Real-time observation of polarization dependence of soft x-ray absorption spectrum during chemical reaction under near-ambient pressure conditions.

The real-time observation of the polarization dependence of soft x-ray absorption spectra during chemical reactions is realized by combining the fluorescence-yield wavelength-dispersive x-ray absorption spectroscopy technique with a 10 Hz switching between horizontal and vertical polarizations. The soft x-ray absorption spectra for both the horizontal and vertical polarizations are recorded every 100 ms with a time difference of 50 ms, which enables the real-time observation of changes in the anisotropic structure around the surface. The technique is applied to the oxidation reaction of a cobalt thin film under an air pressure of up to 25 Pa, and it is suggested that an anisotropic structure appears during the growth of the cobalt oxide species. By using the developed technique, it is expected that the changes in the anisotropic structures, such as molecular orientations, are observed during chemical reactions under near-ambient pressure conditions, which gives a deeper insight into the understanding of the reaction mechanism.

Development of fluorescence-yield wavelength-dispersive x-ray absorption spectroscopy in the soft x-ray region for time-resolved experiments.

A fluorescence-yield wavelength-dispersive x-ray absorption spectroscopy technique in the soft x-ray region, by which the x-ray absorption spectra are recorded without scanning the monochromator, has been developed. The wavelength-dispersed soft x rays, in which the wavelength (photon energy) continuously changes as a function of the position, illuminate the sample, and the emitted fluorescence soft x rays at each position are separately focused by an imaging optics onto each position at a soft x-ray detector. Ni L-edge x-ray absorption spectra for Ni and NiO thin films taken in the wavelength-dispersive mode are shown in order to demonstrate the validity of the technique. The development of the technique paves the way for a real-time observation of time-dependent processes, such as surface chemical reactions, with much higher gas pressure compared to the electron-yield mode, as well as under magnetic and electric fields.

The Effect of Branched Chain Amino Acids-Enriched Nutritional Supplements on Activities of Daily Living and Muscle Mass in Inpatients with Gait Impairments: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of continuous intervention with branched chain amino acids-enriched nutritional supplements from the acute phase to convalescent rehabilitation wards in inpatients with gait impairments. DESIGN: Open-label, randomized, parallel-group comparison study (UMIN Clinical Trials Registry ID: UMIN000018640). SETTING: Acute care and convalescent rehabilitation wards. PARTICIPANTS: We studied 80 patients undergoing stand/gait training. INTERVENTIONS: Participants in the intervention group (RJ group) received nutritional supplements (jelly foods comprising 2500 mg BCAA and 20 IU vitamin D) twice a day until hospital discharge. MEASUREMENTS: The primary outcome was the motor components of the Functional Independence Measure (FIM-m), and the secondary outcome was skeletal muscle mass index. RESULTS: Analyses were conducted on 55 patients who were able to perform stand/gait training continuously from the acute until the recovery phases. FIM-m was significantly elevated in the RJ group and the control group , but no difference was noted between the two groups. Only the RJ group showed a significant increase in skeletal muscle mass index, and the amount of variation was significantly different between the two groups (the control group decreased an average of 2.2% and the RJ group increased an average of 4.3%; P = 0.014). A significant decrease in body weight was found only in the control group (P = 0.084). CONCLUSIONS: Nutritional interventions using branched chain amino acids (BCAA)-enriched nutritional supplements demonstrated no significant difference in activities of daily living; however, an increase in skeletal muscle mass was noted. Skeletal muscle mass and body weight differed significantly between the two groups, and BCAA-enriched nutritional supplements intake in acute and convalescent rehabilitation wards may be effective for the prevention of malnutrition and sarcopenia.

Salvage surgery for a locally persistent or recurrent tumour in maxillary cancer patients who have undergone radiotherapy and concomitant intra-arterial cisplatin: implications for surgical margin assessment.

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

Association between health risks and frailty in relation to the degree of housing damage among elderly survivors of the great East Japan earthquake.

BACKGROUND: Many survivors of the Great East Japan Earthquake that occurred in 2011 were at risk of deteriorating health, especially elderly people living in disaster-stricken areas. The objectives of this prospective study were: a) to clarify the different lifestyle and psychosocial factors associated with frailty by sex among the non-disabled elderly survivors, and b) to describe the differences in characteristics stratified by the degree of disaster-related housing damage. METHODS: We followed 2261 Japanese survivors aged ≥65 years (45.3% male; mean age, 71.7 years) without disability or frailty who completed a self-administered questionnaire at baseline. All participants completed a baseline questionnaire in 2011 and at least one identical follow-up questionnaire between 2012 and 2015 regarding lifestyle (smoking status, alcohol intake, physical activity, sedentary lifestyle, and dietary intake) and psychosocial factors (self-rated health, standard of living, psychological distress, and social networks). Frailty was defined as a score of ≥5 on the Kihon Checklist, which is used by the Japanese government to certify the need for long-term care insurance. Adjusted odds ratios and 95% confidence intervals with frailty as the dichotomous dependent variable and health factors as the independent variables were calculated using a multilevel model for repeated measures by sex, followed by stratification analyses by the degree of housing damage. RESULTS: Over the 4-year study period, 510 participants (22.6%) developed frailty. In the post-disaster setting, many of the psychosocial factors remained more prevalent 4 years later among survivors with extensive housing damage. The presence of risk factors regarding the development of frailty differed by the degree of housing damage. Among men, psychological distress, in parallel with a poor social network, was related to frailty among only the participants with extensive housing damage and those living in temporary housing, whereas among women, worsening psychological distress was associated only with no damage and no displaced survivors. Among women with extensive damage and displacement, health outcomes such as overweight and diabetes and poor social networks were strongly related to frailty. CONCLUSIONS: Lifestyle and psychosocial factors associated with the risk of frailty differ by sex and the degree of housing damage.

The effect of enriched environment across ages: A study of anhedonia and BDNF gene induction.

Enriched environment treatment (EET) is a potential intervention for depression by inducing brain-derived neurotrophic factor (BDNF). However, its age dependency remains unclear. We recently found that EET during early-life development (ED) was effective in increasing exploratory activity and anti-despair behavior, particularly in promoter IV-driven BDNF deficient mice (KIV), with the largest BDNF protein induction in the hippocampus and frontal cortex. Here, we further determined age dependency of EET effects on anhedonia and promoter-specific BDNF transcription, by using the sucrose preference test and qRT-PCR. Wild-type (WT) and KIV mice received 2 months of EET during ED, young-adulthood and old-adulthood (0-2, 2-4 and 12-14 months, respectively). All KIV groups showed reduced sucrose preference, which EET equally reversed regardless of age. EET increased hippocampal BDNF mRNA levels for all ages and genotypes, but increased frontal cortex BDNF mRNA levels only in ED KIV and old WT mice. Transcription by promoters I and IV was age-dependent in the hippocampus of WT mice: more effective induction of exon IV or I during ED or old-adulthood, respectively. Transcription by almost all 9 promoters was age-specific in the frontal cortex, mostly observed in ED KIV mice. After discontinuance of EET, the EET effects on anti-anhedonia and BDNF transcription in both regions persisted only in ED KIV mice. These results suggested that EET was equally effective in reversing anhedonia and inducing hippocampal BDNF transcription, but was more effective during ED in inducing frontal cortex BDNF transcription and for lasting anti-anhedonic and BDNF effects particularly in promoter IV-BDNF deficiency.

Vertical distribution of 236U in the North Pacific Ocean.

The first extensive study on 236U in the North Pacific Ocean has been conducted. The vertical distribution of 236U/238U isotopic ratios and the 236U concentrations were analysed on seven depth profiles, and large variations with depth were found. The range of 236U/238U isotopic ratios was from (0.09 ± 0.03) × 10-10 to (14.1 ± 2.2) × 10-10, which corresponds to 236U concentrations of (0.69 ± 0.24) × 105 atoms/kg and (119 ± 21) × 105 atoms/kg, respectively. The variations in 236U concentrations could mainly be attributed to the different water masses in the North Pacific Ocean and their formation processes. Uranium-236 inventories on the water column of each sampling station were calculated and varied between (3.89 ± 0.08) × 1012 atoms/m2 and (7.03 ± 0.50) × 1012 atoms/m2, which is lower than in former studies on comparable latitudes in the North Atlantic Ocean and the Sea of Japan. The low inventories of 236U found for the North Pacific Ocean in this study can be explained by the lack of additional input sources of artificial radionuclides, apart from global and regional/local fallout. This study expands the use of 236U as oceanographic circulation tracer to yet another ocean basin and shows that this isotope can be used for tracing circulation patterns of water masses in the Pacific Ocean.

A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.

Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.

Prediction of hypotension during spinal anesthesia for elective cesarean section by altered heart rate variability induced by postural change.

BACKGROUND: Maternal hypotension is a common complication during cesarean section performed under spinal anesthesia. Changes in maternal heart rate with postural changes or values of heart rate variability have been reported to predict hypotension. Therefore, we hypothesized that changes in heart rate variability due to postural changes can predict hypotension. METHODS: A total of 45 women scheduled to undergo cesarean section under spinal anesthesia were enrolled. A postural change test was performed the day before cesarean section. The ratio of the power of low and high frequency components contributing to heart rate variability was assessed in the order of supine, left lateral, and supine. Patients who exhibited a ⩾two-fold increase in the low-to-high frequency ratio when moving to supine from the lateral position were assigned to the postural change test-positive group. RESULTS: According to the findings of the postural change test, patients were assigned to the positive (n=22) and negative (n=23) groups, respectively. Hypotension occurred in 35/45 patients, of whom 21 (60%) were in the positive group and 14 (40%) were in the negative group. The incidence of hypotension was greater in the positive group (P<0.01). The total dose of ephedrine was greater in the positive group (15±11 vs. 7±7mg, P=0.005). The area under the receiver operating characteristic curve was 0.76 for the postural change test as a predictor of hypotension. CONCLUSION: The postural change test with heart rate variability analysis may be used to predict the risk of hypotension during spinal anesthesia for cesarean section.

Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.

Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0-2 months), young adult (2-4 months), and old adult (12-14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.

First study on 236U in the Northeast Pacific Ocean using a new target preparation procedure for AMS measurements.

We succeeded in obtaining the depth profile of 236U for a sampling station in the Northeast Pacific Ocean using only one litre of seawater sample from each depth. For this purpose, a new procedure was developed that allowed for the preparation of accelerator mass spectrometry targets for trace uranium using only 100 µg of iron carrier material. The 236U concentrations in water samples from the Northeast Pacific Ocean showed large variations from (9.26 ± 0.42) × 106 atoms/kg at 60 m depth to (0.08 ± 0.02) × 106 atoms/kg at a depth of 3000 m. The high 236U concentrations in surface water reflect the input of 236U by global and local fallout from nuclear weapons tests. The low 236U concentrations in seawater from 1500 m and below are an indicator for the low vertical diffusion of surface water to deeper layers in the North Pacific Ocean. The total inventory of 236U on the water column was (8.35 ± 0.23) × 1012 atoms/m2, which is lower compared to those of other ocean regions solely affected by global fallout on comparable latitudes. This study represents the first dataset for 236U in the Pacific Ocean and shows the possibility of downsizing sample volumes which may help in future applications of 236U as tracer for large ocean areas.

Hip fracture incidence in Japan: Estimates of new patients in 2012 and 25-year trends.

UNLABELLED: We estimated the number of hip fracture patients in 2012 in Japan and investigated the trends in incidence during a 25-year period from 1987 to 2012. Despite the increasing number of patients, the incidence of hip fracture in both men and women aged 70-79 years showed the possibility of decline. INTRODUCTION: The objectives of this study were to estimate the number of hip fracture patients in 2012, to investigate the trends in incidence during a 25-year period from 1987 to 2012, and to determine the regional differences in Japan. METHODS: Data were collected through a nationwide survey based on hospitals by a mail-in survey. Hip fracture incidences by sex and age and standardized incidence ratios by region were calculated. RESULTS: The estimated numbers of new hip fracture patients in 2012 were 175,700 in total (95 % CI 170,300-181,100), 37,600 (36,600-38,600) for men and 138,100 (134,300-141,900) for women. The incidence rates in both men and women aged 70-79 years were the lowest in the 20-year period from 1992 to 2012. The incidence was higher in western areas of Japan than that in eastern areas in both men and women; however, the difference in the incidence of hip fracture between western and eastern areas is becoming smaller. CONCLUSIONS: Despite the increasing number of new patients, the incidence of hip fracture in both men and women aged 70-79 years showed the possibility of decline. The exact reasons for this are unknown, but various drugs for improving bone mineral density or preventing hip fracture might have influenced the results. A decrease in the differences in nutrient intake levels might explain some of the change in regional differences in Japan.

Growth of In x Ga1-x Sb alloy semiconductor at the International Space Station (ISS) and comparison with terrestrial experiments.

BACKGROUND: In x Ga1-x Sb is an important material that has tunable properties in the infrared (IR) region and is suitable for IR-device applications. Since the quality of crystals relies on growth conditions, the growth process of alloy semiconductors can be examined better under microgravity (µG) conditions where convection is suppressed. AIMS: To investigate the dissolution and growth process of In x Ga1-x Sb alloy semiconductors via a sandwiched structure of GaSb(seed)/InSb/GaSb(feed) under normal and µG conditions. METHODS: In x Ga1-x Sb crystals were grown at the International Space Station (ISS) under µG conditions, and a similar experiment was conducted under terrestrial conditions (1G) using the vertical gradient freezing (VGF) method. The grown crystals were cut along the growth direction and its growth properties were studied. The indium composition and growth rate of grown crystals were calculated. RESULTS: The shape of the growth interface was nearly flat under µG, whereas under 1G, it was highly concave with the initial seed interface being nearly flat and having facets at the peripheries. The quality of the µG crystals was better than that of the 1G samples, as the etch pit density was low in the µG sample. The growth rate was higher under µG compared with 1G. Moreover, the growth started at the peripheries under 1G, whereas it started throughout the seed interface under µG. CONCLUSIONS: Kinetics played a dominant role under 1G. The suppressed convection under µG affected the dissolution and growth process of the In x Ga1-x Sb alloy semiconductor.

Lack of BDNF expression through promoter IV disturbs expression of monoamine genes in the frontal cortex and hippocampus.

Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of psychiatric conditions including major depression and schizophrenia. Mice lacking activity-driven BDNF expression through promoter IV (knock-in promoter IV: KIV) exhibit depression-like behavior, inflexible learning, and impaired response inhibition. Monoamine systems (serotonin, dopamine, and noradrenaline) are suggested to be involved in depression and schizophrenia since many of the current antidepressants and antipsychotics increase the brain levels of monoamines and/or act on monoamine receptors. To elucidate the impact of activity-driven BDNF on the monoamine systems, we examined mRNA levels for 30 monoamine-related genes, including receptors, transporters, and synthesizing enzymes, in KIV and control wild-type mice by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). mRNA levels were measured in the frontal cortex and hippocampus, which are regions related to depression and schizophrenia and where promoter IV is active. The frontal cortex of KIV mice showed reduced levels of mRNA expression for serotonin receptors 1b, 2a, and 5b (5HTR1b, 5HTR2a, 5HTR5b), dopamine D2 receptors (DRD2), and adrenergic receptors alpha 1a and 1d (AdRα1a and AdRα1b), but increased levels for serotonin synthesizing enzyme, tryptophan hydroxylase (TPH), and dopamine D4 receptor (DRD4) when compared to control wild-type mice. The hippocampus of KIV mice showed decreased levels of 5HTR5b. Our results provide causal evidence that lack of promoter IV-driven BDNF disturbs expression of monoaminergic genes in the frontal cortex and hippocampus. These disturbed expression changes in the monoamine systems may mediate the depression- and schizophrenia-like behavior of KIV mice. Our results also suggest that antidepressant and antipsychotic treatments may actually interfere with and normalize the disturbed monoamine systems caused by reduced activity-dependent BDNF, while the treatment responses to these drugs may differ in the subject with reduced BDNF levels caused by stress and lack of neuronal activity.

Eleostearic acid induces RIP1-mediated atypical apoptosis in a kinase-independent manner via ERK phosphorylation, ROS generation and mitochondrial dysfunction.

RIP1 is a serine/threonine kinase, which is involved in apoptosis and necroptosis. In apoptosis, caspase-8 and FADD have an important role. On the other hand, RIP3 is a key molecule in necroptosis. Recently, we reported that eleostearic acid (ESA) elicits caspase-3- and PARP-1-independent cell death, although ESA-treated cells mediate typical apoptotic morphology such as chromatin condensation, plasma membrane blebbing and apoptotic body formation. The activation of caspases, Bax and PARP-1, the cleavage of AIF and the phosphorylation of histone H2AX, all of which are characteristics of typical apoptosis, do not occur in ESA-treated cells. However, the underlying mechanism remains unclear. To clarify the signaling pathways in ESA-mediated apoptosis, we investigated the functions of RIP1, MEK, ERK, as well as AIF. Using an extensive study based on molecular biology, we identified the alternative role of RIP1 in ESA-mediated apoptosis. ESA mediates RIP1-dependent apoptosis in a kinase independent manner. ESA activates serine/threonine phosphatases such as calcineurin, which induces RIP1 dephosphorylation, thereby ERK pathway is activated. Consequently, localization of AIF and ERK in the nucleus, ROS generation and ATP reduction in mitochondria are induced to disrupt mitochondrial cristae, which leads to cell death. Necrostatin (Nec)-1 blocked MEK/ERK phosphorylation and ESA-mediated apoptosis. Nec-1 inactive form (Nec1i) also impaired ESA-mediated apoptosis. Nec1 blocked the interaction of MEK with ERK upon ESA stimulation. Together, these findings provide a new finding that ERK and kinase-independent RIP1 proteins are implicated in atypical ESA-mediated apoptosis.

Effect of high-sensitivity C-reactive protein on the development of diabetes as demonstrated by pooled logistic-regression analysis of annual health-screening information from male Japanese workers.

AIM: The aim of this study was to determine the relationship between the development of diabetes mellitus and high-sensitivity C-reactive protein (HsCRP) adjusted for various potential confounders. METHODS: This 5-year prospective cohort study was conducted at a Japanese steel factory and involved male workers who had received annual health screenings between 2005 and 2010. The 7392 male participants were aged 19-75 years. The study endpoint, the development of diabetes mellitus, was defined as HbA(1c) greater or equal to 6.5% or the use of antidiabetic medication. The association between variables was investigated using pooled logistic regression adjusted for various covariates such as age, baseline body mass index (BMI) and increase in BMI from baseline, blood biochemistry, job schedule and job-related stress. RESULTS: The incidence rate of diabetes development per 1000 person-years was 13.9. Multivariate analysis showed a significant relationship between the development of diabetes and elevated levels of baseline HsCRP and increases in levels from baseline. The Odds ratios for a 2.9-fold (±1 geometric standard deviation) increase in baseline HsCRP and increase in HsCRP level from baseline were 1.18 [95% confidence interval (CI): 1.03-1.34; P=0.018] and 1.21 (95% CI: 1.03-1.41; P=0.018), respectively. CONCLUSION: The present study has indicated that HsCRP is an independent predictor for the development of diabetes in men, together with various confounders such as BMI, type of job schedule and job-related stress.

BDNF may play a differential role in the protective effect of the mGluR2/3 agonist LY379268 on striatal projection neurons in R6/2 Huntington's disease mice.

We have found that daily subcutaneous injection with a maximum tolerated dose (MTD) of the mGluR2/3 agonist LY379268 (20mg/kg) beginning at 4 weeks dramatically improves the phenotype in R6/2 mice. For example, we observed normalization of motor function in distance traveled, speed, the infrequency of pauses, and the ability to locomote in a straight line, and a rescue of a 15-20% striatal neuron loss at 10 weeks. As acute LY379268 treatment is known to increase cortical BDNF production, and BDNF is known to be beneficial for striatal neurons, we investigated if the benefit of daily LY379268 in R6/2 mice for striatal projection neurons was associated with increases in corticostriatal BDNF, with assessments done at 10 weeks of age after daily MTD treatment since the fourth week of life. We found that LY379268 increased BDNF expression in layer 5 neurons in motor cortex, which project to striatum, partly rescued a preferential loss of enkephalinergic striatal neurons, and enhanced substance P (SP) expression by SP striatal projection neurons. The enhanced survival of enkephalinergic striatal neurons was correlated with the cortical BDNF increase, but the enhanced SP expression by SP striatal neurons was not. Thus, LY379268 may protect the two main striatal projection neuron types by different mechanisms, enkephalinergic neurons by the trophic benefit of BDNF, and SP neurons by a mechanism not involving BDNF. The SP neuron benefit may perhaps instead involve the anti-excitotoxic action of mGluR2/3 receptor agonists.

The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization.

PURPOSE: 5-chloro-2,4-dihydroxypyridine (gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization. MATERIALS AND METHODS: Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end-joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability. RESULTS: Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42°C or more. The degree of heat sensitization with gimeracil increased as the temperature increased, and the combination of gimeracil and heat-sensitized radiation was more effective than each modality alone. CONCLUSION: Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone.

Understanding Darjeeling tea flavour on a molecular basis.

Darjeeling teas are the highest grown teas in the world and preferred for its flavour, aroma and quality. Apart from the genetic makeup of the plant, earlier reports suggest that insect infestation, particularly jassids and thrips triggers the aroma and flavour formation in Darjeeling tea. The present work encompasses the identification of the genes/transcriptomes responsible for the typical flavour of Darjeeling tea, besides understanding the role of jassids and thrips in particular, in producing the best cup character and quality. The quantitative real time PCR analysis was based on a suppression subtractive hybridisation forward library of B157 (tea clone infested with thrips), providing us transcripts related to aroma and flavour formation. We observed the expression of genes like leucine zipper, ntd, nced, geraniol synthase, raffinose synthase, trehalose synthase, amylase, farnesyl transferase, catalase, methyl transferase, linalool synthase, peroxidases, elicitor responsive proteins, linamarase, nerolidol linalool synthase 2, 12-oxophytodienoate reductase, glucosidase, MYB transcription factor, and alcohol dehydrogenase, highly regulated due to insect infestation, manufacturing stresses and mechanical injury. The first report on gene expression dynamics in thrips infested Darjeeling tea leaves can be extrapolated with increase in volatiles which is responsible for enhancing the quality of Darjeeling tea, specially the flavour and aroma of the infusion. We hope to model these responses in order to understand the molecular changes that occur during Darjeeling tea flavour formation.