Miracle-dz/UniFAR-FTUs huggingface dataset:
The Plastid-Localized AtFtsHi3 Pseudo-Protease of Arabidopsis thaliana Has an Impact on Plant Growth and Drought Tolerance

While drought severely affects plant growth and crop production, the molecular mechanisms of the drought response of plants remain unclear. In this study, we demonstrated for the first time the effect of the pseudo-protease AtFtsHi3 of Arabidopsis thaliana on overall plant growth and in drought tolerance. An AtFTSHi3 knock-down mutant [ftshi3-1(kd)] displayed a pale-green phenotype with lower photosynthetic efficiency and Darwinian fitness compared to wild type (Wt). An observed delay in seed germination of ftshi3-1(kd) was attributed to overaccumulation of abscisic acid (ABA); ftshi3-1(kd) seedlings showed partial sensitivity to exogenous ABA. Being exposed to similar severity of soil drying, ftshi3-1(kd) was drought-tolerant up to 20 days after the last irrigation, while wild type plants wilted after 12 days. Leaves of ftshi3-1(kd) contained reduced stomata size, density, and a smaller stomatic aperture. During drought stress, ftshi3-1(kd) showed lowered stomatal conductance, increased intrinsic water-use efficiency (WUEi), and slower stress acclimation. Expression levels of ABA-responsive genes were higher in leaves of ftshi3-1(kd) than Wt; DREB1A, but not DREB2A, was significantly upregulated during drought. However, although ftshi3-1(kd) displayed a drought-tolerant phenotype in aboveground tissue, the root-associated bacterial community responded to drought.
Comparison of Landfill Leachate Properties by LPI and Phytotoxicity-A Case Study

The formation of leachate is one of the inevitable consequences associated with the operation of landfills. In addition to the study of physicochemical composition, toxicity is an important parameter taken into account, among others because of the need to subject leachate to treatment before discharge into the environment. The aim of this study was to determine the degree of leachate contamination using LPI and toxicity index. An analysis of the relationship between the toxic effect on plants and the calculated LPI values was also carried out to assess whether they could provide a measure of leachate toxicity when selecting a treatment method. The research conducted was to determine the degree of leachate contamination using LPI and toxicity index. An analysis of the relationship between the toxic effect on plants and the calculated LPI values was also carried out to assess whether they could provide a measure of leachate toxicity when selecting a treatment method. Calculated values of the leachate pollution index showed that leachates from selected Polish landfills are characterized by low and medium levels of LPI values. The variation in index values obtained was particularly evident between active and closed landfills and was related to the physicochemical composition of leachates. In closed landfills this value ranged from 7.4 to 11.1, while in active landfills from 12.9 to 15.9. The variation in index values obtained was particularly evident between active and inactive landfills and was related to the physicochemical composition of leachates. Phytotoxicity tests showed that leachate at low concentrations can promote plant growth. At higher concentrations (50 and 100%), leachates caused inhibition of root and shoot growth, which correlated with high LPI values. The results confirmed the relationship between the toxic effect on plants and the LPI values, so it can be considered as a reliable indicator of leachate toxicity.
Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer

Reciprocal signaling between immune cells and ovarian cancer cells in the tumor microenvironment can alter immune responses and regulate disease progression. These signaling events are regulated by multiple factors, including genetic and epigenetic alterations in both the ovarian cancer cells and immune cells, as well as cytokine pathways. Multiple immune cell types are recruited to the ovarian cancer tumor microenvironment, and new insights about the complexity of their interactions have emerged in recent years. The growing understanding of immune cell function in the ovarian cancer tumor microenvironment has important implications for biomarker discovery and therapeutic development. This review aims to describe the factors that shape the phenotypes of immune cells in the tumor microenvironment of ovarian cancer and how these changes impact disease progression and therapy.
Sex Steroids and Osteoarthritis: A Mendelian Randomization Study

Objective Sex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method. Methods Instrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS). Results A positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193–2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008–1.018; P=2.15×10−8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006–1.015; P=4.03×10−7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054–1.855; P=0.020). Conclusions Serum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation.
Multiple Lines of Evidence for a Potentially Seismogenic Fault Along the Central-Apennine (Italy) Active Extensional Belt–An Unexpected Outcome of the MW6.5 Norcia 2016 Earthquake

The Apenninic chain, in central Italy, has been recently struck by the Norcia 2016 seismic sequence. Three mainshocks, in 2016, occurred on August 24 (MW6.0), October 26 (MW 5.9) and October 30 (MW6.5) along well-known late Quaternary active WSW-dipping normal faults. Coseismic fractures and hypocentral seismicity distribution are mostly associated with failure along the Mt Vettore-Mt Bove (VBF) fault. Nevertheless, following the October 26 shock, the aftershock spatial distribution suggests the activation of a source not previously mapped beyond the northern tip of the VBF system. In this area, a remarkable seismicity rate was observed also during 2017 and 2018, the most energetic event being the April 10, 2018 (MW4.6) normal fault earthquake. In this paper, we advance the hypothesis that the Norcia seismic sequence activated a previously unknown seismogenic source. We constrain its geometry and seismogenic behavior by exploiting: 1) morphometric analysis of high-resolution topographic data; 2) field geologic- and morphotectonic evidence within the context of long-term deformation constraints; 3) 3D seismological validation of fault activity, and 4) Coulomb stress transfer modeling. Our results support the existence of distributed and subtle deformation along normal fault segments related to an immature structure, the Pievebovigliana fault (PBF). The fault strikes in NNW-SSE direction, dips to SW and is in right-lateral en echelon setting with the VBF system. Its activation has been highlighted by most of the seismicity observed in the sector. The geometry and location are compatible with volumes of enhanced stress identified by Coulomb stress-transfer computations. Its reconstructed length (at least 13 km) is compatible with the occurrence of MW≥6.0 earthquakes in a sector heretofore characterized by low seismic activity. The evidence for PBF is a new observation associated with the Norcia 2016 seismic sequence and is consistent with the overall tectonic setting of the area. Its existence implies a northward extent of the intra-Apennine extensional domain and should be considered to address seismic hazard assessments in central Italy.
A Mix of Old British and Modern European Breeds: Genomic Prediction of Breed Composition of Smallholder Pigs in Uganda

Pig herds in Africa comprise genotypes ranging from local ecotypes to commercial breeds. Many animals are composites of these two types and the best levels of crossbreeding for particular production systems are largely unknown. These pigs are managed without structured breeding programs and inbreeding is potentially limiting. The objective of this study was to quantify ancestry contributions and inbreeding levels in a population of smallholder pigs in Uganda. The study was set in the districts of Hoima and Kamuli in Uganda and involved 422 pigs. Pig hair samples were taken from adult and growing pigs in the framework of a longitudinal study investigating productivity and profitability of smallholder pig production. The samples were genotyped using the porcine GeneSeek Genomic Profiler (GGP) 50K SNP Chip. The SNP data was analyzed to infer breed ancestry and autozygosity of the Uganda pigs. The results showed that exotic breeds (modern European and old British) contributed an average of 22.8% with a range of 2–50% while “local” blood contributed 69.2% (36.9–95.2%) to the ancestry of the pigs. Runs of homozygosity (ROH) greater than 2 megabase (Mb) quantified the average genomic inbreeding coefficient of the pigs as 0.043. The scarcity of long ROH indicated low recent inbreeding. We conclude that the genomic background of the pig population in the study is a mix of old British and modern pig ancestries. Best levels of admixture for smallholder pigs are yet to be determined, by linking genotypes and phenotypic records.
Circulating Fascin 1 as a Promising Prognostic Marker in Adrenocortical Cancer

Fascin-1 (FSCN1) is an actin-bundling protein associated with an invasive and aggressive phenotype of several solid carcinomas, as it is involved in cell cytoskeleton rearrangement and filopodia formation. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by poor prognosis, particularly when metastatic at diagnosis. Radical resection is the only therapeutic option for ACC patients in addition to the adjuvant treatment with mitotane. Novel specific biomarkers suggestive of tumor progression to refine diagnosis and prognosis of patients with advanced ACC are urgently needed. ACC intratumoral FSCN1 has previously been suggested as a valid prognostic marker. In the present study, we identified FSCN1 in the bloodstream of a small cohort of ACC patients (n = 27), through a specific ELISA assay for human FSCN1. FSCN1 can be detected in the serum, and its circulating levels were evaluated in pre-surgery samples, which resulted to be significantly higher in ACC patients from stage I/II and stage III/IV compared with nontumoral healthy controls (HC, n = 4, FI: 5.5 ± 0.8, P<0.001, and 8.0 ± 0.5, P < 0.001 for stage I/II and stage III/IV group vs HC, respectively). In particular, FSCN1 levels were significantly higher in advanced stage versus stage I/II (22.8 ± 1.1 vs 15.8 ± 1.8 ng/ml, P < 0.005, respectively). Interestingly, circulating levels of pre-surgical FSCN1 can significantly predict tumor progression/recurrence (Log rank = 0.013), but not the overall survival (Log rank=0.317), in patients stratified in high/low PreS FSCN1. In conclusion, these findings—though very preliminary—suggest that circulating FSCN1 may represent a new minimally-invasive prognostic marker in advanced ACC, in particular when measured before surgery enables histological diagnosis.
Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia

Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro results.
Microplastics Increase Soil pH and Decrease Microbial Activities as a Function of Microplastic Shape, Polymer Type, and Exposure Time

Microplastic pollution is a topic of increasing concern, especially since this issue was first addressed in soils. Results have so far been variable in terms of effects, suggesting that there is substantial context-dependency in microplastic effects in soil. To better define conditions that may affect microplastic-related impacts, we here examined effects as a function of microplastic shape and polymer type, and we tested if effects on soil properties and soil microbial activities change with incubation time. In our laboratory study, we evaluated twelve different secondary microplastics representing four microplastic shapes: fibers, films, foams and fragments; and eight polymer types: polyamide (PA), polycarbonate (PC), polyethylene (PE), polyester (PES), polyethylene terephthalate (PET), polypropylene (PP), polystyrene (PS), and polyurethane (PU). We mixed the microplastics with a sandy soil (0.4% w/w) and incubated at 25°C for 31 days. Then, we collected soil samples on the 3rd, 11th, and 31st day, and measured soil pH, respiration and four enzyme activities (soil enzymatic activities). Our results showed that microplastics could affect soil pH, respiration and enzymatic activities depending on microplastic shape and polymer type, effects that were altered with incubation time. Soil pH increased with foams and fragments and overall decreased in the first days of incubation and then increased. Soil respiration increased with PE foams and was affected by the incubation time, declining over time. Overall, acid phosphatase activity was not affected by shape or polymer type. β-D-glucosidase activity decreased with foams, cellobiosidase activity decreased with fibers, films and foams while N-acetyl-β-glucosaminidase activities decreased with fibers and fragments. Enzymatic activities fluctuated during the incubation time, except N-acetyl-β-glucosaminidase, which showed a declining trend with incubation time. Enzymatic activities were negatively correlated with soil pH and this relationship was less strong when microplastics were added to the soil. Our study adds to the evidence that research should embrace the complexity and diversity of microplastics, highlighting the role of microplastic shape and polymer type in influencing effects; additionally, we show that incubation time is also a parameter to consider, as effects are dynamic even in the short term.
Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is a highly heterogeneous malignancy, which makes prognosis prediction of LUAD very challenging. Ferroptosis is an iron-dependent cell death mechanism that is important in the survival of tumor cells. Long non-coding RNAs (lncRNAs) are considered to be key regulators of LUAD development and are involved in ferroptosis of tumor cells, and ferroptosis-related lncRNAs have gradually emerged as new targets for LUAD treatment and prognosis. It is essential to determine the prognostic value of ferroptosis-related lncRNAs in LUAD. In this study, we obtained RNA sequencing (RNA-seq) data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and ferroptosis-related lncRNAs by co-expression analysis. The best predictors associated with LUAD prognosis, including C5orf64, LINC01800, LINC00968, LINC01352, PGM5-AS1, LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, LMO7DN, were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, and the LUAD risk prediction model was successfully constructed. Kaplan-Meier analysis, receiver operating characteristic (ROC) time curve analysis and univariate and multivariate Cox regression analysis and further demonstrated that the model has excellent robustness and predictive ability. Further, based on the risk prediction model, functional enrichment analysis revealed that 12 prognostic indicators involved a variety of cellular functions and signaling pathways, and the immune status was different in the high-risk and low-risk groups. In conclusion, a risk model of 12 ferroptosis related lncRNAs has important prognostic value for LUAD and may be ferroptosis-related therapeutic targets in the clinic.
EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

Background The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19. Methods SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions. Results EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha. Conclusion EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.
Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy

The identification of thalidomide–Cereblon-induced SALL4 degradation has brought new understanding for thalidomide embryopathy (TE) differences across species. Some questions, however, regarding species variability, still remain. The aim of this study was to detect sequence divergences between species, affected or not by TE, and to evaluate the regulated gene co-expression in a murine model. Here, we performed a comparative analysis of proteins experimentally established as affected by thalidomide exposure, evaluating 14 species. The comparative analysis, regarding synteny, neighborhood, and protein conservation, was performed in 42 selected genes. Differential co-expression analysis was performed, using a publicly available assay, GSE61306, which evaluated mouse embryonic stem cells (mESC) exposed to thalidomide. The comparative analyses evidenced 20 genes in the upstream neighborhood of NOS3, which are different between the species who develop, or not, the classic TE phenotype. Considering protein sequence alignments, RECQL4, SALL4, CDH5, KDR, and NOS2 proteins had the biggest number of variants reported in unaffected species. In co-expression analysis, Crbn was a gene identified as a driver of the co-expression of other genes implicated in genetic, non-teratogenic, limb reduction defects (LRD), such as Tbx5, Esco2, Recql4, and Sall4; Crbn and Sall4 were shown to have a moderate co-expression correlation, which is affected after thalidomide exposure. Hence, even though the classic TE phenotype is not identified in mice, a deregulatory Crbn-induced mechanism is suggested in this animal. Functional studies are necessary, especially evaluating the genes responsible for LRD syndromes and their interaction with thalidomide–Cereblon.
Interleukin-1- Receptor Kinase 4 Inhibition: Achieving Immunomodulatory Synergy to Mitigate the Impact of COVID-19

COVID-19 is a viral disease caused by a novel coronavirus, SARS-CoV-2, and is responsible for a pandemic since being identified in January 2020, resulting in a severe acute respiratory syndrome (SARS). Although most patients with COVID-19 may experience an asymptomatic, mild, or selflimited illness, many patients rapidly develop dyspnea and pneumonia, requiring hospitalization for pulmonary support. Patients with severe COVID-19 symptoms manifest cytokine release syndrome (CRS), which is associated with systemic inflammation, hemodynamic instability, and multi-organ failure (1). Progression from milder respiratory symptoms to acute respiratory distress syndrome (ARDS) is currently believed to be driven largely due to CRS and be one of main reasons for COVID-19 mortality.
Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues

Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.g., transcription factors) using a method called Chromatin immunoprecipitation followed by sequencing (ChIP-seq). In this study ChIP-seq was performed to find functional regions in the bovine genome by assaying for four histone modifications (H3K4Me1, H3K4Me3, H3K27ac, and H3K27Me3) and one transcription factor (CTCF) in 6 tissues (heart, kidney, liver, lung, mammary and spleen) from 2 to 3 lactating dairy cows. Eighty-six ChIP-seq samples were generated in this study, identifying millions of functional regions in the bovine genome. Combinations of histone modifications and CTCF were found using ChromHMM and annotated by comparing with active and inactive genes across the genome. Functional marks differed between tissues highlighting areas which might be particularly important to tissue-specific regulation. Supporting the cis-regulatory role of functional regions, the read counts in some ChIP peaks correlated with nearby gene expression. The functional regions identified in this study were enriched for putative causal variants as seen in other species. Interestingly, regions which correlated with gene expression were particularly enriched for potential causal variants. This supports the hypothesis that complex traits are regulated by variants that alter gene expression. This study provides one of the largest ChIP-seq annotation resources in cattle including, for the first time, in the mammary gland of lactating cows. By linking regulatory regions to expression QTL and trait QTL we demonstrate a new strategy for identifying causal variants in cattle.