Miracle-dz/UniFAR-FTUs huggingface dataset:
Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway

Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways.
Scalable and heterogenous mobile robot fleet-based task automation in crowded hospital environments—a field test

In hospitals, trained medical staff are often, in addition to performing complex procedures, spending valuable time on secondary tasks such as transporting samples and medical equipment; or even guiding patients and visitors around the premises. If these non-medical tasks were automated by deploying mobile service robots, more time can be focused on treating patients or allowing well-deserved rest for the potentially overworked healthcare professionals. Automating such tasks requires a human-aware robotic mobility system that can among other things navigate the hallways of the hospital; predictively avoid collisions with humans and other dynamic obstacles; coordinate task distribution and area coverage within a fleet of robots and other IoT devices; and interact with the staff, patients and visitors in an intuitive way. This work presents the results, lessons-learned and the source code of deploying a heterogeneous mobile robot fleet at the Tartu University Hospital, performing object transportation tasks in areas of intense crowd movement and narrow hallways. The primary use-case is defined as transporting time-critical samples from an intensive care unit to the hospital lab. Our work builds upon Robotics Middleware Framework (RMF), an open source, actively growing and highly capable fleet management platform which is yet to reach full maturity. Thus this paper demonstrates and validates the real-world deployment of RMF in an hospital setting and describes the integration efforts.
Genoprotective activity of the Pleurotus eryngii mushrooms following their in vitro and in vivo fermentation by fecal microbiota

Pleurotus eryngii mushrooms are commercially cultivated and widely consumed due to their organoleptic properties, and the low caloric and high nutritional value. In addition, they contain various biologically active and health-promoting compounds; very recently, their genoprotective effect in Caco-2 cells after their fermentation by the human fecal microbiota was also documented. In the current study, the effect of P. eryngii pre- and post-fermentation supernatants in micronuclei formation was evaluated in human lymphocytes. In addition, the genoprotective properties of increasing concentrations of aqueous extracts from P. eryngii mushrooms (150, 300, 600 mg/kg) against the cyclophosphamide-induced DNA damage were studied in young and elderly female and male mice in bone marrow and whole blood cells. The ability of the highest dose (600 mg/kg) to regulate the main cellular signaling pathways was also evaluated in gut and liver tissues of female animals by quantifying the mRNA expression of NrF2, Nfkβ, DNMT1, and IL-22 genes. P. eryngii post-fermentation, but not pre-fermentation, supernatants were able to protect human lymphocytes from the mitomycin C-induced DNA damage in a dose-dependent manner. Similarly, genoprotection was also observed in bone marrow cells of mice treated by gavage with P. eryngii extract. The effect was observed in all the experimental groups of mice (young and elderly, male and female) and was more potent in young female mice. Overexpression of all genes examined was observed in both tissues, mainly among the elderly animals. In conclusion, P. eryngii mushrooms were shown to maintain genome integrity through protecting cells from genotoxic insults. These beneficial effects can be attributed to their antioxidant and immunomodulatory properties, as well as their ability to regulate the cell’s epigenetic mechanisms and maintain cell homeostasis.
Translating advances in microbial bioproduction to sustainable biotechnology

Advances in synthetic biology have radically changed our ability to rewire microorganisms and significantly improved the scalable production of a vast array of drop-in biopolymers and biofuels. The success of a drop-in bioproduct is contingent on market competition with petrochemical analogues and weighted upon relative economic and environmental metrics. While the quantification of comparative trade-offs is critical for accurate process-level decision making, the translation of industrial ecology to synthetic biology is often ambiguous and assessment accuracy has proven challenging. In this review, we explore strategies for evaluating industrial biotechnology through life cycle and techno-economic assessment, then contextualize how recent developments in synthetic biology have improved process viability by expanding feedstock availability and the productivity of microbes. By juxtaposing biological and industrial constraints, we highlight major obstacles between the disparate disciplines that hinder accurate process evaluation. The convergence of these disciplines is crucial in shifting towards carbon neutrality and a circular bioeconomy.
Early-Life Exposure of Pigs to Topsoil Alters miRNA and mRNA Expression in Peripheral Blood Mononuclear Cells

Exposure to less-hygienic conditions during early childhood has been associated with stimulation and development of the immune system. A recent study indicated that exposure of piglets to soil-borne microbes during lactation was related with modulation of gut microbiota and immune function. To identify the potential molecular mechanisms and pathways impacted by early-life topsoil exposure, we analyzed the messenger RNA (mRNA) and micro-RNA (miRNA) expression in peripheral blood mononuclear cells (PBMCs) from these piglets. Total RNA was extracted from the PBMCs of piglets exposed to topsoil only from d 4–d 21 of life (mRNA n = 6; miRNA n = 5) or unexposed control pigs (mRNA n = 6; miRNA n = 8) at 11, 20, and 56 days of age. Small RNA and mRNA were sequenced with 50-bp single-end reads using Illumina chemistry. Sequence data were quality checked with FASTQC software and aligned to the Sscrofa 11.1 genome with the STAR aligner for mRNA and mirDeep2 for miRNA. Differential expression (DE) analysis was performed using PROC Glimmix of SAS to evaluate changes in expression due to topsoil exposure over time with genes declared DE at a false discovery rate (FDR) of q < 0.10. A total of 138 mRNA and 21 miRNAs were identified as DE for the treatment by age interaction. Ontology enrichment analysis of DE mRNA revealed Gene ontology (GO) terms directly involved in the connection between T-cell and antigen-presenting cells that are associated with T-cell activation. Key regulatory genes identified include PTPRJ, ITGB3, TRBV30, CD3D, mir-143, mir-29, and mir-148a. While these results require validation, this study provides data supporting the hypothesis that less-hygienic environments during early life may contribute to the development of the immune system.
Flexible forecast presentation overcomes longstanding obstacles to using probabilistic seasonal forecasts

We describe an innovative forecast presentation that aims to overcome obstacles to using seasonal climate forecasts for decision making, trace factors that influenced how seasonal forecast conventions have evolved, and describe a workshop process for training and supporting farmers in sub-Saharan Africa to use probabilistic seasonal forecasts. Mainstreaming seasonal climate forecasts through Regional Climate Outlook Forums (RCOFs) was an important milestone in the development of climate services. Most RCOFs and National Meteorological Services (NMS) adopted a subjective process to arrive at a consensus among different sources of prediction, and express the forecast as probabilities that rainfall in the upcoming season will fall in “below-normal,” “normal” or “above-normal” historical tercile categories. The Flexible Forecast is an online presentation that rectifies the main criticisms of the tercile convention by presenting downscaled forecasts as full probability distributions in probability-of-exceedance format along with the historical climate distribution. A map view provides seasonal forecast quantities, anomalies, or probabilities of experiencing above or below a user-selected threshold in amount or percentile, at the spatial resolution of the underlying gridded data (typically 4 to 5 km). We discuss factors that contributed to the persistence of the tercile convention, and milestones that paved the way to adopting seasonal forecast methods and formats that better align with user needs. The experience of adopting the new flexible forecast presentation regionally and at a national level in Eastern Africa illustrates the challenges and how they can be overcome. We also describe a seasonal forecast training and planning workshop process that has been piloted with smallholder farmers in several African countries. Beginning with participants' collective memory of past seasonal climate variations, the process leads them incrementally to understand the forecast presented in probability-of-exceedance format, and apply it to their seasonal planning decisions.
Genomic approaches for improving resistance to Phytophthora crown rot caused by P. cactorum in strawberry (Fragaria × ananassa)

Phytophthora crown rot (PhCR) caused by Phytophthora cactorum is one of the most damaging soilborne diseases of strawberry in the United States and worldwide. Limitations on fumigants such as methyl bromide have led to deterioration in the control of P. cactorum in recent years. The development of resistant varieties is a critical component of the strategy for combatting this soilborne disease. Here, we review the biology of the pathogen, molecular mechanisms of infection, and management of PhCR in strawberry. Recent genomics advances in octoploid strawberry breeding have been able to gain a deeper insight into the genetic architecture of resistance to PhCR and identified the genetic resistance sources for the improvement of strawberry varieties against the pathogen. Quantitative trait loci (QTL) associated with PhCR resistance have been identified and introgressed for breeding of PhCR resistance in cultivated octoploid strawberry (F. × ananassa). Further characterizing candidate genes and mechanisms of resistance could facilitate incorporating the resistance genes into commercial varieties through genomics-assisted breeding, respectively. In this review, we address important recent advances and progress for genomics-assisted breeding for the resistance to PhCR and the potential use of CRISPR gene editing in cultivated strawberry.
Application of recombinant antibodies for treatment of Clostridioides difficile infection: Current status and future perspective

Clostridioides difficile (C. difficile), known as the major cause of antibiotic-associated diarrhea, is regarded as one of the most common healthcare-associated bacterial infections worldwide. Due to the emergence of hypervirulent strains, development of new therapeutic methods for C. difficile infection (CDI) has become crucially important. In this context, antibodies have been introduced as valuable tools in the research and clinical environments, as far as the effectiveness of antibody therapy for CDI was reported in several clinical investigations. Hence, production of high-performance antibodies for treatment of CDI would be precious. Traditional approaches of antibody generation are based on hybridoma technology. Today, application of in vitro technologies for generating recombinant antibodies, like phage display, is considered as an appropriate alternative to hybridoma technology. These techniques can circumvent the limitations of the immune system and they can be exploited for production of antibodies against different types of biomolecules in particular active toxins. Additionally, DNA encoding antibodies is directly accessible in in vitro technologies, which enables the application of antibody engineering in order to increase their sensitivity and specificity. Here, we review the application of antibodies for CDI treatment with an emphasis on recombinant fragment antibodies. Also, this review highlights the current and future prospects of the aforementioned approaches for antibody-mediated therapy of CDI.
Late Pleistocene to Holocene variations in marine productivity and terrestrial material delivery to the western South Atlantic

Despite the increased number of paleoceanographic studies in the SW Atlantic in recent years, the mechanisms controlling marine productivity and terrestrial material delivery to the South Brazil Bight remain unresolved. Because of its wide continental shelf and abrupt change in coastline orientation, this region is under the influence of several environmental forcings, causing the region to have large variability in primary production. This study investigated terrestrial organic matter (OM) sources and marine OM sources in the South Brazil Bight, as well as the main controls on marine productivity and terrestrial OM export. We analyzed OM geochemical (bulk and molecular) proxies in sediment samples from a core (NAP 63-1) retrieved from the SW Atlantic slope (24.8°S, 44.3°W, 840-m water depth). The organic proxies were classified into “terrestrial-source” and “marine-source” groups based on a cluster analysis. The two sources presented different stratigraphical profiles, indicating distinct mechanisms governing their delivery. Bulk proxies indicate the predominance of marine OM, although terrestrial input also affected the total OM deposition. The highest marine productivity, observed between 50 and 39 ka BP, was driven by the combined effects of the South Atlantic Central Water upwelling promoted by Brazil Current eddies and fluvial nutrient inputs from the adjacent coast. After the last deglaciation, decreased phytoplankton productivity and increased archaeal productivity suggest a stronger oligotrophic tropical water presence. The highest terrestrial OM accumulation occurred between 30 and 20 ka BP, with its temporal evolution controlled mainly by continental moisture evolution. Sea level fluctuations affected the distance between the coastline and the sampling site. In contrast, continental moisture affected the phytogeography, changing from lowlands covered by grasses and saltmarshes to a landscape dominated by mangroves and the Atlantic Forest. Our results suggest how the OM cycle in the South Brazil Bight may respond to warmer and dryer climate conditions.
Optical fiber flowmeter based on a single mode-multimode-single mode structure

Single mode-Multimode-Single mode (SMS) sensors have been attracted a relevant attention because of their simple manufacturing, their capability of sensing different quantities, and their enhanced sensitivity compared to the most common fiber optic sensor represented by Fiber Bragg Gratings (FBGs). Moreover, SMS sensors exhibit blue-shift sensitivity to strain, opposite to FBGs, making them suitable in applications where strain-temperature cross-sensitivity may be an issue. SMS sensors are made by splicing a short multimode, preferably a two mode or quasi two-mode, optical fiber jumper between single mode pigtails. The interference of the modes propagating at different phase velocities produces a spectral pattern that shifts with temperature, strain or any perturbation of the phase difference among the modes. In this paper we review the main features of SMSs as temperature sensors and we present a potential biomedical application in an all-fiber flowmeter based on the hot-wire principle: a fiber-coupled laser source at 980 nm is used as a controllable heating source of the SMS sensor that, when immersed in fluid flow, converts the temperature variation, caused by the heat removal, into a wavelength shift of the transmitted spectrum. Thermal characterization and proof-of-concept experiments show the feasibility and functionality of the sensor and provide an outlook on possible developments and potential applications.
Pixelated reconfiguration using electrically actuated liquid metal

Discretised liquid metal is actuated in a 2 × 2 pixel grid to demonstrate pixelated reconfiguration. Within each pixel, continuous electro-wetting actuates liquid metal from a lower to an upper reservoir, allowing that pixel to either appear or disappear without employing switches between adjacent pixels. Liquid metal is actuated within 0.3 s and is reversible.
SURROGATE MARKER 1: CALCIUM ABSORPTION

784 In endocrine praxis, all defi ciency is defi ned by a combination of trophic hormone and target hormone. Why then, is vitamin D defi ciency (VDD) defi ned by an isolated value of storage hormone serum 25-hydroxu vitamin D (25OHD), rather than its active hormone, or its relation with target action of vitamin D? Are better surrogate markers available for the defi nition of VDD? This editorial seeks an answer to this seemingly simple answer.
Mosaic mutant Analysis with Spatial and Temporal control of Recombination (MASTR): a new technique for determining the fate of mutant cells using conditional floxed alleles in mice

SUMMARY Mosaic mutant analysis, the study of cellular defects in scattered mutant cells in a wild type environment, is a powerful approach for identifying critical functions of genes and has been applied extensively to invertebrate model organisms. A novel and highly versatile technique was developed in mouse, Mosaic mutant Analysis with Spatial and Temporal control of Recombination (MASTR), that utilizes the increasing number of floxed alleles and simultaneously combines conditional gene mutagenesis and cell marking for fate analysis. A targeted allele (R26 MASTR ) was engineered that expresses a GFPcre fusion protein following FLP-mediated recombination that serves the dual function of deleting floxed alleles and marking mutant cells with GFP. Within 24 hr of tamoxifen administration to R26 MASTR mice carrying a new inducible FlpoER transgene and a floxed allele nearly all GFP-expressing cells have a mutant allele. The fate of single cells lacking FGF8 or SHH signaling in the developing hindbrain was analyzed using MASTR and revealed there is only a short time window when neural progenitors require FGFR1 for viability, and that granule cell precursors differentiate rapidly when SMO is lost. MASTR is a powerful tool that provides cell type specific (spatial) and temporal marking of mosaic mutant cells that is broadly applicable to developmental, cancer and adult stem cell studies.
CaMKIV mediates distinct features of basal and activity-dependent dendrite complexity

Intracellular signaling mechanisms translate extracellular signals, such as neuronal activity, into effects on dendrite complexity. Deciphering these mechanisms has considerable impact on understanding how the brain develops and what can go wrong in developmental disorders. How neurons regulate intracellular signaling to control their dendrite morphology remains poorly understood and is likely to be determined at the level of individual neuronal types. Calcium/ Calmodulin-dependent protein kinase IV (CaMKIV) is a signaling mechanism involved in the regulation of gene expression and dendrite growth. Expression of CaMKIV is developmentally regulated in the cerebral cortex, with highest expression occurring concomitant with the period of extensive dendrite growth and elaboration. Interestingly, cortical neurons heterogeneously expressed CaMKIV in postnatal rat cortices and cortical neurons in vitro. We tested if this differential CaMKIV expression mediated distinct arborization patterns in the dendrites of pyramidal and nonpyramidal neurons. In fact, CaMKIV mediated dendrite complexity via regulation of specific morphological features of the dendrite arbor: branching and elongation, but not primary dendrite formation. We found that siRNA knockdown of CaMKIV decreased basal dendrite complexity indicating that endogenously expressed CaMKIV mediated dendrite complexity. CaMKIV was also required for activity-induced dendrite elaboration. Active CaMKIV expression in cortical neurons increased dendrite elaboration indicating that enzymatic activity was involved. These data indicated neuronal CaMKIV expression was required for basal and activity-induced dendrite complexity. Further, the data presented in this study indicates CaMKIV contributes to the diversity of dendrite arbors via restricted expression and regulation of distinct modes of dendrite elaboration. CaMKIVwt signaling was biased in that it preferentially potentiated an effect on dendrite branching and initiation rather than elongation in these younger cortical neurons. These results indicate CaMKIVwt promoted a highly branched dendrite arbor in response to stimulation. Purkinje neurons and cortical layer 5 pyramidal neurons). We report in the current study that CaMKIV modulated the dendrite arbor through increased formation of dendrite branches and elongation of primary dendrites. We found that both pyramidal and nonpyramidal CaMKIV endogenously expressing neurons had greater branching that was diminished when CaMKIV was knocked down but was rescued by expression of siRNA resistant CaMKIV. Further, expression of a constitutive active CaMKIV increased
Practice of Epidemiology Models to Assess the Association of a Semiquantitative Exposure With Outcomes

A semiquantitative risk factor has 2 components: any exposure (yes/no) and the quantitative amount of exposure (if exposed). We describe the statistical properties of alternative analyses with such a risk factor using linear, logistic, or Cox proportional hazards models. Often analyses employ the amount exposed as a single quantitative covariate, including the nonexposed with value zero. However, this analysis provides a biased estimate of the exposure coefficient (slope) and we describe the magnitude of the bias.This bias can be eliminated by adding a binary covariate for exposed versus not to the model. This 2-factor analysis captures the full risk-factor effect on the outcome. However, the coefficient for any exposure versus not does not have a meaningful interpretation.Alternatively, when exposure values among those exposed are centered (by subtracting the mean), the estimate of this coefficient represents the difference in the outcome between those exposed versus not in aggregate. We also show that the biased model provides biased estimates of the coefficients for other covariates added to the model. Proper analysis of a semiquantitative risk factor should start with a 2-factor model, with centering, to assess the joint contributions of the 2 components of the risk-factor exposure. Properties of models were illustrated using data from a multisite study in North America (1983 – 2019).