
Published: August 2023

As biodiversity plummets due to anthropogenic disturbances, the conservation of oceanic species is made harder by limited knowledge of their distributions and migrations. Indeed, tracking species distributions in the open ocean is particularly challenging due to the scarcity of observations and the complex and variable nature of the ocean system. In this study, we propose a new method that leverages deep learning, specifically convolutional neural networks (CNNs), to capture spatial features of environmental variables. This novelty eliminates the need to predefine these features before modelling and creates opportunities to discover unexpected correlations. Our aim is to present the results of the first trial of this method in the open ocean, discuss limitations and provide feedback for future improvements or adjustments.

In this case study, we considered 38 taxa comprising pelagic fishes, elasmobranchs, marine mammals, marine turtles and birds. We trained a model to predict probabilities from the environmental conditions at any specific point in space and time, using species occurrence data from the Global Biodiversity Information Facility (GBIF) and environmental data from various sources. These variables included sea surface temperature, chlorophyll concentration, salinity and fifteen others.

During the testing phase, the model was applied to environmental data at locations where species occurrences were recorded. The classifier accurately predicted the observed taxon as the most likely taxon in 69% of cases and included the observed taxon among the top three most likely predictions in 89% of cases. These findings show the adequacy of deep learning for species distribution modelling in the open ocean.

Additionally, this purely correlative model was then analysed with explicability tools to understand which variables had an influence on the model’s predictions. While variable importance was species-dependent, we identified finite-size Lyapunov exponents (FSLEs), sea surface temperature, pH and salinity as the most influential variables, in that order. These insights can prove valuable for future species-specific ecology studies.
Narrow, but not broad, spectrum resistance and disease reshape phyllosphere bacterial communities
Authors: Bigott Adam F. , Hutton Samuel F. , Vallad Gary , Lankau Rick , Barak Jeri
Published: August 2023

The phyllosphere is a restrictive environment for microbes, resulting in microbial communities typically dominated by select taxa with specific adaptations for success in this niche. However, biotic stress, especially from plant disease, could disrupt this environment in ways that alter the resulting phyllosphere community, with potential consequences for plant and human health. Additionally, plant disease resistance, through both broad (pattern-triggered immunity) and specific (effector-triggered immunity) resistance, could affect non-pathogenic communities directly or indirectly via effects on disease progression. Here, we tested how transgenic ETI and PTI resistance genes affected the phyllosphere communities of tomato plants in the face of infection byXanthomonas perforansand the resulting bacterial spot disease. We found that the expression of theBs2transgene (ETI) had major effects on phyllosphere communities, while the EFR (PTI) transgene did not. The effect of theBs2resistance gene could be largely attributed to the change in disease symptoms. Diseased leaves harbored reduced bacterial diversity and reductions in major phyllosphere inhabitants (e.g.SphinogmonasandMethylobacterium), while a limited number of bacterial genera showed increased relative abundance on diseased leaves. These results suggest that phyllosphere communities are sensitive to the direct and indirect effects of plant disease and resistance, and the consequences of these shifts for plant and human health deserve further investigation.
Is thermal aptitude a pivotal driver in the establishment of recentPuccinia striiformisf. sp.triticilineages in Europe?
Authors: Meyer Kevin JG , Leconte Marc , Vidal Tiphaine , Goyeau Henriette , Suffert Frédéric
Published: August 2023

In the context of global warming, it is crucial to focus on the effects of temperature on the emergence of new lineages of endemic pathogen species, such asPuccinia striiformisf. sp.tritici(Pst) the causal agent of yellow rust on wheat. We characterized the thermal aptitude of representative isolates from the most recent common EuropeanPstraces. We assessed two key aggressiveness components – infection efficiency (IE) and latency period (LP) – under warm and cold thermal regimes, comparing 10Pstisolates collected from 2010 to 2020 with three “old” reference isolates. The significant differences observed suggest that this species has the potential to adapt to temperature changes, but that such adaptation probably did not drive the establishment of the most recent races and the dominant ‘Warrior’ and ‘Warrior(-)’ they succeeded. These races display “generalist” behavior with respect to temperature, with ‘Warrior(-)’ showing no more aggressiveness than the races replaced since the 1990s. The differences in competitive success between emergingPstlineages are probably due to the deployment of resistance genes in wheat and the advantages of new forms of virulence emerging independently of thermal adaptability. However, variations in thermal adaptability for both aggressiveness components suggested an impact of geographic origin within the ‘Warrior’ and ‘Warrior(-)’ races, as previously reported for the “old” reference isolates. Furthermore, the independence of thermal adaptability established for IE and LP implies that the effects of temperature may depend on the stage of the epidemic (early or late), potentially modifying seasonal dynamics.
Predicting resprouting ofPlatanus×hispanicafollowing branch pruning by means of machine learning
Authors: Shu Qiguan , Yazdi Hadi , Rötzer Thomas , Ludwig Ferdinand
Published: August 2023

Resprouting is a crucial survival strategy following the loss of branches, being it by natural events or artificially by pruning. The prediction of resprouting patterns on a physiological basis is a highly complex approach. However, trained gardeners try to predict a tree’s resprouting after pruning purely based on their empirical knowledge and a visual check of the tree’s geometry. In this study, we explore in how far such predictions can also be made by algorithms, especially using machine learning.

Table-topped annually prunedPlatanus×hispanicatrees at a nursery were documented with terrestrial LiDAR scanners in two consecutive years. Topological structures for these trees were abstracted from point clouds by cylinder fitting. Then, new shoots and trimmed branches were labelled on corresponding cylinders. Binary and multiclass classification models were tested for predicting the location and number of new sprouts.

The accuracy for predicting whether having or not new shoots on each cylinder reaches 90.8% with the LGBMClassifier, the balanced accuracy is 80.3%. The accuracy for predicting the exact numbers of new shoots with GaussianNB model is 82.1% but its balanced accuracy is reduced to 42.9%.

The results were validated with a separate evaluation dataset. It proves a feasibility in predicting resprouting patterns after pruning using this approach. Different tree species, tree forms, and other variables should be addressed in further research.
Glutamate helps unmask the differences in driving forces for phase separation versus clustering of FET family proteins in sub-saturated solutions
Authors: Kar Mrityunjoy , Vogel Laura T. , Chauhan Gaurav , Ausserwöger Hannes , Welsh Timothy J. , Kamath Anjana R. , Knowles Tuomas P. J. , Hyman Anthony A. , Seidel Claus A. M. , Pappu Rohit V.
Published: August 2023

Multivalent proteins undergo coupled segregative and associative phase transitions. Phase separation, a segregative transition, is driven by macromolecular solubility, and this leads to coexisting phases above system-specific saturation concentrations. Percolation is a continuous transition that is driven by multivalent associations among cohesive motifs. Contributions from percolation are highlighted by the formation of heterogeneous distributions of clusters in sub-saturated solutions, as was recently reported for Fused in sarcoma (FUS) and FET family proteins. Here, we show that clustering and phase separation are defined by a separation of length- and energy-scales. This is unmasked when glutamate is the primary solution anion. Glutamate is preferentially excluded from protein sites, and this enhances molecular associations. Differences between glutamate and chloride are manifest at ultra-low protein concentrations. These differences are amplified as concentrations increase, and they saturate as the micron-scale is approached. Therefore, condensate formation in supersaturated solutions and clustering in sub-saturated are governed by distinct energy and length scales. Glutamate, unlike chloride, is the dominant intracellular anion, and the separation of scales, which is masked in chloride, is unmasked in glutamate. Our work highlights how components of cellular milieus and sequence-encoded interactions contribute to amplifying distinct contributions from associative versus segregative phase transitions.
Interkingdom interactions shape the fungal microbiome of mosquitoes
Authors: Hegde Shivanand , Khanipov Kamil , Hornett Emily A , Nilyanimit Pornjarim , Pimenova Maria , Saldaña Miguel A. , de Becker Charissa , Golovko Georgiy , Hughes Grant L.
Published: August 2023

The mosquito microbiome is an important modulator of vector competence and vectoral capacity. Unlike the extensively studied bacterial microbiome, fungal communities in the mosquito microbiome (mycobiome) remain largely unexplored. To work towards getting an improved understanding of the fungi associated with mosquitoes, we sequenced the mycobiome of three field-collected and laboratory-reared mosquito species (Aedes albopictus, Aedes aegypti,andCulex quinquefasciatus). Our analysis showed both environment and host species were contributing to the diversity of the fungal microbiome of mosquitoes. When comparing species,Ae. albopictuspossessed a higher number of diverse fungal taxa thanCx. quinquefasciatus,while strikingly less than 1% of reads fromAe. aegyptisamples were fungal. Fungal reads fromAe. aegyptiwere <1% even after inhibiting host amplification using a PNA blocker, indicating that this species lacked a significant fungal microbiome that was amplified using this sequencing approach. Using a mono-association mosquito infection model, we confirmed that mosquito-derived fungal isolates colonize and forAedesmosquitoes, support growth and development at comparable rates to their bacterial counterparts. Strikingly, native bacterial taxa isolated from mosquitoes impeded the colonization of symbiotic fungi inAe. aegyptisuggesting interkingdom interactions shape fungal microbiome communities. Collectively, this study adds to our understanding of the fungal microbiome of different mosquito species, that these fungal microbes support growth and development, and highlights that microbial interactions underpin fungal colonization of these medically relevent species.
Synergistic control of chloroplast biogenesis byMYB-relatedandGolden2-liketranscription factors
Authors: Frangedakis Eftychios , Yelina Nataliya E. , Billakurthi Kumari , Schreier Tina , Dickinson Patrick J. , Tomaselli Marta , Haseloff Jim , Hibberd Julian M.
Published: August 2023

Chloroplast biogenesis is dependent on master regulators from the GOLDEN2-LIKE (GLK) family of transcription factors, butglkmutants contain residual chlorophyll and therefore other proteins must also be involved. Here we identify MYB-related transcription factors as regulators of chloroplast biogenesis in the liverwortMarchantia polymorphaand angiospermArabidopsis thaliana. In both species, double mutant alleles in MYB-Related genes show very limited chloroplast development, and photosynthesis gene expression is perturbed to a greater extent than in mutants of GLK. InM. polymorphaMYB-related genes act upstream of GLK, while inA. thalianathis relationship has been rewired. In both species, genes encoding enzymes of chlorophyll biosynthesis are controlled by MYB-related and GLK proteins whilst those allowing CO2fixation, photorespiration and photosystem assembly and repair require the MYB-related proteins. Thus,MYB-relatedand GLK genes have overlapping as well as distinct targets. We conclude that together MYB-related and GLK transcription factors orchestrate chloroplast development in land plants.
Ton Motor Conformational Switch and Peptidoglycan Role in Bacterial Nutrient Uptake
Authors: Zinke Maximilian , Lejeune Maylis , Mechaly Ariel , Bardiaux Benjamin , Boneca Ivo Gomperts , Delepelaire Philippe , Izadi-Pruneyre Nadia
Published: August 2023

Active nutrient uptake is fundamental for survival and pathogenicity of Gram-negative bacteria, which operate a multi-protein Ton system to transport essential nutrients like metals and vitamins. This system harnesses the proton motive force at the inner membrane to energize the import through the outer membrane, but the mechanism of energy transfer remains enigmatic. Here, we study the periplasmic domain of ExbD, a crucial component of the proton channel of the Ton system. We show that this domain is a dynamic dimer switching between two conformations representing the proton channel’s open and closed states. Byin vivophenotypic assays we demonstrate that this conformational switch is essential for the nutrient uptake by bacteria. The open state of ExbD triggers a disorder to order transition of TonB, enabling TonB to supply energy to the nutrient transporter. We also reveal the anchoring role of the peptidoglycan layer in this mechanism. Herein, we propose a mechanistic model for the Ton system, emphasizing ExbD duality and the pivotal catalytic role of peptidoglycan. Sequence analysis suggests that this mechanism is conserved in other systems energizing gliding motility and membrane integrity. Our study fills important gaps in understanding bacterial motor mechanism and proposes novel antibacterial strategies.
Synergistic effects of inhibitors targeting PI3K and Aurora Kinase A in preclinical inflammatory breast cancer models
Authors: Al Ali Nadia , Kment Jacob , Young Stephanie , Craig Andrew W.B.
Published: August 2023

Background

Inflammatory breast cancer (IBC) is an aggressive clinical subtype of breast cancer often diagnosed in young women. Lymph node and distant metastases are frequently detected at diagnosis of IBC, and improvements in systemic therapies are needed. For IBC that lack hormone or HER2 expression, no targeted therapies are available. Since the phosphatidyl inositol 3’ kinase (PI3K) pathway is frequently deregulated in IBC, some studies have tested the pan PI3K inhibitor Buparlisib (BKM120). Although the SUM149 IBC cell line was resistant to Buparlisib, a functional genomic screen showed that silencing of Aurora kinase A (AURKA) sensitized cells to killing by Buparlisib. In this study, we tested whether combination treatments of PI3K and AURKA inhibitors act synergistically to kill IBC cells and tumors.

Methods

SUM149 cells were treated with increasing doses of PI3K inhibitor Buparlisib (BKM120) and AURKA inhibitor Alisertib as monotherapies or combination therapies. Effects on target pathways, cytotoxicity, cell cycle, soft agar colony growth and cell migration were analyzed. The individual and combined treatments were also tested in a mammary orthotopic SUM149 tumor xenograft model to measure effects on tumor growth and metastasis

Results

The SUM149 IBC cell line treated with Buparlisib showed reduced PI3K/AKT activation but no significant skewing of cell cycle progression. Parallel studies of Alisertib treatment showed that AURKA inhibition led to a significant block in G2/M transition in SUM149 cells. In cytotoxicity assays, Buparlisib and Alisertib combination treatments were highly synergistic compared to monotherapy controls. Evidence of synergy between Buparlisib and Alisertib also extended to soft agar colony growth and wound healing motility in SUM149 cells. The combination of Buparlisib and Alisertib also reduced IBC tumor growth in mammary orthotopic xenograft assays and reduced spontaneous metastases development in lung tissue.

Conclusions

Although SUM149 IBC cells were relatively resistant to killing by the PI3K inhibitor Buparlisib, our study showed that co-targeting the mitotic kinase AURKA with Alisertib synergized to limit IBC cell growth and motility, as well as IBC tumor growth and metastasis.
Ligand-DisplayingE. coliCells and Minicells for Programmable Delivery of Toxic Payloads via Type IV Secretion Systems
Authors: Li Yang Grace , Kishida Kouhei , Ogawa-Kishida Natsumi , Christie Peter J.
Published: August 2023

Bacterial type IV secretion systems (T4SSs) are highly versatile macromolecular translocators and offer great potential for deployment as delivery systems for therapeutic intervention. One major T4SS subfamily, the conjugation machines, are well-adapted for delivery of DNA cargoes of interest to other bacteria or eukaryotic cells, but generally exhibit modest transfer frequencies and lack specificity for target cells. Here, we tested the efficacy of a surface-displayed nanobody/antigen (Nb/Ag) pairing system to enhance the conjugative transfer of IncN (pKM101), IncF (F/pOX38), or IncP (RP4) plasmids, or of mobilizable plasmids including those encoding CRISPR/Cas9 systems (pCrispr), to targeted recipient cells.Escherichia colidonors displaying Nb’s transferred plasmids toE. coliandPseudomonas aeruginosarecipients displaying the cognate Ag’s at significantly higher frequencies than to recipients lacking Ag’s. Nb/Ag pairing functionally substituted for the surface adhesin activities of F-encoded TraN and pKM101-encoded Pep, although not conjugative pili or VirB5-like adhesins. Nb/Ag pairing further elevated the killing effects accompanying delivery of pCrispr plasmids toE. coliandP. aeruginosatransconjugants bearing CRISPR/Cas9 target sequences. Finally, we determined that anucleateE. coliminicells, which are clinically safer delivery vectors than intact cells, transferred self-transmissible and mobilizable plasmids toE. coliandP. aeruginosacells. Minicell-mediated mobilization of pCrispr plasmids toE. colirecipients elicited significant killing of transconjugants, although Nb/Ag pairing did not enhance conjugation frequencies or killing. Together, our findings establish the potential for deployment of bacteria or minicells as Programmed Delivery Systems (PDSs) for suppression of targeted bacterial species in infection settings.

IMPORTANCE

The rapid emergence of drug-resistant bacteria and current low rate of antibiotic discovery emphasize an urgent need for alternative antibacterial strategies. We engineeredEscherichia colito conjugatively transfer plasmids to specificE. coliandPseudomonas aeruginosarecipient cells through surface display of cognate nanobody/antigen (Nb/Ag) pairs. We further engineered mobilizable plasmids to carry CRISPR/Cas9 systems (pCrispr) for selective killing of recipient cells harboring CRISPR/Cas9 target sequences. In the assembled Programmed Delivery System (PDS), Nb-displayingE. colidonors with different conjugation systems and mobilizable pCrispr plasmids suppressed growth of Ag-displaying recipient cells to significantly greater extents than unpaired recipients. We also showed that anucleate minicells armed with conjugation machines and pCrispr plasmids were highly effective in killing ofE. colirecipients. Together, our findings suggest that bacteria or minicells armed with PDSs may prove highly effective as an adjunct or alternative to antibiotics for antimicrobial intervention.