Auditory or Audiovisual Stimulation Ameliorates Cognitive Impairment and Neuropathology in ApoE4 Knock-In Mice.

We hypothesized that auditory stimulation could reduce the progression of Alzheimer's disease (AD), and that audiovisual stimulation could have additional effects through multisensory integration. We exposed 12 month old Apoetm1.1(APOE*4)Adiuj mice (a mouse model of sporadic AD) to auditory (A) or audiovisual stimulation (AV) at 40 Hz for 14 days in a soundproof chamber system (no stimulation, N). Behavioral tests were performed before and after each session, and their brain tissues were assessed for amyloid-beta expression and apoptotic cell death, after 14 days. Furthermore, brain levels of acetylcholine and apoptosis-related proteins were analyzed. In the Y-maze test, the percentage relative alternation was significantly higher in group A than in group N mice. Amyloid-beta and TUNEL positivity in the hippocampal CA3 region was significantly lower in group A and group AV mice than in group N mice (p < 0.05). Acetylcholine levels were significantly higher in group A and group AV mice than in group N mice (p < 0.05). Compared to group N mice, expression of the proapoptotic proteins Bax and caspase-3 was lower in group A, and expression of the antiapoptotic protein Bcl-2 was higher in group AV. In a mouse model of early-stage sporadic AD, auditory or audiovisual stimulation improved cognitive performance and neuropathology.

Reports of anaphylaxis after coronavirus disease 2019 vaccination, South Korea, 26 February to 30 April 2021.

The South Korea mass vaccination programme administered 3.8 million doses of COVID-19 vaccinations between 26 February and 30 April 2021. After 173 suspected anaphylaxis reports to the nationwide monitoring system for adverse events following immunisation, 44 anaphylaxis cases were confirmed using Brighton Collaboration case definitions. The rates per million doses were 18.2 cases and 6.2 cases for Vaxzevria and Comirnaty, respectively. Median time of onset was 14 min after vaccination and most cases had recovered at the time of review.

De Novo Development of a Quantitative Adverse Outcome Pathway (qAOP) Network for Ultraviolet B (UVB) Radiation Using Targeted Laboratory Tests and Automated Data Mining.

Ultraviolet B (UVB) radiation is a natural nonchemical stressor posing potential hazards to organisms such as planktonic crustaceans. The present study was conducted to revisit the lethal effects of UVB on crustaceans, generate new experimental evidence to fill in knowledge gaps, and develop novel quantitative adverse outcome pathways (qAOPs) for UVB. A combination of laboratory and computational approaches was deployed to achieve the goals. For targeted laboratory tests, Daphnia magna was used as a prototype and exposed to a gradient of artificial UVB. Targeted bioassays were used to quantify the effects of UVB at multiple levels of biological organization. A toxicity pathway network was assembled based on the new experimental evidence and previously published data extracted using a novel computational tool, the NIVA Risk Assessment Database (NIVA RAdb). A network of AOPs was developed, and weight of evidence was assessed based on a combination of the current and existing data. In addition, quantitative key event relationships in the AOPs were developed by fitting the D. magna data to predefined models. A complete workflow for assembly and evaluation of qAOPs has been presented, which may serve as a good example for future de novo qAOP development for chemical and nonchemical stressors.

Epigenetic, transcriptional and phenotypic responses in Daphnia magna exposed to low-level ionizing radiation.

Ionizing radiation is known to induce oxidative stress and DNA damage as well as epigenetic effects in aquatic organisms. Epigenetic changes can be part of the adaptive responses to protect organisms from radiation-induced damage, or act as drivers of toxicity pathways leading to adverse effects. To investigate the potential roles of epigenetic mechanisms in low-dose ionizing radiation-induced stress responses, an ecologically relevant crustacean, adult Daphnia magna were chronically exposed to low and medium level external 60Co gamma radiation ranging from 0.4, 1, 4, 10, and 40 mGy/h for seven days. Biological effects at the molecular (global DNA methylation, histone modification, gene expression), cellular (reactive oxygen species formation), tissue/organ (ovary, gut and epidermal histology) and organismal (fecundity) levels were investigated using a suite of effect assessment tools. The results showed an increase in global DNA methylation associated with loci-specific alterations of histone H3K9 methylation and acetylation, and downregulation of genes involved in DNA methylation, one-carbon metabolism, antioxidant defense, DNA repair, apoptosis, calcium signaling and endocrine regulation of development and reproduction. Temporal changes of reactive oxygen species (ROS) formation were also observed with an apparent transition from ROS suppression to induction from 2 to 7 days after gamma exposure. The cumulative fecundity, however, was not significantly changed by the gamma exposure. On the basis of the new experimental evidence and existing knowledge, a hypothetical model was proposed to provide in-depth mechanistic understanding of the roles of epigenetic mechanisms in low dose ionizing radiation induced stress responses in D. magna.

Comparative sensitivity to gamma radiation at the organismal, cell and DNA level in young plants of Norway spruce, Scots pine and Arabidopsis thaliana.

MAIN CONCLUSION: Persistent DNA damage in gamma-exposed Norway spruce, Scots pine and Arabidopsis thaliana, but persistent adverse effects at the organismal and cellular level in the conifers only. Gamma radiation emitted from natural and anthropogenic sources may have strong negative impact on plants, especially at high dose rates. Although previous studies implied different sensitivity among species, information from comparative studies under standardized conditions is scarce. In this study, sensitivity to gamma radiation was compared in young seedlings of the conifers Scots pine and Norway spruce and the herbaceous Arabidopsis thaliana by exposure to 60Co gamma dose rates of 1-540 mGy h-1 for 144 h, as well as 360 h for A. thaliana. Consistent with slightly less prominent shoot apical meristem, in the conifers growth was significantly inhibited with increasing dose rate ≥ 40 mGy h-1. Post-irradiation, the conifers showed dose-rate-dependent inhibition of needle and root development consistent with increasingly disorganized apical meristems with increasing dose rate, visible damage and mortality after exposure to ≥ 40 mGy h-1. Regardless of gamma duration, A. thaliana showed no visible or histological damage or mortality, only delayed lateral root development after ≥ 100 mGy h-1 and slightly, but transiently delayed post-irradiation reproductive development after ≥ 400 mGy h-1. In all species dose-rate-dependent DNA damage occurred following ≥ 1-10 mGy h-1 and was still at a similar level at day 44 post-irradiation. In conclusion, the persistent DNA damage (possible genomic instability) following gamma exposure in all species may suggest that DNA repair is not necessarily mobilized more extensively in A. thaliana than in Norway spruce and Scots pine, and the far higher sensitivity at the organismal and cellular level in the conifers indicates lower tolerance to DNA damage than in A. thaliana.

No evidence of a protective or cumulative negative effect of UV-B on growth inhibition induced by gamma radiation in Scots pine (Pinus sylvestris) seedlings.

Exposure to ambient UV-B radiation may prime protective responses towards various stressors in plants, though information about interactive effects of UV-B and gamma radiation is scarce. Here, we aimed to test whether UV-B exposure could prime acclimatisation mechanisms contributing to tolerance to low-moderate gamma radiation levels in Scots pine seedlings, and concurrently whether simultaneous UV-B and gamma exposure may have an additive adverse effect on seedlings that had previously not encountered either of these stressors. Responses to simultaneous UV-B (0.35 W m-2) and gamma radiation (10.2-125 mGy h-1) for 6 days with or without UV-B pre-exposure (0.35 W m-2, 4 days) were studied across various levels of organisation, as compared to effects of either radiation type. In contrast to UV-B, and regardless of UV-B presence, gamma radiation at ≥42.9 mGy h-1 caused increased formation of reactive oxygen species and reduced shoot length, and reduced root length at 125 mGy h-1. In all experiments there was a gamma dose rate-dependent increase in DNA damage at ≥10.8 mGy h-1, generally with additional UV-B-induced damage. Gamma-induced growth inhibition and gamma- and UV-B-induced DNA damage were still visible 44 days post-irradiation, even at 20.7 mGy h-1, probably due to genomic instability, but this was reversed after 8 months. In conclusion, there was no evidence of a protective effect of UV-B on gamma-induced growth inhibition and DNA damage in Scots pine, and no additive adverse effect of gamma and UV-B radiation on growth in spite of the additional UV-B-induced DNA damage.

Auxin analysis using laser microdissected plant tissues sections.

BACKGROUND: Quantitative measurement of actual auxin levels in plant tissue is complimentary to molecular methods measuring the expression of auxin related genes. Current analytical methods to quantify auxin have pushed the limit of detection to where auxin can be routinely quantified at the pictogram (pg) level, reducing the amount of tissue needed to perform these kinds of studies to amounts never imagined a few years ago. In parallel, the development of technologies like laser microdissection microscopy (LMD) has allowed specific cells to be harvested from discrete tissues without including adjacent cells. This method has gained popularity in recent years, especially for enabling a higher degree of spatial resolution in transcriptome profiling. As with other quantitative measurements, including hormone quantifications, sampling using traditional LMD is still challenging because sample preparation clearly compromises the preservation of analytes. Thus, we have developed and validated a sample preparation protocol combining cryosectioning, freeze-drying, and capturing with a laser microdissection microscope to provide high-quality and well-preserved plant materials suitable for ultrasensitive, spatially-resolved auxin quantification. RESULTS: We developed a new method to provide discrete plant tissues for indole-3-acetic acid (IAA) quantification while preserving the plant tissue in the best possible condition to prevent auxin degradation. The method combines the use of cryosectioning, freeze-drying and LMD. The protocol may also be used for other applications that require small molecule analysis with high tissue-specificity where degradation of biological compounds may be an issue. It was possible to collect the equivalent to 15 mg of very specific tissue in approximately 4 h using LMD. CONCLUSIONS: We have shown, by proof of concept, that freeze dried cryosections of plant tissue were suitable for LMD harvest and quantification of the phytohormone auxin using GC-MS/MS. We expect that the ability to resolve auxin levels with both spatial- and temporal resolution with high accuracy will enable experiments on complex processes, which will increase our knowledge of the many roles of auxins (and, in time, other phytohormones) in plant development.

Thermoperiodic Control of Floral Induction Involves Modulation of the Diurnal FLOWERING LOCUS T Expression Pattern.

Thermoperiodism is defined as the ability to discriminate between day temperature (DT) and night temperature (NT). Our aim was to shed light on the mechanistic basis of thermoperiodic floral induction with acceleration under lower DT than NT compared with other DT-NT combinations at the same average daily temperature (ADT), a response exploited in temperate area greenhouses. Arabidopsis thaliana floral pathway mutants and a lhy circadian clock mutant as well as the expression of floral integrators and LHY (LATE ELONGATED HYPOCOTYL) were studied under different DT-NT combinations, all at the same ADT. We show that acceleration of floral induction under lower DT than NT is linked to increased FT expression early during the day and generally increased LFY expression preceding visible flower buds, compared with higher DT than NT or equal DT and NT. Consistent with FLOWERING LOCUS T (FT) action through LEAFY (LFY), time to floral transition in ft-1 and lfy-1 was similar under all treatments, in contrast to the situation for soc1-1, which behaved like the wild type (WT). The lhy-21 mutants did not discriminate between opposite DT-NT combinations, whereas LHY expression in the WT differed in these temperature regimes. This might suggest that LHY plays a role in thermoperiodic control of floral induction. We conclude that thermoperiodic control of floral transition is associated with modulation of the diurnal expression patterns of FT, with timing of temperature alteration being important rather than ADT.

Transcriptional profiling of epigenetic regulators in somatic embryos during temperature induced formation of an epigenetic memory in Norway spruce.

MAIN CONCLUSION: A significant number of epigenetic regulators were differentially expressed during embryogenesis at different epitype-inducing conditions. Our results support that methylation of DNA and histones, as well as sRNAs, are pivotal for the establishment of the epigenetic memory. As a forest tree species with long generation times, Norway spruce is remarkably well adapted to local environmental conditions despite having recently, from an evolutionary perspective, recolonized large areas following the last glaciation. In this species, there is an enigmatic epigenetic memory of the temperature conditions during embryogenesis that allows rapid adaptation to changing environment. We used a transcriptomic approach to investigate the molecular mechanisms underlying the formation of the epigenetic memory during somatic embryogenesis in Norway spruce. Nine mRNA libraries were prepared from three epitypes of the same genotype resulting from exposure to epitype-inducing temperatures of 18, 23 and 28 °C. RNA-Seq analysis revealed more than 10,000 differentially expressed genes (DEGs). The epitype-inducing conditions during SE were accompanied by marked transcriptomic changes for multiple gene models related to the epigenetic machinery. Out of 735 putative orthologs of epigenetic regulators, 329 were affected by the epitype-inducing temperatures and differentially expressed. The majority of DEGs among the epigenetic regulators was related to DNA and histone methylation, along with sRNA pathways and a range of putative thermosensing and signaling genes. These genes could be the main epigenetic regulators involved in formation of the epigenetic memory. We suggest considerable expansion of gene families of epigenetic regulators in Norway spruce compared to orthologous gene families in Populus and Arabidopsis. Obtained results provide a solid basis for further genome annotation and studies focusing on the importance of these candidate genes for the epigenetic memory formation.

Dose rate dependent genotoxic and metabolic effects predict onset of impaired development and mortality in Atlantic salmon (S. salar) embryos exposed to chronic gamma radiation.

Release of radionuclides to the environment from either nuclear weapon and fuel cycles or from naturally occurring radionuclides (NORM) may cause long term contamination of aquatic ecosystems and chronic exposure of living organisms to ionizing radiation, which in turn could lead to adverse effects compromising the sustainability of populations. To address the effects of chronic ionizing radiation on the development of fish, Atlantic salmon embryos were exposed from fertilization until hatching (88 days, 550 day-degree) to dose rates from 1 to 30 mGy·h-1 gamma radiation (60Co). The lowest adopted dose rate was similar to the highest doses measured in some water bodies right after the Chernobyl accident (1 mGy·h-1), however, well above current environmentally realistic scenarios (20 µGy·h-1), or the threshold assumed for significant effects on fish population (40 µGy·h-1). Dose dependent effects were observed on survival, hatching, morbidity, DNA damage, antioxidant defenses, and metabolic status. Histopathological analysis showed dose rate dependent impairment of eye and brain tissues development and establishment of epidermal mucus cell layers accompanied by increased DNA damage at doses ≥1.3 Gy (dose rates ≥1 mGy·h-1). At ≥32.8 Gy (dose rates ≥20 mGy·h-1) deformities and developmental growth defects resulted in respective 46 and 95 % pre-hatch mortality. The 10 mGy·h-1 exposure (≥ 12 Gy total dose) caused significantly increased DNA damage, impaired eye development, and both premature and delayed hatching, while no deformities or effect on survival were observed. We observed a dose rate dependent reduction from dose rate ≥ 20 mGy·h-1 (≥ 27 Gy total dose) on antioxidant SOD, catalase and glutathione reductase enzyme activities. The reduction of antioxidant enzyme activities was in line with observed developmental delay and disturbance to time of hatching. Metabolomic profiles showed a clear shift at dose rates ≥10 mGy·h-1 (≥ 12 Gy total dose) in pathways related to oxidative stress, detoxification, DNA damage and repair. Due to gamma radiation exposure, a switch of central metabolism from glycolysis, citric acid cycle and lactate production towards pentose phosphate pathway indicated a rewiring mechanism for increased production of reductive equivalents to maintain redox homeostasis at the expense of energy output and thus embryonic development.

Clinical Implications of the Association between Respiratory and Gastrointestinal Disorders in Migraine and Non-Migraine Headache Patients.

Headaches, particularly migraine, are associated with gastrointestinal (GI) disorders. In addition to the gut-brain axis, the lung-brain axis is suspected to be involved in the relationship between pulmonary microbes and brain disorders. Therefore, we investigated possible associations of migraine and non-migraine headaches (nMH) with respiratory and GI disorders using the clinical data warehouse over 11 years. We compared data regarding GI and respiratory disorders, including asthma, bronchitis, and COPD, among patients with migraine, patients with nMH, and controls. In total, 22,444 patients with migraine, 117,956 patients with nMH, and 289,785 controls were identified. After adjustment for covariates and propensity score matching, the odds ratios (ORs) for asthma (1.35), gastroesophageal reflux disorder (1.55), gastritis (1.90), functional GI disorder (1.35), and irritable bowel syndrome (1.76) were significantly higher in patients with migraine than in controls (p = 0.000). The ORs for asthma (1.16) and bronchitis (1.33) were also significantly higher in patients with nMH than in controls (p = 0.0002). When the migraine group was compared with the nMH group, only the OR for GI disorders was statistically significant. Our findings suggest that migraine and nMH are associated with increased risks of GI and respiratory disorders.

Long term effects of ionising radiation in the Chernobyl Exclusion zone on DNA integrity and chemical defence systems of Scots pine (Pinus sylvestris).

The Chernobyl Nuclear Power Plant (ChNPP) accident in 1986 resulted in extremely high levels of acute ionising radiation, that killed or damaged Scots pine (Pinus sylvestris) trees in the surrounding areas. Dead trees were cleared and buried, and new plantations established a few years later. Today, more than three decades later, gamma and beta-radiation near the ChNPP is still elevated compared with ambient levels but have decreased by a factor of 300 and 100, respectively. In the present work, Scots pine-trees growing at High (220 µGy h-1), Medium (11 µGy h-1), and Low (0.2 µGy h-1) total (internal + external) dose rates of chronically elevated ionising radiation in the Chernobyl Exclusion zone were investigated with respect to possible damage to DNA, cells and organelles, as well as potentially increased levels of phenolic and terpenoid antioxidants. Scots pine from the High and Medium radiation sites had elevated levels of DNA damage in shoot tips and needles as shown by the COMET assay, as well as increased numbers of resin ducts and subcellular abnormalities in needles. Needles from the High radiation site showed elevated levels of monoterpenes and condensed tannins compared with those from the other sites. In conclusion, more than three decades after the ChNPP accident substantial DNA damage and (sub)cellular effects, but also mobilisation of stress-protective substances possessing antioxidant activity were observed in Scots pine trees growing at elevated levels of ionising radiation. This demonstrates that the radiation levels in the Red Forest still significantly impact the plant community.

Surgery Performed Under Propofol Anesthesia Induces Cognitive Impairment and Amyloid Pathology in ApoE4 Knock-In Mouse Model.

Background: Postoperative cognitive dysfunction (POCD) following anesthesia and surgery is a common and severe complication, especially in elderly patients. A pre-existing cognitive impairment may impart susceptibility to further cognitive dysfunction; the mechanism remains unclear. We hypothesized that the specific impacts of anesthesia and surgery on individuals with preclinical Alzheimer's disease (AD) may render them more susceptible to an increase in the risk of cognitive impairment. The aim of this study was to compare the cognitive impairment between normal adult mice and those with preclinical AD after propofol anesthesia and surgery. Methods: We performed abdominal surgery in cognitively pre-symptomatic, 5-month-old male mice with sporadic AD (apolipoprotein E4 allele, ApoE4-KI) and age-matched (C57BL/6J) controls. Propofol anesthesia (170 mg/kg) was induced via retro-orbital injection over 2 h. Morris water maze (MWM) and Y-maze tests were conducted 2 days before and 2, 4, and 7 days after surgery. The mean escape latencies and spontaneous alternation percentages were the major outcomes. Neuronal apoptosis in hippocampal sections was evaluated using the terminal dUTP nick-end labeling (TUNEL) assay. Hippocampal amyloid beta (Aß) levels were assessed via quantitative immunohistochemistry (IHC). Results: The control mice exhibited increased mean escape latencies of MWM at postoperative 2 and 4, but not at day 7; ApoE4-KI mice exhibited such increases at postoperative days 2, 4 and 7. Significant differences between ApoE4-KI and control mice in terms of the mean escape latencies were evident at days 2 and 7 (both P < 0.05). However, performance on a non-hippocampal memory tasks (Y-maze test) did not differ. More TUNEL-positive neurons were evident in the hippocampal CA3 region of ApoE4-KI mice at postoperative days 2 and 4, but not at day 7 compared to the control group (both P < 0.05). IHC revealed significantly elevated Aß deposition in the hippocampal CA3 region of ApoE4-KI mice at postoperative days 4 and 7 compared to control mice (both P < 0.05). Conclusions: Propofol anesthesia followed by surgery induced persistent changes in cognition, and pathological hippocampal changes in pre-symptomatic, but vulnerable AD mice. It would be appropriate to explore whether preclinical AD patients are more vulnerable to POCD development.

Differences in Frontal Lobe Dysfunction in Patients with Episodic and Chronic Migraine.

Neuroimaging and neuropsychological investigations have indicated that migraineurs exhibit frontal lobe-related cognitive impairment. We investigated whether orbitofrontal and dorsolateral functioning differed between individuals with episodic migraine (EM) and chronic migraine (CM), focusing on orbitofrontal dysfunction because it is implicated in migraine chronification and medication overuse headache (MOH) in migraineurs. This cross-sectional study recruited women with CM with/without MOH (CM + MOH, CM - MOH), EM, and control participants who were matched in terms of age and education. We conducted neuropsychological assessments of frontal lobe function via the Trail Making Test (TMT) A and B, the Wisconsin Card Sorting Test (WCST), and the Iowa Gambling Task (IGT). We enrolled 36 CM (19 CM + MOH, 17 CM - MOH), 30 EM, and 30 control participants. The CM patients performed significantly (p < 0.01) worse on the TMT A and B than the EM patients and the control participants. The WCST also revealed significant differences, with poorer performance in the CM patients versus the EM patients and the control participants. However, the net scores on the IGT did not significantly differ among the three groups. Our findings suggest that the CM patients exhibited frontal lobe dysfunction, and, particularly, dorsolateral dysfunction. However, we found no differences in frontal lobe function according to the presence or absence of MOH.

COVID-19 vaccine safety monitoring in the Republic of Korea: February 26, 2021 to April 30, 2021.

OBJECTIVE: On February 26, 2021, coronavirus disease 2019 (COVID-19) vaccination was started for high-priority groups based on the recommendation of the Advisory Committee on Immunization Practices with 2 available COVID-19 vaccines (AstraZeneca and Pfizer-BioNTech) in Korea. This report provides a summary of adverse events following COVID-19 vaccination as of April 30, 2021. METHODS: Adverse events following immunization are notifiable by medical doctors to the Korea Immunization Management System (KIMS) under the national surveillance system. We analyzed all adverse events reports following COVID-19 vaccination to the KIMS from February 26 to April 30, 2021. RESULTS: In total, 16,196 adverse events following 3,586,814 administered doses of COVID-19 vaccines were reported in approximately 2 months (February 26 to April 30, 2021). Of these, 15,658 (96.7%) were non-serious adverse events, and 538 (3.3%) were serious adverse events, including 73 (0.5%) deaths. The majority of adverse events (n=13,063, 80.7%) were observed in women, and the most frequently reported adverse events were myalgia (52.2%), fever (44.9%), and headache (34.9%). Of the 73 deaths following the COVID-19 vaccination, none were related to the vaccines. CONCLUSION: By April 30, 3.6 million doses of the COVID 19 vaccine had been given in Korea, and the overwhelming majority of reports were for non-serious events. The Korea Disease Control and Prevention Agency continues to monitor the safety of COVID-19 vaccination.

Integrative assessment of low-dose gamma radiation effects on Daphnia magna reproduction: Toxicity pathway assembly and AOP development.

High energy gamma radiation is potentially hazardous to organisms, including aquatic invertebrates. Although extensively studied in a number of invertebrate species, knowledge on effects induced by gamma radiation is to a large extent limited to the induction of oxidative stress and DNA damage at the molecular/cellular level, or survival, growth and reproduction at the organismal level. As the knowledge of causal relationships between effects occurring at different levels of biological organization is scarce, the ability to provide mechanistic explanation for observed adverse effects is limited, and thus development of Adverse Outcome Pathways (AOPs) and larger scale implementation into next generation hazard and risk predictions is restricted. The present study was therefore conducted to assess the effects of high-energy gamma radiation from cobalt-60 across multiple levels of biological organization (i.e., molecular, cellular, tissue, organ and individual) and characterize the major toxicity pathways leading to impaired reproduction in the model freshwater crustacean Daphnia magna (water flea). Following gamma exposure, a number of bioassays were integrated to measure relevant toxicological endpoints such as gene expression, reactive oxygen species (ROS), lipid peroxidation (LPO), neutral lipid storage, adenosine triphosphate (ATP) content, apoptosis, ovary histology and reproduction. A non-monotonic pattern was consistently observed across the levels of biological organization, albeit with some variation at the lower end of the dose-rate scale, indicating a complex response to radiation doses. By integrating results from different bioassays, a novel pathway network describing the key toxicity pathways involved in the reproductive effects of gamma radiation were proposed, such as DNA damage-oocyte apoptosis pathway, LPO-ATP depletion pathway, calcium influx-endocrine disruption pathway and DNA hypermethylation pathway. Three novel AOPs were proposed for oxidative stressor-mediated excessive ROS formation leading to reproductive effect, and thus introducing the world's first AOPs for non-chemical stressors in aquatic invertebrates.

Sequential cell wall transformations in response to the induction of a pedicel abscission event in Euphorbia pulcherrima (poinsettia).

Alterations in the detection of cell wall polysaccharides during an induced abscission event in the pedicel of Euphorbia pulcherrima (poinsettia) have been determined using monoclonal antibodies and Fourier transform infrared (FT-IR) microspectroscopy. Concurrent with the appearance of a morphologically distinct abscission zone (AZ) on day 5 after induction, a reduction in the detection of the LM5 (1-->4)-beta-D-galactan and LM6 (1-->5)-alpha-L-arabinan epitopes in AZ cell walls was observed. Prior to AZ activation, a loss of the (1-->4)-beta-D-galactan and (1-->5)-alpha-L-arabinan epitopes was detected in cell walls distal to the AZ, i.e. in the to-be-shed organ. The earliest detected change, on day 2 after induction, was a specific loss of the LM5 (1-->4)-beta-D-galactan epitope from epidermal cells distal to the region where the AZ would form. Such alteration in the cell walls was an early, pre-AZ activation event. An AZ-associated de-esterification of homogalacturonan (HG) was detected in the AZ and distal area on day 7 after induction. The FT-IR analysis indicated that lignin and xylan were abundant in the AZ and that lower levels of cellulose, arabinose and pectin were present. Xylan and xyloglucan epitopes were detected in the cell walls of both the AZ and also the primary cell walls of the distal region at a late stage of the abscission process, on day 7 after induction. These observations indicate that the induction of an abscission event results in a temporal sequence of cell wall modifications involving the spatially regulated loss, appearance and/or remodelling of distinct sets of cell wall polymers.

Characterization and structural analysis of wild type and a non-abscission mutant at the development funiculus (Def) locus in Pisum sativum L.

BACKGROUND: In pea seeds (Pisum sativum L.), the Def locus defines an abscission event where the seed separates from the funicle through the intervening hilum region at maturity. A spontaneous mutation at this locus results in the seed failing to abscise from the funicle as occurs in wild type peas. In this work, structural differences between wild type peas that developed a distinct abscission zone (AZ) between the funicle and the seed coat and non-abscission def mutant were characterized. RESULTS: A clear abscission event was observed in wild type pea seeds that were associated with a distinct double palisade layers at the junction between the seed coat and funicle. Generally, mature seeds fully developed an AZ, which was not present in young wild type seeds. The AZ was formed exactly below the counter palisade layer. In contrast, the palisade layers at the junction of the seed coat and funicle were completely absent in the def mutant pea seeds and the cells in this region were seen to be extensions of surrounding parenchymatous cells. CONCLUSION: The Def wild type developed a distinct AZ associated with palisade layer and counterpalisade layer at the junction of the seed coat and funicle while the def mutant pea seed showed non-abscission and an absence of the double palisade layers in the same region. We conclude that the presence of the double palisade layer in the hilum of the wild type pea seeds plays an important structural role in AZ formation by delimiting the specific region between the seed coat and the funicle and may play a structural role in the AZ formation and subsequent detachment of the seed from the funicle.

Chelidonine Induces Caspase-Dependent and Caspase-Independent Cell Death through G2/M Arrest in the T98G Human Glioblastoma Cell Line.

Chelidonium majus L. (family Papaveraceae), commonly known as greater celandine or tetterwort, has been reported to have antibacterial and anticancer effects and chelidonine is known as a functional metabolite extracted from C.

NDRG2 contributes to cisplatin sensitivity through modulation of BAK-to-Mcl-1 ratio.

The downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be associated with the progression and poor prognosis of several cancers. Sensitivity to anti-cancer may be associated with a good prognosis in cancer patients, and NDRG2, which is induced by p53, sensitizes the cells to chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis under chemotreatment has not been sufficiently studied. In this study, we investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53. NDRG2 promoted the sensitivity to cisplatin through the modulation of the BAK-to-Mcl-1 ratio. The degradation of Mcl-1 and increase in BAK were mediated by JNK activation and the eIF2α/p-eIF2α pathway, respectively, which depended on PKR activation in NDRG2-overexpressed U937 (U937-NDRG2) cells. NOX5 was highly expressed in U937-NDRG2 cells and contributed to ROS production after cisplatin treatment. ROS scavenging or NOX5-knockdown successfully inhibited the sensitivity of U937-NDRG2 cells to cisplatin. Taken together, these findings indicate that NDRG2 contributed to the increased sensitivity to ciplatin through the modulation of Bak-to-Mcl-1 ratio regulated by NOX5-ROS-PKR pathway; therefore, we suggest that NDRG2 may be a molecular target for improving the efficacy of drug treatment in cancer patients.