Winter geometrid moths show striking sexual dimorphism by having female‐specific flightless morphs. The evolutionary grades of wing reduction in winter geometrid moths vary and range from having ...short wings, vestigial wings, to being wingless. Although the ontogenetic processes underlying the development of the wingless or short‐wing morphs in Lepidoptera has been well studied, the mechanisms underlying the development of vestigial wing morphs in winter geometrid moths during metamorphosis are poorly understood. In the winter geometrid moth Sebastosema bubonaria Warren, 1896, the males have functional wings, but the females have vestigial wings. Here, we studied the ontogenetic processes affecting wing reduction in the winter geometrid moth S. bubonaria using light microscopy and transmission electron microscopy, and compared the ontogenetic process of wing reduction in this species with that in another species of the wingless‐female winter moth that we investigated previously. Our results showed that, in the vestigial‐wing morphs, the loss of pupal wing epithelium was terminated in the middle of the wing degeneration process, whereas in the wingless morph, the pupal wing epithelium disappeared almost completely and the final appearance of the wings differed slightly among flightless morphs. We propose that the extent and location of cell death in the pupal wing play an important role in the various patterns of reduced wings that are observed in flightless moths.
This study investigates the developmental processes that lead to wing reduction and vestigial wing morphology in winter geometrid moths. Our findings suggest that the extent and location of cell death in pupal wings contribute significantly to the patterns of wing reduction in moths. The evolutionary grades of wing reduction in these moths range from having short wings to having vestigial wings, and being winglessness. The findings shed light on the mechanisms underlying flightlessness in lepidopteran moths.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The generation of ATP through oxidative phosphorylation is an essential metabolic function for Mycobaterium tuberculosis (Mtb), regardless of the growth environment. The type II NADH dehydrogenase ...(Ndh‐2) is the conduit for electrons into the pathway, and is absent in the mammalian genome, thus making it a potential drug target. Herein, we report the identification of two types of small molecules as selective inhibitors for Ndh‐2 through a multicomponent high‐throughput screen. Both compounds block ATP synthesis, lead to effects consistent with loss of NADH turnover, and importantly, exert bactericidal activity against Mtb. Extensive medicinal chemistry optimization afforded the best analogue with an MIC of 90 nm against Mtb. Moreover, the two scaffolds have differential inhibitory activities against the two homologous Ndh‐2 enzymes in Mtb, which will allow precise control over Ndh‐2 function in Mtb to facilitate the assessment of this anti‐TB drug target.
A tale of two inhibitors: A high‐throughput screen against the Mycobacterium tuberculosis (Mtb) oxidative phosphorylation pathway led to the identification of two inhibitors of the type II NADH dehydrogenase (Ndh‐2). The inhibitors show differential inhibitory activities against one or both of the Ndh‐2 isozymes. Treatment of Mtb with these compounds leads to shutdown of ATP synthesis and bacterial killing.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Dimensionality reduction methods are widely used for processing data efficiently. Recently Imakura et al. proposed a novel dimensionality reduction method using a complex moment-based subspace. Their ...method can use more eigenvectors than the existing matrix trace optimization-based methods which explains its reported higher precision. However, the computational complexity is also higher than that of the existing methods, in particular for the nonlinear kernel version. To reduce the computational complexity, we propose a practical parallel implementation of the method by introducing the Nyström approximation. We evaluate the parallel performance of our implementation using the Oakforest-PACS supercomputer.
The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery ...of two diverse lead series imidazo1,2-apyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure–activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.
•A passive decay heat removal system for an ABWR is discussed using combined system of the reactor and an air cooler.•Effect of number of pass of the finned heat transfer tubes on heat removal is ...investigated.•The decay heat can be removed by air coolers with natural convection.•Two types of air cooler are evaluated, i.e., steam condensing and water cooling types.•Measures how to improve the heat removal rate and to make compact air cooler are discussed.
This paper describes the capability of an air cooling system (ACS) operated under natural convection conditions to remove decay heat from the core of an Advanced Boiling Water Reactor (ABWR). The motivation of the present research is the Fukushima Severe Accident (SA). The plant suffered damages due to the tsunami and entered a state of Station Blackout (SBO) during which seawater cooling was not available. To prevent this kind of situation, we proposed a passive decay heat removal system (DHRS) in the previous study. The plant behavior during the SBO was calculated using the system code NETFLOW++ assuming an ABWR with the ACS. However, decay heat removal under an air natural convection was difficult. In the present study, a countermeasure to increase heat removal rate is proposed and plant transients with the ACS are calculated under natural convection conditions. The key issue is decreasing pressure drop over the tube banks in order to increase air flow rate. The results of the calculations indicate that the decay heat can be removed by the air natural convection after safety relief valves are actuated many times during a day. Duct height and heat transfer tube arrangement of the AC are discussed in order to design a compact and efficient AC for the natural convection mode. As a result, a 4-pass heat transfer tubes with 2-row staggered arrangement is the candidate of the AC for the DHRS under the air natural convection conditions. The heat removal rate is re-evaluated as a function of air mass velocity at the inlet of heat transfer tube banks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A 69-year-old man was diagnosed with diffuse large B-cell lymphoma (DLBCL) negative for Epstein-Barr virus-encoded small nuclear RNA 1 (EBER-1) in October 2011, when he was also diagnosed as having a ...human T-cell leukemia virus type-I (HTLV-1) carrier. He achieved complete response after six courses of R-CHOP therapy. In February 2015, the patient had high fever and markedly elevated serum lactate dehydrogenase (LDH) level. Bone marrow examination revealed infiltration of CD4-positive T-cell malignancy. Based on the tentative diagnosis of adult T-cell leukemia/lymphoma, modified LSG15 therapy was initiated. His symptoms and serum LDH level quickly improved after the start of treatment. During the treatment, HTLV-1 proviral DNA integration was reported negative, allowing his final diagnosis to be peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Despite discontinuation of chemotherapy in the middle of the second course due to the patient's preference, complete remission was reached. He remains in clinical remission at 28 months after the treatment discontinuation. Discordant lymphoma of DLBCL and PTCL-NOS in HTLV-1 carrier has not been well characterized and will be discussed with a literature review.
The ALL-1 gene positioned at 11q23 is directly involved in human acute leukemia either through a variety of chromosome translocations or by partial tandem duplications. ALL-1 is the human homologue ...of Drosophila trithorax which plays a critical role in maintaining proper spatial and temporal expression of the Antennapedia-bithorax homeotic genes determining the fruit fly's body pattern. Utilizing specific antibodies, we found that the ALL-1 protein distributes in cultured cells in a nuclear punctate pattern. Several chimeric ALL-1 proteins encoded by products of the chromosome translocations and expressed in transfected cells showed similar speckles. Dissection of the ALL-1 protein identified within its ≈ 1,100 N-terminal residues three polypeptides directing nuclear localization and at least two main domains conferring distribution in dots. The latter spanned two short sequences conserved with TRITHORAX. Enforced nuclear expression of other domains of ALL-1, such as the PHD (zinc) fingers and the SET motif, resulted in uniform nonpunctate patterns. This indicates that positioning of the ALL-1 protein in subnuclear structures is mediated via interactions of ALL-1 N-terminal elements. We suggest that the speckles represent protein complexes which contain multiple copies of the ALL-1 protein and are positioned at ALL-1 target sites on the chromatin. Therefore, the role of the N-terminal portion of ALL-1 is to direct the protein to its target genes.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
ALL1, the human homologue of Drosophila trithorax, is directly involved in human acute leukemias associated with abnormalities at 11q23. Using the differential display method, we isolated a gene that ...is down-regulated in All1 double-knockout mouse embryonic stem (ES) cells. The gene, designated ARP1 (also termed RIEG, Ptx2, or Otlx2), is a member of a family of homeotic genes containing a short motif shared with several homeobox genes. Using a bacterially synthesized All1 polypeptide encompassing the AT-hook motifs, we identified a 0.5-kb ARP1 DNA fragment that preferentially bound to the polypeptide. Within this DNA, a region of ≈ 100 bp was protected by the polypeptide from digestion with ExoIII and DNase I. Whole-mount in situ hybridization to early mouse embryos of 9.5-10.5 days indicated a complex pattern of Arp1 expression spatially overlapping with the expression of All1. Although the ARP1 gene is expressed strongly in bone marrow cells, no transcripts were detected in six leukemia cell lines with 11q23 translocations. These results suggest that ARP1 is up-regulated by the All1 protein, possibly through direct interaction with an upstream DNA sequence of the former. The results are also consistent with the suggestion that ALL1 chimeric proteins resulting from 11q23 abnormalities act in a dominant negative fashion.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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![Discovery of Imidazo[1,2‑a]...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0022-2623/small "Discovery of Imidazo[1,2‑a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis")
