The Quasi‐Biennial Oscillation initiative (QBOi) is a model intercomparison programme that specifically targets simulation of the QBO in current global climate models. Eleven of the models or model ...versions that participated in a QBOi intercomparison study have upper boundaries in or above the mesosphere and therefore simulate the region where the stratopause semiannual oscillation (SAO) is the dominant mode of variability of zonal winds in the tropical upper stratosphere. Comparisons of the SAO simulations in these models are presented here. These show that the model simulations of the amplitudes and phases of the SAO in zonal‐mean zonal wind near the stratopause agree well with the information derived from available observations. However, most of the models simulate time‐average zonal winds that are more westward than determined from observations, in some cases by several tens of m·s–1. Validation of wave activity in the models is hampered by the limited observations of tropical waves in the upper stratosphere but suggests a deficit of eastward forcing either by large‐scale waves, such as Kelvin waves, or by gravity waves.
The figure shows the climatological annual cycle of equatorial zonally averaged zonal wind for each calendar month from 11 models that participated in the Quasi‐Biennial Oscillation initiative (QBOi), compared with winds derived from SABER observations (lower right). The models simulate a realistic semiannual cycle but the time‐mean winds are more strongly westward than observed.
Abstract
The ‘open’ and ‘compact’ regions of chromatin are considered to be regions of active and silent transcription, respectively. However, individual genes produce transcripts at different ...levels, suggesting that transcription output does not depend on the simple open-compact conversion of chromatin, but on structural variations in chromatin itself, which so far have remained elusive. In this study, weakly crosslinked chromatin was subjected to sedimentation velocity centrifugation, which fractionated the chromatin according to its degree of compaction. Open chromatin remained in upper fractions, while compact chromatin sedimented to lower fractions depending on the level of nucleosome assembly. Although nucleosomes were evenly detected in all fractions, histone H1 was more highly enriched in the lower fractions. H1 was found to self-associate and crosslinked to histone H3, suggesting that H1 bound to H3 interacts with another H1 in an adjacent nucleosome to form compact chromatin. Genome-wide analyses revealed that nearly the entire genome consists of compact chromatin without differences in compaction between repeat and non-repeat sequences; however, active transcription start sites (TSSs) were rarely found in compact chromatin. Considering the inverse correlation between chromatin compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.
The genome of eukaryotic cells is frequently exposed to damage by various genotoxins. Phosphorylation of histone H2AX at Serine 139 (γ‐H2AX) is a hallmark of DNA damage. RNF8 monoubiquitinates γ‐H2AX ...with the Lys63‐linked ubiquitin chain to tether DNA repair molecules at DNA lesions. A high‐throughput screening identified RNF8 as a binding partner of dual‐specificity tyrosine phosphorylation‐regulated kinase 2 (DYRK2). Notably, DNA damage‐induced monoubiquitination of γ‐H2AX is impaired in DYRK2‐depleted cells. The foci formation of p53‐binding protein 1 at DNA double‐strand break sites is suppressed in DYRK2 knockdown cells, which fail to repair the DNA damage. A homologous recombination assay showed decreased repair efficiency in DYRK2‐depleted cells. Our findings indicate direct interaction of DYRK2 with RNF8 in regulating response to DNA damage.
The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of ...this disease. Several treatment strategies using these agents, usually in combination with chemotherapy, but also without or with minimal use of cytotoxic agents, have provided excellent therapeutic results. Cure of APL patients, however, is also dependent on peculiar aspects related to the management and supportive measures that are crucial to counteract life-threatening complications associated with the disease biology and molecularly targeted treatment. The European LeukemiaNet recently appointed an international panel of experts to develop evidence- and expert opinion–based guidelines on the diagnosis and management of APL. Together with providing current indications on genetic diagnosis, modern risk-adapted front-line therapy and salvage treatment, the review contains specific recommendations for the identification and management of most important complications such as the bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA- and ATO-related toxicities, as well as for molecular assessment of response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women.
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•Crack-less and deformation-resistant electroplated Ni/electroless Ni/Pt/Ag metallization layers for Ag-sintered joint was developed.•Three kinds of metallization layers on DBC ...substrate was designed and evaluated during thermal shock test (TST).•The Ag joint structures on different metallization layers exhibited different mechanical behaviors during the harsh TST from −50 ℃ to 250 °C.•Electroplated Ni/electroless Ni/Pt/Ag provided a stable shear strength, in addition to good microstructural maintenance for the Ag-sintered joints.•A thickened Ni layer is expected to suppress the thermal stress and the Ag layer is expected to enhance sinterability with the Ag paste.
Aiming for a suitable die-attached substrate for Ag-sintered joint technology during harsh operating environment, three surface finishes of sputtered Ti/Ag- layers, electroless Ni-/Pt-/Ag- layers, and electroplated Ni-/electroless Ni-/Pt-/Ag- layers were developed to directly bond copper (DBC) substrates, denoted as Ti/Ag, ENPA, and E-ENPA, respectively. The effect of the metallization layers by three deposition technologies on the Ag joint structures was systematically investigated during an extreme thermal shock test (TST) ranging from −50 to 250 °C. The mechanical behaviors and interface evolution considerably varied depending on the metallization layer used. Both ENPA and E-ENPA substrates provided a more robust initial shear strength of approximately 60 MPa. More importantly, both metallization layers were productive in restraining interfacial deformation owing to the effect of the thick Ni plating. A better performance was derived from the electroplated Ni in E-ENPA metallization with crack-less and deformation-resistant, because of electroplated Ni possessed a suitable hardness and toughness, thus the optimal stress-relaxation capability. This study provides insights to the properties of Ag-sintered joints on three metallization layers, where the metallization, mainly by electroplating, exhibited superior reliability beyond that of sputtered and electroless depositions in both strength and microstructure maintenance.
Tumor cells are eliminated by the immune system, including T lymphocytes and natural killer cells; however, many types of tumor cells acquire the immune tolerance by inhibiting T-cell activation and ...functions
immune checkpoint molecules. Immunotherapy targeting immune checkpoint molecules such as Programmed death receptor 1 (PD-1)/Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) have shown successful outcomes for multiple cancer treatments, however some patients show the lack of durable responses. Thus, discovering the chemical compounds or drugs manipulating the expression or function of immune checkpoint molecules are anticipated to overcome the drug resistance of immune checkpoint inhibitors. Function of inhibitory immune checkpoint molecules is often dysregulated by the transcriptional and post-translational levels in tumors. Here, this review focuses on the post-translational modification of intrinsic PD-L1 functions and regulators for PD-L1 transcription.
Downregulation of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. We investigated the role of the miRNAs miR-143 and miR-145 in gastric ...cancers.
The expression levels of miR-143 and miR-145 in the samples from 43 patients with gastric cancer were determined by real-time PCR using TaqMan assay. The growth inhibitory effect was estimated by the transfection of human gastric cancer cells with the miRNA.
The expression levels of miR-143 and -145 were decreased in most human gastric cancers examined, as previously reported to occur in colon tumors. The transfection of human gastric MKN-1 cells with miR-145 resulted in a greater growth inhibitory effect than that with miR-143, results which were contrary to those in colon cancers. In MKN-1 cells, an additive effect on growth inhibition was shown by the combined transfection with miR-143 and miR-145; further, higher sensitivity to 5-fluorouracil was also observed following the transfection with miR-143 or miR-145. The possible candidate target messenger RNAs of miR-145 were identified to be insulin receptor substrate-1 and beta-actin.
Taken together, these findings suggest that miR-143 and miR-145 act as anti-oncomirs common to gastrointestinal tumors.
Individual plants can produce leaves that differ substantially in size, morphology and many other traits. However, leaves that play a specific role in reproduction have rarely been reported. Here, we ...report leaves specialized to enclose fruit clusters and enhance seed production in an annual vine,
. Enclosure leaves were produced at the end of the growing season in late autumn. They were different in greenness and structure from other leaves. Under solar radiation, the ambient temperature inside an intact enclosure was up to 4.6°C higher than that near a fruit cluster whose enclosure leaves had been removed. We found that enclosures were thicker at colder sites. Removal of enclosing leaves negatively affected fruit survival and/or growth, but we could not identify the exact mechanism. The results suggested that enclosures allow the plant to produce seeds under the cold weather the plant encounters at the end of its life. Vegetative and reproductive traits of plants have usually been studied separately. This study indicates how they can dynamically interact, as shown by an examination of associations among leaf and reproductive trait changes according to life stages.
Gibberellins (GAs) are phytohormones essential for many developmental processes in plants. A nuclear GA receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1), has a primary structure similar to that of the ...hormone-sensitive lipases (HSLs). Here we analyse the crystal structure of Oryza sativa GID1 (OsGID1) bound with GA4 and GA3 at 1.9 Å resolution. The overall structure of both complexes shows an / -hydrolase fold similar to that of HSLs except for an amino-terminal lid. The GA-binding pocket corresponds to the substrate-binding site of HSLs. On the basis of the OsGID1 structure, we mutagenized important residues for GA binding and examined their binding activities. Almost all of them showed very little or no activity, confirming that the residues revealed by structural analysis are important for GA binding. The replacement of Ile 133 with Leu or Val-residues corresponding to those of the lycophyte Selaginella moellendorffii GID1s-caused an increase in the binding affinity for GA34, a 2 -hydroxylated GA4. These observations indicate that GID1 originated from HSL and was further modified to have higher affinity and more strict selectivity for bioactive GAs by adapting the amino acids involved in GA binding in the course of plant evolution.
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