Caution: Patient-specific preoperative preparations combined with procedure-specific 5-aminolevulinic acid may lead to critical events

5-Aminolevulinic acid (5-ALA) is orally administered 2-4 hours before surgery to identify tumor location. Hypotension is sometimes observed after 5-ALA administration. Case reoprtWe present a case of a patient with 5-ALA-induced hypotension that resulted in the development of cerebral infarction. An 83-year-old man with a bladder tumor was scheduled for photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) and right radical nephroureterectomy. 5-ALA was orally administered and his ordinary antihypertensive and antianginal agents were also administered an hour after 5-ALA administration. Following this, his blood pressure dropped, and he developed muscle weakness and paralysis in his left upper extremity. Magnetic resonance imaging showed evidence of cerebral infarction. ConclusionsWe cannot conclude definitively that our patient's cerebral infarction was solely caused by 5-ALA-induced hypotension because hypotension under these circumstances is not rare. We consider that additional factors, such as patient-specific doses of antihypertensive and antianginal agents may have played a role in the development of his cerebral infarction

Characterization of an epimastigote-stage-specific hemoglobin receptor of Trypanosoma congolense

Background: Since Trypanosorna spp. lack a complete heme synthesis pathway, the parasites are totally dependent on their host for heme throughout all of the stages of their life -cycle. We herein report the identification and characterization of a T. congolense epimastigote form (EMF)-specific hemoglobin (Hb) receptor. The gene was initially reported to encode a T. congolense haptoglobin (Hp)-Hb complex receptor (TcHpHbR) based on its similarity to a gene encoding a T brucei Hp-Hb complex receptor (TbHpHbR). Methods: Trypanosorna congolense IL3000 was used in this study. A TcHpHbR gene was PCR amplified from the parasite genome. The recombinant protein was used as an immunogen to raise antibodies for immunofluorescence assay and immunoblotting. Hemoglobin uptake by the parasite was examined by using Alexa 488 labelled Hb and visualized by confocal laser scanning microscopy. The qualitative and quantitative interaction between TcHpHbR and its ligand were measured using a surface plasmon resonance assay. Results: We found that, unlike TbHpHbR, TcHpHbR was exclusively expressed in the EMF stage at RNA and protein levels. The recombinant TcHpHbR (rTcHpHbR) was co-precipitated with free-Hb in a GST-pull down assay. Surface plasmon resonance revealed that rTcHpHbR binds free-Hb with high affinity (dissociation constant (K,A) =2.1x10(-8) M) but free-Hp with low affinity (Kd = 2.2x10(-7) M). Furthermore, Alexa 488-labelled-Hb was only taken up by the EMF and co-localized with tomato lectin, which is a marker of endocytic compartments (flagellar pocket and lysosome). Conclusion: We conclude that the T. congolense EMF takes up free-Hb via TcHpHbR, a receptor which is specific to this developmental stage. We therefore propose renaming TcHpHbR as T congolense EMF-specific Hb receptor (TcEpHbR)

Laminated Metal Composites by Infiltration

We show that steel-magnesium alloy laminated metal composites (LMCs) can be produced by gas pressure infiltration of a liquid magnesium alloy between layers of stacked dimpled steel sheets. Resulting LMCs are amenable to subsequent warm rolling. The LMCs are free of pores or brittle intermetallics and feature, in the as-cast condition, metal layers of uniform thickness and spacing. The ultimate tensile strength of the as-cast LMCs, of 260MPa, obeys the "rule-of-mixtures” (ROM). The uniform tensile elongation, of around 20pct, makes the infiltrated LMC nearly as ductile as the bulk steel it contains, implying that the magnesium alloy in the as-cast LMCs has a substantially increased tensile ductility in comparison to its metallurgically equivalent bulk state. Rolling reduces the metal layer thicknesses, causes waviness in the interface, and makes the LMCs stronger but less ductile, by factors in the vicinity of 2 for both properties; the main cause for this is work hardening in the steel layer

High-velocity frictional strength across the Tohoku-Oki megathrust determined from surface drilling torque

High-velocity frictional strength is one of the primary factors controlling earthquake faulting. The Japan Trench Fast Drilling Project drilled through the shallow plate boundary fault, where displacement was ~50 m during the 2011 Tohoku-Oki earthquake. To determine downhole frictional strength, we analyzed the surface drilling torque data acquired at rotation rates equivalent to seismic slip rates (0.8–1.3 m/s). The results show a clear contrast in high-velocity frictional strength across the plate boundary fault: the apparent friction coefficient of frontal prism sediments (hemipelagic mudstones) in the hanging wall is 0.1–0.3, while that of the underthrust sediments (mudstone, laminar pelagic claystone, and chert) in the footwall increases to 0.2–0.4. The apparent friction coefficient of the smectite-rich pelagic clay in the plate boundary fault is 0.08–0.19, which is consistent with that determined from high-velocity (1.1–1.3 m/s) friction experiments. This suggests that surface drilling torque is useful in obtaining downhole frictional strength

Selective deployment of virulence effectors correlates with host specificity in a fungal plant pathogen

なぜ病原菌は特定の作物にのみ感染するのか --植物病原菌の宿主特異性の鍵因子--. 京都大学プレスリリース. 2023-03-23.Fungus has a host of issues: KyotoU discovers how toxic fungi target specific host plants. 京都大学プレスリリース. 2023-06-07.The hemibiotrophic fungal plant pathogen Colletotrichum orbiculare is predicted to secrete hundreds of effector proteins when the pathogen infects cucurbit crops, such as cucumber and melon, and tobacco (Nicotiana benthamiana), a distantly related Solanaceae species. Here, we report the identification of sets of C. orbiculare effector genes that are differentially required for fungal virulence to two phylogenetically distant host species. Through targeted gene knockout screening of C. orbiculare ‘core’ effector candidates defined based on in planta gene expression, we identified: four host-specific virulence effectors (named effector proteins for cucurbit infection, or EPCs) that are required for full virulence of C. orbiculare to cucurbit hosts, but not to the Solanaceae host N. benthamiana; and five host-nonspecific virulence effectors, which collectively contribute to fungal virulence to both hosts. During host infection, only a small subset of genes, including the host-specific EPC effector genes, showed preferential expression on one of the hosts, while gene expression profiles of the majority of other genes, including the five host-nonspecific effector genes, were common to both hosts. This work suggests that C. orbiculare adopts a host-specific effector deployment strategy, in addition to general host-blind virulence mechanisms, for adaptation to cucurbit hosts

Systems Analysis of ATF3 in Stress Response and Cancer Reveals Opposing Effects on Pro-Apoptotic Genes in p53 Pathway

Stress-inducible transcription factors play a pivotal role in cellular adaptation to environment to maintain homeostasis and integrity of the genome. Activating transcription factor 3 (ATF3) is induced by a variety of stress and inflammatory conditions and is over-expressed in many kinds of cancer cells. However, molecular mechanisms underlying pleiotropic functions of ATF3 have remained elusive. Here we employed systems analysis to identify genome-wide targets of ATF3 that is either induced by an alkylating agent methyl methanesulfonate (MMS) or over-expressed in a prostate tumour cell line LNCaP. We show that stress-induced and cancer-associated ATF3 is recruited to 5,984 and 1,423 targets, respectively, in the human genome, 89% of which are common. Notably, ATF3 targets are highly enriched for not only ATF/CRE motifs but also binding sites of several other stress-inducible transcription factors indicating an extensive network of stress response factors in transcriptional regulation of target genes. Further analysis of effects of ATF3 knockdown on these targets revealed that stress-induced ATF3 regulates genes in metabolic pathways, cell cycle, apoptosis, cell adhesion, and signalling including insulin, p53, Wnt, and VEGF pathways. Cancer-associated ATF3 is involved in regulation of distinct sets of genes in processes such as calcium signalling, Wnt, p53 and diabetes pathways. Notably, stress-induced ATF3 binds to 40% of p53 targets and activates pro-apoptotic genes such as TNFRSF10B/DR5 and BBC3/PUMA. Cancer-associated ATF3, by contrast, represses these pro-apoptotic genes in addition to CDKN1A/p21. Taken together, our data reveal an extensive network of stress-inducible transcription factors and demonstrate that ATF3 has opposing, cell context-dependent effects on p53 target genes in DNA damage response and cancer development

Development and tests of a flexible superconducting bus-line for the Large Helical Device

A flexible superconducting bus-line is proposed as an electrical feeder between the superconducting coils of the Large Helical Device (LHD) and the device\u27s power supplies. The bus-line consists of superconducting cables and a cryogenic flexible transfer-line. A specially developed aluminum stabilized NbTi/Cu compacted strand cable satisfies requirements for large current capacity, high stability, high reliability and flexibility. A full-scale model with a length of 20 m was designed and constructed to investigate the feasibility and performance of the superconducting bus-line. Its fabrication, transportation, installation, cooling and excitation tests were successfully carried out. The bus-line was very stable and could be excited up to 40 kA (rated current is 30 kA) without a quench. The stability, current distribution and heat load were also measure