Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiology and Distribution of Archaeal Methanotrophs That Couple Anaerobic Oxidation of Methane with Sulfate Reduction

In marine anaerobic environments, methane is oxidized where sulfate-rich seawater meets biogenic or thermogenic methane. In those niches, a few phylogenetically distinct microbial types, i.e., anaerobic methanotrophs (ANME), are able to grow through anaerobic oxidation of methane (AOM). Due to the relevance of methane in the global carbon cycle, ANME have drawn the attention of a broad scientific community for 4 decades. SUMMARY In marine anaerobic environments, methane is oxidized where sulfate-rich seawater meets biogenic or thermogenic methane. In those niches, a few phylogenetically distinct microbial types, i.e., anaerobic methanotrophs (ANME), are able to grow through anaerobic oxidation of methane (AOM). Due to the relevance of methane in the global carbon cycle, ANME have drawn the attention of a broad scientific community for 4 decades. This review presents and discusses the microbiology and physiology of ANME up to the recent discoveries, revealing novel physiological types of anaerobic methane oxidizers which challenge the view of obligate syntrophy for AOM. An overview of the drivers shaping the distribution of ANME in different marine habitats, from cold seep sediments to hydrothermal vents, is given. Multivariate analyses of the abundance of ANME in various habitats identify a distribution of distinct ANME types driven by the mode of methane transport. Intriguingly, ANME have not yet been cultivated in pure culture, despite intense attempts. Further advances in understanding this microbial process are hampered by insufficient amounts of enriched cultures. This review discusses the advantages, limitations, and potential improvements for ANME laboratory-based cultivation systems.
New Derivatives of Bacteriopurpurin with Thiolated Au (I) Complexes: Dual Dark- and Light Activated Antitumor Potency.

BACKGROUND Conventional antitumor Photosensitizers (PS) are normally low toxic in the dark whereas light activation triggers a massive cell death (photodynamic therapy, PDT). OBJECTIVE To expand the therapeutic potential of PS to dual potency cytocidal agents we took advantage of the use of bacteriopurpurin for a deeper tissue penetration of light, and suitability of the tetrapyrrolic macrocycle for chemical modifications at its periphery. METHODS Conjugation of a pro-oxidant thiolate Au (I) moiety to the bacteriopurpurin core and evaluation of cytotoxicity in cell culture and in vivo. RESULTS New water soluble derivatives showed a micromolar cytotoxicity for cultured human tumor cell lines in the dark, including the subline with an altered drug response due to p53 inactivation. Cellular PDT with the selected conjugate, thiolate Au (I)-dipropoxybacteriopurpurinimide (compound 6) with two triphenylphosphine Au fragments, triggered rapid (within minutes) cell death. Damage to the plasma membrane (necrosis) was a hallmark of cell death by 6 both in the dark and upon light activation. Furthermore, one single i.v. injection of 6 caused retardation of transplanted syngeneic tumors at the tolerable dose. Illumination of tumors that accumulated compound 6 significantly synergized with the effect of 6 in the dark. CONCLUSION Complexes of virtually non-toxic, photoactivatable bacteriopurpurin with the gold containing organic moiety are considered the dual potency antitumor agents, tentatively applicable for intractable tumors.
Organic Ectopy of Immunocompetent Cells

This review summarizes contemporary researches about the role of the resident immune cells in different organs – pineal gland, placenta, ovary, endometrium, liver, skin, gastro-intestinal tract, bronchial system. Mechanisms of the immune response realization reflects the relationship between different cells, tissues and organs, and thus support the notion of the unity of the nervous, immune and endocrine systems. It was established that the interaction of these systems is complex. Populations of various immune cells have common structural and functional features what is the foundation of a safety mechanism of the immune system. Reduction in the correlation of different subpopulations immune cells number in the organism is the foundation of various pathological processes.
Using the Unified Theory of Acceptance and Use of Technology model to analyze cloud-based mHealth service for primary care

Background and Objectives: Cloud-based mHealth services have the potential to make quality healthcare available in remote locations in the world. A practical deployment will involve medicolegal issues involving physicians and patients in different within and across countries. However, the first step is to evaluate such a cloud-based mHealth (MyOnlineClinic). This study aimed to understand and find out the factors that influence the end-user intention to use this new technology in Australia. Materials and Methods: We surveyed 167 end-users in 2015 and performed a Structural Equation Model analysis using Smart PLS to identify the intention to use the system among the participants. Results: The study revealed that the Unified Theory of Acceptance and Use of Technology construct, particularly facilitating condition (FC) (β = 0.355, P = 0.002), has yielded a significant influence on the behavioral intention to use MyOnlineClinic. However, the relationships between performance expectancy and behavioral intention (β = 0.162, P = 0.141), effort expectancy and behavioral intention (β = −0.004, P = 0.971), and social influences and behavioral intention (β = 0.164, P = 0.100) were insignificant. Further, age showed moderating effect on these variables. The majority of the respondents agreed or strongly agreed that technological issues such as sound (92.2%), video qualities (88.6%), and interaction with doctor (89.8%) are good. Conclusion: The end-users’ intentions to use MyOnlineClinic system were particularly influenced by FCs such as hardware, software, and the information technology knowledge/familiarity of users. These factors may get further accentuated when these systems are deployed across countries with different languages, technological infrastructures, and medicolegal environments. Therefore, cloud-based mHealth would help in removing some barriers, such as differences in software versions and interoperability problems of systems at physician and patient ends.
Anomalous Event Detection Methodologies for Surveillance Application: An Insight

Automatic visual surveillance systems serve as in-place threat detection devices being able to detect and recognize anomalous activities which otherwise would lead to potentially harmful situations, and alert the concerned authorities to take appropriate counter actions. However, development of an efficient visual surveillance system is quite challenging. Designing an unusual activity detection mechanism which is accurate and real-time is the primary challenge. Review of literature carried out led to the inference that there are some attributes which are essential for a successful unusual event detection mechanism for surveillance application. The desired approach must detect genuine anomalies in real-world scenarios with acceptable accuracy, should adapt to changing environments and, should require less computational time and memory. In this chapter, an attempt has been made to provide an insight into some of the prominent approaches employed by researchers to solve these issues with a hope that it will benefit researchers towards developing a better surveillance system. Anomalous Event Detection Methodologies for Surveillance Application: An Insight
Space use of Pacific harbor seals (Phoca vitulina richardii) from two haulout locations along the Oregon coast

Background There are approximately 10,000–12,000 Pacific harbor seals (Phoca vitulina richardii) inhabiting the Oregon coast, and unlike other species of pinnipeds in this region, are reliably present year-round. Despite this, and drastic rebounds in population since the enactment of the Marine Mammal Protection Act, limited data is available for the present period regarding their space use at sea, and within estuarine, riverine, or bay areas within the state. Objective To examine site-based differences in space use for 24 adult Pacific harbor seals captured and outfitted with satellite transmitters at two predominant haulout sites on the Oregon Coast, USA. Design We captured 24 adult harbor seals from two haulout sites on the Central Oregon coast between September 2014–16 and fitted them with external Wildlife Computers SPOT5 satellite transmitters to track movement. Using state-space modeled locations derived from satellite telemetry data, we evaluated spatial behavior of these animals using a correlated random walk model via R package crawl. Kernel density estimation was subsequently used to calculate home range and core area for each animal. Percent use of open ocean habitat versus use of estuaries, rivers and bays was quantified, as was an initial examination of presence within five newly-established marine reserves in Oregon. Examination of haulout site-related differences in spatial behavior were examined for seals captured in Netarts and Alsea Bays, Oregon and haul out behavior related to time of day, season, and tidal level was also investigated. Results The average individual home range for seals was 364.47 ± 382.87 km2 with seals captured in Alsea bay demonstrating a significantly higher home range area than those captured in Netarts Bay. Alsea bay seals also tended to range farther from shore than Netarts Bay animals. The average calculated core area for seals encompassed on average 29.41 ± 29.23 km2 per animal, however the home range of one animal was so small, core area could not be calculated. Use of marine reserves was limited for animals in this study, representing less than 2% of locations with a majority occurring in Cape Perpetua Marine Reserve and North Marine Protected Area. Seals were more likely to haul out during low tides and periods of low light (dusk, night and dawn), and hauling out behavior increased in winter months. Significance These findings demonstrate the first major documentation of space use of harbor seals in the state for nearly three decades, and lends itself to future comparison and formation of mechanistically-based hypotheses for behavior of a common marine mammal in the highly productive northern California Current System.
Elevated levels of inflammatory markers in women with rheumatoid arthritis

ABSTRACT Rheumatoid arthritis (RA) is an autoimmune and progressive disease. Evidence indicates that inflammatory mediators may contribute to the genesis and/or evolution of this clinical condition. Thus, the objective was to evaluate and compare the plasma levels of Interleukin-17 (IL-17), Tumor Necrosis Factor-Alpha (TNF-α) and Complement 3 (C3) in women with RA and healthy controls (HC), as well as to evaluate the association them with the disease activity. 25 women with RA and 15 HC were recruited. Plasma levels of biomarkers were measured by ELISA. All statistical analyzes were performed with a significance level set at α = 0.05. In the women with RA, the median age was 55 and, in the HC, was 50 years. The median value of DAS-28 was 3.79. The plasma levels of IL-17 (p = .03), TNF-α (p ≤ 0.01) and C3 (p ≤ 0.01) were higher in women with RA. The ROC curve showed that TNF- α has a higher discriminating ability than IL-17 and C3. DAS-28 score correlated significantly with C3 levels in women with RA (r = 0.91; p < .01). These findings reaffirm the participation of the immune system in pathophysiology of RA, suggest that TNF-α levels may be a good biomarker and that elevated C3 levels contribute to the worsening of the disease.
Ascending aorta and aortic root replacement (with or without valve sparing) in early childhood: surgical strategies and long-term outcomes.

OBJECTIVES Aortic root and ascending aorta replacements (AARs) are rarely required in the paediatric population. We report here a series of AAR performed in young children using different surgical techniques. METHODS Between 1995 and 2017, 32 children under the age of 10 years (median age 5.4 years) underwent AAR procedures at our institution. Twenty-two (69%) had a connective tissue disease (infantile Marfan syndrome or Loeys-Dietz syndrome). We performed 11 AAR using a composite graft with a mechanical prosthesis and 21 valve-sparing procedures (10 Yacoub operations and 11 David operations). Median follow-up for operative survivors was 7.7 years (interquartile range 4.2-12.8 years). RESULTS The cardiac-related early mortality rate was 6%. Patient survival was 91% at both 1 and 10 years. Eleven survivors (38%), all with a status of post-valve-sparing procedure, required an aortic root reintervention with an aortic valve replacement after a median interval of 4.2 years. Interestingly, only patients with infantile Marfan syndrome tended to be associated with risk of reoperation. CONCLUSIONS Aortic root and AARs are safe in young children whatever the surgical procedure. Aortic valve-sparing procedures show good long-term results except in children with infantile Marfan syndrome whose ineluctable aortic annulus dilatation or aortic valve regurgitation requires reintervention after a short period.
Usefulness and limitations of thermal performance curves in predicting ectotherm development under climatic variability.

1.Thermal performance curves (TPCs) have been estimated in multiple ectotherm species to understand their thermal plasticity and adaptation and to predict the effect of global warming. However, TPCs are typically assessed under constant temperature regimes, so their reliability for predicting thermal responses in the wild where temperature fluctuates diurnally and seasonally remains poorly documented. 2.Here we use distant latitudinal populations of five species of sepsid flies (Diptera: Sepsidae) from the temperate region (Europe, North Africa, North America) to compare estimates derived from constant TPCs with observed development rate under fluctuating temperatures in laboratory and field conditions. 3.TPCs changed across gradients in that flies originating from higher latitudes showed accelerated development at higher temperatures, an adaptive response. TPCs were then used to predict development rates observed under fluctuating temperatures; these predictions were relatively accurate in the laboratory but not the field. Interestingly, the precision of TPC-predictions depended not only on the resolution of temperature data, with diurnal and overall temperature summing performing better than hourly temperature summing, but also on the frequency of temperatures falling below the estimated critical minimum temperature. Hourly temperature resolution most strongly underestimated actual development rates, because flies apparently either did not stop growing when temperatures dropped below this threshold, or they sped up their growth when the temperature rose again, thus most severely reflecting this error. 4.We conclude that when flies do not encounter cold temperatures, TPC-predictions based on constant temperatures can accurately reflect performance under fluctuating temperatures if adequately adjusted for non-linearities, but when encountering cold temperatures, this method is more error-prone. 5.Our study emphasizes the importance of the resolution of temperature data and cold temperatures in shaping thermal reaction norms. This article is protected by copyright. All rights reserved.
Functional analyses of ancestral thioredoxins provide insights into their evolutionary history

Thioredoxin (Trx) is a conserved, cytosolic reductase in all known organisms. The enzyme receives two electrons from NADPH via thioredoxin reductase (TrxR) and passes them on to multiple cellular reductases via disulfide exchange. Despite the ubiquity of thioredoxins in all taxa, little is known about the functions of resurrected ancestral thioredoxins in the context of a modern mesophilic organism. Here, we report on functional in vitro and in vivo analyses of seven resurrected Precambrian thioredoxins, dating back 1–4 billion years, in the Escherichia coli cytoplasm. Using synthetic gene constructs for recombinant expression of the ancestral enzymes, along with thermodynamic and kinetic assays, we show that all ancestral thioredoxins, as today's thioredoxins, exhibit strongly reducing redox potentials, suggesting that thioredoxins served as catalysts of cellular reduction reactions from the beginning of evolution, even before the oxygen catastrophe. A detailed, quantitative characterization of their interactions with the electron donor TrxR from Escherichia coli and the electron acceptor methionine sulfoxide reductase, also from E. coli, strongly hinted that thioredoxins and thioredoxin reductases co-evolved and that the promiscuity of thioredoxins toward downstream electron acceptors was maintained during evolution. In summary, our findings suggest that thioredoxins evolved high specificity for their sole electron donor TrxR while maintaining promiscuity to their multiple electron acceptors.
High levels of endothelial progenitor cells and circulating endothelial cells in patients with Behçet's disease and their relationship to disease activity*

Background Behçet's disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behçet's disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis. Objectives To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behçet's disease and to describe their relationship with the disease activity. Methods A total of 45 patients with Behçet's disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry. Results The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behçet's disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells. Study Limitations The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers. Conclusion The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behçet's disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behçet's disease, respectively.
The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase involved in neuronal and gut development. Initially discovered in T cell lymphoma, ALK is frequently affected in diverse cancers by oncogenic translocations. These translocations involve different fusion partners that facilitate multimerisation and autophosphorylation of ALK, resulting in a constitutively active tyrosine kinase with oncogenic potential. ALK fusion proteins are involved in diverse cellular signalling pathways, such as Ras/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt and Janus protein tyrosine kinase (JAK)/STAT. Furthermore, ALK is implicated in epigenetic regulation, including DNA methylation and miRNA expression, and an interaction with nuclear proteins has been described. Through these mechanisms, ALK fusion proteins enable a transcriptional programme that drives the pathogenesis of a range of ALK-related malignancies.
Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population

ABSTRACT Objective The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.
PTEN Tumor-Suppressor: The Dam of Stemness in Cancer

PTEN is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation in PTEN gene/protein levels is commonly observed in a broad spectrum of human cancers, while germline PTEN mutations cause inherited syndromes that lead to increased risk of tumors. PTEN restrains tumorigenesis through different mechanisms ranging from phosphatase-dependent and independent activities, subcellular localization and protein interaction, modulating a broad array of cellular functions including growth, proliferation, survival, DNA repair, and cell motility. The main target of PTEN phosphatase activity is one of the most significant cell growth and pro-survival signaling pathway in cancer: PI3K/AKT/mTOR. Several shreds of evidence shed light on the critical role of PTEN in normal and cancer stem cells (CSCs) homeostasis, with its loss fostering the CSC compartment in both solid and hematologic malignancies. CSCs are responsible for tumor propagation, metastatic spread, resistance to therapy, and relapse. Thus, understanding how alterations of PTEN levels affect CSC hallmarks could be crucial for the development of successful therapeutic approaches. Here, we discuss the most significant findings on PTEN-mediated control of CSC state. We aim to unravel the role of PTEN in the regulation of key mechanisms specific for CSCs, such as self-renewal, quiescence/cell cycle, Epithelial-to-Mesenchymal-Transition (EMT), with a particular focus on PTEN-based therapy resistance mechanisms and their exploitation for novel therapeutic approaches in cancer treatment.