Miracle-dz/UniFAR-FTUs huggingface dataset:
Epithelial to Mesenchymal Transition by TGFβ-1 Induction Increases Stemness Characteristics in Primary Non Small Cell Lung Cancer Cell Line

Background Cancer Stem Cells (CSCs) hypothesis asserts that only a small subset of cells within a tumour is capable of both tumour initiation and sustainment. The Epithelial-Mesenchymal Transition (EMT) is an embryonic developmental program that is often activated during cancer invasion and metastasis. The aim of this study is to shed light on the relationship between EMT and CSCs by using LC31 lung cancer primary cell line. Materials and Methods A549 and LC31 cell lines were treated with 2 ng/ml TGFβ-1 for 30 days, and 80 days, respectively. To evaluate EMT, morphological changes were assessed by light microscopy, immunofluorescence and cytometry for following markers: cytokeratins, e-cadherin, CD326 (epithelial markers) and CD90, and vimentin (mesenchymal markers). Moreover, RT-PCR for Slug, Twist and β-catenin genes were performed. On TGFβ-1 treated and untreated LC31 cell lines, we performed stemness tests such as pneumospheres growth and stem markers expression such as Oct4, Nanog, Sox2, c-kit and CD133. Western Blot for CD133 and tumorigenicity assays using NOD/SCID mice were performed. Results TGFβ-1 treated LC31 cell line lost its epithelial morphology assuming a fibroblast-like appearance. The same results were obtained for the A549 cell line (as control). Immunofluorescence and cytometry showed up-regulation of vimentin and CD90 and down-regulation of cytocheratin, e-cadherin and CD326 in TGFβ-1 treated LC31 and A549 cell lines. Slug, Twist and β-catenin m-RNA transcripts were up-regulated in TGFβ-1 treated LC31 cell line confirming EMT. This cell line showed also over-expression of Oct4, Nanog, Sox2 and CD133, all genes of stemness. In addition, in TGFβ-1 treated LC31 cell line, an increased pneumosphere-forming capacity and tumours-forming ability in NOD/SCID mice were detectable. Conclusions The induction of EMT by TGFβ-1 exposure, in primary lung cancer cell line results in the acquisition of mesenchymal profile and in the expression of stem cell markers.
Visualising the interaction of CD4 T cells and DCs in the evolution of inflammatory arthritis

Objectives Successful early intervention in rheumatoid arthritis (RA) with the aim of resetting immunological tolerance requires a clearer understanding of how specificity, cellular kinetics and spatial behaviour shape the evolution of articular T cell responses. We aimed to define initial seeding of articular CD4+ T cell responses in early experimental arthritis, evaluating their dynamic behaviour and interactions with dendritic cells (DCs) in the inflamed articular environment. Methods Antigen-induced arthritis was used to model articular inflammation. Flow cytometry and PCR of T cell receptor (TCR) diversity genes allowed phenotypic analysis of infiltrating T cells. The dynamic interactions of T cells with joint residing DCs were visualised using intravital multiphoton microscopy. Results Initial recruitment of antigen-specific T cells into the joint was paralleled by accumulation of CD4+ T cells with diverse antigen-receptor expression and ability to produce tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) on mitogenic restimulation. A proportion of this infiltrate demonstrated slower motility speeds and engaged for longer periods with articular DCs in vivo. Abatacept treatment did not disrupt these interactions but did reduce T cell expression of inducible costimulatory (ICOS) molecule. We also demonstrated that non-specific CD4+ T cells could be recruited during these early articular events. Conclusions We demonstrate that CD4+ T cells engage with articular DCs supporting antigen specific T cell reactivation. This cellular dialogue can be targeted therapeutically to reduce local T cell activation.
A robust velocity field control

This paper is devoted to velocity field control (VFC) of uncertain robotic manipulators. We propose a proportional-integral (PI)-type controller derived from modeling error compensation ideas and singular perturbation theory, that requires a minimum knowledge of the plant (i.e., constant estimate of the inertia matrix). It is shown that semiglobal practical stabilization is achieved; that is, given any compact set of initial velocity field errors, there exist PI control gains which guarantee that the robot tracks a desired velocity field with arbitrary accuracy. The proposed controller was experimentally evaluated on a two degrees-of-freedom arm.
Inhibitory effects of dietary calcium on the initial uptake and subsequent retention of heme and nonheme iron in humans: comparisons using an intestinal lavage method.

BACKGROUND Calcium is the only reported dietary inhibitor of both heme- and nonheme-iron absorption. It has been proposed that the 2 forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. OBJECTIVES We aimed to ascertain whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer and to compare the serosal transfer of heme and nonheme iron, which should not differ if the 2 forms have entered a common mucosal iron pool. DESIGN Whole-gut lavage and whole-body counting were used to measure the initial uptake (8 h) and retention (2 wk) of heme and nonheme iron with and without a calcium supplement (450 mg). Two experiments tested basal meals with low iron bioavailability and 360 mg Ca (n = 15) or with high iron bioavailability and 60 mg Ca (n = 12). RESULTS Added calcium reduced the initial uptake of heme iron by 20%, from 49% to approximately 40% from both meals (P = 0.02), and reduced the total iron absorbed from the low- and high-bioavailability meals by approximately 25% [from 0.033 to 0.025 mg (P = 0.06) and from 0.55 to 0.40 mg (P < 0.01), respectively]. Calcium did not affect the serosal transfer of either form of iron. CONCLUSIONS Calcium supplementation reduced heme and total iron without significantly affecting nonheme-iron absorption, regardless of meal bioavailability. Calcium inhibited the initial mucosal uptake rather than the serosal transfer of heme iron. Differences in serosal transfer indicate that heme and nonheme iron did not enter a common absorptive pool within 8 h after a meal.
Vascular fibrinoid necrosis in the urinary bladder of ketamine abusers: A new finding that may provide a clue to the pathogenesis of ketamine‐induced vesicopathy

Two 31‐year‐old women who had abused ketamine, 1 for 8 years and 1 for 5 years, presented with ketamine‐induced vesicopathy with urinary frequency, decreased bladder capacity, and detrusor overactivity. An enterocystoplasty was performed in both cases. The pathology of the urinary bladders in both women showed ulcerative cystitis and fibrinoid necrosis of vessels; the latter was confirmed by Masson trichrome staining. Fibrinoid necrosis of vessels is a kind of immune complex‐mediated vasculitis that induces the release of inflammatory mediators, with subsequent thrombosis, ischemic injury, and eventual tissue necrosis in localized areas, the so‐called Arthus reaction. The new finding of fibrinoid necrosis in the urinary bladders of ketamine abusers may provide a new clue to the pathogenesis of ketamine‐induced vesicopathy.
Video-enabled cue based intervention for relapse prevention

A major goal of long-term management of substance use disorders is to empower recovering individuals in resisting drug use when confronted with real-world high-risk situations (cues). Since opportunities to reproduce and learn from real-life situations are limited in treatment settings, the key is to bring those real-world drug use cues to the treatment setting through vicarious learning. Cue-exposure approaches achieve this by presenting these cues while the usual drug-use response is prevented. This provides opportunity to practice how to deal with the cues before being discharged from the treatment setting. Videos are one way to present the cues as well as demonstrate how to deal with them successfully. In this article, we discuss our experiences with the use of videos to model relapse prevention strategies for specific cues, and provide some future directions for the use of video-based interventions for relapse prevention in substance use disorders.
Anaerobic Ammonium-Oxidizing Bacteria: Unique Microorganisms with Exceptional Properties

SUMMARY Anaerobic ammonium-oxidizing (anammox) bacteria defy many microbiological concepts and share numerous properties with both eukaryotes and archaea. Among their most intriguing characteristics are their compartmentalized cell plan and archaeon-like cell wall. Here we review our current knowledge about anammox cell biology. The anammox cell is divided into three separate compartments by bilayer membranes. The anammox cell consists of (from outside to inside) the cell wall, paryphoplasm, riboplasm, and anammoxosome. Not much is known about the composition or function of both the anammox cell wall and the paryphoplasm compartment. The cell wall is proposed to be proteinaceous and to lack both peptidoglycan and an outer membrane typical of Gram-negative bacteria. The function of the paryphoplasm is unknown, but it contains the cell division ring. The riboplasm resembles the standard cytoplasmic compartment of other bacteria; it contains ribosomes and the nucleoid. The anammoxosome occupies most of the cell volume and is a so-called “prokaryotic organelle” analogous to the eukaryotic mitochondrion. This is the site where the anammox reaction takes place, coupled over the curved anammoxosome membrane, possibly giving rise to a proton motive force and subsequent ATP synthesis. With these unique properties, anammox bacteria are food for thought concerning the early evolution of the domains Bacteria, Archaea, and Eukarya.
Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results.

BACKGROUND Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. OBJECTIVE To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease. DESIGN Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment. PARTICIPANTS Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable. MAIN OUTCOME MEASURES The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. RESULTS Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. CONCLUSION Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.
Maximizing Achievable Rate Strategies for Incremental-Relay Multicarrier Transmission

This paper develops an improved amplify-and-forward (AF) orthogonal frequency-division multiplexing (OFDM) scheme, where an incremental policy is fully utilized to promote the spectrum efficiency of cooperative transmission, and presents several achievable-rate-maximizing resource allocation strategies. The high computational complexity for optimization necessitates our investigation of suboptimal approaches. However, the associated computational burdens are still intensive due to the exhaustive search nature. As a consequence, a low-complexity alternative evolves to achieve a better tradeoff between performance and complexity. Moreover, its average unconditional signal-to-noise ratio (SNR) outage probability is analytically derived. Numerical results are shown to illustrate the benefits of the proposals and verify the validity of the theoretical analysis.
Distributed weighted sum-rate maximization in multicell MU-MIMO OFDMA downlink

This paper considers distributed linear beamforming in downlink multicell multiuser orthogonal frequency-division multiple access networks. A fast convergent solution maximizing the weighted sum-rate with per base station (BS) transmiting power constraint is formulated. We approximate the noncon-vex weighted sum-rate maximization (WSRM) problem with a semidefinite relaxed solvable convex form by means of a series of approximation based on interference alignment (IA) analysis. The WSRM optimization is a two-stage optimization process. In the first stage, the IA conditions are satisfied. In the second stage, the convex approximation of the non-convex WSRM is obtained based on the consequences of IA, and high signal-to-interference-plus-noise ratio assumption. Compared to the conventional iterative distributed algorithms where the BSs exchange additional information at each iteration, the BSs of our proposed solution optimize their beamformers locally without reporting additional information during the iterative procedure.
Identification and Phylogenetic Analysis of Heme Synthesis Genes in Trypanosomatids and Their Bacterial Endosymbionts

It has been known for decades that some insect-infecting trypanosomatids can survive in culture without heme supplementation while others cannot, and that this capability is associated with the presence of a betaproteobacterial endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms involved in this process remained obscure. In this work, we sequence and phylogenetically analyze the heme pathway genes from the symbionts and from their hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our results show that the enzymes responsible for synthesis of heme are encoded on the symbiont genomes and produced in close cooperation with the flagellate host. Our evidence suggests that this synergistic relationship is the end result of a history of extensive gene loss and multiple lateral gene transfer events in different branches of the phylogeny of the Trypanosomatidae.
Thyroid Hormone-Induced Expression of the Hepatic Scaffold Proteins Sestrin2, β-Klotho, and FRS2α in Relation to FGF21-AMPK Signaling.

Thyroid hormone (3,3',5-triiodothyronine, T3) accelerates energy metabolism in the liver through mechanisms involving upregulation of AMP-activated protein kinase (AMPK). This study aims to assess the influence of T3 on the expression of the scaffold proteins β-Klotho, fibroblast growth factor receptor substrate 2α (FRS2α), and Sestrin2 in relation to FGF21-AMPK signaling. Male Sprague-Dawley rats were given 0.1 mg T3/kg or hormone vehicle (controls) and studies were done 24 h after treatment. These include measurements of the mRNA expression (qPCR) of hepatic β-Klotho, FGF21, FGF21 receptor-1 (FGFR1), extracellular-signal-regulated kinase 1/2 (ERK1/2), FRS2α, ribosomal S6 kinase-1 (RSK1), liver kinase B1 (LKB1), AMPK, and Sestrin2. Also, protein levels of FGF21, FGFR1 (ELISA), and ERK1/2 (Western blot) were measured. T3 elicited a calorigenic response with higher hepatic mRNA expression of β-Klotho, FRS2α, and FGF21, increased serum FGF21, without changes in liver FGFR1 mRNA and its plasma levels. In addition, T3 enhanced ERK1/2 phosphorylation and the mRNA expression of ERK1/2, RSK1, LKB1, AMPK, and Sestrin2. T3 administration enhances liver FGF21-AMPK signaling involving upregulation of the scaffold proteins β-Klotho, FRS2α, and Sestrin2. β-Klotho and FRS2 induction favours the operation of the FGF21-FGFR1-β-Klotho complex as evidenced by the enhancement in ERK1/2 phosphorylation, whereas that of Sestrin2 recruits LKB1 to achieved AMPK activation, thus supporting a higher energy expenditure condition that may be desirable in some metabolic disorders.
N‐acetylcysteine attenuates the cuprizone‐induced behavioral changes and oligodendrocyte loss in male C57BL/7 mice via its anti‐inflammation actions

Previous animal studies have linked white matter damage to certain schizophrenia‐like behaviors in cuprizone (CPZ)‐exposed mouse. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and oligodendrocyte loss coexist in the brain of such mice. The aim of this study was to examine effects of the antioxidant N‐acetylcysteine (NAC) on CPZ‐induced behavioral changes and concurrent oligodendrocyte loss, oxidative stress, and neuroinflammation in these animals. Male C57BL/6 mice were given intraperitoneal saline or NAC at doses of 100, 200, and 400 mg/kg/day for 2 weeks; animals were fed a CPZ‐containing diet (0.2%, w/w) during days 5–14. During days 15–17, the mice were examined in open‐field, social recognition, and Y‐maze tests (1 test per day). Six mice in each group were then used for biochemical and enzyme‐linked immunosorbent assay analyses, while the remaining animals were used for immunohistochemical and immunofluorescence staining. The mice exposed to CPZ for 10 days showed significantly lower spontaneous alternation in the Y‐maze, lower activity of total superoxide dismutase, and glutathione peroxidase, but higher levels of malondialdehyde in the cerebral cortex and hippocampus, elevated concentrations of interleukin‐1β and tumor necrosis factor‐α in the brain regions mentioned above and caudate putamen, and a decreased number of mature oligodendrocytes, but increased number of microglia in all the brain regions examined. These changes, however, were not seen or effectively alleviated in NAC‐treated mice at all three doses. These results demonstrate that NAC protected mature oligodendrocytes against the toxic effects of CPZ, likely via its antioxidant and anti‐inflammatory actions.
Miscoding-induced stalling of substrate translocation on the bacterial ribosome

Significance Using single-molecule FRET imaging, we show that programmed base-pair mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically prolong elongation factor G (EF-G)–catalyzed translocation. Mismatched peptidyl-tRNA–mRNA pairing within the pretranslocation complex specifically inhibits peptidyl-tRNA engagement of the small subunit P site, a rate-limiting process in translocation characterized by large-scale, intramolecular conformational changes within the EF-G(GDP)–bound ribosome complex. Consistent with the E site being vacant during this period, we find that elongation factor P (EF-P) can rescue this translocation defect. These findings reveal an unexpected relationship between tRNA decoding at the A site and translocation, and suggest an alternative mode of action for miscoding-inducing drugs as well as a novel function of EF-P in the cell to rescue ribosomes stalled by miscoding errors. Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates wherein peptidyl-tRNA enters the P site of the small ribosomal subunit via reversible, swivel-like motions of the small subunit head domain within the elongation factor G (GDP)-bound ribosome complex. Consistent with translocation being rate-limited by recognition and productive engagement of peptidyl-tRNA within the P site, we now show that base-pairing mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically delay this rate-limiting, intramolecular process. This unexpected relationship between aminoacyl-tRNA decoding and translocation suggests that miscoding antibiotics may impact protein synthesis by impairing the recognition of peptidyl-tRNA in the small subunit P site during EF-G–catalyzed translocation. Strikingly, we show that elongation factor P (EF-P), traditionally known to alleviate ribosome stalling at polyproline motifs, can efficiently rescue translocation defects arising from miscoding. These findings help reveal the nature and origin of the rate-limiting steps in substrate translocation on the bacterial ribosome and indicate that EF-P can aid in resuming translation elongation stalled by miscoding errors.
Gender Separation Increases Somatic Growth in Females but Does Not Affect Lifespan in Nothobranchius furzeri

According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all.