Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.
Negative impacts from latency masked by noise in simulated beamforming

Those experiencing hearing loss face severe challenges in perceiving speech in noisy situations such as a busy restaurant or cafe. There are many factors contributing to this deficit including decreased audibility, reduced frequency resolution, and decline in temporal synchrony across the auditory system. Some hearing assistive devices implement beamforming in which multiple microphones are used in combination to attenuate surrounding noise while the target speaker is left unattenuated. In increasingly challenging auditory environments, more complex beamforming algorithms are required, which increases the processing time needed to provide a useful signal-to-noise ratio of the target speech. This study investigated whether the benefits from signal enhancement from beamforming are outweighed by the negative impacts on perception from an increase in latency between the direct acoustic signal and the digitally enhanced signal. The hypothesis for this study is that an increase in latency between the two identical speech signals would decrease intelligibility of the speech signal. Using 3 gain / latency pairs from a beamforming simulation previously completed in lab, perceptual thresholds of SNR from a simulated use case were obtained from normal hearing participants. No significant differences were detected between the 3 conditions. When presented with 2 copies of the same speech signal presented at varying gain / latency pairs in a noisy environment, any negative intelligibility effects from latency are masked by the noise. These results allow for more lenient restrictions for limiting processing delays in hearing assistive devices.
How Does Bacillus thuringiensis Crystallize Such a Large Diversity of Toxins?

Bacillus thuringiensis (Bt) is a natural crystal-making bacterium. Bt diversified into many subspecies that have evolved to produce crystals of hundreds of pesticidal proteins with radically different structures. Their crystalline form ensures stability and controlled release of these major virulence factors. They are responsible for the toxicity and host specificity of Bt, explaining its worldwide use as a biological insecticide. Most research has been devoted to understanding the mechanisms of toxicity of these toxins while the features driving their crystallization have long remained elusive, essentially due to technical limitations. The evolution of methods in structural biology, pushing back the limits in size of amenable protein crystals now allows access to be gained to structural information hidden within natural crystals of such toxins. In this review, we present the main parameters that have been identified as key drivers of toxin crystallization in Bt, notably in the light of recent discoveries driven by structural biology studies. Then, we develop how the future evolution of structural biology will hopefully unveil new mechanisms of Bt toxin crystallization, opening the door to their hijacking with the aim of developing a versatile in vivo crystallization platform of high academic and industrial interest.
Nanocarriers of Miconazole or Fluconazole: Effects on Three-Species Candida Biofilms and Cytotoxic Effects In Vitro

The contribution of different Candida species in oral fungal infections has stimulated the search for more effective therapies. This study assessed the antibiofilm effects of nanocarriers of miconazole (MCZ) or fluconazole (FLZ) on Candida biofilms, and their cytotoxic effects on murine fibroblasts. Three-species biofilms (Candida albicans/Candida glabrata/Candida tropicalis) were formed on 96-well plates, and they were treated with nanocarriers (iron oxide nanoparticles coated with chitosan—“IONPs-CS”) of MCZ or FLZ at 39/78/156 µg/mL; antifungals alone at 156 µg/mL and artificial saliva were tested as positive and negative controls, respectively. Biofilms were analyzed by colony forming units (CFU), biomass, metabolic activity, and structure/viability. The cytotoxicity (L929 cells) of all treatments was determined via 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Data were submitted to one- or two-way ANOVA, followed by Tukey’s or Fisher LSD’s tests (p < 0.05). IONPs-CS-MCZ at 78 µg/mL promoted similar antibiofilm and cytotoxic effects compared with MCZ at 156 µg/mL. In turn, IONPs-CS-FLZ at 156 µg/mL was overall the most effective FLZ antibiofilm treatment, surpassing the effects of FLZ alone; this nanocarrier was also less cytotoxic compared with FLZ alone. It can be concluded that both nanocarriers are more effective alternatives to fight Candida biofilms compared with their respective positive controls in vitro, being a promising alternative for the treatment of oral fungal infections.
Multiscale Permutation Lempel–Ziv Complexity Measure for Biomedical Signal Analysis: Interpretation and Application to Focal EEG Signals

This paper analyses the complexity of electroencephalogram (EEG) signals in different temporal scales for the analysis and classification of focal and non-focal EEG signals. Futures from an original multiscale permutation Lempel–Ziv complexity measure (MPLZC) were obtained. MPLZC measure combines a multiscale structure, ordinal analysis, and permutation Lempel–Ziv complexity for quantifying the dynamic changes of an electroencephalogram (EEG). We also show the dependency of MPLZC on several straight-forward signal processing concepts, which appear in biomedical EEG activity via a set of synthetic signals. The main material of the study consists of EEG signals, which were obtained from the Bern-Barcelona EEG database. The signals were divided into two groups: focal EEG signals (n = 100) and non-focal EEG signals (n = 100); statistical analysis was performed by means of non-parametric Mann–Whitney test. The mean value of MPLZC results in the non-focal group are significantly higher than those in the focal group for scales above 1 (p < 0.05). The result indicates that the non-focal EEG signals are more complex. MPLZC feature sets are used for the least squares support vector machine (LS-SVM) classifier to classify into the focal and non-focal EEG signals. Our experimental results confirmed the usefulness of the MPLZC method for distinguishing focal and non-focal EEG signals with a classification accuracy of 86%.
Neural Network for Metal Detection Based on Magnetic Impedance Sensor

The efficiency of the metal detection method using deep learning with data obtained from multiple magnetic impedance (MI) sensors was investigated. The MI sensor is a passive sensor that detects metal objects and magnetic field changes. However, when detecting a metal object, the amount of change in the magnetic field caused by the metal is small and unstable with noise. Consequently, there is a limit to the detectable distance. To effectively detect and analyze this distance, a method using deep learning was applied. The detection performances of a convolutional neural network (CNN) and a recurrent neural network (RNN) were compared from the data extracted from a self-impedance sensor. The RNN model showed better performance than the CNN model. However, in the shallow stage, the CNN model was superior compared to the RNN model. The performance of a deep-learning-based (DLB) metal detection network using multiple MI sensors was compared and analyzed. The network was detected using long short-term memory and CNN. The performance was compared according to the number of layers and the size of the metal sheet. The results are expected to contribute to sensor-based DLB detection technology.
Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Simple Summary Breast cancer is a major public health problem with a large impact on the life of patients and their families. It is a highly curable disease when detected early, and an inevitably mortal disease when discovered too late. Therapy resistance and metastases are the most critical clinical issues faced by breast cancer oncologists nowadays. It has become evident that interactions between carcinoma cells and tumor microenvironment are an essential part of tumor growth and progression. Cells that support the function of epithelial cells, like cancer-associated fibroblasts (CAFs), contribute to therapy resistance and metastasis via the production of several secreted factors and direct interaction with cancer cells. Here we review the role of CAFs in radiotherapy, chemotherapy, endocrine and targeted therapies resistance. We also highlight the role of CAFs and fibroblasts from metastatic sites in metastasis progression. Finally, we discuss advances and potential therapeutic strategies to target CAFs for overcoming resistance and preventing metastases. Abstract Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.
Whole-Gene Deletions of FZD4 Cause Familial Exudative Vitreoretinopathy

Familial exudative vitreoretinopathy (FEVR) is an inherited disorder characterized by abnormalities in the retinal vasculature. The FZD4 gene is associated with FEVR, but the prevalence and impact of FZD4 copy number variation (CNV) on FEVR patients are unknown. The aim of this study was to better understand the genetic features and clinical manifestations of patients with FZD4 CNVs. A total of 651 FEVR families were recruited. Families negative for mutations in FEVR-associated genes were selected for CNV analysis using SeqCNV. Semiquantitative multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification were conducted to verify the CNVs. Four probands were found to carry whole-gene deletions of FZD4, accounting for 5% (4/80) of probands with FZD4 mutations and 0.6% (4/651) of all FEVR probands. The four probands exhibited similar phenotypes of unilateral retinal folds. FEVR in probands with CNVs was not more severe than in probands with FZD4 missense mutations (p = 1.000). Although this is the first report of FZD4 CNVs and the associated phenotypes, the interpretation of FZD4 CNVs should be emphasized when analyzing the next-generation sequencing data of FEVR patients because of their high prevalence.
A Case of Concurrent Molybdenosis, Secondary Copper, Cobalt and Selenium Deficiency in a Small Sheep Herd in Northern Germany

Simple Summary Mineral deficiencies are very widespread among small ruminant herds throughout the world and play a big role in small ruminant herd health management. This paper describes the occurrence of a primary molybdenosis causing secondary copper deficiency, combined with ovine white liver disease (cobalt deficiency) and white muscle disease (selenium deficiency) in a group of pastured ram lambs in Northern Germany. To the authors’ knowledge, this is the first proven report of multiple trace element deficiencies in sheep in Germany for decades. Abstract To the author’s knowledge this paper describes the first proven report of a combined primary molybdenosis, secondary copper (Cu) deficiency, Ovine White Liver Disease—Cobalt (Co) deficiency, and selenium (Se) deficiency in a small pedigree herd of White Horned Heath sheep in Germany (8 ewes, 2 rams, 3 yearling ewes, 17 lambs) for decades. Clinical signs associated with these mineral deficiencies in a group of pastured ram lambs included emaciation, conjunctivitis, anaemia, growth retardation, discolouration of the wool and photodermatitis. Morbidities and mortalities arose in 4–6-month-old lambs despite intensive veterinary treatment in the summer of 2014 and 2015 (n = 13, 23% died). Se (3/5), Cu (4/7), and Co (3/3) deficiencies in combination with elevated values for Molybdenum (Mo, 2/2) were found. Hamburg is a large industrial city and an input of heavy metals from surrounding industries and coal-fired power stations in combination with a sandy, non-fertilised soil and monoculture grass species might offer a potential explanation for the severity of mineral deficiencies observed in this herd.
Functional Relevance of the Interaction between Human Cyclins and the Cytomegalovirus-Encoded CDK-Like Protein Kinase pUL97

The replication of human cytomegalovirus (HCMV) is characterized by a complex network of virus–host interaction. This involves the regulatory viral protein kinase pUL97, which represents a viral cyclin-dependent kinase ortholog (vCDK) combining typical structural and functional features of host CDKs. Notably, pUL97 interacts with the three human cyclin types T1, H and B1, whereby the binding region of cyclin T1 and the region conferring oligomerization of pUL97 were both assigned to amino acids 231–280. Here, we addressed the question of whether recombinant HCMVs harboring deletions in this region were impaired in cyclin interaction, kinase functionality or viral replication. To this end, recombinant HCMVs were generated by traceless BACmid mutagenesis and were phenotypically characterized using a methodological platform based on qPCR, coimmunoprecipitation, in vitro kinase assay (IVKA), Phos-tag Western blot and confocal imaging analysis. Combined data illustrate the following: (i) infection kinetics of all three recombinant HCMVs, i.e., ORF-UL97 ∆231–255, ∆256–280 and ∆231–280, showed impaired replication efficiency compared to the wild type, amongst which the largest deletion exhibited the most pronounced defect; (ii) specifically, this mutant ∆231–280 showed a loss of interaction with cyclin T1, as demonstrated by CoIP and confocal imaging; (iii) IVKA and Phos-tag analyses revealed strongly affected kinase activity for ∆231–280, with strong impairment of both autophosphorylation and substrate phosphorylation, but less pronounced impairments for ∆231–255 and ∆256–280; and (iv) a bioinformatic assessment of the pUL97–cyclin T1 complex led to the refinement of our current binding model. Thus, the results provide initial evidence for the functional importance of the pUL97–cyclin interaction concerning kinase activity and viral replication fitness.
PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment

Gene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier—polyethylenimine (PEI, 25 kDa)—the polyamidoamine (PAMAM) dendrimer also has a large number of amino groups. These amino groups can be complexed with nucleic acids after protonation under physiological conditions. However, the concentrated positive charge can cause undesirable cytotoxicity. Cellulose nanocrystals (CNCs) have good biocompatibility and unique needle-like morphology, and have been proven to be efficiently taken up by cells. In this article, three-dimensional spherical PMAMA dendrimers are conjugated onto the surface of CNCs to obtain a kind of needle-like cationic carrier (CNC-PAMAM). PAMAM dendrimers act as anchors to bind the plasmid DNAs (pDNA) to the surface of the CNC. The prepared CNC-based carrier showed high transfection efficiency and low toxicity. The CNC-PAMAM can effectively deliver the suicide gene to the tumor site, enabling the suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine (CD/5-FC)) to play an effective anti-tumor role in vivo. This research demonstrates that the functionalization of CNCs with PAMAM dendrimers is an effective method for developing novel gene delivery systems.
Understanding Risk Perception toward Food Safety in Street Food: The Relationships among Service Quality, Values, and Repurchase Intention

This paper aims to identify service quality dimensions of street food that have an impact on utilitarian and hedonic values and to determine the effect of utilitarian and hedonic values on repurchase intention. It also examines the moderating effect of risk perception toward street food safety on the relationship between service quality and perceived value. An Internet survey was performed in Korea with 285 respondents. The results confirmed that the five dimensions of street food’s service quality—food quality, employee service, physical environment, price, and rapidity of service—had positive impacts on utilitarian and hedonic values. All perceived value (utilitarian, hedonic) has an impact on repurchase intention. Finally, the food quality of street food showed a stronger influence on utilitarian value among the low-risk perception group than the high-risk perception group depending on the consumers’ level of awareness of food safety. This provides new insights for marketing strategies to attract domestic/foreign consumers to street food vendors and for creating a new food culture by emphasizing important domains of service quality, the relation of quality to consumer values, and risk perception toward food safety in street food.
Sprint and Jump Mechanical Profiles in Academy Rugby League Players: Positional Differences and the Associations between Profiles and Sprint Performance

This cross-sectional study evaluated the sprint and jump mechanical profiles of male academy rugby league players, the differences between positions, and the associations between mechanical profiles and sprint performance. Twenty academy rugby league players performed 40-m sprints and squat jumps at increasing loads (0–80 kg) to determine individual mechanical (force-velocity-power) and performance variables. The mechanical variables (absolute and relative theoretical maximal force-velocity-power, force-velocity linear relationship, and mechanical efficiency) were determined from the mechanical profiles. Forwards had significantly (p < 0.05) greater vertical and horizontal force, momentum but jumped lower (unloaded) and were slower than backs. No athlete presented an optimal jump profile. No associations were found between jump and sprint mechanical variables. Absolute theoretical maximal vertical force significantly (p < 0.05) correlated (r = 0.71–0.77) with sprint momentum. Moderate (r = −0.47) to near-perfect (r = 1.00) significant associations (p < 0.05) were found between sprint mechanical and performance variables. The largest associations shifted from maximum relative horizontal force-power generation and application to maximum velocity capabilities and force application at high velocities as distance increased. The jump and sprint mechanical profiles appear to provide distinctive and highly variable information about academy rugby league players’ sprint and jump capacities. Associations between mechanical variables and sprint performance suggest horizontal and vertical profiles differ and should be trained accordingly.
SVM classification of facial functions based on facial landmarks and animation Units

Quantitative assessment and classification of facial paralysis (FP) are essential for treatment selection and progress evaluation of the condition. As part of a comprehensive framework towards this goal, this study aims to classify five normal facial functions: smiling, eye closure, raising the eyebrows, blowing cheeks, and whistling as well as the rest state. 3D facial landmarks and facial animation units (FAUs) were obtained using the Kinect V2, a fast and cost-effective depth camera. These were used to compute the features used in a Support Vector Machine (SVM) classifier. A dataset of 1650 records from 50 normal subjects was compiled for this study. The performances of different SVM kernel models were tested with different feature groups. The best performance (Accuracy = 96.7%, Sensitivity = 90.2%, and Specificity = 98%) was found when using the RBF kernel model applied on just nine differences in FAUs. This research will be developed and extended to include FP classification.
Design and Optimization of a Self-Assembling Complex Based on Microencapsulated Calcium Alginate and Glutathione (CAG) Using Response Surface Methodology

The aim of this work was to characterize and optimize the formation of molecular complexes produced by the association of calcium alginate and reduced glutathione (GSH). The influence of varying concentrations of calcium and GSH on the production of microcapsules was analyzed using response surface methodology (RSM). The microcapsules were characterized by thermogravimetric analysis (TGA-DTG) and infrared spectroscopy (FTIR) in order to assess the hydration of the complexes, their thermal stability, and the presence of GSH within the complexes. The optimum conditions proposed by RSM to reach the maximum concentration of GSH within complexes were a 15% w/v of GSH and 1.25% w/v of CaCl2, with which a theorical concentration of 0.043 mg GSH per mg of CAG complex was reached.