Miracle-dz/UniFAR-FTUs huggingface dataset:
Control of Cytokine mRNA Expression by RNA-binding Proteins and microRNAs

Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post- transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFα, IL-6, and IL-8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3′-untranslated regions (3′UTRs) of the mRNAs. Numerous RNA-binding proteins and microRNAs bind to these 3′UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression.
The Presence of IL-17+/FOXP3+ Double-positive Cells in Periodontitis

Increasing evidence suggests that distinct inflammatory cytokines convert forkhead box protein P3 (FOXP3+) regulatory T-cells (Tregs) into IL-17-producing cells (Th17 cells) in vitro. However, this functional plasticity has not been examined in the pathogenesis of periodontal disease. In this study, we analyzed the IL-17A+FOXP3+ cells present in periodontitis lesions to determine the association between Treg conversion and the pathogenesis of periodontitis. The immunohistochemical analysis of gingival tissues demonstrated that the numbers of Th17 cells (IL-17A+FOXP3−) and Tregs (IL-17A−FOXP3+) were greater in periodontitis lesions than in gingivitis lesions. We further identified a small number of IL-17A+FOXP3+ cells in periodontitis lesions but not in gingivitis lesions. The flow cytometry analysis of CD4+ T-cell lines established from gingival tissues and the peripheral blood of periodontitis patients showed that the proportion of Tregs was reduced and the proportion of IL-17A+FOXP3+ cells among all FOXP3+ cells was elevated in gingival tissue T-cell lines relative to the proportions in peripheral blood T-cell lines. Our findings indicate that Treg-Th17 conversion may occur in periodontitis lesions. Further studies addressing the role of Treg conversion during inflammatory responses against periodontopathic bacteria are needed.
Probiotics for Caries Prevention and Control

Modulation of the microbiota for restoring and maintaining health is a growing issue in medical science. A search for relevant clinical trials on the use of probiotic bacteria as a potential and clinically applicable anti-caries measure was performed. According to predetermined criteria, papers were selected and key data on study design, sample size, intervention, duration, and results were extracted. Two animal and 19 human studies were retrieved. Most studies were short-term and restricted to microbiological endpoints, and only 3 human studies reported a caries endpoint. A high degree of heterogeneity among the included investigations hampered the analysis. Significant reductions of mutans streptococci in saliva or plaque following daily intake of probiotic lactobacilli or bifidobacteria were reported in 12 out of 19 papers, whereas 3 reported an increase of lactobacilli. Three caries trials in preschool children and the elderly demonstrated prevented fractions of between 21% and 75% following regular intakes of milk supplemented with L. rhamnosus. No adverse effects or potential risks were reported. The currently available literature does not exclude the possibility that probiotic bacteria can interfere with the oral biofilm, but any clinical recommendation would be premature. Large-scale clinical studies with orally derived specific anti-caries candidates are still lacking.
Promotion and Prevention 'Report Card': Is Australia Getting it Right?

The last decade has witnessed an increasing international momentum in addressing mental health promotion and prevention of mental disorders. Positive mental health ‘is a state of wellbeing in which the individual realises his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community’ (WHO, 2001). Mental disorders are found in people of all ages, regions, countries and societies, and are present at any point in time in 10% of the adult population. Furthermore, ‘the social and economic costs of mental ill health for societies are wide-ranging, long-lasting and enormous. Mental health promotion and prevention of mental disorder can be effective in leading to health, social and economic gains’ (WHO, 2004a).
Algebraic Description of Curve Structure

The authors propose a compact and concise method of describing curves in terms of the quasi-topological features and the structure of each singular point. The quasi-topological features are the convexity, loop, and connectivity. The quasi-topological structure is analyzed in a hierarchical way, and algebraic structure is presented explicitly for each representation level. The lower-level representations are integrated into the higher-level one in a systematic way. When a curve has singular points (branch points), the curve is decomposed into components, where each is a simple arc or a simple closed curve, by decomposing each singular point. The description scheme is applied to character recognition. >
Requirement of Integrin β3 for Iron Transportation during Enamel Formation

Rodent incisors exhibit pigmentation on their labial surfaces. Although previous studies have shown that this pigment is composed of iron, the existence of other elements has not been investigated. This study found that the lower incisors of CD61, also known as integrin β3, null mice (CD61-/-) lacked pigmentation. Although ameloblasts differentiated and formed enamel normally, no ferric ion accumulation was observed in maturation-stage ameloblasts in CD61-/- mice. Surface elements of control and CD61-/- lower incisors were compared by x-ray photoelectron spectroscopy (XPS). XPS analysis detected C, Ca, N, O, and P on the labial surfaces of lower incisors of both mice, whereas Fe was detected only in control samples. No peak of non-ferrous metal or other element was detected in either group. Quantitative RT-PCR analysis of 18 iron-transportation-related genes with mRNA from maturation-stage ameloblasts and ALC, a pre-ameloblastic cell line, was performed. The results suggested that CD61 regulates the expressions of Slc11a2 and Slc40a1, both of which are involved in iron transportation in epithelial tissues. These results suggested that the pigment on the labial surface of mouse incisors is composed of Fe and that both anemia and reduction of iron-transporting proteins may cause the loss of pigmentation in CD61-/- mice.
Changes in Pharmacodynamic Target Attainment for Antimicrobials Over a 2-Year Period: Results of the 2004 OPTAMA Program in North America

The Optimizing Pharmacodynamic Target Attainment using a Microbiology Antibiogram (OPTAMA) program aims to determine the likelihood that specific antibiotic regimens will achieve bactericidal pharmacodynamic exposures against common nosocomial pathogens. The pharmacokinetic profiles of 5000 subjects were simulated to determine the bactericidal cumulative fraction of response (CFR) for commonly used intravenous β-lactams and ciprofloxacin against Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella species, isolated during the 2004 Meropenem Yearly Susceptibility Test Information Collection surveillance study in North America. Bactericidal CFRs were compared with 2002 OPTAMA results to assess for trends. Compared with 2002 results, declines in susceptibility, with a corresponding decrease in CFR, were observed for many agents against P. aeruginosa and A. baumannii, and for ciprofloxacin against E. coli. Conversely, discordance was observed with ciprofloxacin against Klebsiella species. Among this current population of nosocomial-acquired Gram negatives, the ability to achieve optimal pharmacodynamic exposures is becoming more difficult because of increasing resistance; therefore, continual evaluation of optimal dosing strategies will be necessary.
Bis-enoxacin Inhibits Bone Resorption and Orthodontic Tooth Movement

Enoxacin inhibits binding between the B-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments, and also between osteoclast formation and bone resorption in vitro. We hypothesized that a bisphosphonate derivative of enoxacin, bis-enoxacin (BE), which was previously studied as a bone-directed antibiotic, might have similar activities. BE shared a number of characteristics with enoxacin: It blocked binding between the recombinant B-subunit and microfilaments and inhibited osteoclastogenesis in cell culture with IC50s of about 10 µM in each case. BE did not alter the relative expression levels of various osteoclast-specific proteins. Even though tartrate-resistant acid phosphatase 5b was expressed, proteolytic activation of the latent pro-enzyme was inhibited. However, unlike enoxacin, BE stimulated caspase-3 activity. BE bound to bone slices and inhibited bone resorption by osteoclasts on BE-coated bone slices in cell culture. BE reduced the amount of orthodontic tooth movement achieved in rats after 28 days. Analysis of these data suggests that BE is a novel anti-resorptive molecule that is active both in vitro and in vivo and may have clinical uses. Abbreviations: BE, bis-enoxacin; V-ATPase, vacuolar H+-ATPase; TRAP, tartrate-resistant acid phosphatase; αMEM D10, minimal essential media, alpha modification with 10% fetal bovine serum; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; RANKL, receptor activator of nuclear factor kappa B-ligand; NFATc1, nuclear factor of activated T-cells; ADAM, a disintegrin and metalloprotease domain; OTM, orthodontic tooth movement.
The Specific Role of FAM20C in Amelogenesis

Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice in which Fam20C was ubiquitously inactivated had severe defects in dentin, enamel, and bone, along with hypophosphatemia. It remains to be determined if the enamel defects in the mice with universal inactivation of Family with sequence similarity 20-C (FAM20C) were associated with the dentin defects and whether hypophosphatemia in the knockout mice contributed to the enamel defects. In this study, we crossed Fam20Cfl/fl mice with keratin 14-Cre (K14-Cre) transgenic mice to specifically inactivate Fam20C in the epithelial cells, including the dental epithelial cells that are responsible for forming tooth enamel. X-ray, backscattered scanning electron microscopic, and histological analyses showed that the K14-Cre;Fam20Cfl/fl mice had severe enamel and ameloblast defects, while their dentin and alveolar bone were not significantly affected. Accordingly, serum biochemistry of the K14-Cre;Fam20Cfl/fl mice showed normal phosphate and FGF23 levels in the circulation. Analysis of these data indicates that, while FAM20C is a molecule essential to amelogenesis, its inactivation in the dental epithelium does not significantly affect dentinogenesis. Hypophosphatemia makes no significant contribution to the enamel defects in the mice with the ubiquitous deletion of Fam20C.
M180 Amelogenin Processed by MMP20 is Sufficient for Decussating Murine Enamel

Amelogenin (AMELX) and matrix metalloproteinase-20 (MMP20) are essential for proper enamel development. Amelx and Mmp20 mutations cause amelogenesis imperfecta. MMP20, a protease secreted by ameloblasts, is responsible for processing enamel proteins, including AMELX, during the secretory stage of enamel formation. Of at least 16 different amelogenin splice products, the most abundant isoform found in murine ameloblasts and developing enamel is the M180 protein. To understand the role of MMP20 processing of M180 AMELX, we generated AmelxKO/Mmp20KO (DKO) mice with an amelogenin (M180Tg) transgene. We analyzed the enamel phenotype by SEM to determine enamel structure and thickness, µCT, and by nanoindentation to quantify enamel mechanical properties. M180Tg/DKO mouse enamel had 37% of the hardness of M180Tg/AmelxKO teeth and demonstrated a complete lack of normal prismatic architecture. Although molar enamel of M180Tg/AmelxKO mice was thinner than WT, it had similar mechanical properties and decussating enamel prisms, which were abolished by the loss of MMP20 in the M180Tg/DKO mice. Retention of the C-terminus or complete lack of this domain is unable to rescue amelogenin null enamel. We conclude that among amelogenins, M180 alone is sufficient for normal enamel mechanical properties and prism patterns, but that additional amelogenin splice products are required to restore enamel thickness.
Field‐evolved resistance to Bt maize in sugarcane borer (Diatraea saccharalis) in Argentina

Abstract BACKGROUND Maize technologies expressing Bacillus thuringiensis (Bt) insecticidal proteins are widely used in Argentina to control sugarcane borer (Diatraea saccharalis Fabricius). Unexpected D. saccharalis damage was observed to Bt maize events TC1507 (expressing Cry1F) and MON 89034 × MON 88017 (expressing Cry1A.105 and Cry2Ab2) in an isolated area of San Luis Province. Diatraea saccharalis larvae were sampled from MON 89034 × MON 88017 fields in the area to generate a resistant strain (RR), which was subsequently characterized in plant and diet bioassays. RESULTS Survivorship of the RR strain was high on TC1507 leaf tissue, intermediate on MON 89034 × MON 88017, and low on MON 810 (expressing Cry1Ab). The RR strain had high resistance to Cry1A.105 (186.74‐fold) and no resistance to Cry2Ab2 in diet bioassays. These results indicate resistance to Cry1F and Cry1A.105 (and likely cross‐resistance between them) but not to Cry1Ab or Cry2Ab2. Resistance to MON 89034 × MON 88017 was functionally recessive. Reviews of grower records suggest that resistance initially evolved to Cry1F, conferring cross‐resistance to Cry1A.105, with low refuge compliance as the primary cause. A mitigation plan was implemented in San Luis that included technology rotation, field monitoring, and grower education on best management practices (BMPs) including refuges. CONCLUSION In the affected area, the resistance to Cry1F and Cry1A.105 is being managed effectively through use of MON 89034 × MON 88017 and MON 810 in combination with BMPs, and no spread of resistance to other regions has been observed. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Tropical wood resistance to the West Indian drywood termite Cryptotermes brevis: If termites can't chew….

BACKGROUND The importance and impact of invasive species are usually considered based on their economic implications, particularly the direct damage that they cause. The West Indian drywood termite Cryptotermes brevis (Walker) is an example and is a concern in structural lumber, furniture, and other wood products. Despite its importance, its tropical wood preferences and the wood physical characteristics contributing to resistance have not been investigated to date. Here, we developed wood testing units to allow the X-ray recording of termite colonization and then subsequently tested tropical wood resistance to the termite through free-choice and no-choice bioassays using these wood testing units. The relevance of wood density and hardness as determinants of such resistance was also tested, as was termite mandible wear. RESULTS The wood testing units used allowed the assessment of the termite infestation and wood area loss, enabling subsequent choice bioassays to be performed. While pine (Pinus sp.), jequitiba (Cariniana sp.) and angelim (Hymenolobium petraenum) exhibited the heaviest losses and highest infestations; cumaru (Dipteryx odorata), guariuba (Clarisia racemosa), and purpleheart (Peltogyne sp.) showed the lowest losses and infestations; courbaril (Hymenaea courbaril), eucalyptus (Eucalyptus sp.), and tatajuba (Bagassa guianensis) exhibited intermediary results. CONCLUSION Wood hardness and in particular wood density were key determinants of wood resistance to the termites, which exhibited lower infestations associated with greater mandible wear when infesting harder high-density wood. © 2017 Society of Chemical Industry.
Body Mass Index as a Predictive Factor of Periodontal Therapy Outcomes

Body mass index (BMI) and obesity are associated with the prevalence, extent, and severity of periodontitis. This study investigated the predictive role of overweight/obesity on clinical response following non-surgical periodontal therapy in patients with severe periodontitis. Two hundred sixty adults received an intensive course of non-surgical periodontal therapy. Periodontal status at baseline and 2 months was based upon probing pocket depths (PPD), clinical attachment levels (CAL), and whole-mouth gingival bleeding (FMBS) as assessed by two calibrated examiners. Generalized estimating equations (GEE) were used to estimate the impact of BMI and overweight/obesity on periodontal treatment response while controlling for baseline status, age, smoking status (smoker or non-smoker), and full-mouth dental plaque score. BMI (continuous variable) and obesity (vs. normal weight) were associated with worse mean PPD (p < .005), percentage of PPD > 4 mm (p = .01), but not with FMBS (p > .05) or CAL (p > .05) at 2 months, independent of age, smoking status, or dental plaque levels. The magnitude of this association was similar to that of smoking, which was also linked to a worse clinical periodontal outcome (p < .01). BMI and obesity appear to be independent predictors of poor response following non-surgical periodontal therapy.
High-temperature-pressure Polymerized Resin-infiltrated Ceramic Networks

The aim of this study was to produce composite blocks (CB) for CAD/CAM applications by high-temperature-pressure (HT/HP) polymerization of resin-infiltrated glass-ceramic networks. The effect of network sintering and the absence/presence of initiator was investigated. Mechanical properties were determined and compared with those of Paradigm MZ100 (3M ESPE) blocks and HT/HP polymerized experimental “classic” CB, in which the filler had been incorporated by conventional mixing. The networks were made from glass-ceramic powder (VITA Zahnfabrik) formed by slip casting and were either sintered or not. They were silanized, infiltrated by urethane dimethacrylate, with or without initiator, and polymerized under HT/HP (300 MPa, 180°C) to obtain resin-infiltrated glass-ceramic network (RIGCN) CB. HT/HP polymerized CB were also made from an experimental “classic” composite. Flexural strength (σf), fracture toughness (KIC), and Vickers hardness were determined and analyzed by one- or two-way analysis of variance (ANOVA), Scheffé multiple-means comparisons (α = 0.05), and Weibull statistics (for σf). Fractured surfaces were characterized with scanning electron microscopy. The mechanical properties of RIGCN CB were significantly higher. Sintering induced significant increases in σf and hardness, while the initiator significantly decreased hardness. The results suggested that RIGCN and HT/HP polymerization could be used to obtain CB with superior mechanical properties, suitable for CAD/CAM applications.
Dental Caries and Enamelin Haplotype

In the literature, the enamelin gene ENAM has been repeatedly designated as a possible candidate for caries susceptibility. Here, we checked whether ENAM variants could increase caries susceptibility. To this aim, we sequenced coding exons and exon-intron boundaries of ENAM in 250 children with a severe caries phenotype and in 149 caries-free patients from 9 French hospital groups. In total, 23 single-nucleotide polymorphisms (SNPs) were found, but none appeared to be responsible for a direct change of ENAM function. Six SNPs had a high minor allele frequency (MAF) and 6 others were identified for the first time. Statistical and evolutionary analyses showed that none of these SNPs was associated with caries susceptibility or caries protection when studied separately and challenged with environmental factors. However, haplotype interaction analysis showed that the presence, in a same variant, of 2 exonic SNPs (rs7671281 and rs3796704; MAF 0.12 and 0.10, respectively), both changing an amino acid in the protein region encoded by exon 10 (p.I648T and p.R763Q, respectively), increased caries susceptibility 2.66-fold independent of the environmental risk factors. These findings support ENAM as a gene candidate for caries susceptibility in the studied population.
Strong Association of Variants around FOXE1 and Orofacial Clefting

Nonsyndromic orofacial clefting (nsOFC) is a common, complex congenital disorder. The most frequent forms are nonsyndromic cleft lip with or without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO). Although they are generally considered distinct entities, a recent study has implicated a region around the FOXE1 gene in both nsCL/P and nsCPO. To investigate this hypothesis, we analyzed the 2 most strongly associated markers (rs3758249 and rs4460498) in 2 independent samples of differing ethnicities: Central European (949 nsCL/P cases, 155 nsCPO cases, 1163 controls) and Mayan Mesoamerican (156 nsCL/P cases, 10 nsCPO cases, 338 controls). While highly significant associations for both single-nucleotide polymorphisms were obtained in nsCL/P (rs4460498: pEurope = 6.50 × 10−06, pMayan = .0151; rs3758249: pEurope = 2.41 × 10−05, pMayan = .0299), no association was found in nsCPO (p > .05). Genotyping of rs4460498 in 472 independent European trios revealed significant associations for nsCL/P (p = .016) and nsCPO (p = .043). A meta-analysis of all data revealed a genomewide significant result for nsCL/P (p = 1.31 × 10−08), which became more significant when nsCPO cases were added (pnsOFC = 1.56 × 10−09). These results strongly support the FOXE1 locus as a risk factor for nsOFC. With the data of the initial study, there is now considerable evidence that this locus is the first conclusive risk factor shared between nsCL/P and nsCPO.
Regulatory Interplay between NFIC and TGF-β1 in Apical Papilla-derived Stem Cells

While transforming growth factor-β1 (TGF-β1) can regulate odontoblast differentiation in tooth crown morphogenesis, its effects on cells including stem cells from the apical papilla (SCAPs) involved in root formation are unclear. Nuclear factor I-C (NFIC) has been implicated in the regulation of root development, and interplay with TGF-β1 signaling has been reported in some cell types. We hypothesize that NFIC and TGF-β1 are important to the behavior of SCAPs and that the interplay between these molecules controls the regulation of the odontogenic differentiation of SCAPs. TGF-β1 inhibited the proliferation of SCAPs and their mineralization. Real-time polymerase chain-reaction (RT-PCR) and Western blot results showed that TGF-β1 significantly decreased osteogenic/dentinogenic gene expression. The inhibition of TGF-β/Smad signaling (SIS3) attenuated the suppressive effect of TGF-β1 on SCAPs. Importantly, overexpression of NFIC antagonized the effects of TGF-β1 on SCAPs, while knockdown of NFIC enhanced these effects, demonstrating a key regulatory role for NFIC in modulating TGF-β1 signaling in SCAPs. We conclude that this interplay between NFIC and TGF-β1 regulates SCAPs behavior and can determine the differentiation of these cells. These signaling interactions help inform the development of regenerative strategies aimed at root growth and development in immature teeth for endodontic treatment.