Differentiation stage-specific expression of transcriptional regulators for epithelial mesenchymal transition in dentate granule progenitors.

During the development of the mouse dentate gyrus (DG), granule neuronal progenitors (GNPs) arise from glial fibrillary acidic protein (GFAP)-expressing neural stem cells in the dentate notch. However, the transcriptional regulators that control their stepwise differentiation remain poorly defined. Since neurogenesis involves epithelial-to-mesenchymal transition (EMT)-like processes, we investigated the spatio-temporal expression profiles of the EMT transcription factors Zeb1, Scratch2 (Scrt2) and Nkx6-2 in relation to known GNP markers. Our results show that Zeb1 and Scrt2 exhibit sequential, but partially overlapping expression across embryonic and postnatal stages of GNP differentiation. Zeb1 is highly enriched in gfap-GFP+/Sox2+ neural stem/progenitor pools and subsets of Tbr2+/Prox1+/NeuroD+ intermediate GNPs, whereas Scrt2 predominates in Tbr2+/Prox1+/NeuroD+ GNPs. Strikingly, the neuronal EMT regulator Nkx6-2 shows selective expression in postnatal Tbr2+/Prox1+ GNPs, but it is excluded from embryonic counterparts. This temporally coordinated yet distinct expression of Zeb1, Scrt2 and Nkx6-2 reveals discrete transcriptional programs orchestrating GNP differentiation and neurogenic progression at embryonic versus postnatal stages of DG neurogenesis.

PSmad3+/Olig2- expression defines a subpopulation of gfap-GFP+/Sox9+ neural progenitors and radial glia-like cells in mouse dentate gyrus through embryonic and postnatal development.

In mouse dentate gyrus, radial glia-like cells (RGLs) persist throughout life and play a critical role in the generation of granule neurons. A large body of evidence has shown that the combinatorial expression of transcription factors (TFs) defines cell types in the developing central nervous system (CNS). As yet, the identification of specific TFs that exclusively define RGLs in the developing mouse dentate gyrus (DG) remains elusive. Here we show that phospho-Smad3 (PSmad3) is expressed in a subpopulation of neural progenitors in the DG. During embryonic stage (E14-15), PSmad3 was predominantly expressed in gfap-GFP-positive (GFP+)/Sox2+ progenitors located at the lower dentate notch (LDN). As the development proceeds (E16-17), the vast majority of PSmad3+ cells were GFP+/Sox2+/Prox1low+/Ki67+ proliferative progenitors that eventually differentiated into granule neurons. During postnatal stage (P1-P6) PSmad3 expression was observed in GFP+ progenitors and astrocytes. Subsequently, at P14-P60, PSmad3 expression was found both in GFP+ RGLs in the subgranular zone (SGZ) and astrocytes in the molecular layer (ML) and hilus. Notably, PSmad3+ SGZ cells did not express proliferation markers such as PCNA and phospho-vimentin, suggesting that they are predominantly quiescent from P14 onwards. Significantly PSmad3+/GFP+ astrocytes, but not SGZ cells, co-expressed Olig2 and S100ß. Together, PSmad3+/Olig2- expression serves as an exclusive marker for a specific subpopulation of GFP+ neural progenitors and RGLs in the mouse DG during both embryonic and postnatal period.

Effect of exercise devised to reduce arm tremor in the sighting phase of archery.

BACKGROUND: In archery training, side bridges are performed in a posture similar to archery shooting for training the muscles around the shoulder joint and the shoulder girdle of the pusher. AIM: The purpose of this study was to determine whether a low-tremor side-bridge exercise for 4 weeks improves bow tremor during archery movements. METHODS: Participants were 20 male college students. First, we measured the tremor during side bridges performed with trunk inclinations of 25°, 40°, 55°, and 70° using an accelerometer attached to the elbow joint and identified low-tremor side bridges. The participants were then randomly divided into intervention and non-intervention groups, and the low-tremor side bridges were performed for 4 weeks. RESULTS: The effect of the intervention was determined by measuring the total tremor value using an accelerometer attached to the bow and changes in the median power frequency (MdPF) of the middle deltoid, upper trapezius, and lower trapezius. This intervention reduced the bow tremor and the median power frequency of the middle deltoid (p < 0.05). CONCLUSIONS: The findings suggested that the tremor during the archery sighting phase could be reduced by performing side bridges with a specific trunk angle for a certain period of time. This intervention was also shown to reduce the intermediate frequency of the middle deltoid. The reduced tremor can shorten the sighting phase, which can facilitate injury prevention.

A cross-sectional survey of consistent rehabilitation through long-term care insurance in Japan: a questionnaire survey.

There seems to be a lack of consistency of maintenance/community-based rehabilitation through long-term care insurance. We aimed to clarify whether consistent rehabilitation can be performed through long-term care insurance by questionnaires. Materials and Methods: This study was a cross-sectional study in a nationwide survey among rehabilitation staff and care recipients who completed disease-specific rehabilitation and required maintenance/community-based rehabilitation through long-term care insurance. Consistency of rehabilitation was compared using Fisher's exact tests. The concordance of the rehabilitation evaluation and treatment conducted under medical and long-term care insurance was assessed using the κ coefficient. Results: Six hundred questionnaires from care recipients and staff were analyzed. Of the rehabilitation staff, 264 (44%) obtained rehabilitation plans from medical institutions. There was a significant difference between the responses of "referral from the same medical corporation" and "obtaining the rehabilitation plan" by Fisher's exact test (odds ratio: 3.242; P<0.001). Most rehabilitation treatments under medical insurance comprised walking or training with parallel rods/canes [498 patients (83%)], and 454 patients (76%) received stretching and range-of-motion training for the limbs and spine for long-term care insurance. Muscle strength evaluation was the most frequently conducted under medical and long-term care insurance [383 (73%) and 487 (83%), respectively]. The concordance of the evaluation and treatment content, except for disease-specific evaluation, was low (κ coefficient≤0.6). Conclusions: The rate of provision of rehabilitation plans was low, and evaluation and treatment content under medical and long-term care insurance was inconsistent. Our results draw attention to the need for consistent rehabilitation plans between disease-specific and maintenance/community-based rehabilitation.

Rehabilitation in the long-term care insurance domain: a scoping review.

PURPOSE: Since the enactment of the long-term care insurance (LTCI) act in 2000, the number of LTCI users has increased annually. However, evidence regarding what is being carried out as rehabilitation treatment under LTCI is lacking. In this study, a scoping review was performed to bridge this knowledge gap. METHODS: Articles related to rehabilitation in connection with LTCI published between April 2000 and November 2020 were searched for in PubMed, CINAHL, CENTRAL (Cochrane Central Register of Controlled Trials), Ichushi Web Ver.5, and CiNii and randomized controlled trials (RCTs) of rehabilitation provided under LTCI were examined. RESULTS: Of the 15,572 publications identified, 15 RCTs, including rehabilitation treatment by physiatrists and therapists, met the eligibility criteria of our review and were included. The rehabilitation trials in the 15 RCTs varied and included balance training, exercise therapy, cognitive tasks, and activities such as singing and dancing. The results allowed us to focus on three categories: fall prevention, dementia, and theory and tools interventions related to occupational therapy practice. CONCLUSION: The focal points of attention in the rehabilitation treatment of LTCI were identified. However, the physical function, quality of life, and activities of daily living (ADL) of those who "need support" vary from person to person. Therefore, the consolidation of evidence on rehabilitation treatment of LTCI must be continued.

Cultural validation and language translation of the scientific SCI exercise guidelines for use in Indonesia, Japan, Korea, and Thailand.

CONTEXT: Indonesia, Japan, Korea, Thailand. OBJECTIVE: To culturally validate and translate the Scientific Exercise Guidelines for Adults with Spinal Cord Injury (SEG-SCI) for use in four Asian countries. DESIGN: Systematic Review. PARTICIPANTS: N/A. METHODS: A systematic review was conducted to identify all published English- and local-language studies conducted in Indonesia, Japan, Korea, and Thailand, testing the effects of exercise training interventions on fitness and cardiometabolic health in adults with acute or chronic SCI. Protocols and results from high-quality controlled studies were compared with the SEG-SCI. Forward and backward translation processes were used to translate the guidelines into Bahasa Indonesian, Japanese, Korean and Thai languages. RESULTS: Fifteen studies met the review criteria. At least one study from each country implemented exercise prescriptions that met or exceeded the SEG-SCI. Two were controlled studies. In those two studies, relative to control conditions, participants in exercise conditions achieved significant improvements in fitness or cardiometabolic health outcomes only when the exercise intervention protocol met or exceeded the SEG-SCI. During the language translation processes, end-users confirmed that SEG-SCI language and terminology were clear. CONCLUSION: Clinical researchers in Indonesia, Japan, Korea and Thailand have implemented exercise protocols that meet or exceed the SCI-SEG. Results of high-quality studies align with the SEG-SCI recommendations. Based on this evidence, we recommend that the SEG-SCI be adopted in these countries. The cultural validation and translation of the SEG-SCI is an important step towards establishing consistent SCI exercise prescriptions in research, clinical and community settings around the world.

The polarity and properties of radial glia-like neural stem cells are altered by seizures with status epilepticus: Study using an improved mouse pilocarpine model of epilepsy.

In the adult mouse hippocampus, new neurons are produced by radial glia-like (RGL) neural stem cells in the subgranular zone, which extend their apical processes toward the molecular layer, and express the astrocyte marker glial fibrillary acidic protein, but not the astrocyte marker S100ß. In rodent models of epilepsy, adult hippocampal neurogenesis was reported to be increased after acute and mild seizures, but to be decreased by chronic and severe epilepsy. In the present study, we investigated how the severity of seizures affects neurogenesis and RGL neural stem cells in acute stages of epilepsy, using an improved mouse pilocarpine model in which pilocarpine-induced hypothermia was prevented by maintaining body temperature, resulting in a high incidence rate of epileptic seizures and low rate of mortality. In mice that experienced seizures without status epilepticus (SE), the number of proliferating progenitors and immature neurons were significantly increased, whereas no changes were observed in RGL cells. In mice that experienced seizures with SE, the number of proliferating progenitors and immature neurons were unchanged, but the number of RGL cells with an apical process was significantly reduced. Furthermore, the processes of the majority of RGL cells extended inversely toward the hilus, and about half of the aberrant RGL cells expressed S100ß. These results suggest that seizures with SE lead to changes in the polarity and properties of RGL neural stem cells, which may direct them toward astrocyte differentiation, resulting in the reduction of neural stem cells producing new granule cells. This also suggests the possibility that cell polarity of RGL stem cells is important for maintaining the stemness of adult neural stem cells.

The emissions of CO2 and other volatiles from the world's subaerial volcanoes.

Volcanoes are the main pathway to the surface for volatiles that are stored within the Earth. Carbon dioxide (CO2) is of particular interest because of its potential for climate forcing. Understanding the balance of CO2 that is transferred from the Earth's surface to the Earth's interior, hinges on accurate quantification of the long-term emissions of volcanic CO2 to the atmosphere. Here we present an updated evaluation of the world's volcanic CO2 emissions that takes advantage of recent improvements in satellite-based monitoring of sulfur dioxide, the establishment of ground-based networks for semi-continuous CO2-SO2 gas sensing and a new approach to estimate key volcanic gas parameters based on magma compositions. Our results reveal a global volcanic CO2 flux of 51.3 ± 5.7 Tg CO2/y (11.7 × 1011 mol CO2/y) for non-eruptive degassing and 1.8 ± 0.9 Tg/y for eruptive degassing during the period from 2005 to 2015. While lower than recent estimates, this global volcanic flux implies that a significant proportion of the surface-derived CO2 subducted into the Earth's mantle is either stored below the arc crust, is efficiently consumed by microbial activity before entering the deeper parts of the subduction system, or becomes recycled into the deep mantle to potentially form diamonds.

Non-radial tortuous migration with cell polarity alterations of newly generated granule neurons in the neonatal rat dentate gyrus.

To establish functional neuronal circuits, newborn neurons generally migrate from the ventricular germinal zones to their final positions during embryonic periods. However, most excitatory neurons of the hippocampal dentate gyrus are born postnatally in the hilus, far from the lateral ventricle. Newly generated granule neurons must then migrate to the surrounding granule cell layer (GCL), which suggests that newborn granule cells may migrate by unique cellular mechanisms. In the present study, we describe the migratory behaviors of postnatally generated granule neurons using combined retroviral labeling and time-lapse imaging analysis. Our results show that whereas half of the newly generated neurons undergo radial migration, the remainder engages in more complex migratory patterns with veering and turning movements accompanied by process formation and cell polarity alterations. These data reveal a previously unappreciated diversity of mechanisms by which granule neurons distribute throughout the GCL to contribute to hippocampal circuitry.

The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder.

Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.

Analysis of muscular activity in archery: a comparison of skill level.

BACKGROUND: A series of archery shooting movements requires strong activity of muscles attached to the shoulder girdle and upper extremity. It is unclear which muscles influence archery competition scores. This study aimed to compare muscle activity of the shoulder girdle and upper extremity during shooting movements and to analyze the muscles influencing in archery skill improvement. METHODS: Thirty male archers, who were divided into three groups based on skill level (elite, pre-elite, and beginner), were included in this study. The angle of shoulder joint abduction, horizontal extension, and elbow joint flexion, as well as the electromyographic activity of the upper trapezius, lower trapezius, deltoid middle, deltoid posterior, biceps brachii, and triceps brachii muscles at the point of stabilization during shooting, were measured. RESULTS: In the elite group, the activity of the lower trapezius muscle was significantly higher (P<0.05), while that of the biceps brachii and triceps brachii muscles were significantly lower (P<0.05) compared to the pre-elite and beginner groups. CONCLUSIONS: The lower trapezius muscle of the draw arm is actively involved in scapular fixation during shooting. Therefore, in order to improve the archery competition score, training focused on the lower trapezius muscle is necessary.

Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development.

In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes. Phosphatase analysis suggested that both phosphorylated and dephosphorylated CXCR4 exist on the plasma membrane, whereas CXCR4 in intracellular puncta was mainly dephosphorylated. Intraventricular administration of the CXCR4 antagonist AMD3100 resulted in the disappearance of CXCR4 expression from the intracellular puncta, and its appearance on the plasma membranes. Furthermore, AMD3100 treatment resulted in precocious differentiation, delayed migration, and ectopic GCPs. Taken together, these results suggest that during the development and migration of GCPs, CXCR4 on the plasma membrane is phosphorylated, internalized, sorted to the centrosomes, Golgi apparatus, and lysosomes, and functionally regulates GCP differentiation, migration and positioning.

The Effect of Ankle Taping to Restrict Plantar Flexion on Ball and Foot Velocity During an Instep Kick in Soccer.

CONTEXT: Posterior ankle impingement syndrome is a common disorder in soccer players and ballet dancers. In soccer players, it is caused by the repetitive stress of ankle plantar flexion due to instep kicking. Protective ankle dorsiflexion taping is recommended with the belief that it prevents posterior ankle impingement. However, the relationship between ankle taping and ball-kicking performance remains unclear. OBJECTIVE: To demonstrate the relationship between the restrictions of ankle taping and performance of an instep kick in soccer. DESIGN: Laboratory-based repeated-measures. SETTING: University laboratory. PARTICIPANTS: 11 male university soccer players. INTERVENTION: The subjects' ankle plantar flexion was limited by taping. Four angles of planter flexion (0°, 15°, 30°, and without taping) were formed by gradation limitation. The subjects performed maximal instep kicks at each angle. MAIN OUTCOME MEASURES: The movements of the kicking legs and the ball were captured using 3 high-speed cameras at 200 Hz. The direct linear-transformation method was used to obtain 3-dimensional coordinates using a digitizing system. Passive ankle plantar-flexion angle, maximal plantar-flexion angle at ball impact, ball velocity, and foot velocity were measured. The data were compared among 4 conditions using repeated-measures ANOVA, and the correlations between ball velocity and foot velocity and between ball velocity and toe velocity were calculated. RESULTS: Ankle dorsiflexion taping could gradually limit both passive plantar flexion and plantar flexion at the impact. Furthermore, limitation of 0° and 15° reduced the ball velocity generated by instep kicks. CONCLUSION: Plantar-flexion-limiting taping at 30° has a potential to prevent posterior ankle impingement without decreasing the ball velocity generated by soccer instep kicks.

Radiographic visualization of magma dynamics in an erupting volcano.

Radiographic imaging of magma dynamics in a volcanic conduit provides detailed information about ascent and descent of magma, the magma flow rate, the conduit diameter and inflation and deflation of magma due to volatile expansion and release. Here we report the first radiographic observation of the ascent and descent of magma along a conduit utilizing atmospheric (cosmic ray) muons (muography) with dynamic radiographic imaging. Time sequential radiographic images show that the top of the magma column ascends right beneath the crater floor through which the eruption column was observed. In addition to the visualization of this magma inflation, we report a sequence of images that show magma descending. We further propose that the monitoring of temporal variations in the gas volume fraction of magma as well as its position in a conduit can be used to support existing eruption prediction procedures.

Ninein is essential for the maintenance of the cortical progenitor character by anchoring the centrosome to microtubules.

The mammalian cerebral cortex develops from proliferative apical progenitor cells (APs) that exhibit cell cycle-dependent nuclear movement (interkinetic nuclear migration; INM), which may be important for efficient and continuous production of neurons. The Pax6 transcription factor plays a major role in INM by regulating various downstream molecules. We have previously observed abnormal INM and unstable localization of the centrosome in APs of the Pax6 homozygous mutant rat embryo. To understand the mechanisms of INM, we focused on the centrosomes of APs. One of the centrosomal proteins, ninein, is specifically localized in the centrosome of APs. We observed a dramatic downregulation of ninein in APs of the Pax6 mutant. Moreover, knockdown of ninein by RNAi induced ectopic distribution of reduced numbers of BrdU-positive (S-phase) and PH3-positive (M-phase) cells. Furthermore, time-lapsed imaging demonstrated that knockdown of ninein in vivo induced abnormal INM. Finally, we observed impaired microtubule regrowth in neural progenitors taken from Pax6 homozygous mutant rat embryos, which was recovered by via ninein overexpression. We also found that ninein knockdown enlarged the surface size area of apical endfeet of the APs. Our results suggest that ninein plays a role in the molecular machinery essential for INM by connecting microtubules to the centrosome.

Aggregates with lysozyme and ovalbumin show features of amyloid-like fibrils.

The interaction of egg-white lysozyme with N-ovalbumin, the native form of egg-white ovalbumin with the denaturation temperature, T(m), of 78 °C, was investigated by the inhibition of lysozyme muramidase activity, differential scanning calorimetry, and circular dichroism assay as indicators. Signals for the interaction were the most prominent when the mixture of lysozyme and N-ovalbumin was co-heated at 72 °C, slightly lower than the T(m) of N-ovalbumin. The interaction was also marked when unheated lysozyme was mixed with N-ovalbumin preheated at 72 °C. Moreover, the mixture rapidly formed fibrous precipitates, which were positive for thioflavin T fluorescent emission, a marker for the amyloid fibril formation. Also electron microscopic observation exhibited features of fibrils. The interaction potency of ovalbumin was ascribed to the tryptic fragment ILELPFASGT MSMLVLLPDE VSGLEQLESIINFEK (residues 229-263), derived from the 2B strands 2 and 3 of ovalbumin. From lysozyme, on the other hand, the chymotryptic peptide RNRCKGTDVQAW (residues 112-123), including cluster 6, and the chymotryptic/tryptic peptide GILQINSRW (residues 54-62), including cluster 3, were responsible for the interaction with N-ovalbumin. Interestingly, this nonamer peptide was found to have the ability to self-aggregate. To the authors knowledge, this may be the first report to document the possible involvement of dual proteins in the formation of amyloid-like fibrils.

Differential long-term stimulation of type I versus type III collagen after infrared irradiation.

BACKGROUND: The dermis is composed primarily of type I (soft) and type III (rigid scar-like) collagen. Collagen degradation is considered the primary cause of skin aging. Studies have proved the efficacy of infrared irradiation on collagen stimulation but have not investigated the differential long-term effects of infrared irradiation on type I and type III collagen. OBJECTIVE: To determine differential long-term stimulation of type I and type III collagen after infrared (1,100-1,800 nm) irradiation. METHODS AND MATERIALS: In vivo rat tissue was irradiated using the infrared device. Histology samples were analyzed for type I and III collagen stimulation, visual changes from baseline, and treatment safety up to 90 days post-treatment. RESULTS: Infrared irradiation provided long-term stimulation of type I collagen and temporary stimulation of type III collagen. Treatment also created long-term smoothing of the epidermis, with no observed complications. CONCLUSIONS: Infrared irradiation provides safe, consistent, long-term stimulation of type I collagen but only short-term stimulation in the more rigid type III collagen. This is preferential for cosmetic patients looking for improvement in laxity and wrinkles while seeking smoother, more youthful skin.

Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator.

Pax6 is a highly conserved transcription factor among vertebrates and is important in various developmental processes in the central nervous system (CNS), including patterning of the neural tube, migration of neurons, and formation of neural circuits. In this review, we focus on the role of Pax6 in embryonic and postnatal neurogenesis, namely, production of new neurons from neural stem/progenitor cells, because Pax6 is intensely expressed in these cells from the initial stage of CNS development and in neurogenic niches (the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricle) throughout life. Pax6 is a multifunctional player regulating proliferation and differentiation through the control of expression of different downstream molecules in a highly context-dependent manner.

Facial reanimation by transposition of the masseter muscle combined with tensor fascia lata, using the zygomatic arch as a pulley.

We have created a new way of reanimating the face, involving transposition of the masseter muscle combined with tensor fascia lata, and using the zygomatic arch as a trochlea to reconstruct the inferior facial paralysis. We used it on five patients who had facial palsy after excision of malignant parotid tumours. The wide skin defect that exposed the masseter muscle after total parotidectomy was reconstructed with a free flap. This method differs from those of other methods of transposing the masseter muscle in that force is applied at an upper lateral angle. Our method provided dynamic raising of the upper lip, the corner of the mouth, and the nasolabial fold in four patients. We consider it to be useful, particularly for prompt surgical reconstruction of facial palsy after total parotidectomy with a wide defect in the skin of the cheek.

Correlation between projection of the ear, the inferior crus, and the antihelical body: analysis based on computed tomography.

We investigated the correlation between projection of the ear and the antihelical folding angle to clarify which portion of the antihelix should be corrected in reconstruction of prominent ears using computed tomograms of 15 ears in 11 patients with fractures of the facial bones. The angle of the scaphotriangular fossa indicating the superior crus, cymba conchae-triangular fossa angle indicating the inferior crus, and the scaphoconchal angle indicating the antihelical body were measured. There was no relation between the cranioauricular angle and the angle of the scaphotriangular fossa. However, there were significant relations between the cranioauricular angle and the cymba conchae-triangular fossa angle, and the cranioauricular and scaphoconchal angles, which suggests that emphasis should be placed on reconstruction of the inferior crus and antihelical body when prominent ears are being corrected.