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We have recently shown delayed increases in GABAB receptor (GABABR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3 regions, at 15–30 days after the systemic single administration of trimethyltin (TMT) in mice. An attempt was thus made to determine whether the delayed increases return to the control levels found in naive mice afterward. In the DG on hippocampal slices obtained at 90 days after the administration, however, marked increases were still seen in protein levels of both GABABR1 and GABABR2 subunits without significant changes in calbindin and glial fibrillary acidic protein (GFAP) levels on immunoblotting analysis. Fluoro-Jade B staining clearly revealed the absence of degenerated neurons from the DG at 90 days after the administration. Although co-localization was invariably detected between GABABR2 subunit and GFAP in the DG at 30 days on immunohistochemical analysis, GABABR2-positive cells did not merge well with GFAP-positive cells in the DG at 90 days. These results suggest that both GABABR1 and GABABR2 subunits would be tardily and sustainably up-regulated by cells other than neurons and astrocytes in the murine DG at 90 days after a systemic single injection of TMT.

Study Design Clinical case series. Purpose This study aimed to report dynamization–posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysis-related spondyloarthropathy (HSA), and investigate patients’ postoperative course within 2 years. Overview of Literature HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed “dynamization–PLIF” in hemodialysis patients with destructive vertebral endplate changes. Methods We retrospectively examined patients with HSA who underwent dynamization–PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant. Results We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization–PLIF (lumbar lordosis, 28.4°–35.5°; local lordosis, 2.7°–12.8°; p

Abstract In this study, we propose a method to automate fruit harvesting with a fruit harvesting robot equipped with robotic arms. Given the future growth of the world population, food shortages are expected to accelerate. Since much of Japan’s agriculture is dependent on imports, it is expected to be greatly affected by this upcoming food shortage. In recent years, the number of agricultural workers in Japan has been decreasing and the population is aging. As a result, there is a need to automate and reduce labor in agricultural work using agricultural machinery. In particular, fruit cultivation requires a lot of manual labor due to the variety of orchard conditions and tree shapes, causing mechanization and automation to lag behind. In this study, a dual-armed fruit harvesting robot was designed and fabricated to reach most of the fruits on joint V-shaped trellis that was cultivated and adjusted for the robot. To harvest the fruit, the fruit harvesting robot uses sensors and computer vision to detect and estimate the position of the fruit and then inserts end-effectors into the lower part of the fruit. During this process, there is a possibility of collision within the robot itself or with other fruits depending on the position of the fruit to be harvested. In this study, inverse kinematics and a fast path planning method using random sampling is used to harvest fruits with robot arms. This method makes it possible to control the robot arms without interfering with the fruit or the other robot arm by considering them as obstacles. Through experiments, this study showed that these methods can be used to detect pears and apples outdoors and automatically harvest them using the robot arms.

Introduction: Reportedly, the medialization of the common carotid artery (MCCA) to be a vascular anomaly with a potential risk of intraoperative carotid artery injury. Nevertheless, among spine surgeons, the presence of MCCA has not been well recognized. Methods: We retrospectively reviewed consecutive patients who underwent cervical radiographs and magnetic resonance imaging (MRI) examinations in a single spine center. Using MRI, the MCCA grade was classified into grades 1 to 3 in order of severity. Radiographic measurement included C2-C7 angles as cervical lordosis, cervical sagittal vertical axis (C-SVA), T1 slope (T1S), and T1S-cervical lordosis mismatch. We compared each patient's background and radiographic parameters between patients with each of the three MCCA grades. The continuous variables were compared using the Jonckheere-Terpstra trend test and the proportions were compared using the Cochran-Armitage trend test to investigate the trend of variables in three grades. Results: The present study included data from 133 eligible patients (65 males and 68 females) with a mean age of 63.7 (±14.2) years. The details of MCCA grading were as follows: grade 1, n=101; grade 2, n=27; and grade 3, n=5. With an increasing MCCA grade, age (61.9±14.0, 68.2±13.8, and 76.4±9.4 years for grades 1, 2, and 3, respectively, p=0.005) and proportion of female (p

Among the elderly, even minor injuries can cause cervical spine fractures. With the increasing number of nonagenarians, the opportunities for treatment of cervical spine injuries in nonagenarians are getting to be more common. Conservative therapy is often chosen in nonagenarians with cervical spine injuries because of high risk associated with surgical treatment; however, we present herein the cases of three patients in nonagenarians who underwent surgical treatment for cervical spine injury. After a fall, three cases of nonagenarians who lived alone and independent were diagnosed with a Jefferson fracture and minor dislocated type II odontoid fracture, a C4 fracture with diffuse idiopathic skeletal hyperostosis, and a fracture-dislocation of C2, respectively. Their past medical history included several diseases, but we decided that spine surgery under general anesthesia was acceptable based on their pre-injury condition. We performed posterior fixation for all cases. As a result, while two patients developed postoperative minor complications, all cases showed favorable postoperative courses. They acquired independent or partially assisted walking and were transferred to the hospital for rehabilitation. If fundamental activity of daily living and general condition permit, posterior fixation seems to be a good choice even in nonagenarians.

Abstract Automation and labor saving in agriculture have been required recently. However, mechanization and robots for growing fruits have not been advanced. This study proposes a method of detecting fruits and automated harvesting using a robot arm. A highly fast and accurate method with a Single Shot MultiBox Detector is used herein to detect the position of fruit, and a stereo camera is used to detect the three-dimensional position. After calculating the angles of the joints at the detected position by inverse kinematics, the robot arm is moved to the target fruit’s position. The robot then harvests the fruit by twisting the hand axis. The experimental results showed that more than 90% of the fruits were detected. Moreover, the robot could harvest a fruit in 16 s.

Abstract Nucleotide excision repair (NER) is a versatile DNA repair pathway, which can remove an extremely broad range of base lesions from the genome. In mammalian global genomic NER, the XPC protein complex initiates the repair reaction by recognizing sites of DNA damage, and this depends on detection of disrupted/destabilized base pairs within the DNA duplex. A model has been proposed that XPC first interacts with unpaired bases and then the XPD ATPase/helicase in concert with XPA verifies the presence of a relevant lesion by scanning a DNA strand in 5′-3′ direction. Such multi-step strategy for damage recognition would contribute to achieve both versatility and accuracy of the NER system at substantially high levels. In addition, recognition of ultraviolet light (UV)-induced DNA photolesions is facilitated by the UV-damaged DNA-binding protein complex (UV-DDB), which not only promotes recruitment of XPC to the damage sites, but also may contribute to remodeling of chromatin structures such that the DNA lesions gain access to XPC and the following repair proteins. Even in the absence of UV-DDB, however, certain types of histone modifications and/or chromatin remodeling could occur, which eventually enable XPC to find sites with DNA lesions. Exploration of novel factors involved in regulation of the DNA damage recognition process is now ongoing.

Summary: The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role of mTORC1 in skeletogenesis has been investigated previously, here we show a critical role of mTORC1/4E-BPs/SOX9 axis in regulating skeletogenesis through its expression in undifferentiated mesenchymal cells. Inactivation of Raptor, a component of mTORC1, in limb buds before mesenchymal condensations resulted in a marked loss of both cartilage and bone. Mechanistically, we demonstrated that mTORC1 selectively controls the RNA translation of Sox9, which harbors a 5′ terminal oligopyrimidine tract motif, via inhibition of the 4E-BPs. Indeed, introduction of Sox9 or a knockdown of 4E-BP1/2 in undifferentiated mesenchymal cells markedly rescued the deficiency of the condensation observed in Raptor-deficient mice. Furthermore, introduction of the Sox9 transgene rescued phenotypes of deficient skeletal growth in Raptor-deficient mice. These findings highlight a critical role of mTORC1 in mammalian skeletogenesis, at least in part, through translational control of Sox9 RNA. : Iezaki et al. demonstrated that the mTORC1/SOX9 axis has essential roles in skeletal development through its expression in undifferentiated mesenchymal cells in vivo. Moreover, they identified that mTORC1/4E-BPs cascade regulates the translation of Sox9 RNA in undifferentiated mesenchymal cells, highlighting a critical role of mTORC1/4E-BPs/SOX9 axis in regulating mammalian skeletogenesis. Keywords: mTORC1, translation, Sox9, undifferentiated mesenchymal cells

We previously demonstrated a marked upregulation in the bone morphogenic protein (BMP)/growth differentiation factor (GDF) family member, GDF5, which is capable of promoting brown adipogenesis, in brown adipose tissue (BAT) of obese mice. In this study, we identified other GDF family members, besides GDF5 that are responsive to different obesogenic signals in BAT using inborn and acquired obesity animal models. In BAT from leptin-deficient ob/ob mice, GDF1 expression was preferentially downregulated, whereas the expression of several other genes in the BMP/GDF family, including GDF5, was upregulated. Moreover, in cultured brown adipocytes exposed to tunicamycin and hydrogen peroxide, at concentrations not affecting cellular viability, GDF1 expression was significantly downregulated. Recombinant GDF1 failed to significantly alter brown adipogenesis, despite the promoted phosphorylation of Smad1/5/8 in cultured brown adipocytes, but accelerated Smad1/5/8 phosphorylation with a concomitant increase in the number of migrating cells during exposure in a manner sensitive to activin-like kinase inhibitors in macrophagic RAW264.7 cells. Similarly, accelerated migration was observed in murine peritoneal macrophages exposed to GDF1. These results indicate that obesity could lead to predominant downregulation of GDF1 expression in BAT, which can modulate cellular migration through a mechanism relevant to activation of the downstream Smad signaling pathway in adjacent macrophages.

The capture of antimicrobial resistance genes (ARGs) by mobile genetic elements (MGEs) plays a critical role in resistance acquisition for human-associated bacteria. Although aquaculture environments are recognized as important reservoirs of ARGs, intra- and intercellular mobility of MGEs discovered in marine organisms is poorly characterized. Here, we show a new pattern of interspecies ARGs transfer involving a 'non-conjugative' integrative element. To identify active MGEs in a Vibrio ponticus isolate, we conducted whole-genome sequencing of a transconjugant obtained by mating between Escherichia coli and Vibrio ponticus. This revealed integration of a plasmid (designated pSEA1) into the chromosome, consisting of a self-transmissible plasmid backbone of the MOBH group, ARGs, and a 13.8-kb integrative element Tn6283. Molecular genetics analysis suggested a two-step gene transfer model. First, Tn6283 integrates into the recipient chromosome during suicidal plasmid transfer, followed by homologous recombination between the Tn6283 copy in the chromosome and that in the newly transferred pSEA1. Tn6283 is unusual among integrative elements in that it apparently does not encode transfer function and its excision barely generates unoccupied donor sites. Thus, its movement is analogous to the transposition of insertion sequences rather than to that of canonical integrative and conjugative elements. Overall, this study reveals the presence of a previously unrecognized type of MGE in a marine organism, highlighting diversity in the mode of interspecies gene transfer.

Although β-cryptoxanthin, a xanthophyll carotenoid, has been shown to exert an anabolic effect on bone calcification, little attention has been paid thus far to the precise mechanism of bone remodeling. Daily oral administration of β-cryptoxanthin significantly inhibited osteoclastic activation as well as reduction of bone volume in ovariectomized mice. In vitro studies revealed that β-cryptoxanthin inhibited differentiation and maturation of osteoclasts by repression of the nuclear factor-κB-dependent transcriptional pathway. Our results suggest that supplementation with β-cryptoxanthin would be beneficial for prophylaxis and for therapy of metabolic bone diseases associated with abnormal osteoclast activation.

Purpose: Evaluate in vivo hemodynamic and morphological biomarkers of intracranial aneurysms, using magnetic resonance fluid dynamics (MRFD) and MR-based patient specific computational fluid dynamics (CFD) in order to assess the risk of rupture. Methods: Forty-eight intracranial aneurysms (10 ruptured, 38 unruptured) were scrutinized for six morphological and 10 hemodynamic biomarkers. Morphological biomarkers were calculated based on 3D time-offlight magnetic resonance angiography (3D TOF MRA) in MRFD analysis. Hemodynamic biomarkers were assessed using both MRFD and CFD analyses. MRFD was performed using 3D TOF MRA and 3D cine phase-contrast magnetic resonance imaging (3D cine PC MRI). CFD was performed utilizing patient specific inflow-outflow boundary conditions derived from 3D cine PC MRI. Univariate analysis was carried out to identify statistically significant biomarkers for aneurysm rupture and receiver operating characteristic (ROC) analysis was performed for the significant biomarkers. Binary logistic regression was performed to identify independent predictive biomarkers. Results: Morphological biomarker analysis revealed that aneurysm size [P = 0.021], volume [P = 0.035] and size ratio [P = 0.039] were statistically significantly different between the two groups. In hemodynamic biomarker analysis, MRFD results indicated that ruptured aneurysms had higher oscillatory shear index (OSI) [OSI.max, P = 0.037] and higher relative residence time (RRT) [RRT.ave, P = 0.035] compared with unruptured aneurysms. Correspondingly CFD analysis demonstrated significant differences for both average and maximum OSI [OSI.ave, P = 0.008; OSI.max, P = 0.01] and maximum RRT [RRT.max, P = 0.045]. ROC analysis revealed AUC values greater than 0.7 for all significant biomarkers. Aneurysm volume [AUC, 0.718; 95% CI, 0.491-0.946] and average OSI obtained from CFD [AUC, 0.774; 95% CI, 0.586-0.961] were retained in the respective logistic regression models. Conclusion: Both morphological and hemodynamic biomarkers have significant influence on intracranial aneurysm rupture. Aneurysm size, volume, size ratio, OSI and RRT could be potential biomarkers to assess aneurysm rupture risk. [ABSTRACT FROM AUTHOR]

A new type of smoothed finite element method (S-FEM), F-barES-FEM-T4, is demonstrated in static large deformation elastoplastic cases. F-barES-FEM-T4 combines the edge-based S-FEM (ES-FEM) and the node-based S-FEM (NS-FEM) for 4-node tetrahedral (T4) elements with the aid of the F-bar method in order to resolve the major issues of Selective ES/NS-FEM-T4. As well as most of the other S-FEMs, F-barES-FEM-T4 inherits pure displacement-based formulation and thus has no increase in DOF.Moreover, the cyclic smoothing procedure introduced in F-barES-FEM-T4 is effective to adjust the smoothing level so that pressure checkerboarding (oscillation) is suppressed reasonably. Some examples of static large deformation analyses for elastoplastic materials proof the excellent performance of F-barES-FEM-T4 in contrast to the conventional hybrid T4 element formulation. [ABSTRACT FROM AUTHOR]

Extracellular signal-regulated kinase 5 (Erk5) belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by MAPK/Erk kinase-5 (Mek5), Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrated that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249, which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurfs-Smads-Sox9 axis in mammalian skeletogenesis. [ABSTRACT FROM AUTHOR]

The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro. The expression of solute carrier family 38 member 1 ( Slc38a1 ; gene encoding sodium-coupled neutral amino acid transporter 1) was preferentially upregulated in the BAT of both genetic and acquired obesity mice in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress through hypoxiainducible factor-1α, which is a master transcription factor of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These results indicate that Slc38a1 is an obesity- associated gene in BAT and a hypoxia-responsive gene in brown adipocytes. [ABSTRACT FROM AUTHOR]

This study aims at representation of carbon-aluminium galvanic corrosion in a saltwater film environment. In numerical simulation, multiphysics problems, including electric field, electrophoresis, mass diffusion, chemical reactions, and moving boundaries, are taken into account. In mass transport analysis, the simulator is sped up by using an implicit method. In chemical reaction analysis, the distribution of pH and precipitation is accurately represented by considering four chemical reactions of aluminium ions. Additionally, the simulator is validated through galvanic corrosion experiments. [ABSTRACT FROM AUTHOR]

Bone homeostasis is maintained by the synergistic actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here, we show that the transcriptional coactivator/repressor interferon-related developmental regulator 1 (Ifrd1) is expressed in osteoclast lineages and represents a component of the machinery that regulates bone homeostasis. Ifrd1 expression was transcriptionally regulated in preosteoclasts by receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) through activator protein 1. Global deletion of murine Ifrd1 increased bone formation and decreased bone resorption, leading to a higher bone mass. Deletion of Ifrd1 in osteoclast precursors prevented RANKL-induced bone loss, although no bone loss was observed under normal physiological conditions. RANKL-dependent osteoclastogenesis was impaired in vitro in Ifrd1-deleted bone marrow macrophages (BMMs). Ifrd1 deficiency increased the acetylation of p65 at residues K122 and K123 via the inhibition of histone deacetylase- dependent deacetylation in BMMs. This repressed the NF-κB-dependent transcription of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), an essential regulator of osteoclastogenesis. These findings suggest that an Ifrd1/NF-κB/NFATc1 axis plays a pivotal role in bone remodeling in vivo and represents a therapeutic target for bone diseases. [ABSTRACT FROM AUTHOR]

Emergence of antibiotic-resistant bacteria in the aquaculture environment is a significant problem for disease control of cultured fish as well as in human public health. Conjugative mobile genetic elements (MGEs) are involved in dissemination of antibiotic resistance genes (ARGs) among marine bacteria. In the present study, we first designed a PCR targeting traI gene encoding essential relaxase for conjugation. By this new PCR, we demonstrated that five of 83 strains isolated from a coastal aquaculture site had traI-positive MGEs. While one of the five strains that belonged to Shewanella sp. was shown to have an integrative conjugative element of the SXT/R391 family (ICEVchMexlike), the MGEs of the other four strains of Vibrio spp. were shown to have the backbone structure similar to that of previously described in pAQU1. The backbone structure shared by the pAQU1-like plasmids in the four strains corresponded to a ?100-kbp highly conserved region required for replication, partition and conjugative transfer, suggesting that these plasmids constituted "pAQU group." The pAQU group plasmids were shown to be capable of conjugative transfer of tet(M) and other ARGs from the Vibrio strains to E. coli. The pAQU group plasmid in one of the examined strains was designated as pAQU2, and its complete nucleotide sequence was determined and compared with that of pAQU1. The results revealed that pAQU2 contained fewer ARGs than pAQU1 did, and most of the ARGs in both of these plasmids were located in the similar region where multiple transposases were found, suggesting that the ARGs were introduced by several events of DNA transposition into an ancestral plasmid followed by drug selection in the aquaculture site. The results of the present study indicate that the "pAQU group" plasmids may play an important role in dissemination of ARGs in the marine environment. [ABSTRACT FROM AUTHOR]