Miracle-dz/UniFAR-FTUs huggingface dataset:
A coarse-grained DNA model to study protein-DNA interactions and liquid-liquid phase separation

Recent advances in coarse-grained (CG) computational models for DNA have enabled molecular- level insights into the behavior of DNA in complex multiscale systems. However, most existing CG DNA models are not compatible with CG protein models, limiting their applications for emerging topics such as protein-nucleic acid assemblies. Here, we present a new computationally efficient CG DNA model. We first use experimental data to establish the model’s ability to predict various aspects of DNA behavior, including melting thermodynamics and relevant local structural properties such as the major and minor grooves. We then employ an all-atom hydropathy scale to define non-bonded interactions between protein and DNA sites, to make our DNA model compatible with an existing CG protein model (HPS-Urry), that is extensively used to study protein phase separation, and show that our new model reasonably reproduces the experimental binding affinity for a prototypical protein-DNA system. To further demonstrate the capabilities of this new model, we simulate a full nucleosome with and without histone tails, on a microsecond timescale, generating conformational ensembles and provide molecular insights into the role of histone tails in influencing the liquid-liquid phase separation (LLPS) of HP1α proteins. We find that histone tails interact favorably with DNA, influencing the conformational ensemble of the DNA and antagonizing the contacts between HP1α and DNA, thus affecting the ability of DNA to promote LLPS of HP1α. These findings shed light on the complex molecular framework that fine-tunes the phase transition properties of heterochromatin proteins and contributes to heterochromatin regulation and function. Overall, the CG DNA model presented here is suitable to facilitate micron-scale studies with sub-nm resolution in many biological and engineering applications and can be used to investigate protein-DNA complexes, such as nucleosomes, or LLPS of proteins with DNA, enabling a mechanistic understanding of how molecular information may be propagated at the genome level.
Anopheles salivary apyrase regulates blood meal hemostasis and drives malaria parasite transmission

Mosquito salivary proteins play a crucial role in regulating hemostatic responses at the bite site during blood feeding. In this study, we investigate the function of Anopheles gambiae salivary apyrase (AgApyrase) in Plasmodium transmission. Our results demonstrate that salivary apyrase interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protein previously shown to be required for Plasmodium transmission. Microscopy imaging shows that mosquitoes ingest a substantial amount of apyrase during blood feeding which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. Supplementation of Plasmodium infected blood with apyrase significantly enhanced Plasmodium infection in the mosquito midgut. In contrast, AgApyrase immunization inhibited Plasmodium mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for Plasmodium transmission to mosquitoes and to the mammal host, underscoring the potential for new strategies to prevent malaria transmission.
Periodic hypothalamic attractor-like dynamics during the estrus cycle

Cyclic changes in hormonal state are well-known to regulate mating behavior during the female reproductive cycle, but whether and how these changes affect the dynamics of neural activity in the female brain is largely unknown. The ventromedial hypothalamus, ventro-lateral subdivision (VMHvl) contains a subpopulation of VMHvlEsr1+,Npy2r- neurons that controls female sexual receptivity. Longitudinal single cell calcium imaging of these neurons across the estrus cycle revealed that overlapping but distinct subpopulations were active during proestrus (mating-accepting) vs. non-proestrus (rejecting) phases. Dynamical systems analysis of imaging data from proestrus females uncovered a dimension with slow ramping activity, which generated approximate line attractor-like dynamics in neural state space. During mating, the neural population vector progressed along this attractor as male mounting and intromission proceeded. Attractor-like dynamics disappeared in non-proestrus states and reappeared following re-entry into proestrus. They were also absent in ovariectomized females but were restored by hormone priming. These observations reveal that hypothalamic line attractor-like dynamics are associated with female sexual receptivity and can be reversibly regulated by sex hormones, demonstrating that attractor dynamics can be flexibly modulated by physiological state. They also suggest a potential mechanism for the neural encoding of female sexual arousal.
Identification of novel interactors of PP2A-B’ζ

Protein phosphatase 2A (PP2A) is a heterotrimeric conserved serine/threonine phosphatase complex including a catalytic, scaffolding, and regulatory subunit. Three A Subunits, 17 B subunits, and five C subunits are encoded by the Arabidopsis genome, allowing 255 possible PP2A holoenzyme combinations. The regulatory subunits are crucial for substrate specificity and PP2A complex localization and are classified into B, B’, and B’’ non-related families in land plants. In Arabidopsis , the close homologs B’η, B’θ, B’γ, and B’ζ are further classified into a subfamily of B’ called B’η. Previous studies suggest a role of mitochondrial targeted PP2A subunit (B’ζ) in energy metabolism. Potentially, the PP2A-B’ζ holoenzyme is involved in the regulation of the mitochondrial succinate/fumarate translocator or affects enzymes involved in energy metabolism. To investigate this hypothesis, the interaction between PP2A-B’ζ and enzymes involved in the mitochondrial energy flow was investigated using bimolecular fluorescence complementation in tobacco and onion cells. Interaction of B’ζ subunit was proven with the Krebs cycle proteins Succinate-fumarate translocator (mSFC1), Malate dehydrogenase (mMDH2), and Aconitase (ACO3). Additional interacting candidates were identified by comparing the total phosphoproteomes of wild type and B’ζ mutants: the mitochondrial regulator Arabidopsis pentatricopeptide repeat 6 (PPR6) and the two metabolic enzymes Phosphoenolpyruvate carboxylase (PPC3) and Phosphoenolpyruvate carboxykinase (PCK1). Overall, this study identified potential PP2A substrates and highlighted the role of PP2A in regulating energy metabolism in mitochondria.
Antimicrobial efficacy of composite irrigation solution against dominant pathogens in seawater immersion wound and in vivo wound healing assessment

Seawater immersion wound is inevitably accompanied by bacterial infection. Effective irrigation is critical for bacterial infection prevention and wound healing. In this study, the antimicrobial efficacy of a designed composite irrigation solution against several dominant pathogens in seawater immersion wounds was evaluated, and in vivo wound healing assessment was conducted in a rat model. According to the time–kill result, the composite irrigation solution exhibits excellent and rapid bactericidal effect against Vibrio alginolyticus and Vibrio parahaemolyticus within 30 s of treatment while eliminating Candida albicans, Pseudomonas aeruginosa, Escherichia coli, and the mixed microbes after 1 h, 2 h, 6 h, and 12 h of treatment, respectively. Significant bacterial count reduction of Staphylococcus aureus was observed after 5 h treatment. In addition to its skin non-irritating attribute, the in vivo wound healing results further demonstrated that the irrigation solution showed high repair efficiency in the skin defect model inoculated with the mixed microbes. The wound healing rate was significantly higher than that of the control and normal saline groups. It could also effectively reduce the number of viable bacteria on the wound surface. The histological staining indicated that the irrigation solution could reduce inflammatory cells and promote collagen fibers and angiogenesis, thereby promoting wound healing. We believed that the designed composite irrigation solution has great potential for application in the treatment of seawater immersion wounds. Graphical abstract
Laboratory diagnosis of Trypanosoma cruzi infection: a narrative review

Trypanosoma cruzi infection, currently endemic in 21 countries, is a public health problem not only in the Americas but also in countries with Latin American migrants. However, it is estimated that two-thirds of people with Chagas disease currently live in urban areas and that only 10% of them are aware of it. This review summarizes the most important aspects of the diagnosis of human T. cruzi infection by describing the following aspects of clinical laboratory diagnosis: the most widely used tests available in Latin America and those expected to improve access to diagnosis of the affected population with their implementation; the advantages, disadvantages, and sensitivity of the tests in the different phases of infection; and their usefulness in the acute or chronic phases of infection and in the context of immunosuppression. In this way, we hope to contribute to broadening the knowledge about this prevalent infection in the Americas. Graphical Abstract
Extracellular vesicle-mediated intercellular and interorgan crosstalk of pancreatic islet in health and diabetes

Diabetes mellitus (DM) is a systemic metabolic disease with high mortality and morbidity. Extracellular vesicles (EVs) have emerged as a novel class of signaling molecules, biomarkers and therapeutic agents. EVs-mediated intercellular and interorgan crosstalk of pancreatic islets plays a crucial role in the regulation of insulin secretion of β-cells and insulin action in peripheral insulin target tissues, maintaining glucose homeostasis under physiological conditions, and it’s also involved in pathological changes including autoimmune response, insulin resistance and β-cell failure associated with DM. In addition, EVs may serve as biomarkers and therapeutic agents that respectively reflect the status and improve function and viability of pancreatic islets. In this review, we provide an overview of EVs, discuss EVs-mediated intercellular and interorgan crosstalk of pancreatic islet under physiological and diabetic conditions, and summarize the emerging applications of EVs in the diagnosis and treatment of DM. A better understanding of EVs-mediated intercellular and interorgan communication of pancreatic islets will broaden and enrich our knowledge of physiological homeostasis maintenance as well as the development, diagnosis and treatment of DM.
Mitochondrial DNA methylation in metabolic associated fatty liver disease

Introduction Hepatic lipid accumulation and mitochondrial dysfunction are hallmarks of metabolic associated fatty liver disease (MAFLD), yet molecular parameters underlying MAFLD progression are not well understood. Differential methylation within the mitochondrial DNA (mtDNA) has been suggested to be associated with dysfunctional mitochondria, also during progression to Metabolic Steatohepatitis (MeSH). This study further investigates whether mtDNA methylation is associated with hepatic lipid accumulation and MAFLD. Methods HepG2 cells were constructed to stably express mitochondria-targeted viral and prokaryotic cytosine DNA methyltransferases (mtM.CviPI or mtM.SssI for GpC or CpG methylation, respectively). A catalytically inactive variant (mtM.CviPI-Mut) was constructed as a control. Mouse and human patients’ samples were also investigated. mtDNA methylation was assessed by pyro- or nanopore sequencing. Results and discussion Differentially induced mtDNA hypermethylation impaired mitochondrial gene expression and metabolic activity in HepG2-mtM.CviPI and HepG2-mtM.SssI cells and was associated with increased lipid accumulation, when compared to the controls. To test whether lipid accumulation causes mtDNA methylation, HepG2 cells were subjected to 1 or 2 weeks of fatty acid treatment, but no clear differences in mtDNA methylation were detected. In contrast, hepatic Nd6 mitochondrial gene body cytosine methylation and Nd6 gene expression were increased in mice fed a high-fat high cholesterol diet (HFC for 6 or 20 weeks), when compared to controls, while mtDNA content was unchanged. For patients with simple steatosis, a higher ND6 methylation was confirmed using Methylation Specific PCR, but no additional distinctive cytosines could be identified using pyrosequencing. This study warrants further investigation into a role for mtDNA methylation in promoting mitochondrial dysfunction and impaired lipid metabolism in MAFLD.
CSSQ: a ChIP-seq signal quantifier pipeline

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has revolutionized the studies of epigenomes and the massive increase in ChIP-seq datasets calls for robust and user-friendly computational tools for quantitative ChIP-seq. Quantitative ChIP-seq comparisons have been challenging due to noisiness and variations inherent to ChIP-seq and epigenomes. By employing innovative statistical approaches specially catered to ChIP-seq data distribution and sophisticated simulations along with extensive benchmarking studies, we developed and validated CSSQ as a nimble statistical analysis pipeline capable of differential binding analysis across ChIP-seq datasets with high confidence and sensitivity and low false discovery rate with any defined regions. CSSQ models ChIP-seq data as a finite mixture of Gaussians faithfully that reflects ChIP-seq data distribution. By a combination of Anscombe transformation, k-means clustering, estimated maximum normalization, CSSQ minimizes noise and bias from experimental variations. Further, CSSQ utilizes a non-parametric approach and incorporates comparisons under the null hypothesis by unaudited column permutation to perform robust statistical tests to account for fewer replicates of ChIP-seq datasets. In sum, we present CSSQ as a powerful statistical computational pipeline tailored for ChIP-seq data quantitation and a timely addition to the tool kits of differential binding analysis to decipher epigenomes.
Where on the face do we look during phonemic restoration: An eye-tracking study

Face to face communication typically involves audio and visual components to the speech signal. To examine the effect of task demands on gaze patterns in response to a speaking face, adults participated in two eye-tracking experiments with an audiovisual (articulatory information from the mouth was visible) and a pixelated condition (articulatory information was not visible). Further, task demands were manipulated by having listeners respond in a passive (no response) or an active (button press response) context. The active experiment required participants to discriminate between speech stimuli and was designed to mimic environmental situations which require one to use visual information to disambiguate the speaker’s message, simulating different listening conditions in real-world settings. Stimuli included a clear exemplar of the syllable /ba/ and a second exemplar in which the formant initial consonant was reduced creating an /a/−like consonant. Consistent with our hypothesis, results revealed that the greatest fixations to the mouth were present in the audiovisual active experiment and visual articulatory information led to a phonemic restoration effect for the /a/ speech token. In the pixelated condition, participants fixated on the eyes, and discrimination of the deviant token within the active experiment was significantly greater than the audiovisual condition. These results suggest that when required to disambiguate changes in speech, adults may look to the mouth for additional cues to support processing when it is available.
A broadband-sensitive upconverter La(Ga0.5Sc0.5)O3:Er,Ni,Nb for crystalline silicon solar cells

We have developed an upconverter that significantly broadens the sensitive range, to overcome the shortcoming that conventional Er3+-doped upconverters used for crystalline silicon solar cells can utilize only a small portion of the solar spectrum at around 1.55 μm. We have designed the combination of the sensitizers and host material to utilize photons not absorbed by silicon or Er3+ ions. Ni2+ ions have been selected as the sensitizers that absorb photons in the wavelength range between the silicon absorption edge (1.1 μm) and the Er3+ absorption band and transfer the energies to the Er3+ emitters, with La(Ga,Sc)O3 as the host material. The Ga to Sc ratio has been optimized to tune the location of the Ni2+ absorption band for sufficient energy transfer. Co-doping with Nb5+ ions is needed for charge balance to introduce divalent Ni2+ ions into the trivalent Ga3+ and Sc3+ sites. In addition to 1.45–1.58 μm photons directly absorbed by the Er3+ ions, we have demonstrated upconversion of 1.1–1.35 μm photons.
Recent trends in the use of bacteriophages as replacement of antimicrobials against food-animal pathogens

A major public health impact is associated with foodborne illnesses around the globe. Additionally, bacteria are becoming more resistant to antibiotics, which pose a global threat. Currently, many scientific efforts have been made to develop and implement new technologies to combat bacteria considering the increasing emergence of multidrug-resistant bacteria. In recent years, there has been considerable interest in using phages as biocontrol agents for foodborne pathogens in animals used for food production and in food products themselves. Foodborne outbreaks persist, globally, in many foods, some of which lack adequate methods to control any pathogenic contamination (like fresh produce). This interest may be attributed both to consumers’ desire for more natural food and to the fact that foodborne outbreaks continue to occur in many foods. Poultry is the most common animal to be treated with phage therapy to control foodborne pathogens. A large number of foodborne illnesses worldwide are caused by Salmonella spp. and Campylobacter, which are found in poultry and egg products. Conventional bacteriophage-based therapy can prevent and control humans and animals from various infectious diseases. In this context, describing bacteriophage therapy based on bacterial cells may offer a breakthrough for treating bacterial infections. Large-scale production of pheasants may be economically challenging to meet the needs of the poultry market. It is also possible to produce bacteriophage therapy on a large scale at a reduced cost. Recently, they have provided an ideal platform for designing and producing immune-inducing phages. Emerging foodborne pathogens will likely be targeted by new phage products in the future. In this review article, we will mainly focus on the Bacteriophages (phages) that have been proposed as an alternative strategy to antibiotics for food animal pathogens and their use for public health and food safety.
Clinical management of finger joint capsulitis/synovitis in a rock climber

This case study presents a 23-year-old male recreational rock climber, who climbed an average of 3–4 times per week and presented with finger joint capsulitis/synovitis after increasing his climbing intensity and training from moderate to high over 6 months, which led up to injury. During the exam, the diagnosis was ruled in with clinical orthopedic testing. Additional movement analyses revealed improper gripping mechanics contributing to asymmetric finger loading. A comprehensive rehabilitation program was developed based on the concept of a progressive framework that included unloading of the affected tissues, increasing mobility, improving muscle performance, and correcting suboptimal climbing movements. After 6 weeks, the climber's pain 24 h after climbing, which was rated on a visual analog pain scale (VAS), decreased from 5.5/10 to 1.5/10 and 0/10 at the 12-month follow-up. His patient-specific functional scale improved from 0% at the initial evaluation to 43% after 6 weeks and to 98% after 12 months. His sports-specific disabilities of the arm, shoulder, and hand improved from 69% to 34% to 6% during the initial evaluation, 6-week follow-up, and 12-month discharge. He made a full recovery to his previous grade of V8 bouldering. This is the first case study of its kind to provide a rehabilitation framework for the management of finger joint capsulitis/synovitis in a rock climber.
3D-bioprinting of patient-derived cardiac tissue models for studying congenital heart disease

Introduction Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies. Methods To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521. Results Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including spontaneous contraction. Contraction remained consistent during 30 days of culture based on displacement measurements. Furthermore, tissue constructs demonstrated progressive maturation based on sarcomere structure and gene expression analysis. Gene expression analysis also revealed enhanced maturation in 3D constructs compared to 2D cell culture. Discussion This combination of patient-derived cardiomyocytes and 3D-bioprinting represents a promising platform for studying congenital heart disease and evaluating individualized treatment strategies.
Enhancement of agri-food by-products: green extractions of bioactive molecules with fungicidal action against mycotoxigenic fungi and their mycotoxins

Introduction Today, alternative strategies based on the use of bioactive compounds have been proposed to reduce mycotoxin contamination and limit the use of chemical fungicides. Methods In the present work, several by-products collected from the agri-food chain (i.e., red and white grape marc, red grapevine leaves, grape seeds and stalks, pear, apple, green beans, tomato, and spent hops) were subjected to green extraction protocols (i.e., steam distillation, Ultrasound-Assisted, and Naviglio® extraction) to obtain extracts rich in polyphenols and terpenes. Each extract was assessed in vitro for its ability to inhibit the development of the main mycotoxigenic species and related mycotoxins. Results and Discussion Aspergillus flavus and A. carbonarius were significantly reduced by pear (from −45 to −47%) and grape marc (from −21 to −51%) extracts, while F. graminearum was shown to be highly influenced by grape stalk, pear, and grape marc extracts (−24% on average). On the contrary, F. verticillioides was inhibited only by pear (−18%) and to a very low and negligible extent by apple (−1%) and green beans (−3%). Regarding the reduction of mycotoxins, the extracts were able to inhibit OTA from 2 to 57%, AFB1 from 5 to 75%, and DON from 14 to 72%. The highest percentages of reduction were obtained against FBs (from 11 to 94%), ZEN (from 17 to 100%), and Alternaria toxins (from 7 to 96%). In conclusion, this work provided promising results for the production of bioactive extracts obtained from agri-food by-products, which could be exploited as potential biofungicides against the development of mycotoxigenic fungi and related mycotoxins.