No change in dopamine D1 receptor in vivo binding in rats after sub-chronic haloperidol treatment

A frequent side effect in the long-term treatment of schizophrenia with the dopamine D2 antagonist haloperidol (HAL) is the appearance of tardive dyskinesia or, in animals, of repetitive involuntary vacuous chewing movements (VCMs). In rats, chronic HAL-induced or D1 receptor-stimulated VCMs are suppressed by D1 antagonists, suggesting that this behavioral supersensitivity is mediated by D1 receptors. The goal of this study was to investigate in vivo the possible relationship between D1 receptor binding and D1-mediated behavioral supersensitivity, after subchronic HAL treatments. D1 agonist R-SKF 82957 and antagonist SCH 23390, both labeled with carbon-11, were used to assess in vivo D1 receptor binding. Rats were treated with HAL (1.5 mg/kg, i.p.) or vehicle for 21 days, followed by a 4 day washout period. No significant difference was found in the regional brain binding of either radioligand. D1 receptor-mediated behaviors including VCMs, grooming, and rearing were measured in control or HAL-treated rats. VCMs were significantly increased in HAL-treated rats, suggesting D1 receptor stimulation and possibly receptor supersensitivity. This study failed to link the purported D1 receptor-mediated behaviors with in vivo receptor binding measures of R-[11C]SKF 82957 or [11C]SCH 23390 in rat brain regions.     

Water demand and stress from oil palm-based biodiesel production in Thailand

Purpose

The use and production of biofuels have been strongly promoted in Thailand. In order to achieve a 25 % renewable energy target in 2021, feedstock expansion is needed to satisfy the increased demand for biofuel production putting more pressure on freshwater resources. This is an important implication of biofuel production which has not yet been taken into consideration. Thus, this study intends to address the impact from freshwater use due to the biodiesel target based on life cycle assessment approach as well as to evaluate suitable areas for expansion of oil palm.

Methods

The amount of water for growing oil palm throughout its lifespan is estimated based on theoretical crop water requirement, while water demand for producing biodiesel is referred to from literature. Then, the potential impact on freshwater resources is assessed in terms of water deprivation using the water stress index of Thailand. The Alternative Energy Development Plan for 2012–2021 and areas recommended by the Ministry of Agriculture and Cooperatives are referred in this study. Additionally, two scenarios for increasing new plantation in suitable areas are proposed as expansion in a single region or spread over the three regions.

Results and discussion

The highest water requirement for oil palm-based biodiesel production is found in the central region followed by the eastern and southern (4–9, 5–16, and 4–19 m³ L^?1 biodiesel, respectively). This is because oil palm plantations in the central region are not yet fully mature. As a result, the ratio of crop water requirement associated to crop productivity will be reduced while the water productivity will be increased yearly in yield. Also, more than 99 % of the total water is required during the cultivation period. To achieve the 2021 biodiesel target with a concern towards the impact from freshwater use by means of low water deprivation, cultivating oil palm is recommended entirely in the eastern and the southern parts without expansion to the central region.

Conclusions

The impact on freshwater resources is an important implication of biofuel production as most of the water requirement of palm oil biodiesel was for oil palm cultivation. Accounting the water deprivation as one of the criteria on impact from freshwater use will provide useful support for selecting areas having less potential for inducing water stress in a watershed leads to people in these areas being less vulnerable to water stress.

     

The eIF4E RNA regulon promotes the Akt signaling pathway

Eukaryotic initiation factor 4E (eIF4E) promotes cellular proliferation and can rescue cells from apoptotic stimuli such as serum starvation. However, the mechanisms underlying apoptotic rescue are not well understood. In this study, we demonstrate that eIF4E overexpression leads to enhanced survival signaling through Akt and that eIF4E requires Akt1 to rescue serum-deprived fibroblasts. Furthermore, a mutant form of eIF4E (W73A), which is messenger RNA (mRNA) export competent but does not promote translation, rescues cells as readily as wild-type eIF4E. We show that eIF4E mediates Akt activation via up-regulation of Nijmegen breakage syndrome 1 (NBS1), a phosphoinositide-3 kinase-Akt pathway upstream activator. Additionally, eIF4E coordinately up-regulates the expression of downstream effectors of the Akt pathway, thereby amplifying Akt signaling effects. A negative regulator of eIF4E, the promyelocytic leukemia protein (PML), suppresses Akt activation and apoptotic rescue. These PML activities likely arise, at least in part, through its inhibition of eIF4E-mediated NBS1 mRNA export. In summary, eIF4E coordinately regulates gene expression to potentiate Akt activation, an activity required for apoptotic rescue.     

Search for alpha-glucosidase inhibitors: new N-substituted valienamine and conduramine F-1 derivatives

A solid-phase synthesis of new N-substituted valienamines has been developed and new synthesis of (+/-)-conduramine F-1, (-)-conduramine F-1, and (+)-ent-conduramine F-1 is presented, together with the preparation of N-benzylated conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1 improves their inhibitory activity toward alpha-glucosidases significantly. The additional hydroxymethyl group makes valienamine derivatives more active than their (+)-ent-conduramine F-1 analogues.