Miracle-dz/UniFAR-FTUs huggingface dataset:
Decrypting the complexity of the human malaria parasite biology through systems biology approaches

The human malaria parasite, Plasmodium falciparum, is a unicellular protozoan responsible for over half a million deaths annually. With a complex life cycle alternating between human and invertebrate hosts, this apicomplexan is notoriously adept at evading host immune responses and developing resistance to all clinically administered treatments. Advances in omics-based technologies, increased sensitivity of sequencing platforms and enhanced CRISPR based gene editing tools, have given researchers access to more in-depth and untapped information about this enigmatic micro-organism, a feat thought to be infeasible in the past decade. Here we discuss some of the most important scientific achievements made over the past few years with a focus on novel technologies and platforms that set the stage for subsequent discoveries. We also describe some of the systems-based methods applied to uncover gaps of knowledge left through single-omics applications with the hope that we will soon be able to overcome the spread of this life-threatening disease.
Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells

Many preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression. To elucidate the effect of positive pressure on lung tissue mechanics and cell behavior, we mimic the effect of overpressure by employing an uniaxial load onto fetal and adult rat lungs with different deformation rates. Additionally, tissue expansion during tidal breathing due to a negative intrathoracic pressure was addressed by uniaxial tension. We found a hyperelastic deformation behavior of fetal tissues under compression and tension with a remarkable strain stiffening. In contrast, adult lungs exhibited a similar response only during compression. Young’s moduli were always larger during tension compared to compression, while only during compression a strong deformation-rate dependency was found. In fact, fetal lung tissue under compression showed clear viscoelastic features even for small strains. Thus, we propose that the fetal lung is much more vulnerable during inflation by mechanical ventilation compared to normal inspiration. Electrophysiological experiments with different hydrostatic pressure gradients acting on primary fetal distal lung epithelial cells revealed that the activity of the epithelial sodium channel (ENaC) and the sodium-potassium pump (Na,K-ATPase) dropped during pressures of 30 cmH2O. Thus, pressures used during mechanical ventilation might impair alveolar fluid clearance important for normal lung function.
Alkaloid ligands enable function of homomeric human α10 nicotinic acetylcholine receptors

In the nervous system, nicotinic acetylcholine receptors (nAChRs) rapidly transduce a chemical signal into one that is electrical via ligand-gated ion flux through the central channel of the receptor. However, some nAChR subunits are expressed by non-excitable cells where signal transduction apparently occurs through non-ionic mechanisms. One such nAChR subunit, α10, is present in a discreet subset of immune cells and has been implicated in pathologies including cancer, neuropathic pain, and chronic inflammation. Longstanding convention holds that human α10 subunits require co-assembly with α9 subunits for function. Here we assessed whether cholinergic ligands can enable or uncover ionic functions from homomeric α10 nAChRs. Xenopus laevis oocytes expressing human α10 subunits were exposed to a panel of ligands and examined for receptor activation using voltage-clamp electrophysiology. Functional expression of human α10 nAChRs was achieved by exposing the oocytes to the alkaloids strychnine, brucine, or methyllycaconitine. Furthermore, acute exposure to the alkaloid ligands significantly enhanced ionic responses. Acetylcholine-gated currents mediated by α10 nAChRs were potently inhibited by the snake toxins α-bungarotoxin and α-cobratoxin but not by α-conotoxins that target α9 and α9α10 nAChRs. Our findings indicate that human α10 homomers are expressed in oocytes and exposure to certain ligands can enable ionic functions. To our knowledge, this is the first demonstration that human α10 subunits can assemble as functional homomeric nAChRs. These findings have potential implications for receptor regulatory-mechanisms and will enable structural, functional, and further pharmacological characterization of human α10 nAChRs.
Maternal obesity and the impact of associated early-life inflammation on long-term health of offspring

The prevalence of obesity is increasingly common in the United States, with ~25% of women of reproductive age being overweight or obese. Metaflammation, a chronic low grade inflammatory state caused by altered metabolism, is often present in pregnancies complicated by obesity. As a result, the fetuses of mothers who are obese are exposed to an in-utero environment that has altered nutrients and cytokines. Notably, both human and preclinical studies have shown that children born to mothers with obesity have higher risks of developing chronic illnesses affecting various organ systems. In this review, the authors sought to present the role of cytokines and inflammation during healthy pregnancy and determine how maternal obesity changes the inflammatory landscape of the mother, leading to fetal reprogramming. Next, the negative long-term impact on offspring’s health in numerous disease contexts, including offspring’s risk of developing neuropsychiatric disorders (autism, attention deficit and hyperactive disorder), metabolic diseases (obesity, type 2 diabetes), atopy, and malignancies will be discussed along with the potential of altered immune/inflammatory status in offspring as a contributor of these diseases. Finally, the authors will list critical knowledge gaps in the field of developmental programming of health and diseases in the context of offspring of mothers with obesity, particularly the understudied role of hematopoietic stem and progenitor cells.
Wrapped into sound: Development of the Immersive Music Experience Inventory (IMEI)

Although virtual reality, video entertainment, and computer games are dependent on the three-dimensional reproduction of sound (including front, rear, and height channels), it remains unclear whether 3D-audio formats actually intensify the emotional listening experience. There is currently no valid inventory for the objective measurement of immersive listening experiences resulting from audio playback formats with increasing degrees of immersion (from mono to stereo, 5.1, and 3D). The development of the Immersive Music Experience Inventory (IMEI) could close this gap. An initial item list (N = 25) was derived from studies in virtual reality and spatial audio, supplemented by researcher-developed items and items extracted from historical descriptions. Psychometric evaluation was conducted by an online study (N = 222 valid cases). The N = 222 Participants (female = 112, mean age = 38.6) were recruited via mailing lists (n = 34) and via a panel provider (n = 188). Based on controlled headphone playback, participants listened to four songs/pieces, each in the three formats of mono, stereo, and binaural 3D audio. The latent construct “immersive listening experience” was determined by probabilistic test theory (item response theory, IRT) and by means of the many-facet Rasch measurement (MFRM). As a result, the specified MFRM model showed good model fit (62.69% of explained variance). The final one-dimensional inventory consists of 10 items and will be made available in English and German.
Optimizing reduced capture antibody conjugation to encoded hydrogel microparticles for enhanced multiplex immunoassays

Multiplex detection of protein biomarkers in biological fluids facilitates high-throughput detection using small-volume samples, thereby enhancing efficacy of diagnostic assays and proteomic studies. Graphically encoded hydrogel microparticles conjugated with capture antibodies have shown great potential in multiplex immunoassays by providing superior sensitivity and specificity, a broad dynamic range, and large encoding capacity. Recently, the process of post-synthesis conjugation of reduced capture antibodies to unreacted acrylate moieties in hydrogel particles has been developed to efficiently prevent the aggregation of capture antibodies inside particles, which occurs when using conventional conjugation methods. This direct conjugation process yielded robust assay performance through homogeneous conjugation of the capture antibodies, and avoided the use of hydrolytically unstable linker additives. However, no research has been conducted to optimize the process of conjugating capture antibodies to the particles. We here present a strategy to optimize capture antibody conjugation based on the finding that excessive addition of capture antibodies during incubation can rather lower the amount of capture antibodies conjugated to the particles for some types of capture antibodies. Based on our optimized capture antibody conjugation process, a singleplex immunoassay for a selected target was conducted. Enhanced sensitivity compared with previous studies was confirmed. We also validated the increased specificity of multiplex detection through our optimization process. We believe that the optimization process presented herein for capture antibody conjugation will advance the field of encoded hydrogel microparticle-based immunoassays.
Risk Factor-Driven Prehabilitation Prior to Abdominal Wall Reconstruction to Improve Postoperative Outcome. A Narrative Review

All abdominal wall reconstructions find themselves on a scale, varying between simple to highly complex procedures. The level of complexity depends on many factors that are divided into patient comorbidities, hernia characteristics, and wound characteristics. Preoperative identification of modifiable risk factors provides the opportunity for patient optimization. Because this so called prehabilitation greatly improves postoperative outcome, reconstructive surgery should not be scheduled before all modifiable risk factors are optimized to a point where no further improvement can be expected. In this review, we discuss the importance of preoperative risk factor recognition, identify modifiable risk factors, and utilize options for patient prehabilitation, all aiming to improve postoperative outcome and therewith long-term success of the reconstruction.
Intestinal permeability of agaro-oligosaccharides: Transport across Caco-2 cell monolayers and pharmacokinetics in rats

Agaro-oligosaccharides (AOSs), even-numbered oligosaccharides prepared from agar, are applied to various food, including supplements, drinks, and jellies because of their biological activities. This study aimed to evaluate the AOS permeation in the gastrointestinal tract in vivo and in vitro. Agarobiose (Abi), agarotetraose (Ate), and agarohexaose (Ahe) were detected in rat plasma after oral administration of AOSs. The detection level of agarobiose in the plasma was higher than that of agarohexaose, which was consistent with the permeation study using Caco-2 cell monolayers. Further, the adenosine triphosphate inhibitor (sodium azide) or endocytosis inhibitor (colchicine) did not inhibit AOS permeation through Caco-2 cell monolayers. Conversely, AOS permeation enhanced upon treatment with cytochalasin B, a tight junction disrupter, suggesting that AOSs might have passed mainly through the tight junctions between the intestinal epithelial cells. These results indicate that AOSs, especially agarobiose, can be absorbed as an intact form via the gastrointestinal tract across the intestinal epithelium through the paracellular pathway.
Procedures between training and reactivation influence the destabilization of instrumental sucrose memory

Memory destabilization and reconsolidation is hypothesized to be a fundamental mnemonic process that can underpin memory updating. Instrumental memories have been shown recently to be destabilized following a reactivation session that involves a change in instrumental reward contingency. However, the acquisition and performance of an instrumental response occurs in the presence of the learning of other reward-related memories. This may influence the ability of a given reactivation session to destabilize the previously learned instrumental memory. Here we present a series of experiments in male rats involving an instrumental memory trained on an FR1 schedule over 10 days, and then reactivated in a session that imposed a VR5 schedule of reinforcement. When MK-801 was injected prior to the VR5 reactivation session, it reliably impaired subsequent instrumental performance at test only when the reactivation session occurred 48 h, and not 24 h, after the end of training. The interposition between the end of training and the reactivation session of a context extinction session, an additional VR5 reactivation session, or indeed the simple experience of being handled and injected with vehicle, resulted in MK-801 no longer having an amnestic effect on test performance. While we do not have a clear account for the process and mechanism underpinning this apparent selectivity of the effect of the VR5 session to destabilize the instrumental memory, it does additionally highlight the need for greater understanding of the conditions that facilitate reactivation-induced memory destabilization.
The DNA damage checkpoint: A tale from budding yeast

Studies performed in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have led the way in defining the DNA damage checkpoint and in identifying most of the proteins involved in this regulatory network, which turned out to have structural and functional equivalents in humans. Subsequent experiments revealed that the checkpoint is an elaborate signal transduction pathway that has the ability to sense and signal the presence of damaged DNA and transduce this information to influence a multifaceted cellular response that is essential for cancer avoidance. This review focuses on the work that was done in Saccharomyces cerevisiae to articulate the checkpoint concept, to identify its players and the mechanisms of activation and deactivation.
More than a marker: potential pathogenic functions of MAP2

Microtubule-associated protein 2 (MAP2) is the predominant cytoskeletal regulator within neuronal dendrites, abundant and specific enough to serve as a robust somatodendritic marker. It influences microtubule dynamics and microtubule/actin interactions to control neurite outgrowth and synaptic functions, similarly to the closely related MAP Tau. Though pathology of Tau has been well appreciated in the context of neurodegenerative disorders, the consequences of pathologically dysregulated MAP2 have been little explored, despite alterations in its immunoreactivity, expression, splicing and/or stability being observed in a variety of neurodegenerative and neuropsychiatric disorders including Huntington’s disease, prion disease, schizophrenia, autism, major depression and bipolar disorder. Here we review the understood structure and functions of MAP2, including in neurite outgrowth, synaptic plasticity, and regulation of protein folding/transport. We also describe known and potential mechanisms by which MAP2 can be regulated via post-translational modification. Then, we assess existing evidence of its dysregulation in various brain disorders, including from immunohistochemical and (phospho) proteomic data. We propose pathways by which MAP2 pathology could contribute to endophenotypes which characterize these disorders, giving rise to the concept of a “MAP2opathy”—a series of disorders characterized by alterations in MAP2 function.
Development of the PDF kinetic approach for modelling inertial particle dispersion in turbulent boundary layers

This thesis presents developments in the use of probability density function (PDF) kinetic equations to model the dispersion of inertial particles in turbulent boundary layers. The PDF kinetic equation is used as a master equation from which to construct continuum equations for the particle-phase, and these continuum equations form an infinite set of coupled equations which require closure in the particle velocity statistics. Furthermore, the continuum equations contain dispersion tensors which describe the effect of the underlying fluid turbulence on the dispersion of the particles throughout the flow field. These dispersion tensors themselves require closure and in this thesis new closure models are developed which are non-local and attempt to take into account the effects of turbulence inhomogeneity, anisotropy and particle-wall collisions on the dispersion tensors. The first closure model developed is for particles dispersing under Stokes drag forcing only; appropriate for particles whose material density is much greater than that of the fluid in which they are dispersed. This closure model is tested against equivalent particle tracking simulation data over a range of particle sizes and the closure model predictions are found to be in excellent agreement. In contrast to the new closure model predictions, the traditional ‘local’ approximations to the dispersion tensors are found to be in significant error when compared to the particle tracking data. The closure model is then developed to account for particles dispersing under Stokes drag, added mass and gravitational forcing; added mass forcing being important for particles whose material density is comparable to or less than that of the fluid in which they are dispersed. The modelling is presented and a discussion is given regarding the various complex terms that require approximation in this closure model. The closure model predictions are then compared against the alternative local approximations. It is seen that with added mass forcing the local approximations can be qualitatively and quantitatively different to the non-local predictions, whereas under only a drag force, errors in the local approximations are mainly quantitative. Finally, consideration is given to the forms of the dispersion tensors appearing in the PDF and continuum equations. It is shown theoretically that the dispersion tensors (and therefore the PDF and continuum equations themselves) are free from the so called ‘spurious drift’ phenomena associated with certain types of models for predicting the dispersion of fluid particles in incompressible, inhomogeneous turbulent flows. However, it is also shown that closure approximations applied to the dispersion tensors may result in the introduction of a spurious drift. Nevertheless, it is demonstrated that the artificial drift introduced by closure approximations does not have any appreciable affect on the dispersion tensors when they are describing the dispersion of inertial particles.
Integrated bioinformatics analysis for novel miRNAs markers and ceRNA network in diabetic retinopathy

In order to seek a more outstanding diagnosis and treatment of diabetic retinopathy (DR), we predicted the miRNA biomarkers of DR and explored the pathological mechanism of DR through bioinformatics analysis. Method: Based on public omics data and databases, we investigated ncRNA (non-coding RNA) functions based on the ceRNA hypothesis. Result: Among differentially expressed miRNAs (DE-miRNAs), hsa-miR-1179, -4797-3p and -665 may be diagnosis biomarkers of DR. Functional enrichment analysis revealed differentially expressed mRNAs (DE-mRNAs) enriched in mitochondrial transport, cellular respiration and energy derivation. 18 tissue/organ-specific expressed genes, 10 hub genes and gene cluster modules were identified. The ceRNA networks lncRNA FBXL19-AS1/miR-378f/MRPL39 and lncRNA UBL7-AS1/miR-378f/MRPL39 might be potential RNA regulatory pathways in DR. Conclusion: Differentially expressed hsa-miR-1179, -4797-3p and -665 can be used as powerful markers for DR diagnosis, and the ceRNA network: lncRNA FBXL19-AS1/UBL7-AS1-miR-378f-MRPL39 may represent an important regulatory role in DR progression.
The Impact of Malignancy on Assisted Reproductive Outcomes for Cancer Survivors: A Retrospective Case–Control Study

Background Related studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes. Methods This retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes. Results This study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P<0.001) between the two groups. The total gonadotropin dose, number of oocytes retrieved, fertilization rate, cleavage rate, high-quality embryo rate, blastocyst rate and first-time embryo-transfer (ET) implantation rate were nonsignificantly lower in the cancer group than in the control group (P>0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes. Conclusions Overall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes.