Differential expression of mitogen activating protein kinases in periodontitis

Aim Following toll‐like receptor ( TLR ) engagement, lipopolysaccharide ( LPS ) can stimulate the expression of pro‐inflammatory cytokines thus activating the innate immune response. The production of inflammatory cytokines results, in part, from the activation of kinase‐induced signalling cascades and transcriptional factors. Of the four distinct classes of mitogen‐activated protein kinases ( MAPK ) described in mammals, p38, c‐Jun N‐terminal activated kinases ( JNK 1‐3) and extracellular activated kinases ( ERK 1,2) are the best studied. Previous data have established that p38 MAPK signalling is required for inflammation and bone loss in periodontal disease pre‐clinical animal models. Materials & Methods In this study, we obtained healthy and diseased periodontal tissues along with clinical parameters and microbiological parameters. Excised fixed tissues were immunostained with total and phospho‐specific antibodies against p38, JNK and ERK kinases. Results Intensity scoring from immunostained tissues was correlated with clinical periodontal parameters. Rank correlations with clinical indices were statistically significantly positive ( p ‐value < 0.05) for total p38 (correlations ranging 0.49–0.68), phospho‐p38 (range 0.44–0.56), and total ERK (range 0.52–0.59) levels, and correlations with JNK levels also supported association (range 0.42–0.59). Phospho‐ JNK and phospho‐ ERK showed no significant positive correlation with clinical parameters of disease. Conclusion These data strongly implicate p38 MAPK as a major MAPK involved in human periodontal inflammation and severity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98997/1/jcpe12123.pd

Local sales restrictions significantly reduce the availability of menthol tobacco: findings from four Minnesota cities

BACKGROUND In 2017 and 2018, Minneapolis, St. Paul, Duluth and Falcon Heights, Minnesota were among the first US cities to restrict the sale of menthol tobacco to adult-only stores. The study examined changes in the availability and marketing of these products following policy implementation. METHODS Retail store audits were conducted approximately 2 months pre-policy and post-policy implementation. Tobacco retail stores (n=299) were sampled from tobacco licensing lists in Minneapolis, St. Paul, Duluth and Falcon Heights, as well as six comparison cities without menthol policies. The presence of menthol tobacco was assessed, along with the number of interior and exterior tobacco ads and promotions at each store. RESULTS The majority of policy intervention stores (grocery, convenience stores and pharmacies) were compliant (Minneapolis, 84.4%; Duluth, 97.5%; and St. Paul and Falcon Heights, 100.0%) and did not sell menthol tobacco. In contrast, menthol tobacco was available in all comparison city stores, and most (96.0%) exempted tobacco shops and liquor stores post-policy implementation. Two Minneapolis convenience stores added interior tobacco shops, allowing them to continue selling menthol tobacco. Significant decreases in menthol tobacco marketing post-policy were observed in the stores' interior in Minneapolis, St. Paul and Duluth (p<0.001) and on the stores' exterior in Duluth (p=0.023). CONCLUSIONS Findings demonstrate high rates of compliance, indicating that sales restrictions can significantly reduce the availability of menthol tobacco. However, challenges to policy adherence underscore the need for continued monitoring and enforcement action

Comparison of the sidereal angular velocity of subphotospheric layers and small bright coronal structures during the declining phase of solar cycle 23

Context. We compare solar differential rotation of subphotospheric layers derived from local helioseismology analysis of GONG++ dopplergrams and the one derived from tracing small bright coronal structures (SBCS) using EIT/SOHO images for the period August 2001 - December 2006, which correspond to the declining phase of solar cycle 23. Aims. The study aims to find a relationship between the rotation of the SBCS and the subphotospheric angular velocity. The northsouth asymmetries of both rotation velocity measurements are also investigated. Methods. Subphotospheric differential rotation was derived using ring-diagram analysis of GONG++ full-disk dopplergrams of 1 min cadence. The coronal rotation was derived by using an automatic method to identify and track the small bright coronal structures in EIT full-disk images of 6 hours cadence. Results. We find that the SBCS rotate faster than the considered upper subphotospheric layer (3Mm) by about 0.5 deg/day at the equator. This result joins the results of several other magnetic features (sunspots, plages, faculae, etc.) with a higher rotation than the solar plasma. The rotation rate latitudinal gradients of the SBCS and the subphotospheric layers are very similar. The SBCS motion shows an acceleration of about 0.005 deg/day/month during the declining phase of solar cycle 23, whereas the angular velocity of subsurface layers does not display any evident variation with time, except for the well known torsional oscillation pattern. Finally, both subphotospheric and coronal rotations of the southern hemisphere are predominantly larger than those of the northern hemisphere. At latitudes where the north-south asymmetry of the angular velocity increases (decreases) with activity for the SBCS, it decreases (increases) for subphotospheric layers.Comment: 6pages, 8 figures, Accepted for publication in Astronomy and Astrophysic

A study of possible temporal and latitudinal variations in the properties of the solar tachocline

Temporal variations of the structure and the rotation rate of the solar tachocline region are studied using helioseismic data from the Global Oscillation Network Group (GONG) and the Michelson Doppler Imager (MDI) obtained during the period 1995--2000. We do not find any significant temporal variation in the depth of the convection zone, the position of the tachocline or the extent of overshoot below the convection zone. No systematic variation in any other properties of the tachocline, like width, etc., is found either. Possibility of periodic variations in these properties is also investigated. Time-averaged results show that the tachocline is prolate with a variation by about 0.02R_sun in its position. The depth of the convection zone or the extent of overshoot does not show any significant variation with latitude.Comment: To appear in MNRA

Dynamo action by differential rotation in a stably stratified stellar interior

Magnetic fields can be created in stably stratified (non-convective) layers in a differentially rotating star. A magnetic instability in the toroidal field (wound up by differential rotation) replaces the role of convection in closing the field amplification loop. Tayler instability is likely to be the most relevant magnetic instability. A dynamo model is developed from these ingredients, and applied to the problem of angular momentum transport in stellar interiors. It produces a prodominantly horizontal field. This dynamo process might account for the observed pattern of rotation in the solar core.Comment: Expanded version as accepted by Astron. Astrophy

Bisphosphonates Inhibit Expression of p63 by Oral Keratinocytes

Osteonecrosis of the jaw (ONJ), a side-effect of bisphosphonate therapy, is characterized by exposed bone that fails to heal within eight weeks. Healing time of oral epithelial wounds is decreased in the presence of amino-bisphosphonates; however, the mechanism remains unknown. We examined human tissue from individuals with ONJ and non-bisphosphonate-treated controlindividuals to identify changes in oral epithelium and connective tissue. Oral and intravenous bisphosphonate-treated ONJ sites had reduced numbers of basal epithelial progenitor cells, as demonstrated by a 13.8 ± 1.1% and 31.9 ± 5.8% reduction of p63 expression, respectively. No significant differences in proliferation rates, vessel density, or macrophage number were noted. In vitro treatment of clonal and primary oral keratinocytes with zoledronic acid (ZA) inhibited p63, and expression was rescued by the addition of mevalonate pathway intermediates. In addition, both ZA treatment and p63 shRNA knock-down impaired formation of 3D Ex Vivo Produced Oral Mucosa Equivalents (EVPOME) and closure of an in vitro scratch assay. Analysis of our data suggests that bisphosphonate treatment may delay oral epithelial healing by interfering with p63-positive progenitor cells in the basal layer of the oral epithelium in a mevalonate-pathway-dependent manner. This delay in healing may increase the likelihood of osteonecrosis developing in already-compromised bone

The case for a distributed solar dynamo shaped by near-surface shear

Arguments for and against the widely accepted picture of a solar dynamo being seated in the tachocline are reviewed and alternative ideas concerning dynamos operating in the bulk of the convection zone, or perhaps even in the near-surface shear layer, are discussed. Based on the angular velocities of magnetic tracers it is argued that the observations are compatible with a distributed dynamo that may be strongly shaped by the near-surface shear layer. Direct simulations of dynamo action in a slab with turbulence and shear are presented to discuss filling factor and tilt angles of bipolar regions in such a model.Comment: 10 pages, 6 figures, Astrophys. J. 625 (scheduled for the 1 June 2005 issue

Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas

Familial Non-Medullary Thyroid Carcinoma (fNMTC) represents 3–7% of all thyroid tumours and is associated with some of the highest familial risks among all cancers, with an inheritance pattern compatible with an autosomal dominant model with reduced penetrance. We previously mapped a predisposing locus, TCO (Thyroid tumour with Cell Oxyphilia) on chromosome 19p13.2, for a particular form of thyroid tumour characterised by cells with an abnormal proliferation of mitochondria (oxyphilic or oncocytic cells). In the present work, we report the systematic screening of 14 candidate genes mapping to the region of linkage in affected TCO members, that led us to identify two novel variants respectively in exon 9 and exon 13 of TIMM44, a mitochondrial inner membrane translocase for the import in the mitochondria of nuclear-encoded proteins. These variants were co-segregating with the TCO phenotype, were not present in a large group of controls and were predicted to negatively affect the protein (exon 9 change) or the transcript (exon 13 change). Functional analysis was performed in vitro for both changes and although no dramatic loss of function effects were identified for the mutant alleles, subtler effects might still be present that could alter Timm44 function and thus promote oncocytic tumour development. Thus we suggest that TIMM44 should be considered for further studies in independent samples of affected individuals with TCO