Tooth Eruption Results from Bone Remodelling Driven by Bite Forces Sensed by Soft Tissue Dental Follicles: A Finite Element Analysis

Intermittent tongue, lip and cheek forces influence precise tooth position, so we here examine the possibility that tissue remodelling driven by functional bite-force-induced jaw-strain accounts for tooth eruption. Notably, although a separate true ‘eruptive force’ is widely assumed, there is little direct evidence for such a force. We constructed a three dimensional finite element model from axial computerized tomography of an 8 year old child mandible containing 12 erupted and 8 unerupted teeth. Tissues modelled included: cortical bone, cancellous bone, soft tissue dental follicle, periodontal ligament, enamel, dentine, pulp and articular cartilage. Strain and hydrostatic stress during incisive and unilateral molar bite force were modelled, with force applied via medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain was maximal in the soft tissue follicle as opposed to surrounding bone, consistent with follicle as an effective mechanosensor. Initial numerical analysis of dental follicle soft tissue overlying crowns and beneath the roots of unerupted teeth was of volume and hydrostatic stress. To numerically evaluate biological significance of differing hydrostatic stress levels normalized for variable finite element volume, ‘biological response units’ in Nmm were defined and calculated by multiplication of hydrostatic stress and volume for each finite element. Graphical representations revealed similar overall responses for individual teeth regardless if incisive or right molar bite force was studied. There was general compression in the soft tissues over crowns of most unerupted teeth, and general tension in the soft tissues beneath roots. Not conforming to this pattern were the unerupted second molars, which do not erupt at this developmental stage. Data support a new hypothesis for tooth eruption, in which the follicular soft tissues detect bite-force-induced bone-strain, and direct bone remodelling at the inner surface of the surrounding bony crypt, with the effect of enabling tooth eruption into the mouth.     

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target.     

A decade of diabetes: keeping children out of hospital.

OBJECTIVES--To document the number of children aged less than 15 years who developed diabetes and were managed within one large health district, and to evaluate the outcome of those children managed without hospital admission at diagnosis. DESIGN--A retrospective study over 1979-88, when a paediatrician and a physician with special interests in childhood diabetes initiated joint clinics. Data collected from the district diabetes register and files of consultants and health visitors specialising in diabetes. SETTING--Referral of children to consultants in Leicestershire (total population 863,000). MAIN OUTCOME MEASURES--The proportion of children managed without hospital admission, comparison of readmission rates and glycated haemoglobin concentrations between children admitted and those not admitted. RESULTS--Over 10 years 236 children aged 10-14 years developed diabetes (annual incidence rate 12.8/100,000 child population (95% confidence interval 11.3 to 14.7)). In total 138 were not admitted to hospital but received supervised management based at home. Admitted children were younger or acidotic or their family doctors did not contact the diabetes team. Duration of admission declined from seven days in 1979-80 to three days in 1987-8. Ninety two were not admitted to hospital during the 10 years for any reason. Significantly fewer children who received management at home were readmitted for reasons related to diabetes than the group treated in hospital (30 (22%) v 40 (41%); p = 0.004). Concentrations of glycated haemoglobin were no different between the two groups. CONCLUSIONS--Children with newly diagnosed diabetes may be safely and effectively managed out of hospital. Domiciliary or community based management depends on the commitment of consultants specialising in diabetes working in close cooperation with general practitioners, specialist nurses in diabetes, and dietitians.     

A- and B-type lamins are differentially expressed in normal human tissues

 A selection of normal human tissues was investigated for the presence of lamins B1, B2, and A-type lamins, using a panel of antibodies specific for the individual lamin subtypes. By use of immunoprecipitation and two-dimensional immunoblotting techniques we demonstrated that these antibodies do not cross-react with other lamin subtypes and that a range of different phosphorylation isoforms is recognized by each antibody. The lamin B2 antibodies appeared to decorate the nuclear lamina in all tissues examined, except hepatocytes, in which very little lamin B2 expression was observed. In contrast to previous studies, which suggested the ubiquitous expression of lamin B1 in mammalian tissues, we show that lamin B1 is not as universally distributed throughout normal human tissues as was to be expected from previous studies. Muscle and connective tissues are negative, while in epithelial cells lamin B1 seemed to be preferentially detected in proliferating cells. These results correspond well with those obtained for lamin B1 in chicken tissues. The expression of A-type lamins is most prominent in well-differentiated epithelial cells. Relatively undifferentiated and proliferating cells in epithelia showed a clearly reduced expression of A-type lamins. Furthermore, most cells of neuroendocrine origin as well as most hematopoietic cells were negative for A-type lamin antibodies. Accepted: 4 February 1997     

Genome‐wide detection of CNVs associated with beak deformity in chickens using high‐density 600K SNP arrays

Beak deformity (crossed beaks) is found in several indigenous chicken breeds including Beijing‐You studied here. Birds with deformed beaks have reduced feed intake and poor production performance. Recently, copy number variation (CNV) has been examined in many species and is recognized as a source of genetic variation, especially for disease phenotypes. In this study, to unravel the genetic mechanisms underlying beak deformity, we performed genome‐wide CNV detection using Affymetrix chicken high‐density 600K data on 48 deformed‐beak and 48 normal birds using penncnv . As a result, two and eight CNV regions (CNVRs) covering 0.32 and 2.45 Mb respectively on autosomes were identified in deformed‐beak and normal birds respectively. Further RT‐qPCR studies validated nine of the 10 CNVRs. The ratios of six CNVRs were significantly different between deformed‐beak and normal birds (P < 0.01). Within these six regions, three and 21 known genes were identified in deformed‐beak and normal birds respectively. Bioinformatics analysis showed that these genes were enriched in six GO terms and one KEGG pathway. Five candidate genes in the CNVRs were further validated using RT‐qPCR. The expression of LRIG2 (leucine rich repeats and immunoglobulin like domains 2) was lower in birds with deformed beaks (P < 0.01). Therefore, the LRIG2 gene could be considered a key factor in view of its known functions and its potential roles in beak deformity. Overall, our results will be helpful for future investigations of the genomic structural variations underlying beak deformity in chickens.     

In Vivo Study of Transverse Carpal Ligament Stiffness Using Acoustic Radiation Force Impulse (ARFI) Imaging

The transverse carpal ligament (TCL) forms the volar boundary of the carpal tunnel and may provide mechanical constraint to the median nerve, leading to carpal tunnel syndrome. Therefore, the mechanical properties of the TCL are essential to better understand the etiology of carpal tunnel syndrome. The purpose of this study was to investigate the in vivo TCL stiffness using acoustic radiation force impulse (ARFI) imaging. The shear wave velocity (SWV) of the TCL was measured using Virtual Touch IQ^TM software in 15 healthy, male subjects. The skin and the thenar muscles were also examined as reference tissues. In addition, the effects of measurement location and ultrasound transducer compression on the SWV were studied. The SWV of the TCL was dependent on the tissue location, with greater SWV values within the muscle-attached region than those outside of the muscle-attached region. The SWV of the TCL was significantly smaller without compression (5.21 ± 1.08 m/s) than with compression (6.62 ± 1.18 m/s). The SWV measurements of the skin and the thenar muscles were also affected by transducer compression, but to different extents than the SWV of the TCL. Therefore to standardize the ARFI imaging procedure, it is recommended that a layer of ultrasound gel be maintained to minimize the effects of tissue compression. This study demonstrated the feasibility of ARFI imaging for assessing the stiffness characteristics of the TCL in vivo, which has the potential to identify pathomechanical changes of the tissue.     

The Neural Basis of Responsibility Attribution in Decision-Making

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.