bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal Discovery Analysis Reveals Insights into Psychosis Proneness, Brain Function, and Environmental Factors among Young Individuals
Authors: Sahin-Ilikoglu Tuba , Ma Sisi , Kummerfeld Erich , Rawls Eric , Tan Hao Yang , Toulopoulou Timothea 
Published: February 2024

AbstractBackgroundExperiencing symptoms of psychosis, such as delusions and hallucinations, are observed in general, nonclinical populations. These experiences are sometimes described as psychosis proneness (PP) and potentially part of the psychosis continuum. The directional relationships among various factors contributing to psychosis proneness and its interactions, encompassing both environmental and neural mechanisms, lack comprehensive description. We aimed to identify targets to prevent psychosis proneness and its interactions by characterizing pathways using causal discovery analysis (CDA).MethodsParticipants were 194 healthy adolescent and young adult twin and sibling pairs aged between 14-24 years from Türkiye. They completed comprehensive assessments evaluating sociodemographic status, environmental risk, general intelligence, self-schema, PP, and working memory (WM) performance during fMRI (37 variables). CDA was applied, a novel machine learning algorithm, to understand the causal relationships of PP.ResultsThe analysis identified negative self-schema as having the largest causal effect among all assessments in PP [Effect size (ES)= 0.55]. Secondly, social cohesion and trust (SC&T) had a protective causal effect on PP [ES= −0.18]. Lastly, PP was identified as a direct cause of greater activation in DLPFC (BA9a-BA46v) during manipulation in the WM (ES= 0.14).ConclusionsCDA provides directionality of the 37 variables which were not presented earlier. The findings highlight the significance of negative self-schema and SC&T in the general population with PP, emphasizing the potential for preventive interventions targeting these factors. These findings also suggest a role for DLPFC as a potential target in this regard. To our knowledge, this is the first study using data-driven analysis to model causal mechanisms in PP in the general population.
The Co-Evolution of Jawed Vertebrates and Interferon Regulatory Factor 5 Generates Unique Inflammation and Innate Immunity
Authors: Hubing Vanessa , Marquis Avery , Ziemann Chanasei , Moriyama Hideaki , Moriyama Etsuko N. , Zhang Luwen 
Published: February 2024

AbstractThe emergence of jaws in early vertebrates introduced a novel feeding apparatus and potent oral defenses but also increased the risk of physical injury and pathogen exposure. Innate immunity and inflammation constitute the body’s first line of defense against invading microbes and tissue damage, aiming to eliminate threats and restore internal homeostasis. Interferon regulatory factor 5 (IRF5) plays a critical role in orchestrating innate immunity and inflammation by regulating the transcription of genes that encode type I interferons (IFNs) and pro-inflammatory cytokines. Despite this, the evolution of IRF5 has remained poorly understood. We have identified the IRF5 and IRF6 genes in cartilaginous fish, including sharks. As cartilaginous fish represent one of the oldest surviving jawed vertebrate lineages, the presence of these genes suggests the genes have ancient origins potentially dating back hundreds of millions of years to early jawed vertebrates. Furthermore, our analysis shows that IRF5 has conserved nuclear export sequences and phosphorylation sites for activation throughout evolution from cartilaginous fish to humans, indicating these regulatory elements evolved early and have been maintained across jawed vertebrates. Additionally, the shift in subcellular localization of IRF5 from nucleus to cytosol, and of other interferon related IRFs, aligns with functional enhancements of IRFs in innate immunity and the emergence of IFNs across jawed vertebrates. This analysis implies that the evolution of jaws may have driven the emergence of new IRF members, the expansion of their functions, and the development of a unique inflammation and innate immune system.
Development of a whole-cell biosensor for ethylene oxide and ethylene
Authors: Moratti Claudia F. , Yang Sui Nin Nicholas , Scott Colin , Coleman Nicholas V. 
Published: February 2024

AbstractEthylene and ethylene oxide are widely used in the chemical industry, and ethylene is also important for its role in fruit ripening. Better sensing systems would assist risk management of these chemicals. Here, we characterise the ethylene regulatory system inMycobacteriumstrain NBB4 and use these genetic parts to create a biosensor. The regulatory genesetnR1andetnR2and cognate promoter Petnwere combined with a fluorescent reporter gene (fuGFP) in aMycobacteriumshuttle vector to create plasmid pUS301-EtnR12P. Cultures ofM. smegmatismc2-155(pUS301-EtnR12P) gave a fluorescent signal in response to ethylene oxide with a detection limit of 0.2 µM (9 ppb). By combining the epoxide biosensor cells with another culture expressing the ethylene monooxygenase, the system was converted into an ethylene biosensor. The co-culture was capable of detecting ethylene emission from banana fruit. These are the first examples of whole-cell biosensors for epoxides or aliphatic alkenes. This work also resolves long-standing questions concerning the regulation of ethylene catabolism in bacteria.
Voice patches in the marmoset auditory cortex revealed by wide-field calcium imaging
Authors: Zhang Yang , Song Xindong , Guo Yueqi , Chen Chenggang , Osmanski Michael S , Wang Xiaoqin 
Published: February 2024

ABSTRACTSpecies-specific vocalizations are behaviorally critical sounds. Similar to faces, species-specific vocalizations are important for the survival and social interactions of both humans and vocal animals. Face patches have been found in the brains of both human and non-human primates. In humans, a voice patch system has been identified on the lateral superior temporal gurus (STG) that is selective to human voices over other sounds. In non-human primates, while vocalization-selective regions were found on the rostral portion of the temporal lobe outside of the auditory cortex in both macaques and marmosets using functional magnetic resonance imaging (fMRI), it is yet clear whether vocalization-selective regions are present in the auditory cortex. Using wide-field calcium imaging, a technique with both high temporal and high spatial resolution, we discovered two voice patches in the marmoset auditory cortex that preferentially respond to marmoset vocalizations over other sounds and carry call types and identity information. One patch is located on the posterior primary auditory cortex (A1), and the other one is located on the anterior non-core region of the auditory cortex. These voice patches are functionally connected and hierarchically organized as shown by latency and selectivity analyses. Our findings reveal the existence of voice patches in the auditory cortex of marmosets and support the notion that similar cortical architectures are adapted for recognizing communication signals for both vocalizations and faces in different primate species.
Maternal Immune Activation Alters Temporal Precision of Spike Generation of CA1 Pyramidal Neurons by Unbalancing GABAergic Inhibition in the Offspring
Authors: Griego Ernesto , Cerna Camila , Sollozo-Dupont Isabel , Fuenzalida Marco , Galván Emilio J. 
Published: February 2024

AbstractMaternal immune activation (MIA) represents a risk factor for neuropsychiatric disorders associated with neurodevelopmental alterations. A growing body of evidence from rodents and non-human primates shows that MIA induced by viral or bacterial infections results in several neurobiological alterations in the offspring. These changes may play an important role in the pathophysiology of psychiatric disorders like schizophrenia and autism spectrum disorders, whose clinical features include impairments in cognitive processing and social performance. Such alterations are causally associated with the maternal inflammatory response to infection rather than with the infection itself. Previously, we reported that CA1 pyramidal neurons of mice exposed to MIA exhibit increased excitability accompanied by a reduction in dendritic complexity. However, potential alterations in cellular and synaptic rules that shape the neuronal computational properties of the offspring remain to be determined. In this study, using mice as subjects, we identified a series of cellular and synaptic alterations endured by CA1 pyramidal neurons of the dorsal hippocampus in a lipopolysaccharide-induced MIA model. Our data provide evidence that MIA reshapes the excitation-inhibition balance by decreasing the perisomatic GABAergic inhibition impinging on CA1 pyramidal neurons. These alterations yield a dysregulated amplification of the temporal and spatial synaptic integration. In addition, MIA-exposed offspring displayed social and anxiety-like abnormalities. Collectively, these findings contribute to the understanding of the cellular and synaptic alterations underlying the behavioral symptoms present in neurodevelopmental disorders associated with MIA.HighlightsLPS injection during pregnancy (MIA) increases cytokine production and decreases litter size.MIA increases the temporal summation of EPSPs in hippocampal neurons.MIA alters spatial summation and increases the probability of action potential discharge.MIA alters the inhibitory/excitatory balance of CA1 pyramidal cells.MIA alters the expression of GAD-positive interneurons.MIA alters the performance of several behavioral tests in offspring.
Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters
Authors: Dong Mei , Lin Haofeng , Pan Margaret , Huang Minghong , Liu Meiqin , Jiang Rendi , Lai Yana , Shi Aimin , Yao Bing , Hu Ben , Shi Zhengli , Zhang Aihua , Gao Yun , Zeng Wentao , Jianmin Li 
Published: February 2024

AbstractThis study aims to comprehensively characterize the SARS-CoV-2 BA.5 variants using K18 hACE2 transgenic mice and golden hamsters as model organisms. Previous research on SARS-CoV-2 has utilized both mouse and hamster models, leading to conflicting results concerning the virus’s lethality. In our study, the finding suggests that H11-K18 hACE2 golden hamsters closely mimic the disease progression observed in human COVID-19 cases caused by BA.5 variants, demonstrating consistent severity and symptoms comparable to severe infections.Additionally, hamsters exhibit heightened respiratory viral replication, accurately reflecting the clinical viral kinetics observed in humans. The study emphasizes the critical importance of selecting an appropriate animal model for SARS-CoV-2 research, while also providing robust support for the hypothesis that BA.5 variants contribute to fatal outcomes in COVID-19 cases. These findings highlight the pivotal role of the golden hamster model in advancing our understanding of the pathogenic mechanisms underlying SARS-CoV-2 variants, as well as in the development of targeted therapeutic strategies.Significance StatementOur research work explores groundbreaking insights that could reshape our understanding of COVID-19 and pave the way for targeted therapies. We use golden hamster models to express the possibility of different animal models could contribute to human diseases. We hope this finding could clarify some conflicts existed, and help further development of medication for COVID.
Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling
Authors: Horwitz Tanya B. , Zorina-Lichtenwalter Katerina , Gustavson Daniel E. , Grotzinger Andrew D. , Stallings Michael C. 
Published: February 2024

AbstractExternalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SU), substance use disorder (SUD), and other (non-SU/SUD) “behavioral disinhibition” (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models—each describing SUB, SUD, or BD traits--based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then applied trivariate Cholesky decomposition to these factors in order to identify BD-specific genomic variation and assess the partitioning of BD’s genetic covariance with each of the other facets. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large zero-order correlation (rg=.803). BD correlated strongly with the SUD (rg=.774) and SUB factors (rg=.778). In our initial decompositions, 33% of total BD variance remained after removing variance associated with SUD and SUB. The majority of covariance between BD and SU and between BD and SUD was shared across all factors. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their zero-order correlation increased to rg=.861; in corresponding decompositions, BD-specific variance decreased to 27%. In summary, BD, SU, and SUD were highly genetically correlated at the latent factor level, and a significant minority of genomic BD variation was not shared with SU and/or SUD. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates.
Nanobody-targeted conditional antimicrobial therapeutics
Authors: Ngambenjawong Chayanon , Ko Henry , Pishesha Novalia , Ploegh Hidde L. , Bhatia Sangeeta N. 
Published: February 2024

AbstractConditional therapeutics that rely on disease microenvironment-specific triggers for activation are a promising strategy to improve therapeutic cargos. Among the investigated triggers, protease activity is used most often, because of its dysregulation in several diseases. How to optimally fine-tune protease activation for different therapeutic cargos remains a challenge. Here, we designed nanobody-targeted conditional antimicrobial therapeutics to deliver a model therapeutic peptide and protein to the site of bacterial infection. We explored several parameters that influence proteolytic activation. We report the use of targeting nanobodies to enhance the activation of therapeutics that are otherwise activated inefficiently, despite extensive optimization of the cleavable linker. Specifically, pairing of Ly6G/C or ADAM10-targeting nanobodies with ADAM10-cleavable linkers improved activation via proximity-enabled reactivity. More broadly, this optimization framework provides a guideline for the development of conditional therapeutics to treat various diseases where protease activity is dysregulated.
In-situ microscopy-assisted meniscus-guided coating for highly sensitive reduced graphene oxide-based nanocomposite biosensor
Authors: Kim Su Yeong , Kim Min , Lee Jeong-Chan , Jeon Byeongjoo , Kim Hanul , Choi Siyoung Q. , Oh Byungkook , Kang Heemin , Kim Hyung-Ryong , Park Steve 
Published: February 2024

AbstractMeniscus-guided coating provides great potential for fabricating the nanomaterial-based thin film into high-performance biomedical devices due to the strong relationship between its experimental parameters and the resulting structural properties. However, the complex leverages of various fluid dynamics phenomena hamper optimization of structural properties and device performances. This is due to the absence of in-depth analytical techniques to observe, interpret, and control the solidification process. In this work, we propose an analytical strategy based on the rheological properties of a rGO-based solution using computational fluid dynamics modeling and in situ high-speed microscopy. Through this, we reveal the principles of the solidification mechanism that creates a rGO-based nanocomposite in the form of highly- and evenly-wrinkled thin film and the experimental condition at which this mechanism occurs. The optimized thin film presents high electroconductivity, low chip-to-chip signal variation, and multiplexed electrochemical biosensing performance for three classes of antibodies related to the excessive enrichment of endoplasmic reticulum stress, with detection limits of picomolar levels. This optimizing technique can be universally applied to understanding various solution-based coating systems, and can streamline the production of large-area and high-quality nanocomposite biosensors.
Modeling heterogeneity in single-cell perturbation states enhances detection of response eQTLs
Authors: Valencia Cristian , Nathan Aparna , Kang Joyce B. , Rumker Laurie , Lee Hyunsun , Raychaudhuri Soumya 
Published: February 2024

AbstractIdentifying response expression quantitative trait loci (reQTLs) can help to elucidate mechanisms of disease associations. Typically, such studies model the effect of perturbation as discrete conditions. However, perturbation experiments usually affect perturbed cells heterogeneously. We demonstrated that modeling of per-cell perturbation state enhances power to detect reQTLs. We use public single-cell peripheral blood mononuclear cell (PBMC) data, to study the effect of perturbations withInfluenza A virus(IAV),Candida albicans(CA),Pseudomonas aeruginosa(PA), andMycobacterium tuberculosis(MTB) on gene regulation. We found on average 36.9% more reQTLs by accounting for single cell heterogeneity compared to the standard discrete reQTL model. For example, we detected a decrease in the eQTL effect of rs11721168 forPXKin IAV. Furthermore, we found that on average of 25% reQTLs have cell-type-specific effects. For example, in IAV the increase of the eQTL effect of rs10774671 forOAS1was stronger in CD4+T and B cells. Similarly, in all four perturbation experiments, the reQTL effect forRPS26was stronger in B cells. Our work provides a general model for more accurate reQTL identification and underscores the value of modeling cell-level variation.
Pooled CRISPR interference screening identifies crucial transcription factors in gas-fermentingClostridium ljungdahlii
Authors: Zhang Huan , Feng Huibao , Xing Xin-Hui , Jiang Weihong , Zhang Chong , Gu Yang 
Published: February 2024

AbstractGas-fermentingClostridiumspecies hold tremendous promise for one-carbon biomanufacturing. To unlock their full potential, it is crucial to unravel and optimize the intricate regulatory networks that govern these organisms; however, this aspect is currently underexplored. In this study, we employed pooled CRISPR interference (CRISPRi) screening to uncover a wide range of functional transcription factors (TFs) inClostridium ljungdahlii, a representative species of gas-fermentingClostridium, with a special focus on the TFs associated with the utilization of carbon resources. Among the 425 TF candidates, we identified 75 and 68 TF genes affecting the heterotrophic and autotrophic growth ofC. ljungdahlii, respectively. We directed our attention on two of the screened TFs, NrdR and DeoR, and revealed their pivotal roles in the regulation of deoxyribonucleotides (dNTPs) supply, carbon fixation, and product synthesis inC. ljungdahlii, thereby influencing the strain performance in gas fermentation. Based on this, we proceeded to optimize the expression ofdeoRinC. ljungdahliiby adjusting its promoter strength, leading to improved growth rate and ethanol synthesis ofC. ljungdahliiwhen utilizing syngas. This study highlights the effectiveness of pooled CRISPRi screening in gas-fermentingClostridiumspecies, expanding the horizons for functional genomic research in these industrially important bacteria.
Nasal commensals reduceStaphylococcus aureusproliferation by restricting siderophore availability
Authors: Zhao Y , Bitzer A , Power JJ , Belikova D , Torres-Salazar B , Adolf LA , Gerlach DL , Krismer B , Heilbronner S 
Published: February 2024

BackgroundThe human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens such as methicillin-resistantStaphylococcus aureuscan reside within the nasal microbiota which increases the risk of infections. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species andS. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration but their role in the nasal microbiome is unknown.ResultsHere we show that siderophore acquisition is crucial forS. aureusnasal colonizationin vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced byS. aureus.We found that 80% of the strains engaged in siderophoremediated interactions withS. aureus.Non-pathogenic corynebacterial species were found to be prominent consumers ofS. aureussiderophores. In co-culture experiments, consumption of siderophores by competitors reducedS. aureusgrowth in an iron-dependent fashion.ConclusionsOur data show a wide network of siderophore mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displaceS. aureusfrom the nasal cavity of humans.
Enhanced cardiac mitochondrial biogenesis by nitro-oleic acid remedies diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction
Authors: Müller Marion , Schubert Torben , Welke Cornelius , Schulz Tina Johanna , Patschkowski Thomas , Maske Tibor , Lengenfelder Luisa Andrea , Landwehrjohann Lucia , Donhauser Elfi , Vogt Elisa Theres , Stratmann Bernd , Hense Jurek , Lüdtke Simon , Düfer Martina , Tolstik Elen , Dierks Johann , Hormann Felix-Levin , Heiles Sven , Lorenz Kristina , Reil Jan-Christian , Schopfer Francisco Jose , Freeman Bruce A. , Rudolph Volker , Schlomann Uwe , Klinke Anna 
Published: February 2024

AbstractPrevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, while treatment options are inadequate. Hypertension and obesity-related metabolic dysfunctions contribute to HFpEF progression. Nitro-oleic acid (NO2-OA) impacts metabolic processes by improving glucose tolerance and adipocyte function. In this study, 4 week treatment with NO2-OA ameliorated diastolic dysfunction in a HFpEF mouse model induced by high-fat diet and inhibition of the endothelial nitric oxide synthase. A proteomic analysis of left ventricular tissue revealed, that one third of the identified proteins, mostly mitochondrial proteins, were upregulated in hearts of NO2-OA-treated HFpEF mice compared to controls and vehicle-treated HFpEF mice, which was confirmed by immunoblot. Activation of the 5’-adenosine-monophosphate-activated-protein-kinase (AMPK) signaling pathway mediated an enhancement of mitochondrial biogenesis in hearts of NO2-OA-treated HFpEF mice. In cardiomyocytes under metabolic stress, NO2-OA increased mitochondrial protein level accompanied by enhanced oxidative phosphorylation. In conclusion, targeting mitochondrial integrity in HFpEF leads to improved diastolic function.