In Vivo Assessment of Astrocyte Reactivity in Patients with Progressive Supranuclear Palsy.

OBJECTIVE: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity. METHODS: We included 30 patients with PSP-Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18F-florzolotau positron emission tomography. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations. RESULTS: The levels of myo-inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo-inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss. INTERPRETATION: We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo-inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024.

Transient anterior subcapsular vacuolar lens opacities after Tanito microhook trabeculotomy: report of six cases.

OBJECTIVE: To present six cases exhibiting transient anterior subcapsular vacuolar lens opacities following early postoperative Tanito microhook trabeculotomy (TMH) performed by the same surgeon. METHODS: Six patients who underwent lens-sparing TMH at Meizankai Shimizu Eye Clinic from November 2021 to May 2023, and developed anterior subcapsular vacuolar lens opacities postoperatively were reviewed. Detailed records of surgeries, follow-up findings were collected and reported. RESULTS: In all six cases, anterior vacuolar subcapsular lens opacities were observed on the day after surgery, gradually decreasing without affecting visual acuity or contrast sensitivity. In all cases, without any specific interventions, the opacities disappeared by 21 months postoperatively. CONCLUSION: Anterior subcapsular cataracts, characterized by a vacuolar appearance and transient existence, should be recognized as an early complication of ab interno glaucoma surgery, possibly linked to use of distributed ophthalmic viscosurgical devices and excessive anterior chamber irrigation leading to traumatic cataracts on the lens surface.

Acute respiratory failure caused by brainstem demyelinating lesions in an older patient with an atypical relapsing autoimmune disorder.

An 84-year-old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high-intensity signal lesions on fluid-attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well-defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8-positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti-AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing-remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS.

Recent advances in liquid biopsy of central nervous system lymphomas: case presentations and review of the literature.

Surgical biopsy is the gold standard for diagnosing central nervous system (CNS) lymphomas. However, reliable liquid biopsy methods for diagnosing CNS lymphomas have quickly developed and have been implicated in clinical decision-making. In the current report, we introduce two patients for whom liquid biopsy was essential for diagnosing CNS lymphomas and discuss the rapidly growing applications of this technology.

Coupling and uncoupling growth and product formation for producing chemicals.

Microbial fermentation employs two strategies: growth- and nongrowth-coupled productions. Stoichiometric metabolic models with flux balance analysis enable pathway engineering to couple target synthesis with growth, yielding numerous successful results. Growth-coupled engineering also contributes to improving bottleneck flux through subsequent adaptive evolution. However, because growth-coupled production inevitably shares resources between biomass and target syntheses, the cost-effective production of bulk chemicals mandates a nongrowth-coupled approach. In such processes, understanding how and when to transition the metabolic state from growth to production modes becomes crucial, as does maintaining cellular activity during the nongrowing state to achieve high productivity. In this paper, we review recent technologies for growth-coupled and nongrowth-coupled production, considering their advantages and disadvantages.

Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies. To address these knowledge gaps, we conducted a comprehensive 'stage-dependent' investigation of immune cell elements in situ in human NMOSD lesions, based on neuropathological techniques for autopsied/biopsied CNS materials. The present study provided three major findings. First, activated or netting neutrophils and melanoma cell adhesion molecule-positive (MCAM+) helper T (TH) 17/cytotoxic T (TC) 17 cells are prominent, and the numbers of these correlate with the size of NMOSD lesions in the initial or early-active stages. Second, forkhead box P3-positive (FOXP3+) regulatory T (Treg) cells are recruited to NMOSD lesions during the initial, early-active or late-active stages, suggesting rapid suppression of proinflammatory autoimmune events in the active stages of NMOSD. Third, compartmentalized resident memory immune cells, including CD103+ tissue-resident memory T (TRM) cells with long-lasting inflammatory potential, are detected under "standby" conditions in all stages. Furthermore, CD103+ TRM cells express high levels of granzyme B/perforin-1 in the initial or early-active stages of NMOSD in situ. We infer that stage-dependent compartmentalized immune traits orchestrate the pathology of anti-AQP4 antibody-guided NMOSD in situ. Our work further suggests that targeting activated/netting neutrophils, MCAM+ TH17/TC17 cells, and CD103+ TRM cells, as well as promoting the expansion of FOXP3+ Treg cells, may be effective in treating and preventing relapses of NMOSD.

Metabolome analysis of metabolic burden in Escherichia coli caused by overexpression of green fluorescent protein and delta-rhodopsin.

Overexpression of proteins by introducing a DNA vector is among the most important tools for the metabolic engineering of microorganisms such as Escherichia coli. Protein overexpression imposes a burden on metabolism because metabolic pathways must supply building blocks for protein and DNA synthesis. Different E. coli strains have distinct metabolic capacities. In this study, two proteins were overexpressed in four E. coli strains (MG1655(DE3), W3110(DE3), BL21star(DE3), and Rosetta(DE3)), and their effects on metabolic burden were investigated. Metabolomic analysis showed that E. coli strains overexpressing green fluorescent protein had decreased levels of several metabolites, with a positive correlation between the number of reduced metabolites and green fluorescent protein expression levels. Moreover, nucleic acid-related metabolites decreased, indicating a metabolic burden in the E. coli strains, and the growth rate and protein expression levels were improved by supplementation with the five nucleosides. In contrast, two strains overexpressing delta rhodopsin, a microbial membrane rhodopsin from Haloterrigena turkmenica, led to a metabolic burden and decrease in the amino acids Ala, Val, Leu, Ile, Thr, Phe, Asp, and Trp, which are the most frequent amino acids in the delta rhodopsin protein sequence. The metabolic burden caused by protein overexpression was influenced by the metabolic capacity of the host strains and the sequences of the overexpressed proteins. Detailed characterization of the effects of protein expression on the metabolic state of engineered cells using metabolomics will provide insights into improving the production of target compounds.

Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors.

PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis.

Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

Effects of n-butanol production on metabolism and the photosystem in Synecococcus elongatus PCC 7942 based on metabolic flux and target proteome analyses.

Although n-butanol (BuOH) is an ideal fuel because of its superior physical properties, it has toxicity to microbes. Previously, a Synechococcus elongatus PCC 7942 derivative strain that produces BuOH from CO2 was developed by introducing six heterologous genes (BUOH-SE strain). To identify the bottleneck in BuOH production, the effects of BuOH production and its toxicity on central metabolism and the photosystem were investigated. Parental (WT) and BUOH-SE strains were cultured under autotrophic conditions. Consistent with the results of a previous study, BuOH production was observed only in the BUOH-SE strain. Isotopically non-stationary 13C-metabolic flux analysis revealed that the CO2 fixation rate was much larger than the BuOH production rate in the BUOH-SE strain (1.70 vs 0.03 mmol gDCW-1 h-1), implying that the carbon flow for BuOH biosynthesis was less affected by the entire flux distribution. No large difference was observed in the flux of metabolism between the WT and BUOH-SE strains. Contrastingly, in the photosystem, the chlorophyll content and maximum O2 evolution rate per dry cell weight of the BUOH-SE strain were decreased to 81% and 43% of the WT strain, respectively. Target proteome analysis revealed that the amounts of some proteins related to antennae (ApcA, ApcD, ApcE, and CpcC), photosystem II (PsbB, PsbU, and Psb28-2), and cytochrome b6f complex (PetB and PetC) in photosystems decreased in the BUOH-SE strain. The activation of photosynthesis would be a novel approach for further enhancing BuOH production in S. elongatus PCC 7942.

Multicolor optogenetics for regulating flux ratio of three glycolytic pathways using EL222 and CcaSR in Escherichia coli.

Optogenetics is an attractive synthetic biology tool for controlling the metabolic flux distribution. Here, we demonstrated optogenetic flux ratio control of glycolytic pathways consisting of the Embden-Meyerhof-Parnas (EMP), pentose phosphate (PP), and Entner-Doudoroff (ED) pathways by illuminating multicolor lights using blue light-responsive EL222 and green/red light-responsive CcaSR in Escherichia coli. EL222 forms a dimer and binds to a particular DNA sequence under blue light; therefore, target gene expression can be reduced or induced by inserting a recognition sequence into its promoter regions. First, a flux ratio between the PP and ED pathways was controlled by blue light using EL222. After blocking the EMP pathway, the EL222-recognition sequence was inserted between the -35 and -10 regions of gnd to repress the PP flux and was also inserted upstream of the -35 region of edd to induce ED flux. After adjusting light intensity, the PP:ED flux ratios were 60:39% and 29:70% under dark and blue light conditions, respectively. Finally, a CcaSR-based pgi expression system was implemented to control the flux ratio between the EMP and PP + ED pathways by illuminating green/red light. The EMP:PP:ED flux ratios were 80:9:11%, 14:35:51%, and 33:5:62% under green, red, and red and blue light, respectively.

Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases.

BACKGROUND: Germinomatous germ cell tumor is highly sensitive to chemoradiotherapy; patients are expected to survive for decades. Many radiation-induced malignant gliomas (RIMGs) occur >10 years after radiotherapy. Standard therapy for RIMGs has not been established because of the lesion's rarity, the patient's shorter survival period, and the risk of radiation necrosis by repeat radiation. OBSERVATIONS: Two patients, a 32-year-old man and a 50-year-old man, developed glioblastomas more than 20 years after radiation monotherapy for germinoma with or without mature teratoma. The first patient showed a tumor in the left frontotemporal region with disseminated lesions and died 2 months after partial resection of the tumor without responding to the chemotherapy with temozolomide and bevacizumab. Methylation classifier analysis classified the pathology as closest to diffuse pediatric-type high-grade glioma, Rtk1 subtype. The second patient showed a tumor mass in the brainstem and left cerebellar peduncle, which worsened progressively during chemotherapy with temozolomide and bevacizumab. The tumor transiently responded to stereotactic radiotherapy with the CyberKnife. However, the patient died of RIMG recurrence-related aspiration pneumonia 11 months after the biopsy. Methylation classifier analysis classified the pathology as closest to infratentorial pilocytic astrocytoma. LESSONS: Chemoradiotherapy may improve the survival of patients with RIMGs. Furthermore, molecular features may influence the clinical, locoregional, and pathological features of RIMG.

Transarterial embolization for ruptured pancreaticoduodenal artery aneurysm due to segmental arterial mediolysis combined with median arcuate ligament syndrome: a case report.

A 75-year-old female with a history of Parkinson's disease treatment and hypertension presented at the emergency section with sudden onset of right abdominal pain. Contrast-enhanced computed tomography revealed beaded irregular stenosis and dilation of the superior mesenteric artery (SMA) and an aneurysm in the branch of the pancreaticoduodenal artery (PDA) that communicates with the common hepatic artery and SMA. Additionally, a hematoma had formed in the retroperitoneal space, and extravasation of contrast medium from the pancreaticoduodenal artery aneurysm (PDAA) into the hematoma was observed. The celiac artery (CA) was compressed by the median arcuate ligament; stenosis of the CA at its origin and dilation on the distal side were observed. Based on the imaging findings, it was diagnosed that PDAA was ruptured, SMA developed segmental arterial mediolysis (SAM), and CA developed median arcuate ligament syndrome (MALS). The ruptured PDAA was thought to be caused by SAM combined with MALS. Transcatheter arterial embolization (TAE) was performed for the ruptured PDAA. To the best of our knowledge, there have been no reports of TAE for a ruptured PDAA caused by SAM and MALS. After TAE, the PDAA did not re-rupture.

Neurofibromatosis Type 1 with a Giant Diffuse Plexiform Neurofibroma Invading the Liver.

Plexiform neurofibromas (PNs) occur in approximately 50% of patients with neurofibromatosis type 1 (NF1). PNs are rare in the abdominal cavity and especially rare in hepatobiliary lesions. A 31-year-old man with NF1 had a tumor extending along the celiac artery, superior mesenteric artery, and intrahepatic portal vein. We diagnosed him with diffuse PN based on liver tumor biopsy findings and the tumor form. Because the tumor had invaded along the intrahepatic portal vein, surgical resection was deemed difficult, and the patient was followed up with imaging studies. The patient remained asymptomatic without tumor growth.

Vapor-Phase Indium Intercalation in van der Waals Nanofibers of Atomically Thin W6Te6 Wires.

One-dimensional (1D) conducting materials are of great interest as potential building blocks for integrated nanocircuits. Ternary 1D transition-metal chalcogenides, consisting of M6X6 wires with intercalated A atoms (M = Mo or W; X = S, Se, or Te; A = alkali or rare metals, etc.), have attracted much attention due to their 1D metallic behavior, superconductivity, and mechanical flexibility. However, the conventional solid-state reaction usually produces micrometer-scale bulk crystals, limiting their potential use as nanoscale conductors. Here we demonstrate a versatile method to fabricate indium (In)-intercalated W6Te6 (In-W6Te6) bundles with a nanoscale thickness. We first prepared micrometer-long, crystalline bundles of van der Waals W6Te6 wires using chemical vapor deposition and intercalated In into the crystal via a vapor-phase reaction. Atomic-resolution electron microscopy revealed that In atoms were surrounded by three adjacent W6Te6 wires. First-principles calculations suggested that their wire-by-wire stacking can transform through postgrowth intercalation. Individual In-W6Te6 bundles exhibited metallic behavior, as theoretically predicted. We further identified the vibrational modes by combining polarized Raman spectroscopy and nonresonant Raman calculations.

Application of the symbolic regression program AI-Feynman to psychology.

The discovery of hidden laws in data is the core challenge in many fields, from the natural sciences to the social sciences. However, this task has historically relied on human intuition and experience in many areas, including psychology. Therefore, discovering laws using artificial intelligence (AI) has two significant advantages. First, it makes it possible to detect laws that humans cannot discover. Second, it will help construct more accurate theories. An AI called AI-Feynman was released in a very different field, and it performed impressively. Although AI-Feynman was initially designed to discover laws in physics, it can also work well in psychology. This research aims to examine whether AI-Feynman can be a new data analysis method for inter-temporal choice experiments by testing whether it can discover the hyperbolic discount model as a discount function. An inter-temporal choice experiment was conducted to accomplish these objectives, and the data were input into AI-Feynman. As a result, seven discount function candidates were proposed by AI-Feynman. One candidate was the hyperbolic discount model, which is currently considered the most accurate. The three functions of the root-mean-squared errors were superior to the hyperbolic discount model. Moreover, one of the three candidates was more "hyperbolic" than the standard hyperbolic discount function. These results indicate two things. One is that AI-Feynman can be a new data analysis method for inter-temporal choice experiments. The other is that AI-Feynman can discover discount functions that humans cannot find.

Mixed high-grade serous and large cell neuroendocrine carcinoma arising from rectal endometriosis 11 years after hysterectomy.

The malignant gastrointestinal endometriosis transformation is represented by endometriosis-associated intestinal tumors. Endometrioid adenocarcinoma and clear cell adenocarcinoma are most common among the endometrial cancers of all organs. Only four cases of mixed serous carcinoma and large cell neuroendocrine carcinoma have been reported, and all these cases originated from the uterus. A 59-year-old woman with a month's history of bloody stools was admitted. She was stable until the hematochezia occurred but is 11 years post-hysterectomy. A circumferential type-3 advanced upper rectum tumor was seen on colonoscopy. Adenocarcinoma was revealed from the forceps biopsies of the type-3 tumor component. Computed tomography showed narrowed lumen with a thickened rectum wall, a continuing mass, and a component on the anorectal side. Swollen lymph nodes were observed around the rectum, but no distant metastatic lymph nodes or organs were found. To treat the lesion, rectal surgical resection with D3 lymph node dissection was performed. Histological examination revealed combined high-grade serous and large cell neuroendocrine carcinomas. Tumor was contiguous to the endometrium in the sub-serosa. Endometriosis was determined to be the origin of both carcinomas. Therefore, endometriosis-associated intestinal tumors should be included in the differential diagnosis when rectal tumors with cystic structures are found post-hysterectomy.

Influence of the thickening agent contained in a phosphoric acid etchant on bonding between feldspar porcelain and resin cement with a silane coupling agent.

Phosphoric acid (PA) etchants are widely used for the bonding pretreatment of teeth; however, their influences on the bonding between glass-ceramics and resin cement have not been clarified yet. This study investigated the effect of a thickening agent on the bonding strength between feldspar porcelain treated with a PA etchant and resin cement with a silane coupling agent. The experiments were performed using two PA etchants: commercial one and prepared one consisting a PA aqueous solution and poly(ethylene glycol) thickening agent. The samples were evaluated by shear bond strength testing, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The obtained results revealed that the thickening agent adhered to the porcelain surface and inhibited cement bonding. Meanwhile, PA remained on the surface due to the presence of the thickening agent and activated the silane coupling agent. Overall, the PA etchant did not improve the bond durability.

Effect of light fluctuations on photosynthesis and metabolic flux in Synechocystis sp. PCC 6803.

In nature, photosynthetic organisms are exposed to fluctuating light, and their physiological systems must adapt to this fluctuation. To maintain homeostasis, these organisms have a light fluctuation photoprotective mechanism, which functions in both photosystems and metabolism. Although the photoprotective mechanisms functioning in the photosystem have been studied, it is unclear how metabolism responds to light fluctuations within a few seconds. In the present study, we investigated the metabolic response of Synechocystis sp. PCC 6803 to light fluctuations using 13 C-metabolic flux analysis. The light intensity and duty ratio were adjusted such that the total number of photons or the light intensity during the low-light phase was equal. Light fluctuations affected cell growth and photosynthetic activity under the experimental conditions. However, metabolic flux distributions and cofactor production rates were not affected by the light fluctuations. Furthermore, the estimated ATP and NADPH production rates in the photosystems suggest that NADPH-consuming electron dissipation occurs under fluctuating light conditions. Although we focused on the water-water cycle as the electron dissipation path, no growth effect was observed in an flv3-disrupted strain under fluctuating light, suggesting that another path contributes to electron dissipation under these conditions.