Comparative evaluation of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography for distinguishing between primary central nervous system lymphoma and isocitrate dehydrogenase-wildtype glioblastoma.

PURPOSE: Distinguishing between primary central nervous system lymphoma (PCNSL) and isocitrate dehydrogenase (IDH)-wildtype glioblastoma is important for therapeutic decision-making. This study aimed to compare the performance of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing between these two major malignant brain tumors. METHODS: We retrospectively conducted qualitative and semiquantitative analyses of pre-treatment MET and FDG PET/computed tomography (CT) images of 22 patients with PCNSL and 64 patients with IDH-wildtype glioblastoma. For semiquantitative analysis, we calculated the tumor-to-normal tissue (T/N) ratio by dividing the maximum standardized uptake value (SUV) for the tumor (T) by the average SUV for the normal tissue (N). For performance evaluation, we employed receiver operating characteristic curve analysis and calculated the areas under the curve (AUC) values. RESULTS: In the qualitative analysis, all PCNSLs and IDH-wildtype glioblastomas were MET-positive, while 95% and 84% of PCNSLs and IDH-wildtype glioblastomas, respectively, were FDG-positive. Eleven patients were excluded from the FDG PET/CT semiquantitative analysis because of hyperglycemia. There was no difference in MET T/N ratio between PCNSL and IDH-wildtype glioblastoma (p = 0.37). FDG T/N ratio was significantly higher in PCNSL than in IDH-wildtype glioblastoma (p < 0.001). The AUC value for distinguishing PCNSL from IDH-wildtype glioblastoma was significantly higher for the FDG T/N ratio (0.871) than for the MET T/N ratio (0.565) (p = 0.0027). CONCLUSION: MET PET could detect both PCNSL and IDH-wildtype glioblastoma, but unlike FDG PET, it could not distinguish between these two major malignant brain tumors.

Linear Response Theory of Evolved Metabolic Systems.

Predicting cellular metabolic states is a central problem in biophysics. Conventional approaches, however, sensitively depend on the microscopic details of individual metabolic systems. In this Letter, we derived a universal linear relationship between the metabolic responses against nutrient conditions and metabolic inhibition, with the aid of a microeconomic theory. The relationship holds in arbitrary metabolic systems as long as the law of mass conservation stands, as supported by extensive numerical calculations. It offers quantitative predictions without prior knowledge of systems.

A linear reciprocal relationship between robustness and plasticity in homeostatic biological networks.

In physics of living systems, a search for relationships of a few macroscopic variables that emerge from many microscopic elements is a central issue. We evolved gene regulatory networks so that the expression of core genes (partial system) is insensitive to environmental changes. Then, we found the expression levels of the remaining genes autonomously increase to provide a plastic (sensitive) response. A feedforward structure from the non-core to core genes evolved autonomously. Negative proportionality was observed between the average changes in core and non-core genes, reflecting reciprocity between the macroscopic robustness of homeostatic genes and plasticity of regulator genes. The proportion coefficient between those genes is represented by their number ratio, as in the "lever principle", whereas the decrease in the ratio results in a transition from perfect to partial adaptation, in which only a portion of the core genes exhibits robustness against environmental changes. This reciprocity between robustness and plasticity was satisfied throughout the evolutionary course, imposing an evolutionary constraint. This result suggests a simple macroscopic law for the adaptation characteristic in evolved complex biological networks.

Autotoxin-mediated latecomer killing in yeast communities.

Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.

Distinguishing between primary central nervous system lymphoma and glioblastoma using [18F]fluoromisonidazole and [18F]FDG PET.

OBJECTIVE: The purpose of this study was to assess the diagnostic value of [18F]fluoromisonidazole (FMISO) and 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET to discriminate primary central nervous system lymphoma (PCNSL) from glioblastoma. METHODS: FMISO and FDG PET/CT scans before therapy obtained in 13 patients with PCNSL and in 62 patients with glioblastoma were retrospectively reviewed. PET results were evaluated by visual and semiquantitative analysis. For semiquantitative analysis, the maximum standardized uptake value (SUV) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. The performance in discriminating PCNSL and glioblastoma was evaluated using a receiver-operating characteristics analysis. Area-under-the-curve (AUC) values for the discrimination were calculated. RESULTS: On visual analysis, 54% of PCNSL and 89% of glioblastoma showed positive on FMISO PET. All patients with PCNSL and glioblastoma were FDG positive. FMISO T/N ratio in PCNSL (mean ± SD = 1.80 ± 0.59) was significantly lower than that in glioblastoma (mean ± SD = 2.75 ± 0.84) (P < 0.001). FDG T/N ratio in PCNSL (mean ± SD = 3.01 ± 1.11) was significantly higher than that in glioblastoma (mean ± SD = 1.77 ± 0.79) (P < 0.001). For discrimination of patients with PCNSL from glioblastoma, the AUC values for the FMISO T/N ratio, FDG T/N ratio and combination of the two parameters were 0.833, 0.825 and 0.900, respectively. CONCLUSION: FMISO PET is as helpful for differentiating PCNSL from glioblastoma as FDG PET.

Temporal and spatial changes in reactive astrogliosis examined by 18F-THK5351 positron emission tomography in a patient with severe traumatic brain injury.

BACKGROUND: The positron emission tomography (PET) radioligand 18F-THK5351 is now used to evaluate monoamine oxidase B expression in the reactive astrogliosis seen in various central nervous diseases. Traumatic brain injury (TBI) is known to induce reactive astrogliosis in the lesion site. This is a first report to examine the spatial and temporal changes in reactive astrogliosis as evaluated by 18F-THK5351 after a severe TBI. CASE PRESENTATION: A 27-year-old man suffering from a severe TBI with multiple brain contusions was examined using 18F-THK5351 PET/CT in the subacute and chronic phases after the injury. The first PET scan, performed 46 days after the TBI, showed intense uptake of 18F-THK5351 in and around the brain contusions. The second PET scan, performed 271 days after the TBI, showed reduced uptake of 18F-THK5351 at the original sites of the brain contusions and increased uptakes in the white matter surrounding the contusions and the corpus callosum. The patient exhibited sustained improvement of neuropsychological impairment between the two PET examinations and remarkable recovery from the severe TBI. CONCLUSIONS: There were evident temporal and spatial changes in 18F-THK5351 uptake in the traumatized brain between the two PET examinations. These changes may have been related to the remarkable neurological recovery in this patient. The degree and distribution of reactive astrogliosis detected by 18F-THK5351 PET may be useful in assessing pathophysiology and predicting prognosis in TBI patients.

Fractal analysis of 11C-methionine PET in patients with newly diagnosed glioma.

BACKGROUND: The present study tested the possible utility of fractal analysis from L-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. METHODS: Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. RESULTS: There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p < 0.001). CONCLUSIONS: The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.

Microeconomics of Metabolism: The Warburg Effect as Giffen Behaviour.

Metabolic behaviours of proliferating cells are often explained as a consequence of rational optimization of cellular growth rate, whereas microeconomics formulates consumption behaviours as optimization problems. Here, we pushed beyond the analogy to precisely map metabolism onto the theory of consumer choice. We thereby revealed the correspondence between long-standing mysteries in both fields: the Warburg effect, a seemingly wasteful but ubiquitous strategy where cells favour aerobic glycolysis over more energetically efficient oxidative phosphorylation, and Giffen behaviour, the unexpected consumer behaviour where a good is demanded more as its price rises. We identified the minimal, universal requirements for the Warburg effect: a trade-off between oxidative phosphorylation and aerobic glycolysis and complementarity, i.e. impossibility of substitution for different metabolites. Thus, various hypotheses for the Warburg effect are integrated into an identical optimization problem with the same universal structure. Besides, the correspondence between the Warburg effect and Giffen behaviour implies that oxidative phosphorylation is counter-intuitively stimulated when its efficiency is decreased by metabolic perturbations such as drug administration or mitochondrial dysfunction; the concept of Giffen behaviour bridges the Warburg effect and the reverse Warburg effect. This highlights that the application of microeconomics to metabolism can offer new predictions and paradigms for both biology and economics.

[Points to Note about Neuropsychological Impairment in the Acute Management of Traumatic Brain Injury].

Neuropsychological impairment after traumatic brain injury(TBI)is occasionally difficult to diagnose and called "invisible or hidden impairment," especially when physical impairment is mild. Patients and their family do not recognize the impairment during hospitalization and even after discharge. However, they manifest many problems when they return to real life and society. Here, we have presented the characteristics and tips to diagnose neuropsychological impairment after TBI that are important for clinical neurosurgeons working at acute care hospitals. They are as follows: 1)In the emergency room, accurate evaluation of the consciousness state is the first step. 2)In the acute phase after TBI, do not mix up acute symptomatic seizure and post-traumatic epilepsy. 3)Soon after stabilization of the general condition, detailed radiological examinations should be performed to detect organic brain damages with MRI including DWI, FLAIR, T2*, and SWI. 4)At discharge, it is necessary to provide information about neuropsychological impairment to the patients and their family members. Neurosurgeons should diagnose and treat the patients with accurate understanding of neuropsychological impairment in the acute management of TBI.

Long-term Multidisciplinary Rehabilitation Efficacy in Older Patients After Traumatic Brain Injury: Assessed by the Functional Independence Measure.

Instances of traumatic brain injury (TBI) in the elderly have been increasing along with the aging of popula-tions. In the present study, we examined the effect of aging on long-term multidisciplinary in-patient rehabili-tation efficacy after TBI. Sixty-three patients with physical and cognitive impairments after TBI were enrolled in this study. Patients were divided into 4 age groups (≤ 24, 25-44, 45-64, ≥ 65 years) and the clinical charac-teristics and rehabilitation efficacy of each age group were determined. Functional disability was evaluated using motor and cognitive Functional Independence Measure (FIM) scores. Rehabilitation efficacy was assessed by FIM gains during rehabilitation and compared among the groups. There were no statistically significant dif-ferences in motor and cognitive FIM gains among the age groups. However, cognitive FIM gain was limited in a subset of ≥ 65 patients, and initial cognitive measures could not predict cognitive FIM improvement. These results indicate that chronological age is insufficient to accurately predict rehabilitation efficacy in older TBI patients, and that such patients should be considered candidates for intensive rehabilitation programs based on these results. Accurate prognostication of rehabilitation efficacy with continuing data collection is important when using rehabilitation resources for older TBI patients.

Correlation of 4'-[methyl-11C]-thiothymidine PET with Ki-67 immunohistochemistry separately in patients with newly diagnosed and recurrent gliomas.

OBJECTIVE: 4'-[methyl-11C]-thiothymidine (4DST) uptake on PET was correlated with proliferative activity separately in patients with newly diagnosed and recurrent gliomas. METHODS: A total of 29 patients, 18 with newly diagnosed gliomas and 11 with recurrent gliomas who underwent 4DST PET/computed tomography (CT) were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) of tumor (T) and the mean SUV of normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Proliferative tumor volume (PTV) and total lesion proliferation (TLP) were also calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with 4DST PET parameters. RESULTS: All gliomas but three newly diagnosed gliomas had 4DST uptake on PET. No significant differences in SUVmax, T/N ratio, PTV, or TLP were observed between the newly diagnosed and recurrent gliomas. In the former, correlations between SUVmax (r = 0.57, P = 0.02), T/N ratio (r = 0.51, P = 0.03), PTV (r = 0.74, P < 0.001), and TLP (r = 0.76, P < 0.001) and the Ki-67 index were found. In the latter, the results did not seem to suggest any correlations between any of the PET parameters and Ki-67 index. CONCLUSION: Although preliminary, these results suggest that 4DST PET may be useful for the noninvasive evaluation of proliferation in patients with newly diagnosed gliomas. These data in a small recurrent patient population do not support a clear-cut correlation between 4DST uptake and proliferation.

Correlation of 4'-[methyl-11C]-thiothymidine PET with Gd-enhanced and FLAIR MRI in patients with newly diagnosed glioma.

PURPOSE: To elucidate the biological association between tumor proliferation, tumor infiltration and neovascularization, we analyzed the association between volumetric information of 4'-[methyl-11C]thiothymidine (4DST) positron emission tomography (PET) and fluid-attenuated inversion recovery (FLAIR) and T1-weighted gadopentetate dimeglumine (Gd)-enhanced magnetic resonance imaging (MRI), in patients with newly diagnosed glioma. METHODS: A total of 23 patients with newly diagnosed glioma who underwent both 4DST PET/CT and Gd-enhanced MRI before therapy were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Proliferative tumor volume (PTV) from 4DST PET and the volume of Gd enhancement (GdV) and hyperintense region on FLAIR (FLAIRV) from MRI were calculated. RESULTS: All gliomas but 3 diffuse astrocytomas and one anaplastic astrocytoma had 4DST uptake and Gd enhancement on MRI. There was no significant difference between PTV and GdV although the exact edges of the tumor differed in each modality. The FLAIRV was significantly larger than PTV (P < 0.001). Significant correlations between PTV and GdV (ρ = 0.941, P < 0.001) and FLAIRV (ρ = 0.682, P < 0.001) were found. CONCLUSION: These preliminary results indicate that tumor proliferation assessed by 4DST PET is closely associated with tumor-induced neovascularization determined by Gd-enhanced MRI in patients with newly diagnosed glioma.

Multiple positron emission tomography tracers for use in the classification of gliomas according to the 2016 World Health Organization criteria.

BACKGROUND: The molecular diagnosis of gliomas such as isocitrate dehydrogenase (IDH) status (wild-type [wt] or mutation [mut]) is especially important in the 2016 World Health Organization (WHO) classification. Positron emission tomography (PET) has afforded molecular and metabolic diagnostic imaging. The present study aimed to define the interrelationship between the 2016 WHO classification of gliomas and the integrated data from PET images using multiple tracers, including 18F-fluorodeoxyglucose (18F-FDG), 11C-methionine (11C-MET), 18F-fluorothymidine (18F-FLT), and 18F-fluoromisonidazole (18F-FMISO). METHODS: This retrospective, single-center study comprised 113 patients with newly diagnosed glioma based on the 2016 WHO criteria. Patients were divided into 4 glioma subtypes (Mut, Codel, Wt, and glioblastoma multiforme [GBM]). Tumor standardized uptake value (SUV) divided by mean normal cortical SUV (tumor-normal tissue ratio [TNR]) was calculated for 18F-FDG, 11C-MET, and 18F-FLT. Tumor-blood SUV ratio (TBR) was calculated for 18F-FMISO. To assess the diagnostic accuracy of PET tracers in distinguishing glioma subtypes, a comparative analysis of TNRs and TBR as well as the metabolic tumor volume (MTV) were calculated by Scheffe's multiple comparison procedure for each PET tracer following the Kruskal-Wallis test. RESULTS: The differences in mean 18F-FLT TNR and 18F-FMISO TBR were significant between GBM and other glioma subtypes (P < .001). Regarding the comparison between Gd-T1WI volumes and 18F-FLT MTVs or 18F-FMISO MTVs, we identified significant differences between Wt and Mut or Codel (P < .01). CONCLUSION: Combined administration of 4 PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.

Hypoxic stress visualized in the cervical spinal cord of ALS patients.

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET) study for hypoxic stress has been conducted in the spinal cord of ALS patients.Methods: In the present study, we examined cervical spinal hypoxic stress of nineALS patients with upper extremity (U/E) atrophy by18F-fluoromisonidazole (FMISO) PET.Results: On the ipsilateral side of C1 and C5 levels, 18F-FMISO uptake increased significantly compared with the contralateral side (*p < 0.05) and the control subject (**p < 0.01). In addition, a strong correlation was found between 18F-FMISO uptake of the C5 level and the rate of progression of the ALS FRS-R score (R = 0.781, *p = 0.013).Conclusion: These results indicate that hypoxic stress increased in the spinal cord of ALS patients with a close link to ALS progression. Both hypoxic stress and a compromised response to hypoxia, which may lead to subsequent motor neuron death, could be a potential therapeutic target for ALS.

Clinicopathologic Factors Associated with Tumor Necrosis after Preoperative Embolization of Meningiomas.

Objective: Preoperative embolization of meningiomas induces necrosis prior to surgery and facilitates resection. Lack of contrast enhancement on postembolization MRI correlates with pathological findings of necrosis and can be used to assess embolization efficacy. This study aimed to examine clinicopathologic factors associated with tumor necrosis after embolization. Methods: A total of 119 patients with intracranial meningioma who underwent 145 surgical resections between 2010 and 2019 at our institute were reviewed. Inclusion criteria for the study were preoperative embolization with trisacryl gelatin microspheres (Embosphere) or absorbable gelatine sponge (Gelfoam). Postembolization Gd-enhanced T1-weighted and angiographic imaging, and histopathologic examination results were reviewed to evaluate the effectiveness of embolization. Results: In all, 66 patients satisfied the inclusion criteria. In total, 36 patients were embolized with Embosphere and 30 patients were embolized with Gelfoam. Patients embolized with Embosphere had a significantly higher necrosis rate (NR) than patients with Gelfoam (21% vs. 7.1%, P <0.01). The 36 Embosphere patients were analyzed regarding clinicopathologic factors associated with NR. Tumors in 12 patients were located in the parasagittal/falx region; these patients had a significantly lower NR compared with tumors in other locations (10.6% vs. 26.2%, P = 0.016). In all, 13 patients had feeders arising from only the middle meningeal artery (MMA), which was associated with a significantly higher NR (29.3% vs. 14.4%, P = 0.015). In total, 11 patients had meningeal feeders arising from internal carotid artery (ICA), which was associated with a significantly lower NR (9.0% vs. 26.3%, P <0.01). Conclusion: This study showed embolization agent, tumor location, and blood supply were important factors predicting necrosis after preoperative embolization.

18F-THK5351 PET Can Identify Lesions of Acute Traumatic Brain Injury.

A 67-year-old woman sustained a mild traumatic brain injury (TBI) in a traffic accident and had an initial Glasgow Coma Scale score of 13. She underwent F-THK5351 PET 18 days after TBI. Fused F-THK5351 PET/MRI showed that the location of F-THK5351 accumulations corresponded anatomically to intraparenchymal lesions of acute TBI on MRI. F-THK5351 reportedly binds to monoamine oxidase B highly expressed in astrocytes. Furthermore, TBI induces reactive astrogliosis or blood-brain barrier breakdown included in primary brain injury. Therefore, F-THK5351 uptake may represent primary brain injury in acute TBI lesions.

Association between carotid 18F-NaF and 18F-FDG uptake on PET/CT with ischemic vascular brain disease on MRI in patients with carotid artery disease.

OBJECTIVE: Atherosclerosis is a dynamic and complex process characterized by the formation and progression of plaque mediated by various pathophysiologic steps including inflammation and calcification. The present study aimed to evaluate the association between carotid 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) uptake with the severity of ischemic vascular brain disease on MRI in patients with carotid artery disease. METHODS: A total of 28 patients who were scheduled to undergo clinically indicated carotid endarterectomy or stenting for carotid artery disease were examined with 18F-NaF and 18F-FDG PET/CT and brain MRI. The PET/CT images were evaluated by qualitative and semiquantitative analyses. The maximum standardized uptake value (SUV) for the plaque and the average of mean SUV within the lumen of both internal jugular veins was calculated, and the target-to-blood pool ratio (TBR) was determined. The ischemic vascular brain disease on MRI was graded separately in the bilateral hemisphere as 0, 1, 2, and 3, with 0 being absent and 3 being the most severe. RESULTS: In two patients, only a unilateral carotid artery was analyzed because of previous indwelling stent. 18F-NaF focal uptake was observed in 50 carotid arteries. 18F-FDG focal uptake was observed in 47 carotid arteries. The mean (± SD) 18F-NaF TBR (2.93 ± 0.89) was significantly higher than the mean (± SD) 18F-FDG TBR (2.41 ± 0.84) (p < 0.001). The mean (± SD) values of 18F-NaF TBR were 2.63 ± 0.76 in grade 1, 2.90 ± 0.91 in grade 2, and 3.81 ± 0.60 in grade 3. Significant differences in 18F-NaF TBR were observed between grades 1 and 3 (p < 0.001) and grades 2 and 3 (p = 0.02). The mean (± SD) values of 18F-FDG TBR were 2.35 ± 0.77 in grade 1, 2.23 ± 0.48 in grade 2, and 2.87 ± 1.32 in grade 3. No significant differences in 18F-FDG TBR were noted between any of the ischemic vascular brain disease grades. CONCLUSIONS: These preliminary results suggest that carotid 18F-NaF uptake in patients with carotid artery disease may be associated with the severity of the ischemic vascular brain disease observed on MRI.

Coordination of Polyploid Chromosome Replication with Cell Size and Growth in a Cyanobacterium.

Homologous chromosome number (ploidy) has diversified among bacteria, archaea, and eukaryotes over evolution. In bacteria, model organisms such as Escherichia coli possess a single chromosome encoding the entire genome during slow growth. In contrast, other bacteria, including cyanobacteria, maintain multiple copies of individual chromosomes (polyploid). Although a correlation between ploidy level and cell size has been observed in bacteria and eukaryotes, it is poorly understood how replication of multicopy chromosomes is regulated and how ploidy level is adjusted to cell size. In addition, the advantages conferred by polyploidy are largely unknown. Here we show that only one or a few multicopy chromosomes are replicated at once in the cyanobacterium Synechococcus elongatus and that this restriction depends on regulation of DnaA activity. Inhibiting the DnaA intrinsic ATPase activity in S. elongatus increased the number of replicating chromosomes and chromosome number per cell but did not affect cell growth. In contrast, when cell growth rate was increased or decreased, DnaA level, DnaA activity, and the number of replicating chromosomes also increased or decreased in parallel, resulting in nearly constant chromosome copy number per unit of cell volume at constant temperature. When chromosome copy number was increased by inhibition of DnaA ATPase activity or reduced culture temperature, cells exhibited greater resistance to UV light. Thus, it is suggested that the stepwise replication of the genome enables cyanobacteria to maintain nearly constant gene copy number per unit of cell volume and that multicopy chromosomes function as backup genetic information to compensate for genomic damage.IMPORTANCE Polyploidy has evolved many times across the kingdom of life. The relationship between cell growth and chromosome replication in bacteria has been studied extensively in monoploid model organisms such as Escherichiacoli but not in polyploid organisms. Our study of the polyploid cyanobacterium Synechococcus elongatus demonstrates that replicating chromosome number is restricted and regulated by DnaA to maintain a relatively stable gene copy number/cell volume ratio during cell growth. In addition, our results suggest that polyploidy confers resistance to UV, which damages DNA. This compensatory polyploidy is likely necessitated by photosynthesis, which requires sunlight and generates damaging reactive oxygen species, and may also explain how polyploid bacteria can adapt to extreme environments with high risk of DNA damage.

A Rare Case of Postoperative Symptomatic Cyst Formation After Resection of a Large Convexity Meningioma.

BACKGROUND: Symptomatic cyst formation after brain tumor resection is a rare complication of the early postoperative phase. We describe a complicated case of postoperative symptomatic cyst formation after gross total removal of a convexity meningioma. CASE DESCRIPTION: A 59-year-old woman presented with recent onset motor aphasia. Magnetic resonance imaging revealed a left convexity tumor. We performed gross total resection of the tumor, which was pathologically diagnosed as an atypical meningioma. Tumor resection and decompression of the normal cerebral hemisphere improved aphasia. However, 3 days after surgery, her motor aphasia worsened. Computed tomography scan confirmed that the frontal lobe was being compressed by an enlargement of the postoperative tumor cavity. Conservative therapy did not shrink the cavity, and her motor aphasia persisted. Therefore, 21 days after surgery, a drainage tube was inserted into the enlarged cavity using a neuroendoscope, which promoted shrinkage of the cavity and improved her motor aphasia. We suspected that the enlargement of the postoperative cavity was because of the presence of a valve-like structure. CONCLUSIONS: Even though formation of symptomatic cystic lesions after brain tumor resection is rare, neurosurgeons should be aware of such early postoperative complications and their management strategies.