An improved neutron autoradiography set-up for 10B concentration measurements in biological samples

Aim

Boron Neutron Capture Therapy (BNCT) is a binary hadrontherapy which exploits the neutron capture reaction in boron, together with a selective uptake of boronated substances by the neoplastic tissue. There is increasing evidence that future improvements in clinical BNCT will be triggered by the discovery of new boronated compounds, with higher selectivity for the tumor with respect to clinically used sodium borocaptate (BSH) and boronophenylalanine (BPA).

Background

Therefore, a ¹⁰B quantification technique for biological samples is needed in order to evaluate the performance of new boronated formulations.

Materials and methods

This article describes an improved neutron autoradiography set-up employing radiation sensitive films where the latent tracks are made visible by proper etching conditions.

Results

Calibration curves for both liquid and tissue samples were obtained.

Conclusions

The obtained calibration curves were adopted to set-up a mechanism to point out boron concentration in the whole sample.     

Effect of exposure to atmospheric pollution on microbial activity in soil

Summary Surface samples of a brown earth soil, showing signs of podzolization were transferred from an unpolluted woodland site and exposed to heavy atmospheric pollution for a period of one year. Although exposure resulted in a decrease in soil pH from 4.2 to 3.7, no significant changes in microbial numbers; nitrification rate; respiration rate; solubilization of insoluble phosphate; or the activity of a range of soil enzymes occurred. The rate of ammonification was, however, higher in the exposed than the control soil.Microbial activity in the unpolluted soil was not, therefore, substantially impaired by exposure to heavy atmospheric pollution, despite the fact that the pH of the soil was reduced.     

15N natural abundance in plants of the Amazon River floodplain and potential atmospheric N2 fixation

Summary The¹⁵N natural abundance values of various Amazon floodplain (várzea) plants was investigated. Samples of young leaf tissues were collected during three different periods of the river hydrography (low water, mid rising water and high water) and during one period in the Madeira River (high water). A large variation of¹⁵N abundance was observed, both among the different plant types and between the different flood stages. This variation probably, reflected, in part, the highly variable nature of the floodplain, sometimes dry and oxygenated and at other times inundated and anaerobic and, in part, changes in plant nitrogen metabolism. Comparison of the nitrogen isotopic composition of leguminous plants with that of non-leguminous plants showed that, on average, the¹⁵N abundance was lower in the legumes than non-legumes, suggesting active N-fixation. Also, the¹⁵N natural abundance in aquatic grasses of the generaPaspalum, was in general, lower than the¹⁵N abundance of aquatic grasses of the generaEchinochloa. As both of these grasses grow in the same general habitat, it appears thatPaspalum grasses may also be nitrogen fixers.     

Correlation between the atmospheric conditions and the asthmatic symptom

A point process model is suitable for analysis of a sequence of binary variables, each of which may be dependent on the preceeding one. This model was used for analysis of the correlation between the state of the atmosphere and the presence or absence of asthmatic symptom known from diaries in which a day was divided into four parts. The diaries were kept during summer and autumn of a year by 19 adult and 12 child patients in Sapporo (43°03 N, 141°20 E), 39 adult and 20 child patients in Tokyo (35°41 N, 139°46 E), and 26 adult and 18 child patients in Naha (26°14 N, 127°41 E).Low temperature and decrease in temperature significantly related to the asthmatic symptom during the seasons. No reversions on correlations as to temperature were observed among places, between the adult and the child, and before and after taking in effects of the preceding symptom and/or the circadian rhythm. Some correlations relating to humidity or to barometric pressure, on the other hand, reversed from place to place, from the adult to the child, and from before to after taking in the effects.Availability of this model for further study on the correlation between the air with contents and the asthmatic symptom is shortly discussed.     

大气CO2浓度升高对农田土壤微生物及其相关因素的影响

综述了大气CO2浓度升高条件下,农田土壤微生物区系、土壤呼吸、土壤微生物生物量;植物-微生物共生体--内生菌根、根瘤及其与农田土壤微生物活动相关因素发生的变化。该方面的研究虽然受实验条件限制,在国内外开展研究的持续时间较短,但现有的研究表明,大气CO2浓度升高主要通过影响植物生长而间接影响农田土壤微生物活性。     

Elevated invasive potential of glioblastoma stem cells

Glioblastomas (GBMs) are the most lethal and common types of primary brain tumors. The hallmark of GBMs is their highly infiltrative nature. The cellular and molecular mechanisms underlying the aggressive cancer invasion in GBMs are poorly understood. GBM displays remarkable cellular heterogeneity and hierarchy containing self-renewing glioblastoma stem cells (GSCs). Whether GSCs are more invasive than non-stem tumor cells and contribute to the invasive phenotype in GBMs has not been determined. Here we provide experimental evidence supporting that GSCs derived from GBM surgical specimens or xenografts display greater invasive potential in vitro and in vivo than matched non-stem tumor cells. Furthermore, we identified several invasion-associated proteins that were differentially expressed in GSCs relative to non-stem tumor cells. One of such proteins is L1CAM, a cell surface molecule shown to be critical to maintain GSC tumorigenic potential in our previous study. Immunohistochemical staining showed that L1CAM is highly expressed in a population of cancer cells in the invasive fronts of primary GBMs. Collectively, these data demonstrate the invasive nature of GSCs, suggesting that disrupting GSCs through a specific target such as L1CAM may reduce GBM cancer invasion and tumor recurrence.     

Therapeutic potential of hepatocyte transplantation

Liver repopulation with transplanted cells offers unique opportunities for treating a variety of diseases and for studies of fundamental mechanisms in cell biology. Our understanding of the basis of liver repopulation has come from studies of transplanted cells in animal models. A variety of studies established that transplanted hepatocytes as well as stem/progenitor cells survive, engraft, and function in the liver. Transplanted cells survive life-long, although cells do not proliferate in the normal liver. On the other hand, the liver is repopulated extensively when diseases or other injuries afflict native hepatocytes but spare transplanted cells. The identification of ways to repopulate the liver with transplanted cells has greatly reinvigorated the field of liver cell therapy. The confluence of insights in stem/progenitor cells, transplantation immunology, cryobiology, and liver repopulation in specific models of human diseases indicates that the field of liver cell therapy will begin to reap the promised fruit in the near future.     

Therapeutic potential of melatonin ligands

Melatonin is a neurohormone that is believed to be involved in a wide range of physiological functions. In humans, appropriate clinical trials confirm the efficacy of melatonin or melatoninergic agonists for the MT1 and MT2 receptor subtypes in circadian rhythm sleep disorders only. Nevertheless, preclinical animal model studies relevant to human pathologies involving validated reference compounds lead to other therapeutic possibilities. Among these is a recently developed treatment concept for depression, which has been validated by the clinical efficacy of agomelatine, an agent having both MT1 and MT2 agonist and 5-HT2C antagonist activity. A third melatonin binding site has been purified and characterized as the enzyme quinone reductase 2 (QR2). The physiological role of this enzyme is not yet known. Recent results obtained by different groups suggest: (1) that inhibition of QR2 may lead to "protective" effects and (2) that over-expression of this enzyme may have deleterious effects. The inhibitory effect of melatonin on QR2 observed in vitro may explain the protective effects reported for melatonin in different animal models, such as cardiac or renal ischemia-effects that have been attributed to the controversial antioxidant properties of the hormone. The development of specific ligands for each of these melatonin binding sites is necessary to link physiological and/or therapeutic effects.     

Therapeutic potential of human elafin

Elafin is an endogenous human protein composed of an N-terminal transglutaminase substrate motif and a C-terminal WAP (whey acidic protein)-domain with antiproteolytic properties. Elafin is expressed predominantly in epithelial tissue and potently inhibits the neutrophil-derived serine proteases elastase and proteinase-3 by a competitive tight-binding mechanism. Furthermore, it inhibits EVE (endogenous vascular elastase). Studies on several animal models show that antiprotease augmentation with human elafin is an effective strategy in the treatment of inflammatory vascular, systemic and pulmonary diseases and of inflammation triggered by reperfusion injury. This raises the possibility that elafin might be effective in the treatment of a variety of human inflammatory diseases. In a Phase I clinical trial, elafin was well tolerated. Phase II trials are underway to investigate the therapeutic effects of elafin on post-operative inflammation and the clinical consequences of major surgery. Of particular interest is the reduction of post-operative morbidity after oesophagus cancer surgery, coronary artery bypass surgery and kidney transplantation.     

Responses of Sphagnum species to atmospheric nitrogen and sulphur deposition

The responses of Sphagnum species to atmospheric pollution by sulphur and nitrogen oxides are reviewed. An explanation of the tolerance of sulphur dioxide in Sphagnum cuspidatum is provided. This involves an exclusion mechanism by the oxidation of bisulphite ions to less toxic sulphate ions catalysed by the presence of iron and possibly other metals on the cell wall cation-exchange sites. Tolerance is influenced by changing the iron content of the plants. A similar mechanism may account for sulphur dioxide tolerance in Sphagnum recurvum.
Evidence for a close coupling of nitrate assimilation with the atmospheric nitrogen supply in ombrotrophic Sphagnum species in unpolluted regions is reviewed, and this coupling is shown to be lost in polluted environments with high atmospheric nitrogen supply. The potential effects of a supra-optimal atmospheric nitrogen supply to Sphagnum species on the ecology of mires is discussed.
The effects of nitrogen and sulphur pollutants on Sphagnum species are used to make broad generalizations as to how other bryophyte species might respond to these pollutants and to explain known effects of atmospheric pollution on bryophyte communities.     

Impact of temperature and atmospheric pressure on the incidence of major acute cardiovascular events

Background

The impact of meteorological conditions on the occurrence of various cardiovascular events has been reported internationally. Data about the Dutch situation are limited.

Objectives

We sought to find out a correlation between weather conditions and the incidence of major acute cardiovascular events such as type A acute aortic dissection (AAD), acute myocardial infarction (AMI) and acutely presented abdominal aortic aneurysms (AAAA).

Methods

Between January 1998 and February 2010, patients who were admitted to our hospital (Catharina Hospital, Eindhoven, the Netherlands) because of AAD (n = 212), AMI (n = 11389) or AAAA (n = 1594) were registered. These data were correlated with the meteorological data provided by the Royal Dutch Meteorological Institute (KNMI) over the same period.

Results

During the study period, a total number of 11,412 patients were admitted with AMI, 212 patients with AAD and 1593 patients with AAAA. A significant correlation was found between the daily temperature and the number of hospital admissions for AAD. The lower the daily temperature, the higher the incidence of AAD (p = 0.002). Lower temperature was also a predictor of a higher incidence of AMI (p = 0.02). No significant correlation was found between daily temperature and onset of AAAA.

Conclusions

Cold weather is correlated with a higher incidence of AAD and AMI.     

Leveraging Metabolomics to Assess the Next Generation of Temozolomide-based Therapeutic Approaches for Glioblastomas

Glioblastoma multiforme (GBM) is the most common adult primary tumor of the central nervous system. The current standard of care for glioblastoma patients involves a combination of surgery, radiotherapy and chemotherapy with the alkylating agent temozolomide. Several mechanisms underlying the inherent and acquired temozolomide resistance have been identified and contribute to treatment failure. Early identification of temozolomide-resistant GBM patients and improvement of the therapeutic strategies available to treat this malignancy are of uttermost importance. This review initially looks at the molecular pathways underlying GBM formation and development with a particular emphasis placed on recent therapeutic advances made in the field. Our focus will next be directed toward the molecular mechanisms modulating temozolomide resistance in GBM patients and the strategies envisioned to circumvent this resistance. Finally, we highlight the diagnostic and prognostic value of metabolomics in cancers and assess its potential usefulness in improving the current standard of care for GBM patients.     

大气CO2浓度和温度升高对作物生理生态的影响

论述了大气CO2浓度和温度升高下的植物生长,光合作用,产量以及水分养分利用效率等方面的研究进展,未来高CO2浓度下,光合作用速率有不同程度的提高,生物量和产量增加;气孔导度降低,水分利用效率（WUE）提高,一般地上部分和根系尤其是细根生物量增加,凋落物量随之增加,C/N比率提高,植物残体的腐解速率降低,CO2浓度升高后,会给根际微生物带来更多的底物,从而提高了微生物活性,加速养分的矿化过程,改善植物的养分状况。     

Therapeutic potential of circulating endothelial cells

The discovery of circulating endothelial progenitors (EPCs) in human blood has completely modified the concept of post natal angiogenesis. Many studies have further confirmed the existence of EPCs, their medullar origin and capacity to be integrated in vascular structures at the sites of neoangiogenesis. They suggest that EPCs could be naturally involved in the prevention of ischemia by participating directly to the formation of collateral vessels. These cells have a high tropism for the sites of angiogenesis. They may thus be used as a powerful tool to prevent or treat ischemic diseases and constitute an alternative to the risky local injection of pro-angiogenic growth factors. The efficiency of bone marrow cells autologous transplantation was recently proved by the first clinical trials. Bone marrow mononuclear cells locally injected to patients with limb or cardiac ischemia have been shown to improve reperfusion in ischemic tissues. These trials are still preliminary: they were performed with heterogeneous cells only on few patients and were not randomized. However they raise important questions, essentially on the necessity of cell purification prior to injection and on the nature of the bone marrow cells which are really involved in ischemic tissue regeneration. Further investigations are then required to improve the cell therapy outcome by 1) using more defined cell population, 2) clearly demonstrating the long term improvement of vascular function and 3) performing extensive analysis of the possible side effects.     

Therapeutic potential of monoacylglycerol lipase inhibitors

Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown beneficial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects that discourage their chronic usage, including cognitive deficits and gastrointestinal toxicity, respectively. Recent studies have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the endocannabinoid and eicosanoid systems together through hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific tissues. Studies in recent years have shown that MAGL inhibitors elicit anti-nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated withdrawal symptoms in addiction paradigms through enhancing endocannabinoid signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action in the brain and protect against neurodegeneration through lowering eicosanoid production. In cancer, MAGL inhibitors have been shown to have anti-cancer properties not only through modulating the endocannabinoid–eicosanoid network, but also by controlling fatty acid release for the synthesis of protumorigenic signaling lipids. Thus, MAGL serves as a critical node in simultaneously coordinating multiple lipid signaling pathways in both physiological and disease contexts. This review will discuss the diverse (patho)physiological roles of MAGL and the therapeutic potential of MAGL inhibitors in treating a vast array of complex human diseases.     

陆生植物气孔参数与大气CO_2浓度变化

陆生植物的起源与演化与全球气候和环境的变化密不可分,利用植物气孔参数(气孔密度和气孔指数)来指示或重建古大气CO2浓度变化是近年来全球变化研究的热点之一。就陆生植物气孔参数的研究进行了概述,对研究中存在的问题及其前景作了简要探讨,并对植物生物学方法在定量研究古气候和古环境变化的趋势进行了分析。