Is Diet a Determining Factor in the Induction of Gingival Inflammation by Dental Plaque? A Secondary Analysis of Clinical Studies.

The aim was to determine the association between plaque and gingival inflammation reported by dietary interventions. Data of four clinical studies dealing with changed nutrition and gingival examination were reanalyzed with regard to gingival inflammation (GI), plaque (PI), and bleeding on probing (BOP). Dietary changes basically involved avoiding sugar, white flour and sweetened drinks and focusing on whole foods for 4 weeks. The control groups were to maintain their usual diet. All participants had to reduce their oral hygiene efforts. Linear regression models taking the clustering of the data due to several studies into account were applied. In total, data of 92 participants (control groups: 39, test-groups 53) were reanalyzed. While both groups showed a slight increase in dental plaque, only the test groups showed a significant decrease in inflammatory parameters: GI (mean value difference End-Baseline (Δ): -0.31 (±SD 0.36)) and BOP (Δ: -15.39% (±16.07)), both p < 0.001. In the control groups, there was a constant relation between PI and GI, while the experimental group showed a decreasing relationship in GI/PI (p = 0.016), and even an inverted relationship BOP/PI under a changed diet (p = 0.031). In conclusion, diet seems to be a determining factor how the gingiva reacts towards dental plaque.

Revisiting bicoid function: complete inactivation reveals an additional fundamental role in Drosophila egg geometry specification.

INTRODUCTION: The bicoid (bcd) gene in Drosophila has served as a paradigm for a morphogen in textbooks for decades. Discovered in 1986 as a mutation affecting anterior development in the embryo, its expression pattern as a protein gradient later confirmed the prediction from transplantation experiments. These experiments suggested that the protein fulfills the criteria of a true morphogen, with the existence of a homeodomain crucial for activation of genes along the anterior-posterior axis, based on the concentration of the morphogen. The bcd gene undergoes alternative splicing, resulting in, among other isoforms, a small and often neglected isoform with low abundance, which lacks the homeodomain, termed small bicoid (smbcd). Most importantly, all known classical strong bcd alleles used in the past to determine bcd function apparently do not affect the function of this isoform. RESULTS: To overcome the uncertainty regarding which isoform regulates what, I removed the bcd locus entirely using CRISPR technology. bcdCRISPR eggs exhibited a short and round appearance. The phenotype could be ascribed to smbcd because all bcd alleles affecting the function of the major transcript, termed large bicoid (lgbcd) showed normally sized eggs. Several patterning genes for the embryo showed expression in the oocyte, and their expression patterns were altered in bcdCRISPR oocytes. In bcdCRISPR embryos, all downstream segmentation genes showed altered expression patterns, consistent with the expression patterns in "classical" alleles; however, due to the altered egg geometry resulting in fewer blastoderm nuclei, additional constraints came into play, further affecting their expression patterns. CONCLUSIONS: This study unveils a novel and fundamental role of bcd in shaping the egg's geometry. This discovery demands a comprehensive revision of our understanding of this important patterning gene and prompts a reevaluation of past experiments conducted under the assumption that bcd mutants were bcdnull-mutants.

chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche.

Niches maintain a finite pool of stem cells via restricted space and short-range signals. Stem cells compete for limited niche resources, but the mechanisms regulating competition are poorly understood. Using the Drosophila testis model, we show that germline stem cells (GSCs) lacking the transcription factor Chinmo gain a competitive advantage for niche access. Surprisingly, chinmo-/- GSCs rely on a new mechanism of competition in which they secrete the extracellular matrix protein Perlecan to selectively evict non-mutant GSCs and then upregulate Perlecan-binding proteins to remain in the altered niche. Over time, the GSC pool can be entirely replaced with chinmo-/- cells. As a consequence, the mutant chinmo allele acts as a gene drive element; the majority of offspring inherit the allele despite the heterozygous genotype of the parent. Our results suggest that the influence of GSC competition may extend beyond individual stem cell niche dynamics to population-level allelic drift and evolution.

Modulating the bicoid gradient in space and time.

BACKGROUND: The formation of the Bicoid (Bcd) gradient in the early Drosophila is one of the most fascinating observations in biology and serves as a paradigm for gradient formation, yet its mechanism is still not fully understood. Two distinct models were proposed in the past, the SDD and the ARTS model. RESULTS: We define novel cis- and trans-acting factors that are indispensable for gradient formation. The first one is the poly A tail length of the bcd mRNA where we demonstrate that it changes not only in time, but also in space. We show that posterior bcd mRNAs possess a longer poly tail than anterior ones and this elongation is likely mediated by wispy (wisp), a poly A polymerase. Consequently, modulating the activity of Wisp results in changes of the Bcd gradient, in controlling downstream targets such as the gap and pair-rule genes, and also in influencing the cuticular pattern. Attempts to modulate the Bcd gradient by subjecting the egg to an extra nuclear cycle, i.e. a 15th nuclear cycle by means of the maternal haploid (mh) mutation showed no effect, neither on the appearance of the gradient nor on the control of downstream target. This suggests that the segmental anlagen are determined during the first 14 nuclear cycles. Finally, we identify the Cyclin B (CycB) gene as a trans-acting factor that modulates the movement of Bcd such that Bcd movement is allowed to move through the interior of the egg. CONCLUSIONS: Our analysis demonstrates that Bcd gradient formation is far more complex than previously thought requiring a revision of the models of how the gradient is formed.

Quantification reveals early dynamics in Drosophila maternal gradients.

The Bicoid (Bcd) protein is a primary determinant of early anterior-posterior (AP) axis specification in Drosophila embryogenesis. This morphogen is spatially distributed in an anterior-high gradient, and affects particular AP cell fates in a concentration-dependent manner. The early distribution and dynamics of the bicoid (bcd) mRNA, the source for the Bcd protein gradient, is not well understood, leaving a number of open questions for how Bcd positional information develops and is regulated. Confocal microscope images of whole early embryos, stained for bcd mRNA or the Staufen (Stau) protein involved in its transport, were processed to extract quantitative AP intensity profiles at two depths (apical-under the embryo surface but above the nuclear layer; and basal-below the nuclei). Each profile was quantified by a two- (or three-) exponential equation. The parameters of these equations were used to analyze the early developmental dynamics of bcd. Analysis of 1D profiles was compared with 2D intensity surfaces from the same images. This approach reveals strong early changes in bcd and Stau, which appear to be coordinated. We can unambiguously discriminate three stages in early development using the exponential parameters: pre-blastoderm (1-9 cleavage cycle, cc), syncytial blastoderm (10-13 cc) and cellularization (from 14A cc). Key features which differ in this period are how fast the first exponential (anterior component) of the apical profile drops with distance and whether it is higher or lower than the basal first exponential. We can further discriminate early and late embryos within the pre-blastoderm stage, depending on how quickly the anterior exponential drops. This relates to the posterior-wards spread of bcd in the first hour of development. Both bcd and Stau show several redistributions in the head cytoplasm, quite probably related to nuclear activity: first shifting inwards towards the core plasm, forming either protrusions (early pre-blastoderm) or round aggregations (early nuclear cleavage cycles, cc, 13 and 14), then moving to the embryo surface and spreading posteriorly. These movements are seen both with the 2D surface study and the 1D profile analysis. The continued spreading of bcd can be tracked from the time of nuclear layer formation (later pre-blastoderm) to the later syncytial blastoderm stages by the progressive loss of steepness of the apical anterior exponential (for both bcd and Stau). Finally, at the beginning of cc14 (cellularization stage) we see a distinctive flip from the basal anterior gradient being higher to the apical gradient being higher (for both bcd and Stau). Quantitative analysis reveals substantial (and correlated) bcd and Stau redistributions during early development, supporting that the distribution and dynamics of bcd mRNA are key factors in the formation and maintenance of the Bcd protein morphogenetic gradient. This analysis reveals the complex and dynamic nature of bcd redistribution, particularly in the head cytoplasm. These resemble observations in oogenesis; their role and significance have yet to be clarified. The observed co-localization during redistribution of bcd and Stau may indicate the involvement of active transport.

Anti-Fibrotic Activity of an Antimicrobial Peptide in a Drosophila Model.

Fibrotic lesions accompany several pathological conditions, including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components, including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apicobasal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide drosomycin (Drs), which also restores the secretory activity of the SGs. In addition to extracellular matrix components, both Drs and F-actin localize to fibrotic lesions.

The centenary of Hereditas - almost a fairytale.

This is the Editorial for a series of articles illuminating the history and success story of Hereditas, one of the oldest journals in the area of genetics. For this reason, we invite you to read this special series on a journal with a distinct reputation and which can celebrate its Centenary in 2020.

MONOPOL - A traveling-wave magnetic neutron spin resonator for tailoring polarized neutron beams.

We report on first experimental tests of a neutron magnetic spin resonator at a very cold neutron beam port of the high flux reactor at the ILL Grenoble. When placed between two supermirror neutron polarizers and operated in a pulsed traveling-wave mode it allows to decouple its time- and wavelength-resolution and can therefore be used simultaneously as electronically tunable monochromator and fast beam chopper. As a first 'real' scientific application we intend its implementation in the PERC (p roton and e lectron r adiation c hannel) project related to high-precision experiments in neutron beta decay.

bicoid RNA localization requires the trans-Golgi network.

BACKGROUND: The formation of the bicoid (bcd) mRNA gradient is a crucial step for Bcd protein gradient formation in Drosophila. In the past, a microtubule (MT)-based cortical network had been shown to be indispensable for bcd mRNA transport to the posterior. RESULTS: We report the identification of a MT-binding protein CLASP/Chb as the first component associated with this cortical MT network. Since CLASPs in vertebrates were shown to serve as an acentriolar microtubule organization center (aMTOC) in concert with trans-Golgi proteins, we examined the effect of the Drosophila trans-Golgins on bcd localization and gradient formation. Using a genetic approach, we demonstrate that the Drosophila trans-Golgins dGCC88, dGolgin97 and dGCC185 indeed affect bcd mRNA localization during oocyte development. Consequently, the bcd mRNA is already mislocalized before the egg is fertilized. The expression domains of genes downstream of the hierarchy of bcd, e.g. of the gap gene empty spiracles or of the pair-rule gene even-skipped are changed, indicating an altered segmental anlagen, due to a faulty bcd gradient. Thus, at the end of embryogenesis, trans-Golgin mutants show bcd-like cuticle phenotypes. CONCLUSIONS: Our data provides evidence that the Golgi as a cellular member of the secretory pathway exerts control on bcd localization which indicates that bcd gradient formation is probably more intricate than previously presumed.

Discovery of Teneurins.

Teneurins were first discovered and published in 1993 and 1994, in Drosophila melanogaster as Ten-a and Ten-m. They were initially described as cell surface proteins, and as pair-rule genes. Later, they proved to be type II transmembrane proteins, and not to be pair-rule genes. Ten-m might nonetheless have had an ancestral function in clock-based segmentation as a Ten-m oscillator. The turn of the millennium saw a watershed of vertebrate Teneurin discovery, which was soon complemented by Teneurin protein annotations from whole genome sequence publications. Teneurins encode proteins with essentially invariant domain order and size. The first years of Teneurin studies in many experimental systems led to key insights, and a unified picture, of Teneurin proteins.

Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning.

Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed of Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). Recent in vivo studies challenged the initially proposed role of NDG as a major ECM linker molecule by revealing dispensability for viability and BM formation. Here, we report the characterization of the single Ndg gene in Drosophila. Embryonic Ndg expression was primarily observed in mesodermal tissues and the chordotonal organs, whereas NDG protein localized to all BMs. Although loss of Laminin strongly affected BM localization of NDG, Ndg-null mutants exhibited no overt changes in the distribution of BM components. Although Drosophila Ndg mutants were viable, loss of NDG led to ultrastructural BM defects that compromised barrier function and stability in vivo Moreover, loss of NDG impaired larval crawling behavior and reduced responses to vibrational stimuli. Further morphological analysis revealed accompanying defects in the larval peripheral nervous system, especially in the chordotonal organs and the neuromuscular junction (NMJ). Taken together, our analysis suggests that NDG is not essential for BM assembly but mediates BM stability and ECM-dependent neural plasticity during Drosophila development.

Private-sector investor's intention and motivation to invest in Land Degradation Neutrality.

Private-sector investors could be key players in combatting global land degradation and realising the emerging concept of Land Degradation Neutrality (LDN). To better understand how to incentivize private-sector investors for LDN, we conducted an online-survey of 68 private-sector investors. Structural equation modelling based on the theory of planned behavior was performed to investigate how cognitive, social, emotional, motivational and financial determinants influence their intention and motivation to invest in LDN. Good knowledge and a positive attitude towards both LDN and investing sustainably were found to be main predictors for intention. In contrast, perceived social pressure had little effect on the intention to invest towards combating land degradation. The general motivation to invest sustainably was mainly triggered by a consciousness for sustainability and emotional attachment, less by the desire for short-term profit maximisation whilst prospects of long-term financial return are important. Overall, strong homogeneity in psychological determinants was found for both traditional and impact investors. As the determinants of the intention and the motivation to invest sustainably do not substantially differ across different investor types, our study implies that investors should be targeted as a uniform group when mobilising interest for LDN. Emphasis should be placed on the psychological determinants traditional and impact investors commonly share, rather than on the type-specific characteristics that may distinguish different investor types.

Seeing is believing: the Bicoid protein reveals its path.

In this commentary, I will review the latest findings on the Bicoid (Bcd) morphogen in Drosophila, a paradigm for gradient formation taught to biology students for more than two decades. "Seeing is believing" also summarizes the erroneous steps that were needed to elucidate the mechanisms of gradient formation and the path of movement of Bcd. Initially proclaimed as a dogma in 1988 and later incorporated into the SDD model where the broad diffusion of Bcd throughout the embryo was the predominant step leading to gradient formation, the SDD model was irrefutable for more than two decades until first doubts were raised in 2007 regarding the diffusion properties of Bcd associated with the SDD model. This led to re-thinking of the issue and the definition of a new model, termed the ARTS model which could explain most of the physical constraints that were inherently associated with the SDD model. In the ARTS model, gradient formation is mediated by the mRNA which is redistributed along cortical microtubules to form a mRNA gradient which is translated to form the protein gradient. Contrary to the SDD model, there is no Bcd diffusion from the tip. The ARTS model is also compatible with the observed cortical movement of Bcd. I will critically compare the SDD and the ARTS models as well as other models, analyze the major differences, and highlight the path where Bcd is localized during early nuclear cycles.

The Impact of Orthodontic Bands on the Marginal Periodontium of Maxillary First Molars: A Retrospective Cross-Sectional Radiographic Analysis.

AIM: Available information on the effect of orthodontic treatment on crestal alveolar bone levels measured in radiographs is contradictory. The aim of this study was to compare the alveolar bone level and periodontal ligament space of banded upper first molars to untreated controls. MATERIALS AND METHODS: This retrospective cross-sectional radiographic study investigated alveolar bone levels of upper first molars of an orthodontic test group and an untreated control group of comparable age (15-16.25 years), using existing bitewing radiographs.Eighty-six individuals were included in each group. Three parameters were measured mesially and distally on both sides of the patient as follows: I) Alveolar Bone Level (ABL): measured as the distance between the cemento-enamel junction and the alveolar crest, II) the Periodontal Ligament Space (PLS): measured as the most coronal distance between the alveolar crest and the tooth surface, and III) angle between the lines (alveolar crests mesial and distal) and (cemento-enamel junction mesial and distal). RESULTS: The mean duration of the orthodontic treatment in the test group was 2.5 years. The periodontal ligament space was statistically significantly wider on mesial areas of right molars (mean 0.2 mm, p<0.01), but there was no statistically significant difference found in the three other areas (distal part of the right molar, mesial and distal parts of the left molar). There was a statistically significant mean alveolar bone loss in the right and left mesial areas, respectively accounting for 0.3 mm (p<0.001) and 0.2 mm (p<0.01). No statistically significant alveolar bone loss was measured on the distal surfaces of the upper molars. The angle was wider on both sides for the test group (right p<0.001 and left p<0.05). CONCLUSIONS: A significant alveolar bone loss on the mesial tooth surface of upper first molars after orthodontic treatment was found with concurrent different levelling angles in the test group. On all other sites, no statistically significant changes were found. There was some minimal statistical significant alveolar bone loss after finishing treatment in patients who had orthodontic bands placed on their maxillary 1st molars, but no clinical significance was found.

Correction: Cortical movement of Bicoid in early Drosophila embryos is actin- and microtubule-dependent and disagrees with the SDD diffusion model.

[This corrects the article DOI: 10.1371/journal.pone.0185443.].

Drosophila exoribonuclease nibbler is a tumor suppressor, acts within the RNAi machinery and is not enriched in the nuage during early oogenesis.

BACKGROUND: micro RNAs (miRNAs) are important regulators of many biological pathways. A plethora of steps are required to form, from a precursor, the mature miRNA that eventually acts on its target RNA to repress its expression or to inhibit translation. Recently, Drosophila nibbler (nbr) has been shown to be an important player in the maturation process of miRNA and piRNA. Nbr is an exoribonuclease which helps to shape the 3' end of miRNAs by trimming the 3' overhang to a final length. RESULTS: In contrast to previous reports on the localization of Nbr, we report that 1) Nbr is expressed only during a short time of oogenesis and appears ubiquitously localized within oocytes, and that 2) Nbr was is not enriched in the nuage where it was shown to be involved in piwi-mediated mechanisms. To date, there is little information available on the function of nbr for cellular and developmental processes. Due to the fact that nbr mutants are viable with minor deleterious effects, we used the GAL4/UAS over-expression system to define novel functions of nbr. We disclose hitherto unknown functions of nbr 1) as a tumor suppressor and 2) as a suppressor of RNAi. Finally, we confirm that nbr is a suppressor of transposon activity. CONCLUSIONS: Our data suggest that nbr exerts much more widespread functions than previously reported from trimming 3' ends of miRNAs only.

The Effect of Enamel Sandblasting on Enhancing Bond Strength of Orthodontic Brackets: A Systematic Review and Meta-analysis.

PURPOSE: To critically appraise the evidence regarding the effect of enamel sandblasting on the bond strength of orthodontic brackets on either the labial or lingual tooth surface. MATERIALS AND METHODS: An electronic database search of published and unpublished literature was performed. Search terms included sandblasting, enamel abrasion, tooth surface, bond strength, bond failure, and adhesive remnant; data were extracted in standardized piloted forms. Risk of bias was assessed using the Cochrane risk of bias tool, adapted for in vitro studies where necessary. RESULTS: Of the 81 articles initially retrieved, 13 were eligible for inclusion in the systematic review. All of the latter were in vitro studies with unclear risk of bias primarily due to unclear reporting of blinding of outcome assessors. Eight studies assessed the combined effect of enamel sandblasting and etching, while only five evaluated the isolated effect of sandblasting on the buccal enamel surface. In view of the apparently heterogeneous study settings, intervention protocols, specimen preparation and storage sequences, only two studies were deemed eligible for quantitative synthesis. Random effects meta-analysis revealed no evidence to support sandblasting prior to etching over etching alone with regard to shear bond strength of orthodontic brackets bonded in vitro to lingual enamel surfaces of extracted premolars (standardized mean difference: 0.36; 95% CI: -0.21, 0.94; p = 0.22). CONCLUSIONS: The findings of the present study cannot support lingual enamel sandblasting prior to etching for augmentation of the bond strength of orthodontic brackets.

Cortical movement of Bicoid in early Drosophila embryos is actin- and microtubule-dependent and disagrees with the SDD diffusion model.

The Bicoid (Bcd) protein gradient in Drosophila serves as a paradigm for gradient formation in textbooks. The SDD model (synthesis, diffusion, degradation) was proposed to explain the formation of the gradient. The SDD model states that the bcd mRNA is located at the anterior pole of the embryo at all times and serves a source for translation of the Bicoid protein, coupled with diffusion and uniform degradation throughout the embryo. Recently, the ARTS model (active RNA transport, synthesis) challenged the SDD model. In this model, the mRNA is transported at the cortex along microtubules to form a mRNA gradient which serves as template for the production of Bcd, hence little Bcd movement is involved. To test the validity of the SDD model, we developed a sensitive assay to monitor the movement of Bcd during early nuclear cycles. We observed that Bcd moved along the cortex and not in a broad front towards the posterior as the SDD model would have predicted. We subjected embryos to hypoxia where the mRNA remained strictly located at the tip at all times, while the protein was allowed to move freely, thus conforming to an ideal experimental setup to test the SDD model. Unexpectedly, Bcd still moved along the cortex. Moreover, cortical Bcd movement was sparse, even under longer hypoxic conditions. Hypoxic embryos treated with drugs compromising microtubule and actin function affected Bcd cortical movement and stability. Vinblastine treatment allowed the simulation of an ideal SDD model whereby the protein moved throughout the embryo in a broad front. In unfertilized embryos, the Bcd protein followed the mRNA which itself was transported into the interior of the embryo utilizing a hitherto undiscovered microtubular network. Our data suggest that the Bcd gradient formation is probably more complex than previously anticipated.

Segmentation gene expression patterns in Bactrocera dorsalis and related insects: regulation and shape of blastoderm and larval cuticle.

The oriental fruit fly, Bactrocera dorsalis, is regarded as a severe pest of fruit production in Asia. Despite its economic importance, only limited information regarding the molecular and developmental biology of this insect is known to date. We provide a detailed analysis of B. dorsalis embryology, as well as the expression patterns of a number of segmentation genes known to act during patterning of Drosophila and compare these to the patterns of other insect families. An anterior shift of the expression of gap genes was detected when compared to Drosophila. This shift was largely restored during the step where the gap genes control expression of the pair-rule genes. We analyzed and compared the shapes of the embryos of insects of different families, B. dorsalis and the blow fly Lucilia sericata with that of the well-characterized Drosophila melanogaster. We found distinct shapes as well as differences in the ratios of the length of the anterior-posterior axis and the dorsal-ventral axis. These features were integrated into a profile of how the expression patterns of the gap gene Krüppel and the pair-rule gene even-skipped were observed along the A-P axis in three insects families. Since significant differences were observed, we discuss how Krüppel controls the even-skipped stripes. Furthermore, we discuss how the position and angles of the segmentation gene stripes differed from other insects. Finally, we analyzed the outcome of the expression patterns of the late acting segment polarity genes in relation to the anlagen of the naked-cuticle and denticle belt area of the B. dorsalis larva.

Ancient role of ten-m/odz in segmentation and the transition from sequential to syncytial segmentation.

BACKGROUND: Until recently, mechanisms of segmentation established for Drosophila served as a paradigm for arthropod segmentation. However, with the discovery of gene expression waves in vertebrate segmentation, another paradigm based on oscillations linked to axial growth was established. The Notch pathway and hairy delay oscillator are basic components of this mechanism, as is the wnt pathway. With the establishment of oscillations during segmentation of the beetle Tribolium, a common segmentation mechanism may have been present in the last common ancestor of vertebrates and arthropods. However, the Notch pathway is not involved in segmentation of the initial Drosophila embryo. In arthropods, the engrailed, wingless pair has a much more conserved function in segmentation than most of the hierarchy established for Drosophila. RESULTS: Here, we work backwards from this conserved pair by discussing possible mechanisms which could have taken over the role of the Notch pathway. We propose a pivotal role for the large transmembrane protein Ten-m/Odz. Ten-m/Odz may have had an ancient role in cell-cell communication, parallel to the Notch and wnt pathways. The Ten-m protein binds to the membrane with properties which resemble other membrane-based biochemical oscillators. CONCLUSION: We propose that such a simple transition could have formed the initial scaffold, on top of which the hierarchy, observed in the syncytium of dipterans, could have evolved.