Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression, cloning, and characterization of a Candida albicans gene, ALA1, that confers adherence properties upon Saccharomyces cerevisiae for extracellular matrix proteins

Adherence of Candida albicans to host tissues is a necessary step for maintenance of its commensal status and is likely a necessary step in the pathogenesis of candidiasis. The extracellular matrix (ECM) proteins are some of the host tissue and plasma proteins to which C. albicans adheres through adhesins located on the fungal cell surface. To isolate genes encoding ECM adhesins, an assay was developed based on the ability of yeast cells to adhere to magnetic beads coated with the ECM protein fibronectin, type IV collagen, or laminin. A C. albicans genomic library was constructed by cloning XbaI-partially-digested and size-selected fragments into pAUR112, an Escherichia coli-yeast low-copy-number shuttle vector. The C. albicans library was transformed into Saccharomyces cerevisiae YPH 499, and clones capable of adherence were selected by using ECM protein-coated magnetic beads. A plasmid containing an approximately 8-kb insert was isolated from 29 adherent clones. These clones exhibited adherence to all ECM protein-coated magnetic beads and to human buccal epithelial cells. The ALA1 gene (for agglutinin-like adhesin) was localized by subcloning it into a 5-kb XbaI fragment which retained the adherence phenotype in both orientations. The complete DNA sequence of the 5-kb insert was determined, and an open reading frame (ORF) encoding 1,419 amino acid residues was identified. Deletions from the 5' and 3' ends extending into the DNA sequence encoding the 1,419-amino-acid ORF product inactivated the adherence phenotype, suggesting that it is the coding region of the ALA1 gene. A database search identified ALA1 to be similar to the C. albicans ALS1 (for agglutinin-like sequence 1) protein and the S. cerevisiae agglutinin protein (AG alpha1), although the homology at the primary amino acid sequence level is limited to the first half of each of these proteins. ALA1 contains a central domain of six tandem repeats of 36 amino acids. We discuss the significance of various predicted ALA1 structural motifs and their relationships to function in the adherence process.
Dietary Beliefs and Behaviors Among Parents of Children with Inflammatory Bowel Disease.

Diet is regarded as one of the important environmental factors triggering inflammatory bowel disease (IBD). Many IBD patients avoid numerous types of foods in fear of disease exacerbation. The aim of the study was to investigate dietary beliefs and food avoidance among pediatric patients with IBD. This questionnaire-based study was conducted in three University-affiliated children's hospitals in Poland. Data were collected from parents of children who were diagnosed with IBD. A total of 155 parents of IBD patients participated in the survey: 104 (67.1%) had a child with Crohn's disease and 51 (32.9%) with ulcerative colitis. Parents of older children and those with longer disease duration predicted diet being considered one of the causative agents of IBD, and differences were statistically significant (P = .01 and P = .04, respectively). Also, patients with a shorter history of disease rarely shared food with other family members (P = .02). In total, 61.5% of patients avoided some kind of food in fear of disease flares. In the parent's opinion, the food the children liked but avoided included fried dishes, sweets (e.g., chocolate, cookies, cakes, candies, jellies), and fast food. Due to their dietary beliefs, parents of children with IBD commonly introduced dietary restrictions for their offspring. Frequent and unjustified food avoidance may influence not only nutritional status but also general well-being of pediatric patients. Our results underscore the urgent need for IBD patients and parents of ill children to receive reliable dietary advice based on strong scientific evidence.
Isotypic Decompositions of Lattice Determinants

Theq,t-Macdonald polynomials are conjectured by Garsia and Haiman to have a representation theoretic interpretation in terms of theSn-moduleM? spanned by the derivatives of a certain polynomial? (x1,x2,? ,xn;y1,y2,? ,yn). The diagonal action of a permutation? Snon a polynomialP=P(x1,x2,? ,xn;y1 ,y2,? ,yn) is defined by setting? P=P(x? 1,x? 2< F,? ,x? n;y? 1,y? 2,? ,y? n). Since the polynomial? alternates under the diagonal action,M? isSn-invariant. We analyze here the diagonal action ofSnonM? and show that its decomposition into irreducibles is equivalent to a certain isotypic expansion for the translate? (x1+x? 1,x2+x ? 2,? ,xn+x? n;y1+y? 1,y2+y? 2,? ,yn +y? n) of the polynomial?
INNOVATIONS IN WOOD-BASED PROCESS INDUSTRIES IN TRANSITION : MANAGEMENT & POLICY IMPLICATIONS

EXTENDED ABSTRACT As any mature industry the forest industries have gone through many transformations and structural changes. Historically, forest industries in the Northern hemisphere (North America and Northern European countries) have been rather successful by moving forward in the value chain in order to avoid market decline or raw material shortage (Hylander 2009). From timber exports and charcoal in the 17th-18th century; sawmill products in the 19th century; pulp and papermaking transformed by using sawmill residues in the early 20th century for production of graphic papers; and by inventing chemical pulping technologies in the early 20th century particularly for hygiene products and stronger paperboard which expanded in the mid-20th century. However, in recent decades the pulp and paper industries located in the Northern hemisphere are confronted by manifold challenges while the incumbents has got stuck into its " big is beautiful " paradigm. Most of these challenges are connected to global transformation pressures, due to digitalization and multimedia (i.e. decline of printed media), competition from fast-growing economies in the Southern hemisphere, uncertain energy supplies, and environmental challenges (not least climate change) which increase the pressure on resource intensive process industries such as the pulp and paper industries in Western industry nations (UNECE/FAO 2009/2011). In this short paper I will concentrate on the nature of innovation in pulp and paper industries (P&P), the largest biomass infrastructure on earth, and its implications for management and policymakers. The point of departure is the academic discourse on disruptive innovation followed by industry specific cases in order to explain the nature of innovation in process industries. Clayton Christensen (2000) settled an important distinction between disruptive and sustaining innovations. A disruptive innovation is an innovation that generates a new market and value chain, and finally disrupts an established market and value chain by shifting trajectory or replacing earlier technologies. A sustaining innovation may be looked upon as either incremental (or evolutionary) or a more radical innovation. The incremental innovation contains gradual upgrading that improves a product in an existing market by means that customers are expecting, while the more radical innovation contains a major shift and
Effect of a Single Aspirin Dose Prior to Fecal Immunochemical Testing on Test Sensitivity for Detecting Advanced Colorectal Neoplasms: A Randomized Clinical Trial

Importance Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men. Objective To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling. Design, Setting, and Participants A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017). Interventions Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test. Main Outcome and Measures The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-&mgr;g Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma). Results Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, −3.1% to 22.2%, P = .14) at cutoff 10.2-&mgr;g Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, −5.7% to 17.5%, P = .32) at cutoff 17-&mgr;g Hb/g stool. Conclusions and Relevance Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test. Trial registration Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE
The Structure of a Chondroitin Sulfate-binding Domain Important in Placental Malaria

Adhesive PfEMP1 proteins are displayed on the surface of malaria-infected red blood cells. They play a critical role in the disease, tethering infected cells away from destruction by the spleen and causing many severe symptoms. A molecular understanding of how these domains maintain their binding properties while evading immune detection will be important in developing therapeutics. In malaria of pregnancy, domains from the var2csa-encoded PfEMP1 protein interact with chondroitin sulfate on the placenta surface. This causes accumulation of infected red blood cells, leading to placental inflammation and block of blood flow to the developing fetus. This is associated with maternal anemia, low birth weight, and premature delivery and can lead to the death of mother and child. Here I present the structure of the chondroitin sulfate-binding DBL3X domain from a var2csa-encoded PfEMP1 protein. The domain adopts a fold similar to malarial invasion proteins, with extensive loop insertions. One loop is flexible in the unliganded structure but observed in the presence of sulfate or disaccharide, where it completes a sulfate-binding site. This loop, and others surrounding this putative carbohydrate-binding site, are flexible and polymorphic, perhaps protecting the binding site from immune detection. This suggests a model for how the domain maintains ligand binding while evading the immune response and will guide future drug and vaccine development.
Protective Influence of Phyllanthus Muellarianus on Ciprofloxacin-Induced Neurotoxicity in Male Rats

Abstract Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) leaves are widely used in the treatment of neurological disorders in Nigeria. We investigated the protective effect of aqueous leaf extract of Phyllanthus muellarianus on ciprofloxacin neurotoxicity in male rats. Control rats (Group A) received distilled water, Groups C–E According to the Animal grouping and treatment section, Group B did not receive P. muellarianus> rats were administered 100, 200, and 400 mg/kg body weight P. muellarianus, respectively, and Group F rats received 200 mg/kg body weight valproate orally for 7 days. In addition, groups B–F rats were orally administered ciprofloxacin for 7 days. Motor coordination and motor function were assessed using narrow beam and landing foot splay distance. The levels of neurotransmitter and oxidative stress biomarkers were also determined. Aqueous leaf extract of P. muellarianus significantly attenuated ciprofloxacin-mediated increases in narrow beam, landing foot splay distance, and gait scores. Ciprofloxacin-mediated depletion of acetylcholine and dopamine in the brains of rats was significantly annulled by P. muellarianus. Furthermore, the extract significantly reversed ciprofloxacin-mediated increases in acetylcholinesterase, monoamine oxidase A, and monoamine oxidase B by 73.13%, 71.52%, and 86.54%, respectively. The altered biomarkers of oxidative stress were significantly reversed by P. muellarianus. Overall, the results of this study show that P. muellarianus reversed ciprofloxacin-induced neurotoxicity by restoring ciprofloxacin-mediated alterations in acetylcholine, dopamine, acetylcholinesterase, monoaminergic enzymes, and oxidative stress biomarkers in the brains of rats.
Live imaging of ERK signalling dynamics in differentiating mouse embryonic stem cells

ABSTRACT Stimulation of the ERK/MAPK pathway is required for the exit from pluripotency and onset of differentiation in mouse embryonic stem cells (ESCs). The dynamic behaviour of ERK activity in individual cells during this transition is unclear. Using a FRET-based biosensor, we monitored ERK signalling dynamics of single mouse ESCs during differentiation. ERK activity was highly heterogeneous, with considerable variability in ERK signalling between single cells within ESC colonies. Different triggers of differentiation induced distinct ERK activity profiles. Surprisingly, the dynamic features of ERK signalling were not strongly coupled to loss of pluripotency marker expression, regardless of the differentiation stimulus, suggesting the normal dynamic range of ERK signalling is not rate-limiting in single cells during differentiation. ERK signalling dynamics were sensitive to the degree of cell crowding and were similar in neighbouring cells. Sister cells from a mitotic division also showed more similar ERK activity, an effect that was apparent whether cells remained adjacent or moved apart after division. These data suggest a combination of cell lineage and niche contributes to the absolute level of ERK signalling in mouse ESCs. Summary: Live imaging of ERK activity reveals a cell lineage component to signalling strength and suggests the normal variation in ERK activity does not determine the rate of pluripotency exit.
Eps15 Homology Domain-NPF Motif Interactions Regulate Clathrin Coat Assembly during Synaptic Vesicle Recycling*

Although genetic and biochemical studies suggest a role for Eps15 homology domain containing proteins in clathrin-mediated endocytosis, the specific functions of these proteins have been elusive. Eps15 is found at the growing edges of clathrin-coated pits, leading to the hypothesis that it participates in the formation of coated vesicles. We have evaluated this hypothesis by examining the effect of Eps15 on clathrin assembly. We found that although Eps15 has no intrinsic ability to assemble clathrin, it potently stimulates the ability of the clathrin adaptor protein, AP180, to assemble clathrin at physiological pH. We have also defined the binding sites for Eps15 on squid AP180. These sites contain an NPF motif, and peptides derived from these binding sites inhibit the ability of Eps15 to stimulate clathrin assembly in vitro. Furthermore, when injected into squid giant presynaptic nerve terminals, these peptides inhibit the formation of clathrin-coated pits and coated vesicles during synaptic vesicle endocytosis. This is consistent with the hypothesis that Eps15 regulates clathrin coat assembly in vivo, and indicates that interactions between Eps15 homology domains and NPF motifs are involved in clathrin-coated vesicle formation during synaptic vesicle recycling.
Grouping of Poorly Soluble Low (Cyto)Toxic Particles: Example with 15 Selected Nanoparticles and A549 Human Lung Cells

Poorly soluble, low (cyto)toxic particles (PSLTs) are often regarded as one group, but it is important that these particles can be further differentiated based on their bioactivity. Currently, there are no biological endpoint based groupings for inhaled nanoparticles (NPs) that would allow us to subgroup PSLTs based on their mode of action. The aim of this study was to group NPs based on their cytotoxicity and by using the in vitro response of the endo-lysosomal system as a biological endpoint. The endo-lysosomal system is a main cellular loading site for NPs. An impaired endo-lysosomal system in alveolar type II cells may have serious adverse effects on the maintenance of pulmonary surfactant homeostasis. The 15 different NPs were tested with human lung adenocarcinoma (A549) cells. The highly soluble NPs were most cytotoxic. With respect to PSLTs, only three NPs increased the cellular load of acid and phospholipid rich organelles indicating particle biopersistence. All the rest PSLTs could be regarded as low hazardous. The presented in vitro test system could serve as a fast screening tool to group particles according to their ability to interfere with lung surfactant metabolism. We discuss the applicability of the suggested test system for bringing together substances with similar modes-of-action on lung epithelium. In addition, we discuss this approach as a benchmark test for the comparative assessment of biopersistence of PSLTs.
Effect of metabolic syndrome on prognosis and clinical characteristics of revascularization in patients with coronary artery disease

Background People with metabolic syndrome are at higher risk for developing coronary artery disease (CAD). The effect of the metabolic syndrome on outcomes in patients with preexisting CAD has not been well studied. This study was conducted to assess the prevalence, characteristics, in hospital and long term prognosis of CAD with metabolic syndrome and to determine the factors influencing the prognosis of the disease. Methods The DESIRE registry contains data of 3696 patients with CAD between 2001 and 2004. Mean long term followup was (829±373) days. Diagnosis of metabolic syndrome was based on modified International Diabetes Federation (IDF) Worldwide Definition of the Metabolic Syndrome, using body mass index (BMI) instead of waist circumference. Results Of 2596 patients with complete records of height, weight, and so on, 1280 (49.3%) were identified with metabolic syndrome. The patients with metabolic syndrome had higher level of body mass index, systolic blood pressure, diastolic blood pressure, fasting glucose and disordered blood lipid (all P<0.0001), with higher creatinine [(10.5±4.3) mg/L vs (9.9±2.9) mg/L, P<0.0001] and the number of white blood cells [(7.49±2.86) ×109/L vs (7.19±2.62) ×109/L, P=0.008) compared with those without metabolic syndrome. The patients with metabolic syndrome showed severer coronary angiographic alterations (left main artery and/or ≥2‐vessel) (73.6% vs 69.6%, P=0.031). There were no significant differences of major adverse cardiac and cerebral events (MACCE) or mortality in hospital between the two groups. During followup, the ratio of MACCE in CAD with metabolic syndrome patients increased significantly (11.8% vs 10.0%, P=0.044). Fasting blood glucose (≥1000 mg/L) and triglyceride (TG, ≥1500 mg/L) were responsible for most of the increased risk associated with the metabolic syndrome (adjusted OR 1.465, 95% CI 1.037–1.874, P=0.032; OR 1.378, 95% CI 1.014–1.768, P=0.044). Conclusions The prevalence of metabolic syndrome was very high in CAD patients. The metabolic syndrome confers a higher risk of long term MACCE in patients with CAD, and dysglycaemia and hypertriglycaemia appear to be responsible for most of the associated risk. Chin Med J2006;119(22):1871–1876
Relationship Between Genetic Polymorphisms of the TNF Gene and Hallux Valgus Susceptibility.

Background: Hallux valgus (HV) is a type of forefoot deformity affecting ∼23% of adults. Previous studies have shown that HV is highly heritable. Tumor necrosis factor (TNF) is an important proinflammatory cytokine involved in bone remodeling and plays essential roles in osteoarthritis and chronic inflammatory bone diseases, including HV. Methods: A total of 1,788 Chinese women comprising 637 HV subjects and 1,151 controls were recruited. Twelve single nucleotide polymorphisms (SNPs) located in TNF and its promoter regions were selected and genotyped. Genetic association analyses were performed to investigate potential susceptibility SNPs. Bioinformatic and expression quantitative trait loci (eQTL) analyses were conducted to examine the functional consequences of the SNPs identified as being significantly associated with HV. Results: SNP rs1800629, which is located at the 5' end of the promoter region of TNF, was identified as significantly associated with HV status in Chinese women (OR = 0.56, p = 2.12 × 10-6). Bioinformatic analyses using RegulomeDB indicated that this SNP has important functional significance, but subsequent eQTL analyses did not identify a significant association between rs1800629 and TNF gene expression. In addition, 26 genes with cis-eQTL for rs1800629 were identified. Conclusions: This study identified a susceptibility SNP for HV located within the promoter region of the TNF gene. Bioinformatic and eQTL analyses linked this SNP to 26 genes but not to TNF. Functional studies are needed to more fully characterize the effects of this SNP.