bluuebunny/crossref_metadata_2025 huggingface dataset:
EARLY ANALYSIS OF ENDOTHELIAL MARKERS TO PREDICT SEPSIS IN THE EMERGENCY DEPARTMENT
Authors: Galtung Noa , Stein Vanessa , Prpic Monika , Boyraz Burak , Ulke Jannis , Kurz Stephan , Dernedde Jens , Diehl-Wiesenecker Eva , Bauer Wolfgang , Kappert Kai
Published: October 2024

Background: Acute infections and sepsis are a leading cause of death. These patients are primarily encountered at the emergency department (ED), where early assessment for sepsis is necessary to improve outcome. In sepsis, the inflammatory response causes several characteristic pathophysiological changes, including a dysregulated and generalized activation of the endothelium. This study aimed to analyze endothelial markers released to the blood as diagnostic biomarkers for acute infection and sepsis in the ED, as smaller studies have previously shown promising results in other settings. Methods: Serum samples from n = 312 adult patients with suspected acute infections at presentation to the ED were utilized. Patients’ courses of disease and outcomes were assessed by clinical adjudication. E-selectin, P-selectin, ICAM-1, and VCAM-1 were measured by ELISAs. The accuracy of each marker for predicting bacterial infection, sepsis, and in-hospital mortality was evaluated. Results: For sepsis, E-selectin and ICAM-1 both showed an area under the receiver operating characteristic (AUROC) of 0.62, lower than procalcitonin with 0.77 (both P < 0.01) and lactate with 0.73 (P = 0.030 and 0.046, respectively), but similar to CRP with 0.60 (P = 0.758 and 0.876, respectively). For 28-day in-hospital mortality among patients with infection, ICAM-1 performed best with an AUROC of 0.75. Conclusions: Despite promising results in small studies and specific cohorts, particularly in intensive care units, this large-scale evaluation of four endothelial biomarkers highlights their limited diagnostic utility in a broader inclusion setup design at the earliest possible time point of evaluation.
Primary care follow-up improves outcomes in older adults following emergency general surgery admission
Authors: Guttman Matthew P. , Tillmann Bourke W. , Nathens Avery B. , Bronskill Susan E. , Saskin Refik , Jaakkimainen Liisa , Huang Anjie , Haas Barbara
Published: October 2024

BACKGROUND

While preoperative optimization improves outcomes for older adults undergoing major elective surgery, no such optimization is possible in the emergent setting. Surgeons must identify postoperative interventions to improve outcomes among older emergency general surgery (EGS) patients. The objective of this cohort study was to examine the association between early follow-up with a primary care physician (PCP) and the risk of nursing home acceptance or death in the year following EGS admission among older adults.

METHODS

Using population-based administrative health data in Ontario, Canada (2006–2016), we followed all older adults (65 years or older) for 1 year after hospital admission for EGS conditions. A multivariable Cox model was used to identify the association between early postdischarge follow-up with a patient's PCP and the time to nursing home acceptance or death while adjusting for confounders.

RESULTS

Among 76,568 older EGS patients, 32,087 (41.9%) were seen by their usual PCP within 14 days of discharge, and 9,571 (12.5%) were accepted to a nursing home or died within 1 year. Primary care physician follow-up was associated with a 13% reduced risk of nursing home acceptance or death compared with no follow-up (hazard ratio 0.87; 95% confidence interval 0.84–0.91). This effect was consistent across age and frailty strata, patients managed operatively and nonoperatively, and patients who had both high and low baseline continuity of care with their PCP.

CONCLUSION

Early follow-up with a familiar PCP was associated with a reduced risk of nursing home acceptance or death among older adults following EGS admission. Structures and processes of care are needed to ensure that such follow-up is routinely arranged at discharge.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Translational Neuroscience Contributes to Understanding Neurodevelopmental Outcomes of Dostoyevsky's “Brothers Karamazov” With Treatment Implications
Authors: Deutsch Stephen I. , Burket Jessica A. , Elikan Jeffrey , Spiegel David R.
Published: October 2024

Dostoyevsky's novels raise profound ethical, moral, philosophical and theological issues and, as a result, both he and his novels serve as fertile subjects of scholarly inquiry across a variety of academic disciplines. In particular, major characters in “The Brothers Karamazov” lend themselves to classical psychodynamic formulations, such as the influence of adverse childhood experiences on adult social and occupational outcomes, which in the case of Dmitry, the eldest son of Fyodor Pavlovich Karamazov, are considered in exquisitely fine detail. Prosecutor and defense attorney provide differing interpretations of how early traumas, largely due to paternal neglect and abuse, affected Dmitry's adult outcome in the climactic trial over his alleged patricide. The novel also captures an extreme, and perhaps fanciful, description of an Oedipal rivalry between Dmitry and his father for the affection of a love interest leading to tragic and unpredictable consequences for both. The novel has been dissected by scholars across a variety of diverse and seemingly unrelated disciplines and continues to serve as a springboard for collaborative discussion. Re-reading the novel led the authors to wonder if translational developments in clinical neuroscience could further understanding of poor developmental trajectories of the novel's characters, as well as offer therapeutic recommendations for promoting more favorable occupational and social outcomes. Advances in basic neuroscience have been translated into actionable individualized, interdisciplinary, multimodal treatment plans leading to improved functional outcomes for children like Dmitry, Ivan, and Smerdyakov. Translational neuroscience enriches understanding of neurodevelopmental outcomes of characters in Dostoyevsky's novel “The Brothers Karamazov,” especially in the context of genetic risk and in utero environmental insults.
Genetic and evolutionary divergence of harbour seals (
Phoca vitulina
) in Iliamna Lake, Alaska
Authors: Ferrer Tatiana , Boveng Peter , Hauser Donna D. W. , Withrow David , Burkanov Vladimir , Quinn Thomas P. , O'Corry-Crowe Greg
Published: October 2024

Freshwater populations of typically marine species present unique opportunities to investigate biodiversity, evolutionary divergence, and the adaptive potential and niche width of species. A few pinniped species have populations that reside solely in freshwater. The harbour seals inhabiting Iliamna Lake, Alaska constitute one such population. Their remoteness, however, has long hindered scientific inquiry. We used DNA from seal scat and tissue samples provided by Indigenous hunters to screen for mitochondrial DNA and microsatellite variation within Iliamna Lake and eight regions across the Pacific Ocean. The Iliamna seals (i) were substantially and significantly discrete from all other populations (

x

¯

F

st-mtDNA
= 0.544,

x

¯

Φ

st

-

mtDNA
= 0.541,

x

¯

F

st-microsatellites
= 0.308), (ii) formed a discrete genetic cluster separate from all marine populations (modal ∆
k
= 2, PC1 = 14.8%), had (iii) less genetic diversity (Hd,
π
,
H
exp
), and (iv) higher inbreeding (
F
) than marine populations. These findings are both striking and unexpected revealing that Iliamna seals have likely been on a separate evolutionary trajectory for some time and may represent a unique evolutionary legacy for the species. Attention must now be given to the selective processes driving evolutionary divergence from harbour seals in marine habitats and to ensuring the future of the Iliamna seal.
Males discriminate between substrate-borne cues of conspecific females based on age and mating status in the jumping spider,
Habronattus brunneus
Authors: Humbel Ellen , Kimball Rebecca , Taylor Lisa A.
Published: October 2024

Sexual selection is often studied with a focus on female mate choice, wherein females evaluate male signals to select an optimal mate. However, in some systems, males should also make careful decisions about the females they choose to court, particularly when faced with the risk of precopulatory sexual cannibalism. Here, we explore the idea that male jumping spiders (
Habronattus brunneus
) may mitigate this risk by responding to female cues probably associated with female aggression and/or receptivity. We tested mature male spiders’ ability to discriminate between substrate-borne cues (i.e. silk and excreta) produced by conspecific females of different ages and mating statuses. We found that males spent more time exploring cues produced by mature, non-mated females compared with either immature females or mated females. Heightened interest in cues produced by females that are sexually mature but not yet mated may allow males to reduce cannibalism risk, reduce wasted courtship effort and increase their reproductive success. The use of chemical and/or tactile cues in jumping spider courtship behaviour has been vastly understudied compared with the ways they use vision; this study provides the groundwork for understanding how these sensory modalities interact.
A nonlinear spectral core–periphery detection method for multiplex networks
Authors: Bergermann Kai , Stoll Martin , Tudisco Francesco
Published: October 2024

Core–periphery detection aims to separate the nodes of a complex network into two subsets: a core that is densely connected to the entire network and a periphery that is densely connected to the core but sparsely connected internally. The definition of core–periphery structure in multiplex networks that record different types of interactions between the same set of nodes on different layers is non-trivial since a node may belong to the core in some layers and to the periphery in others. We propose a nonlinear spectral method for multiplex networks that simultaneously optimizes a node and a layer coreness vector by maximizing a suitable non-convex homogeneous objective function by a provably convergent alternating fixed-point iteration. We derive a quantitative measure for the quality of a given multiplex core–periphery structure that allows the determination of the optimal core size. Numerical experiments on synthetic and real-world networks illustrate that our approach is robust against noisy layers and significantly outperforms baseline methods while improving the latter with our novel optimized layer coreness weights. As the runtime of our method depends linearly on the number of edges of the network, it is scalable to large-scale multiplex networks.
Homotopy classification of knotted defects in ordered media
Authors: Nozaki Y. , Kálmán T. , Teragaito M. , Koda Y.
Published: October 2024

We give a homotopy classification of the global defects in ordered media and explain it via the example of biaxial nematic liquid crystals, that is, systems where the order parameter space is the quotient of the three-sphere

S
3

by the quaternion group

Q

. As our mathematical model, we consider continuous maps from complements of spatial graphs to the space

S
3

/
Q

modulo a certain equivalence relation and find that the equivalence classes are enumerated by the six subgroups of

Q

. Through monodromy around meridional loops, the edges of our spatial graphs are marked by conjugacy classes of

Q

; once we pass to planar diagrams, these labels can be refined to elements of

Q

associated with each arc. The same classification scheme applies not only in the case of

Q

but also to arbitrary groups.
The moon’s influence on the activity of tropical forest mammals
Authors: Bischof Richard , Vallejo-Vargas Andrea F. , Semper-Pascual Asunción , Schowanek Simon D. , Beaudrot Lydia , Turek Daniel , Jansen Patrick A. , Rovero Francesco , Johnson Steig E. , Guimarães Moreira Lima Marcela , Santos Fernanda , Uzabaho Eustrate , Espinosa Santiago , Ahumada Jorge A. , Bitariho Robert , Salvador Julia , Mugerwa Badru , Sainge Moses N. , Sheil Douglas
Published: October 2024

Changes in lunar illumination alter the balance of risks and opportunities for animals, influencing activity patterns and species interactions. We examined if and how terrestrial mammals respond to the lunar cycle in some of the darkest places: the floors of tropical forests. We analysed long-term camera trapping data on 86 mammal species from 17 protected forests on three continents. Conservative categorization of activity during the night revealed pronounced avoidance of moonlight (lunar phobia) in 12 species, compared with pronounced attraction to moonlight (lunar philia) in only three species. However, half of all species in our study responded to lunar phases, either changing how nocturnal they were, altering their overall level of activity, or both. Avoidance of full moon was more common, exhibited by 30% of all species compared with 20% of species that exhibited attraction. Nocturnal species, especially rodents, were over-represented among species that avoided full moon. Artiodactyla were more prominent among species attracted to full moon. Our findings indicate that lunar phases influence animal behaviour even beneath the forest canopy. Such impacts may be exacerbated in degraded and fragmented forests. Our study offers a baseline representing relatively intact and well-protected contexts together with an intuitive approach for detecting activity shifts in response to environmental change.
Food intake enhances hippocampal sharp wave-ripples
Authors: Kaya Ekin , Wegienka Evan , Akhtarzandi-Das Alexandra , Do Hanh , Eban-Rothschild Ada , Rothschild Gideon
Published: October 2024

Effective regulation of energy metabolism is critical for survival. Metabolic control involves various nuclei within the hypothalamus, which receive information about the body’s energy state and coordinate appropriate responses to maintain homeostasis, such as thermogenesis, pancreatic insulin secretion, and food-seeking behaviors. It has recently been found that the hippocampus, a brain region traditionally associated with memory and spatial navigation, is also involved in metabolic regulation. Specifically, hippocampal sharp wave ripples (SWRs), which are high-frequency neural oscillations supporting memory consolidation and foraging decisions, have been shown to reduce peripheral glucose levels. However, whether SWRs are enhanced by recent feeding– when the need for glucose metabolism increases, and if so, whether feeding-dependent modulation of SWRs is communicated to other brain regions involved in metabolic regulation, remains unknown. To address these gaps, we recorded SWRs from the dorsal CA1 region of the hippocampus of mice during sleep sessions before and after consumption of meals of varying caloric values. We found that SWRs occurring during sleep are significantly enhanced following food intake, with the magnitude of enhancement being dependent on the caloric content of the meal. This pattern occurred under both food-deprived andad libitumfeeding conditions. Moreover, we demonstrate that GABAergic neurons in the lateral hypothalamus, which are known to regulate food intake, exhibit a robust SWR-triggered increase in activity. These findings identify the satiety state as a factor modulating SWRs and suggest that hippocampal-lateral hypothalamic communication is a potential mechanism by which SWRs could modulate peripheral metabolism and food intake.
Mobility resolution needed to inform predictive epidemic models for spatial transmission from mobile phone data
Authors: Pullano Giulia , Bansal Shweta , Rubrichi Stefania , Colizza Vittoria
Published: October 2024

Mobility flows extracted from mobile phone data have been extensively used in recent years to inform spatial epidemic models for the study of various infectious disease epidemics, including Malaria, Cholera, and Ebola. Most recently, the COVID-19 pandemic marked a historic shift, as it led to the sharing of unprecedented fine-scale mobility data. This abundancy of data illuminated the geographical variability in transmission patterns and underscored the importance of the use of mobility data for public health questions. Little attention has been devoted however to (i) the definition of the mobility process that is relevant to the epidemic spread, and (ii) the mobility data resolution that is needed to describe the invasion dynamics. We take advantage of a real-world dataset, gathered from mobile phone users in Senegal to define three epidemiological couplings between locations, based on different characterizations of the mobility process, and at varying resolution levels. They are based respectively on: (i) the total number of displacements between any two municipalities on two consecutive calls (Displacement-basedD); (ii) the number of calls made by residents in each location (Location-basedL); (iii) the most visited location of residents during daytime (Most visited location-basedC). To assess the impact of the different coupling definitions on the epidemic diffusion, we use them to inform mobility in a spatial epidemic model. We found that preserving any displacement on the observed trajectories from mobile phone data does not capture the epidemiological link between different locations, for infections where daily mobility is important (e.g. airborne or direct contact diseases). Most importantly, we found that at the country scale, places in which individuals spend most of their time including workplaces, schools or particular point of interests like restaurants or theater and are the dominant driver of disease diffusion. In fact, tracking in detail individual activities beyond home and all visited locations during the day does not add epidemiological important information. Novel paradigms for the release of mobile phone data to researchers can therefore be envisioned that strengthen privacy and confidentiality, while at the same time providing enough details - specifically aggregated home-visited locations coupling - to inform predictive epidemic models.
Privacy-Preserving Visualization of Brain Functional Connectivity
Authors: Tao Ye , Sarwate Anand D. , Panta Sandeep , Plis Sergey , Calhoun Vince D.
Published: October 2024

Privacy protection is important in visualization due to the risk of leaking personal sensitive information. In this paper, we study the problem of privacy-preserving visualizations using differential privacy, employing biomedical data from neuroimaging as a use case. We investigate several approaches based on perturbing correlation values and characterize their privacy cost and the impact of pre- and post-processing. To obtain a better privacy/visual utility tradeoff, we propose workflows for connectogram and seed-based connectivity visualizations, respectively. These workflows successfully generate visualizations similar to their non-private counterparts. Experiments show that qualitative assessments can be preserved while guaranteeing privacy. These results show that differential privacy is a promising method for protecting sensitive information in data visualization.
Thermodynamic consistency of autocatalytic cycles
Authors: Kosc Thomas , Kuperberg Denis , Rajon Etienne , Charlat Sylvain
Published: October 2024

Autocatalysis is seen as a potential key player in the origin of life, and perhaps more generally in the emergence of Darwinian dynamics. Building on recent formalizations of this phenomenon, we tackle the computational challenge of exhaustively detecting minimal autocatalytic cycles (autocatalytic cores) in reaction networks, and further evaluate the impact of thermodynamic constraints on their realization under mass action kinetics. We first characterize the complexity of the detection problem by proving its NP-completeness. This justifies the use of constraint solvers to list all cores in a given reaction network, and also to group them into compatible sets, composed of cores whose stoichiometric requirements are not contradictory. Crucially, we show that the introduction of thermodynamic realism does constrain the composition of these sets. Compatibility relationships among autocatalytic cores can indeed be disrupted when the reaction kinetics obey thermodynamic consistency throughout the network. On the contrary, these constraints have no impact on the realizability of isolated cores, unless upper or lower bounds are imposed on the concentrations of the reactants. Overall, by better characterizing the conditions of autocatalysis in complex reaction systems, this work brings us a step closer to assessing the contribution of this collective chemical behavior to the emergence of natural selection in the primordial soup.
A Streamlined High-Throughput LC-MS Assay for Quantifying Peptide Degradation in Cell Culture
Authors: Rozans Samuel J. , Moghaddam Abolfazl S. , Pashuck E. Thomas
Published: October 2024

Peptides are widely used in biomaterials due to their easy of synthesis, ability to signal cells, and modify the properties of biomaterials. A key benefit of using peptides is that they are natural substrates for cell-secreted enzymes, which creates the possibility of utilizing cell-secreted enzymes for tuning cell-material interactions. However, these enzymes can also induce unwanted degradation of bioactive peptides in biomaterials, or in peptide therapies. Liquid chromatography-mass spectrometry (LC-MS) is a widely used, powerful methodology that can separate complex mixtures of molecules and quantify numerous analytes within a single run. There are several challenges in using LC-MS for the multiplexed quantification of cell-induced peptide degradation, including the need for non-degradable internal standards and the identification of optimal sample storage conditions. Another problem is that cell culture media and biological samples typically contain both proteins and lipids that can accumulate on chromatography columns and degrade their performance. However, removing these constituents can be expensive, time consuming, and increases sample variability. Here we show that directly injecting samples onto the LC-MS without any purification enables rapid and accurate quantification of peptide concentration, and that hundreds of LC-MS runs can be done on a single column without a significantly diminish the ability to quantify the degradation of peptide libraries. We also show that column failure is evident when hydrophilic peptides fail to be retained on the column, and this can be easily identified using standard peptide mixtures for column benchmarking. In total, this work introduces a simple and effective method for simultaneously quantifying the degradation of dozens of peptides in cell culture. By providing a streamlined and cost-effective method for the direct quantification of peptide degradation in complex biological samples, this work enables more efficient assessment of peptide stability and functionality, facilitating the development of advanced biomaterials and peptide-based therapies.
Balanced polymorphisms in gamete-binding genes are not associated with human infertility
Authors: Hart M. W. , Crespi B. , Seethram K.
Published: October 2024

Genes expressed in gametes that mediate sperm interaction with the mammalian egg are of considerable interest to evolutionary biologists because the evolution of such genes can account for variation in reproductive compatibility between mates and reproductive isolation between species. The human orthologs of such genes are also potential targets for both contraception and treatment of infertility. One gene system of particular interest is the sperm-binding genes of the inner egg coat or zona pellucida (Zp2, Zp3) and their cognate protein in the mouse sperm acrosome (Zp3r). Previous population genetic analyses in humans pointed toward three balanced polymorphisms (one in each geneZP2, ZP3, andZP3R) as potential targets of some form of balancing selection in the evolution of human fertility. We tested that association using genetic analysis of couples seeking fertility assistance, but we could not reject the null hypothesis of no association between balanced polymorphisms and infertility. Our study was based on a small sample of couples, but the data were sound: the allele frequencies at those three balanced polymorphisms were not different from random expectation in that clinical sample. If an effect of those allele frequencies on infertility exists it is probably small. Our study was based in part on an old error in gene annotation that was only recently discovered (after the start of participant recruitment for this genetic analysis), and this error may account for our results, which argue against a role for balancing selection on those three genes in humans.
SeqDance: A Protein Language Model for Representing Protein Dynamic Properties
Authors: Hou Chao , Shen Yufeng
Published: October 2024

Proteins perform their functions by folding amino acid sequences into dynamic structural ensembles. Despite the important role of protein dynamics, their complexity and the absence of efficient representation methods have limited their integration into studies on protein function and mutation fitness, especially in deep learning applications. To address this, we present SeqDance, a protein language model designed to learn representation of protein dynamic properties directly from sequence alone. SeqDance is pre-trained on dynamic biophysical properties derived from over 30,400 molecular dynamics trajectories and 28,600 normal mode analyses. Our results show that SeqDance effectively captures local dynamic interactions, co-movement patterns, and global conformational features, even for proteins lacking homologs in the pre-training set. Additionally, we showed that SeqDance enhances the prediction of protein fitness landscapes, disorder-to-order transition binding regions, and phase-separating proteins. By learning dynamic properties from sequence, SeqDance complements conventional evolution- and static structure-based methods, offering new insights into protein behavior and function.
TE-Seq: A Transposable Element Annotation and RNA-Seq Pipeline
Authors: Kelsey Maxfield M.G. , Kalekar Radha L. , Sedivy John M.
Published: October 2024

The recognition that transposable elements (TEs) play important roles in many biological processes has elicited growing interest in analyzing sequencing data derived from this mobile ‘dark genome’. The TE-Seq pipeline conducts an end-to-end analysis of RNA-sequencing data, examining both genes and TEs. It implements the most current computational methods tailor-made for TEs, enabling a comprehensive analysis of TE expression at both the individual element level and at the TE clade level. If supplied with long-read DNA sequencing data, it creates a TE-complete genome incorporating non-reference (polymorphic) TE-loci, enabling the functional characterization of the evolutionarily youngest mobile elements in the genome.
New QTLs involved in the control of stigma position in tomato
Authors: Riccini Alessandro , Olivieri Fabrizio , Farinon Barbara , Bitton Frederique , Diouf Isidore , Carretero Yolande , Soler Salvador , del Rosario Figàs Maria , Prohens Jaime , Monforte Antonio Jose , Granell Antonio , Causse Mathilde , Mazzucato Andrea
Published: October 2024

The tomato mating system was strongly affected by domestication events. Mutations disrupting self-incompatibility paralleled by changes retracting the stigma position (SP) within the staminal cone conferred strict autogamy and self-fertility to the cultivated forms. Although major genes affecting these changes have been identified, SP control in domesticated forms retaining a non-inserted or a heat-inducible SP needs elucidation. To widen the possibility of identifying SP genetic determinants, we analysed the trait in four populations (two germplasm collections, a multiparental recombinant inbred and a biparental progeny) under different environmental conditions (normal and heat stressed). Overall, 36 markers significantly associated with the trait were discovered. Several co-localizations were found, both among regions firstly reported in this work and among them and previously reported positions. This supported the reliability of the analysis. Three of such regions, in the long arms of chromosome 1, 8 and 11, were validated in an independent segregating population and candidate genes in confidence intervals were identified among transcription factors and hormone, stress and cell-wall-related genes. In conclusion, the work supported the hypothesis that the SP phenotype is controlled by different key-genes in tomato, paving the way to identifying novel players and novel mechanisms involved in the regulation of herkogamy.

Highlight

The study of three germplasm collections in tomato allowed the identification new significant markers for the stigma position trait while confirmed several previously reported QTLs.
Rapid cyclic stretching induces a synthetic, proinflammatory phenotype in cultured human intestinal smooth muscle, with the potential to alter signaling to adjacent bowel cells
Authors: Wolfson Sharon M. , Beigel Katherine , Anderson Sierra E. , Deal Brooke , Weiner Molly , Lee Se-Hwan , Taylor Deanne , Heo Su Chin , Heuckeroth Robert O. , Hashmi Sohaib K.
Published: October 2024

Background and Aims

Bowel smooth muscle experiences mechanical stress constantly during normal function, and pathologic mechanical stressors in disease states. We tested the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching.

Methods

Primary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-ε-caprolactone nano-fibrous scaffolds, were subjected to pathologic, high frequency (1 Hz) uniaxial 3% cyclic stretch (loaded) or kept unloaded in culture for 6 hours. Total RNA sequencing, qRT-PCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells.

Results

Loading induced differential expression of 4537 genes in HISMCs. Loaded HISMCs had a less contractile phenotype, with increased expression of synthetic SMC genes, proinflammatory cytokines, and altered expression of axon guidance molecules, growth factors and morphogens. Many differentially expressed genes encode secreted ligands that could act cell-autonomously on smooth muscle and on other cells in the bowel wall.

Discussion

HISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMCs into proliferative, fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.
Biotic interactions and environmental filtering both determine earthworm alpha and beta diversity in tropical rainforests
Authors: Goulpeau Arnaud , Hedde Mickaël , Ganault Pierre , Lapied Emmanuel , Maggia Marie-Eugénie , Marcon Eric , Decaëns Thibaud
Published: October 2024

Understanding the relative importance of biotic interactions, multiple environmental drivers, and neutral processes in shaping community diversity and composition is a central question for both theoretical and applied ecology.

We analysed a dataset describing 125 earthworm communities sampled in 10 localities in French Guiana. DNA barcodes were used to delimit operational taxonomic units (OTUs) that we considered as species surrogates to avoid the taxonomic deficit and calculate community-scale species richness and pair-wise Sørensen beta-diversity. We used log-ratio and generalised linear models to highlight the effects of biotic interactions and environment as drivers of alpha diversity, and generalised dissimilarity models to figure out the relative contribution of space and environment to beta-diversity at different spatial extents.

Community-scale alpha diversity was mainly explained by habitat filtering (soil texture) and interspecific competition that limit the number of locally co-existing species.

Beta diversity between pairs of communities was mainly explained by distance when comparing communities in similar habitats, by topography and available soil phosphorus when comparing communities in different habitats, and by distance, elevation and climate when comparing all possible pairs of communities.

While community composition is determined locally by neutral processes and environmental filtering, biogeographic processes linked to dispersal limitation and adaptation to local environment are the most influential on a regional scale. This highlights the complex interplay of dispersal limitation, biotic interactions and environmental filtering during the process of community assembly.
Wild Florida Mottled Ducks demonstrate strong heterogeneity in their humoral innate immune response
Authors: Ayala Andrea J. , Cheng Matthew , Hellinger Thomas A. , Mark McBride K. , Webb Jonathan , Fanning Andrew , Snyder Paul , Ferragamo Margherita , Garcia Samantha C. , Sterner Nyah , Bischoff Karyn L. , Moreno Salvador-Almagro , Ogbunugafor C. Brandon
Published: October 2024

The Florida Mottled Duck (Anas fulvigula fulvigula) is a unique subspecies of waterfowl whose range is limited to peninsular Florida, USA. As an endemic species, Florida Mottled Ducks face numerous conservation stressors, such as habitat conversion and hybridization with non-native Mallards (Anas platyrhynchos). In addition to these numerous stressors, Mottled Ducks are also contending with emerging and/or geographically expanding waterborne pathogens such asVibriospp., due to the effects of climate change. However, even given their conservation needs, little is known with respect to the health, physiology and the immunity of wild Mottled Ducks in Florida. Given this lack of data, we performed health assessments of Mottled Ducks in the Central Florida area.

Specifically, we examined the humoral innate immune system, i.e., plasma, of Mottled Ducks in response to a common, but extraneous pathogen,Escherichia colistrain ATCC number 8739. We utilized a bactericidal assay (BKA) commonly used in eco-immunology, to provide insight into the bactericidal capacities of captured Florida Mottled Ducks. We statistically tested the BKA capacity of 23 Mottled Ducks in response to age and whole blood lead levels (Pb). We found that there was no statistically significant relationship between the covariates we measured and Mottled Duck BKA capacity againstE. coli. However, the variability we observed in the BKA capacity of this subspecies warrants further research into additional physiological and ecological covariates coupled with potential immune stressors that Florida Mottled Ducks may be contending with.
MSFragger-DDA+ Enhances Peptide Identification Sensitivity with Full Isolation Window Search
Authors: Yu Fengchao , Deng Yamei , Nesvizhskii Alexey I.
Published: October 2024

Liquid chromatography-mass spectrometry (LC-MS) based proteomics, particularly in the bottom-up approach, relies on the digestion of proteins into peptides for subsequent separation and analysis. The most prevalent method for identifying peptides from data-dependent acquisition (DDA) mass spectrometry data is database search. Traditional tools typically focus on identifying a single peptide per tandem mass spectrum (MS2), often neglecting the frequent occurrence of peptide co-fragmentations leading to chimeric spectra. Here, we introduce MSFragger-DDA+, a novel database search algorithm that enhances peptide identification by detecting co-fragmented peptides with high sensitivity and speed. Utilizing MSFragger’s fragment ion indexing algorithm, MSFragger-DDA+ performs a comprehensive search within the full isolation window for each MS2, followed by robust feature detection, filtering, and rescoring procedures to refine search results. Evaluation against established tools across diverse datasets demonstrated that, integrated within the FragPipe computational platform, MSFragger-DDA+ significantly increases identification sensitivity while maintaining stringent false discovery rate (FDR) control. It is also uniquely suited for wide-window acquisition (WWA) data. MSFragger-DDA+ provides an efficient and accurate solution for peptide identification, enhancing the detection of low-abundance co-fragmented peptides. Coupled with the FragPipe platform, MSFragger-DDA+ enables more comprehensive and accurate analysis of proteomics data.
Heterologous expression and optimization of fermentation conditions for recombinant ikarugamycin production
Authors: Evers Julia K. , Glöckle Anna , Wiegand Monique , Schuler Sebastian , Einsiedler Manuel , Gulder Tobias A. M.
Published: October 2024

Ikarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis. It is therefore used as a tool compound to study diverse biological processes. However, ikarugamycin commercial prices are very high, with up to 1300 € per 1 mg, thus limiting its application. We therefore set out to develop a high-yielding recombinant production platform of ikarugamycin by screening different expression vectors, recombinant host strains, and cultivation conditions. Overall, this has led to overproduction levels of more than 100 mg/L, which, together with a straightforward purification protocol, establishes biotechnological access to affordable ikarugamycin enabling its increased use in biomedical research in the future.
Assembloid model to study loop circuits of the human nervous system
Authors: Miura Yuki , Kim Ji-il , Jurjuț Ovidiu , Kelley Kevin W. , Yang Xiao , Chen Xiaoyu , Thete Mayuri Vijay , Revah Omer , Cui Bianxiao , Pachitariu Marius , Pașca Sergiu P.
Published: October 2024

Neural circuits connecting the cerebral cortex, the basal ganglia and the thalamus are fundamental networks for sensorimotor processing and their dysfunction has been consistently implicated in neuropsychiatric disorders1-9. These recursive, loop circuits have been investigated in animal models and by clinical neuroimaging, however, direct functional access to developing human neurons forming these networks has been limited. Here, we use human pluripotent stem cells to reconstruct anin vitrocortico-striatal-thalamic-cortical circuit by creating a four-part loop assembloid. More specifically, we generate regionalized neural organoids that resemble the key elements of the cortico-striatal-thalamic-cortical circuit, and functionally integrate them into loop assembloids using custom 3D-printed biocompatible wells. Volumetric and mesoscale calcium imaging, as well as extracellular recordings from individual parts of these assembloids reveal the emergence of synchronized patterns of neuronal activity. In addition, a multi–step rabies retrograde tracing approach demonstrate the formation of neuronal connectivity across the network in loop assembloids. Lastly, we apply this system to study heterozygous loss ofASH1Lgene associated with autism spectrum disorder and Tourette syndrome and discover aberrant synchronized activity in disease model assembloids. Taken together, this human multi-cellular platform will facilitate functional investigations of the cortico-striatal-thalamic-cortical circuit in the context of early human development and in disease conditions.
Insights into a clock’s fidelity through vesicular encapsulation
Authors: Tu Li Alexander Zhan , LiWang Andy , Subramaniam Anand Bala
Published: October 2024

The single-celled cyanobacterium,Synechococcus elongatus, generates circadian rhythms with exceptional fidelity and synchrony despite their femtoliter volumes. Here, we explore the mechanistic aspects of this fidelity, by reconstituting the KaiABC post-translational oscillator (PTO) in cell-mimetic giant vesicles (GUVs) under well-defined conditionsin vitro. PTO proteins were encapsulated with a coefficient of variation that closely matched protein variations observed in live cells. Using fluorescently labeled KaiB and confocal microscopy, we were able to measure circadian rhythms generated by thousands of encapsulated PTOs at the single-vesicle level for several days as a function of protein concentration and GUV size. We find that PTO fidelity decreased with decreasing levels of encapsulated PTO proteins and in smaller GUVs. We also observed that in encapsulated PTOs, a significant fraction of KaiB localized to GUV membranes like it does in cyanobacteria. A mathematical model that uses empirical bulk concentration and stoichiometry limitations suggests that cyanobacteria overcome challenges to fidelity by expressing high levels of PTO proteins along with the CikA and SasA proteins, which buffer stochastic variations in the levels of KaiA and KaiB, respectively. Further, the model suggests that the transcription-translation feedback loop (TTFL) contributes at most a small percentage to the overall fidelity of the cyanobacterial circadian clock under constant conditions but is essential for maintaining phase synchrony. Our results are the first experimental demonstration of populations of synthetic cells that can autonomously keep circadian time. Additionally, the approach of using bulk relationships to understand complex phenomena in cell-like systems could be useful for understanding other collective behavior important in biology, such as liquid-liquid phase separation.
An intracellular calcium sensory complex CPKs/ECA1 controls cytosolic calcium homeostasis for plant osmosensitivity
Authors: Liang Xiaoju , Zhou Yeling , Xu Weifeng , Liang Jiansheng
Published: October 2024

Intracellular Ca2+controls various cellular functions and local Ca2+dynamics is tightly regulated upon environmental cues. Maintaining cellular Ca2+balance is essential for plant survival. Here we report a calcium-dependent protein kinases (CPKs)-mediated signaling pathway, in conjunction with the ER membrane-resident Ca2+-ATPase ECA1, acts influentially for cytosolic Ca2+homeostasis and osmotic stress tolerance. We show that targeting cytosolic Ca2+efflux via specific inhibitors oreca1mutation results in augmented [Ca2+]cyt spikes, elevated cytoplasmic ABA ([ABA]cyt) level and ultimately hypersensitive to osmotic stress. Screening ofArabidopsisCPKs revealed direct binding of CPK2/6/11 to ECA1. Moreover, CPK2/6/11 phosphorylate the N-terminal of ECA1 at Ser5, thereby enhancing its activity for cytosolic Ca2+efflux into ER and subsequently lower [ABA]cyt. The cumulative effect of ECA1 and CPKs mutation onArabidopsisplant sensitivity to osmotic stress further illustrates that CPKs/ECA1 acts an intracellular sensory module for plant stress tolerance via regulating [Ca2+]cyt and [ABA]cyt homeostasis.

One-sentence summary:CPKs/ECA1 acts an intracellular sensory module for plant osmotic stress tolerance via regulating cytosolic Ca2+and ABA homeostasis.
Thermal biology of aphids and implications for agriculture and food security
Authors: Villena Oswaldo C , Arab Ali , Armbruster Peter A , Markovich Elizabeth , Zhang Kevin , Tonnang Henry E , Sokame Bonoukpoe M , Kreuze Jan Frederik , Carhuapoma Pablo F , Gamarra Heidy A , Johnson Leah R
Published: October 2024

Climate change poses significant challenges to agriculture and food security, particularly through its effects on insect vector populations and the pathogens they transmit. Aphids are one of the biggest group of ectotherms that transmit viruses to plants; more than 200 species have been identified as pathogen vectors. These aphids are responsible for transmitting over 300 viruses. The life-history traits of aphids such as fecundity and survival respond strongly and non-linearly to temperature and therefore to global warming. In this study, we elaborate the thermal responses for the main life-history traits (i.e, development and mortality rate) for aphid species for which data were available or generated. Also, thermal responses for virus transmission rates were elaborated to describe plant host to vector and vector to plant host dynamics. With these data, we elaborated thermal suitability models which were used to map current and projected scenarios for the transmission of viruses by aphids. Data was only available/generated for 19 aphid species, many of which only have data either at the lower or upper thermal limits. For virus transmission rates, from host plant to vector and from vector to plant data was only available/generated for potato virus Y (PVY), potato virus A (PVA), and potato leaf roll virus (PLRV) transmitted by the aphidMyzus persicae. Projections show that virus transmission by aphids will shift to northern latitudes. Understanding the thermal biology of aphids is crucial for developing effective measures to safeguard agriculture, especially staple crops, and food security in the context of climate change.
Impact of an Oxidative RNA Lesion on in vitro Replication Catalyzed by SARS-CoV-2 RNA-dependent RNA Polymerase
Authors: Akagawa Masataka , Sugasawa Kaoru , Ura Kiyoe , Sassa Akira
Published: October 2024

The production of reactive oxygen species in response to RNA virus infection results in the oxidation of viral genomic RNA within infected cells. These oxidative RNA lesions undergo replication catalyzed by the viral replisome. G to U transversion mutations are frequently observed in the SARS-CoV-2 genome and may be linked to the replication process catalyzed by RNA-dependent RNA polymerase (RdRp) past the oxidative RNA lesion 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG). To better understand the mechanism of viral RNA mutagenesis, it is crucial to elucidate the role of RdRp in replicating across oxidative lesions. In this study, we investigated the RNA synthesis catalyzed by the reconstituted SARS-CoV-2 RdRp past a single 8-oxo-rG. The RdRp-mediated primer extension was significantly inhibited by 8-oxo-rG on the template RNA. During the blockage of the extension reaction, the rate of product release by RdRp was extremely slow, indicating that the RdRp machinery remained bound to the replicating primer/template RNA. Once RdRp was able to bypass 8-oxo-rG, it preferentially incorporated rCMP, with a lesser amount of rAMP opposite 8-oxo-rG. In contrast, RdRp demonstrated greater activity in extending from the mutagenic rA:8-oxo-rG terminus compared to the lower efficiency of extension from the rC:8-oxo-rG pair. Based on steady-state kinetic analyses for the incorporation of rNMPs opposite 8-oxo-rG and chain extension from rC:8-oxo-rG or rA:8-oxo-rG, the relative bypass frequency for rA:8-oxo-rG was found to be seven-fold higher than that for rC:8-oxo-rG. Therefore, the properties of RdRp indicated in this study may contribute to the mechanism of mutagenesis of the SARS-CoV-2 genome.