Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet Pathogen Reduction Technologies Alter the MicroRNA Profile of Platelet-Derived Microparticles

Despite improvements in donor screening and increasing efforts to avoid contamination and the spread of pathogens in clinical platelet concentrates (PCs), the risks of transfusion-transmitted infections remain important. Relying on an ultraviolet photo activation system, pathogen reduction technologies (PRTs), such as Intercept and Mirasol, utilize amotosalen, and riboflavin (vitamin B2), respectively, to mediate inactivation of pathogen nucleic acids. Although they are expected to increase the safety and prolong the shelf life of clinical PCs, these PRTs might affect the quality and function of platelets, as recently reported. Upon activation, platelets release microparticles (MPs), which are involved in intercellular communications and regulation of gene expression, thereby mediating critical cellular functions. Here, we have used small RNA sequencing (RNA-Seq) to document the effect of PRT treatment on the microRNA profiles of platelets and derived MPs. PRT treatment did not affect the microRNA profile of platelets. However, we observed a specific loading of certain microRNAs into platelet MPs, which was impaired by treatment with Intercept or its Additive solution (SSP+). Whereas, Intercept had an impact on the microRNA profile of platelet-derived MPs, Mirasol did not impact the microRNA profile of platelets and derived MPs, compared to non-treated control. Considering that platelet MPs are able to transfer their microRNA content to recipient cells, and that this content may exert biological activities, those findings suggest that PRT treatment of clinical PCs may modify the bioactivity of the platelets and MPs to be transfused and argue for further investigations into PRT-induced changes in clinical PC content and function.
Manipulating Gibberellin Control Over Growth and Fertility as a Possible Target for Managing Wild Radish Weed Populations in Cropping Systems

Wild radish is a major weed of Australian cereal crops. A rapid establishment, fast growth, and abundant seed production are fundamental to its success as an invasive species. Wild radish has developed resistance to a number of commonly used herbicides increasing the problem. New innovative approaches are needed to control wild radish populations. Here we explore the possibility of pursuing gibberellin (GA) biosynthesis as a novel molecular target for controlling wild radish, and in doing so contribute new insights into GA biology. By characterizing ga 3-oxidase (ga3ox) mutants in Arabidopsis, a close taxonomic relative to wild radish, we showed that even mild GA deficiencies cause considerable reductions in growth and fecundity. This includes an explicit requirement for GA biosynthesis in successful female fertility. Similar defects were reproducible in wild radish via chemical inhibition of GA biosynthesis, confirming GA action as a possible new target for controlling wild radish populations. Two possible targeting approaches are considered; the first would involve developing a species-specific inhibitor that selectively inhibits GA production in wild radish over cereal crops. The second, involves making crop species insensitive to GA repression, allowing the use of existing broad spectrum GA inhibitors to control wild radish populations. Toward the first concept, we cloned and characterized two wild radish GA3OX genes, identifying protein differences that appear sufficient for selective inhibition of dicot over monocot GA3OX activity. We developed a novel yeast-based approach to assay GA3OX activity as part of the molecular characterization, which could be useful for future screening of inhibitory compounds. For the second approach, we demonstrated that a subset of GA associated sln1/Rht-1 overgrowth mutants, recently generated in cereals, are insensitive to GA reductions brought on by the general GA biosynthesis inhibitor, paclobutrazol. The location of these mutations within sln1/Rht-1, offers additional insight into the functional domains of these important GA signaling proteins. Our early assessment suggests that targeting the GA pathway could be a viable inclusion into wild radish management programs that warrants further investigation. In drawing this conclusion, we provided new insights into GA regulated reproductive development and molecular characteristics of GA metabolic and signaling proteins.
Investigation of miRNA and mRNA Co-expression Network in Ependymoma

Ependymoma (EPN) is a rare primary tumor of the central nervous system (CNS) that affects both children and adults. Despite the definition and classification of distinct molecular subgroups, there remains a group of EPNs with a balanced genome, which makes it difficult to predict a prognosis of patients with EPN. The role of miRNA-mRNA network on EPN is still poorly understood. We assessed the involvement of miRNA-mRNA pairs in EPN by applying a weighted co-expression network analysis (WGCNA) approach. Using whole genome expression profile analysis followed by functional enrichment, we detected hub genes involved in active proliferation and DNA replication of nerve cells. Key genes including CYP11B1, KRT33B, RUNX1T1, SIK1, MAP3K4, MLANA, and SFRP5 identified in co-expression networks were regulated by miR-15a and miR-24-1. These seven miRNA-mRNA pairs were considered to influence not only pathways in cancer and tumor suppression process, but also MAPK, NF-kappaB, and WNT signaling pathways which were associated with tumorigenesis and development. This study provides a novel insight into potential diagnostic biomarkers of EPN and may have value in choosing therapeutic targets with clinical utility.
Skeletal Muscle Extracellular Matrix – What Do We Know About Its Composition, Regulation, and Physiological Roles? A Narrative Review

Skeletal muscle represents the largest body-composition component in humans. In addition to its primary function in the maintenance of upright posture and the production of movement, it also plays important roles in many other physiological processes, including thermogenesis, metabolism and the secretion of peptides for communication with other tissues. Research attempting to unveil these processes has traditionally focused on muscle fibers, i.e., the contractile muscle cells. However, it is a frequently overlooked fact that muscle fibers reside in a three-dimensional scaffolding that consists of various collagens, glycoproteins, proteoglycans, and elastin, and is commonly referred to as extracellular matrix (ECM). While initially believed to be relatively inert, current research reveals the involvement of ECM cells in numerous important physiological processes. In interaction with other cells, such as fibroblasts or cells of the immune system, the ECM regulates muscle development, growth and repair and is essential for effective muscle contraction and force transmission. Since muscle ECM is highly malleable, its texture and, consequently, physiological roles may be affected by physical training and disuse, aging or various diseases, such as diabetes. With the aim to stimulate increased efforts to study this still poorly understood tissue, this narrative review summarizes the current body of knowledge on (i) the composition and structure of the ECM, (ii) molecular pathways involved in ECM remodeling, (iii) the physiological roles of muscle ECM, (iv) dysregulations of ECM with aging and disease as well as (v) the adaptations of muscle ECM to training and disuse.
Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study

Background Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies. Objective To evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects. Patients and Methods A total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed. Results The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25–1.0 μg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 μg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses. Conclusion The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT. Clinical Trial Registration Chinese Clinical Trial Registry: ChiCTR1900026294.
Target Complexity Modulates Syntactic Priming During Comprehension

Syntactic priming is known to facilitate comprehension of the target sentence if the syntactic structure of the target sentence aligns with the structure of the prime (Branigan et al., 2005; Tooley and Traxler, 2010). Such a processing facilitation is understood to be constrained due to factors such as lexical overlap between the prime and the target, frequency of the prime structure, etc. Syntactic priming in SOV languages is also understood to be influenced by similar constraints (Arai, 2012). Sentence comprehension in SOV languages is known to be incremental and predictive. Such a top-down parsing process involves establishing various syntactic relations based on the linguistic cues of a sentence and the role of preverbal case-markers in achieving this is known to be critical. Given the evidence of syntactic priming during comprehension in these languages, this aspect of the comprehension process and its effect on syntactic priming becomes important. In this work, we show that syntactic priming during comprehension is affected by the probability of using the prime structure while parsing the target sentence. If the prime structure has a low probability given the sentential cues (e.g., nominal case-markers) in the target sentence, then the chances of persisting with the prime structure in the target reduces. Our work demonstrates the role of structural complexity of the target with regard to syntactic priming during comprehension and highlights that syntactic priming is modulated by an overarching preference of the parser to avoid rare structures.
Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation

Early-life stress and its possible correlations to genes, environment, and later health outcomes can only be studied retrospectively in humans. Animal models enable the exploration of such connections with prospective, well-controlled study designs. However, with the recent awareness of replicability issues in preclinical research, the reproducibility of results from animal models has been highlighted. The present study aims to reproduce the behavioral effects of maternal separation (MS) previously observed in the multivariate concentric square fieldTM (MCSF) test. A second objective was to replicate the adolescent behavioral profiles previously described in the MCSF test. Male rats, subjected to short or prolonged MS or standard rearing, were subjected to behavioral testing in early adolescence and early adulthood. As seen in previous studies, the behavioral effects of MS in the MCSF were small at both tested time points. When tested in early adolescence, the animals exhibited a similar behavioral profile as previously seen, and the finding of adolescent behavioral types was also reproduced. The distribution of animals into the behavioral types was different than in the initial study, but in a manner consistent with developmental theories, as the current cohort was younger than the previous. Notably, the Shelter seeker behavioral type persisted through development, while the Explorer type did not. The lack of basal behavioral effect after MS is in line with the literature on this MS paradigm; the working hypothesis is that the prolonged MS gives rise to a phenotype predisposed to negative health outcomes but which is not apparent without additional provocation.
Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells

One of the approaches to address cancer treatment is to develop new drugs not only to obtain compounds with less side effects, but also to have a broader set of alternatives to tackle the resistant forms of this pathology. In this regard, growing evidence supports the use of bacteria-derived peptides such as bacteriocins, which have emerged as promising anti-cancer molecules. In addition to test the activity of these molecules on cancer cells in culture, their in vivo antitumorigenic properties must be validated in animal models. Although the standard approach for such assays employs experiments in nude mice, at the initial stages of testing, the use of high-throughput animal models would permit rapid proof-of-concept experiments, screening a high number of compounds, and thus increasing the possibilities of finding new anti-cancer molecules. A validated and promising alternative animal model are zebrafish larvae harboring xenografts of human cancer cells. Here, we addressed the anti-cancer properties of the antibacterial peptide microcin E492 (MccE492), a bacteriocin produced by Klebsiella pneumoniae, showing that this peptide has a marked cytotoxic effect on human colorectal cancer cells in vitro. Furthermore, we developed a zebrafish xenograft model using these cells to test the antitumor effect of MccE492 in vivo, demonstrating that intratumor injection of this peptide significantly reduced the tumor cell mass. Our results provide, for the first time, evidence of the in vivo antitumoral properties of a bacteriocin tested in an animal model. This evidence strongly supports the potential of this bacteriocin for the development of novel anti-cancer therapies.
Cell Type-Specific Gene Network-Based Analysis Depicts the Heterogeneity of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder characterized by substantial heterogeneity. To identify the convergence of disease pathology on common pathways, it is essential to understand the correlations among ASD candidate genes and study shared molecular pathways between them. Investigating functional interactions between ASD candidate genes in different cell types of normal human brains may shed new light on the genetic heterogeneity of ASD. Here we apply cell type-specific gene network-based analysis to analyze human brain nucleus gene expression data and identify cell type-specific ASD-associated gene modules. ASD-associated modules specific to different cell types are relevant to different gene functions, for instance, the astrocytes-specific module is involved in functions of axon and neuron projection guidance, GABAergic interneuron-specific modules are involved in functions of postsynaptic membrane, extracellular matrix structural constituent, and ion transmembrane transporter activity. Our findings can promote the study of cell type heterogeneity of ASD, providing new insights into the pathogenesis of ASD. Our method has been shown to be effective in discovering cell type-specific disease-associated gene expression patterns and can be applied to other complex diseases.
Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions

Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability and higher detectability of long-term depression after motor learning compared with slices prepared at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.
An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95

Phosphorylation-dependent peptidyl-prolyl cis-trans isomerization plays key roles in cell cycle progression, the pathogenesis of cancer, and age-related neurodegeneration. Most of our knowledge about the role of phosphorylation-dependent peptidyl-prolyl cis-trans isomerization and the enzyme catalyzing this reaction, the peptidyl-prolyl isomerase (Pin1), is largely limited to proteins not present in neurons. Only a handful of examples have shown that phosphorylation-dependent peptidyl-prolyl cis-trans isomerization, Pin1 binding, or Pin1-mediated peptidyl-prolyl cis-trans isomerization regulate proteins present at excitatory synapses. In this work, I confirm previous findings showing that Pin1 binds postsynaptic density protein-95 (PSD-95) and identify an alternative binding site in the phosphorylated N-terminus of the PSD-95. Pin1 associates via its WW domain with phosphorylated threonine (T19) and serine (S25) in the N-terminus domain of PSD-95 and this association alters the local conformation of PSD-95. Most importantly, I show that proline-directed phosphorylation of the N-terminus domain of PSD-95 alters the local conformation of this region. Therefore, proline-directed phosphorylation of the N-terminus of PSD-95, Pin1 association, and peptidyl-prolyl cis-trans isomerization may all play a role in excitatory synaptic function and synapse development.
RAD-Seq Analysis and in situ Monitoring of Nassau Grouper Reveal Fine-Scale Population Structure and Origins of Aggregating Fish

Nassau grouper (Epinephelus striatus, Bloch 1792) are globally critically endangered and an important fishery species in The Commonwealth of The Bahamas (hereafter The Bahamas) and parts of the Caribbean, with an urgent need for better management and conservation. Here, we adopted a combined approach, integrating restriction-site-associated DNA sequencing (RAD-seq) and acoustic telemetry to establish country-wide demographic structure, diversity and connectivity, and the origins of Nassau grouper using an active fish spawning aggregation (FSA) in the central Bahamas. RAD-seq analysis of 94 Nassau grouper sampled from nine locations in The Bahamas generated a working dataset of 13,241 single nucleotide polymorphisms (SNPs). Similar levels of genetic diversity were found among sampled locations. Evidence of population sub-structuring across The Bahamas was demonstrated and supported by discriminate analysis of principal components (DAPCs) along with analyses of molecular variance (AMOVAs). Associated acoustic telemetry data indicated Nassau grouper tagged at an active FSA in the central Bahamas during the 2016–2017 spawning season migrated to the Exumas at the conclusion of the spawning period. Telemetry data suggest the likely origins of five individuals, which traveled one-way distances of up to 176 km from the FSA in the central Bahamas to two sites within a no-take marine protected area (MPA). Analyses of high-resolution SNP markers (including candidate loci under selection) illustrated patterns of spatial structure and genetic connectivity not reflected by telemetry data alone. Nassau grouper from Exuma and Long Island appear to have genetic signatures that differ from other islands and from the Hail Mary FSA. Collectively, these findings provide novel information on the intraspecific population dynamics of Nassau grouper within The Bahamian archipelago and within an active FSA.
Tidal Dynamics Control on Cold-Water Coral Growth: A High-Resolution Multivariable Study on Eastern Atlantic Cold-Water Coral Sites

Cold-water coral (CWC) communities form complex benthic ecosystems in a distinct part of the water column. The exact processes supporting CWC reef growth and changes with time are still partly unsolved. Besides local hydrographic conditions, noticeable interactions of tidal flow with topography have been reported for CWC sites. Recent studies have suggested a tidally driven hydraulic control of flow over topographic features as a driver for local overturning at cold-water coral sites. This mechanism proposed a link between surface productivity and coral growth depths and is a driver of resuspension of the bottom material. Only few studies have concentrated on how these processes vary with the health status and structure of the cold-water coral occurrences. In this study, we explore the processes over tidal cycles by analyzing in situ stratification, hydrography and velocity data which we then combine with local topography from seven Desmophyllum pertusum (previously Lophelia pertusa) dominated eastern Atlantic CWC sites, from the Arctic to the southern hemisphere. The “quality” of CWC sites varies from thriving to declining and dead reefs. We show that living and healthy corals are concentrated at sites, where local hydrodynamics create overturning and mixing which overcomes on a daily basis gravitational particle sinking and thus re-supply food to filter-feeding corals. We find a very wide range of local hydrographic and biogeochemical conditions at the sites which suggests they play only a secondary role for CWC health.
Enhancing the Conductivity of Cell-Laden Alginate Microfibers With Aqueous Graphene for Neural Applications

Microfluidically manufacturing graphene-alginate microfibers create possibilities for encapsulating rat neural cells within conductive 3D tissue scaffolding to enable the creation of real-time 3D sensing arrays with high physiological relavancy. Cells are encapsulated using the biopolymer alginate, which is combined with graphene to create a cell-containing hydrogel with increased electrical conductivity. Resulting novel alginate-graphene microfibers showed a 2.5-fold increase over pure alginate microfibers, but did not show significant differences in size and porosity. Cells encapsulated within the microfibers survive for up to 8 days, and maintain ~20% live cells over that duration. The biocompatible aqueous graphene suspension used in this investigation was obtained via liquid phase exfoliation of pristine graphite, to create a graphene-alginate pre-hydrogel solution.
UbiquiTouch

We present UbiquiTouch, an ultra low power wireless touch interface. With an average power consumption of 30. 91μW, UbiquiTouch can run on energy harvested from ambient light. It achieves this performance through low power touch sensing and passive communication to a nearby smartphone using ambient FM backscatter. This approach allows UbiquiTouch to be deployed in mobile situations both in indoor and outdoor locations, without the need for any additional infrastructure for operation. To demonstrate the potential of this technology, we evaluate it in several different and realistic scenarios. Finally, we address the future application space for this technology.