[Coordination of Community-Based Integrated Care and Cancer Treatment-In Order to Live Safe Local Life Naturally].

Cancer has been the leading cause of death among Japanese people continuously since 1981. With recent advances in cancer drug therapy and the increasing number of treatment options, it is not uncommon for patients in a state of physical decline who have been transferred to home care to request continuation of treatment. Under such circumstances, it is an important issue for local major hospitals and medical institutions, such as clinics, providing community medical care to be able to cooperate and support patients together. The Japanese government has proposed the Community-based Integrated Care System as a way to support the home care provided by the health care team so that patients can live safe local life naturally in their neighborhoods as long as they could. For example, in order to smoothly build a relationship of trust between patients/families and visiting physicians, the treating physicians and visiting physicians should collaborate with each other from the later stages of chemotherapy treatment. In this collaboration, it is necessary to have someone who can pick up the needs of patients and their families, bridge the gap between the team medical members involved in community medical care (doctors, visiting nurses, visiting pharmacists, care managers, etc)and the local major hospital, and play a coordinating role. As such, it is useful to utilize specialists who are skilled in assessment, care, and coordination of cancer patients, such as professional nurses and certified nurses.

Long-Term Analgesic Efficacy of Neurolytic Splanchnic Nerve Block via the Transintervertebral Disc Approach to Retrocrural Space: A Multicenter Retrospective Study.

INTRODUCTION: The celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via the transintervertebral disc approach was the first choice of treatment. The short-term efficacy of this technique has been reported, but the long-term efficacy is not clear. In the present study, we investigated the long-term analgesic efficacy of this technique. METHODS: This multicenter, retrospective, observational study reviewed the medical records of patients who underwent neurolytic splanchnic nerve block (NSNB) via the transintervertebral disc approach for intractable cancer pain at five tertiary hospitals in Japan from April 2005 to October 2020. The primary outcome was the long-term analgesic efficacy of a one-time NSNB via the transintervertebral disc approach. RESULTS: In total, 76 patients were included in the analysis. The median lowest numerical rating scale (NRS) score was 1 within 14 days. At 1, 2, 3, and 6 months after the nerve block, the median NRS score was also ≤ 2, while the median equivalent oral morphine dose did not show any clinically noticeable increase at those times. CONCLUSION: The long-term analgesic efficacy of NSNB via the transintervertebral disc approach in patients with intractable cancer pain has been demonstrated.

The celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. The celiac plexus nerve block relieves intractable cancer pain arising from the pancreas or other organs in close proximity, and the splanchnic nerve block is considered clinically equivalent to the celiac plexus block for analgesia. At our affiliated institution, fluoroscopy-guided neurolytic splanchnic nerve block with a single needle via the transintervertebral disc approach is the first choice of treatment because it is technically simpler and less invasive than other approaches. While the short-term efficacy of this technique is known, its long-term efficacy remains unclear. Thus, this multicenter, retrospective, observational study aimed to investigate the long-term analgesic efficacy of a neurolytic splanchnic nerve block via the transintervertebral disc approach. The medical records of patients in whom intractable cancer pain was managed using this technique at five tertiary hospitals in Japan were analyzed. The primary outcome was the long-term analgesic efficacy of a one-time neurolytic splanchnic nerve block via the transintervertebral disc approach. The median lowest numerical rating scale score was 1 within 14 days. At 1, 2, 3, and 6 months after the nerve block, the median numerical rating scale score was also ≤ 2, while the median equivalent oral morphine dose did not show any clinically noticeable increase at those times. This technique may reduce opioid dose and associated side effects compared with long-term conventional pharmacotherapy alone.

Efficacy and Safety of Neurolytic Splanchnic Nerve Block via Transintervertebral Disc Approach to Retrocrural Space: A Multicenter Retrospective Study.

INTRODUCTION: Celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. Several guiding techniques such as fluoroscopy, computed tomography, and endoscopy have been devised, and the target of the block has varied in previous studies as both the celiac plexus and splanchnic nerve, which is the main origin of the celiac plexus, have been targeted. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via transintervertebral disc approach is the first choice. However, there have been few reports on the use of this technique. This study investigated the efficacy and safety of this technique. METHODS: This multicenter retrospective observational study reviewed the medical records of patients who underwent neurolytic splanchnic nerve block (NSNB) via transintervertebral disc approach for intractable cancer pain at five tertiary hospitals in Japan from April 2005 to October 2020. The primary outcome was the clinical success ratio of NSNB, and the secondary outcome was the incidence ratio of NSNB-related adverse events. RESULTS: In total, 103 patients were included in the analysis. Of these, 77 patients met the definition of clinical success, with a ratio of 74.8%. The incidence ratio of NSNB-related adverse events was 40.8% (hypotension, 21.4%; alcohol intoxication, 13.6%; diarrhea, 11.7%; and vascular puncture, 3.9%; duplicates were present). All adverse events improved with observation and symptomatic treatment only. No patient had infection or serious adverse events such as organ or nerve damage. CONCLUSIONS: The clinical success ratio of this technique was 74.8%. Although the incidence of adverse events was 40.8%, all events were mild and no serious adverse events were observed. The findings demonstrate the efficacy and safety of our NSNB in patients with intractable cancer pain.

In patients with intractable pain from abdominal cancer, fluoroscopy-guided neurolytic splanchnic nerve block via transintervertebral disc approach is an effective and safe procedure. It can be completed with a single needle puncture, and is anatomically less likely to cause organ or nerve damage compared with other approaches. The analgesia produced by this technique, along with conventional pharmacotherapy for cancer pain, may reduce opioid dose and its side effects and improve patients' quality of life.

Sulphate repression of ssuD-dependent alkanesulphonate-sulphur assimilation in Escherichia coli.

Escherichia coli cells utilize alkanesulphonates including taurine as the sulphur source. We previously reported that when E. coli cells carrying a double deletion in tauD and cysN were inoculated into a taurine-containing minimal medium, they started to grow only after long-term incubation (Nishikawa et al. 2018, Microbiology 164: 1446-1456). We show here that cells that can induce ssuD-dependent alkanesulphonate-sulphur assimilation (SASSA) are essentially rare, but suppressors that can induce SASSA appear during long-term incubation. Mutant cells carrying ΔtauD and ΔcysN, ΔcysC or ΔcysH generated suppressor cells that can induce SASSA at a frequency of about 10-6 in a population. Whereas ΔtauD ΔcysN cells without prior SASSA did not express ssuD even when necessary, the cells with prior SASSA properly expressed ssuD. Whole-genome DNA sequencing of a clone isolated from ΔtauD ΔcysN cells with prior SASSA revealed that the influx of sulphate or thiosulphate may be related to the regulation of SASSA. To clarify whether sulphate or thiosulphate affects the induction of SASSA, the effect of mutations in sbp and cysP, which are responsible for sulphate and thiosulphate uptake with different preferences for substrates, was examined. Only the ΔtauD ΔcysN Δsbp mutant did not show repression of SASSA when no sulphate was added to the medium. When the concentration of the sulphate added was over 10 µM, the Δsbp mutant showed repression of SASSA. Therefore, it was considered that the influx of extracellular sulphate resulted in repression of SASSA.

Subanesthetic Dose of Propofol Activates the Reward System in Rats.

BACKGROUND: Propofol has addictive properties, even with a single administration, and facilitates dopamine secretion in the nucleus accumbens (NAc). Activation of the dopaminergic circuits of the midbrain reward system, including the ventral tegmental area (VTA) and NAc, plays a crucial role in addiction. However, the effects of propofol on synaptic transmission and biochemical changes in the VTA-NAc circuit remain unclear. METHODS: We investigated the effects of subanesthetic doses of propofol on rat VTA neurons and excitatory synaptic transmission in the NAc using slice patch-clamp experiments. Using immunohistochemistry and western blot analyses, we evaluated the effects of intraperitoneal propofol administration on the expression of addiction-associated transcription factor ΔFosB (truncated form of the FBJ murine osteosarcoma viral oncogene homolog B protein) in the NAcs in 5-week-old rats. RESULTS: In the current-clamp mode, a subanesthetic dose (0.5-5 µmol/L) of propofol increased the action potential frequency in about half the VTA neurons (excited neurons: control: 9.4 ± 3.0 Hz, propofol 0.5 µmol/L: 21.5 ± 6.0 Hz, propofol 5 µmol/L: 14.6 ± 5.3 Hz, wash: 2.0 ± 0.7 Hz, n = 14/27 cells; unchanged/suppressed neurons: control: 1.68 ± 0.94 Hz, propofol 0.5 µmol/L: 1.0 ± 0.67 Hz, propofol 5 µmol/L: 0.89 ± 0.87 Hz, wash: 0.16 ± 0.11 Hz, n = 13/27 cells). In the voltage-clamp mode, about half the VTA principal neurons showed inward currents with 5 µmol/L of propofol (inward current neurons: control: -20.5 ± 10.0 pA, propofol 0.5 µmol/L: -62.6 ± 14.4 pA, propofol 5 µmol/L: -85.2 ± 18.3 pA, propofol 50 µmol/L: -17.1 ± 39.2 pA, washout: +30.5 ± 33.9 pA, n = 6/11 cells; outward current neurons: control: -33.9 ± 14.6 pA, propofol 0.5 µmol/L: -29.5 ± 16.0 pA, propofol 5 µmol/L: -0.5 ± 20.9 pA, propofol 50 µmol/L: +38.9 ± 18.5 pA, washout: +40.8 ± 32.1 pA, n = 5/11 cells). Moreover, 0.5 µmol/L propofol increased the amplitudes of evoked excitatory synaptic currents in the NAc, whereas >5 µmol/L propofol decreased them (control: 100.0 ± 2.0%, propofol 0.5 µmol/L: 118.4 ± 4.3%, propofol 5 µmol/L: 98.3 ± 3.3%, wash [within 10 min]: 70.7 ± 3.3%, wash [30 minutes later]: 89.9 ± 2.5%, n = 13 cells, P < .001, Dunnett's test comparing control and propofol 0.5 µmol/L). Intraperitoneally administered subanesthetic dose of propofol increased ΔFosB expression in the NAc, but not in VTA, 2 and 24 hours after administration, compared with the Intralipid control group (propofol 2 hours: 0.94 ± 0.15, 24 hours: 0.68 ± 0.07; Intralipid 2 hours: 0.40 ± 0.03, 24 hours: 0.37 ± 0.06, P = .0002 for drug in the 2-way analysis of variance). CONCLUSIONS: Even a single administration of a subanesthetic dose of propofol may cause rewarding change in the central nervous system. Thus, there is a potential propofol rewarding effect among patients receiving anesthesia or sedation with propofol, as well as among health care providers exposed to propofol.

Mutations in hik26 and slr1916 lead to high-light stress tolerance in Synechocystis sp. PCC6803.

Increased tolerance to light stress in cyanobacteria is a desirable feature for their applications. Here, we obtained a high light tolerant (Tol) strain of Synechocystis sp. PCC6803 through an adaptive laboratory evolution, in which the cells were repeatedly sub-cultured for 52 days under high light stress conditions (7000 to 9000 µmol m-2 s-1). Although the growth of the parental strain almost stopped when exposed to 9000 µmol m-2 s-1, no growth inhibition was observed in the Tol strain. Excitation-energy flow was affected because of photosystem II damage in the parental strain under high light conditions, whereas the damage was alleviated and normal energy flow was maintained in the Tol strain. The transcriptome data indicated an increase in isiA expression in the Tol strain under high light conditions. Whole genome sequence analysis and reverse engineering revealed two mutations in hik26 and slr1916 involved in high light stress tolerance in the Tol strain.

Bilateral atrophy of the extensor digitorum brevis muscle might be a useful sign for diagnosing diabetic polyneuropathy in Japanese men who do not sit in the traditional "seiza" style.

AIMS/INTRODUCTION: As the extensor digitorum brevis muscle is a small muscle in the most distal part of the legs, its atrophy (EDBA) might reflect symmetric polyneuropathy (SPN). We aimed to clarify the EDBA-related factors and the usefulness of bilateral EDBA detection for diagnosing SPN, especially diabetic SPN (DSPN). MATERIALS AND METHODS: In 1,893 participants from the Japanese general population (investigation I) and 133 established diabetes patients (investigation II), relationships between EDBA and various factors including the traditional sitting style called "seiza'" (kneeling and sitting on one's heels) were investigated. Analyses were carried out by univariate and multivariate analysis, and SPN or DSPN was diagnosed by the criteria of "Probable DSPN" of the Toronto Consensus. The validity of EDBA detection for diagnosing SPN/DSPN was also evaluated. RESULTS: Investigation I: EDBA was more prevalent in women than men (44% vs 20%). Significant EDBA-related factors were aging and seiza habit regardless of sex. Male-specific EDBA-related factors were SPN and known diabetes. In men without seiza habit, EDBA was significantly associated with SPN regardless of diabetes, so EDBA seemed to be a useful sign for diagnosing SPN/DSPN. Investigation II: In men, DSPN was more prevalent in the EDBA group than the non-EDBA group (71% vs 33%). Sensitivity, specificity, positive predictive value and kappa coefficient of EDBA detection for diagnosing DSPN were 44, 87, 67% and 0.323, showing fair agreement. CONCLUSIONS: EDBA detection might be a useful method to screen for distal symmetric polyneuropathy, such as DSPN in men, although the exclusion of individuals with seiza habit is necessary to improve accuracy.

Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT-R).

BACKGROUND: Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. AIMS: To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. METHODS: Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8. RESULTS: Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. CONCLUSION: Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

Taurine dioxygenase (tauD)-independent taurine assimilation in Escherichia coli.

On the basis of previous studies on taurine assimilation in Escherichia coli, TauD, an iron- and α-ketoglutarate-dependent taurine dioxygenase, has been regarded as an indispensable factor for assimilation. However, we found that tauD-deficient strains did not lose their taurine assimilation ability when there was no deletion of ssuD, which encodes a reduced flavin mononucleotide [FMNH(2)]-dependent alkanesulfonate monooxygenase, which is responsible for the desulfonation of alkanesulfonates. There were no significant differences in lag phase time, growth rate and final growth yield between the tauD-deficient strain and the tauD wild-type strain. Iron increased the growth rate and final growth yield of the ssuD mutant, but not those of the tauD mutant. The double deletion of tauD and ssuD resulted in the loss of the ability to assimilate taurine. When ssuD was artificially expressed in the double-deletion mutant, the mutant recovered its taurine assimilation ability. These findings indicate that there is another taurine assimilation pathway that is dependent on ssuD but independent of tauD.

Transcriptome analysis of the cyanobacterium Synechocystis sp. PCC 6803 and mechanisms of photoinhibition tolerance under extreme high light conditions.

Photoinhibition, or cell damage caused by excessively intense light is a major issue for the industrial use of cyanobacteria. To investigate the mechanism of responses to extreme high light intensity, gene expression analysis was performed using the model cyanobacterium Synechocystis sp. PCC 6803 (PCC 6803) cultured under various light intensities. The culture profile data demonstrated that, in contrast to the slow cell growth observed under low light intensities (30 and 50 µmol m-2 s-1), maximal cell growth was observed under mid light conditions (300 and 1000 µmol m-2 s-1). PCC 6803 cells exhibited photoinhibition when cultured under excessive high light intensities of 1100 and 1300 µmol m-2 s-1. From the low to the mid light conditions, the expression of genes related to light harvesting systems was repressed, whereas that of CO2 fixation and of D1 protein turnover-related genes was induced. Gene expression data also revealed that the down-regulation of genes related to flagellum synthesis (pilA2), pyridine nucleotide transhydrogenase (pntA and pntB), and sigma factor (sigA and sigF) represents the key responses of PCC 6803 under excessive high light conditions. The results obtained in this study provide further understanding of high light tolerance mechanisms and should help to improve the productivity of bioprocess using cyanobacteria.

Difference in normal limit values of nerve conduction parameters between Westerners and Japanese people might need to be considered when diagnosing diabetic polyneuropathy using a Point-of-Care Sural Nerve Conduction Device (NC-stat®/DPNCheck™).

AIM/INTRODUCTION: Studies on a novel point-of-care device for nerve conduction study called DPNCheck have been limited to Westerners. We aimed to clarify Japanese normal limits of nerve action potential amplitude (Amp) and conduction velocity by DPNCheck (investigation I), and the validity of DPNCheck to identify diabetic symmetric sensorimotor polyneuropathy (DSPN; investigation II). MATERIALS AND METHODS: For investigation I, 463 non-neuropathic Japanese participants underwent DPNCheck examinations. Regression formulas calculating the normal limits of Amp and conduction velocity (Japanese regression formulas [JRF]) were determined by quantile regression and then compared with regression formulas of individuals from the USA (USRF). For investigation II, in 92 Japanese diabetes patients, 'probable DSPN' was diagnosed and nerve conduction abnormalities (NCA1: one or more abnormalities, and NCA2: two abnormalities in Amp and conduction velocity) were determined. Validity of NCAs to identify 'probable DSPN' was evaluated by determining sensitivity, specificity, reproducibility (kappa-coefficient) and the area under the curve of receiver operating characteristic curves. RESULTS: For investigation I, JRF was different from USRF, and normal limits by JRF were higher than that of USRF. The prevalence of Amp abnormality calculated by JRF was significantly higher than that of USRF. For investigation II, the sensitivity, specificity and reproducibility of NCA1 and NCA2 judged from JRF were 85%, 86% and 0.57, and 43%, 100% and 0.56, respectively. These values of JRF were higher than those of USRF. The area under the curve of JRF (0.89) was larger than USRF (0.82). CONCLUSIONS: A significant difference in the normal limits of nerve conduction parameters by DPNCheck between Japanese and USA individuals was suggested. Validity to identify DSPN of NCAs might improve by changing the judgment criteria from USRF to JRF.

Loop of Streptomyces Feruloyl Esterase Plays an Important Role in the Enzyme's Catalyzing the Release of Ferulic Acid from Biomass.

Feruloyl esterases (FAEs) are key enzymes required for the production of ferulic acid from agricultural biomass. Previously, we identified and characterized R18, an FAE from Streptomyces cinnamoneus NBRC 12852, which showed no sequence similarity to the known FAEs. To determine the region involved in its catalytic activity, we constructed chimeric enzymes using R18 and its homolog (TH2-18) from S. cinnamoneus strain TH-2. Although R18 and TH2-18 showed 74% identity in their primary sequences, the recombinant proteins of these two FAEs (recombinant R18 [rR18] and rTH2-18) showed very different specific activities toward ethyl ferulate. By comparing the catalytic activities of the chimeras, a domain comprised of residues 140 to 154 was found to be crucial for the catalytic activity of R18. Furthermore, we analyzed the crystal structure of rR18 at a resolution of 1.5 Å to elucidate the relationship between its activity and its structure. rR18 possessed a typical catalytic triad, consisting of Ser-191, Asp-214, and His-268, which was characteristic of the serine esterase family. By structural analysis, the above-described domain was found to be present in a loop-like structure (the R18 loop), which possessed a disulfide bond conserved in the genus Streptomyces Moreover, compared to rTH2-18 of its parental strain, the TH2-18 mutant, in which Pro and Gly residues were inserted into the domain responsible for forming the R18 loop, showed markedly high kcat values using artificial substrates. We also showed that the FAE activity of TH2-18 toward corn bran, a natural substrate, was improved by the insertion of the Gly and Pro residues.IMPORTANCEStreptomyces species are widely distributed bacteria that are predominantly present in soil and function as decomposers in natural environments. They produce various enzymes, such as carbohydrate hydrolases, esterases, and peptidases, which decompose agricultural biomass. In this study, based on the genetic information on two Streptomyces cinnamoneus strains, we identified novel feruloyl esterases (FAEs) capable of producing ferulic acid from biomass. These two FAEs shared high similarity in their amino acid sequences but did not resemblance any known FAEs. By comparing chimeric proteins and performing crystal structure analysis, we confirmed that a flexible loop was important for the catalytic activity of Streptomyces FAEs. Furthermore, we determined that the catalytic activity of one FAE was improved drastically by inserting only 2 amino acids into its loop-forming domain. Thus, differences in the amino acid sequence of the loop resulted in different catalytic activities. In conclusion, our findings provide a foundation for the development of novel enzymes for industrial use.

Minimally invasive plate osteosynthesis using posterolateral approach for distal tibial and tibial shaft fractures.

OBJECTIVE: The objective of the study was to evaluate the effectiveness of the posterolateral minimally invasive plate osteosynthesis (MIPO) method for managing distal tibial or tibial shaft fractures with severe anterior and medial soft tissue injuries. MATERIALS AND METHODS: Five consecutive patients with three distal tibial and two tibial shaft fractures (three open fractures) at a level-1 trauma and tertiary referral center were retrospectively reviewed. All patients were definitively treated and followed to bone union. Main outcome was measured by American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, complications, and bone union on radiographs. RESULTS: The average follow-up period was 15.8 months (range, 12-24 months). The average AOFAS score was 88.2 (range, 81-90). There were no complications, such as incision breakdown, deep infection, or impingement of the flexor hallucis longus tendon. Bone union was achieved in all cases. CONCLUSIONS: Posterolateral MIPO is a feasible option when treating these fractures, especially in cases with severe anterior and medial soft tissue injuries.

Relationship between ventral lumbar disc protrusion and contrast medium leakage during sympathetic nerve block.

Ventral disc protrusions have been neglected because they are asymptomatic. Lumbar sympathetic nerve block (LSNB) is one of the clinical choices for refractory low back pain treatment. Leakage of the contrast medium may occur and lead to complications, especially when using a neurolytic agent. In this study, we retrospectively reviewed the magnetic resonance images (MRIs) of 52 consecutive patients with refractory low back pain due to lumbar spinal canal stenosis who underwent LSNB, and graded ventral disc protrusion at the L1/2 to L5/S1 vertebral discs on a three-point scale (grade 0 = no protrusion, grade 1 = protrusion without migration, grade 2 = protrusion with migration). We also determined if there was leakage of contrast medium in LSNB. Ventral disc protrusion was observed in all patients, and 75 % (39/52) had grade 2 protrusion in the L1/2-L3/4 vertebral discs. Moreover, the incidence of contrast medium leakage was significantly higher at the vertebrae that had grade 2 protrusion than at those with less protrusion. We revealed a higher incidence of ventral disc protrusion of the lumbar vertebrae than previously reported, and that the incidence of leakage in LSNB increased when ventral disc protrusion was present. To avoid complications, attention should be paid to ventral disc protrusions before performing LSNB.

Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth.

In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass.

Role of nerve growth factor-tyrosine kinase receptor A signaling in paclitaxel-induced peripheral neuropathy in rats.

The mechanisms underlying paclitaxel-induced peripheral neuropathy remain unknown. Nerve growth factor (NGF) is a representative neurotrophic factor that maintains neuronal function, promotes survival, and mediates neuropathic pain. We investigated expression levels of NGF and its receptors in the dorsal root ganglia (DRG) and spinal dorsal horn (DH) following paclitaxel treatment. Intraperitoneal (I.P.) administration of paclitaxel induced significant mechanical hypersensitivity and cold allodynia in rats, significantly increased the expression of NGF and its receptor tyrosine kinase receptor A (trkA) in the DRG, and increased NGF expression in the DH. In contrast, paclitaxel treatment did not alter the mRNA levels of NGF or its receptors in the DRG, DH, sciatic nerve, or hindpaw skin. Moreover, expression of NEDD4-2, a negative regulator of trkA, was significantly increased in the DRG of paclitaxel-treated rats. Intrathecal (I.T.) administration of the tyrosine kinase receptor inhibitor k252a significantly alleviated mechanical hypersensitivity in paclitaxel-treated rats. Our results suggest that NGF-trkA signaling is involved in mechanical allodynia in paclitaxel-induced neuropathy.

Integrated transcriptomic and metabolomic analysis of the central metabolism of Synechocystis sp. PCC 6803 under different trophic conditions.

Cyanobacteria have received considerable attention as a sustainable energy resource because of their organic material production capacity using light energy and CO2 as a carbon source. Therefore, it is important to understand the cellular metabolism of cyanobacteria for metabolic engineering. In this study, to shed light on the central metabolism of cyanobacteria, we performed transcriptomic and metabolomic analyses of a glucose-tolerant strain of the cyanobacterium Synechocystis sp. PCC 6803, which was cultured under auto- and mixotrophic conditions. Our results indicate that the oxidative pentose phosphate pathway and glycolysis are activated under mixotrophic conditions rather than autotrophic conditions. Moreover, we examined the effect of atrazine, a photosynthesis inhibitor, on the metabolism of PCC 6803 under mixotrophic conditions, which was defined as photoheterotrophic conditions, by transcriptomics and metabolomics. We demonstrated that the activity of the glycolytic pathway decreased due to the indirect effect of atrazine. In addition, the difference in transcriptional and metabolic changes between auto- and photoheterotrophic conditions could also be captured. The omics dataset reported herein provides clues for understanding the metabolism of cyanobacteria.

Bioelectrocatalytic oxidation of glucose with antibiotic channel-containing liposomes.

We developed an efficient bioelectrocatalytic system for glucose oxidation by introducing hydrophilic glucose-permeable antibiotic channels into liposomes.

Overexpression of GSH1 gene mimics transcriptional response to low temperature during seed vernalization treatment of Arabidopsis.

Keeping imbibed seeds at low temperatures for a certain period, so-called seed vernalization (SV) treatment, promotes seed germination and subsequent flowering in various plants. Vernalization-promoting flowering requires GSH. However, we show here that increased GSH biosynthesis partially mimics SV treatment in Arabidopsis thaliana. SV treatment (keeping imbibed seeds at 4°C for 24 h) induced a specific pattern of gene expression and promoted subsequent flowering in WT A. thaliana. A similar pattern was observed at 22°C in transgenic (35S-GSH1) plants overexpressing the γ-glutamylcysteine synthetase gene GSH1, coding for an enzyme limiting GSH biosynthesis, under the control of the cauliflower mosaic virus 35S promoter. This pattern of gene expression was further strengthened at 4°C and indistinguishable from the WT pattern at 4°C. However, flowering in 35S-GSH1 plants was less responsive to SV treatment than in WT plants. There was a difference in the transcript behavior of the flowering repressor FLC between WT and 35S-GSH1 plants. Unlike other genes responsive to SV treatment, the SV-dependent decrease in FLC in WT plants was reversed in 35S-GSH1 plants. SV treatment increased the GSSG level in WT seeds while its level was high in 35S-GSH1 plants, even at a non-vernalizing temperature. Taking into consideration that low temperatures stimulate GSH biosynthesis and cause oxidative stress, GSSG is considered to trigger a low-temperature response, although enhanced GSH synthesis was not enough to completely mimic the SV treatment.

Differences in cerebral blood flow between missed and generalized seizures with electroconvulsive therapy: a positron emission tomographic study.

While examining the acute effects of electroconvulsive therapy (ECT) on regional cerebral blood flow (rCBF), we could compare the changes in rCBF between missed (not generalized) and generalized seizures using H(2)(15)O positron emission tomography in patients with depression under anesthesia. In contrast to missed seizures, rCBF was increased extensively, particularly in the centrencephalic structures in generalized seizures. These results further support the centrencephalic theory of seizure generalization.