Synthesis and properties of Asante Calcium Red—A novel family of long excitation wavelength calcium indicators

Although many synthetic calcium indicators are available, a search for compounds with improved characteristics continues. Here, we describe the synthesis and properties of Asante Calcium Red-1 (ACR-1) and its low affinity derivative (ACR-1-LA) created by linking BAPTA to seminaphthofluorescein. The indicators combine a visible light (450–540 nm) excitation with deep-red fluorescence (640 nm). Upon Ca²⁺ binding, the indicators raise their fluorescence with longer excitation wavelengths producing higher responses. Although the changes occur without any spectral shifts, it is possible to ratio Ca²⁺-dependent (640 nm) and quasi-independent (530 nm) emission when using visible (<490 nm) or multiphoton (∼780 nm) excitation. Therefore, both probes can be used as single wavelength or, less dynamic, ratiometric indicators. Long indicator emission might allow easy [Ca²⁺]_i measurement in GFP expressing cells. The indicators bind Ca²⁺ with either high (K_d = 0.49 ± 0.07 μM; ACR-1) or low affinity (K_d = 6.65 ± 0.13 μM; ACR-1-LA). Chelating Zn²⁺ (K_d = 0.38 ± 0.02 nM) or Mg²⁺ (K_d ∼ 5 mM) slightly raises and binding Co²⁺ quenches dye fluorescence. New indicators are somewhat pH-sensitive (pK_a = 6.31 ± 0.07), but fairly resistant to bleaching. The probes are rather dim, which combined with low AM ester loading efficiency, might complicate in situ imaging. Despite potential drawbacks, ACR-1 and ACR-1-LA are promising new calcium indicators.     

Consequences of the Ban of By-Products from Terrestrial Animals in Livestock Feeding in Germany and The European Union: Alternatives,Nutrient and Energy Cycles,Plant Production,and Economic Aspects

Consequences of the ban of meat and bone meal (MBM) and animal fat with regard to livestock feeding, cropping, ecology and economy where investigated with an inter-disciplinary approach for Germany and the European Union. Calculations were made for different production systems with pigs and poultry on the basis of statistical data for the production and for the feed markets as well as from requirement data for the respective species and production system. (1.) The ban of MBM from feeding caused a need for alternative protein sources. If all the amount of protein from MBM is to be replaced by soybean meal, in Germany and the EU about 0.30 and 2.30 · 10⁶t would be needed each year (supplementary amino acids not considered). Alternatively, doubling the grain legume acreage in Germany to about 420,000ha would supply a similar amount of protein. A wider application of phase feeding with adjusted dietary amino acid concentrations, however, would allow for saving protein to an extent which is similar to the amount of protein that was contributed by MBM in recent years. Thus, the ban is a minor problem in terms of ensuring amino acid supply. (2.) However, alternative plant ingredients cannot compensate for the gap in P supply that is caused by the ban. An additional demand for inorganic feed phosphates of about 14,000 and 110,000t per year is given in Germany and the EU, respectively. So far, this gap is filled almost completely by increased mining of rock phosphates. Alternatively, a general application of microbial phytase to all diets would largely fill this gap. Until the ban, MBM contributed to 57% of the supplementation of P that was needed for pigs and poultry. The ban of MBM makes large amounts of P irreversibly disappearing from the food chain. (3.) Energy from slaughter offal and cadavers can be utilized in different technologies, in the course of which the efficiency of energy utilisation depends on the technology applied. It is efficient in the cement work or rotation furnace if heat is the main energy required. In contrast, the energetic efficiency of fermentation is low. (4.) Incineration or co-incineration of MBM and other by-products causes pollution gas emissions amounting to about 1.4kg CO₂ and 0.2kg NO_x per kg. The CO₂ production as such is hardly disadvantageous, because heat and electrical energy can be generated by the combustion process. The prevention of dangerous gaseous emissions from MBM burning is current standard in the incineration plants in Germany and does not affect the environment inadmissibly. (5.) The effects of the MBM ban on the price for compound feed is not very significant. Obviously, substitution possibilities between different feed ingredients helped to exchange MBM without large price distortions. However, with each kg MBM not used in pig and poultry feeding economic losses of about 0.14¢ have to considered. In conclusion, the by far highest proportion of raw materials for MBM comes as by-products from the slaughter process. Coming this way, and assuring that further treatment is safe from the hygienic point of view, MBM and animal fat can be regarded as valuable sources of amino acids, minerals and energy in feeding pigs and poultry. Using them as feedstuffs could considerably contribute to the goal of keeping limited nutrients, phosphorus in particular, within the nutrient cycle and dealing responsible with limited resources.     

Design,Synthesis, Lipophilic Properties,and Binding Affinities of Potential Ligands in Positron Emission Tomography (PET) for Visualization of Brain Dopamine D4 Receptors

We report the synthesis of compounds structurally related to the high‐affinity dopamine D₄ receptor ligand N‐{2‐[4‐(3‐cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐methoxybenzamide ( 1e ). All compounds were specifically designed as potential PET radioligands for brain D₄ receptor visualization, having lipophilicity within a range for brain uptake and weak non‐specific binding (0.75<cLogP<3.15) and bearing a substituent for easy access to labeling with the positron emitter isotope ¹¹C or ¹⁸F. The best compound of the series, N‐{2‐[4‐(4‐chlorophenyl)piperazin‐1‐yl]ethyl}‐6‐fluoropyridine‐3‐carboxamide ( 7a ), displayed excellent selectivity over D₂ and D₃ receptors (>100‐fold), but its D₄ receptor affinity was suboptimal for imaging of brain D₄ receptors (K_i=30 nM ).     

Observed and projected impacts of climate on radial growth of three endangered conifers in northern Mexico indicate high vulnerability of drought-sensitive species from mesic habitats

A decline in productivity and radial growth in conifer forests from mesic areas has been associated with increased drought stress induced by climate warming. Nevertheless, studies showing how vulnerable tree species will be in response to forecasted warming conditions are scarce in such mesic habitats. Here we address this issue by analyzing how growth responds to drought and to observed and projected climate conditions in a conifer forest from northern Mexico, which is a hotspot of conifer diversity. We quantify the trends in radial growth (quantified as basal area increment, BAI) of three species (Abies durangensis, Picea chihuahuana, Cupressus lusitanica) using dendrochronology and a process-based model of tree growth. Growth decreased in A. durangensis and P. chihuahuana from the late 1980s onwards in response to warmer and drier conditions, whereas C. lusitanica growth showed very low sensitivity to precipitation and increased as temperature did. Winter-spring dry conditions adversely affected the growth of A. durangensis and P. chihuahuana. Our modeling approach anticipates growth reductions and an increase in the vulnerability of A. durangensis and the endangered P. chihuahuana against the warmer and more arid conditions predicted after the 2050s. Future warmer and drier climatic conditions could reduce the productivity and lead to growth decline of these mesic conifer forests triggering dieback episodes in highly drought-sensitive species as A. durangensis and P. chihuahuana.     

川中丘陵区冬灌田甲烷和氧化亚氮排放研究

采用静态暗箱/气相色谱法对川中丘陵区冬灌田CH₄和N₂O排放特征进行连续一年的田间原位测定.结果表明,种植水稻区(种植区)在水稻生长季平均CH₄排放速率为22.76±2.76 mg·m^-2·h^-1,休闲期平均为1.43±0.20 mg·m^-2·h^-1,全年平均为9.64±1.17 mg·m^-2·h^-1;全年CH₄排放主要集中在水稻生长季,其累计CH₄排放量占全年总CH₄排放量的91.2%未种植水稻区(对照区) 全年CH₄平均排放速率为2.03±0.18 mg·m^-2·h^-1,水稻生长季CH₄排放量占全年总排放量的86.2%.N₂O的排放在稻田落干时呈现脉冲排放.在水稻生长季,对照区CH₄和N₂O的季节排放速率分别为4.53±0.38mg·m^-2·h^-1和32.01±5.02 μg·m^-2·h^-1,而种植区则分别为22.76±2.76 mg·m^-2·h^-1和73.04±5.03 μg·m^-2·h^-1,植株参与导致CH₄和N₂O排放速率分别增加302%和128%.CH₄和N₂O的排放随土水分条件的变化呈互为消长关系.在冬灌田中,即使考虑500年的时间尺度,全年N₂O排放产生的全球增温潜势也只有CH₄的7.9%,与CH₄相比,冬灌田排放的N₂O所产生的温室效应很小.     

Correlation of structure and emission in solid state copper(I) complexes; [Cu4I4(CH3CN)2(L)2], L = aniline derivative

Four complexes of the type [Cu₄I₄(CH₃CN)₂(L)₂], L = aniline derivative: Cu₄I₄(CH₃CN)₂(2,6-dimethylaniline)₂ (I), triclinic, , a = 12.449(3), B = 14.108(6), C = 10.606(4) Å, = 73.46(3), β = 95.00(2), γ = 73.42(3)°, V = 1682.3(10) ų; Cu₄I₄(CH₃CN)₂(o-ethylaniline)₂ (II), triclinic,

Full-size image

, V = 1734.0(8) ų; Cu₄I₄(CH₃CN)₂(6-ethyl-o-toluidine)₂ (III), orthorhombic, Pnam, a = 14.976(6), b = 21.187(6), C = 12.545(2) Å, V = 3980.7(2) ų; Cu₄I₄(CH₃CN)₂(p-anisidine)₂ (IV), monoclinic, A2/a, A = 20.032(10), B = 7.863(1), C = 18.715(9) Å, β = 101.56(4)°, V = 2888.0(2) ų; were examined by single crystal X-ray diffraction. Complexes I and II have no internal symmetry elements, III has an internal mirror and IV has a two-fold axis. Ab initio calculations based on the atomic positional parameters of complexes containing the three types of symmetry elements reveal HOMO orbitals to be dominated by the p orbitals of the iodine atoms whereas the LUMO orbitals contain major contributions from copper based p orbitals.     

Overview of the biogenic sources of atmospheric trace compounds due to agricultural activities

All human activities profoundly affect the chemical composition and properties of the atmosphere. The present overview highlights the impact of agricultural practices, including livestock raising, on the biogeochemical cycles of carbon and nitrogen and discusses the relevant environmental issues. Emissions from agriculture significantly contribute to the atmospheric budget of methane and nitrous oxide, which in turn contribute to the greenhouse effect. Agricultural activities are also the predominant source of ammonia to the atmosphere, so affecting the acidity of atmospheric depositions. A minor role is expected from agriculture in the production of tropospheric ozone through nitrogen oxides and volatile organic compound emissions.     

Primary photophysical and photochemical processes in visual excitation

The color of visual pigments is experimentally shown to be controlled by excited state effects. These effects which define the primary absorption of light by rhodopsin are considered together with results obtained from emission and picosecond spectroscopy. In addition, the molecular changes induced in rhodopsin when a photon is absorbed are analyzed using resonance Raman spectroscopy. The molecular changes observed are compared in bacterial and photoreceptor rhodopsins. This comparison yields a unique explanation for the biological role of the cis-trans isomerization in visual transduction.Presented at the EMBO-Workshop on Transduction Mechanism of Photoreceptors, Jülich, Germany, October 4–8, 1976     

Magnetic resonance imaging detects white adipose tissue beiging in mice following PDE10A inhibitor treatment

Weight gain is a common harmful side effect of atypical antipsychotics used for schizophrenia treatment. Conversely, treatment with the novel phosphodiesterase-10A (PDE10A) inhibitor MK-8189 in clinical trials led to significant weight reduction, especially in patients with obesity. This study aimed to understand and describe the mechanism underlying this observation, which is essential to guide clinical decisions. We hypothesized that PDE10A inhibition causes beiging of white adipose tissue (WAT), leading to weight loss. Magnetic resonance imaging (MRI) methods were developed, validated, and applied in a diet-induced obesity mouse model treated with a PDE10A inhibitor THPP-6 or vehicle for measurement of fat content and vascularization of adipose tissue. Treated mice showed significantly lower fat fraction in white and brown adipose tissue, and increased perfusion and vascular density in WAT versus vehicle, confirming the hypothesis, and matching the effect of CL-316,243, a compound known to cause adipose tissue beiging. The in vivo findings were validated by qPCR revealing upregulation of Ucp1 and Pcg1-α genes, known markers of WAT beiging, and angiogenesis marker VegfA in the THPP-6 group. This work provides a detailed understanding of the mechanism of action of PDE10A inhibitor treatment on adipose tissue and body weight and will be valuable to guide both the use of MK-8189 in schizophrenia and the potential application of the target for weight loss indication.