Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined MEK and Pi3′-kinase inhibition reveals synergy in targeting thyroid cancer in vitro and in vivo

Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3′-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo. The combination of MEK and Pi’3-kinase inhibition shows a synergistic effect in term of proliferation and apoptosis induction through Survivin down-regulation in vitro. We show for the first time the effects of the combination of a MEK inhibitor and Pi3′-kinase inhibitor in a genetically engineered mouse model of aggressively lethal thyroid cancer. In fine, the two drugs cooperate to promote tumor shrinkage by inducing a proliferation arrest and an elevation of apoptosis in vivo. Moreover, a phenotypic reversion is also observed with a partial restoration of normal thyroid marker transcription, and thyroid cancer marker expression reduction. In conclusion, combination therapy of MEK and Pi3′-kinase inhibition synergizes to target double mutant thyroid cancer in vitro and in vivo. This multidrug approach could readily be translated into clinical practice and bring new perspectives for the treatment of incurable thyroid carcinoma.
Comparative Phylogeography in Rainforest Trees from Lower Guinea, Africa

Comparative phylogeography is an effective approach to assess the evolutionary history of biological communities. We used comparative phylogeography in fourteen tree taxa from Lower Guinea (Atlantic Equatorial Africa) to test for congruence with two simple evolutionary scenarios based on physio-climatic features 1) the W-E environmental gradient and 2) the N-S seasonal inversion, which determine climatic and seasonality differences in the region. We sequenced the trnC-ycf6 plastid DNA region using a dual sampling strategy: fourteen taxa with small sample sizes (dataset 1, mean n = 16/taxon), to assess whether a strong general pattern of allele endemism and genetic differentiation emerged; and four taxonomically well-studied species with larger sample sizes (dataset 2, mean n = 109/species) to detect the presence of particular shared phylogeographic patterns. When grouping the samples into two alternative sets of two populations, W and E, vs. N and S, neither dataset exhibited a strong pattern of allelic endemism, suggesting that none of the considered regions consistently harboured older populations. Differentiation in dataset 1 was similarly strong between W and E as between N and S, with 3–5 significant F ST tests out of 14 tests in each scenario. Coalescent simulations indicated that, given the power of the data, this result probably reflects idiosyncratic histories of the taxa, or a weak common differentiation pattern (possibly with population substructure) undetectable across taxa in dataset 1. Dataset 2 identified a common genetic break separating the northern and southern populations of Greenwayodendron suaveolens subsp. suaveolens var. suaveolens, Milicia excelsa, Symphonia globulifera and Trichoscypha acuminata in Lower Guinea, in agreement with differentiation across the N–S seasonal inversion. Our work suggests that currently recognized tree taxa or suspected species complexes can contain strongly differentiated genetic lineages, which could lead to misinterpretation of phylogeographic patterns. Therefore the evolutionary processes of such taxa require further study in African tropical rainforests.
Time, Temperature, and Cationic Dependence of Alkali Activation of Slag: Insights from Fourier Transform Infrared Spectroscopy and Spectral Deconvolution

The use of waste/by-product materials, such as slag or fly ash, activated using alkaline agents to create binding materials for construction applications (in lieu of portland cement) is on the rise. The influence of activation parameters (SiO2 to Na2O ratio or Ms of the activator, Na2O to slag ratio or n, cation type K+ or Na+) on the process and extent of alkali activation of slag under ambient and elevated temperature curing, evaluated through spectroscopic techniques, is reported in this paper. Fourier transform infrared spectroscopy along with a Fourier self-deconvolution method is used. The major spectral band of interest lies in the wavenumber range of ∼950 cm−1, corresponding to the antisymmetric stretching vibration of Si–O–T (T = Si or Al) bonds. The variation in the spectra with time from 6 h to 28 days is attributed to the incorporation of Al in the gel structure and the enhancement in degree of polymerization of the gel. 29Si nuclear magnetic resonance spectroscopy is used to quantify the Al incorporation with time, which is found to be higher when Na silicate is used as the activator. The Si–O–T bond wavenumbers are also generally lower for the Na silicate activated systems.
Assessing universality of DNA barcoding in geographically isolated selected desert medicinal species of Fabaceae and Poaceae

In pursuit of developing fast and accurate species-level molecular identification methods, we tested six DNA barcodes, namely ITS2, matK, rbcLa, ITS2+matK, ITS2+rbcLa, matK+rbcLa and ITS2+matK+rbcLa, for their capacity to identify frequently consumed but geographically isolated medicinal species of Fabaceae and Poaceae indigenous to the desert of Cholistan. Data were analysed by BLASTn sequence similarity, pairwise sequence divergence in TAXONDNA, and phylogenetic (neighbour-joining and maximum-likelihood trees) methods. Comparison of six barcode regions showed that ITS2 has the highest number of variable sites (209/360) for tested Fabaceae and (106/365) Poaceae species, the highest species-level identification (40%) in BLASTn procedure, distinct DNA barcoding gap, 100% correct species identification in BM and BCM functions of TAXONDNA, and clear cladding pattern with high nodal support in phylogenetic trees in both families. ITS2+matK+rbcLa followed ITS2 in its species-level identification capacity. The study was concluded with advocating the DNA barcoding as an effective tool for species identification and ITS2 as the best barcode region in identifying medicinal species of Fabaceae and Poaceae. Current research has practical implementation potential in the fields of pharmaco-vigilance, trade of medicinal plants and biodiversity conservation.
Wake-up stroke is not associated with sleep-disordered breathing in women

Background We sought to investigate the frequency of wake-up stroke (WUS) and its association with sleep-disordered breathing (SDB) in women. Methods Within a population-based study, women with acute ischemic stroke were asked about their stroke symptom onset time. SDB screening was performed with the well-validated ApneaLink Plus device; SDB was defined by a respiratory event index ≥10. Logistic regression was used to test the association between SDB presence and severity and WUS unadjusted and adjusted for potential confounders including prestroke depression and sleep duration. Results Among 466 participants, the median age was 67.0 years (interquartile range [IQR] 58.0, 77.0), 55% were Mexican American, and the median initial NIH Stroke Scale score was 3.0 (IQR 1.0, 6.0). Stroke symptom onset occurred during nocturnal sleep (25.3%), during a nap (3.9%), during wakefulness (65.9%), or unknown (4.9%). In those with SDB screening performed (n = 259), a median of 11 days (IQR 5, 17) poststroke, WUS was not associated with the presence or severity (respiratory event index) of SDB in unadjusted or adjusted analysis. Conclusions In this population-based study, WUS represented about 30% of all generally mild severity ischemic strokes in women and was not associated with SDB.
Laser-Induced Photofragmentation Fluorescence Imaging of Alkali Compounds in Flames

Laser-induced photofragmentation fluorescence has been investigated for the imaging of alkali compounds in premixed laminar methane–air flames. An ArF excimer laser, providing pulses of wavelength 193 nm, was used to photodissociate KCl, KOH, and NaCl molecules in the post-flame region and fluorescence from the excited atomic alkali fragment was detected. Fluorescence emission spectra showed distinct lines of the alkali atoms allowing for efficient background filtering. Temperature data from Rayleigh scattering measurements together with simulations of potassium chemistry presented in literature allowed for conclusions on the relative contributions of potassium species KOH and KCl to the detected signal. Experimental approaches for separate measurements of these components are discussed. Signal power dependence and calculated fractions of dissociated molecules indicate the saturation of the photolysis process, independent on absorption cross-section, under the experimental conditions. Quantitative KCl concentrations up to 30 parts per million (ppm) were evaluated from the fluorescence data and showed good agreement with results from ultraviolet absorption measurements. Detection limits for KCl photofragmentation fluorescence imaging of 0.5 and 1.0 ppm were determined for averaged and single-shot data, respectively. Moreover, simultaneous imaging of KCl and NaCl was demonstrated using a stereoscope with filters. The results indicate that the photofragmentation method can be employed for detailed studies of alkali chemistry in laboratory flames for validation of chemical kinetic mechanisms crucial for efficient biomass fuel utilization.
Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies

Introduction: Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs that inhibit the pro-inflammatory effects of lipopolysaccharide (LPS) and improve outcome when added to conventional sepsis treatments are lacking. Eritoran tetrasodium (E5564) is a promising candidate therapy for sepsis belonging to a new class of such drugs which inhibit LPS-induced inflammation by blocking toll-like receptor 4. Areas covered: This review focuses on the rationale for the use of eritoran tetrasodium in sepsis as well as on its pharmacokinetics, pharmacodynamics, efficacy and safety. Preclinical and clinical studies from a MEDLINE/PubMed literature search in August 2010 with the search terms ‘eritoran’ and ‘E5564’ are discussed. Expert opinion: Preclinical in vitro and in vivo studies of eritoran tetrasodium indicate it can limit excessive inflammatory mediator release associated with LPS and improve survival in sepsis models. While early clinical results are promising, its efficacy and safety for treating patients with sepsis are currently under investigation. Even if the ongoing Phase III clinical trial enrolling patients with severe sepsis and increased risk of death shows benefit from eritoran, questions remain and confirmatory studies would be necessary to define its clinical usage.
microRNAs involved in auxin signalling modulate male sterility under high‐temperature stress in cotton (Gossypium hirsutum)

Male sterility caused by long-term high-temperature (HT) stress occurs widely in crops. MicroRNAs (miRNAs), a class of endogenous non-coding small RNAs, play an important role in the plant response to various abiotic stresses. To dissect the working principle of miRNAs in male sterility under HT stress in cotton, a total of 112 known miRNAs, 270 novel miRNAs and 347 target genes were identified from anthers of HT-insensitive (84021) and HT-sensitive (H05) cotton cultivars under normal-temperature and HT conditions through small RNA and degradome sequencing. Quantitative reverse transcriptase-polymerase chain reaction and 5'-RNA ligase-mediated rapid amplification of cDNA ends experiments were used to validate the sequencing data. The results show that miR156 was suppressed by HT stress in both 84021 and H05; miR160 was suppressed in 84021 but induced in H05. Correspondingly, SPLs (target genes of miR156) were induced both in 84021 and H05; ARF10 and ARF17 (target genes of miR160) were induced in 84021 but suppressed in H05. Overexpressing miR160 increased cotton sensitivity to HT stress seen as anther indehiscence, associated with the suppression of ARF10 and ARF17 expression, thereby activating the auxin response that leads to anther indehiscence. Supporting this role for auxin, exogenous Indole-3-acetic acid (IAA) leads to a stronger male sterility phenotype both in 84021 and H05 under HT stress. Cotton plants overexpressing miR157 suppressed the auxin signal, and also showed enhanced sensitivity to HT stress, with microspore abortion and anther indehiscence. Thus, we propose that the auxin signal, mediated by miRNAs, is essential for cotton anther fertility under HT stress.
The effects of inactivation methods of Yersinia ruckeri on the efficacy of single dip vaccination in Atlantic salmon (Salmo salar).

Yersinia ruckeri causes significant losses in farmed salmonids (Tobback et al., 2009) and is the causative agent of both enteric red mouth disease in rainbow trout in the Northern Hemisphere (Tobback et al., 2009) and yersiniosis in Atlantic salmon (Salmo salar) in the Southern Hemisphere (Carson & Wilson, 2009). The first commercial yersiniosis vaccine was licensed in 1976 as formalin-killed whole cells of Y. ruckeri (see Bridle, Koop, & Nowak, 2012). Formalin inactivation is most commonly used for commercial fish vaccine production (Sommerset, Krossoy, Biering, & Frost, 2005). Inactivation of bacteria by formalin influences the physicochemical characteristics of surface antigens and may reduce protective efficacy against pathogenic bacteria (Tu, Chu, Zhuang, & Lu, 2010).
Harnessing Neutrophil Survival Mechanisms during Chronic Infection by Pseudomonas aeruginosa: Novel Therapeutic Targets to Dampen Inflammation in Cystic Fibrosis

More than two decades after cloning the cystic fibrosis transmembrane regulator (CFTR) gene, the defective gene in cystic fibrosis (CF), we still do not understand how dysfunction of this ion channel causes lung disease and the tremendous neutrophil burden which persists within the airways; nor why chronic colonization by Pseudomonas aeruginosa develops in CF patients who are thought to be immunocompetent. It appears that the microenvironment within the lung of CF patients provides favorable conditions for both P. aeruginosa colonization and neutrophil survival. In this context, the ability of bacteria to induce hypoxia, which in turn affects neutrophil survival is an additional level of complexity that needs to be accounted for when controlling neutrophil fate in CF. Recent studies have underscored the importance of neutrophils in innate immunity and their functions appear to extend far beyond their well-described role in antibacterial defense. Perhaps a disturbance in neutrophil reprogramming during the course of an infection severely modulates the inflammatory response in CF. Furthermore there is an emerging concept that the CFTR itself may be an immune modulator and stimulating CFTR function in CF patients could promote neutrophil and macrophages antimicrobial function. Fostering the resolution of inflammation by favoring neutrophil apoptosis could preserve their microbicidal activities but decrease their proinflammatory potential. In this context, triggering neutrophil apoptosis with roscovitine may be a potential therapeutic option and this is currently being evaluated in CF patients. In the present review we discuss how neutrophils functions are disturbed in CF and how this may relate to chronic infection with P. aeuginosa and we propose novel research directions aimed at modulating neutrophil survival, dampening lung inflammation and ultimately leading to an amelioration of the lung disease.
Effect of Feeding ofTinospora cordifoliaon Immune Response in Cattle

Thirty two apparently healthy local non descript cows were experimentally divided into two groups viz. treatment and control group having 16 animals each. The animals under treatment group were fed dried stem powder of Tinospora cordifolia (100 mg/kg BW) by mixing it in concentrate mixture for a period of 5 days. The control group animals were fed equal amount of the basal concentrate mixture without T. cordifolia supplementation. Blood and serum samples collected on day 0, 15, 30 and 45 day after feeding of T. cordifolia were subjected for concentration and purification of IgG, phagocytic activity by neutrophils, T cell count and haemolytic complement activity to assess the level of immune response in animals. Significant increase (P 0.05) between treatment and control group. In conclusion, it can be stated that T. cordifolia feeding had significant immunomodulatory effect in cows.
UBE2T knockdown inhibits gastric cancer progression

Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in which nude mice were injected with UBE2T knockdown human gastric cancer cells confirmed that suppression of UBE2T also decreased tumor formation and growth in vivo. Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were all affected by UBE2T knockdown. These results suggest that UBE2T plays a critical role in gastric cancer, and that it may serve as a useful prognostic biomarker and therapeutic target in gastric cancer patients.
HIV-related thought avoidance, sexual risk, and alcohol use among men who have sex with men

ABSTRACT HIV-related “cognitive escape” refers to a tendency to avoid thoughts associated with HIV, which may be particularly common among men who have sex with men (MSM) who are often inundated with HIV information, potentially to the point of fatigue. HIV-related cognitive escape is associated with increased sexual risk behaviors, such as condomless sex, and heavier alcohol use patterns. Other studies show that some MSM may use alcohol specifically to facilitate sex. These sexual motives for drinking (SMDs) could be one mechanism whereby cognitive escape leads to health risk behaviors. In this study, we tested models exploring whether cognitive escape was associated with markers of sex risk (condom use, number of sex partners) and alcohol use/problems, and examined whether SMDs mediated these associations. Heavy drinking, HIV-negative men (N = 196) aged ≥ 21 years who self-reported past year condomless anal sex with men completed assessments as part of a larger study. Results suggest that cognitive escape was associated with higher number of anal sex partners (incidence rate ratio [IRR] = 1.50, SE = 0.04, p < .001), decreased condom use (B = −0.30, SE = 0.14, p = .028), and increased alcohol-related problems (IRR = 1.28, SE = 0.07, p = .001) but not with drinking quantity. Sexual motives for drinking appeared to partially mediate the observed relationship between cognitive escape and alcohol-related problems, but other relationships did not show evidence of mediation. Findings suggest that those who tend to avoid HIV-related thoughts may be at increased risk for HIV and alcohol-related problems. Drinking to facilitate sex may partially account for the higher risk for alcohol-related problems conferred by cognitive escape. Alcohol interventions for MSM may be more effective if they address alcohol’s role in coping with HIV threat and in facilitating sex under these circumstances.
Mutation Screening of the Krüppel-like Factor 1 Gene in Individuals With Increased Fetal Hemoglobin Referred for Hemoglobinopathy Investigation in South of Iran

Background: Any mutation in the Krüppel-like factor 1 (KLF1) gene may interfere with its proper related function in the erythropoiesis process and lead to alterations in proper activation of its downstream protein through globin switching, which results in an increase in fetal hemoglobin (HbF). This study aimed to investigate whether KLF1 mutation can associate with high level of HbF in individuals with increased fetal hemoglobin referred for screening of hemoglobinopathies in south of Iran. Materials and Methods: The human KLF1 gene was amplified via the polymerase chain reaction procedure, and sequencing was used to determine any mutation in these patients. Moreover, XmnI polymorphisms in the position of −158 of &ggr;-globin gene promoter were analyzed in all patients by polymerase chain reaction restriction fragment length polymorphism. Result: Analysis of sequencing revealed a missense mutation in the KLF1 gene, p.Ser102Pro (c.304T>C), which was detectable in 10 of 23 cases with elevated HbF level. This mutation was only detected in individuals who had a HbF level between 3.1% and 25.6%. Statistical analysis showed that the frequency of C allele is significantly correlated with a high level of HbF (P<0.05). The allele frequency of positive result of XmnI polymorphism in individuals with increased HbF level was also significant, which showed an association with increased HbF level (P<0.05). Conclusions: To the best of our knowledge, this is the first report of p.Ser102Pro (c.304T>C) in the KLF1 gene in &bgr;-thalassemia patients with increased level of fetal hemoglobin. According to statistical results of p.Ser102Pro mutation and XmnI polymorphism, it has been strongly suggested that both polymorphisms have an association with increased HbF samples. These nucleotide changes alone may not be the only elements raising the level of HbF, and other regulatory and modifying factors also play a role in HbF production.
Predatory strategies and behaviours in cephalopods are altered by elevated CO2

There is increasing evidence that projected near‐future carbon dioxide (CO2) levels can alter predator avoidance behaviour in marine invertebrates, yet little is known about the possible effects on predatory behaviours. Here we tested the effects of elevated CO2 on the predatory behaviours of two ecologically distinct cephalopod species, the pygmy squid, Idiosepius pygmaeus, and the bigfin reef squid, Sepioteuthis lessoniana. Both species exhibited an increased latency to attack and altered body pattern choice during the attack sequence at elevated CO2. I. pygmaeus also exhibited a 20% decrease in predation rate, an increased striking distance, and reduced preference for attacking the posterior end of prey at elevated CO2. Elevated CO2 increased activity levels of S. lessoniana comparable to those previously shown in I. pygmaeus, which could adversely affect their energy budget and increase their potential to be preyed upon. The effects of elevated CO2 on predatory behaviours, predation strategies and activity levels of cephalopods reported here could have far‐reaching consequences in marine ecosystems due to the ecological importance of cephalopods in the marine food web.