Disruption of Paneth and goblet cell homeostasis and increased endoplasmic reticulum stress in Agr2−/− mice

Anterior Gradient 2 (AGR2) is a protein disulfide isomerase that plays important roles in diverse processes in multiple cell lineages as a developmental regulator, survival factor and susceptibility gene for inflammatory bowel disease. Here, we show using germline and inducible Agr2−/− mice that Agr2 plays important roles in intestinal homeostasis. Agr2−/− intestine has decreased goblet cell Mucin 2, dramatic expansion of the Paneth cell compartment, abnormal Paneth cell localization, elevated endoplasmic reticulum (ER) stress, severe terminal ileitis and colitis. Cell culture experiments show that Agr2 expression is induced by ER stress, and that siRNA knockdown of Agr2 increases ER stress response. These studies implicate Agr2 in intestinal homeostasis and ER stress and suggest a role in the etiology of inflammatory bowel disease.     

Tracking down human contamination in ancient human teeth

DNA contamination arising from the manipulation of ancient calcified tissue samples is a poorly understood, yet fundamental, problem that affects the reliability of ancient DNA (aDNA) studies. We have typed the mitochondrial DNA hypervariable region I of the only 6 people involved in the excavation, washing, and subsequent anthropological and genetic study of 23 Neolithic remains excavated from Granollers (Barcelona, Spain) and searched for their presence among the 572 clones generated during the aDNA analyses of teeth from these samples. Of the cloned sequences, 17.13% could be unambiguously identified as contaminants, with those derived from the people involved in the retrieval and washing of the remains present in higher frequencies than those of the anthropologist and genetic researchers. This finding confirms, for the first time, previous hypotheses that teeth samples are most susceptible to contamination at their initial excavation. More worrying, the cloned contaminant sequences exhibit substitutions that can be attributed to DNA damage after the contamination event, and we demonstrate that the level of such damage increases with time: contaminants that are >10 years old have approximately 5 times more damage than those that are recent. Furthermore, we demonstrate that in this data set, the damage rate of the old contaminant sequences is indistinguishable from that of the endogenous DNA sequences. As such, the commonly used argument that miscoding lesions observed among cloned aDNA sequences can be used to support data authenticity is misleading in scenarios where the presence of old contaminant sequences is possible. We argue therefore that the typing of those involved in the manipulation of the ancient human specimens is critical in order to ensure that generated results are accurate.     

Bonding acrylic teeth to acrylic resin denture bases: a review

Partial or complete dentures are more commonly constructed for the elderly group of the population. Teeth debonding from the dentures can be frustrating to the patients as well as the dentist. Research has been carried out and is continuing to study the issue of bonding acrylic teeth to the denture base resin. The present review takes into account the majority of research papers published in the last five decades for determining the bond strength. Selection of more compatible combinations of denture base resins and acrylic teeth may reduce the number of prosthesis fractures and the resultant repairs.     

Prevalence of periodontopathic bacteria on the tongue dorsum of elderly people

Objectives: The aim of this study was to analyse the prevalence of oral bacteria on the dorsum of the tongue. In addition, the relationship between the number of teeth and the microflora present on the coating of the tongue in a population of 85‐year‐old people was assessed. Subjects and methods: Two hundred and five individuals (89 males, 116 females) from the same geographical area who were 85 years of age were examined. Five periodontopathic bacteria (Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Treponema denticola) and one cariogenic bacterium (Streptococcus mutans) were analysed using a polymerase chain reaction assay of tongue samples from the population. Results: Periodontal bacteria‐positive individuals have more teeth than that of periodontal bacteria‐negative people. Between the periodontal bacteria‐positive and ‐negative individuals, there were significant differences in the mean number of teeth for P. gingivalis (p < 0.0001), T. denticola (p < 0.001), F. nucleatum (p = 0.002), and T. forsythia (p = 0.005), while there were no significant differences for A. actinomycetemcomitans (p = 0.998) or S. mutans (p = 0.147). Conclusions: A wide range of species, including anaerobes, was detected in 85‐year‐old subjects. It was found that the detection of periodontal bacteria on the tongue coating increased with the number of teeth. There was a positive relationship between the tooth number and periodontopathic bacteria, except for A. actinomycetemcomitans.These results suggest that tongue care is essential for preventing oral disease and needs to be part of any oral care programme in elderly people.     

Fluid Mechanics of the Human Eye: Aqueous Humour Flow in The Anterior Chamber

We consider and compare the various different kinds of flow that may take place in the anterior chamber of a human eye. The physical mechanisms responsible for causing such flows may be classified as follows: (i) buoyancy-driven flow arising from the temperature difference between the anterior surface of the cornea and the iris, (ii) flow generated by the aqueous production of the ciliary body, (iii) flow generated by the interaction between buoyancy and gravity while sleeping while sleeping in a face-up position, (iv) flow generated by phakodenesis (lens tremor), (v) flow generated by Rapid Eye Movement (REM) during sleep. Each flow is studied using a traditional fluid mechanics/asymptotic analysis approach. We also assess the veracity of a hypothesis that was recently advanced [see Maurice, D.M., 1998. The Von Sallman Lecture 1996: An ophthalmological explanation of REM sleep. Exp. Eye. Res. 66, 139–145, for details] to suggest that, contrary to previous opinion, the purpose of REM during sleep is to ensure corneal respiration in the absence of the buoyant mixing that routinely takes place due to (i) above during waking conditions.     

Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo

After implantation, mouse embryos deficient for the activity of the transforming growth factor-beta member Nodal fail to form both the mesoderm and the definitive endoderm. They also fail to specify the anterior visceral endoderm, a specialized signaling center which has been shown to be required for the establishment of anterior identity in the epiblast. Our study reveals that Nodal-/- epiblast cells nevertheless express prematurely and ectopically molecular markers specific of anterior fate. Our analysis shows that neural specification occurs and regional identities characteristic of the forebrain are established precociously in the Nodal-/- mutant with a sequential progression equivalent to that of wild-type embryo. When explanted and cultured in vitro, Nodal-/- epiblast cells readily differentiate into neurons. Genes normally transcribed in organizer-derived tissues, such as Gsc and Foxa2, are also expressed in Nodal-/- epiblast. The analysis of Nodal-/-;Gsc-/- compound mutant embryos shows that Gsc activity plays no critical role in the acquisition of forebrain characters by Nodal-deficient cells. This study suggests that the initial steps of neural specification and forebrain development may take place well before gastrulation in the mouse and highlights a possible role for Nodal, at pregastrula stages, in the inhibition of anterior and neural fate determination.     

Development of midline cell types and commissural axon tracts requires Fgfr1 in the cerebrum

The adult cerebral hemispheres are connected to each other by specialized midline cell types and by three axonal tracts: the corpus callosum, the hippocampal commissure, and the anterior commissure. Many steps are required for these tracts to form, including early patterning and later axon pathfinding steps. Here, the requirement for FGF signaling in forming midline cell types and commissural axon tracts of the cerebral hemispheres is examined. Fgfr1, but not Fgfr3, is found to be essential for establishing all three commissural tracts. In an Fgfr1 mutant, commissural neurons are present and initially project their axons, but these fail to cross the midline that separates the hemispheres. Moreover, midline patterning defects are observed in the mutant. These defects include the loss of the septum and three specialized glial cell types, the indusium griseum glia, midline zipper glia, and glial wedge. Our findings demonstrate that FGF signaling is required for generating telencephalic midline structures, in particular septal and glial cell types and all three cerebral commissures. In addition, analysis of the Fgfr1 heterozygous mutant, in which midline patterning is normal but commissural defects still occur, suggests that at least two distinct FGF-dependent mechanisms underlie the formation of the cerebral commissures.     

GnRH相关肽在大鼠垂体前叶的细胞学定位

本研究应用特异性抗GnRH相关肽(GAP)N端11个氨基酸的抗血清和六种垂体前叶激素的抗血清,通过免疫组织化学双重染色技术观察GAP在大鼠垂体前叶细胞的定位。结果发现,GAP样免疫反应性物质存在于LH细胞和FSH细胞,而未见于GH、PRL、TSH和ACTH细胞。本文首次证明GAP存在于正常大鼠垂体促性腺激素细胞,为GAP调节LH和FSH的分泌提供了形态学证据;也支持GAP的功能序列在其分子的N端,或GAP进一步裂解出N端片段而发挥作用。     

Relationship between oral impacts on daily performance and chewing ability among independent elders residing in Daejeon City, Korea

doi: 10.1111/j.1741‐2358.2011.00504.x
Relationship between oral impacts on daily performance and chewing ability among independent elders residing in Daejeon City, Korea Objective: The aim of this study was to assess the association between oral health‐related quality of life (OHRQoL) measured by the oral impacts on daily performances (OIDP) inventory and chewing ability. Methods: The cluster sampling method was used to select a sample of 634 socially active independent community‐dwelling elders. An oral examination was conducted and a questionnaire was implemented. After bivariate comparisons, a multivariable two‐level logistic model was developed for the dichotomous OIDP indicator using the generalised linear mixed model. Results: The mean age of the participants was 74 years and 56.6% were women. Eight percent were edentulous, and the mean number of teeth was 17.7. Overall, 39.3% of participants had one or more oral impacts on daily performance. Elders with chewing ability of 0–49, 50–74 and 75–99% were approximately 120, 20 and seven times more likely to have oral impacts compared with those with full chewing ability, respectively. Elders reporting their oral health as ‘fair’ or ‘better’ were 68% less likely to have oral impacts than those with poor or very poor self‐reported oral health. Conclusion: Among independent elders, amelioration of chewing ability including delivery of appropriate prosthodontic care might independently contribute to improving OHRQoL of elders by improving their physical, psychological and social wellbeing.