bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tropical invertebrate community assembly processes are robust to a gradient of land use intensity
Authors: Granville Natasha R. , Barclay Maxwell V. L. , Boyle Michael J. W. , Chung Arthur Y. C. , Fayle Tom M. , Hah Huai En , Hardwick Jane L. , Kinneen Lois , Kitching Roger L. , Maunsell Sarah C. , Miller Jeremy A. , Sharp Adam C. , Stork Nigel E. , Wai Leona , Yusah Kalsum M. , Ewers Robert M. 
Published: February 2023

AbstractUnderstanding how community assembly processes drive biodiversity patterns is a central goal of community ecology. While it is generally accepted that ecological communities are assembled by both stochastic and deterministic processes, quantifying their relative importance remains challenging. Few studies have investigated how the relative importance of stochastic and deterministic community assembly processes vary among taxa and along gradients of habitat degradation. Using data on 1,645 arthropod species across seven taxonomic groups in Malaysian Borneo, we quantified the importance of ecological stochasticity and of a suite of community assembly processes across a gradient of logging intensity. The relationship between logging and community assembly varied depending on the specific combination of taxa and stochasticity metric used, but, in general, the processes that govern invertebrate community assembly were remarkably robust to changes in land use intensity.
Uncovering the consequences of batch effect associated missing values in omics data analysis
Authors: Hui Harvard Wai Hann , Goh Wilson Wen Bin 
Published: February 2023

ABSTRACTStatistical analyses in high-dimensional omics data are often hampered by the presence of batch effects (BEs) and missing values (MVs), but the interaction between these two issues is not well-studied nor understood. MVs may manifest as a BE when their proportions differ across batches. These are termed as Batch-Effect Associated Missing values (BEAMs). We hypothesized that BEAMs in data may introduce bias which can impede the performance of missing value imputation (MVI). To test this, we simulated data with two batches, then introduced over 100 iterations, either 20% and 40% MVs in each batch (BEAMs) or 30% in both (control). K-nearest neighbours (KNN) was then used to perform MVI, in a typical global approach (M1) and a supposed superior batch-sensitized approach (M2). BEs were then corrected using ComBat. The effectiveness of the MVI was evaluated by its imputation accuracy and true and false positive rates. Notably, when BEAMs existed, M2 was generally undesirable as the differing application of MV filtering in M1 and M2 strategies resulted in an overall coverage deficiency. Additionally, both M1 and M2 strategies suffered in the presence of BEAMs, highlighting the need for a novel approach to handle MVI in data with BEAMs.Author summaryData in high-throughput omics data are often combined from different sources (batches), which creates batch effects in the data. Missing values are a common occurrence in these data, and their proportions are assumed to be equal across batches. However, instances exist when these proportions vary between batches, such as one batch having more missing values than another, resulting in batch effect associated missing values. Missing values are often dealt with through missing value imputation, but whether the variation in missing value proportions across batches affects imputation outcomes is unknown. In this paper, we investigate the consequence of performing imputation when this issue persists. We simulated data with equal and unequal missing value proportions, then assessed the performance of k-nearest neighbours imputation by its imputation accuracy and downstream analysis outcomes. This revealed that unequal missing value proportions worsens imputation and establishes the need for smarter imputation strategies to handle this complication.
UTRGAN: Learning to Generate 5’ UTR Sequences for Optimized Translation Efficiency and Gene Expression
Authors: Barazandeh Sina , Ozden Furkan , Hincer Ahmet , Seker Urartu Ozgur Safak , Cicek A. Ercument 
Published: February 2023

AbstractThe 5’ untranslated region (5’ UTR) of mRNA is crucial for the molecule’s translatability and stability, making it essential for designing synthetic biological circuits for high and stable protein expression. Several UTR sequences are patented and widely used in laboratories. This paper presents UTRGAN, a Generative Adversarial Network (GAN)-based model for generating 5’ UTR sequences, coupled with an optimization procedure to ensure high expression for target gene sequences or high ribosome load and translation efficiency. The model generates sequences mimicking various properties of natural UTR sequences and optimizes them to achieve (i) up to 5-fold higher average expression on target genes, (ii) up to 2-fold higher mean ribosome load, and (iii) a 34-fold higher average translation efficiency compared to initial UTR sequences. UTRGAN-generated sequences also exhibit higher similarity to known regulatory motifs in regions such as internal ribosome entry sites, upstream open reading frames, G-quadruplexes, and Kozak and initiation start codon regions. In-vitro experiments show that the UTR sequences designed by UTRGAN result in a higher translation rate for the human TNF-αprotein compared to the human Beta Globin 5’ UTR, a UTR with high production capacity.
Trade-offs between immunity and competitive ability in fighting ant males
Authors: Metzler Sina , Kirchner Jessica , Grasse Anna V , Cremer Sylvia 
Published: February 2023

AbstractBackgroundFighting disease while fighting rivals exposes males to constraints and tradeoffs during male-male competition. We here tested how both the stage and intensity of infection with the fungal pathogenMetarhizium robertsiiinterfered with fighting success inCardiocondyla obscuriorant males. Males of this species have evolved long lifespans during which they can gain many matings with the young queens of the colony, if successful in male-male competition. Since male fights occur inside the colony, the outcome of male-male competition can further be biased by interference of the colony’s worker force.ResultsWe found that severe, but not yet mild, infection strongly impaired male fighting success. In late-stage infection, this could be attributed to worker aggression directed towards the infected rather than the healthy male and an already very high male morbidity even in the absence of fighting. Shortly after pathogen exposure, however, male mortality was particularly increased during combat. Since these males mounted a strong immune response, their reduced fighting success suggests a trade-off between immune investment and competitive ability already early in the infection. Even if the males themselves showed no difference in the number of attacks they raised against their healthy rivals across infection stages and levels, severely infected males were thus losing in male-male competition from an early stage of infection on.ConclusionsMales of the antC. obscuriorhave evolved high immune investment, triggering an effective immune response very fast after fungal exposure. This allows them to cope with mild pathogen exposures without cost to their success in male-male competition, and hence to gain multiple mating opportunities with the emerging virgin queens of the colony. Under severe infection, however, they are weak fighters and rarely survive a combat already at early infection when raising an immune response, as well as at progressed infection, when they are morbid and preferentially targeted by worker aggression. Workers thereby remove males that pose a future disease threat by biasing male-male competition. Our study thus revealed a novel social immunity mechanism how social insect workers protect the colony against disease risk.
Input-specific synaptic depression shapes temporal integration in mouse visual cortex
Authors: Li Jennifer Y. , Glickfeld Lindsey L. 
Published: February 2023

SummaryEfficient sensory processing requires the nervous system to adjust to ongoing features of the environment. In primary visual cortex (V1), neuronal activity strongly depends on recent stimulus history. Existing models can explain effects of prolonged stimulus presentation, but remain insufficient for explaining effects observed after shorter durations commonly encountered under natural conditions. We investigated the mechanisms driving adaptation in response to brief (100 ms) stimuli in L2/3 V1 neurons by performingin vivowhole-cell recordings to measure membrane potential and synaptic inputs. We find that rapid adaptation is generated by stimulus-specific suppression of excitatory and inhibitory synaptic inputs. Targeted optogenetic experiments reveal that these synaptic effects are due to input-specific short-term depression of transmission between layers 4 and 2/3. Thus, distinct mechanisms are engaged following brief and prolonged stimulus presentation and together enable flexible control of sensory encoding across a wide range of time scales.
Epitenon-derived cells comprise a distinct progenitor population that contributes to both tendon fibrosis and regeneration following acute injury
Authors: Nichols Anne E.C. , Wagner Nicholas W. , Ketonis Constantinos , Loiselle Alayna E. 
Published: February 2023

SUMMARYFlexor tendon injuries are common and heal poorly owing to both the deposition of function- limiting peritendinous scar tissue and insufficient healing of the tendon itself. Therapeutic options are limited due to a lack of understanding of the cell populations that contribute to these processes. Here, we identified a bi-fated progenitor cell population that originates from the epitenon and goes on to contribute to both peritendinous fibrosis and regenerative tendon healing following acute tendon injury. Using a combination of genetic lineage tracing and single cell RNA-sequencing (scRNA-seq), we profiled the behavior and contributions of each cell fate to the healing process in a spatio-temporal manner. Branched pseudotime trajectory analysis identified distinct transcription factors responsible for regulation of each fate. Finally, integrated scRNA-seq analysis of mouse healing with human peritendinous scar tissue revealed remarkable transcriptional similarity between mouse epitenon- derived cells and fibroblasts present in human peritendinous scar tissue, which was further validated by immunofluorescent staining for conserved markers. Combined, these results clearly identify the epitenon as the cellular origin of an important progenitor cell population that could be leveraged to improve tendon healing.
Association between the magnitude of melatonin circadian rhythm and personality in the threespine stickleback
Authors: Philippe Morgane Anita , Aubin-Horth Nadia 
Published: February 2023

ABSTRACTMelatonin secretion follows a circadian pattern with a maximum level at night in many species. However, in zebrafish (Danio rerio, a diurnal fish species) large inter-individual variations in daily rhythmicity of melatonin levels are present and are associated with variation in behaviour. Melatonin secretion rhythm of proactive individuals that are more active and exploratory are of larger amplitude compared to reactive individuals. In threespine sticklebacks (Gasterosteus aculeatus), a nocturnal species, inter-individual variability of behaviour is well described. However, inter-individual variation of melatonin rhythm and its association with variation in behaviour has never been measured in this species, which would allow to test if patterns found in zebrafish can be generalized for diurnal and nocturnal species. We measured large inter-individual variation in melatonin levels and found that activity was positively correlated with plasma melatonin concentration measured at night. We did not observe any significant difference in nigh-day variation in melatonin concentration between very active and less active groups. However, we found that individuals classified as reactive based on their propensity to wall-hugging, a measure of anxiety in fish, showed large variation in melatonin between night and day, while this rhythm was not seen in proactive individuals that frequently used the centre of the aquarium. Overall, our study suggests that melatonin may directly modulate specific behaviours in wild sticklebacks, and that while interindividual variation in melatonin rhythm may be widespread in fish, different patterns of association with behaviours should be expected.
Four-color fluorescence cross-correlation spectroscopy with one laser and one camera
Authors: Gandhi Sonali A. , Sanders Matthew A. , Granneman James G. , Kelly Christopher V. 
Published: February 2023

AbstractThe diffusion and reorganization of phospholipids and membrane-associated proteins are fundamental for cellular function. Fluorescence cross-correlation spectroscopy (FCCS) measures the diffusion and molecular interactions at nanomolar concentration in biological systems. We have developed a novel, economical method to simultaneously monitor diffusion and oligomerization with the use of super-continuum laser and spectral deconvolution from a single detector. Customizable excitation wavelengths were chosen from the wide-band source and spectral fitting of the emitted light revealed the interactions for up to four spectrally overlapping fluorophores simultaneously. This method was applied to perform four-color FCCS, as demonstrated with polystyrene nanoparticles, lipid vesicles, and membrane-bound molecules. Up to four individually customizable excitation channels were selected from the broad-spectrum fiber laser to excite the diffusers within a diffraction-limited spot. The fluorescence emission passed through a cleanup filter and a dispersive prism prior to being collected by a sCMOS or EMCCD camera with up to 10 kHz frame rates. The emission intensity versus time of each fluorophore was extracted through a linear least-square fitting of each camera frame and temporally correlated via custom software. Auto- and cross-correlation functions enabled the measurement of the diffusion rates and binding partners. We have measured the induced aggregation of nanobeads and lipid vesicles in solution upon increasing the buffer salinity. Because of the adaptability of investigating four fluorophores simultaneously with a cost-effective method, this technique will have wide application for examining complex homo- and heterooligomerization in model and living systems.
A hypothalamic node for the cyclical control of female sexual rejection
Authors: Gutierrez-Castellanos Nicolas , Husain Basma Fatima Anwar , Dias Inês C. , Nomoto Kensaku , Duarte Margarida A. , Ferreira Liliana , Lacoste Bertrand , Lima Susana Q. 
Published: February 2023

AbstractInternal state-dependent behavioral responses, such as the switch between rejection and acceptance of sexual advances depending on a female’s reproductive capacity, are fundamental to maintain social interactions and wellbeing. Here we characterize a dedicated circuit for the cyclical control of rejection behavior in the mouse, located in the anterior ventrolateral ventromedial hypothalamus (aVMHvl).In vivorecordings reveal that progesterone receptor expressing neurons of the aVMHvl (aVMHvlPr+) are active during rejection but silent when females accept the male. Moreover, we show that aVMHvlPr+neurons receive reduced excitatory to inhibitory synaptic input balance during the receptive phase of the reproductive cycle. Finally, optogenetic activation of aVMHvlPr+neurons in receptive females is sufficient to increase rejection behavior, disrupting the probability of copulation, without affecting other male-directed interactions. This population of aVMHvlPr+ neurons is thus a key neural substrate controlling female sexual behavior, providing an additional barrier to mating when fertilization is not possible.
Fundamentals of biofilm formation in soil: From functionalized self-assembled monolayers to rewilding
Authors: Hendiani Saghar , Hansen Mads Frederik , Kontopoulos Ioannis , Verma Taru , Pucetaite Milda , Burmølle Mette , Ramstedt Madeleine , Svenninggaard Sand Karina Krarup 
Published: February 2023

AbstractSurface energy and surface charges play crucial roles in bacterial adhesion and biofilm formation, however the mechanisms underlying the bacteria-surface interaction, particularly on the formation of soil biofilms, remain unclear. In spite of considering the spatiotemporal dynamics of biofilm formation on different soil surfaces, we compared the impact of four different substrates on bacterial attachment and biofilm formation. The substrates were constituted of gold layer covered by NH2+, CH3, COO-and OH-terminated self-assembled monolayers (SAMS). Two soil habitat bacteria with different Gram barriers,Bacillus subtilisandAcinetobacter baylyi, were grown with incubation times of 6-72 h on each type of surfaces. Bacterial attachment and biofilm formation was assessed using metabolic activity of the cells adhered to the surfaces. The spatial distribution of adhere bacteria was visualized by scanning electron microscopy and confocal laser scanning microscopy. We also investigated whether the surface impacts the biofilm matrix composition. A general view of our results suggests a major influence of the surface chemistry on bacterial potential to form biofilms. The hydrophobic or positively charged substrates attract bacteria while a lack of attachment and biofilm formation on hydrophilic and negatively charged surfaces. This work points out the potential of surface treatments in the environment where it is intended to either repel or attract bacteria.
Single cell DNA methylation ageing in mouse blood
Authors: Bonder Marc Jan , Clark Stephen J. , Krueger Felix , Luo Siyuan , de Sousa João Agostinho , Hashtroud Aida M. , Stubbs Thomas M. , Stark Anne-Katrien , Rulands Steffen , Stegle Oliver , Reik Wolf , von Meyenn Ferdinand 
Published: February 2023

ABSTRACTAgeing is the accumulation of changes and overall decline of the function of cells, organs and organisms over time. At the molecular and cellular level, the concept of biological age has been established and biomarkers of biological age have been identified, notably epigenetic DNA-methylation based clocks. With the emergence of single-cell DNA methylation profiling methods, the possibility to study biological age of individual cells has been proposed, and a first proof-of-concept study, based on limited single cell datasets mostly from early developmental origin, indicated the feasibility and relevance of this approach to better understand organismal changes and cellular ageing heterogeneity.Here we generated a large single-cell DNA methylation and matched transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages (10-101 weeks of age). We observed that the number of genes expressed increased at older ages, but gene specific changes were small. We next developed a robust single cell DNA methylation age predictor (scEpiAge), which can accurately predict age in a broad range of publicly available datasets, including very sparse data and it also predicts age in single cells. Interestingly, the DNA methylation age distribution is wider than technically expected in 19% of single cells, suggesting that epigenetic age heterogeneity is presentin vivoand may relate to functional differences between cells. In addition, we observe differences in epigenetic ageing between the major blood cell types. Our work provides a foundation for better single-cell and sparse data epigenetic age predictors and highlights the significance of cellular heterogeneity during ageing.Highlights- Model to estimate DNA methylation age in single cells- Large multi-omics dataset of single cells from murine blood- Epigenetic age deviations from chronological age are greater than technical expected from technical variability- Number of genes expressed increases with chronological and epigenetic age
Rewiring of the host cell metabolome and lipidome during lytic gammaherpesvirus infection is essential for infectious virus production
Authors: Clark Sarah A. , Vazquez Angie , Furiya Kelsey , Splattstoesser Madeleine K. , Bashmail Abdullah K. , Schwartz Haleigh , Russell Makaiya , Bhark Shun-Je , Moreno Osvaldo K. , McGovern Morgan , Owsley Eric R. , Nelson Timothy A. , Sanchez Erica , Delgado Tracie 
Published: February 2023

ABSTRACTOncogenic virus infections are estimated to cause ∼15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein Barr Virus (EBV) and Kaposi’s Sarcoma Herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors.IMPORTANCEViruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus induced cancers and infections in humans.