Miracle-dz/UniFAR-FTUs huggingface dataset:
Co-culture of type I and type II pneumocytes as a model of alveolar epithelium

The epithelial tissues of the distal lung are continuously exposed to inhaled air, and are of research interest in studying respiratory exposure to both hazardous and therapeutic materials. Pharmaco-toxicological research depends on the development of sophisticated models of the alveolar epithelium, which better represent the different cell types present in the native lung and interactions between them. We developed an air-liquid interface (ALI) model of the alveolar epithelium which incorporates cell lines representative of both type I (NCI-H441) and type II (hAELVi) epithelial cells. We compared morphology of single cells and the structure of cell layers of the two lines using light and electron microscopy. Working both in monotypic cultures and cocultures, we measured barrier function by trans-epithelial electrical resistance (TEER), and demonstrated that barrier properties can be maintained for 30 days. We created a mathematical model of TEER development over time based on these data in order to make inferences about the interactions occurring in these culture systems. We assessed expression of a panel of relevant genes that play important roles in barrier function and differentiation. The coculture model was observed to form a stable barrier akin to that seen in hAELVi, while expressing surfactant protein C, and having a profile of expression of claudins and aquaporins appropriate for the distal lung. We described cavities which arise within stratified cell layers in NCI-H441 and cocultured cells, and present evidence that these cavities represent an aberrant apical surface. In summary, our results support the coculture of these two cell lines to produce a model which better represents the breadth of functions seen in native alveolar epithelium.
Detection of the germline specific NAC protein paralog enriched by intrinsically disordered regions in Drosophila melanogaster

Nascent polypeptide associated complex (NAC) consisting of α- and β-subunits is an essential conserved ubiquitously expressed ribosome-associated protein in eukaryotes. NAC is considered as a chaperone and co-translational regulator of nascent protein sorting providing homeostasis of cellular proteins. Here we discovered the germinal cell specific NAC (gNAC) homologue, which differs from the ubiquitously expressed NAC by the presence of expanded intrinsically disordered regions (IDRs) at the N- and C-ends of the α- and β-subunits, respectively. We propose these evolutionary acquisition of long IDRs drive gNAC to endow both the specific conformational plasticity for binding client proteins and novel functions regulated by post-transcriptional modifications (PTM). At the same time, we demonstrated that the well-known lethal effect of the loss of ubiquitous NAC-β is suppressed by ectopic expression of its germinal paralog indicating the absence of strict functional differences between the ubiquitous and germline NAC-β subunit paralogs for protein homeostasis.
The N501Y spike substitution enhances SARS-CoV-2 transmission

Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1. 1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 UK spike mutations, suggesting it is a major determinant responsible for increased transmission of this variant. Mechanistically, the N501Y substitution improved the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil and South Africa, our results indicate that N501Y substitution is a major adaptive spike mutation of major concern.
Quantitative theory for the diffusive dynamics of liquid condensates

To unravel the biological functions of membraneless liquid condensates it is crucial to develop a quantitative understanding of the physics underlying their dynamics. Key processes within such condensates are diffusion and material exchange with their environment. Experimentally, diffusive dynamics are typically probed via fluorescent labels. However, to date we lack a physics-based quantitative framework for the dynamics of labeled condensate components. Here, we derive the corresponding theory, building on the physics of phase separation, and quantitatively validate this framework via experiments. We show that using our theory we can precisely determine diffusion coefficients inside liquid condensates via a spatio-temporal analysis of fluorescence recovery after photobleaching (FRAP) experiments. We showcase the accuracy and precision of our approach by considering space- and time-resolved data of protein condensates and two different polyelectrolyte-coacervate systems. Strikingly, our theory can also be used to determine the diffusion coefficient in the dilute phase and the partition coefficient, without relying on fluorescence measurements in the dilute phase. This bypasses recently described quenching artefacts in the dense phase, which can underestimate partition coefficients by orders of magnitude. Our experimentally verified theory opens new avenues for theoretically describing molecule dynamics in condensates, measuring concentrations based on the dynamics of fluorescence intensities and quantifying rates of biochemical reactions in liquid condensates.
Electrophysiological signatures of hierarchical learning

Human perception and learning is thought to rely on a hierarchical generative model that is continuously updated via precision-weighted prediction errors (pwPEs). However, the neural basis of such cognitive process and how it unfolds during decision making, remain poorly understood. To investigate this question, we combined a hierarchical Bayesian model (i.e., Hierarchical Gaussian Filter, HGF) with electrophysiological (EEG) recording, while participants performed a probabilistic reversal learning task in alternatingly stable and volatile environments. Behaviorally, the HGF fitted significantly better than two control, non-hierarchical, models. Neurally, low-level and high-level pwPEs were independently encoded by the P300 component. Low-level pwPEs were reflected in the theta (4-8 Hz) frequency band, but high-level pwPEs were not. Furthermore, the expressions of high-level pwPEs were stronger for participants with better HGF fit. These results indicate that the brain employs hierarchical learning, and encodes both low- and high-level learning signals separately and adaptively.
From synaptic activity to human in vivo quantification of neurotransmitter dynamics: a neural modelling approach

Understanding the role of neurotransmitters glutamate and GABA during normal and abnormal brain function and under external stimulation in humans are critical neuroscientific and clinical goals. The recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neuro-transmitter activity in vivo for the first time. However, the physiological basis of the observed fMRS signal remains unclear. It has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible, to extracellular and cytosolic pools, where they are visible. Here we bridge the gap between neural dynamics and fMRS by developing a mean-field model to link the neurotransmitter dynamics at the microscopic-level to the macroscopic-level imaging measurements. GABA and glutamate are described as cycling between three metabolic pools: in the vesicles; active in the cleft; or undergoing recycling in the astrocytic or neuronal cytosol. We interrogate the model by applying a current to manipulate the mean membrane potential and firing rate of the neural populations. We find that by disregarding the contribution from the vesicular pool, our model predicts activity-dependent changes in the MRS signal, which are consistent with reported empirical findings. Further, we show that current magnitude and direction has a selective effect on the GABA/glutamate-MRS signal: inhibitory stimulation leads to reduction of both metabolites, whereas excitatory stimulation leads to increased glutamate and decreased GABA. In doing so, we link neural dynamics and fMRS and provide a mechanistic account for the activity-dependent change in the observed MRS signal. Key Points Summary The recent development of functional 1H-Magnetic resonance spectroscopy (fMRS) has allowed us to study neurotransmitter activity in vivo for the first time in humans. However, the physiological basis of the observed fMRS signal is unclear. It has been proposed that fMRS detects shifts in metabolite concentrations as they move from presynaptic vesicles, where they are largely invisible to MRS, to extracellular and cytosolic pools, where they are visible to MRS. We test this hypothesis using a mean field model which links the neural dynamics of neurotransmitters at the microscopic-level to the macroscopic-level imaging measurements obtained in experimental studies. By disregarding activity in the vesicular pool, our model can generate activity-dependent changes in the MRS signal in response to stimulation which are consistent with experimental findings in the literature. We provide a mechanistic account for the activity-dependent change in observed neurotransmitter concentrations using MRS.
Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase (A) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of the cAMP pathway is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis. AUTHOR SUMMARY The human fungal pathogen Candida albicans switches between budding and filamentous hyphal morphologies to gain advantages for virulence and survival in the host. Although adenylyl cyclase has been thought to be a master regulator that controls this switch, we identified C. albicans pseudorevertant mutants that grow better and form hyphae in the absence of adenylyl cyclase and cAMP. The mutant cells were also able to induce hyphal-associated genes in the absence of cAMP that are needed for virulence. Integrating information from different omics approaches identified cAMP-independent mechanisms that promote hyphal growth. This includes phosphoproteomic studies that revealed key roles for the Cdc28 cyclin-dependent kinase and casein kinase 1 in promoting hyphal growth. In addition, integrating transcriptomic and proteomic data revealed that post-transcriptional mechanisms regulate the levels of a set of key transcription factors that are important for hyphal induction, suggesting a novel form of translational regulation. These studies better define the pathways that stimulate C. albicans to switch from budding to hyphal growth, which is important for invasion into tissues, escape from the immune system, and biofilm formation.
Partial oxidation of methane in hollow‐fiber membrane reactors based on alkaline‐earth metal‐free CO2‐tolerant oxide

The U-shaped alkaline-earth metal-free CO2-stable oxide hollow-fiber membranes based on (Pr0.9La0.1)2(Ni0.74Cu0.21Ga0.05)O4+δ (PLNCG) are prepared by a phase-inversion spinning process and applied successfully in the partial oxidation of methane (POM) to syngas. The effects of temperature, CH4 concentration and flow rate of the feed air on CH4 conversion, CO selectivity, H2/CO ratio, and oxygen permeation flux through the PLNCG hollow-fiber membrane are investigated in detail. The oxygen permeation flux arrives at approximately 10.5 mL/min cm2 and the CO selectivity is higher than 99.5% with a CH4 conversion of 97.0% and a H2/CO ratio of 1.8 during 140 h steady operation. The spent hollow-fiber membrane still maintains a dense microstructure and the Ruddlesden-Popper K2NiF4-type structure, which indicates that the U-shaped alkaline-earth metal-free CO2-tolerant PLNCG hollow-fiber membrane reactor can be steadily operated for POM to syngas with good performance. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3587–3595, 2014
Binary Mutual Diffusion Coefficients of Aqueous Solutions of β-Cyclodextrin at Temperatures from 298.15 to 312.15 K

Binary mutual diffusion coefficients (interdiffusion coeffcients) have been measured for aqueous solutions of β-cyclodextrin (β-CD) at concentrations from (0.002 to 0.008) mol·dm-3. The effect of temperature, from (298.15 to 312.15) K, was also analyzed. The concentration dependence of D is discussed on the basis of Hartley's equation. The activation energy for the diffusion process, 18719 J·mol-1, was calculated from data of D at different temperatures. This activation energy is in good agreement with that estimated using Stokes−Einstein equation (18644 J·mol-1). Activity coefficients for aqueous β-CD solutions were also estimated from Hartley equation and experimental D.
The Roles of

One of the primary causes of morbidity and mortality in those with short bowel syndrome (SBS) is sepsis, caused by bacterial translocation (BT). Since synbiotics can cease gut-related bacterial overgrowth, they may serve as a supportive dietary supplement–based strategy after gastrointestinal surgery. This study was conducted to determine the effects of Lactobacillus acidophilus and pectin on BT and gut adaptation after extensive small bowel resection in the rat. Forty rats were distributed in four groups. Group A suffered laparotomy, group B suffered gut transection and reanastomosis, SBS rats (group C) suffered 75% small gut resection, and finally, Group D suffered gut resection and treated with a synbiotic cocktail from day 7 before the surgery to day 14 after it. Intestinal structural changes and BT to mesenteric lymph nodes, liver, portal blood, and peripheral blood were detected on day 15 post-surgery. Treatment with a synbiotic cocktail led to a considerable reduction in bacterial translocation to liver and portal vein (degree II) compared with SBS untreated rats. Also, synbiotic administration significantly increased jejunum and ileum villus height and crypt depth, ileum villus width, and percentage of goblet cells in jejunum and ileum compared with SBS rats. In the rat model of short bowel syndrome, L. acidophilus, and pectin, as a potential synbiotic compound, could decrease the BT from the gut and improve the bowel adaptation.
Direct Extraction of Propionic Acid from Propionibacterium acidipropionici Broths with Tri‐n‐octylamine

The direct reactive extraction of propionic acid from Propionibacterium acidipropionici broths with solutions of tri-n-octylamine in dichloromethane, n-butyl acetate or n-heptane underlined the strong negative influence of the cells, due to the blockage of the interface by their adsorption. The magnitude of this effect depends on the affinity of the cells for the organic phase, which is more important for n-heptane, but only at biomass concentrations below 18 g L–1 d.w. (dry weight). Moreover, the interfacial mass transfer of the acid is also controlled by the solvent polarity, and is accelerated from n-heptane to dichloromethane and by the addition to the organic phase of 1-octanol as a phase modifier. The influences of the biomass concentration, the rotation speed and the solvent dielectric constant were included in a mathematical model describing the solute mass flow from the aqueous to the organic phase.
Drainage and Rupture of Partially Mobile Films during Coalescence in Liquid-Liquid Systems under a Constant Interaction Force

A numerical description is developed of the process of film drainage and rupture during drop coalescence in liquid-liquid systems. The model is based on various simplifying approximations, corresponding to the regime in which interfacial mobility is controlled by the drop viscosity (partially mobile films). The constant force approach of a drop relative to another drop or to a free interface, taking into account the van der Waals attractive forces, is considered in this paper. The results are presented and compared with a simple analytical model proposed earlier for effective critical film-rupture thickness, which is found to provide a good first approximation.
Relativistic effects in gold chemistry. VI. Coupled cluster calculations for the isoelectronic series AuPt-, Au2, and AuHg+

Nonrelativistic and scalar relativistic pseudopotential calculations were carried out for the isoelectronic series of diatomic molecules AuPt−, Au2, and AuHg+ at the Hartree–Fock, second-order Mo/ller–Plesset (MP2), and coupled-cluster [CCSD(T)] level. For Au2 we performed large scale fully relativistic Dirac–Hartree–Fock and MP2 benchmark calculations in order to test the reliability of the pseudopotential approximation. Both methods yield almost identical spectroscopic properties for Au2. The comparison further reveals that pseudopotentials correctly describe the effects of relativity on the spectroscopic properties of Au2. The yet unknown diatomic species AuPt− and AuHg+ are stable compounds, and their rotational–vibrational constants are predicted. These show striking similarities compared to the values of Au2. MP2 results including a set of three g-functions per metal atom indicate that higher angular momentum functions are important for accurately predicting the bond distance of these molecules.
Exosome in Hepatocellular Carcinoma: an update

Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Intercellular communication among cancer cells and their microenvironment is crucial to disease progression. Exosomes are extracellular vesicles secreted by multiple types of cells into the extracellular space, which contain a variety of active components of secretory cells, including lipids, proteins, RNA and DNA. This vesicle structure involves in the exchange of materials and information between cells and plays an important role in the development of many diseases. Studies have shown that exosomes participate in the communication between HCC cells and non-HCC cells and regulate the occurrence and development of hepatocellular carcinoma. Therefore, exosomes may be specific biomarkers for early diagnosis and metastasis of HCC, which are also potential targets for the treatment of HCC. This review summarizes the characteristic, types and biological functions of exosomes and discusses their research progress and application prospects in the diagnosis and treatment of HCC.
Leaf Carbon Isotope Discrimination in Gossypium hirsutum under Drought Conditions

The breeding programme at CIFA Las Torres-Tomejil (Andalucia, Spain) has aimed at developing cotton cultivars with economic yield for conditions of restricted water supply since 1989. Increasing water-use efficiency may be one way for obtaining greater crop yield with limited water. The determination of carbon isotope discrimination (Δ) in plants provides timeintegrated measures of physiological activity and plant interaction with the environment. The relationship found between Δ and water-use efficiency (WUE) supports the possibility of using Δ as a criterion to select for WUE in breeding programmes. In this study, we investigated the effects of the environment on Δ and gas exchange parameters in different cultivars of G. hirsutum. Cotton genotypes were cultivated under irrigation in Las Torresand dryland in Tomejil. Gas exchange measurements and samplings for Δ determination were carried out under different levels of water availability. The relationship between gas exchange parameters and Δ changed across the environments. No relationship was found between Δ and estimates of WUE after witholding irrigation but a positive association was found between Δ and photosynthesis/transpiration ratio (A/E) in dryland. Several factors affect gas exchange measurements that make them unreliable for estimating WUE, but variability of Δ across environments requires further studies for its use as a surrogate for WUE in breeding programmes.
Undecided? A board game about intertemporal choices in software projects

Software projects teem with choices that have a temporal component – i.e. they involve uncertain future outcomes that are spread in time. In the field of Judgment and Decision Making, such decisions are called “Intertemporal Choice” situations. The board game “Undecided? ” simulates a software project through a series of intertemporal choices made by a team decision. It is designed to be educational and fun, but its aim is to provide a platform for cognitive and social studies of decision making in software projects. This paper describes the game and outlines possible research designs
RF Sputter-Deposited Nanostructured CuO Films for Micro-Supercapacitors

Copper oxide is considered as an alternative electrode material for supercapacitors due to its low cost, chemical stability and high theoretical specific capacitance. In the present work, nanostructured copper oxide (CuO) films are prepared by radio-frequency (RF) magnetron sputtering, and the influence of the substrate temperature on the microstructure and supercapacitive properties was studied. The copper oxide films prepared at 350 °C exhibit a predominant (1¯11) orientation corresponding to the monoclinic Cu(II)O phase with a crystallite size of 24 nm. The surface of the film consists of uniformly distributed oval-like grains providing a high surface roughness of 45 nm. The films exhibit an optical bandgap of 1.68 ± 0.01 eV and an electrical conductivity of 0.4 S cm−1 at room temperature. The as-prepared CuO films deliver a discharge specific capacitance of 387 mF cm−2 (375 F g−1) at a current density of 1 mA cm−2 with excellent cyclic capacitance retention of 95% (367 mF cm−2) even after 1000 cycles. Hence, these films are potential electrodes for micro-supercapacitors.