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False contextual fear memory has been attributed to a time-dependent loss of precision in contextual memory representations. In this study, we investigated the role of protein kinase M zeta (PKMζ), a key molecule in the maintenance of hippocampus-dependent long-term memory, in false contextual fear memory within the dorsal (dHPC) and ventral hippocampus (vHPC). Two weeks prior to behavioral testing, male C57BL/6J mice (7-10 weeks old) received bilateral injections of adeno-associated virus (AAV PHP.eB) into the dHPC or vHPC to induce PKMζ knockdown (PKMζ KD), overexpression of wild-type PKMζ (PKMζ WT), or kinase-inactive PKMζ (PKMζ K281R). False contextual fear memory was assessed by measuring freezing behavior in Context B at 3 and 24 h following exposure to Context A with or without unconditioned stimulus presentation [US(+) and US(-), respectively]. Spatial recognition memory was evaluated using the two-trial novel arm recognition test in the Y-maze. As shown in our previous work, mice exhibited freezing in Context B after receiving a US in Context A, whereas mice that did not receive such a stimulus showed minimal freezing. These data confirmed that freezing in Context B reflects false contextual fear memory. False fear responses were evident at 3 h and were further increased at 24 h. Freezing at 24 h was markedly enhanced in dHPC PKMζ knockdown mice compared with that in AAV control-injected mice. PKMζ WT overexpression prevented the increase in freezing at 24 h, whereas PKMζ K281R overexpression mimicked the effects of PKMζ KD. Furthermore, PKMζ knockdown in the dHPC impaired spatial recognition memory, indicating that hippocampus-dependent spatial processing was disrupted. In contrast, PKMζ manipulation in the vHPC did not affect false contextual fear memory but did impair spatial recognition memory. These findings are consistent with the possibility that functional loss of PKMζ in the dHPC affects contextual memory processes in a manner that may contribute to the time-dependent increase in false contextual fear and impaired spatial recognition memory.

This study aimed to develop a deep learning (DL)-based deliverable whole pelvic volumetric arc radiation therapy (VMAT) for patients with gynecologic cancer using a prototype DL-based automated planning support system, named RatoGuide, to evaluate its clinical validity. In our hospital, 110 patients with gynecologic cancer were registered. The prescribed dose was 50.4 Gy/28 fr. A DL-based three-dimensional dose prediction model was first trained by the dose distribution and structure data of whole pelvic VMAT ( n  = 100) created on the Monaco treatment planning system (TPS). The structure data of the test data ( n  = 10) were then input to RatoGuide, and RatoGuide predicted the dose distribution of the whole pelvic VMAT plan (PreDose). We established deliverable plans with Monaco and Eclipse TPS (DeliDose) based on PreDose and vendor-supplied optimization objectives. Medical physicists then manually developed plans (CliDose) for the test data. Finally, we evaluated and compared the dose distribution and dose constraints of PreDose, DeliDose, and CliDose. DeliDose, in both Eclipse and Monaco, was comparable to PreDose in most Dose constraints, planning target volume (PTV) coverage, and Dmax of the bladder, rectum, and bowel bag were better for DeliDose than for PreDose. Additionally, DeliDose demonstrated no significant difference from CliDose in most dose constraints. The blinded average scores of radiation oncologists for DeliDose and CliDose were 4.2 ± 0.4 and 4.3 ± 0.5, respectively, in Eclipse, and 4.0 ± 0.6 and 3.9 ± 0.5, respectively, in Monaco (5 is the max score and 3 is clinically acceptable). We indicated that RatoGuide can eliminate variations in plan quality between hospitals in whole pelvic VMAT irradiation and help develop VMAT plans in a short time.

In the Perak River, which flows into Malaysia, a tidal zone extends approximately 40 km from the mouth of the river, and turbid water is always present. Therefore, a detailed field survey is necessary to reveal the dynamical phenomenon of turbid water associated with the tidal zone. However, it is efficient to specify the survey area and conditions by clarifying the rough spatiotemporal variability characteristics in advance. In this study, water sampling and turbidity measurements were conducted in the tidal sensitive area of the Perak River during the satellite Sentinel-2 transit. An equation to estimate turbidity from surface reflectance at near-infrared wavelengths was experimentally developed using fine sand collected from the Perak River, and this equation was applied to past Sentinel-2 images to clarify the spatiotemporal variability characteristics of turbidity in the tidal zone. The results showed a large longitudinal variation in turbidity in the 20 km section from the mouth of the river, and a convergence zone of suspended sediment was identified when turbidity was relatively high.

Abstract There are no quantitative selection criteria for identifying high-grade glioma (HGG) patients who are suited for volumetric-modulated arc therapy (VMAT). This study aimed to develop selection criteria that can be used for the selection of the optimal treatment modality in HGG. We analyzed 20 patients with HGG treated by 3D conformal radiotherapy (3DCRT). First, VMAT plans were created for each patient retrospectively. For each plan, the normal tissue complication probability (NTCP) for normal brain was calculated. We then divided the patients based on the NTCPs of the 3DCRT plans for normal brain, using the threshold of 5%. We compared the NTCPs of the two plans and the gross tumor volumes (GTVs) of the two groups. For the GTVs, we used receiver operating characteristic curves to identify the cut-off value for predicting NTCP < 5%. We determined the respective correlations between the GTV and the GTV’s largest cross-sectional diameter and largest cross-sectional area. In the NTCP ≥ 5% group, the NTCPs for the VMAT plans were significantly lower than those for the 3DCRT plans (P = 0.0011). The NTCP ≥ 5% group’s GTV was significantly larger than that of the NTCP < 5% group (P = 0.0016), and the cut-off value of the GTV was 130.5 cm3. The GTV was strongly correlated with the GTV’s largest cross-sectional diameter (R2 = 0.82) and largest cross-sectional area (R2 = 0.94), which produced the cut-off values of 7.5 cm and 41 cm2, respectively. It was concluded that VMAT is more appropriate than 3DCRT in cases in which the GTV is ≥130.5 cm3.

Some patients undergoing breast reconstruction require post-mastectomy radiation therapy, but the metallic ports used in temporary tissue expanders attenuate the X-rays. In this study, we evaluated by the film method, the attenuation of 4 MV and 6 MV X-rays after passing through a metallic port, with the aim of identifying a useful method for determining the appropriate density to use in the radiation treatment planning system (RTPS), taking into account the distance between the metallic port and the targets. Radiochromic film was used to measure depth doses after the X-rays passed through the metallic port. The physical density allotted to the metal port portion was varied on the RTPS within the range 1-16 g/cm3, and the physical density values were calculated that best reproduced the depth-dose distribution extrapolated from the film method. When the metallic port was orientated perpendicularly, the attenuation of the X-rays peaked at ~7% at both 4 MV and 6 MV. In the parallel orientation, the X-rays were attenuated by up to ~40% at 4 MV and by up to ~30% at 6 MV. We estimated the optimum physical density to be 9.8 g/cm3, which yielded the best fit with the actual measurements. We demonstrated the most likely range for the target depth from the CT images of actual patients and, within this range, we identified the optimum physical density at which the measured and calculated values were most consistent with each other.

We investigated virus infection rates in Japanese garlic plants and found that a potyvirus, onion yellow dwarf virus (OYDV) was always associated with another potyvirus, leek yellow stripe virus (LYSV). When the OYDV HC-Pro genes from those viral isolates were PCR-amplified and sequenced, we found that all the HC-Pros isolated from Japanese garlic lacked a long stretch of the N-terminal amino acids (~ 100 residues) including the KITC motif, suggesting possible loss of viral aphid transmission. Our phylogenetic analysis revealed that HC-Pros were divided into three major groups and that they did not branch from a single common ancestor, suggesting different mechanisms for generation of the short HC-Pros from the intact ones. Because HC-Pro is a well-known RNA silencing suppressor (RSS), we then analyzed the RSS activity of HC-Pro using the conventional agroinfiltration assay with Nicotiana benthamiana and also with onion, which is a natural host of OYDV. The results demonstrated that the short HC-Pro had reduced RSS activity compared to the long HC-Pro while both type HC-Pros were well expressed in the agroinfiltrated tissues. In addition, the tested OYDV HC-Pros exhibited more efficient RSS activity in onion than in N. benthamiana. We presume that OYDV with reduced RSS activity of HC-Pro may take advantage of mixed infection with LYSV to survive.

Ma-LMM01 is a lytic phage infecting the toxic cyanobacterium Microcystis aeruginosa . We have investigated the transcription dynamics of host genes during phage infection using quantitative reverse transcriptase-PCR. No significant shutdown of host transcription occurred. There was no change in the transcript levels of the psbA genes [photosystem II D1 (PSII D1)], but the transcript levels of the stress response genes and the alternative σ factor gene sigB were upregulated. The transcript levels of the Calvin cycle genes and pentose phosphate pathway genes did not change or only slightly decreased, suggesting that sufficient amounts of NADPH and nucleic acid were available without redirection of the carbon flux. These results suggest that Ma-LMM01 infection induces protection of the host’s photosynthetic apparatus, conserves the host’s PSII through phycobilisome degradation using its own NblA and provides protection to the photosystem using host stress response genes. This protection of the host’s photosystem without extensive genetic manipulation may have some benefits for viruses infecting cyanobacteria that inhabit surface waters and may also be advantageous for Ma-LMM01 to avoid the host defense systems.

Purpose To investigate the effects of a respiratory gating and multifield technique on the dose-volume histogram (DVH) in radiotherapy for esophageal cancer. Methods and materials Twenty patients who underwent four-dimensional computed tomography for esophageal cancer were included. We retrospectively created the four treatment plans for each patient, with or without the respiratory gating and multifield technique: No gating-2-field, No gating-4-field, Gating-2-field, and Gating-4-field plans. We compared the DVH parameters of the lung and heart in the No gating-2-field plan with the other three plans. Result In the comparison of the parameters in the No gating-2-field plan, there are significant differences in the Lung V 5Gy , V 20Gy , mean dose with all three plans and the Heart V 25Gy –V 40Gy with Gating-2-field plan, V 35Gy , V 40Gy , mean dose with No Gating-4-field plan and V 30Gy –V 40Gy , and mean dose with Gating-4-field plan. The lung parameters were smaller in the Gating-2-field plan and larger in the No gating-4-field and Gating-4-field plans. The heart parameters were all larger in the No gating-2-field plan. Conclusion The lung parameters were reduced by the respiratory gating technique and increased by the multifield technique. The heart parameters were reduced by both techniques. It is important to select the optimal technique according to the risk of complications.

The genus Allexivirus currently includes eight virus species that infect allium plants. Previously, we showed that there are two distinct groups of allexiviruses (deletion [D]-type and insertion [I]-type) based on the presence or absence of a 10- to 20-base insert (IS) between the coat protein (CP) and cysteine rich protein (CRP) genes. In the present study of CRPs to analyze their functions, we postulated that evolution of allexiviruses may have been largely directed by CRPs and thus proposed two evolutionary scenarios for allexiviruses based mainly on the presence or absence of IS and determined by how the allexiviruses challenge host resistance mechanisms (RNA silencing and autophagy). We found that both CP and CRP are RNA silencing suppressors (RSS), that they can inhibit each other’s RSS activity in the cytoplasm, and that CRP becomes a target of host autophagy in the cytoplasm but not CP. To mitigate CRP interference with CP, and to increase the CP’s RSS activity, allexiviruses developed two strategies: confinement of D-type CRP in the nucleus and degradation of I-type CRP by autophagy in the cytoplasm. Here, we demonstrate that viruses of the same genus achieve two completely different evolutionary scenarios by controlling expression and subcellular localization of CRP.

Managing complications in Type 1 diabetes (T1D) remains challenging. HLA genes, particularly DR and DQ, are linked to T1D susceptibility. We studied 48 Japanese T1D inpatients and revealed associations between DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes and complications, offering a new perspective for future research. •Specific HLA haplotypes (DRB104:05-DQB104:01, DRB109:01-DQB103:03) linked to T1D.•Genetic markers offer insights, aiding tailored management.•Study identifies HLA haplotype links to T1D issues in Japan.