In amniotes, the development of the primitive streak and its accompanying 'organizer' define the first stages of gastrulation. Although these structures have been characterized in detail in model ...organisms, the human primitive streak and organizer remain a mystery. When stimulated with BMP4, micropatterned colonies of human embryonic stem cells self-organize to generate early embryonic germ layers
. Here we show that, in the same type of colonies, Wnt signalling is sufficient to induce a primitive streak, and stimulation with Wnt and Activin is sufficient to induce an organizer, as characterized by embryo-like sharp boundary formation, markers of epithelial-to-mesenchymal transition and expression of the organizer-specific transcription factor GSC. Moreover, when grafted into chick embryos, human stem cell colonies treated with Wnt and Activin induce and contribute autonomously to a secondary axis while inducing a neural fate in the host. This fulfils the most stringent functional criteria for an organizer, and its discovery represents a milestone in human embryology.
Insulin stimulated translocation of the glucose transporter GLUT4 from the cytosol to the plasma membrane in a concentration (1 nM–1 μM)-dependent manner and increased glucose uptake in 3T3-L1 ...adipocytes. Insulin-induced GLUT4 translocation to the cell surface was prevented by the phosphoinositide 3 kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase 1 (PDK1) inhibitor BX912 or the Akt1/2 inhibitor MK2206, and by knocking-down PI3K, PDK1 or Akt1/2. Insulin increased phosphorylation of Akt1/2 at Thr308/309 and Ser473/474, to activate Akt1/2, in the adipocytes. Insulin-induced phosphorylation of Akt1/2 was suppressed by wortmannin and knocking-down PI3K, while no significant inhibition of the phosphorylation was obtained with BX912 or knocking-down PDK1. In the cell-free Akt assay, PI3K phosphorylated Akt1 both at Thr308 and Ser473 and Akt2 at Ser474 alone. In contrast, PDK1 phosphorylates Akt1 at Thr308 and Akt2 at Thr309. The results of this study indicate that PI3K activates Akt1, independently of PDK1, and Akt2 by cooperating with PDK1 in the insulin signal transduction pathway linked to GLUT4 translocation.
As a part of a research program aiming to mobilize marine gas hydrate deposits as an energy resource, the worlds' first gas production attempt was performed in early 2013 in the Daini Atsumi Knoll, ...Eastern Nankai Trough, off Honshu Island, Japan. The test concluded with 119 000 m
3
(under ambient conditions) of methane gas production during six consecutive days of depressurization operation through a borehole drilled at 1000 m water depth. As thermal and mass transportation in a heterogeneous geological formation are the governing factors of efficiency and effectiveness of the resource, the test was associated with intensive underground temperature monitoring. Temperature sensors installed in one production and two observation boreholes could detect temperature variations during gas production due to the endothermic gas hydrate dissociation process and mass/heat transport around the boreholes. The measurements in the observation holes started one year before the test and continued until plug-and-abandonment, and thus enabled monitoring of both the initial temperature and temperature change arizing from recovery processes. The depth profiles of measured temperatures in all holes can be related to the geological features of the corresponding formation, and those thermal responses revealed the intervals where gas hydrate dissociation predominantly occurred. By analyzing the energy conservation in the production borehole, the gas and water production profiles could be estimated and major gas and water production zones were identified. Preliminary numerical analysis results show the range of formation permeability and that the observed temperature drop is equivalent to the heat consumption by hydrate dissociation for the volume of produced methane gas. Moreover, the thermal responses could provide some clues about the location and mechanism of the sand production event. This sand production event ultimately terminated the production operations on the seventh day of flow.
As a part of a research program aiming to mobilize marine gas hydrate deposits as an energy resource, the worlds' first gas production attempt was performed in early 2013 in the Daini Atsumi Knoll, Eastern Nankai Trough, off Honshu Island, Japan.
DNA methylation is a type of epigenetic marking that strongly influences chromatin structure and gene expression in plants and mammals. Over the past decade, DNA methylation has been intensively ...investigated in order to elucidate its control mechanisms. These studies have shown that small RNAs are involved in the induction of DNA methylation, that there is a relationship between DNA methylation and histone methylation, and that the base excision repair pathway has an important role in DNA demethylation. Some aspects of DNA methylation have also been shown to be shared with mammals, suggesting that the regulatory pathways are, in part at least, evolutionarily conserved. Considerable progress has been made in elucidating the mechanisms that control DNA methylation; however, many aspects of the mechanisms that read the information encoded by DNA methylation and mediate this into downstream regulation remain uncertain, although some candidate proteins have been identified. DNA methylation has a vital role in the inactivation of transposons, suggesting that DNA methylation is a key factor in the evolution and adaptation of plants.
summary The aims of this paper were to review the literature on shortened dental arches with special focus on publications of the Käyser/Nijmegen group, and to evaluate the discussions on the ...shortened dental arch concept found in the literature. A MEDLINE (PubMed) search was conducted for articles in English published in the dental literature from 1966 to November 2005. The search revealed epidemiological, cross‐sectional and longitudinal clinical studies as well as opinion papers, the majority of which were published by the Dutch group. The studies found in general no clinically significant differences between subjects with shortened dental arches of three to five occlusal units and complete dental arches regarding variables such as masticatory ability, signs and symptoms of temporomandibular disorders, migration of remaining teeth, periodontal support, and oral comfort. The findings from cross‐sectional studies were corroborated longitudinally. No systematic clinical study with conflicting results was found. The shortened dental arch concept was accepted by a great majority of dentists but not widely practised. The studies reviewed showed that shortened dental arches comprising anterior and premolar teeth in general fulfil the requirements of a functional dentition. It may therefore be concluded that the concept deserves serious consideration in treatment planning for partially edentulous patients. However, with ongoing changes, e.g. in dental health and economy, the concept requires continuing research, evaluation and discussion. Patients’ needs and demands vary much and should be individually assessed but the shortened dental arch concept deserves to be included in all treatment planning for partially edentulous patients.
Bovine leukemia virus (BLV) is an economically important pathogen that both causes fatal enzootic bovine leukosis (EBL) and reduces lifetime milk production, reproductive efficiency, carcass weight, ...and longevity in dairy cows. The virus can be divided into two categories based on the amino acid at position 233 in Tax protein, which activates viral transcription and probably plays crucial roles in leukemogenesis. We recently reported that early-onset EBL in Japanese Black (JB) cattle was frequently caused by L233-Tax–carrying virus. This study examined the impact of BLV infection, the proviral load (PVL), and amino acid 233 in Tax on the outcomes of JB cattle. We measured PVL in cattle enrolled between February 2016 and December 2018, determined the Tax type of the isolates, and performed follow-up until March 2022. The results demonstrated that BLV infection increased the risk of involuntary culling and mortality in JB cattle in a PVL-dependent manner. Infection with L233-Tax–carrying virus increased the likelihood of mortality by 1.6-fold compared with the effects of P233-Tax–carrying virus infection. Intrauterine and perinatal infections were frequently caused by L233-Tax–carrying virus, and these infections were likely to influence the early onset of EBL in JB cattle. Conversely, breeding cows infected with P233-Tax–carrying virus were often eliminated by involuntary culling. These findings indicate that amino acid 233 in Tax has importance in terms of preventing economic loss attributable to EBL in JB cattle.
•BLV infection increased the risk of involuntary culling and mortality in JB cattle.•L233-Tax-carrying BLV increased the mortality risk versus P233-Tax-carrying BLV.•In utero and perinatal infections were frequently caused by L233-Tax-carrying BLV.•These infections were likely to influence the early onset of EBL in JB cattle.
The present study analyzed the kinetics of low-temperature degradation (LTD) in zirconia, and evaluated the influence of LTD and cyclic loading on the fracture resistance of monolithic zirconia molar ...crowns. Bar-shaped zirconia specimens were divided into nine groups and autoclaved at 134°C for 0–200h to induce LTD. The surface fraction and penetration depth of the monoclinic phase were examined using X-ray diffraction and scanning electron microscopy. Monolithic zirconia molar crowns were prepared for crown fracture testing. The crowns were autoclaved for 0–100h (n=6) and cemented to dies. Six crown-die samples that were not autoclaved and six samples that were autoclaved for 100h were subjected to cyclic loading with a load of 300N for 240,000 cycles. All samples were tested in a load-to-failure test. The monoclinic fraction on the surface increased with autoclaving time and reached a plateau after 50h. The depth of the monoclinic phase increased without reaching a plateau. The fracture load of the crowns significantly decreased from 5683N (SD: 342) to 3975N (SD: 194) after 100h of autoclaving. Cyclic loading did not significantly affect the fracture resistance of the crowns in all cases. Kinetic analysis showed no linear correlation between the surface fraction and depth of the monoclinic phase after 50h of autoclaving. Even though LTD increased the monoclinic phase, resulting in lower strength, the fracture resistance of the monolithic zirconia crowns was still sufficient to withstand the loading conditions in the molar regions.
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•The monoclinic fraction on the zirconia surface increased with autoclaving time.•The monoclinic fraction reached plateau after 50h of autoclaving.•The penetration depth of the monoclinic phase increased without reaching a plateau.•Autoclaving decreased the fracture resistance of the monolithic zirconia crowns.•Cyclic loading did not affect the fracture resistance of monolithic zirconia crowns.
Ref. 7 from Benvenisty and colleagues was inadvertently omitted; this has now been cited in the text and added to the reference list, and subsequent references have been renumbered. The Letter has ...been corrected online.
The removal of titanium miniplates is a controversial topic in oral and maxillofacial surgery. This retrospective study examined the timing of and reasons for titanium plate removal after ...orthognathic surgery. The study included 240 orthognathic surgery patients (71 male, 169 female; age range 16–55 years, mean 25.0±8.8 years) who had maxillofacial osteosynthesis plates inserted or inserted and then removed at the Division of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, between April 2003 and March 2017. During the study period, a total of 717 miniplates were inserted in the 240 patients, and 71 of the patients (29.6%) had 236 plates (32.9%) removed. Ten patients (14.1%) had their plates removed within a year due to early complications. Although no patient had their plate removed due to complications at 1–5 years postoperative, a further 14 patients (19.7%) had their plates removed after more than 5 years of long-term follow-up due to plate-related complications. Complications requiring plate removal were evidently biphasic, occurring within 1 year after the operation and at ≥5 years after the operation. Therefore, after confirming postoperative bone healing, it is necessary to explain to patients the risks of plate removal and the importance of long-term follow-up.
Abstract
In ungulate assemblages, although interspecific differences in body size and gregariousness are thought to have a direct impact on winning or losing in interference competition, this has not ...been fully investigated. We observed a total of 64 instances of interspecific contact between larger-gregarious sika deer and smaller-solitary Japanese serows over eight years field observations. Deer-to-serow aggression were never observed. Whereas, serows showed antagonistic behaviour, such as walk push and chasing, to deer, but could rarely displace deer. Serows showed higher alertness to deer than deer did to serows. These results suggest that larger-gregarious ungulates do not necessarily exclude smaller-solitary ones and serows are sensitive to the presence of deer. Differences in aggressiveness and alertness between deer and serows may reflect differences in territoriality: serows may be more sensitive to the invasion of deer into their territory. Serows’ sensitivity to deer may have a negative effect on their population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK