Ear Hole Research Articles

PLOD2, a key factor for MRL MSC metabolism and chondroprotective properties

BackgroundInitially discovered for its ability to regenerate ear holes, the Murphy Roth Large (MRL) mouse has been the subject of multiple research studies aimed at evaluating its ability to regenerate other body tissues and at deciphering the mechanisms underlying it. These enhanced abilities to regenerate, retained during adulthood, protect the MRL mouse from degenerative diseases such as osteoarthritis (OA). Here, we hypothesized that mesenchymal stromal/stem cells (MSC) derived from the regenerative MRL mouse could be involved in their regenerative potential through the release of pro-regenerative mediators.MethodTo address this hypothesis, we compared the secretome of MRL and BL6 MSC and identified several candidate molecules expressed at significantly higher levels by MRL MSC than by BL6 MSC. We selected one candidate, Plod2, and performed functional in vitro assays to evaluate its role on MRL MSC properties including metabolic profile, migration, and chondroprotective effects. To assess its contribution to MRL protection against OA, we used an experimental model for osteoarthritis induced by collagenase (CiOA).ResultsAmong the candidate molecules highly expressed by MRL MSC, we focused our attention on procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). Plod2 silencing induced a decrease in the glycolytic function of MRL MSC, resulting in the alteration of their migratory and chondroprotective abilities in vitro. In vivo, we showed that Plod2 silencing in MRL MSC significantly impaired their capacity to protect mouse from developing OA.ConclusionOur results demonstrate that the chondroprotective and therapeutic properties of MRL MSC in the CiOA experimental model are in part mediated by PLOD2.

Effects of pericyte and smooth muscle specific knock-out of CXCL12 on cardiac function after myocardial ischemia in mice

Abstract Introduction Ischemic cardiomyopathy as a result of myocardial infarction represents one of the most common causes of heart failure (1). The C-X-C motif chemokine ligand 12 (CXCL12) and its receptor CXCR4 facilitate cardiac repair after myocardial ischemia (MI) and play fundamental roles in cardiovascular development (2). However, the cell- and tissue-specific actions of CXCL12 are poorly understood, limiting the introduction of targeted therapies. Here, we aimed to examine the role of pericyte and smooth muscle cell-specific CXCL12 expression on myocardial function after MI. Methods We generated a smooth muscle protein 22-alpha-Cre and a pericyte protein NG2-Cre driven mouse model to ablate CXCL12 specifically in smooth muscle cells (SM22-Cre x CXCL12flox/flox) and in pericytes (NG2-Cre x CXCL12flox/flox). Genotyping was performed using ear hole biopsy by PCR. Hearts were analysed morphologically by histology and immunofluorescence. Cardiac function and dimensions of the wall thicknesses and cardiac cavities were determined by echocardiography. Myocardial infarction was induced in the animals and cardiac function was further investigated 28 days after MI. Results In immunofluorescence, we found that CXCL12 is highly expressed in SM22+ smooth muscle cells and in cells surrounding arterial blood vessels (3). NG2-CXCL12-/- mice did not show increased mortality, they behaved inconspicuously and no obvious developmental defects could be detected. Echocardiographic analysis of cardiac function in NG2-Cre x CXCL12flox/flox mice without infarction showed no significant difference in left ventricular (LV) performance and no evidence of abnormal geometry of the ventricles compared with controls. Assessment of SM22-Cre x CXCL12flox/flox mice after MI revealed reduced ejection fraction (EF) (29.0%±9.7 vs. 40.0%±8.1; n=10; p=0.027) and stroke volume (SV) (19.0µl±3.3 vs. 32.7µl±10.3; n=10; p=0.002) compared to non-transgenic controls. In contrast NG2-Cre x CXCL12flox/flox mice showed no significant changes in EF (34.6%±11.4 vs. 40.0%±8.1; n=10; p=0.368) and SV (27.7µl±7.3 vs. 32.7µl±10.3; n=10; p=0.303). Conclusion Our findings suggest that pericyte specific CXCL12 plays no major role in cardiac development and function after MI. In contrast, KO of CXCL12 in smooth muscle seems to deteriorate cardiac function after ischemia.

Near-field modeling of the head-related transfer function by using the dummy head sound source

Various approaches based on direct measurement have been used to obtain the precise headrelated transfer function (HRTF). However, several problems persist, such as scattering of sound source and distance effect, which are related to the measurement configuration. In this work, the modified dummy head having two sound sources located at the ear positions is applied as the sound source reciprocally to overcome the trouble. By using the near-field acoustic holography, the sound sources located in the ear holes are reconstructed from the measured data in the near-field hologram. One can predict the acoustic transfer function between the ear holes and the field positions at any point using the recovered source information described in spherical harmonics. The obtained transfer function is valid for predicting the binaural response from any sound source position. This configuration is possible to measure the near-field response with the relatively small scattering effect because of the low Helmholtz number of microphones. The far-field reconstruction of HRTF is also possible with the near-field measurement data using acoustical holography. The proposed method is demonstrated with the modified B&K HATS system, in which the microphones in the ear holes are replaced by pipe sources connected to the loudspeaker.

Hole-retaining Lobeplasty for Type I Ear Lobe Deformities.

The aesthetic aspect of Type I incomplete split ear lobe is underestimated. Most of the hole-retaining techniques described for large and split ear lobes are difficult to perform in Type I deformity. (1) To conduct a pilot study based on the postoperative review of the cases of Type I ear lobe deformities surgically managed with hole-retaining lobeplasty in a tertiary care centre in South India.(2) To assess the postoperative outcome of the hole retaining lobeplasty based on the Global aesthetic improvement scale and Patient satisfaction in Likert scale. A pilot study of hole-retaining lobeplasty technique was done based on the postoperative review of 6 patients with bilateral type1 incomplete split ear lobes who were operated in our institution with the same. The results were validated based on descriptive statistics and postoperative outcomes using GAIS score and Patient Satisfaction Score measured in a Likert scale. None of the patients had any postoperative complications. At six months follow up, all patients had centrally placed, circular ear holes, well settled support flap and rounded lobe contour with an average GAIS score of 4.83 ± 0.38. All the patients were satisfied with their newly created ear hole and lobe contour, with an average Patient Satisfaction Score of 4.8 ± 0.4. Hole- retaining lobeplasty is a simple, cost effective, single staged, day-case procedure for repair of Type I large ear holes, that can be easily duplicated by young plastic surgeons with is aesthetically better, circular and centrally placed ear hole with a more rounded ear lobe with support to prevent recurrence.

Finite Element Analysis to Study Tensile Strength Differences between Free and Attached Ear Lobules.

Recurrent ear lobule deformity is a chronic condition with aesthetic implications. The problem is normally addressed by certain improvisations of the traditional lobuloplasty technique. These include introduction of autologous tissue components like cartilage pieces to improve the structural integrity. Certain authors also advocate a different site for repiercing of the ear hole away from the lobuloplasty scar. Our study tries to understand the differences in the tensile strength between free and attached ear lobules, using finite element analysis. Eighteen healthy female volunteers with attached (eight subjects) and free ear lobules (10 subjects) were chosen, and the lobules were scanned using Artec 3D scanner. The model was then converted to free form or attached form (opposite to the form in which it was present originally) by decreasing or increasing the area of contact using geomagic software. Finite element analysis was then performed on both the models, and their yield max and, hence, the maximum load at the yield max at 0.7 strains according to previous studies were estimated and compared. The yield max and the corresponding load were found to be lesser in the free variety than in the attached variety. This experiment helps us to understand that when a structural difference in the ear lobule surgically may bring about a change in the tensile strength of the lobules. However, further clinical trials are required to clinically translate the same.

Vision-based driver ear recognition and spatial reconstruction

How to identify the ear hole more accurately and more quickly are critical for the active noise reduction in the road vehicle. Obscurations, causing by the long hair, the earphone, and some kind of caps, make the spatial location and orientation of the driver’s ears almost impossible. To solve these two problems, a new method was proposed to replace the original image scaling detection by combining the Haar-like algorithm with the scale size of the variable detection window in the recognition process. A depth positioning camera is added to the ear recognition, which may offer more accurate point vectors for the driver’s two ear holes. A simplified spatial reconstruction model was developed to assist the search when the piercing was occluded. After calculating the image-camera-cab projection mapping relationship, only four feature points are enough for the model’s data requirement. The test results show that the detection Frame Per Second (FPS) was improved to 8.8, and the ear hole’s positioning error is less than 0.1 cm. The proposed system can locate ear holes even with 100% obscurations. The research may have potential application as a front-end subsystem for the active noise reduction and voice interaction systems, improving the quality of acoustic control in cars.

Proximal ear hole injury heals by limited regeneration during the early postnatal phase in mice.

Ear pinna is a particular feature of mammals that shows several repair responses depending on age. Two millimeter hole made in the pinna of middle-aged female mice heals due to partial reconstitution of new tissues (limited regeneration), whereas a hole punched in the ear of young mice forms a scar tissue. In these studies, the injury is made in the center of the ear pinna, but little is known about the type of reparative response along the proximodistal polarity of the ear. This study evaluated the effect of pinna polarity, age, and sex in the ear hole-repairing response in Balb/c mice. Proximal injuries were repaired more efficiently by limited regeneration than wounds made in the middle region. Non-injured ear histological analysis revealed a higher presence of muscle, adipose tissue, cartilage, and larger blood vessels in the proximal ear area, which could influence ear hole closure by limited regeneration. To evaluate the healing response during ear growth, we punched a standard hole in the proximal area of the ear on postnatal day21 and 8-month-old mice (adults). Thirty-five days after the wound, both groups reached the same wound closure, despite the greater proportional size of holes made in the younger mice. Ear growth also improved ear hole closure in male mice. These results suggest that ear growth accelerates hole closure, providing an example of enhanced regenerative abilities in growing structures. Finally, hole closure kinetics in the growing ear indicated an early re-differentiation phase exhibited at 14 days post-wound. In conclusion, ear topography and growth positively influenced the healing response to ear holes, making it a tractable model to study in mammals.

Regenerative Drug Discovery Using Ear Pinna Punch Wound Model in Mice.

The ear pinna is a complex tissue consisting of the dermis, cartilage, muscles, vessels, and nerves. Ear pinna healing is a model of regeneration in mammals. In some mammals, including rabbits, punch wounds in the ear pinna close spontaneously; in common-use laboratory mice, they remain for life. Agents inducing ear pinna healing are potential regenerative drugs. We tested the effects of selected bioactive agents on 2 mm ear pinna wound closure in BALB/c mice. Our previous research demonstrated that a DNA methyltransferase inhibitor, zebularine, remarkably induced ear pinna regeneration. Although experiments with two other demethylating agents, RG108 and hydralazine, were unsuccessful, a histone deacetylase inhibitor, valproic acid, was another epigenetic agent found to increase ear hole closure. In addition, we identified a pro-regenerative activity of 4-ketoretinoic acid, a retinoic acid metabolite. Attempts to counteract the regenerative effects of the demethylating agent zebularine, with folates as methyl donors, failed. Surprisingly, a high dose of methionine, another methyl donor, promoted ear hole closure. Moreover, we showed that the regenerated areas of ear pinna were supplied with nerve fibre networks and blood vessels. The ear punch model proved helpful in testing the pro-regenerative activities of small-molecule compounds and observations of peripheral nerve regeneration.

12주간 발레프로그램이 초등 저학년 여학생의 건강체력과 자세에 미치는 영향

The purpose of this study is to verify the effect on the Health-related physical fitness (muscular strength, flexibility, muscular endurance, cardiorespiratory endurance, and body composition), posture, and stress coping of elementary school lower grade girls. A total of 30 subjects(EG n=15, CG n=15) was collected with a 60-minute ballet exercise program for 12 weeks. For analysis, two-way ANOVA was conducted to analyze interactions effects, the main effect, and the simple main effect. Results are 12 weeks ballet exercise program has effected positively of the flexibility and muscular endurance. At ASIS height showed an effect between groups. The right knee had a positive effect on pre and post-test. In the posterior posture, the 7th cervical vertebras, PSIS were positive on pre and post-test. The difference between groups of the right and left ear holes in the lateral posture. The left pelvic inclination has effected significantly differences in the pre and post-test of the experimental group. In the foot pressure, the right and left sides of the total foot pressure had positive effects on the balance on pre and post-test.

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.

Adult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation. We orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt. Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25±0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm-final ear hole size], mean±SEM), whereas MRL-vehicle mice healed well (1.4±0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74±0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3±0.1 vs. MRL-vehicle 1.4±0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63±0.03mm, mean±SEM vs. B6-vehicle control:0.25±0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice. In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.

Ear Crease Features Are Associated with Complexity of Coronary Lesions.

BackgroundThe presence of a Frank’s sign ear crease is closely correlated with coronary artery disease (CAD). The SYNTAX score indicates the complexity of coronary lesions. This present investigation sought to identify the correlation between SYNTAX score and several specific ear creases.Material/MethodsFour specific types of ear creases – crossing crease not originated from ear hole (CC-NEH), crossing crease originated from ear hole (CC-EH), vertical creases on the face side (VC-F), and vertical creases dividing earlobe and face (VC-EF) – were investigated in patients undergoing coronary angiography. A Frank’s sign score system was introduced based on the 4 creases. Demographic data, clinical data, and SYNTAX score were also documented. The association between ear creases and SYNTAX score, as well as the correlation between Frank’s score and SYNTAX score, were statistically analyzed.ResultsCC-NEH had the highest positive predictive value (positive predictive value=0.439), and VC-F had the highest negative predictive value for the detection of intermediate and high SYNTAX score (negative predictive value=1.000). VC-EF and CC-NEH were associated with intermediate and high SYNTAX scores (OR=2.913–7.694, all P<0.05). Only 2.9% of patients with Frank’s score=0 had intermediate or high SYNTAX scores, and 52.2% and 50.0% of patients with Frank’s sign score=3 and 4 had intermediate or high SYNTAX scores, respectively. The Frank’s sign score was significantly and positively correlated with SYNTAX score (r=0.457, P<0.001).ConclusionsFeatures of specific ear creases and Frank’s sign scores were associated with intermediate and high complexity of coronary lesions.

P21−/− Mice Exhibit Spontaneous Articular Cartilage Regeneration Post-Injury

Recent studies have implicated the cyclin dependent kinase inhibitor, p21, in enhanced tissue regeneration observed in MRL/MpJ "super-healer" mice. Specifically, p21 is downregulated in MRL cells and similar ear hole closure to MRL mice has been observed in p21-/- mice. However, the direct implications of p21 deletion in endogenous articular cartilage regeneration remain unknown. In this study, we investigated the role of p21 deletion in the ability of mice to heal full-thickness cartilage defects (FTCDs). C57BL/6 and p21-/- (Cdkn1atm1Tyj) mice were subjected to FTCD and assessment of cartilage healing was performed at 1 hour, 3 days, 1 week, 2 weeks, and 4 weeks post-FTCD using a 14-point histological scoring system. X-ray microscopy was used to quantify cartilage healing parameters (e.g., cartilage thickness, surface area/volume) between C57BL/6 and p21-/- mice. Absence of p21 resulted in increased spontaneous articular cartilage regeneration by 3 days post-FTCD. Furthermore, p21-/- mice presented with increased cartilage thickness at 1 and 2 weeks post-FTCD compared with uninjured controls, returning to baseline by 4 weeks post-FTCD. We report that p21-/- mice display enhanced articular cartilage regeneration post-FTCD compared with C57BL/6 mice. Furthermore, cartilage thickness was increased in p21-/- mice at 1 week post-FTCD compared with uninjured p21-/- mice and C57BL/6 mice.

Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse

BackgroundMost studies on regenerative medicine focus on cell-based therapies and transplantations. Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensively investigated in regenerative research. It is known that healing potential decreases with development and developmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerative capacity. MethodsWe applied zebularine, a nucleoside inhibitor of DNA methyltransferases, to stimulate the regenerative response in a model of ear pinna injury in mice. FindingsWe observed the regeneration of complex tissue that was manifested as improved ear hole repair in mice that received intraperitoneal injections of zebularine. Six weeks after injury, the mean hole area decreased by 83.2 ± 9.4% in zebularine-treated and by 43.6 ± 15.4% in control mice (p < 10−30). Combined delivery of zebularine and retinoic acid potentiated and accelerated this effect, resulting in complete ear hole closure within three weeks after injury. We found a decrease in DNA methylation and transcriptional activation of neurodevelopmental and pluripotency genes in the regenerating tissues. InterpretationThis study is the first to demonstrate an effective induction of complex tissue regeneration in adult mammals using zebularine. We showed that the synergistic action of an epigenetic drug (zebularine) and a transcriptional activator (retinoic acid) could be effectively utilized to induce the regenerative response, thus delineating a novel pharmacological strategy for regeneration. The strategy was effective in the model of ear pinna regeneration in mice, but zebularine acts on different cell types, therefore, a similar approach can be tested in other tissues and organs.

Regeneration-Competent and -Incompetent Murids Differ in Neutrophil Quantity and Function.

Regeneration is rare in mammals, but spiny mice (Acomys spp.) naturally regenerate skin and ear holes. Inflammation is thought to inhibit regeneration during wound healing, but aspects of inflammation contribute to both regeneration and pathogen defense. We compared neutrophil traits among uninjured, regeneration-competent (Acomys: A. cahirinus, A. kempi, A. percivali) and -incompetent (Mus musculus: Swiss Webster, wild-caught strains) murids to test for constitutive differences in neutrophil quantity and function between these groups. Neutrophil quantity differed significantly among species. In blood, Acomys had lower percentages of circulating neutrophils than Mus; and in bone marrow, Acomys had higher percentages of band neutrophils and lower percentages of segmented neutrophils. Functionally, Acomys and Mus neutrophils did not differ in their ability to migrate or produce reactive oxygen species, but Acomys neutrophils phagocytosed more fungal zymosan. Despite this enhanced phagocytosis activity, Acomys neutrophils were not more effective than Mus neutrophils at killing Escherichia coli. Interestingly, whole blood bacteria killing was dominated by serum in Acomys versus neutrophils only or neutrophils and serum in Mus, suggesting that Acomys primarily rely on serum to kill bacteria whereas Mus do not. These subtle differences in neutrophil traits may allow regeneration-competent species to offset damaging effects of inflammation without compromising pathogen defense.

Concise Review: Translating Regenerative Biology into Clinically Relevant Therapies: Are We on the Right Path?

Despite approaches in regenerative medicine using stem cells, bio‐engineered scaffolds, and targeted drug delivery to enhance human tissue repair, clinicians remain unable to regenerate large‐scale, multi‐tissue defects in situ. The study of regenerative biology using mammalian models of complex tissue regeneration offers an opportunity to discover key factors that stimulate a regenerative rather than fibrotic response to injury. For example, although primates and rodents can regenerate their distal digit tips, they heal more proximal amputations with scar tissue. Rabbits and African spiny mice re‐grow tissue to fill large musculoskeletal defects through their ear pinna, while other mammals fail to regenerate identical defects and instead heal ear holes through fibrotic repair. This Review explores the utility of these comparative healing models using the spiny mouse ear pinna and the mouse digit tip to consider how mechanistic insight into reparative regeneration might serve to advance regenerative medicine. Specifically, we consider how inflammation and immunity, extracellular matrix composition, and controlled cell proliferation intersect to establish a pro‐regenerative microenvironment in response to injuries. Understanding how some mammals naturally regenerate complex tissue can provide a blueprint for how we might manipulate the injury microenvironment to enhance regenerative abilities in humans. Stem Cells Translational Medicine 2018;7:220–231

PENGUKURAN ANTROPOMETRI UNTUK DESAIN PERALATAN YANG TERKAIT DENGAN TELINGA : SEBUAH SURVEI PENDAHULUAN

This study is a preliminary survey of a main study on anthropometry of ear. This study was done since the availability of ear anthropometry for Indonesian population was very limited. On the other, the availability of the ear anthropometry is very important. The current study aims to collect anthropometric data that are possible to consider in designing ear-related products. Thirty subjects aged in the range of 18-20 years old were involved in the measurement. Three dimensions of the outer ear, namely: ear hole length, ear connection length, and pinna length were measured. Result of this study shows an initial description of the outer ear dimensions that is useful in designing ear-related products, especially for Indonesian young adults.

The Rolling Earlobe Flap for Dilated Ear Holes Following Ear Gauging: A Novel Approach to Aesthetically Preserving Earlobe Soft Tissue Volume.

Patients are increasingly seeking repair of their earlobes following ear gauging. Research has shown that current repair techniques either excessively reduce the lobular volume or leave an obvious scar along the free edge of the earlobe. In our case series, we describe the use of a novel technique for repairing earlobes following ear gauging using a rolling earlobe flap that preserves the lobular volume and avoids leaving a scar on the free edge of the lobule. The procedure was performed on 3 patients (6 earlobes) who had defects from ear gauging that ranged from 3.0 to 6.5 cm. There were no postoperative complications of infection, wound dehiscence, flap necrosis, hypertrophic scars, or keloids, and all patients were highly satisfied with the postoperative results. This versatile technique allows for an aesthetically pleasing reconstruction of the lobule with the advantages of: the absence of a surgical scar on the free edge of the lobule, preserving the lobule volume, and presenting a highly customizable technique that allows lobules to be created with various shapes and volumes.

Of Salamanders and Spiny Mice: Common Features of Regeneration and Stem Cells

This review identifies the salient cellular and molecular features of regeneration of the skin and limbs of salamanders to see whether any of these features are in common with recent reports on the spiny mouse (Acomys), a mammal with some remarkable regenerative behavior. Other reports of mammalian regeneration are also highlighted. Mammals have classically been regarded as non-regenerating, but the regeneration of several embryonic and post-natal tissues as well as reports of adult skin and ear hole regeneration have recently been described. Common features of these regenerating systems and those of salamanders are discussed in terms of their immune systems, cytokine responses, matrix composition, and matrix metalloproteinases (MMP) activation as well as the occurrence of blastemas in these diverse organisms. The common involvement of stem cells in regenerating systems is also addressed. Mammals may not have lost all their regenerative powers, and a more diverse approach across other new model systems may reveal surprising behavior such as that seen in Acomys, the spiny mouse. Mammalian regenerating tissues share many common features with the champions of regeneration, the salamanders.

A Novel Earphone Type Sensor for Measuring Mealtime: Consideration of the Method to Distinguish between Running and Meals.

In this study, we describe a technique for estimating meal times using an earphone-type wearable sensor. A small optical sensor composed of a light-emitting diode and phototransistor is inserted into the ear hole of a user and estimates the meal times of the user from the time variations in the amount of light received. This is achieved by emitting light toward the inside of the ear canal and receiving light reflected back from the ear canal. This proposed technique allowed “meals” to be differentiated from having conversations, sneezing, walking, ascending and descending stairs, operating a computer, and using a smartphone. Conventional devices worn on the head of users and that measure food intake can vibrate during running as the body is jolted more violently than during walking; this can result in the misidentification of running as eating by these devices. To solve this problem, we used two of our sensors simultaneously: one in the left ear and one in the right ear. This was based on our finding that measurements from the left and right ear canals have a strong correlation during running but no correlation during eating. This allows running and eating to be distinguished based on correlation coefficients, which can reduce misidentification. Moreover, by using an optical sensor composed of a semiconductor, a small and lightweight device can be created. This measurement technique can also measure body motion associated with running, and the data obtained from the optical sensor inserted into the ear can be used to support a healthy lifestyle regarding both eating and exercise.

Abstract PR02: The SWI/SNF component Arid1a regulates regenerative capacity and carcinogenesis in a dose-dependent fashion

Abstract It is unclear if regenerative capacity can be dissociated from cancer risk, a question that is highly relevant for liver carcinogenesis. Frequent SWI/SNF and Arid1a loss-of-function mutations suggest tumor suppressive roles, but the functional impact of these mutations in tissue homeostasis and cancer is unclear. Mice without Arid1a possessed improved healing abilities after an array of injuries. After liver resection, chemical hepatocyte injury, and toxic bile duct injury, Arid1a deficient livers exhibited increased regeneration, reduced tissue damage, and improved organ function. Moreover, global homozygous Arid1a loss potentiated soft tissue healing after ear hole punch and hematopoietic recovery after irradiation. The chromatin state as reprogrammed by Arid1a loss restricted access to promoters by lineage-specific transcription factors that ordinarily suppress cell cycle reentry, thus increasing regeneration after injury. Intriguingly, the homozygous Arid1a deficient state protected mice from chemical injury induced hepatocellular carcinoma (HCC) and extended survival in a MYC-driven hepatoblastoma model. Since Arid1a mutations are most frequently heterozygous in human HCC genome studies, we examined the haploinsufficient state in these mouse models and observed accelerated carcinogenesis and metastasis. Transcriptome analysis identified dysregulated differentiation, proliferation, and metastasis programs. These models show that full deletion of Arid1a can enhance mammalian regeneration without increasing cancer risk, but that Arid1a’s tumor suppressor functions are highly sensitive to dose. This abstract is also presented as Poster A16. Citation Format: Xuxu Sun, Sam Wang, Thomas Maples, Lin Li, Liem Nguyen, Jen-Chieh Chuang, Mahsa Sorouri, Shuyuan Zhang, Linwei Wu, Cemre Celen, Hao Zhu. The SWI/SNF component Arid1a regulates regenerative capacity and carcinogenesis in a dose-dependent fashion. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr PR02.