Weight gain is associated with medial contact site of subthalamic stimulation in Parkinson's disease

The aim of our study was to assess changes in body-weight in relation to active electrode contact position in the subthalamic nucleus. Regular body weight measurements were done in 20 patients with advanced Parkinson's disease within a period of 18 months after implantation. T1-weighted (1.5T) magnetic resonance images were used to determine electrode position in the subthalamic nucleus and the Unified Parkinson's disease rating scale (UPDRS-III) was used for motor assessment. The distance of the contacts from the wall of the third ventricle in the mediolateral direction inversely correlated with weight gain (r = -0.55, p<0.01) and with neurostimulation-related motor condition expressed as the contralateral hemi-body UPDRS-III (r = -0.42, p<0.01). Patients with at least one contact within 9.3 mm of the wall experienced significantly greater weight gain (9.4 ± (SD)4.4 kg, N = 11) than those with both contacts located laterally (3.9 ± 2.7 kg, N = 9) (p<0.001). The position of the active contact is critical not only for motor outcome but is also associated with weight gain, suggesting a regional effect of subthalamic stimulation on adjacent structures involved in the central regulation of energy balance, food intake or reward.     

In vivo patellofemoral forces in high flexion total knee arthroplasty

This study compares the in vivo patellofemoral contact forces generated in high flexion fixed bearing posterior cruciate retaining Nexgen CR-Flex (PCR) and high flexion posterior stabilized Nexgen LPS-Flex (LPS) TKAs with that of normal knees from full knee extension to maximum weight bearing flexion. Ten patients with the PCR total knee arthroplasty (TKA), ten with the LPS TKA and seven patients having normal knees were fluoroscoped while performing a deep knee bend activity. In vivo femorotibial kinematics, obtained from 3D-to-2D registration technique, and patellar kinematics obtained by direct measurements from the fluoroscopic images were entered into a 3D inverse dynamics mathematical model to determine the in vivo contact forces at the knee. The variation in the patellofemoral and quadriceps forces with flexion were found to be similar across the three groups-increasing from full extension to 90 degrees of flexion, reaching a maximum between 90 degrees and 120 degrees of flexion and then decreasing until maximum flexion. At maximum knee flexion, these forces were found to be significantly lower in the normal knees than in the TKAs. The patellar ligament to quadriceps force ratio decreased with the increase in knee flexion while the patellofemoral to quadriceps force ratio increased. A strong correlation was found to exist between the patellofemoral forces, the femorotibial contact forces and the forces in the extensor mechanism. The PCR TKA in this study exhibited greater resemblance to the normal patients with respect to the patellofemoral forces than the LPS TKA though significant differences in the two implant types were not observed.     

Planar microfluidic chamber for generation of stable and steep chemoattractant gradients

The extracellular availability of growth factors, hormones, chemokines, and neurotransmitters under gradient conditions is required for directional cellular responses such as migration, axonal pathfinding, and tissue patterning. These responses are, in turn, important in disease and developmental processes. This article addresses critical barriers toward devising a chemotaxis assay that is broadly applicable for different kinds of cancer cells through the design of a microfluidic chamber that produces a steep gradient of chemoattractant. Photolithography was used to create microchannels for chemoattractant delivery, flow diversion barriers/conduits, and small outlets in the form of apertures. The 1-μm apertures were made at the active surface by uncapping a thin (1.5 μm) layer of AZ1518. This process also created a vertical conduit that diverted the flow such that it occurred perpendicularly to the active, experimental surface where the gradients were measured. The other side of the vertical conduit opened to underlying 20-μm deep channels that carried microfluidic flows of tracer dyes/growth factors. Modeled data using computational fluid dynamics produced gradients that were steep along the horizontal, active surface. This simulation mirrors empirically derived gradients obtained from the flow analyses of fluorescent compounds. The open chamber contains a large buffer volume, which prevents chemoattractant saturation and permits easy cell and compound manipulation. The technique obviates the use of membranes or laminar flow that may hinder imaging, rinsing steps, cell seeding, and treatment. The utility of the chamber in the study of cell protrusion, an early step during chemotaxis, was demonstrated by growing cancer cells in the chamber, inducing a chemoattractant gradient using compressed air at 0.7 bar, and performing time-lapse microscopy. Breast cancer cells responded to the rapidly developed and stable gradient of epidermal growth factor by directing centroid positions toward the gradient and by forming a leading edge at a speed of 0.45 μm/min.     

The role of the corpus callosum in the interhemispheric transmission of epileptic electrical activity.

In acute experiments on 49 curarized adult rats without general anaesthesia, we studied the transmission of discharges of cortical penicillin foci between the two hemispheres after transecting the corpus callosum. Projected discharges of the cortical penicillin focus appeared in the contralateral hemisphere later than in the controls and had a very different shape. The interhemispheric response of the experimental rats consisted of a small positive and a small negative deflection with long latent periods. Focal discharges could be triggered by electrical stimulat;on of the contralateral hemisphere only irregularly and for short periods of time. In rats with a transected corpus callosum, two symmetrical cortical foci at first behaved independently of each other; their synchronization then slowly improved, but never attained 100 per cent. The corpus callosum is the preferential pathway for interhemispheric transmission of focal activity. Transection of this pathway makes the transmission conditions much worse, but further connections, with a longer conduction time and lower efficacy, gradually come into action.     

Cat Cultures and Threefold Modelling of Human-Animal Interactions: on the Example of Estonian Cat Shelters

Interaction between humans and cats in urban environments is subject to dynamic change. Based on the frequency and quality of relations with humans, we can distinguish several populations of domestic cats (Felis catus): pedigree, pet, semi-feral, feral, and pseudo-wild. Bringing together theoretical perspectives of the Tartu school of biosemiotics and ethological studies of animal societies, we distinguish two basic types of cat cultures: the culture of street cats and the humano-cat culture of pets. The difference between these cultures is documented on the level of zoosemiotic interactions, ecological relations, and human representations. We introduce a threefold model of human-animal interactions in urban environments which steer a careful course between the Scylla of realistic ontology and the Charybdis of social constructivism. A case study on Estonian cat shelters illustrates the significance of cultural representations and institutionalized actions in human-cat cohabitation.     

Bioluminescence determination of enzyme activity of firefly luciferase in the presence of pesticides.

Firefly luciferase (EC 1.13.12.5) (FL) is the key enzyme in the firefly bioluminescence method (FB), which is widely used to determine the viability of living cells. The FB method can also be applied to monitoring the influence of different pollutants, such as pesticides. Firefly luciferase is a hydrophobic enzyme and its activity depends on the type of solvent, pH and substances present in the reaction mixture. The influence of three aromatic pesticides, including fenoxaprop-p-ethyl (I), diclofop-methyl (II) and metsulfuron methyl (III), on the enzyme activity was indirectly evaluated through the measurement of emitted light in the bioluminescence reaction, expressed in relative luminescence units (RLU). The reaction mixture used in the bioluminescence measurements consisted of: Tris buffer (pH 7.75), adenosine triphosphate (ATP) and ATP monitoring reagent, where FL is present. Ethanol-water solutions of each pesticide were then added at concentrations of 2.4 x 10(-4)-2.4 x 10(-8) mol/L. The FL activity inhibition factors (FL In%) were determined. The FL activity was maximally inhibited in the presence of all pesticides under study at a concentration of 2.4 x 10(-4) mol/L and was lowered by about 15-26% for pesticide I at concentrations of 2.4 x 10(-5)-2.4 x 10(-8) mol/L, whereas pesticides II and III, applied in the same concentration range, showed smaller FL inhibition values (5.3-20%). The pesticide degradation products (obtained after a 1 month period), measured in the same experimental conditions, in most cases exhibited a much less inhibitory effect on the enzyme activity than the corresponding initial pesticide.     

Impact of windstorm on a community of centipedes (Chilopoda) in a beech forest in Western Poland

The study was carried out in the years 2016–2017, five years after a windstorm which destroyed 1/3 of the protected beech forest area in the west of Poland. The community of centipedes in the area affected by the windstorm was depleted in terms of the species richness, diversity, and population density. The dominance structures were shortened and the species composition was rebuilt. The areas that proved to be the richest in terms of species richness and diversity among the sites affected by the windstorm were the one where windfallen trees were left and the other where beech trees had been planted by humans. In total, the quantitative and qualitative samples collected four times throughout a year featured 608 specimens from 11 species of two centipede orders – Lithobiomorpha and Geophilomorpha. Lithobius curtipes and L. forficatus were found in all of the investigated areas. L. pelidnus and L. piceus were captured at control sites exclusively. Only one species –L. erythrocephalus was found solely at the damaged site. The most numerous and most frequently found species in the community were L. curtipes, L. mutabilis, and Strigamia acuminata respectively. Although windstorms are natural phenomena their consequences may lead to significant changes in the community of the investigated soil animals. The importance of coarse woody debris, significantly contributing to the improvement and maintenance of species richness and diversity of Chilopoda, has once again been confirmed.     

Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro

Prion diseases, or transmissible spongiform encephalopathies (TSEs) are typically characterised by CNS accumulation of PrP(Sc), an aberrant conformer of a normal cellular protein PrP(C). It is thought PrP(Sc) is itself infectious and the causative agent of such diseases. To date, no chemical modifications of PrP(Sc), or a sub-population thereof, have been reported. In this study we have investigated whether chemical modification of amino acids within PrP might cause this protein to exhibit aberrant properties and whether these properties can be propagated onto unmodified prion protein. Of particular interest were post-translational modifications resulting from physiological conditions shown to be associated with TSE disease. Here we report that in vitro exposure of recombinant PrP to conditions that imitate the end effects of oxidative/nitrative stress in TSE-infected mouse brains cause the protein to adopt many of the physical characteristics of PrP(Sc). Most interestingly, these properties could be propagated onto unmodified PrP protein when the modified protein was used as a template. These data suggest that post-translational modifications of PrP might contribute to the initiation and/or propagation of prion protein-associated plaques in vivo during prion disease, thereby high-lighting novel biochemical pathways as possible therapeutic targets for these conditions.