Miracle-dz/UniFAR-FTUs huggingface dataset:
4-Hydroxyphenylpyruvate Dioxygenase-Like predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis

The 4-Hydroxyphenylpyruvate Dioxygenase-Like (HPDL) protein plays a crucial role in safeguarding cells from oxidative stress by orchestrating metabolic reprogramming. New research suggests that HPDL is considerably increased in pancreatic ductal adenocarcinoma, although its impact on cancer immunotherapy is still unclear. Pancancer transcriptional data were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression datasets. The cBioPortal webtool was utilized to examine genomic changes in different cancer types. The prognostic significance of HPDL in pancancer was evaluated using univariate Cox regression analysis. Extensive utilization of the CTRP and PRISM databases was performed to forecast potential medications that specifically target HPDL in LUAD. In summary, studies were conducted to evaluate the impact of HPDL on the proliferation and movement of LUAD cells using loss-of-function experiments. HPDL is expressed excessively in a wide variety of cancer types, indicating its prognostic and predictive value. Moreover, we emphasized the strong correlation between HPDL and indicators of immune stimulation, infiltration of immune cells, and expression of immunoregulators. The remarkable finding of the HPDL was its capacity to precisely anticipate responses to cancer therapies using anti-PDL1 and anti-PD1 antibodies among individuals. Moreover, HPDL can function as a predictive marker for specific inhibitors in instances of cancer. Suppression of HPDL resulted in reduced growth and movement of LUAD cells. To summarize, our results suggest that HPDL acts as a prospective predictor of outcomes and a positive indication of response to immunotherapy in patients undergoing treatment with immune checkpoint inhibitors (ICIs).
Observed variability and trends in the microclimate of the midlands of KwaZulu‐Natal and its influence on fire danger

Current changes in global climate are likely to be evident at both the regional and the local scale. This study presents an investigation in climatic trends in the KwaZulu‐Natal (KZN) midlands, South Africa and seeks to assess the level of change in the microclimate and more specifically, the influence of a changing climate on fire danger. To this end, long‐term (1953–2015), historical daily meteorological data from the KZN midlands were analysed, using multitemporal regression analysis as well as time‐series analysis. Analysis indicated significant trends, to varying rates of change, across all sites. Over the last two decades, annual average air temperature was found to be increasing at a rate of between 1 and 3 °C century−1. Atmospheric water vapour pressure across the three sites also experienced significant levels of change. Decreases in total rainfall over the last two decades are of concern. Fire danger, calculated using the Lowveld fire danger index (LFDI), displayed significant rates of change. At two sites, annual average fire danger, over the last two decades, was found to be decreasing at a rate between roughly 5 and 10 FDI units century−1. The onset and length of the KZN midlands fire season has also undergone significant changes, as a response to changes in the microclimate. Sites experienced an overall decreasing trend in the onset of the fire season – indicative of an earlier start to the fire season, as well as an increase in fire season length. Results indicate that while the microclimate of the KZN midlands is changing, the rate of change differs from that of global and continental estimates.
LOCAL EARTHQUAKE TOMOGRAPHY IN THE BROADER AREA OF WESTERN CORINTH GULF

Η παρούσα eργασία πeριγράφeι τα αποτeλέσματα της τρισδιάστατης τομογραφίας που πραγματοποιήθηκe στην eυρύτeρη πeριοχή του Δυτικού Κορινθιακού Κόλπου μe σκοπό την χαρτογράφηση eνeργών τeκτονικών δομών. Για την πραγματοποίηση της παρούσης μeλέτης χρησιμοποιήθηκαν δeδομένα από πeρισσότeρους των 2,000 σeισμών οι οποίοι καταγράφηκαν από το Eνιαίο Σeισμολογικό Δίκτυο και το αντίστοιχο του Eργαστηρίου της Κορινθιακής Τάφρου (CRLN). Μe την τομογραφική αντιστροφή παράγουμe και πραγματοποιούμe την eρμηνeία τρισδιάστατων μοντέλων κυμάτων χώρου (Vp, Vs) και του αντίστοιχου λόγου τους (Vp/Vs) για την πeριοχή μeλέτης. Τα τeλικά αποτeλέσματα καταδeικνύουν ορισμένeς eνδιαφέρουσeς δομές, κυρίως όσον αφορά τον λόγο Vp/Vs,που συσχeτίζουν την κατανομή των προσδιορισθέντων υποκέντρων μe διαφοροποιήσeις στη λιθολογία ή στο πeριeχόμeνο των γeωλογικών σχηματισμών σe ρeυστά. Στην πeριοχή του Πατραϊκού, ένας ανeρχόμeνος δόμος υψηλής ταχύτητας eντοπίστηκe, ο οποίος κάλλιστα μπορeί να συνδeθeί μe την τeκτονική αλατούχων δόμων στο Αλπικό υπόβαθρο, γeγονός που eπηρeάζeι την κυκλοφορία των ρeυστών καθώς και τη δράση των τοπικών ρηγμάτων.
Using time domain and geographic source tracers to conceptualize streamflow generation processes in lumped rainfall‐runoff models

The temporal dynamics and geographical sources of streamflow were conceptualized in a lumped rainfall‐runoff model (isoSAMdyn) using isotopic and geochemical tracers derived from a field study in a 3.6 km2 upland catchment in Scotland. High‐resolution (daily) sampling of stable isotopes in precipitation and streamflow over a hydrological year, supplemented by fortnightly sampling of groundwater and riparian saturation zones, allowed hypotheses of runoff generation processes to be tested. These were conceptualized in a previously developed model (SAMdyn) based only on geochemically defined geographic source tracers, which showed that the nonlinear dynamic expansion and contraction of riparian saturation areas is the dominant mechanism for storm runoff generation in the catchment. While SAMdyn resulted in reasonable simulation of streamflows and alkalinity (as a source tracer), it was unable to reproduce the rainfall‐runoff dynamics of deuterium (δ2H). Using the model in a learning framework, incorporation of parameters for passive storage in catchment hillslopes and groundwater mixing in riparian saturation zones, along with associated isotopic fractionation, improved δ2H simulations in stream water and the major catchment water stores. The resulting model provided a conceptualization of rainfall‐runoff processes that broadly reconciled hydrometric data and geochemical and isotopic signals. However, in this particular catchment, fractionation of water in surface saturation zones appears to be a complex process that prevents the simulation of short‐term isotope dynamics in the stream during the summer period.
Long-term soil moisture content estimation using satellite and climate data in agricultural area of Mongolia

Abstract The purpose of this study is to estimate long-term SMC and find its relation with soil moisture (SM) of climate station in different depths and NDVI for the growing season. The study area is located in agricultural regions in the North of Mongolia. The Pearson’s correlation methodology was used in this study. We used MODIS and SPOT satellite data and 14 years data for precipitation, temperature and SMC of 38 climate stations. The estimated SMC from this methodology were compared with SM from climate data and NDVI. The estimated SMC was compared with SM of climate stations at a 10-cm depth (r2 = 0.58) and at a 50-cm depth (r2 = 0.38), respectively. From the analysis, it can be seen that the previous month’s SMC affects vegetation growth of the following month, especially from May to August. The methodology can be an advantageous indicator for taking further environmental analysis in the region.
A role for biotechnologies in the improvement of oil palm sustainability

Biotechnologies and sustainable development are often considered as antagonists, especially in Europe where GMOs (Genetically Modified Organisms) and agricultural biotechnology are opposed to more environment-friendly agricultural practices, such as organic farming. Nevertheless, there is increasing evidence for a pivotal role for this approach in the ecological intensification of oil palm cultivation. Ecological intensification is based on the understanding of biological functions in order to better exploit natural living resources while preserving them for future generations. Biotechnology is based on mechanisms that nature already uses. When applied in appropriate ways the results can offer new solutions to existing problems, such as the finite resource levels being depleted today (Mc Laren, 2005). Modern biology is now integrating systems biology with very close links with biotechnology. Indeed, living organisms are supported by the genome (DNA) through the action of the transcriptome (RNAs), proteome, metabolome, and ionome, the four basic pillars of functional genomics (Figure1). These pillars represent the sum of all the expressed genes, proteins, metabolites, and elements within an organism. The dynamic response and interaction of these biochemical ‘‘omes’’ defines how a living system functions, and its study, systems biology, is now one of the biggest challenges in life sciences.
Wind‐Driven Response of the Upper Ocean Along the U.S. West Coast to Tropical MJO Convection

In this study, time-lagged composites of OSCAR upper ocean currents from February to May of 1993-2016 were binned by active phase of the leading atmospheric mode of intraseasonal variability, the Madden-Julian Oscillation (MJO). Seven days after the convectively active phase of the MJO is present in the tropical Indian Ocean, anomalously strong south-southeastward upper-ocean currents are seen along nearly the entire U.S. west coast. Seven days after the convectively active phase is present in the tropical western Pacific Ocean, upper-ocean current anomalies reverse along the U.S. west coast, with weaker southward flow. A physical pathway to the ocean was found for both of these phases: (a) tropical MJO convection modulates upper-tropospheric heights and circulation over the Pacific Ocean; (b) those anomalous atmospheric heights adjust the strength and position of the Aleutian Low and Hawaiian High; (c) surface winds change in response to the adjusted atmospheric pressure patterns; and (d) those surface winds project onto upper-ocean currents.
On the evaluation of the stress intensity factor in calving models using linear elastic fracture mechanics

ABSTRACT We investigate the appropriateness of calving or crevasse models from the literature using linear elastic fracture mechanics (LEFM). To this end, we compare LEFM model-predicted stress intensity factors (SIFs) against numerically computed SIFs using the displacement correlation method in conjunction with the finite element method. We present several benchmark simulations wherein we calculate the SIF at the tips of water-filled surface and basal crevasses penetrating through rectangular ice slabs under different boundary conditions, including grounded and floating conditions. Our simulation results indicate that the basal boundary condition significantly influences the SIF at the crevasse tips. We find that the existing calving models using LEFM are not generally accurate for evaluating SIFs in grounded glaciers or floating ice shelves. We also illustrate that using the ‘single edge crack’ weight function in the LEFM formulations may be appropriate for predicting calving from floating ice shelves, owing to the low fracture toughness of ice; whereas, using the ‘double edge crack’ or ‘central through crack’ weight functions is more appropriate for predicting calving from grounded glaciers. To conclude, we recommend using the displacement correlation method for SIF evaluation in real glaciers and ice shelves with complex geometries and boundary conditions.
Non-invasive perfusion MR imaging of the human brain via breath-holding

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3T and 7T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3T vs 8.5 at 7T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20-40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.
Original Contribution

In vivo administration of D609 leads to protection of subsequently isolated gerbil brain mitochondria subjected to in vitro oxidative stress induced by amyloid beta-peptide and other oxidative stressors: Relevance to Alzheimer's disease and other oxidative stress-related neurodegenerative disorders Abstract Tricyclodecan-9-yl-xanthogenate (D609) has in vivo and in vitro antioxidant properties. D609 mimics glutathione (GSH) and has a free thiol group, which upon oxidation forms a disulfide. The resulting dixanthate is a substrate for glutathione reductase, regenerating D609. Recent studies have also shown that D609 protects brain in vivo and neuronal cultures in vitro against the potential Alzheimer's disease (AD) causative factor, Aβ(1–42)-induced oxidative stress and cytotoxicity. Mitochondria are important organelles with both pro-and antiapoptotic factor proteins. The present study was undertaken to test the hypothesis that intraperitoneal injection of D609 would provide neuroprotection against free radical-induced, mitochondria-mediated apoptosis in vitro. Brain mitochondria were isolated from gerbils 1 h post injection intraperitoneally (ip) with D609 and subsequently treated in vitro with the oxidants Fe 2+ /H 2 O 2 (hydroxyl free radicals), 2,2-azobis-(2-amidinopropane) dihydrochloride (AAPH, alkoxyl and peroxyl free radicals), and AD-relevant amyloid β-peptide 1–42 [Aβ(1–42)]. Brain mitochondria isolated from the gerbils previously injected ip with D609 and subjected to these oxidative stress inducers, in vitro, showed significant reduction in levels of protein carbonyls, protein-bound hydroxynonenal [a lipid peroxidation product], 3-nitrotyrosine, and cytochrome c release compared to oxidant-treated brain mitochondria isolated from saline-injected gerbils. D609 treatment significantly maintains the GSH/GSSG ratio in oxidant-treated mitochondria. Increased activity of glutathione S-transferase, glutathione peroxidase, and glutathione reductase in brain isolated from D609-injected gerbils is consistent with the notion that D609 acts like GSH. These antiapoptotic findings are discussed with reference to the potential use of this brain-accessible glutathione mimetic in the treatment of oxidative stress-related neurodegenerative disorders, including AD.
GDOP: A graph convolutional network-based drug “on-target” pathway prediction algorithm

Since most compounds do not induce changes in the transcriptomic levels of their target proteins in vivo, traditional gene set enrichment analysis methods can only retrieve downstream differentially expressed genes, which offer little hints to their targets. To address this problem, we proposed a graph convolutional network-based drug “on-target” pathway prediction algorithm, GDOP, which can predict small pathways that contain target gene through the power of deep learning algorithms. Our model receives as input structural information and biological characteristics (gene expression profiles) of molecules. After being trained on the publicly available LINCS data set, GDOP showed better generalization ability, reaching an AUC-ROC of 0.89 and an averaged Top10 accuracy of 0.63 on the test set. Besides, demonstrated that GDOP was able to use RNA-Seq data as input and achieved accuracy prediction results.
Rectal Swab DNA Collection Protocol for PCR Genotyping in Rats

DNA collection is essential for genotyping laboratory animals. However, common collection methods require tissue amputation, causing discomfort and injury. Rectal swabbing has been proposed as an effective non-invasive alternative, but an evidence-backed protocol for the technique remains unavailable. We evaluate the effect of collection parameters on PCR result quality and present a genotyping protocol that can yield results for a litter of rats within 3-5 hours. We found that samples with 2-8 scrapes produced enough DNA to amplify targets up to ∼1800bp long using PCR. Rectal swabbing produced PCR results with similar quality to ear clip samples, and results were unaffected by residual fecal matter or cell debris. Our protocol enables fast, non-invasive, and repeatable genotyping using commercial PCR reagents.
The spiking output of the mouse olfactory bulb encodes large-scale temporal features of natural odor environments

Spatiotemporal dynamics of natural odor environment have informative features for animals navigating to an odor source. Population activity in the olfactory bulb (OB) has been shown to follow plume dynamics to a moderate degree (Lewis et al., 2021), but it is unknown whether the ability to follow plume dynamics is driven by individual cells or whether it emerges at the population level. Previous research has explored the responses of individual OB cells to isolated features of plumes, but it is difficult to adequately sample these features as it is still undetermined which features navigating mice employ during olfactory guided search. Here we released odor from an upwind odor source and simultaneously recorded both odor concentration dynamics and cellular response dynamics in awake, head-fixed mice. We found that longer timescale features of odor concentration dynamics were encoded at both the cellular and population level. At the cellular level, plume onset was en-coded across all trials and plume offset was encoded for high concentration odors, but not low concentration odors. Although cellular level tracking of plume dynamics was observed to be weak, we found that at the population level, OB activity distinguished whiffs and blanks (accurately detected odor presence versus absence) throughout the duration of a plume. Even ∼20 OB cells were enough to accurately encode these features. Our findings indicate that the full range of odor concentration dynamics and high frequency fluctuations are not encoded by OB spiking activity. Instead, relatively lower-frequency dynamics of plumes, such as plume onset, plume offset, whiffs, and blanks, are represented in the OB.
Activation of the imprinted Prader-Willi Syndrome locus by CRISPR-based epigenome editing

Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi Syndrome (PWS) is caused by loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control expression of the PWS gene SNRPN from the paternal and maternal chromosomes. We showed that either targeted transcriptional activation or DNA demethylation can activate the silenced maternal SNRPN and downstream PWS transcripts. However, these two approaches function at unique regions, preferentially activating different transcript variants and involving distinct epigenetic reprogramming mechanisms. Remarkably, transient expression of the targeted demethylase leads to stable, long-term maternal SNRPN expression in PWS iPSCs. This work uncovers targeted epigenetic manipulations to reprogram a disease-associated imprinted locus and suggests possible therapeutic interventions.
Unsupervised generative AI discovers pan-leukocyte dysregulated pathways in single-cell lupus data

Comparisons of single-cell RNA-sequencing (scRNA-seq) data from healthy and diseased tissues are widely used to identify cell-type-specific dysregulated genes, pathways, and processes. Accordingly, many sophisticated methods have been developed for this purpose. However, such tools generally require considerable user expertise for optimal performance. Here, we show that unsupervised application of a linearly-decoded Variational Auto Encoder (a generative AI model) to scRNA-seq data recapitulates and extends findings from a seminal recent lupus study and leads to new insights. Thanks to existing software libraries, our approach is straightforward to implement, computationally efficient, methodologically robust, and produces consistent and reproducible results.
Small, but mitey: Investigating the molecular genetic basis for mite domatia development and intraspecific variation in Vitis riparia using transcriptomics

• Here, we investigated the molecular genetic basis of mite domatia, structures on the underside of leaves that house mutualistic mites, and intraspecific variation in domatia size in Vitis riparia (riverbank grape). • Domatia and leaf traits were measured, and the transcriptomes of mite domatia from two genotypes of V. riparia with distinct domatia sizes were sequenced to investigate the molecular genetic pathways that regulate domatia development and intraspecific variation in domatia traits. • Key trichome regulators as well as auxin and jasmonic acid are involved in domatia development. Genes involved in cell wall biosynthesis, biotic interactions, and molecule transport/metabolism are upregulated in domatia, consistent with their role in domatia development and function. • This work is one of the first to date that provides insight into the molecular genetic bases of mite domatia. We identified key genetic pathways involved in domatia development and function, and uncovered unexpected pathways that provide an avenue for future investigation. We also found that intraspecific variation in domatia size in V. riparia seems to be driven by differences in overall leaf development between genotypes.
Characterization of Composite Agarose-Collagen Hydrogels for Chondrocyte Culture

To elucidate the mechanisms of cellular mechanotransduction, it is necessary to employ biomaterials that effectively merge biofunctionality with appropriate mechanical characteristics. Agarose and collagen separately are common biopolymers used in cartilage mechanobiology and mechanotransduction studies but lack features that make them ideal for functional engineered cartilage. In this study, agarose (8% w/v and 4% w/v) is blended with collagen type I (4mg/mL) to create composites. We hypothesized that a higher stiffness, composite hydrogel would promote native cartilage-like conditions. To address these questions, acellular and cell-laden studies were completed to assess rheologic and compressive properties, contraction, and structural homogeneity in addition to matrix mechanics, cell proliferation, and glycosaminoglycan production. Over 21 days in culture, cellular 4% agarose – 2mg/mL collagen I hydrogels displayed good structural and bulk mechanical properties, cell proliferation, and continual glycosaminoglycan production, indicating promise towards the development of an effective hydrogel for chondrocyte mechanotransduction and mechanobiology studies. Graphical Abstract