bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale fMRI dataset for the design of motor-based Brain-Computer Interfaces
Authors: Bom Magnus S , Brak Annette MA , Raemaekers Mathijs , Ramsey Nick F , Vansteensel Mariska J , Branco Mariana P
Published: July 2024

Functional Magnetic Resonance Imaging (fMRI) data is commonly used to map sensorimotor cortical organization and to localise electrode target sites for implanted Brain-Computer Interfaces (BCIs). Functional data recorded during motor and somatosensory tasks from both adults and children specifically designed to map and localise BCI target areas throughout the lifespan is rare. Here, we describe a large-scale dataset collected from 155 human participants while they performed motor and somatosensory tasks involving the fingers, hands, arms, feet, legs, and mouth region. The dataset includes data from both adults and children (age range: 6-89 years) performing a set of standardized tasks. This dataset is particularly relevant to study developmental patterns in motor representation on the cortical surface and for the design of paediatric motor-based implanted BCIs.
Loss of heterozygosity in gastric cancers in a set of Mexican patients
Authors: Larios-Serrato Violeta , Valdez-Salazar Hilda-Alicia , Torres Javier , Camorlinga-Ponce Margarita , Piña-Sánchez Patricia , Minauro-Sanmiguel Fernando , Ruiz-Tachiquín Martha-Eugenia
Published: July 2024

Worldwide, gastric cancer (GC) is a common malignancy with the highest mortality rate among digestive system diseases. The present study of GC and loss of heterozygosity (LOH) is relevant to understanding tumor biology and establishing essential aspects of cancer. Here, DNA samples from Mexican patients with diffuse GC (DGC), intestinal GC (IGC), or non-atrophic gastritis (NAG; control) were purified, and whole-genome high-density arrays were performed. Posteriorly, LOH was identified among the tissue samples, and cancer genes and signaling pathways were analyzed to determine the most altered. Detailed bioinformatics analysis was developed to associate LOH with the Hallmarks of Cancer according to their frequency in patient samples, participation in metabolic pathways, network interactions, and enrichment of Cancer Hallmark genes. LOH-genes in GC were PTPR, NDUFS3, PAK3, IRAK1, IKBKG, TKTL1, PRPS1, GNAI2, RHOA, MAPKA, and MST1R. Genes that stand out at NAG involve proliferation and growth; those at IGC trigger genomic instability, tissue invasion, metastasis, and arrest of cell death; and those at DGC involve energy metabolism, the destruction of immune evasion, and replicative immortality. Other events, such as sustained angiogenesis, were similar between NAG-IGC-DGC. Together, these are molecular, cellular, and metabolic events that must be monitored in GC patients. Our findings must be validated to develop molecular tests for diagnosis, prognosis, treatment response, and, most importantly, screening tests.
A comparative analysis of the performance of chatGPT4, Gemini and Claude for the Polish Medical Final Diploma Exam and Medical-Dental Verification Exam
Authors: Wójcik Dorota , Adamiak Ola , Czerepak Gabriela , Tokarczuk Oskar , Szalewski Leszek
Published: July 2024

In the realm of medical education, the utility of chatbots is being explored with growing interest. One pertinent area of investigation is the performance of these models on standardized medical examinations, which are crucial for certifying the knowledge and readiness of healthcare professionals. In Poland, dental and medical students have to pass crucial exams known as LDEK (Medical-Dental Final Examination) and LEK (Medical Final Examination) exams respectively. The primary objective of this study was to conduct a comparative analysis of chatbots: ChatGPT-4, Gemini and Claude to evaluate their accuracy in answering exam questions of the LDEK and the Medical-Dental Verification Examination (LDEW), using queries in both English and Polish. The analysis of Model 2, which compared chatbots within question groups, showed that the chatbot Claude achieved the highest probability of accuracy for all question groups except the area of prosthetic dentistry compared to ChatGPT-4 and Gemini. In addition, the probability of a correct answer to questions in the field of integrated medicine is higher than in the field of dentistry for all chatbots in both prompt languages. Our results demonstrate that Claude achieved the highest accuracy in all areas analysed and outperformed other chatbots. This suggests that Claude has significant potential to support the medical education of dental students. This study showed that the performance of chatbots varied depending on the prompt language and the specific field. This highlights the importance of considering language and specialty when selecting a chatbot for educational purposes.
Causal effect of the gut microbiota on the risk of psychiatric disorders and the mediating role of immunophenotypes
Authors: Hong Zhisheng , He Ao , Huang Guanglong , Chen Xiaofeng , Wang Xiaoyu , Li Xiaoyang , Chen Hailun , Zhao Xinqi , Xu Ying , Xu Yangheng , Ouyang Pei , Wang Hai , Deng Jiapeng , Chen Pengyu , Zhang Xian , Qi Songtao , Li Yaomin
Published: July 2024

Background

Growing evidence indicates a significant correlation between the gut microbiota, immune system, and psychiatric disorders. Nevertheless, the impacts and interactions of the gut microbiota and immunophenotypes on psychiatric disorders remain unclear.

Methods

We utilized a bidirectional Mendelian randomization (MR) study to evaluate the causal associations among the gut microbiota, immunophenotypes, and psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and Tourette’s syndrome (TS). The primary analysis was conducted using the inverse variance weighted (IVW) method, with several complementary sensitivity analyses being performed to ensure the reliability of the results.

Results

Our study reveals significant causal relationships between 22 immunophenotypes, 15 types of gut microbiota, and various psychiatric disorders. We further sought to ascertain whether immunophenotypes act as intermediaries in the pathway from gut microbiota to psychiatric disorders. In particular, three immunophenotypes were identified that mediate the causal effects of different gut microbiota on ADHD. Additionally, one immunophenotype was detected to mediate the causal effects of gut microbiota on PTSD.

Conclusions

Our study indicates that immunophenotypes partially mediate the pathway from the gut microbiota to psychiatric disorders.
Caries incidence in school-based oral health programs
Authors: Ruff Ryan Richard
Published: July 2024

Background

School-based caries prevention can increase access to critical dental services and reduce oral health inequities. However, little is known regarding the incidence of dental caries in children participating in school caries prevention, and caries diagnosis is often interval censored.

Methods

In this paper, we used data from a longitudinal, school-based, randomized clinical trial of minimally invasive treatments for dental caries to estimate the per-visit incidence rate and compare the hazard of dental caries in children receiving either silver diamine fluoride or glass ionomer dental sealants. To account for interval censoring, we used semiparametric transformation models for univariate failure time data and imputed the caries incidence using G-imputation.

Results

There were 3040 children that met inclusion criteria for analysis, 1516 (49.9%) of which were randomly assigned to receive silver diamine fluoride and 1524 (50.1%) assigned to receive glass ionomer dental sealants. There were no differences in the hazard of caries between treatments (HR = 0.98, 95% CI = 0.73, 1.24), while children with caries at baseline had a significant increase in the hazard of new caries (HR = 2.54, 95% CI = 2.26, 2.83) compared to those that were caries-free. The per-visit caries incidence ranged from 4.8 to 11.1 per 1000 person-years and increased with each successive study observation.

Conclusions

School-based caries prevention can positively affect caries incidence, and results can be used to inform future program design and implementation.
K-mer Genome-wide Association Study for Anthracnose andBCMVResistance in the Andean Diversity Panel
Authors: Wiersma Andrew T. , Hamilton John P. , Vaillancourt Brieanne , Brose Julia , Awale Halima E. , Wright Evan M. , Kelly James D. , Buell C. Robin
Published: July 2024

Limited genomic resources and closely linked marker-trait associations for common beans (Phaseolus vulgarisL.) have limited breeders from fully utilizing molecular genetics technologies to maximize genetic gain. The emergence of virulent races of anthracnose (caused byColletotrichum lindemuthianum) andBean Common Mosaic Virus(BCMV) highlight the need for improved methods to identify and incorporate pan-genomic variation in breeding for disease resistance. We sequenced theP. vulgarisAndean Diversity Panel (ADP) and performed a genome-wide association study (GWAS) to identify associations for resistance to BCMV and eight races of anthracnose. Historical single nucleotide polymorphism (SNP)-chip and phenotypic data enabled a three-way comparison between SNP-chip, reference-based whole genome shotgun sequence (WGS)-SNP, and reference-freek-mer GWAS. Across all traits, there was excellent concordance between SNP-chip, WGS-SNP, andk-mer GWAS results—albeit at a much higher marker resolution for the WGS data sets. Significantk-merhaplotype variation revealed selection of the linkedI-gene andCo-utraits in North American breeding lines and cultivars. Due tok-mer mapping criteria and the absence of target loci in the reference genome due to structural variation, only 9.1 to 47.3% of the significantly associatedk-mers were mapped to the reference genome. To determine the genetic context ofcis-associatedk-mers, we generated whole genome assemblies of four ADP accessions and identified an expanded local repertoire of disease resistance genes associated with resistance to anthracnose and BCMV. With access to variant data in the context of a pan-genome, high resolution mapping of agronomic traits for common bean is now feasible.

CORE IDEAS

K-mer-based GWAS offers new advantages for mapping pan-genomic variation

Comparison of reference-based SNP to reference-freek-mer GWAS

Novel discovery ofcis-associatedk-mers for dry bean disease resistance

PLAIN LANGUAGE SUMMARY

Improving disease resistance in crop species such as bean is critical. We surveyed the genomes of a diverse set of bean lines and identified sequences associated with resistance to a fungal and viral pathogen. Access to the genomes of this diversity panel of beans will permit additional discoveries on the role of structural variation in phenotypes, including disease resistance.
Pervasive neurovascular dysfunction in the ventromedial prefrontal cortex of female depressed suicides with a history of childhood abuse
Authors: Wakid Marina , Almeida Daniel , Denniston Ryan , Chawla Anjali , Aouabed Zahia , Davoli Maria Antonietta , Ellerbeck Kristin , Rahimian Reza , Yerko Volodymyr , Leonova-Erko Elena , Turecki Gustavo , Mechawar Naguib
Published: July 2024

Exposure to early life adversity (ELA) poses a significant global public health concern, with profound pathophysiological implications for affected individuals. Studies suggest that ELA contributes to endothelial dysfunction, bringing into question the functional integrity of the neurovascular unit in brain regions vulnerable to chronic stress. Despite the importance of the neurovasculature in maintaining normal brain physiology, human neurovascular cells remain poorly characterized, particularly with regard to their contributory role in ELA-associated pathophysiologies. In this study, we present the first comprehensive transcriptomic analysis of intact microvessels isolated from postmortem ventromedial prefrontal cortex samples from adult healthy controls (CTRL) and matched depressed suicides with histories of ELA. Our findings point to substantive differences between men and women, with the latter exhibiting widespread gene expression changes at the neurovascular unit, including the key vascular nodal regulatorsKLF2andKLF4, alongside a broad downregulation of immune-related pathways. These results suggest that the neurovascular unit plays a larger role in the neurobiological consequences of ELA in human females.
Three-Dimensional Quantitative Structure-Activity Relationships and Molecular Dynamic Simulations Studies to Discover Aurora Kinase-B Inhibitors
Authors: Anand Selvam Athavan Alias , Kabilan Senthamaraikannan
Published: July 2024

The serine-threonine kinase gene Aurora–B kinase plays a critical role in spindle assembly, chromosome alignment, mitotic checkpoint activation, and cytokinesis. The overexpression of Aurora-B causes errors in cell division and multinucleation in centrosome numbers leads to cancer. Three–dimensional Quantitative Structure-Activity Relationship studies were conducted on known inhibitors to find valid pharmacophore hypotheses. The five features hypothesis AADRR with better parameters using partial least square analysis has been selected for virtual screening. Molecular docking was applied to find the binding mode interactions of ligands with the Aurora-B binding pocket. Lys 106, Ala 157, Glu 161, and Phe 219 were identified as crucial residues that formed several interactions with the ligands which are essential for Aurora–B inhibition. After the different levels of screening, five compounds from the National Cancer Institute database were acknowledged as novel inhibitors of Aurora–B. The active site interactions of the protein-ligand complex were examined by molecular dynamics simulation studies.

Graphical Abstract
Model of a striatal circuit exploring biological mechanisms underlying decision-making during normal and disordered states
Authors: Beck Dirk W. , Heaton Cory N. , Davila Luis D. , Rakocevic Lara I. , Drammis Sabrina M. , Tyulmankov Danil , Vara Paulina , Giri Atanu , Umashankar Beck Shreeya , Zhang Qingyang , Pokojovy Michael , Negishi Kenichiro , Batson Serina A , Salcido Alexis A. , Reyes Neftali F. , Macias Andrea Y. , Ibanez-Alcala Raquel J. , Hossain Safa B. , Waller Graham L. , O’Dell Laura E. , Moschak Travis M. , Goosens Ki A. , Friedman Alexander
Published: July 2024

Decision-making requires continuous adaptation to internal and external contexts. Changes in decision-making are reliable transdiagnostic symptoms of neuropsychiatric disorders. We created a computational model demonstrating how the striosome compartment of the striatum constructs a mathematical space for decision-making computations depending on context, and how the matrix compartment defines action value depending on the space. The model explains multiple experimental results and unifies other theories like reward prediction error, roles of the direct versus indirect pathways, and roles of the striosome versus matrix, under one framework. We also found, through new analyses, that striosome and matrix neurons increase their synchrony during difficult tasks, caused by a necessary increase in dimensionality of the space. The model makes testable predictions about individual differences in disorder susceptibility, decision-making symptoms shared among neuropsychiatric disorders, and differences in neuropsychiatric disorder symptom presentation. The model reframes the role of the striosomal circuit in neuroeconomic and disorder-affected decision-making.

Highlights

Striosomes prioritize decision-related data used by matrix to set action values.

Striosomes and matrix have different roles in the direct and indirect pathways.

Abnormal information organization/valuation alters disorder presentation.

Variance in data prioritization may explain individual differences in disorders.

eTOC

Beck et al. developed a computational model of how a striatal circuit functions during decision-making. The model unifies and extends theories about the direct versus indirect pathways. It further suggests how aberrant circuit function underlies decision-making phenomena observed in neuropsychiatric disorders.
Deciphering the transcriptional regulatory network ofYarrowia lipolyticausing machine learning
Authors: Kerssemakers Abraham A.J. , Krishnan Jayanth , Rychel Kevin , Zielinski Daniel C. , Palsson Bernhard O. , Sudarsan Suresh
Published: July 2024

The transcriptional regulatory network (TRN) in Yarrowia lipolytica coordinates its cellular processes, including the response to various stimuli. The TRN has been difficult to study due to its complex nature. In industrial-size fermenters, environments are often not homogenous, resulting in Yarrowia experiencing fluctuating conditions during a fermentation. Compared with homogenous laboratory conditions, these fluctuations result in altered cellular states and behaviors due to the action of the TRN. Here, a machine learning approach was deployed to modularize the transcriptome to enable meaningful description of its changing composition. To provide a sufficiently broad dataset, a wide range of relevant fermentation conditions (nutrient limitations, growth rates, pH values, oxygen availability and CO2 stresses) were run and samples obtained for RNA-Seq generation. We thus significantly increased the number of publicly available transcriptomic dataset on Y. lipolytica W29. In total, 23 independently modulated gene sets (termed iModulons) were identified of which 9 could be linked to corresponding regulons in S. cerevisiae. Strong responses were found in relation to oxygen limitation and elevated CO2 concentrations represented by (i) altered ribosomal protein synthesis, (ii) cell cycle disturbances, (iii) respiratory gene expression, and (iv) redox homeostasis. These results provide a fine-grained systems-level understanding of the Y. lipolytica TRN in response to industrially meaningful stresses, providing engineering targets to design more robust production strains. Moreover, this study provides a guide to perform similar work with poorly characterized single-cellular eukaryotic organisms.

Highlights

- A large screening setup significantly expands the public RNA-Seq library onY. lipolytica.

- This work provides a systems-level understanding of the TRN in response to industrial stresses.

- iModulon analysis can help accelerate bioprocess development.

- Results can guide similar work on poorly characterized single-cellular eukaryotic organisms.
Carbon monoxide-driven bioethanol production operates via a tungsten-dependent catalyst
Authors: Lemaire Olivier N. , Belhamri Mélissa , Shevchenko Anna , Wagner Tristan
Published: July 2024

Microbial alcohol production from waste gasses is a game changer for sustainable carbon cycling and remediation. While the biotechnological process employingClostridium autoethanogenumto transform syngas (H2/CO2/CO) is blooming, the reactions involved in ethanol biosynthesis remain to be demonstrated. Here, we experimentally showed that ethanol production initiates via a tungsten-dependent aldehyde:ferredoxin oxidoreductase (AFOR), which reduces acetate to acetaldehyde. Such an unfavourable reaction has often been considered unsuitable for a biological process. To answer this riddle, we demonstrated that the thermodynamic pull of CO-oxidation and ethanol synthesis is crucial for triggering acetate reduction. The experimental setup performed with native CO-dehydrogenase and AFOR highlighted the key role of ferredoxin in stimulating the activity of both metalloenzymes and electron shuttling. The crystal structure of holo AFOR refined to 1.59-Å resolution, together with its biochemical characterisation, provides new insights into the reaction mechanism and the specificities of this enzyme fundamental to sustainable biofuel production.
Investigation of Bactericidal effect of Earwax onEscherichia coliandStaphylococcus aureusisolated from skin and stool samples of undergraduate students, Federal University of Agriculture Makurdi, Benue State, Nigeria
Authors: Tsenongu Aondongu Joseph , Ichor Tersagh Smart , Ashar Saaondo James , Mena Ajekwe Stephen , Kwaghve Avalumun
Published: July 2024

Earwax is a normal product of the ear, which protects the skin of the ear from water, dirt dust and infection. The aim of this study was to determine the antibacterial activity of earwax onStaphylococcus aureusandEscherichia coliisolated from skin and stool respectively. Bacteriological investigations were carried out using culture and morphological characteristics, conventional biochemical tests and antibiotic susceptibility testing of both earwax and conventional antibiotics against the presumptive isolates. Occurrence ofStaphylococcus aureus(58.3%) andEscherichia coli(45.8%) in skin and stool samples were respectively determined based on cultural and morphological characteristics. Conventional biochemical tests were carried out on the 14 and 10 presumptiveStaphylococcus aureusandEscherichia coliisolates and then 10 and 8 presumptive isolates were detected respectively. The antibacterial activity of the test agent was determined using the agar well diffusion technique; five different concentrations (20% v/v, 40% v/v, 60% v/v, 80% v/v, and 100% v/v) of the test agents were evaluated against the bacterial isolates. The earwax showed antibacterial activity against both isolates (except the 20% v/v forStaphylococcus aureus) at all concentrations used with antibacterial activity directly proportional to earwax concentration and a better antibacterial activity againstStaphylococcus aureus(zone of inhibition 20mm)aureusthanEscherichia coli. Antibiotic susceptibility testing was carried out on the 10(41.7%) and 8(33.3%) presumptive isolates ofStaphylococcus aureusandEscherichia colirespectively based on Kirby Bauer method. Highest rate of susceptibilities of theStaphylococcus aureusisolates to antibiotics were observed in Erythromycin (100%), while forEscherichia coliwere observed in Erythromycin and Levofloxacin (100%). Meanwhile, highest rate of resistant toStaphylococcus aureusisolates were observed in Gentamicin (100%) while forEscherichia coliwas observed in Amoxicillin (100%). This study shows that earwax plays a critical role in the fight against infectious microorganisms as some of the antibiotics.
Contrast gain control is a reparameterization of a population response curve
Authors: Tring Elaine , Moosavi S. Amin , Dipoppa Mario , Ringach Dario L.
Published: July 2024

Neurons in primary visual cortex (area V1) adapt in different degrees to the average contrast of the environment, suggesting that the representation of visual stimuli may interact with the state of cortical gain control in complex ways. To investigate this possibility, we measured and analyzed the responses of neural populations to visual stimuli as a function of contrast in different environments, each characterized by a unique distribution of contrast. Our findings reveal that, for a given stimulus, the population response can be described by a vector functionr(gec), where the gaingeis a decreasing function of the mean contrast of the environment. Thus, gain control can be viewed as a reparameterization of a population response curve, which is invariant across environments. Different stimuli are mapped to distinct curves, all originating from a common origin, corresponding to a zero-contrast response. Altogether, our findings provide a straightforward, geometric interpretation of contrast gain control at the population level and show that changes in gain are well coordinated among members of a neural population.
Nonenzymatic, prebiotic aminoacylation couples chirality of RNA and protein
Authors: Davisson Joshua A. , Kalb Evan M. , Knudson Isaac J. , Schepartz Alanna , Engelhart Aaron E. , Adamala Katarzyna P.
Published: July 2024

Life as we know it depends on the homochirality of nucleic acids and proteins. However, there is no widely accepted explanation for why life uses only D-sugars for nucleic acids and L-amino acids for proteins. Here we demonstrate a prebiotically plausible method of nonenzymatic aminoacylation in a water ice-eutectic phase. These reactions produce high yields of aminoacyl-tRNAs, which are active in translation. Surprisingly, we discovered these nonenzymatic aminoacylation conditions were stereoselective, favoring coupling of amino acids and RNA of “opposite” L- and D- configurations. D-RNA shows greater aminoacylation yields for L-amino acids. The opposite was true for L-RNA, which had greater yields with D-amino acids. Nucleic acid backbone chirality influencing stereoselectivity of aminoacylation presents the missing link in the origin of modern biochemistry. This phenomenon provides insight into the chirality of the RNA world, and helps to explain the “opposite” stereochemistry of modern biomolecules.
Fast Targeted Metabolomics for Analyzing Metabolic Diversity of Bacterial Indole Derivatives in ME/CFS Gut Microbiome
Authors: Tian Huidi , Wang Lei , Aiken Elizabeth , Ortega Robert Jervine V. , Hardy Rachel , Placek Lindsey , Kozhaya Lina , Unutmaz Derya , Oh Julia , Yao Xudong
Published: July 2024

Disruptions in microbial metabolite interactions due to gut microbiome dysbiosis and metabolomic shifts may contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other immune-related conditions. The aryl hydrocarbon receptor (AhR), activated upon binding various tryptophan metabolites, modulates host immune responses. This study investigates whether the metabolic diversity—the concentration distribution—of bacterial indole pathway metabolites can differentiate bacterial strains and classify ME/CFS samples. A fast targeted liquid chromatography-parallel reaction monitoring method at a rate of 4 minutes per sample was developed for large-scale analysis. This method revealed significant metabolic differences in indole derivatives amongB. uniformisstrains cultured from human isolates. Principal component analysis identified two major components (PC1, 68.9%; PC2, 18.7%), accounting for 87.6% of the variance and distinguishing two distinctB. uniformisclusters. The metabolic difference between clusters was particularly evident in the relative contributions of indole-3-acrylate and indole-3-aldehyde. We further measured concentration distributions of indole derivatives in ME/CFS by analyzing fecal samples from 10 patients and 10 healthy controls using the fast targeted metabolomics method. An AdaBoost-LOOCV model achieved moderate classification success with a mean LOOCV accuracy of 0.65 (Control: precision of 0.67, recall of 0.60, F1-score of 0.63; ME/CFS: precision of 0.64, recall of 0.7000, F1-score of 0.67). These results suggest that the metabolic diversity of indole derivatives from tryptophan degradation, facilitated by the fast targeted metabolomics and machine learning, is a potential biomarker for differentiating bacterial strains and classifying ME/CFS samples. Mass spectrometry datasets are accessible at the National Metabolomics Data Repository (ST002308, DOI: 10.21228/M8G13Q; ST003344, DOI: 10.21228/M8RJ9N; ST003346, DOI: 10.21228/M8RJ9N).
Templating of Monomeric Alpha-Synuclein Induces Inflammation and SNpc Dopamine Neuron Death in a Genetic Mouse Model of Synucleinopathy
Authors: Byrne Matthew D. , Petramfar Peyman , Smeyne Richard J
Published: July 2024

While the etiology of most cases of Parkinson’s disease (PD) are idiopathic, it has been estimated that 5-10% of PD arise from known genetic mutations. The first mutations described that leads to the development of an autosomal dominant form of PD are in the SNCA gene that codes for the protein alpha-synuclein (α-syn). α-syn is an abundant presynaptic protein that is natively disordered and whose function is still unclear. In PD, α-syn misfolds into multimeric β-pleated sheets that aggregate in neurons (Lewy Bodies/neurites) and spread throughout the neuraxis in a pattern that aligns with disease progression. Here, using IHC, HPLC, and cytokine analysis, we examined the sequelae of intraparenchymal brain seeding of oligomeric pre-formed fibrils (PFFs) and monomeric α-syn in C57BL/6J (WT) and A53T SNCA mutant mice. We found that injection of PFFs, but not monomeric α-syn, into the striatum of C57BL/6J mice induced spread of aggregated α-syn, loss of SNpc DA neurons and increased neuroinflammation However, in A53T SNCA mice, we found that both PFFs and monomeric α-syn induced this pathology. This suggests that the conformation changes in α-syn seen in the A53T strain can recruit wild-type α-syn to a pathological misfolded conformation which may provide a mechanism for the induction of PD in humans with SNCA duplication/triplication.
Variability in Individual Native Fibrin Fiber Mechanics
Authors: Helms Christine C.
Published: July 2024

Fibrin fibers are important structural elements in blood coagulation. They form a mesh network that acts as a scaffold and imparts mechanical strength to the clot. A review of published work measuring the mechanics of fibrin fibers reveals a range of values for fiber extensibility. This study investigates fibrinogen concentration as a possible variable responsible for variability in fibrin fiber mechanics. It expands previous work to describe the modulus, strain hardening, extensibility, and the force required for fiber failure when fibers are formed with different fibrinogen concentrations. Lateral force atomic force microscopy was used to create stress-strain curves for individual nanofibers and data was obtained from fibers formed from 0.5 NIH U/ml thrombin, 55 Loewy U/ml FXIII, and 1 mg/ml or 2 mg/ml fibrinogen. Analysis of the mechanical properties showed fiber formed from 1 mg/ml fibrinogen and 2 mg/ml fibrinogen had significantly different mechanical properties. To help clarify our findings we developed two behavior profiles to describe individual fiber mechanics. The first describes a fiber with low initial modulus and high extensible, that undergoes strain hardening around 100 % strain, and has moderate strength. A majority of fibers formed with 1 mg/ml fibrinogen showed this behavior profile. The second profile describes a fiber with a high initial modulus, minimal strain hardening, high strength, and low extensibility. Most fibrin fibers formed with 2 mg/ml fibrinogen were described with this second behavior profile. In conclusion, we see a range of behaviors from fibers formed from native fibrinogen molecules but various fibrinogen concentrations. Potential differences in fiber formation is investigated with SEM. It is likely this range of behaviors also occurs in vivo. Understanding the variability in mechanical properties could contribute to a deeper understanding of pathophysiology of coagulative disorders.
The Unkempt RNA binding protein reveals a local translation program in centriole overduplication
Authors: Martinez Abraham , Stemm-Wolf Alexander J. , Sheridan Ryan M. , Taliaferro Matthew J. , Pearson Chad G.
Published: July 2024

Excess centrosomes cause defects in mitosis, cell-signaling, and cell migration, and therefore their assembly is tightly regulated. Plk4 controls centriole duplication at the heart of centrosome assembly, and elevation of Plk4 promotes centrosome amplification (CA), a founding event of tumorigenesis. Here, we investigate the transcriptional consequences of elevated Plk4 and find Unkempt, a gene encoding an RNA binding protein with roles in translational regulation, to be one of only two upregulated mRNAs. Unk protein localizes to centrosomes and Cep131-positive centriolar satellites and is required for Plk4-induced centriole overduplication in an RNA-binding dependent manner. Translation is enriched at centrosomes and centriolar satellites with Unk and Cep131 promoting this localized translation. A transient centrosomal downregulation of translation occurs early in Plk4-induced CA. CNOT9, an Unk interactor and component of the translational inhibitory CCR4-NOT complex, localizes to centrosomes at this time. In summary, centriolar satellites and Unk promote local translation as part of a translational program that ensures centriole duplication.
Effects of two different compounds on seizure suppression using the zebrafish PTZ-seizure model
Authors: Araujo Fernández Jhonathan Angel , de Moura Thatiane Cristina , Vila Sabela Fernández , Gaytán Juan Andrés Rubiolo , López-Díaz Iñaki , Learte-Aymamí Soraya , Vázquez M. Eugenio , Mayán Maria D. , Sánchez Laura , Maurer-Morelli Claudia Vianna
Published: July 2024

Epilepsies are a common and severe neurological condition characterized by spontaneous and recurrent seizures. Although anti-seizure medications are effective for most patients, about 30% remain pharmacoresistant. Moreover, uncontrolled seizures are associated with risk factors and shortened life expectancy for individuals with refractory epilepsy. Preclinical studies are an essential step for drug discovery and the zebrafish (Danio rerio) has been successfully employed for this purpose. In this study, we applied the zebrafish PTZ-seizure model to investigate the effect of two compounds on seizure suppression, Tripeptide (p-BTX-I) and the Cx43 peptide CX2. Zebrafish larvae at 6 days post-fertilization (dpf) were exposed to both compounds, according to their group, 24h prior to PTZ-seizure induction. We quantified the compounds’ effect on seizure latency, number of seizures and transcript levels of genes related to inflammation, oxidative stress, and apoptosis (il1b, tnfa, cox1, cox2a, il6, casp3a, casp9, baxa, bcl2a, nox1, sod1andcat).

Our results showed that CX2 at a concentration of 0.1 μM/mL yielded the best outcome for seizure suppression as it reduced the number of seizures and increased the seizure latency. Additionally, CX2 treatment before PTZ-induced seizures decreased the transcript ofil1b, il6, tnfaandcox1genes, all related to inflammation. A bio-distribution study showed that the CX2 reached the zebrafish brain at both times investigated, 1h and 6h. Similarly, the tripeptide exhibited anti-inflammatory and anti-apoptotic action, reducing mRNA expression of theil1bandcasp9genes. Our findings suggest that both Tripeptide and CX2 hold translational potential for seizure suppression.
Understanding the Pathogenicity of Parkin Catalytic Domain Mutants
Authors: Wagner Julian P. , Sauvé Véronique , Gehring Kalle
Published: July 2024

Mutations in the E3 ubiquitin ligase parkin cause a familial form of Parkinson’s disease (PD). Parkin and the mitochondrial kinase PINK1 assure quality control of mitochondria through selective autophagy of mitochondria (mitophagy). Whereas numerous parkin mutations have been functionally characterized and their structural basis revealed, several pathogenic PD mutations found in the catalytic RING2 domain remain poorly understood. Here, we characterize two pathogenic RING2 mutants, T415N and P437L and shed light on the underlying structural causes. For this purpose, we use biochemicalin vitroassays in combination with AlphaFold modeling. We demonstrate that both mutants exhibit impaired activity using autoubiquitination and ubiquitin vinyl sulfone assays. After determining the parkin minimal ubiquitin binding region, we show that both mutants display impaired binding to the ubiquitin molecule charged onto the E2 enzyme. Finally, we employ the most recent version of AlphaFold 3 to generate a structural model of the phospho-parkin/phospho-ubiquitin/ubiquitin-charged E2 complex. This model consolidates our findings and provides a structural understanding for the pathogenicity of these two parkin variants. A better understanding of the different PD mutations at the molecular level can pave the way for personalized treatments and the design of small molecule therapeutics for the treatment of PD.
Exploring potential targets for quercetin treatment of colorectal cancer through network pharmacology and molecular docking technology
Authors: Qian Yuanyuan , Wang Zhaojunli , Ji Jiancheng , Fu Wenlong
Published: July 2024

Objective

To explore the potential targets of quercetin in the treatment of colorectal cancer through network pharmacology and molecular docking technology.

Method

Download the 3D structure of quercetin from Pubchem database, use PharmaMapper database for reverse docking, and screen protein targets based on zscore; GEO database screening for colorectal cancer datasets and screening for differentially expressed genes; Screening common genes for protein targets and differentially expressed genes using Wayne diagrams; Use DAVID database for GO and KEGG analysis. Use ChemDraw, 20.0 AutoDock, and Pymol for molecular docking.

Result

The results showed that 24 common genes and 13 signaling pathways were identified from the reverse docking data of quercetin and the GSE33113 gene chip data of colorectal cancer; Molecular docking results showed that quercetin showed good binding energy with 1ykc, 1k3y, 1kbq, 2bkz, 1xo2, 1og5, 2bsm.

Conclusion

Quercetin may exert its therapeutic effect on colorectal cancer through a multi target and multi channel mechanism.
A new tuna specimen (GenusAuxis) from the Duho Formation (Miocene) of South Korea
Authors: Suh Dayun , Kim Su-Hwan , Nam Gi-Soo
Published: July 2024

A partially preserved caudal vertebrae imprint of a tuna was discovered from the Duho Formation (Miocene) of South Korea. This specimen was assigned to the genusAuxisand represents the second record of fossilAuxisfound in South Korea and in the world. We compared the vertebral morphology of the studied specimen to that of currently known species ofAuxis, including extinct taxa. However, the specimen could not be assigned to any extant or new species ofAuxisdue to anatomical differences and a lack of comparability. The discovery of a new specimen ofAuxisaligns with theories of high marine biodiversity in the East Sea (Sea of Japan) and its opening in the Early to Middle Miocene. A widely opened East Sea and upwelling activities might have increased the abundance and diversity of large oceanic fishes such as tunas during the deposition of the Duho Formation. The specimen supports paleoenvironmental interpretations of the Duho Formation as pelagic and subtropical. A taphonomic scenario of the specimen was inferred based on the lack of anal pterygiophores and the leaf imprint on the matrix. The specimen would have been exposed for at least a month in a low-energy sedimentary environment at the deep-sea bottom and would have undergone disintegration before being buried.
Comparing coherent and incoherent models for quantum homogenization
Authors: Beever Anna , Violaris Maria , Marletto Chiara , Vedral Vlatko
Published: July 2024

Here we investigate the role of quantum interference in the quantum homogenizer, whose convergence properties model a thermalization process. In the original quantum homogenizer protocol, a system qubit converges to the state of identical reservoir qubits through partial-swap interactions, that allow interference between reservoir qubits. We design an alternative, incoherent quantum homogenizer, where each system-reservoir interaction is moderated by a control qubit using a controlled-swap interaction. We show that our incoherent homogenizer satisfies the essential conditions for homogenization, being able to transform a qubit from any state to any other state to arbitrary accuracy, with negligible impact on the reservoir qubits' states. Our results show that the convergence properties of homogenization machines that are important for modeling thermalization are not dependent on coherence between qubits in the homogenization protocol. We then derive bounds on the resources required to re-use the homogenizers for performing state transformations. This demonstrates that both homogenizers are universal for any number of homogenizations, for an increased resource cost.

Published by the American Physical Society
2024
Nuclear medium meson structures from the Schwinger proper-time Nambu–Jona-Lasinio model
Authors: Gifari Geoffry , Hutauruk Parada T. P. , Mart Terry
Published: July 2024

In this paper, we report the results of our study on the nuclear medium modifications of the meson electromagnetic form factors in the framework of the Nambu–Jona-Lasinio model with the help of the Schwinger proper-time regularization scheme to tame the loop divergence and simulate the effect of QCD confinement. In our current approach, the meson structure and nuclear medium are constructed in the same Nambu–Jona-Lasinio model at the quark level. We examine the free-space and in-medium charge radii of kaon and pion, the spacelike elastic electromagnetic form factors of kaon and pion, and their quark-sector form factors, which reflect their internal structures. By comparing our result to experimental data, we found that the free-space elastic electromagnetic form factors of the mesons are consistent with the data, while the in-medium elastic electromagnetic form factors of the mesons are found to decrease as the nuclear matter density increases, leading to a rise of meson charge radius, which is consistent with the prediction of other theoretical calculations. We also predict the axial nucleon coupling constant gA in nuclear medium computed via the Goldberger-Treiman relation, which is crucial for searching the neutrinoless double beta decay (0νββ).

Published by the American Physical Society
2024
Ratios of the light quark masses: Cubic curve versus ellipse
Authors: Osipov A. A.
Published: July 2024

The bounds on the light quark masses are obtained by fitting the squares of pseudoscalar meson masses mπ2 and mK2 to second order in 1/Nc expansion. The result is an algebraic cubic curve whose coefficients are the known Weinberg values for the quark mass ratios mu/md and ms/md. Additional restrictions arise when using the ratio ms/mud=27.23(10) quoted by FLAG for lattice simulations with four quark flavors. This provides a tight constraint on the ratio mu/md=0.455(8).

Published by the American Physical Society
2024
Probing conversion-driven freeze-out at the LHC
Authors: Heisig Jan , Lessa Andre , Ramos Lucas Magno D.
Published: July 2024

Conversion-driven freeze-out is an appealing mechanism to explain the observed relic density while naturally accommodating the null results from direct and indirect detection due to a very weak dark matter coupling. Interestingly, the scenario predicts long-lived particles decaying into dark matter with lifetimes favorably coinciding with the range that can be resolved at the LHC. However, the small mass splitting between the long-lived particle and dark matter renders the visible decay products soft, thus challenging current search strategies. We consider four different classes of searches covering the entire range of lifetimes: heavy stable charge particles, disappearing tracks, displaced vertices, and missing energy searches. We discuss the applicability of these searches to conversion-driven freeze-out and derive current constraints highlighting their complementarity. For the displaced vertex search, we demonstrate how a slight modification of the current analysis significantly improves its sensitivity to the scenario.

Published by the American Physical Society
2024
Enhancement of direct
CP
asymmetry in
Z′
models
Authors: Gangal Shireen Niteen
Published: July 2024

We consider CP-violating Z′ models to account for the anomalies in b→sℓℓ decays. Using the updated constraints from lepton flavor universality violating ratios, b→sμμ CP-conserving and CP-violating observables, Bs−B¯s mixing and neutrino trident we obtain the favored parameter space of two classes of Z′ models generating the new physics scenarios with Re[C9μNP]<0 and [C9μNP=−C10μNP,C9eNP=−C10eNP]. We study the predictions of direct CP asymmetry ACP in B+→K+μμ decays and CP asymmetric angular observables in these models. The favored 1σ parameter space of Z′ models generating scenario Re[C9μNP]<0 allows for an enhancement in the integrated ACP in q2=[8,9]  GeV2 bin up to ±25%, while the [C9μNP=−C10μNP,C9eNP=−C10eNP] scenario allows only positive values of ACP. However, these ACP values flip sign depending on the choice of J/ψ phase, hence distinguishing these two Z′ models through a measurement in this bin requires a more reliable determination of the J/ψ phase. The prediction of ACP in the q2=[16,17]  GeV2 bin are promising as they allow for an enhancement only in the positive direction for [C9μNP=−C10μNP,C9eNP=−C10eNP] scenario, irrespective of the choice of strong phase, while both positive and negative values are allowed for the scenario Re[C9μNP]. We also find that a future more precise measurement of CP-asymmetric angular observables A8 and A9 in the low-q2 bins can provide distinguishing signatures of these two Z′ models and help constrain new physics CP-violating phases.

Published by the American Physical Society
2024
Radiative corrections to aid the direct detection of the Higgsino-like neutralino dark matter: Spin-independent interactions
Authors: Bisal Subhadip , Chatterjee Arindam , Das Debottam , Pasha Syed Adil
Published: July 2024

The lightest neutralino (χ˜10) is a good dark matter (DM) candidate in the R-parity conserving minimal supersymmetric Standard Model. In this work, we consider the light Higgsino-like neutralino as the lightest stable particle, thanks to a rather small Higgsino mass parameter μ. We then estimate the prominent radiative corrections to the neutralino-neutralino-Higgs boson vertices. We show that for Higgsino-like χ˜10, these corrections can significantly influence the spin-independent direct detection cross section, even contributing close to 100% in certain regions of the parameter space. These corrections, therefore, play an important role in deducing constraints on the mass of the Higgsino-like lightest neutralino DM, and thus the μ parameter.

Published by the American Physical Society
2024
Anomalous Fluctuations in a Droplet of Chemically Active Colloids or Enzymes
Authors: Prathyusha K. R. , Saha Suropriya , Golestanian Ramin
Published: July 2024

Chemically active colloids or enzymes cluster into dense droplets driven by their phoretic response to collectively generated chemical gradients. Employing Brownian dynamics simulation techniques, our study of the dynamics of such a chemically active droplet uncovers a rich variety of structures and dynamical properties, including the full range of fluidlike to solidlike behavior, and non-Gaussian positional fluctuations. Our work sheds light on the complex dynamics of the active constituents of metabolic clusters, which are the main drivers of nonequilibrium activity in living systems.

Published by the American Physical Society
2024