Miracle-dz/UniFAR-FTUs huggingface dataset:
SARS-CoV-2 Causes Severe Epithelial Inflammation and Barrier Dysfunction

SARS-CoV-2 challenges health care systems and societies worldwide in unprecedented ways. Although numerous new studies have been conducted, research to better understand the molecular pathogen-host interactions are urgently needed. ABSTRACT Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be asymptomatic, but they can also be accompanied by a variety of symptoms that result in mild to severe coronavirus disease-19 (COVID-19) and are sometimes associated with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human chip model composed of epithelial, endothelial, and mononuclear cells. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including interferon expression. In contrast, the adjacent endothelial layer was neither infected nor did it show productive virus replication or interferon release. With prolonged infection, both cell types were damaged, and the barrier function deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokines or components induced during infection, which further results in damage of the epithelial/endothelial barrier function and viral dissemination. IMPORTANCE SARS-CoV-2 challenges health care systems and societies worldwide in unprecedented ways. Although numerous new studies have been conducted, research to better understand the molecular pathogen-host interactions is urgently needed. For this, experimental models have to be developed and adapted. In the present study we used mono-cell culture systems, and we established a complex chip model, where epithelial and endothelial cells are cultured in close proximity. We demonstrate that epithelial cells can be infected with SARS-CoV-2, while the endothelium did not show any infection signs. Since SARS-CoV-2 is able to establish viremia, the link to thromboembolic events in severe COVID-19 courses is evident. However, whether the endothelial layer is damaged by the viral pathogens or whether other endothelial-independent homeostatic factors are induced by the virus is essential for understanding the disease development. Therefore, our study is important, as it demonstrates that the endothelial layer could not be infected by SARS-CoV-2 in our in vitro experiments, but we were able to show the destruction of the epithelial-endothelial barrier in our chip model. From our experiments, we can assume that virus-induced host factors disturbed the epithelial-endothelial barrier function and thereby promote viral spread.
Warming effects on the early decomposition of three litter types, Eastern Tibetan Plateau, China

Temperature and litter quality are two of the key factors controlling litter decomposition. Predicted global warming and vegetation succession will therefore have profound impacts. This study was conducted to assess effects of experimental warming on litter decomposition and nutrient dynamics of two contrasting tree species (red birch, Betula albosinensis Burk., and dragon spruce, Picea asperata Mast.) and a mixture of the two with the heating cable method in the eastern Tibetan Plateau of China. This treatment raised surface soil temperature by 3.2°C and resulted in a 5.2% decline in soil moisture 10 cm below the soil surface. The water content of dragon spruce, red birch and mixed litter was decreased by 18, 11 and 13%, respectively. Marked differences between the two species in the decomposition rates and nutrient remaining percentages were detected. Moreover, we found positive, non‐additive effects of litter mixture. Experimental warming did not affect mass loss and nutrient release of dragon spruce litter but significantly increased mass loss and affected nutrient release of red birch and mixed litter during the early decomposition period. Overall, inter‐specific (red birch and dragon spruce) differences in decomposability were substantially larger than warming‐induced responses. Thus, a warming‐induced community succession towards dragon spruce forests in the Tibetan Plateau region could have a greater impact on early litter decomposition than warming itself.
A 19 μW, 50 kS/s, 0.008-400 V/s Cyclic Voltammetry Readout Interface With a Current Feedback Loop and On-Chip Pattern Generation

A cyclic voltammetry electrochemical sensing chip was implemented with a time-based readout circuit and a current feedback control loop for wide-range and high-linearity current detection. The design utilizes a chopper-stabilized, low-noise potentiostat circuit and a delay chain time-to-digital converter to improve accuracy and the conversion rate. A current feedback loop is employed to mitigate nonlinearity of the current-to-frequency converter. Also, an on-chip pattern generator with a current reducer is used to create area-efficient, multi-rate ramp signals for cyclic voltammetry and fast-scan cyclic voltammetry measurements. The chip is fabricated using a 0.18-μm CMOS process. It achieves an 8-nA current resolution in the current range of −7 μA to 10 μA with an R2 linearity of 0.999 while consuming 19 μW. The Allan deviation floor is 4.83 Hz at the 7-second integration window, resulting in an 87-pArms input-referred current noise. The applicable limit of detection for K3[Fe(CN)6] concentration is 31 pM. To measure various reactions, the scan rate can be adjusted from 0.008 V/s to 400 V/s with a throughput data rate of up to 50 kS/s.
Modeling of the Equilibrium Moisture Content (EMC) of Tarragon (Artemisia Dracunculus L.)

The equilibrium moisture content of tarragon, Artemisia dracunculus L. (stem and leaf separately) was determined by using the saturated salt solutions method at three temperatures (25, 50 and 70°C) within a range of 5 to 90% relative humidity. Both adsorption and desorption methods were used for stem and leaf of two varieties: Russian and French tarragon. Experimental curves of moisture sorption isotherms were fitted by modified Henderson, modified Halsey, modified Oswin, modified Chung-Pfost and GAB equations and evaluated by residual sum squares, standard error of estimate and mean relative deviation. The modified Halsey and GAB equations were found to be the most suitable for describing the relationship among equilibrium moisture content, relative humidity and temperature. There was no significant difference between the equilibrium moisture content of the Russian and French tarragon.
Cholesterol-lowering effect of β-glucan from oat bran in mildly hypercholesterolemic subjects may decrease when β-glucan is incorporated into bread and cookies

Cholesterol-lowering effect of beta-glucan from oat bran in mildly hypercholesterolemic subjects may decrease when beta-glucan is incorporated into bread and cookies. Kerckhoffs DA, Hornstra G, Mensink RP. Department of Human Biology, Maastricht University, Maastricht, The Netherlands. BACKGROUND: Findings about the effects of beta-glucan on serum lipoproteins are conflicting. OBJECTIVE: The study investigated the effects of beta-glucan from oat bran in bread and cookies (study 1) and in orange juice (study 2) on serum lipoproteins in mildly hypercholesterolemic subjects. DESIGN: In study 1, 48 subjects (21 men, 27 women) received for 3 wk control bread and cookies rich in wheat fiber. For the next 4 wk, by random assignment, 23 subjects continued to consume the control products, and 25 received bread and cookies rich in beta-glucan. Mean daily intake of beta-glucan was 5.9 g. Total dietary fiber intake did not differ significantly between the groups. In study 2, the same sources of control fiber and beta-glucan (5 g/d) as in study 1 were provided. For 2 wk, 25 of the original 48 subjects (10 men, 15 women) were randomly assigned to consume orange juice containing either wheat fiber (n = 13) or beta-glucan from oat bran (n = 12). After a washout period of 1 wk, dietary regimens were crossed over. RESULTS: In study 1, the change in LDL cholesterol did not differ significantly (-0.12 mmol/L; P = 0.173) between the 2 groups. In study 2, the drink rich in beta-glucan decreased LDL cholesterol by 0.26 +/- 0.07 mmol/L (6.7 +/- 1.8%; P = 0.001) and the ratio of total to HDL cholesterol by 0.26 +/- 0.11 (5.4 +/- 2.1%; P = 0.029) compared with the other drink. HDL-cholesterol and triacylglycerol concentrations did not change significantly. CONCLUSIONS: The food matrix or the food processing, or both, could have adverse effects on the hypocholesterolemic properties of oat beta-glucan.
Activated ALK Cooperates with N-Myc via Wnt/β-Catenin Signaling to Induce Neuroendocrine Prostate Cancer

These findings demonstrate that coactivation of ALK and N-Myc induces NEPC by stimulating the Wnt/β-catenin pathway, which can be targeted therapeutically. Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with poor prognosis, and there is a critical need for novel therapeutic approaches. NEPC is associated with molecular perturbation of several pathways, including amplification of MYCN. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the pathogenesis of neuroblastoma and other malignancies where it cooperates with N-Myc. We previously identified the first case of ALK F1174C-activating mutation in a patient with de novo NEPC who responded to the ALK inhibitor, alectinib. Here, we show that coactivation of ALK and N-Myc (ALK F1174C/N-Myc) is sufficient to transform mouse prostate basal stem cells into aggressive prostate cancer with neuroendocrine differentiation in a tissue recombination model. A novel gene signature from the ALK F1174C/N-Myc tumors was associated with poor outcome in multiple human prostate cancer datasets. ALK F1174C and ALK F1174C/N-Myc tumors displayed activation of the Wnt/β-catenin signaling pathway. Chemical and genetic ALK inhibition suppressed Wnt/β-catenin signaling and tumor growth in vitro in NEPC and neuroblastoma cells. ALK inhibition cooperated with Wnt inhibition to suppress NEPC and neuroblastoma proliferation in vitro and tumor growth and metastasis in vivo. These findings point to a role for ALK signaling in NEPC and the potential of cotargeting the ALK and Wnt/β-catenin pathways in ALK-driven tumors. Activated ALK and N-Myc are well known drivers in neuroblastoma development, suggesting potential similarities and opportunities to elucidate mechanisms and therapeutic targets in NEPC and vice versa. Significance: These findings demonstrate that coactivation of ALK and N-Myc induces NEPC by stimulating the Wnt/β-catenin pathway, which can be targeted therapeutically.
The Mechanism of Sugar Export from Long Conifer Needles.

The green leaves of plants are optimized for carbon fixation and the production of sugars, which are used as central units of carbon and energy throughout the plant. However, there are physical limits to this optimization that remain insufficiently understood. Here, quantitative anatomical analysis combined with mathematical modeling and sugar transport rate measurements were employed to determine how effectively sugars are exported from the needle-shaped leaves of conifers in relation to leaf length. Mathematical modeling indicated that phloem anatomy constrains sugar export in long needles. However, we identified two mechanisms by which this constraint is overcome, even in needles longer than 20 cm: i) the grouping of transport conduits, and ii) a shift in the diurnal rhythm of sugar metabolism and export in needle tips. The efficiency of sugar transport in the phloem can have a significant influence on leaf function. The constraints on sugar export described here for conifer needles are likely to also be relevant in other groups of plants, such as grasses and angiosperm trees.
Levetiracetam‐responsive paroxysmal exertional dyskinesia in a Welsh Terrier

Abstract A 5‐and‐a‐half‐year old, 9‐kg, spayed, female Welsh Terrier presented with a 12 month history of paroxysmal exertion‐induced dyskinesia (PED) characterized by recurrent episodes of involuntary hyperkinetic movements, abnormal muscle tone, and contractions triggered by exercise. A single episode occurred within 2 hours after exercise, lasted from 7 to 10 minutes, and resolved without treatment. The owner sought treatment for the dog when the episodes began to last longer (20‐30 minutes), and occurred as long as 2.5 to 8 hours after exercise. Diazepam administered intranasally at the start of an episode promptly alleviated the symptoms. Maintenance therapy with levetiracetam proved effective, such that the dog was gradually returned to exercise. However, attempts to wean the dog off the drug resulted in reoccurrence. Although the pathophysiology of PED is not fully understood, the clinical presentation and the positive response to antiepileptic therapy highlight the overlap between disease pathways in epilepsy and PED in dogs.
The foggy world(s) of p63 isoform regulation in normal cells and cancer

The p53 family member p63 exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways. TAp63 has roles in senescence and metabolism, and in germ cell genome maintenance, where it is activated post‐transcriptionally by phosphorylation cascades after DNA damage. The function and regulation of TAp63 in mesenchymal and haematopoietic cells is less clear but may involve epigenetic control through DNA methylation. ΔNp63 functions to maintain stem/progenitor cells in various epithelia and is overexpressed in squamous and certain other cancers. ΔNp63 is transcriptionally regulated through multiple enhancers in concert with chromatin modifying proteins. Many signalling pathways including growth factors, morphogens, inflammation, and the extracellular matrix influence ΔNp63 levels, with inconsistent results reported. There is also evidence for reciprocal regulation, including ΔNp63 activating its own transcription. ΔNp63 is downregulated during cell differentiation through transcriptional regulation, while post‐transcriptional events cause proteasomal degradation. Throughout the review, we identify knowledge gaps and highlight discordances, providing potential explanations including cell‐context and cell–matrix interactions. Identifying individual p63 variants has roles in differential diagnosis and prognosis, and understanding their regulation suggests clinically approved agents for targeting p63 that may be useful combination therapies for selected cancer patients. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Pouring petrol on the flames: Using oncolytic virotherapies to enhance tumour immunogenicity

Oncolytic viruses possess the ability to infect, replicate and lyse malignantly transformed tumour cells. This oncolytic activity amplifies the therapeutic advantage and induces a form of immunogenic cell death, characterized by increased CD8 + T‐cell infiltration into the tumour microenvironment. This important feature of oncolytic viruses can result in the warming up of immunologically ‘cold’ tumour types, presenting the enticing possibility that oncolytic virus treatment combined with immunotherapies may enhance efficacy. In this review, we assess some of the most promising candidates that might be used for oncolytic virotherapy: immunotherapy combinations. We assess their potential as separate agents or as agents combined into a single therapy, where the immunotherapy is encoded within the genome of the oncolytic virus. The development of such advanced agents will require increasingly sophisticated model systems for their preclinical assessment and evaluation. In vivo rodent model systems are fraught with limitations in this regard. Oncolytic viruses replicate selectively within human cells and therefore require human xenografts in immune‐deficient mice for their evaluation. However, the use of immune‐deficient rodent models hinders the ability to study immune responses against any immunomodulatory transgenes engineered within the viral genome and expressed within the tumour microenvironment. There has therefore been a shift towards the use of more sophisticated ex vivo patient‐derived model systems based on organoids and explant co‐cultures with immune cells, which may be more predictive of efficacy than contrived and artificial animal models. We review the best of those model systems here.
Structural and free‐volume analysis for alkyl‐substituted palladium‐catalyzed poly(norbornene): A combined experimental and Monte Carlo investigation

Increasing the length of an alkyl side chain on a rigid polynorbornene (PNB) backbone is shown to decrease the glass-transition temperature of the resultant polymer, decrease the density of the bulk polymer, decrease the number and average free-volume element size present, and decrease the permeability of gases through the polymer. Methyl-, butyl-, and hexyl-substituted PNBs were investigated. Experimental results were compared with predictions based on molecular modeling. By using models that provided good agreement between the experimental and simulated wide-angle diffraction patterns, the distributions of free-volume elements were predicted. These predictions clearly indicate that the number of large free-volume elements decreases as the length of the side chain increases, suggesting that the flexible aliphatic side chains can be largely accommodated within the free volume between the rigid PNB backbones. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 215–233, 2006
Intestinal microbiota and host metabolism — A complex relationship

In the current issue of Acta Physiologica, Lundberg and co-workers publish a paper entitled "Germ-free mice are not protected against diet-induced obesity and metabolic dysfunction" in which the authors show that feeding a Western diet to both conventionally raised and germ-free mice results in weight gain, increased fat mass, fatty liver, glucose intolerance and adipose tissue inflammation1 . This indicates that development of obesity and components of the metabolic syndrome is not dependent on the presence of gut microbiota and adds to the ongoing discussion regarding the causal role of intestinal microbiota in the development of obesity.
Computational design of the intermediate-band solar cells based on the quantum dot superlattices

Intermediate-band (IB) solar cells were predicted to have the photovoltaic (PV) efficiency exceeding the Shockley-Queisser limit for a single junction cell. A possible practical implementation of the IB solar cells can be based on the quantum dot superlattices (QDS). The parameters of such QDS structure have to be carefully tuned in order to achieve the desired charge carrier dispersion required for the IB solar cell operation. We used the first-principle theoretical models for calculating the carrier states and light absorption in QDS. This approach allowed us to determine the actual dimensions of the quantum dots and the inter-dot spacing for inducing the carrier miniband in the band-gap region where the miniband can play the role of the IB. Using the Shockley-Queisser detailed balance theory we determined that the upper-bound PV efficiency of such IB solar cells can be as high as ~ 51%. The required QDS dimensions for the IB implementation on the basis of InAsN/GaAsSb are technologically challenging but feasible: ~ 2 - 6 nm. The proposed computational design approach may help with implementation of other solar cell concepts for advanced light-to-energy conversion enabled by nanostructures.
Surface Adsorption Mechanism: A Molecular Self‐Assembly Phenomenon with Application to Surface Protection

Molecular self‐assembly may be defined as the assembly of molecules without guidance or interference from an external environment. There are two types of self‐assembly molecular (SAM) phenomenon occurring naturally, namely, intramolecular and intermolecular SAM. The intramolecular SAMs are often complex polymers and they have the ability to assemble random coil conformation into well‐defined stable molecular structure. In contrast, the intermolecular SAMs are molecules with the ability to form supramolecular structures. Protein molecular folding and the formation of micellae by surfactant molecules are respectively, some examples. Some corrosion inhibitors function through surface adsorption that is, either through chemisorption or physisorption or both occurring simultaneously. The assembly of these molecules and hence the protection mechanism offered resembles to the characteristic of micellae formed when surfactant is added into an aqueous environment. In this research, aliphatic amides were synthesize.
Effect of pH, iron and aluminum on survival of early life history stages of the endangered freshwater pearl mussel, Margaritifera margaritifera

Glochidium larvae and juveniles of the endangered freshwater pearl mussel Margaritifera margaritifera may be sensitive to low pH and metal exposure, but to our knowledge, no tolerance tests have been performed. Therefore, we exposed glochidia, fish-attached glochidia, and juveniles of the pearl mussel to low pH and increased iron (Fe) and aluminum (Al) by using realistic pH (6.0–4.5), Fe (0.5–2.0 mg L−1), and Al (0.25–1.0 mg L−1) levels periodically observed in this study site. Survival of glochidia decreased with decreasing pH, increasing Fe, and increasing Al, as well as with increasing Fe + Al concentration in a 72 h exposure. All glochidia died within 24 h in pH 4.5 and Fe 2.0 mg L−1. When infected trout, Salmo trutta, were exposed to increased Fe and Al from 4 days before to 76 days after infection, the numbers of encysted glochidia did not differ from unexposed control fish. In juvenile mussels, a slight decrease in survival was observed in lowered pH and increased Al and a combination of Al + Fe in a 168 h experiment. Results indicate that episodes of low pH and high metal concentrations may harm glochidia and potentially contribute to local decline of M. margaritifera.
I've Got All My Readers With Me: A Model of Reading as a Social Activity

Reading is not simply a solitary activity. It occurs in a social context, which influences both a reader's choices about what to read, and their understanding about what they read. Digitally, direct personal communication and online discussions are two examples of social reading activity. However, our understanding of social reading is still young: we know some elements of the activity, but we lack a comprehensive picture of its behavioural elements and how they interact. This study aims to bridge that existing gap. We undertook a diary study, supplemented with interviews to capture readers' social reading behaviours. Based on a qualitative analysis of that data, we propose a social reading journey model, that includes four activities: Inspiration and Motivation, Reading, Understanding and Enrich, and Social Interaction. We identify the flow of information interaction behaviour across the social reading journey, and the sources of online information that influence readers' reading choices and inform their understanding of what they read. Our findings provide a first model of social reading behaviour, that is a foundation for future research.