The Subthalamic Microlesion Story in Parkinson's Disease: Electrode Insertion-Related Motor Improvement with Relative Cortico-Subcortical Hypoactivation in fMRI

Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson''s disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson''s Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9–15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.     

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag) OspC (rOspC) could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N'' or C'' terminal His-tag. This is the case in mice immunized: (a) with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b) with free rOspC and Montanide PET GEL A; (c) with free rOspC and alum; or (d) with adjuvant-free rOspC. Stronger responses are noted with all N''-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N'' and C'' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N'' to C'' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C'' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.     

Imaging of multi-color fluorescence emission from leaf tissues

Multi-color fluorescence emission from leaf tissues is presented as a powerful reporter on plant biochemistry and physiology that can be applied both at macro- and micro-scales. The blue–green fluorescence emission is typically excited by ultraviolet (UV) excitation. However, this approach cannot be applied in investigating intact leaf interior because the UV photons are largely absorbed in the epidermis of the leaf surface. This methodological barrier is eliminated by replacing the UV photon excitation by excitation with two infra-red photons of the same total energy. We demonstrate this approach by using two-photon excitation for microscopy of Arabidopsis thaliana leaves infected by pathogenic bacterium Pseudomonas syringae. The leaf structures are visualized by red chlorophyll fluorescence emission reconstructed in 3-D images while the bacteria are detected by the green emission of engineered fluorescence protein.     

Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL-induced apoptosis

Identification of mechanisms of modulation of the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis is important for its potential use in anticancer therapy. Ethanol can induce cell death in vitro and in vivo by different signalling pathways. Its effect in combination with death ligands is unknown. We investigated how ethanol modulates the effects of TRAIL in colon cancer cells. After combined TRAIL and ethanol treatment, a potentiation of caspase-8, -9, -3 activation, a proapoptotic Bid protein cleavage, a decrease of mitochondrial membrane potential, a complete poly(ADP)ribose polymerase cleavage, and disappearance of antiapoptotic Mcl-1 protein were demonstrated. Ethanol acts as a potent agent sensitizing colon cancer cells to TRAIL-induced apoptosis.     

Mahalanobis distance screening of Arabidopsis mutants with chlorophyll fluorescence

Rapid nondestructive screening of mutants is a common step in many research projects in plant biology. Here we report the development of a method that uses kinetic imaging of chlorophyll fluorescence to detect phenotypes that differ from wild-type plants. The method uses multiple fluorescence features simultaneously in order to catch different types of photosynthesis-related mutants with a single assay. The Mahalanobis distance was used to evaluate the degree of similarity in fluorescence features between the wild-type and test plants, and plants differing strongly from the wild-type were classified as mutants. The method was tested on a collection of photosynthesis-related mutants of Arabidopsis thaliana. The plants were evaluated from images in which the color of each pixel depended on the Mahalanobis distance of the fluorescence features. Two parameters of the color-coding procedure were used to adjust the trade-off between detection of true mutants and erratic classification of wild-type plants as mutants. We found that a large percentage of photosynthesis-related mutants can be detected with this method. Scripts for the free statistics software R are provided to facilitate the practical application of the method.     

Effect of selected dimethylaminochalcones on some mitochondrial activities

Chalcones and their synthetic cyclic analogues have been shown to possess a full scale of biological activities in a variety of experimental systems. They were assessed to be mostly effective in defense against free radicals in the organism, but several compounds exhibited cytotoxic pro-oxidant activities. The respiratory response and antioxidant status in mitochondria were investigated upon addition of 4′-dimethylaminochalcone (1a) and its cyclic analogues, (E)-2-(4′-((CH₃)₂?N)-benzylidene)-1-indanone (1b), -1-tetralone (1c), and -1-benzosuberone (1d). Selected structures were able to change the respiratory response of mitochondria and showed an ability to modify mitochondrial metabolic and redox efficiency, though they did not indicate redox reactivity towards glutathione in adduct-free incubations. The results of the study indicate that -chalcone and -tetralone derivatives cause suppression of reactive oxygen species affecting mitochondrial respiration by mild uncoupling. In addition, (E)-2-(4′-((CH₃)₂?N)-indanone (1b), and to a greater extent, -benzosuberone (1d), showed pro-oxidant effects, which partially explain their cytotoxicity.     

Laminar Alterations in γ-Aminobutyric AcidA, Muscarinic, and β Adrenoceptors and Neuron Degeneration in Cingulate Cortex in Alzheimer''s Disease

The laminar distribution of binding to a number of postsynaptic neurotransmitter receptors was assessed autoradiographically in postmortem samples of area 23a in posterior cingulate cortex from 13 Alzheimer and nine age-matched control cases. Specific binding in all Alzheimer cases was compared to that in control cases, and the following alterations were observed: reduced muscimol binding in most layers; no changes in pirenzepine binding; and elevated cyanopindolol binding in layers Ic, IIIc, and IV. The Alzheimer cases were classified further on the basis of neuronal degeneration: class 1, no neuron loss; class 2, greatest losses in layer II or III; class 3, greatest losses in layer IV; and class 4, greatest losses in layer V or VI. This classification uncovered further alterations in ligand binding patterns. First, muscimol binding was reduced in layers II and III only in class 2 cases and in layers V and VI only in class 4 cases. Second, pirenzepine binding was reduced in layers Ic, IIIa-b, and VI of class 1 cases and layers Va and VI of class 4 cases. In spite of neuron degeneration in classes 2 and 3, there was no change in pirenzepine binding in these classes. Third, elevated cyanopindolol binding occurred in classes 3 and 4, whereas classes 1 and 2 had normal levels of binding. These results suggest that cases of Alzheimer's disease express heterogeneities in neocortical pathology which are reflected in the laminar patterns of binding to postsynaptic receptors. Reductions in muscimol binding to the gamma-aminobutyric acidA receptor had the closest relationship with neuron degeneration, whereas pirenzepine binding appeared to reflect a compensation in muscarinic receptors for changes in neuron densities.     

Plant response to destruxins visualized by imaging of chlorophyll fluorescence

Kinetic fluorescence imaging was used to set a new detection limit for plant exposure to low levels of destruxins – phytotoxins of Alternaria brassicae . A general experimental algorithm is presented that can be used to identify the combination of fluorescence parameters providing the highest contrast between the affected and unaffected plants or plant segments. Leaves of canola ( Brassica napus ) and white mustard ( Sinapis alba ) were exposed to various concentrations of destruxins and images of key fluorescence signals ( F ₀, F _M, F _P, and of F _S) were captured in a single kinetic experiment. Contrast was quantified within these images between the leaf areas exposed to destruxins and the untreated areas. The highest contrast was found in the image constructed by pixel-to-pixel division of images F ₀ by F _P and F ₀ by F _M. Using the F ₀/ F _M ratio image, we were able to detect exposure to destruxin concentration as low as approximately 0.05 mg l⁻¹ applied to canola leaf and approximately 10 mg l⁻¹ when applied to mustard. The detection limits were significantly lower than those obtained by optical microscopy indicating that kinetic chlorophyll fluorescence imaging can be used as a diagnostic tool in screening for varieties with an enhanced resistance to destruxins of Alternaria brassicae .     

Fasciculin II,a protein inhibitor of acetylcholinesterase,tested on central synapses ofAplysia

Fasciculin II, a potential inhibitor of acetylcholinesterase (AChE), was tested on two types of Aplysia cholinergic receptors: H type, opening Cl- channels; and D type, opening cationic channels. Evoked postsynaptic inhibitory responses and responses to ionophoretic application of acetylcholine (ACh) or carbachol onto H-type receptors were potentiated in the presence of fasciculin II at 10(-9) M, whereas the same concentration of this drug was without effect on the evoked postsynaptic excitatory responses or on the application of ACh or carbachol on D-type receptors. The observed effects of fasciculin II were identical to those obtained with other inhibitors of AChE on the same preparation. The facilitatory effect on the carbachol response in H-type cells indicates that fasciculin II, as other AChE inhibitors, does not act on H-type synapses solely by blocking the hydrolysis of ACh. We concluded that fasciculin II was a good inhibitor of acetylcholinesterase on neuronal preparations in vivo. The results are further discussed as a new element in favor of a previously proposed hypothesis of a molecular interaction between AChE and ACh H-type receptors.     

An analysis of book review criteria and motivation

Abstract. The book review process for multi-authored volumes such as symposia proceedings and compendia is analysed and discussed. The criteria used in book reviewing as listed by Keddy (1991) as well as a set of new ones have been screened in a selection of 142 multi-authored volumes reviewed in Ecology, Journal of Ecology, Vegetatio, and Journal of Vegetation Science. Too often many important book review criteria have not been taken into account at all. Use of a standard set of book review criteria is suggested to avoid personal bias as much as possible.