Stabilization of ATF4 protein is required for the regulation of epithelial–mesenchymal transition of the avian neural crest

AbstractEpithelial–mesenchymal transition (EMT) permits neural crest cells to delaminate from the epithelial ectoderm and to migrate extensively in the embryonic environment. In this study, we have identified ATF4, a basic-leucine-zipper transcription factor, as one of the neural crest EMT regulators. Although ATF4 alone was not sufficient to drive the formation of migratory neural crest cells, ATF4 cooperated with Sox9 to induce neural crest EMT by controlling the expression of cell–cell and cell–extracellular matrix adhesion molecules. This was likely, at least in part, by inducing the expression of Foxd3, which encodes another neural crest transcription factor. We also found that the ATF4 protein level was strictly regulated by proteasomal degradation and p300-mediated stabilization, allowing ATF4 protein to accumulate in the nuclei of neural crest cells undergoing EMT. Thus, our results emphasize the importance of the regulation of protein stability in the neural crest EMT

Regulation of male germline transmission patterns by the Trp53-Cdkn1a pathway

A small number of offspring are born from the numerous sperm generated from spermatogonial stem cells (SSCs). However, little is known regarding the rules and molecular mechanisms that govern germline transmission patterns. Here we report that the Trp53 tumor suppressor gene limits germline genetic diversity via Cdkn1a. Trp53-deficient SSCs outcompeted wild-type (WT) SSCs and produced significantly more progeny after co-transplantation into infertile mice. Lentivirus-mediated transgenerational lineage analysis showed that offspring bearing the same virus integration were repeatedly born in a non-random pattern from WT SSCs. However, SSCs lacking Trp53 or Cdkn1a sired transgenic offspring in random patterns with increased genetic diversity. Apoptosis of KIT⁺ differentiating germ cells was reduced in Trp53- or Cdkn1a-deficient mice. Reduced CDKN1A expression in Trp53-deficient spermatogonia suggested that Cdkn1a limits genetic diversity by supporting apoptosis of syncytial spermatogonial clones. Therefore, the TRP53-CDKN1A pathway regulates tumorigenesis and the germline transmission pattern

Prolapse of Intussusception through the Anus as a Result of Sigmoid Colon Cancer

Adult intussusception is rare and most often associated with cancer. We report a case of intussuscepted sigmoid colon into the rectum protruding from the anus of a 47-year-old woman. The cause of the intussusception was sigmoid colon cancer. We removed the intussuscepted part of the sigmoid colon as well as the rectum and regional lymph nodes. The patient recovered uneventfully and there has been no evidence of recurrence of the cancer

Transcranial Direct Current Stimulation of the Temporoparietal Junction and Inferior Frontal Cortex Improves Imitation-Inhibition and Perspective-Taking with no Effect on the Autism-Spectrum Quotient Score

Lesions to brain regions such as the temporoparietal junction (TPJ) and inferior frontal cortex (IFC) are thought to cause autism-spectrum disorder (ASD). Previous studies indicated that transcranial direct current stimulation (tDCS) of the right TPJ improves social cognitive functions such as imitation-inhibition and perspective-taking. Although previous work shows that tDCS of the right IFC improves imitation-inhibition, its effects on perspective-taking have yet to be determined. In addition, the role of the TPJ and IFC in determining the Autism-Spectrum Quotient (AQ), which is a measure of autism spectrum traits, is still unclear. Thus, the current study performed tDCS on the right TPJ and the right IFC of healthy adults, and examined its effects on imitation-inhibition, perspective-taking and AQ scores. Based on previous studies, we hypothesized that anodal tDCS of the right IFC and right TPJ would improve imitation-inhibition, perspective-taking and the AQ score. Anodal tDCS of the right TPJ or IFC significantly decreased the interference effect in an imitation-inhibition task and the cost of perspective-taking in a perspective-taking task, in comparison to the sham stimulation control. These findings indicated that both the TPJ and the IFC play a role in imitation-inhibition and perspective-taking, i.e., control of self and other representations. However, anodal stimulation of the right TPJ and the right IFC did not alter participants’ AQ. This finding conflicts with results from previous brain imaging studies, which could be attributed to methodological differences such as variation in sex, age and ASD. Therefore, further research is necessary to determine the relationship between the TPJ and IFC, and the AQ

大腿四頭筋の超音波画像を用いた等尺性膝関節伸展筋力の推定

Muscle echo intensity (EI) determined by ultrasonography has recently been reported asan index of intramuscular fat. The muscle thickness (MT) and EI of the quadriceps femorismuscle were reported to be influenced by the muscle strength (MS) of the knee extensors.This study was performed to investigate whether the MT and EI of the quadriceps femorisare associated with the MS of knee extensors, and to establish a predictive formula for themaximal isometric MS of knee extensors.Forty healthy volunteers 20-59 years old were included in this study. The maximalisometric MS of knee extensors on the dominant extremity was measured at kneeflexion of 60°, and was defined as the maximal value over three repeated measurements.Transverse ultrasound images of the quadriceps on the dominant extremity were obtainedwith a B-mode ultrasound imaging device and multi-frequency linear transducer. Duringmeasurements, the participants were completely relaxed and sat comfortably withthe knee flexed at 90°. A 10-MHz transducer with gain of 58 dB was used during allmeasurements. The transducer was positioned perpendicular to the longitudinal axis ofthe quadriceps femoris, at the midpoint between the anterior superior iliac spine andthe proximal end of the patella. The same investigator then obtained three consecutiveimages. The subcutaneous fat thickness, MT of each muscle, and EI of each muscle wereanalyzed from three images acquired for the rectus femoris (RF) and vastus intermedius(VI), and the mean values of the three measurements were recorded. Pearson’s andSpearman’s correlation coefficients were calculated to investigate the relationships betweensubcutaneous fat thickness, MT, EI, physical characteristics, and MS. Stepwise multipleregression analysis was then performed with MS value as the dependent variable, and thecharacteristics of the participants and values from the ultrasound images as independentvariables. In addition, multiple regression analysis was performed in two groups dividedaccording to age, i.e., the young adult group and the middle-aged group.There were no significant differences in height, weight, BMI, or muscle circumferencebetween the young adult group and middle-aged group. MS showed significant negativecorrelations with subcutaneous fat thickness, RFEI, and VIEI, and significant positivecorrelations with height, weight, circumference, RFMT, and VIMT. Stepwise regressionanalysis identified height and VIMT as factors significantly associated with MS (adjustedR2 = 0.65). Height and VIMT contributed to MS in young and middle-aged individuals

Analysis of Ca²⁺ Response of Osteocyte Network by Three-dimensional Time-lapse Imaging in Living Bone

Osteocytes form a three-dimensional (3D) cellular network within the mineralized bone matrix. The cellular network has important roles in mechanosensation and mechanotransduction related to bone homeostasis. We visualized the embedded osteocyte network in chick calvariae and observed the flow-induced Ca²⁺ signaling in osteocytes using 3D time-lapse imaging. In response to the flow, intracellular Ca²⁺ ([Ca²⁺]i) significantly increased in developmentally mature osteocytes in comparison with young osteocytes in the bone matrix. To investigate the differences in response between young and developmentally mature osteocytes in detail, we evaluated the expression of osteocyte-related genes using the osteocyte-like cell line MLO-Y4, which was 3D-cultured within type I collagen gels. We found that the c-Fos, Cx43, Panx3, Col1a1, and OCN mRNA levels significantly increased on day 15 in comparison with day 7. These findings indicate that developmentally mature osteocytes are more responsive to mechanical stress than young osteocytes and have important functions in bone formation and remodeling