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Phytochromes are red light (R) and far-red light (FR) receptors that play important roles in many aspects of plant growth and development. Phytochromes mainly function in the nucleus and regulate sets of genes by inhibiting negatively acting basic helix-loop-helix transcription factors named PHYTOCHROME INTERACTING FACTORs (PIFs) in Arabidopsis thaliana. Although R/FR photoreversible responses and phytochrome genes are well documented in diverse lineages of plants, the extent to which phytochrome signaling is mediated by gene regulation beyond angiosperms remains largely unclear. Here, we show that the liverwort Marchantia polymorpha, an emerging model basal land plant, has only one phytochrome gene, Mp-PHY, and only one PIF gene, Mp-PIF. These genes mediate typical low fluence responses, which are reversibly elicited by R and FR, and regulate gene expression. Mp-phy is light-stable and translocates into the nucleus upon irradiation with either R or FR, demonstrating that the single phytochrome Mp-phy exhibits combined biochemical and cell-biological characteristics of type I and type II phytochromes. Mp-phy photoreversibly regulates gemma germination and downstream gene expression by interacting with Mp-PIF and targeting it for degradation in an R-dependent manner. Our findings suggest that the molecular mechanisms for light-dependent transcriptional regulation mediated by PIF transcription factors were established early in land plant evolution.

Light regulates various aspects of development throughout the life cycle of sessile land plants. Photoreceptors, such as the red (R) and far-red (FR) light receptors phytochromes, play pivotal roles in modulating developmental programs. Reflecting high developmental plasticity, plants can regenerate tissues, organs, and whole bodies from varieties of cells. Among land plants, bryophytes exhibit extraordinary competency of regeneration under hormone-free conditions. As an environmental factor, light plays critical roles in regeneration of bryophytes. However, how light regulates regeneration remains unknown. Here we show that using the liverwort Marchantia polymorpha , which contains a single phytochrome gene, the phytochrome regulates re-entry into the cell cycle and cell shape in newly regenerating tissues. Our morphological and cytological observations revealed that S-phase entry of G 1 -arrested epidermal cells around the midrib on the ventral surface of thallus explants was greatly retarded in the dark or under phytochrome-inactive R/FR cycle irradiation conditions, where, nevertheless, small, laterally narrow regenerants were eventually formed. Thus, consistent with earlier descriptions published over a century ago, light is not essential for, but exerts profound effects on regeneration in M. polymorpha . Ventral cells in regenerants grown under R/FR cycle conditions were longer and narrower than those under R cycle. Expression of a constitutively active mutant of M. polymorpha phytochrome allowed regeneration of well grown, widely expanded thalli even in the dark when sugar was supplied, further demonstrating that the phytochrome signal promotes cell proliferation, which is rate-limited by sucrose availability. Similar effects of R and FR irradiation on cell division and elongation were observed in sporelings as well. Thus, besides activation of photosynthesis, major roles of R in regeneration of M. polymorpha are to facilitate proliferation of rounder cells through the phytochrome by mechanisms that are likely to operate in the sporeling.

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues 1 – 6 . Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis 2 , 7 , 8 . Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes 4 , 5 , 9 . However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1 —the key mediator for BAT-thermogenesis—ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers. Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.

A physically based snow albedo model (PBSAM), which can be used in a general circulation model, is developed. PBSAM calculates broadband albedos and the solar heating profile in snowpack as functions of snow grain size and concentrations of snow impurities, black carbon and mineral dust, in snow with any layer structure and under any solar illumination condition. The model calculates the visible and near‐infrared (NIR) albedos by dividing each broadband spectrum into several spectral subbands to simulate the change in spectral distribution of solar radiation in the broadband spectra at the snow surface and in the snowpack. PBSAM uses (1) the look‐up table method for calculations of albedo and transmittance in spectral subbands for a homogeneous snow layer, (2) an “adding” method for calculating the effect of an inhomogeneous snow structure on albedo and transmittance, and (3) spectral weighting of radiative parameters to obtain the broadband values from the subbands. We confirmed that PBSAM can calculate the broadband albedos of single‐ and two‐layer snow models with good accuracy by comparing them with those calculated by a spectrally detailed radiative transfer model (RTM). In addition, we used radiation budget measurements and snow pit data obtained during the two winters from 2007 to 2009 at Sapporo, Hokkaido, Japan, for simulation of the broadband albedos by PBSAM and compared the results with the in situ measurements. A five‐layer snow model with one visible subband and three NIR subbands were necessary for accurate simulation. Comparison of solar heating profiles calculated by PBSAM with those calculated by the spectrally detailed RTM showed that PBSAM calculated accurate solar heating profiles when at least three subbands were used in both the visible and NIR bands. Key Points Broadband snow albedo model as function of snow parameters for GCM is presented The model was validated with long‐term radiation budget and snow pit work data Solar heating profile in snowpack can be calculated as well

Retardation of growth and development is a well-known late effect after radiotherapy for pediatric patients. The goal of the study was to examine the effect of proton beam therapy (PBT) on the growth of muscles included in the irradiated area. The subjects were 17 pediatric patients (age ≤ 5 years) who received PBT with a treatment field including a muscle on only one side out of a pair of symmetrical bilateral muscles and had imaging evaluations for at least 1 year after PBT. The thicknesses of the irradiated and non-irradiated (contralateral) muscles were measured retrospectively on CT or MRI axial images collected before and after PBT. The change of thickness divided by the period (years) for each muscle was compared between the irradiated and contralateral sides. Correlations of muscle growth with irradiation dose and age at the start of treatment were also evaluated. The median observation period was 39.2 months. The measurement sites included the erector spinae (n = 9), gluteus maximus (n = 5) and rhomboids + trapezius (n = 3) muscles. The average changes in muscle thickness were 0.24 mm/year on the irradiated side and 1.19 mm/year on the contralateral side, showing significantly reduced growth on the irradiated side (P = 0.001). Younger patients had greater muscle growth. Irradiation dose was not significant, but muscle growth tended to decrease as the dose increased, and muscles irradiated at >50 Gy (RBE) showed little growth. These results show that muscle growth is affected by PBT and that long-term follow-up is needed to evaluate muscle growth retardation.

PurposeWhilst proton beam therapy (PBT) for children with cancer is expected to reduce their comorbidities, to date only a limited number of studies have been published. To analyze the long-term comorbidity and health-related quality of life (HRQoL) of childhood cancer survivors (CCSs) after PBT, we conducted a questionnaire-based study.MethodsQuestionnaires were sent to CCSs who underwent PBT at the University of Tsukuba Hospital during the period from 1984 to 2020. Scores from 41 CCSs who did not undergo PBT (noPBT-CCSs) and from the general population were used for comparison.ResultsIn total, 110 individuals who underwent PBT participated in the study. Among them, 40 individuals were longitudinally analyzed. The range of change in the scores was significantly greater in the CCSs whose initial scores were low. Although the comorbidity levels were more severe, HRQoL tended to be better in the PBT-CCSs than in the noPBT-CCSs with central nervous system (CNS) or solid tumors, respectively. When compared with the general population, the psychosocial health summary scores and its components were not different in the noPBT-CNS-CCSs. On the other hand, the psychosocial health summary scores and/or at least one of the scores of emotional, social, and school functioning were significantly higher in the other CCSs groups.ConclusionsThe HRQoL scores of CCSs with low initial scores can be greatly changed over time. Appropriate psychosocial support for this population is warranted. PBT may avoid reduction in HRQoL in terms of the psychosocial functioning of CCSs with CNS tumors.

We developed a multilayered physical snowpack model named Snow Metamorphism and Albedo Process (SMAP), which is intended to be incorporated into general circulation models for climate simulations. To simulate realistic physical states of snowpack, SMAP incorporates a state‐of‐the‐art physically based snow albedo model, which calculates snow albedo and solar heating profile in snowpack considering effects of snow grain size and snow impurities explicitly. We evaluated the performance of SMAP with meteorological and snow impurities (black carbon and dust) input data measured at Sapporo, Japan during two winters: 2007–2008 and 2008–2009, and found SMAP successfully reproduced all observed variations of physical properties of snowpack for both winters. We have thus confirmed that SMAP is suitable for climate simulations. With SMAP, we also investigated the effects of snow impurities on snowmelt at Sapporo during the two winters. We found that snowpack durations at Sapporo were shortened by 19 days during the 2007–2008 winter and by 16 days during the 2008–2009 winter due to radiative forcings caused by snow impurities. The estimated radiative forcings due to snow impurities during the accumulation periods were 3.7 W/m2 (it corresponds to albedo reduction in 0.05) and 3.2 W/m2 (albedo reduction in 0.05) for the 2007–2008 and 2008–2009 winters, respectively. While during the ablation periods they were 25.9 W/m2 (albedo reduction in 0.18) and 21.0 W/m2 (albedo reduction in 0.17) for each winter, respectively. Key Points A physical snowpack model named SMAP is developed The model is validated in detail using observations Snowpack durations at Sapporo were shortened by impurities

Aggregation of small forest stands into larger management units has been one of the main challenges to improve the management scheme in Japan where the majority of forest owners are small-scale owners. Doing so can improve the efficiency of thinning operations by expanding forest operation sites and by building more efficient road networks over the aggregated management units through the coordination and consolidation of the management practices of small-scale forest owners and resulting in reduced operating costs. We develop a spatially explicit 0–1optimization model that searches for optimal aggregation patterns considering spatial locations of nearby forest roads. In order to take into account the connectivity of forest roads among aggregated management units for logging and hauling, we assume aggregated units located away from a nearby road must be treated only after the aggregated units that act as the pathway to the road are harvested. We solve the 0–1 integer programming problem sequentially in each period of time. We demonstrate our approach using a part of a forest in Nasushiobara, Tochigi prefecture, Japan. Our study forest consists of 1346 forest management units covering an area of 876 ha. We consider various management scenarios and search for the optimal solution to each scenario. Each management scenario has a different set of constraints (e.g., volume flow constraint, the maximum allowable area for aggregation per period, etc.) to be satisfied. Our simulation results show that our proposed approach is able to provide useful information to help forest managers to develop an aggregation plan based on analytical framework that allows us to consider forest growth within and among aggregated units as well as the potential road network connectivity for the entire landscape.

[Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4–93.3%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6543; 80.0% (95% CI: 75.7–83.6%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5–76.7%) vs. 40.2% (95% CI: 31.6–48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8–50% after PT and 0–4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings.

Background/Objectives: PBT enables precise targeting of tumors, which reduces side effects on surrounding organs, with particularly significant benefits for pediatric tumors. However, the efficacy of PBT compared to photon RT for pediatric medulloblastoma is unclear. A meta-analysis to assess the efficacy of PBT vs. photon RT for this disease was performed. Methods: Articles focusing on postoperative primary medulloblastoma from 1990 to 2022 were systematically reviewed and survival outcomes were extracted for medulloblastoma treated with PBT or photon RT. Meta-regression was used to identify predictive factors for treatment outcomes, including modality (PBT vs. photon RT), disease risk classification, gender, and age. Results: From 935 records, 18 articles were included (14 on photon RT, with 6 focusing on high-risk cases, and 4 on PBT). In standard-risk cases, the 1-, 3-, and 5-year overall survival (OS) rates were 95.5% (95% CI: 87.2–98.4%) vs. 96.7% (95% CI: 93.5–98.4%) (p = 0.1210); 89.8% (95% CI: 85.3–92.9%) vs. 88.0% (95% CI: 83.7–91.3%) (p = 0.5416); and 82.9% (95% CI: 76.6–87.6%) vs. 82.4% (95% CI: 77.2–86.5%) (p = 0.8313), respectively. For high-risk cases, the OS rates were 88.9% (95% CI: 85.5–91.6%); 73.6% (95% CI: 60.9–82.8%); and 68.6% (95% CI: 56.1–78.3%), respectively. The 1-, 3-, and 5-year progression-free survival (PFS) rates in standard-risk cases were 95.2% (95% CI: 91.8–97.2%) vs. 93.8% (95% CI: 89.4–96.5%) (p = 0.5275); 82.9% (95% CI: 77.3–87.2%) vs. 82.5% (95% CI: 80.1–84.7%) (p = 0.4294); and 79.6% (95% CI: 73.1–84.6%) vs. 77.0% (95% CI: 72.7–80.8%) (p = 0.3938), respectively. For high-risk cases, the PFS rates were 83.5% (95% CI: 77.0–88.3%); 64.8% (95% CI: 53.2–74.2%); and 60.4% (95% CI: 47.0–71.4%), respectively. Meta-regression analysis indicated no significant differences in 1- to 5-year OS and PFS between radiation modalities. Standard-risk cases were significantly associated with better OS and PFS. Younger age was significantly associated with 1- and 2-year OS and 1-year PFS, and male gender was significantly associated with 3-year OS and 3-year PFS. Conclusions: Postoperative irradiation for pediatric medulloblastoma using PBT has a therapeutic effect comparable to that of photon RT. This suggests that PBT is a useful option among RT modalities for medulloblastoma.