Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the Role of SRC in Extraocular Muscle Fibrosis of the Graves’ Ophthalmopathy

The Graves’ disease is an autoimmune disease highly associated with thyroid cancer. The Graves’ ophthalmopathy (GO) is a special Graves’ disease with inflammatory ophthalmopathy being a typical extrathymic complication. GO is caused by the formation of orbital fat and extraocular muscle fibrosis due to the inflammation of orbital connective tissues. Thus, controlling extraocular muscle fibrosis is critical for the prognosis of GO. The objective of this study is to identify and experimentally validate key genes associated with GO and explore their potential function mechanisms especially on extraocular muscle fibrosis. Specifically, we first created a GO mouse model, and performed RNA sequencing on the extraocular muscles of fibrotic GO mice and controls. SRC was identified as the most significant unstudied differentially expressed gene between GO mice and controls. Thus, we conducted a few in vitro analyses to explore the roles and functions of SRC in GO, for which we selected primary cultured orbital fibroblast (OF) as the in vitro cell line model. It is known that myofibroblast (MFB), which expresses α-SMA, is an important target cell in the process of fibrosis. Our experiment suggests that TGF-β can induce the transformation from OF to MFB, however, the transformation was inhibited by silencing the SRC gene in OF. In addition, we also inhibited TGF-β/Smad, NF-κB, and PI3K/Akt signaling pathways to analyze the interaction between these pathways and SRC. In conclusion, the silence of SRC in OF can inhibit the transformation from OF to MFB, which might be associated with the interaction between SRC and a few pathways such as TGF-β/Smad, NF-κB, and PI3K/Akt.
Alignment of Continuous Auditory and Visual Distractor Stimuli Is Leading to an Increased Performance

Information across different senses can affect our behavior in both positive and negative ways. Stimuli aligned with a target stimulus can lead to improved behavioral performances, while competing, transient stimuli often negatively affect our task performance. But what about subtle changes in task-irrelevant multisensory stimuli? Within this experiment we tested the effect of the alignment of subtle auditory and visual distractor stimuli on the performance of detection and discrimination tasks respectively. Participants performed either a detection or a discrimination task on a centrally presented Gabor patch, while being simultaneously subjected to a random dot kinematogram, which alternated its color from green to red with a frequency of 7.5 Hz and a continuous tone, which was either a frequency modulated pure tone for the audiovisual congruent and incongruent conditions or white noise for the visual control condition. While the modulation frequency of the pure tone initially differed from the modulation frequency of the random dot kinematogram, the modulation frequencies of both stimuli could align after a variable delay, and we measured accuracy and reaction times around the possible alignment time. We found increases in accuracy for the audiovisual congruent condition suggesting subtle alignments of multisensory background stimuli can increase performance on the current task.
The Domestication Makeup: Evolution, Survival, and Challenges

Animal domestication is considered a complex and multistage process that altered behaviorally, morphologically, and physiologically the domesticates relative to their wild ancestors. Ever since Darwin, scientists have been concerned about the history of domestication. To determine the domestication origins of the species, it is crucial to discover their ancestors and identify the approximate local domestication. Domestication has been the focus of several studies from different specialties. Studying when, where, and how domestication happened is essential to understand the origins of civilizations and the evolution of domesticated species. The development of both humans and domestic animals is hard to justify, and the genetic variations that occurred during the early animal domestication process remain vague. The recent and potential applications of evolutionary biology may deliver answers for main social challenges. It is important to examine the relationship among the environment and the traits of organisms that have been influenced through the adaptation to modern environments and the patterns of selection triggered by their environments during domestication period. Once domestication occurred, several events such as gene flow and selective pressures occurred, leading to genomic and phenotypic alterations. In this review, we discuss the current knowledge about the spatiotemporal outlines of domestication and debates surrounding the intent, speed, and evolutionary landscapes of this event. We also focus on the core challenges for future research. In conclusion, we argue that although the current growth in domestication information has been remarkable, the next era will produce even more significant insights into not only how domestication occurred but also where and when it did so.
The Use of Mononucleosome Immunoprecipitation for Analysis of Combinatorial Histone Post-translational Modifications and Purification of Nucleosome-Interacting Proteins

The nucleosome is the principal structural unit of chromatin. Although many studies focus on individual histone post-translational modifications (PTMs) in isolation, it is important to recognize that multiple histone PTMs can function together or cross-regulate one another within the nucleosome context. In addition, different modifications or histone-binding surfaces can synergize to stabilize the binding of nuclear factors to nucleosomes. To facilitate these types of studies, we present here a step-by-step protocol for isolating high yields of mononucleosomes for biochemical analyses. Furthermore, we discuss differences and variations of the basic protocol used in different publications and characterize the relative abundance of selected histone PTMs and chromatin-binding proteins in the different chromatin fractions obtained by this method.
Effect of heating on canola meal protein degradation in the rumen and digestion in the lower gastrointestinal tract of steers

Commercially available canola meal (CM) was moist heat treated at 127 °C with steam-pressure of 117 kPa for 15, 30, 45, 60 and 90 min. The effect of moist heat treatment of CM on rumen degradability and lower gastrointestinal (GI) tract digestibility of rumen escape dry matter (DM) and nitrogen (N) was determined using three rumen and two duodenal cannulated steers. Rumen degradability was estimated by incubating sample-filled small nylon bags in the rumen of steers for 10 and 16 h. Lower GI tract digestibility was estimated using a sequence of ruminal in situ incubation, in vitro incubation in an acid-pepsin solution and a mobile nylon bag technique. DM and N degradation of treated CM were significantly (P < 0.01) reduced in the rumen while the digestibility of DM and N in the lower GI tract was increased at all treatment times. At 16 h incubation, N disappearance declined in the rumen from 74.4 to 18.9% and increased in the lower GI tract from 16.2 to 64.2% for control and for CM heat treated for 45 min.
Karyological observations on the occurrence of meiosis in the life cycle of Porphyra haitanensis Chang et Zheng (Bangiales, Rhodophyta)

Abstract The occurrence of meiosis in the life cycle of the heteromorphic dioecious marine red alga, Porphyra haitanensis, is described. Chromosome numbers indicated that conchosporangial cells and conchospores are diploid (2n=10), while two- and three-celled stages of conchospore germlings, vegetative cells and spermatia of the gametophytic blades are haploid (n=5). We observed karyological changes in leptotene, zygotene, pachytene, diakinesis, metaphase and anaphase of the meiosis, and the change in ploidy at the two-celled stage of conchospore germling. Characteristics of the first division of the conchospore and the change in ploidy at the two-celled stage indicated that meiosis I occurs during the germination division of conchospore in this species.
Fungi as a Potential Source of Pigments: Harnessing Filamentous Fungi

The growing concern over the harmful effects of synthetic colorants on both the consumer and the environment has raised a strong interest in natural coloring alternatives. As a result the worldwide demand for colorants of natural origin is rapidly increasing in the food, cosmetic and textile sectors. Natural colorants have the capacity to be used for a variety of industrial applications, for instance, as dyes for textile and non-textile substrates such as leather, paper, within paints and coatings, in cosmetics, and in food additives. Currently, pigments and colorants produced through plants and microbes are the primary source exploited by modern industries. Among the other non-conventional sources, filamentous fungi particularly ascomycetous and basidiomycetous fungi (mushrooms), and lichens (symbiotic association of a fungus with a green alga or cyanobacterium) are known to produce an extraordinary range of colors including several chemical classes of pigments such as melanins, azaphilones, flavins, phenazines, and quinines. This review seeks to emphasize the opportunity afforded by pigments naturally found in fungi as a viable green alternative to current sources. This review presents a comprehensive discussion on the capacity of fungal resources such as endophytes, halophytes, and fungi obtained from a range or sources such as soil, sediments, mangroves, and marine environments. A key driver of the interest in fungi as a source of pigments stems from environmental factors and discussion here will extend on the advancement of greener extraction techniques used for the extraction of intracellular and extracellular pigments. The search for compounds of interest requires a multidisciplinary approach and techniques such as metabolomics, metabolic engineering and biotechnological approaches that have potential to deal with various challenges faced by pigment industry.
Competition and Drought Alter Optimal Stomatal Strategy in Tree Seedlings

A better understanding of plant stomatal strategies holds strong promise for improving predictions of vegetation responses to drought because stomata are the primary mechanism through which plants mitigate water stress. It has been assumed that plants regulate stomata to maintain a constant marginal water use efficiency and forego carbon gain when water is scarce. However, recent hypotheses pose that plants maximize carbon assimilation while also accounting for the risk of hydraulic damage via cavitation and hydraulic failure. This “gain-risk” framework incorporates competition in stomatal regulation because it takes into account that neighboring plants can “steal” unused water. This study utilizes stomatal models representing both the water use efficiency and carbon-maximization frameworks, and empirical data from three species in a potted growth chamber experiment, to investigate the effects of drought and competition on seedling stomatal strategy. We found that drought and competition responses in the empirical data were best explained by the carbon-maximization hypothesis and that both drought and competition affected stomatal strategy. Interestingly, stomatal responses differed substantially by species, with seedlings employing a riskier strategy when planted with a high water use competitor, and seedlings employing a more conservative strategy when planted with a low water use competitor. Lower water users in general had less stomatal sensitivity to decreasing ΨL compared to moderate to high water users. Repeated water stress also resulted in legacy effects on plant stomatal behavior, increasing stomatal sensitivity (i.e., conservative behavior) even when the seedling was returned to well-watered conditions. These results indicate that stomatal strategies are dynamic and change with climate and competition stressors. Therefore, incorporating mechanisms that allow for stomatal behavioral changes in response to water limitation may be an important step to improving carbon cycle projections in coupled climate-Earth system models.
The most efficient metazoan swimmer creates a ‘virtual wall’ to enhance performance

It has been well documented that animals (and machines) swimming or flying near a solid boundary get a boost in performance1-6. This ground effect is often modeled as an interaction between a mirrored pair of vortices represented by a true vortex and an opposite sign ‘virtual vortex’ on the other side of the wall7. However, most animals do not swim near solid surfaces and thus near body vortex-vortex interactions in open-water swimmers have been poorly investigated. In this study we examine the most energetically efficient metazoan swimmer known to date, the jellyfish Aurelia aurita, to elucidate the role that vortex interactions can play in animals that swim away from solid boundaries. We used high speed video tracking, laser-based digital particle image velocimetry (dPIV) and an algorithm for extracting pressure fields from flow velocity vectors to quantify swimming performance and the effect of near body vortex-vortex interactions. Here we show that a vortex ring (stopping vortex), created underneath the animal during the previous swim cycle, is critical for increasing propulsive performance. This well positioned stopping vortex acts in the same way as a virtual vortex during wall-effect performance enhancement, by helping converge fluid at the underside of the propulsive surface and generating significantly higher pressures which result in greater thrust. These findings advocate that jellyfish can generate a wall-effect boost in open water by creating what amounts to a ‘virtual wall’ between two real, opposite sign vortex rings. This explains the significant propulsive advantage jellyfish possess over other metazoans and represents important implications for bio-engineered propulsion systems.
PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma

Approximately 50% of human cutaneous melanomas carry activating mutations in the serine/threonine protein kinase BRAF. BRAF inhibitors (BRAFi) selectively target the oncogenic BRAFV600E/K and are effective in approximately 80% of patients carrying the mutation. However, resistance to BRAFi is common and emerges within a median time of 6-7 months of treatment and is prolonged to 11 months when combined with MEK inhibitors. Better characterization of the underlying molecular processes is therefore needed to further improve treatments. Inactivation of the tumor suppressor gene PTEN has been suggested to occur during melanomagenesis and drug resistance development. We recently demonstrated that transcription of PTEN is negatively regulated by an antisense RNA from the PTEN pseudogene (PTENP1-AS) and here set out to investigate the impact of this molecular pathway on the resistance to BRAFi and clinical outcome. We used a panel of BRAFi resistant A375 sublines, and observed increased levels of PTENP1-AS associated with reduced expression of PTEN. Furthermore, this loss of PTEN expression was correlated to increased recruitment of Enhancer of zeste homolog 2 (EZH2) and formation of the transcriptional repression mark H3K27me3 at the PTEN promoter in the resistant cells. We demonstrated that targeting of PTENP1-AS was able to re-activate the expression of PTEN and sensitize resistant melanoma cells to BRAFi. Finally, we showed that PTENP1-AS is a promising prognostic marker for clinical outcome in melanoma patients as high expression of PTENP1-AS in regional lymph node metastases from stage III melanoma patients correlated with poor survival.
In situ hybridization studies of stromelysin and tissue inhibitor of metalloproteinase 1 in IgA nephropathy

Summary: Accumulation of the extracellular matrix (ECM) in IgA nephropathy (IgAN) is thought to cause deterioration of glomerular function. Stromelysin and tissue inhibitor of matrix proteinase 1 (TIMP1) may play an important role in the turnover of the glomerular ECM. However, the expression of these enzymes in human renal tissues remains undefined. In the present study, non‐radioactive in situ mRNA hybridization, which permitted the analysis at a cellular level, was performed to localize stromelysin and TIMP1 in renal tissue of IgAN. We also determined the percentage of cells positive for stromelysin or TIMP1 mRNA among intraglomerular cells. A total of 16 patients with IgAN were examined, including eight patients with severe histopathological changes and eight with mild changes. Three patients without glomerular disease were also studied. Stromelysin and TIMP1 mRNA were weakly expressed in the mesangium of normal kidneys and IgAN renal tissues with mild damage. However, the expression of both mRNA was significantly increased in the area of mesangial proliferation, in glomerular epithelial cells and in Bowman's capsule of advanced lesions. Several cells in the area of mesangial proliferation were double positive for stromelysin and TIMP1 mRNA, while certain cells positive for stromelysin mRNA did not express TIMP1 mRNA. In the interstitium, epithelial cells of certain tubules and some mononuclear cells were positively stained for these mRNA, especially in advanced lesions. Our results indicated that stromelysin and TIMP1 genes were expressed in glomerular resident cells, tubular epithelial cells and infiltrated mononuclear cells in IgAN, and their expression was enhanced in advanced tissue damage. the demonstration of a co‐expression and discordant expression of the genes indicates that each gene expression may be regulated in a cell type‐specific manner and that it could also be altered by cellular environmental factors.
Artistoo: build, share, and explore simulations of cells and tissues in the web browser

Summary The Cellular Potts Model (CPM) is a powerful in silico method for simulating diverse biological processes at tissue scale. Because of its inherently graphical nature, this model should in theory be accessible to a large audience of biologists – without requiring extensive mathematical expertise. But in practice, CPMs are mostly implemented in specialized frameworks that users need to master before they can run and modify the simulation. We here present Artistoo (Artificial Tissue Toolbox), a JavaScript library for building “explorable” CPM simulations where users can change model parameters and see their effects in real time. Artistoo simulations run directly in the web browser and do not require any third-party software, plugins, or back-end servers. Although implemented in JavaScript, Artistoo does not suffer from a major performance loss compared to frameworks written in C++; it remains sufficiently fast to let users interact with simulations in real time. Artistoo provides an opportunity to unlock CPM models for a broader audience: interactive simulations can be shared through a simple URL in a zero-install setting. We discuss how such model sharing may benefit modelling research, science dissemination, open science, and education. Availability and Implementation Artistoo is an open-source library released under the MIT license, and is freely available on GitHub at https://github.com/ingewortel/artistoo. Contact Johannes.Textor@radboudumc.nl
In Vivo β-Secretase 1 Inhibition Leads to Brain Aβ Lowering and Increased α-Secretase Processing of Amyloid Precursor Protein without Effect on Neuregulin-1

β-Secretase (BACE) cleavage of amyloid precursor protein (APP) is one of the first steps in the production of amyloid β peptide Aβ42, the putative neurotoxic species in Alzheimer's disease. Recent studies have shown that BACE1 knockdown leads to hypomyelination, putatively caused by a decline in neuregulin (NRG)-1 processing. In this study, we have tested a potent cell-permeable BACE1 inhibitor (IC50 ∼ 30 nM) by administering it directly into the lateral ventricles of mice, expressing human wild-type (WT)-APP, to determine the consequences of BACE1 inhibition on brain APP and NRG-1 processing. BACE1 inhibition, in vivo, led to a significant dose- and time-dependent lowering of brain Aβ40 and Aβ42. BACE1 inhibition also led to a robust brain secreted (s)APPβ lowering that was accompanied by an increase in brain sAPPα levels. Although an increase in full-length NRG-1 levels was evident in 15-day-old BACE1 homozygous knockout (KO) (–/–) mice, in agreement with previous studies, this effect was also observed in 15-day-old heterozygous (+/–) mice, but it was not evident in 30-day-old and 2-year-old BACE1 KO (–/–) mice. Thus, BACE1 knockdown led to a transient decrease in NRG-1 processing in mice. Pharmacological inhibition of BACE1 in adult mice, which led to significant Aβ lowering, was without any significant effect on brain NRG-1 processing. Taken together, these results suggest that BACE1 is the major β-site cleavage enzyme for APP and that its inhibition can lower brain Aβ and redirect APP processing via the potentially nonamyloidogenic α-secretase pathway, without significantly altering NRG-1 processing.
Design and Development of a Low-Cost Arduino-Based Electrical BioImpedance Spectrometer

Background: Bioimpedance spectroscopy (BIS) is a device used to measure electrical impedance at frequencies from 0 Hz to 1 MHz. Many clinical diagnosis and fundamental researches, especially in the field of physiology and pathology, rely on this device. The device can be used to estimate human body composition, through the information of total body water, extracellular fluid and intracellular fluid, fat-free mass, and fat mass from its impedance. BIS analysis can provide physiological statuses such as ischemia, pulmonary edema, skin cancer, and intramuscular tumors. BIS is expected to be used even more widely, both for hospital or home-based use, particularly because BIS handy, compact, inexpensive, and less power-consuming with adequately accurate real-time. In previous research, the BIS design was based on the magnitude-ratio and phase-difference detection using the AD8302 gain-phase detector method which resulted in an operating range between 20 kHz and 1 MHz. However, the impedance was obtained from the logarithmic ratio magnitude which caused the device to have limited accuracy at frequencies <20 kHz. Methods: In this research, we conduct design and development of a low-cost arduino-based electrical bioimpedance spectrometer. Results: The low-cost bioimpedance spectrometry was successfully developed using AD9850 as the programmable function generator, OPA2134 as the OpAm of voltage-controlled current source, AD620A as the instrument amplifier and AD536A as the alternating current to direct current converter which could work accurately from 0 Hz to 100 kHz. Conclusion: The multi-frequency bioimpedance device developed in this research has the capability to safely measure the impedance of the human body due to its relatively stable electric current, which is equal to (0.370 ± 0.003) mA with frequencies ranging from 5 to 200 kHz and has an accuracy of over 90% in the frequency range of 10 Hz to 100 kHz.