bluuebunny/crossref_metadata_2025_split huggingface dataset:
A selective alternative pathway complement inhibitor for treatment of paroxysmal nocturnal hemoglobinuria
Authors: Sülzen Hagen , Tulmin Hanna , Hájek Miroslav , Čermák Jaroslav , Kadlecová Alžběta , Pompach Petr , Votrubová Jitka , Zoltner Martin , Zoll Sebastian 
Published: June 2024

ABSTRACTThe complement system, a critical component of the human innate immune system, enhances the ability to clear microbes and damaged cells. Dysregulation of this system, particularly the alternative pathway (AP), can lead to several rare blood disorders such as paroxysmal nocturnal hemoglobinuria (PNH). This study introduces SH-01, a blood parasite-derived, novel recombinant protein which selectively inhibits the AP. We show that SH-01 effectively prevents the lysis of erythrocytes isolated from PNH patients. Unlike current treatments such as eculizumab, SH-01 targets the AP without impairing the classical or lectin pathways, reducing the risk of infections and extravascular hemolysis. SH-01 functions through a unique two-stage mechanism, preventing C3b deposition and inhibiting AP C5 convertase activity while maintaining the amplification loop’s functionality. Immunization studies in mice showed no significant immune response against SH-01, and the protein exhibited high stability and no acute toxicity. These findings suggest SH-01 as a promising candidate for treatment of PNH and other diseases characterized by AP hyperactivation, offering a more targeted therapeutic and thus safer approach.
A next generation neural mass model with neuromodulation
Authors: Depannemaecker Damien , Duprat Chloé , Casagrande Gabriele , Saggio Marisa , Athanasiadis Anastasios Polykarpos , Angiolelli Marianna , Carbonell Carola Sales , Wang Huifang , Petkoski Spase , Sorrentino Pierpaolo , McIntosh Anthony Randal , Sheheitli Hiba , Jirsa Viktor 
Published: June 2024

AbstractThe study of brain activity and its function requires the development of computational models alongside experimental investigations to explore different effects of multiple mechanisms at play in the central nervous system. Chemical neuromodulators, such as dopamine, play central roles in regulating the dynamics of neuronal populations. In this work, we propose a modular framework to capture the effects of neuromodulators at the neural mass level. Using this framework, we formulate a specific model for dopamine dynamics affecting D1-type receptors. We detail the dynamical repertoire associated with dopamine concentration evolution and characterize the transitions across qualitatively different oscillatory states as a function of relevant parameters, along with the variations in frequency of the emergent multi-scale oscillations.
Substance P receptor signaling contributes to host maladaptive responses during enteric bacterial infection
Authors: Cremin Michael , Ramirez Valerie T. , Sanchez Kristina , Tay Emmy , Murray Kaitlin , Brust-Mascher Ingrid , Reardon Colin 
Published: June 2024

AbstractImmune responses in the intestine are intricately balanced to prevent pathogen entry without inducing immunopathology. The nervous system is well-established to interface with the immune system to fine-tune immunity in various organ systems including the gastrointestinal tract. Specialized sensory neurons can detect bacteria, bacterial products, and the resulting inflammation, to coordinate the immune response in the gastrointestinal tract. These sensory neurons release peptide neurotransmitters such as Substance P (SP), to induce both neuronal signaling and localized responses in non-neuronal cells. With this in mind, we assessed the immunoregulatory roles of SP receptor signaling during enteric bacterial infection with the non-invasive pathogenCitrobacter rodentium. Pharmacological antagonism of the SP receptor significantly reduced bacterial burden and prevented colonic crypt hyperplasia. Mice with SP receptor signaling blockade had significantly reduced inflammation and recruitment of T-cells in the colon. Reduced colonic T-cell recruitment is due to reduced expression of adhesion molecules on colonic endothelial cells in SP receptor antagonist-treated mice. Using SP receptor T-cell conditional knockout mice, we further confirmed SP receptor signaling enhanced select aspects of T-cell responses. Our data demonstrates that SP receptor signaling can significantly reduce inflammation and prevent host-maladaptive responses without impinging upon host protection.
Within and Across Species Variation in Plant Traits in Response to Long-Term Experimental Herbivore Exclusion in a Semi-Arid Shrubland
Authors: Fernández-Murillo María del Pilar , Alfaro Fernando Daniel , Kelt Douglas A. , Meserve Peter L. , Gutiérrez Julio R. , Troncoso Alejandra J. , Craven Dylan 
Published: June 2024

SUMMARY1) Herbivores shape multiple facets of biodiversity patterns and ecosystem processes, yet are increasingly threatened by habitat loss and climate change. Here, we use a long-term experiment to examine how excluding herbivores, a proxy for biodiversity loss, restructures dominant plant ecological strategies within and across species.2) We measured twelve functional traits of four dominant annual plant species in the semi-arid shrublands of Chile. We evaluated changes in trait distributions within and across species and changes in the coordination between above- and below-ground strategies in response to vertebrate herbivore exclusion.3) Our study reveals three dominant ecological strategies characterizing trait variation within and across species, with an increase in the coordination between above- and below-ground strategies in the presence of herbivores. Our results show that herbivores induce shifts in ecological strategies, leading to conservative resource use, increased herbivore tolerance, reduced collaboration with soil microorganisms, and greater intraspecific diversity, facilitating species coexistence.4) We empirically demonstrate how herbivores shape ecological strategies within and across species, and demonstrate that the absence of herbivores alters the diversity of adaptation strategies of plants and leads to a decoupling of resource acquisition strategies above- and below-ground. These results advance understanding of annual plant responses to herbivore loss.
Interannual changes in nutrient and phytoplankton dynamics in the Eastern Mediterranean Sea (EMS) predict the consequences of climate change; results from the Sdot-Yam Time-series station 2018-2022
Authors: Ben-Ezra Tal , Blachinsky Alon , Gozali Shiran , Tsemel Anat , Fadida Yotam , Tchernov Dan , Lehahn Yoav , Tsagaraki Tatiana Margo , Berman-Frank Ilana , Krom Michael 
Published: June 2024

AbstractGlobal climate change is predicted to reduce nutrient fluxes into the photic zone, particularly in tropical and subtropical ocean gyres, while the occasional major storms will result in increased nutrient pulses. In this study the nutrient and phytoplankton dynamics have been determined at a new time-series station in the southeastern Levantine basin of the Eastern Mediterranean Sea (EMS) over 4.5 years (2017-2022). In 2018 and 2019, there was a moderate concentration of residual nitrate and nitrite (N+N) in the photic zone (280-410nM) in winter, resulting in phytoplankton dynamics dominated by cyanobacteria with relatively few picoeukaryotes (280± 90 μgC m−2). Winter storm driven mixing was much reduced in 2020 and particularly in 2021, resulting in a lower concentration of N+N in the photic zone, which decreased during summer stratification, such that by August 2021, the N+N was highly depleted (<60 nM) resulting in an integrated phytoplankton biomass of 23 μgC m−2. A major storm in December 2021 (Storm Carmel) injected high N+N (750 nM; max = 1090 nM) in the upper 100 m, which stimulated pico and nanophytoplankton biomass (∼2400 μgC m−2) and probably increased eukaryotes (diatoms). The pattern of measured silica reinforced our conclusion that we sampled 3 different nutrient and ecosystem states. Phosphate was always at or close to LoD because of rapid uptake by cyanobacteria into their periplasm. These results predict that climate change in the EMS will result in periods of nutrient and phytoplankton depletion (Famine) interrupted by short periods of Mesotrophy (Feast) caused by major storms.Highlights–Nutrient dynamics from 4 years of Time-series station in the S.E. Levantine basin–Defined ecosystem status of normal, depleted and temporarily mesotrophic which are predicted status’ caused by climate change–Winters with low deep mixing resulted in severely nutrient depleted conditions subsequently–Major storm and relatively shallow nutricline resulted in temporary mesotrophic status
Mutant scaling laws reveal that accelerated evolution via gene amplification requires spatially structured population growth
Authors: Komarova Natalia L. , Pritchard Justin , Wodarz Dominik 
Published: June 2024

AbstractPrinciples of evolution in spatially structured expanding populations have recently received much attention, but more work remains to be performed, especially for complex, multi-step evolutionary processes, where mutations are accumulated in an expanding population. A key limitation is that the simulation of spatially explicit stochastic computational models is essential, but not feasible for larger population sizes characteristic of prokaryotic and eukaryotic cell populations. We describe a methodological advance by deriving scaling laws that allow the straightforward prediction of the number of single-hit, double-hit and multi-hit mutants as a function of wild-type population size in spatially expanding populations. While this is a versatile tool to address a range of cutting-edge evolutionary questions, here we apply this methodology to reconcile apparently contradicting data from experimental evolution studies regarding the role of gene amplifications for the emergence of point mutations in bacteria. Applying the scaling laws, we demonstrate that in populations that expand in a 2D or a 3D spatial setting, gene amplifications can significantly promote mutant emergence, and that this is not possible in well-mixed populations. In support of the predictions, experiments that do show accelerated mutant evolution through gene amplifications grew bacteria in spatially restricted lawns, while those that failed to show an effect grew bacteria in non-spatial liquid media.
The evolution of sequence specificity in a DNA binding protein family
Authors: Nandy Meghna , Sharda Mohak , Seshasayee Aswin Sai Narain 
Published: June 2024

AbstractTranscriptional regulation enables bacteria to adjust to its environment. This is driven by transcription factors (TFs), which display DNA site recognition specificity with some flexibility built-in. TFs however are not considered essential to a minimal cellular life. How do they evolve? It has been hypothesised that TFs evolve by gaining specificity (and other functions) on a background of non-specific chromosome structuring proteins. We used the IHF/HU family of DNA binding proteins, in which IHF binds DNA in a sequence specific manner whereas HU binds more indiscriminately, to test this hypothesis. We show that neither protein was present in the last common bacterial ancestor, and that HU evolved first in early-branching clades. By reconstructing ancestral sequencesin-silicoon a rooted phylogeny of IHF/HU we show that the common ancestor of this family was probably HU-like and therefore non-specific in binding DNA. Various residues characteristic of IHF and shown to be involved in specific sequence recognition (at least inE. coli) evolved gradually with several gains and losses along the phylogeny. Finally, we suggest that the evolution of the IHF/HU from a HU-like ancestor to IHF, and by inference the evolution of DNA site specificity in this family, was driven by selection.
Distinct dopaminergic spike-timing-dependent plasticity rules are suited to different functional roles
Authors: Sosis Baram , Rubin Jonathan E. 
Published: June 2024

AbstractVarious mathematical models have been formulated to describe the changes in synaptic strengths resulting from spike-timing-dependent plasticity (STDP). A subset of these models include a third factor, dopamine, which interacts with spike timing to contribute to plasticity at specific synapses, notably those from cortex to striatum at the input layer of the basal ganglia. Theoretical work to analyze these plasticity models has largely focused on abstract issues, such as the conditions under which they may promote synchronization and the weight distributions induced by inputs with simple correlation structures, rather than on scenarios associated with specific tasks, and has generally not considered dopamine-dependent forms of STDP. In this paper we introduce three forms of dopamine-modulated STDP adapted from previously proposed plasticity rules. We then analyze, mathematically and with simulations, their performance in three biologically relevant scenarios. We test the ability of each of the three models to maintain its weights in the face of noise and to complete simple reward prediction and action selection tasks, studying the learned weight distributions and corresponding task performance in each setting. Interestingly, we find that each plasticity rule is well suited to a subset of the scenarios studied but falls short in others. Different tasks may therefore require different forms of synaptic plasticity, yielding the prediction that the precise form of the STDP mechanism present may vary across regions of the striatum, and other brain areas impacted by dopamine, that are involved in distinct computational functions.
MAGMa: Your Comprehensive Tool for Differential Expression Analysis in Mass-Spectrometry Proteomic Data
Authors: Gupta Shagun , Kang Jin Joo , Sun Yu , Kumar Yugandhar , Wagner Mateusz , Comstock Will , Booth James , Smolka Marcus , Yu Haiyuan 
Published: June 2024

AbstractProteomics, the study of proteins and their functions, plays a vital role in understanding biological processes. In this study, we sought to address the challenges in analyzing complex proteomic datasets, where subtle changes in protein abundance are difficult to detect. Utilizing a newly developed tool,MaximalAggregation ofGood protein signal fromMass spectrometric data (MAGMa), we demonstrated its superior performance in accurately identifying true signals while effectively filtering out noise. Here we show that MAGMa strikes a balance between sensitivity and specificity on benchmarking datasets, offering a robust solution for analyzing various quantitative proteomic datasets. These findings advance the field by providing researchers with a powerful tool to uncover subtle changes in protein abundance, contributing to our understanding of complex biological systems and potentially facilitating the discovery of new therapeutic targets.
Just add water: A simple floral bud injection method for stableAgrobacterium-mediated transformation in two ecotypes ofMimulus guttatus
Authors: Stanley Lauren E. , Lowry David B. 
Published: June 2024

ABSTRACTStable transformation is the biggest challenge for studying gene function in plants. In most plant species, stable transformation requires the development of arduous tissue culture and regeneration methods that often fail and can cause undesirable genetic changes. Floral transformation methods bypass these challenges by infiltratingAgrobacteriumdirectly into the ovules of developing flowers. However, this method has had limited success outside of a handful of plant species and genotypes within those species. Here, we demonstrate that the floral infiltration method is effective for some, but not all genotypes of the yellow monkeyflower,Mimulus guttatus, a model system for studies of ecology and evolution. To conduct transformation in genotypes where infiltration failed, we developed a novel floral injection method. Beyond expanding the number of genotypes that can be transformed, the floral injection method has other advantages, such as allowing plants to be infiltrated multiple times and a reduction in floral abscission and male sterility. Through a combination of floral infiltration and injection methods, we were able to transform both coastal perennial and inland annual genotypes ofM. guttatus, which sets the stage for understanding the molecular genetic underpinnings of local adaptation to the divergent habitats occupied by these distinctive ecotypes. Overall, the development of these efficient transformation methods will open up a wide range of new research avenues in theM. guttatusspecies complex.
NKp30 and NKG2D contribute to natural killer recognition of HIV-infected cells
Authors: Zhao Nancy Q. , Pi Ruoxi , Nguyen David N. , Ranganath Thanmayi , Seiler Christof , Holmes Susan , Marson Alexander , Blish Catherine A. 
Published: June 2024

SummaryNatural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 prevention and control strategies harnessing NK cells could be enabled by mechanistic understanding of how NK cells recognize HIV-infected T cells. Here, we profiled the phenotype of human primary NK cells responsive to autologous HIV-1-infected CD4+T cells in vitro. We characterized the patterns of NK cell ligand expression on CD4+T cells at baseline and after infection with a panel of transmitted/founder HIV-1 strains to identify key receptor-ligand pairings. CRISPR editing of CD4+T cells to knockout the NKp30 ligand B7-H6, or the NKG2D ligands MICB or ULBP2 reduced NK cell responses to HIV-infected cells in some donors. In contrast, overexpression of NKp30 or NKG2D in NK cells enhanced their targeting of HIV-infected cells. Collectively, we identified receptor-ligand pairs including NKp30:B7-H6 and NKG2D:MICB/ULBP2 that contribute to NK cell recognition of HIV-infected cells.
Broad-spectrum RNA antiviral inspired by ISG15-/-deficiency
Authors: Akalu Yemsratch T. , Patel Roosheel S. , Taft Justin , Canas-Arranz Rodrigo , Richardson Ashley , Buta Sofija , Martin-Fernandez Marta , Sazeides Christos , Pearl Rebecca L. , Mainkar Gayatri , Kurland Andrew P. , Geltman Rachel , Rosberger Haylen , Kang Diana D. , Kurian Ann Anu , Kaur Keerat , Altman Jennie , Dong Yizhou , Johnson Jeffrey R. , Zhangi Lior , Lim Jean K. , Albrecht Randy A. , García-Sastre Adolfo , Rosenberg Brad R. , Bogunovic Dusan 
Published: June 2024

SummaryType I interferons (IFN-I) are cytokines with potent antiviral and inflammatory capacities. IFN-I signaling drives the expression of hundreds of IFN-I stimulated genes (ISGs), whose aggregate function results in the control of viral infection. A few of these ISGs are tasked with negatively regulating the IFN-I response to prevent overt inflammation. ISG15 is a negative regulator whose absence leads to persistent, low-grade elevation of ISG expression and concurrent, self-resolving mild autoinflammation. The limited breadth and low-grade persistence of ISGs expressed in ISG15 deficiency are sufficient to confer broad-spectrum antiviral resistance. Inspired by ISG15 deficiency, we have identified a nominal collection of 10 ISGs that recapitulate the broad antiviral potential of the IFN-I system. The expression of the 10 ISG collection in an IFN-I non-responsive cell line increased cellular resistance to Zika, Vesicular Stomatitis, Influenza A (IAV), and SARS-CoV-2 viruses. A deliverable prophylactic formulation of this syndicate of 10 ISGs significantly inhibited IAV PR8 replicationin vivoin mice and protected hamsters against a lethal SARS-CoV-2 challenge, suggesting its potential as a broad-spectrum antiviral against many current and future emerging viral pathogens.One-Sentence SummaryHuman inborn error of immunity-guided discovery and development of a broad-spectrum RNA antiviral therapy
Destabilized host-parasite dynamics in newly founded populations
Authors: Bolnick Daniel I. , Barrett Rowan D.H. , Choi Emma , Eckert Lucas , Hendry Andrew P. , Kerns Emily V. , Lind Åsa J. , Milligan-McClellan Kathryn , Peichel Catherine L. , Sasser Kristofer , Thornton Alice R , Wolf Cole , Steinel Natalie C. , Weber Jesse N. 
Published: June 2024

AbstractWhen species disperse into previously unoccupied habitats, new populations encounter unfamiliar species interactions such as altered parasite loads. Theory predicts that newly founded populations should exhibit destabilized eco-evolutionary fluctuations in infection rates and immune traits. However, to understand founder effects biologists typically rely on retrospective studies of range expansions, missing early-generation infection dynamics. To remedy this, we experimentally founded whole-lake populations of threespine stickleback. Infection rates were temporally stable in native source lakes. In contrast, newly founded populations exhibit destabilized host-parasite dynamics: high starting infection rates led to increases in a heritable immune trait (peritoneal fibrosis), suppressing infection rates. The resulting temporal auto-correlation between infection and immunity suggest that newly founded populations can exhibit rapid host-parasite eco-evolutionary dynamics.
Bilingual language processing relies on shared semantic representations that are modulated by each language
Authors: Chen Catherine , Gong Xue L. , Tseng Christine , Klein Daniel L. , Gallant Jack L. , Deniz Fatma 
Published: June 2024

ABSTRACTBillions of people throughout the world are bilingual and can extract meaning from multiple languages. While some evidence suggests that there is a shared system in the human brain for processing semantic information from native and non-native languages, other evidence suggests that semantic processing is language-specific. We conducted a study to determine how semantic representations in the brains of bilinguals can support both shared and language-specific processing for different languages. Functional magnetic resonance imaging (fMRI) was used to record brain responses while participants read several hours of natural narratives in their native (Chinese) and non-native (English) languages. These data were then used to specifically and comprehensively compare semantic representations between the two languages. First, we show that semantic representations are largely shared between languages. Second, we show that there are finer-grained differences that systematically alter how the same meaning is represented between different languages. Our results suggest that for bilinguals, semantic representations in the brain are shared across languages but modulated by each language. These results reconcile current competing theories of bilingual language processing.