Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans

Dioxins are one of the most potent anthropogenic poisons, causing systemic disorders in embryonic development and pathologies in adults. The mechanism of dioxin action requires an aryl hydrocarbon receptor (AhR), but the downstream mechanisms are not yet precisely clear. Here, we performed a meta-analysis of all available transcriptome datasets taken from human cell cultures exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Differentially expressed genes from different experiments overlapped partially, but there were a number of those genes that were systematically affected by TCDD. Some of them have been linked to toxic dioxin effects, but we also identified other attractive targets. Among the genes that were affected by TCDD, there are functionally related gene groups that suggest an interplay between retinoic acid, AhR, and Wnt signaling pathways. Next, we analyzed the upstream regions of differentially expressed genes and identified potential transcription factor (TF) binding sites overrepresented in the genes responding to TCDD. Intriguingly, the dioxin-responsive element (DRE), the binding site of AhR, was not overrepresented as much as other cis-elements were. Bioinformatics analysis of the AhR binding profile unveils potential cooperation of AhR with E2F2, CTCFL, and ZBT14 TFs in the dioxin response. We discuss the potential implication of these predictions for further dioxin studies.
Meta-analysis of the human brain transcriptome identifies heterogeneity across human AD coexpression modules robust to sample collection and methodological approach

Alzheimer’s disease (AD) is a complex and heterogenous brain disease that affects multiple inter-related biological processes. This complexity contributes, in part, to existing difficulties in the identification of successful disease-modifying therapeutic strategies. To address this, systems approaches are being used to characterize AD-related disruption in molecular state. To evaluate the consistency across these molecular models, a consensus atlas of the human brain transcriptome was developed through coexpression meta-analysis across the AMP-AD consortium. Consensus analysis was performed across five coexpression methods used to analyze RNA-seq data collected from 2114 samples across 7 brain regions and 3 research studies. From this analysis, five consensus clusters were identified that described the major sources of AD-related alterations in transcriptional state that were consistent across studies, methods, and samples. AD genetic associations, previously studied AD-related biological processes, and AD targets under active investigation were enriched in only three of these five clusters. The remaining two clusters demonstrated strong heterogeneity between males and females in AD-related expression that was consistently observed across studies. AD transcriptional modules identified by systems analysis of individual AMP-AD teams were all represented in one of these five consensus clusters except ROS/MAP-identified Module 109, which was specific for genes that showed the strongest association with changes in AD-related gene expression across consensus clusters. The other two AMP-AD transcriptional analyses reported modules that were enriched in one of the two sex-specific Consensus Clusters. The fifth cluster has not been previously identified and was enriched for genes related to proteostasis. This study provides an atlas to map across biological inquiries of AD with the goal of supporting an expansion in AD target discovery efforts.
Prevention of Clostridium difficile Infection and Associated Diarrhea: An Unsolved Problem

For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen.
Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease

Altered glucose metabolism has been implicated in the pathogenesis of Alzheimer’s disease (AD). Aerobic glycolysis from astrocytes is a critical metabolic pathway for brain energy metabolism. Disturbances of circadian rhythm have been associated with AD. While the role of circadian locomotor output cycles kaput (CLOCK) and brain muscle ARNT-like1 (BMAL1), the major components in the regulation of circadian rhythm, has been identified in the brain, the mechanism by which CLOCK and BMAL1 regulates the dysfunction of astrocytes in AD remains unclear. Here, we show that the protein levels of CLOCK and BMAL1 are significantly elevated in impaired astrocytes of cerebral cortex from patients with AD. We demonstrate that the over-expression of CLOCK and BMAL1 significantly suppresses aerobic glycolysis and lactate production by the reduction in hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) protein levels in human astrocytes. Moreover, the elevation of CLOCK and BMAL1 induces functional impairment by the suppression of glial fibrillary acidic protein (GFAP)-positive filaments in human astrocytes. Furthermore, the elevation of CLOCK and BMAL1 promotes cytotoxicity by the activation of caspase-3-dependent apoptosis in human astrocytes. These results suggest that the elevation of CLOCK and BMAL1 contributes to the impairment of astrocytes by inhibition of aerobic glycolysis in AD.
Insulin Infusion Computer Calculator Programmed Directly Into Electronic Health Record Medication Administration Record

Background: Computerized insulin infusion protocols have demonstrated higher staff satisfaction, better compliance with protocols, and increased time with glucose in range compared to paper protocols. At University of California San Diego Health (UCSDH), we implemented an insulin infusion computer calculator (IICC) and transitioned it from a web-based platform directly into the electronic medication administration record (eMAR) of our primary electronic health record (EHR). Methods: This is a retrospective analysis of 6306 adult patients at UCSDH receiving intravenous (IV) insulin infusion from March 7, 2013 to May 30, 2019. We created three periods of the study—(1) the pre-eMAR integration period; (2) the eMAR integration period; and (3) the post-eMAR integration period—and looked at the percentage of readings within goal range (90-150 mg/dL for intensive care unit [ICU], 90-180 mg/dL for non-ICU) in patients with and without hyperglycemic emergencies. As our safety endpoints, we elected to look at incidence of blood glucose (BG) readings <70 mg/dL, <54 mg/dL, and <40 mg/dL. Results: Pre-eMAR 69.8% of readings were in the 90-150 mg/dL range compared to 70.2% post-eMAR (P = .03) and 82.7% of readings were in the 90-180 mg/dL range pre-eMAR versus 82.9% (P = .09) post-eMAR in patients without hyperglycemic emergencies. Rates of hypoglycemia with BG <70 mg/dL were 0.43%, <54 mg/dL were 0.07%, and <40 mg/dL were 0.01% of readings pre- and post-eMAR. Conclusions: At UCSDH, our IICC has shown to be safe and effective in a wide variety of clinical situations and we were able to successfully transition it from a web-based platform directly into the eMAR of our primary EHR.
Daytime Neurophysiological Hyperarousal in Chronic Insomnia: A Study of qEEG

Background: The hyperarousal model demonstrates that instability of sleep-wake regulation leads to insomnia symptoms and various neurophysiological hyperarousal states. Previous studies have shown that hyperarousal states that appear in chronic insomnia patients are not limited to sleep at nighttime but are stable characteristics that extend into the daytime. However, this phenomenon is mainly measured at bedtime, so it hard to determine whether it is maintained throughout a 24 h cycle or if it just appears at bedtime. Methods: We examined the resting state qEEG (quantitative electroencephalogram) and ECG (electrocardiogram) of chronic insomnia patients (n = 24) compared to good sleepers (n = 22) during the daytime. Results: As compared with controls, participants with insomnia showed a clearly high beta band activity in eyes closed condition at all brain areas. They showed a low frequency band at the frontal area; high frequency bands at the central and parietal areas were found in eyes open condition. Significantly higher heart rates were also found in the chronic insomnia group. Conclusion: These findings suggest that chronic insomnia patients were in a state of neurophysiological hyperarousal during the middle of the day due to abnormal arousal regulation.
Efficacy of Local Minocycline Agents in Treating Peri-Implantitis: An Experimental In Vivo Study in Beagle Dogs

Background: Local delivery agents (LDA) have the advantage of delivering the antibiotics at high concentrations to the targeted sites. However, the constant flow of gingival crevicular fluids and saliva may restrict their efficacy. Therefore, the drug sustainability and pharmacodynamic properties of any proposed LDA should be evaluated. Methods: Four dental implants were placed unilaterally in the edentulous mandible of six beagle dogs. Peri-implantitis were experimentally induced using silk-ligatures. Each implant was randomly allocated to receive one of the following four treatments: (i) MC (Chitosan-alginate (CA) minocycline), (ii) MP (CA-without minocycline), (iii) PG (Polyacrylate-glycerin minocycline), and (iv) Control (mechanical debridement only). Mechanical therapies and LDAs were administered into the gingival sulcus two times at a 4-week interval. Drug sustainability as well as clinical, radiographical, and immunohistochemical (IHC) analyses were conducted to evaluate the efficacies of treatments. Results: Reduced mean probing depth was observed in all of the test groups after the second delivery. A minimal marginal bone level change was observed during the treatment period (MP (−0.06 ± 0.53 mm) to PG (−0.25 ± 0.42 mm)). The distribution of IHC cell marker analysis of all targeted antibodies ranged from 6.34% to 11.33%. All treatment outcomes between the test groups were comparable. A prolonged retention of LDA was observed from CA microspheres (MC and MP) at both administrations (p < 0.017) and prolonged sustainability of bacteriostatic effect was observed from MC compared to PG after the second administration (p < 0.05). Conclusions: Prolonged retention of CA microspheres was observed and the longer bacteriostatic effect was observed from the MC group. Mechanical debridement with adjunct LDA therapy may impede peri-implantitis progression, however, prolonged drug action did not lead to improved treatment outcome.
The Untapped Australasian Diversity of Astaxanthin-Producing Yeasts with Biotechnological Potential—Phaffia australis sp. nov. and Phaffia tasmanica sp. nov.

Phaffia is an orange-colored basidiomycetous yeast genus of the order Cystofilobasidiales that contains a single species, P. rhodozyma. This species is the only fungus known to produce the economically relevant carotenoid astaxanthin. Although Phaffia was originally found in the Northern hemisphere, its diversity in the southern part of the globe has been shown to be much greater. Here we analyze the genomes of two Australasian lineages that are markedly distinct from P. rhodozyma. The two divergent lineages were investigated within a comprehensive phylogenomic study of representatives of the Cystofilobasidiales that supported the recognition of two novel Phaffia species, for which we propose the names of P. australis sp. nov. and P. tasmanica sp. nov. Comparative genomics and other analyses confirmed that the two new species have the typical Phaffia hallmark—the six genes necessary for the biosynthesis of astaxanthin could be retrieved from the draft genome sequences, and this carotenoid was detected in culture extracts. In addition, the organization of the mating-type (MAT) loci is similar to that of P. rhodozyma, with synteny throughout most regions. Moreover, cases of trans-specific polymorphism involving pheromone receptor genes and pheromone precursor proteins in the three Phaffia species, together with their shared homothallism, provide additional support for their classification in a single genus.
Future changes in hydrological extremes of a Mediterranean catchment: what can we say in an uncertainty context?

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Mangroves as a Source of Alkalinity and Dissolved Carbon to the Coastal Ocean: A Case Study from the Everglades National Park, Florida

Most research evaluating the potential of mangroves as a sink for atmospheric carbon has focused on carbon burial. However, the few studies that have quantified lateral exchange of carbon and alkalinity indicate that the dissolved carbon and alkalinity export may be several-fold more important than burial. This study aims to investigate rates and drivers of alkalinity, dissolved carbon and greenhouse gas fluxes of the mangrove-dominated Shark River estuary located in the Everglades National Park in Florida, USA. Time series and spatial surveys were conducted to assess total alkalinity (TAlk), organic alkalinity (OAlk), dissolved inorganic carbon (DIC), dissolved organic carbon (DOC), carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O). Dominant metabolic processes driving dissolved carbon and greenhouse gas dynamics varied along the estuarine salinity gradient. Dissolved carbon and greenhouse gas concentrations were strongly coupled to porewater input, which was examined using radon-222. Shark River was a source of CO2 (92 mmol/m2/d), CH4 (60 μmol/m2/d) and N2O (2 μmol/m2/d) to the atmosphere. Dissolved carbon export (DIC = 142 mmol/m2/d, DOC = 39 mmol/m2/d) was several-fold higher than burial ( ̃28 mmol/m2/d) and represents an additional carbon sink. Furthermore, the estuary was a source of TAlk (97 mmol/m2/d, normalised to mangrove area) to the coastal ocean, potentially buffering coastal acidification. Organic alkalinity was also exported to the coastal ocean (1.9 mmol/m2/d, normalised to mangrove area). By integrating our results with previous studies, we argue that alkalinity, dissolved carbon and greenhouse gas fluxes should be considered in future blue carbon budgets.
On Consistent Discretization of Finite-time Stable Homogeneous Differential Inclusions

This paper deals with the problem of consistent discretization of the generalized homogeneous differential inclusions which appear, in particular, as mathematical models of many sliding mode systems. An algorithm of consistent implicit discretization for homogeneous finite-time stable system is developed. It preserves the finite-time stability property and reduces the numerical chattering. The scheme is demonstrated for the so-called "nested" second order sliding mode algorithm.
From Differential Stains to Next Generation Physiology: Chemical Probes to Visualize Bacterial Cell Structure and Physiology

Chemical probes have been instrumental in microbiology since its birth as a discipline in the 19th century when chemical dyes were used to visualize structural features of bacterial cells for the first time. In this review article we will illustrate the evolving design of chemical probes in modern chemical biology and their diverse applications in bacterial imaging and phenotypic analysis. We will introduce and discuss a variety of different probe types including fluorogenic substrates and activity-based probes that visualize metabolic and specific enzyme activities, metabolic labeling strategies to visualize structural features of bacterial cells, antibiotic-based probes as well as fluorescent conjugates to probe biomolecular uptake pathways.
Black soot exposure induced hypothalamic and testicular oxidative stress and apoptosis in male rats

Air pollution constitutes the largest cause of environmental risks today. At present, no scientific publication linking environmental black soot and derangement in the hypothalamus and testis of rats exists. This study investigated the effect of black soot exposure on hypothalamic and testicular functions of male rats exposed to black soot for 4, 8 and 12 weeks respectively. The hypothalamus and testis were processed for biochemical analysis. Results show that black soot exposure for 4, 8 and 12 weeks significantly (p < .05) increased oxidative stress markers both in the testis and in the hypothalamus of rats. Also, black soot exposure significantly (p < .05) decreased the alkaline phosphatase, acid phosphatase as well as lactate dehydrogenase activities in the testis. Furthermore, the result demonstrated an upregulation of the protein expression of caspase‐3, an indication of increased apoptosis which led to the disruption of the histological architecture of the hypothalamus and testis. Taken together, black soot exposure induced hypothalamic and testicular oxidative stress and apoptosis in male rats.
Evaluating Asthma Mobile Apps to Improve Asthma Self-Management: User Ratings and Sentiment Analysis of Publicly Available Apps

Background The development and use of mobile health (mHealth) apps for asthma management have risen dramatically over the past two decades. Asthma apps vary widely in their content and features; however, prior research has rarely examined preferences of users of publicly available apps. Objective The goals of this study were to provide a descriptive overview of asthma mobile apps that are publicly available and to assess the usability of asthma apps currently available on the market to identify content and features of apps associated with positive and negative user ratings. Methods Reviews were collected on June 23, 2020, and included publicly posted reviews until June 21, 2020. To characterize features associated with high or low app ratings, we first dichotomized the average user rating of the asthma app into 2 categories: a high average rating and a low average rating. Asthma apps with average ratings of 4 and above were categorized as having a high average rating. Asthma apps with average ratings of less than 4 were categorized as having a low average rating. For the sentiment analysis, we modeled both 2-word (bi-gram) and 3-word (tri-gram) phrases which commonly appeared across highly rated and lowly rated apps. Results Of the 10 apps that met the inclusion criteria, a total of 373 reviews were examined across all apps. Among apps reviewed, 53.4% (199/373) received high ratings (average ratings of 4 or 5) and 47.2% (176/373) received low ratings (average ratings of 3 or less). The number of ratings across all apps ranged from 188 (AsthmaMD) to 10 (My Asthma App); 30% (3/10) of apps were available on both Android and iOS. From the sentiment analysis, key features of asthma management that were common among highly rated apps included the tracking of peak flow readings (n=48), asthma symptom monitoring (n=11), and action plans (n=10). Key features related to functionality that were common among highly rated apps included ease of use (n=5). Users most commonly reported loss of data (n=14) and crashing of app (n=12) as functionality issues among poorly rated asthma apps. Conclusions Our study results demonstrate that asthma app quality, maintenance, and updates vary widely across apps and platforms. These findings may call into question the long-term engagement with asthma apps, a crucial factor for determining their potential to improve asthma self-management and asthma clinical outcomes.
Tissue‐disruption‐induced cellular stochasticity and epigenetic drift: Common origins of aging and cancer?

Age‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase in phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis.
Cloning and in silico and expression analyses of the heterotrimeric G protein α subunit gene (EjLGA1) from loquat (Eriobotrya japonica) fruits under cold storage with different pretreatments

ABSTRACT Cold-stored fruits of the loquat (Eriobotrya japonica Lindl.) plant suffer from strong lignification, which leads to a hard texture and a crude mouthfeel of the pulp. However, the signalling mechanisms of loquat fruits under cold storage remain unclear. In this study, the heterotrimeric G protein α subunit (Gα) gene (EjLGA1) from loquat was isolated, and in silico analysis was performed. The levels of EjLGA1 expression in cold-stored loquat fruits with different pretreatments were also investigated. The largest open-reading frame of EjLGA1 is 1173 bp, encoding a polypeptide of 390 amino acids. The nucleotide and amino acid sequences of the Gα subunit are highly conserved among loquat and 48 other seed plants, indicating that the loquat Gα subunit likely has similar functions in other plants. A reliable model of the loquat Gα subunit was constructed, which revealed the structure of the subunit. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) results showed that EjLGA1 is highly expressed under cold storage, which suggests the significance of EjLGA1 function in loquat fruits in response to cold stress. However, ethephon and 1-methylcyclopropene (1-MCP) pretreatments did not regulate EjLGA1expression. These results provide new insight into the signalling mechanism in cold-stored loquat fruits.