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Computing spike directivity with tetrodes.

The ability of neurons to generate electrical signals is strongly dependent on the evolution of ion-specific pumps and channels that allow the transfer of charges under the influence of electric fields and concentration gradients. This paper presents a novel method by which flow of these charge fluxes may be computed to provide directivity of charge movement. Simulations of charge flow as well as actual electrophysiological data recorded by tetrodes are used to demonstrate the method. The propagation of charge fluxes in space in data from simulation and actual recordings during action potential can be analyzed using signals recorded by tetrodes. Variation in spike directivity can be estimated by computing singular value decomposition of the estimated 3D trajectory data. The analysis of the spike model can be accomplished by performing simulations of presumed equivalent moving charges recorded by the tetrode tips. For in vivo spike recordings, the variation of spike directivity could be obtained using several spikes of selected neurons considering the charge movement model (CMM). The relationship between computer simulation results and tetrode data recordings is examined. The paper concludes by showing that the method for calculating directivity in actual spike recordings is robust. The method allows for improved filtering of data and more importantly may shed light on furthering the study of spatio-temporal encoding in neurons.

Action Potentials↗

Building spike representation in tetrodes.

This paper presents a new technique for analyzing the recorded information from tetrodes in freely behaving rats, based on independent component analysis (ICA). The ion-specific pumps and channels allow fast transfer of charges such as Na+, K+, Cl- and eventually Ca2+ during each action potential (AP). These groups of charges under an electrical field have distinct spatial trajectories. Therefore, the generated signals within a tetrode are considered to be composed mainly by statistically independent signal sources that can be obtained by performing ICA. In order to compute the position of independent sources during AP generation, the triangulation method uses an iterative Newton-Raphson algorithm. The representation of the independent signal sources in three-dimensional tetrode space is then obtained. Since the charge movements are extensively spread on the neuron's surface, the representation in tetrode space reveals electrical spatial patterns of activation during each AP. The analysis of several spikes coming from the same neuron reveals small changes from spike to spike in the 3D shape. Since information within spikes is highly transferred by ionic fluxes these electrical patterns of activation reflect neuronal computation occurring during each AP.

Action Potentials↗

Is there a tipping point in neuronal ensembles during learning?

Learning is important for humans and can be disrupted by disease. However, the essence of how learning may be represented within a neuronal network is still elusive. Spike trains generated by neurons have been demonstrated to carry information which is relevant for learning. The present study uses well-established mutual information (MI) analysis techniques to better understand learning within neuronal ensembles. Spike trains in tetrode recordings from the dorso-lateral striatum were used for computing MI as rats learnt a T-maze procedural task. We demonstrate that in in-vivo recordings the growth of MI is reflected in the behavioral response as learning proceeds. These changes in MI are seen to correspond to three phases, a low MI value, namely early learning, a rapid increase in MI value, task-acquisition and stabilization of MI, over-training. Over multiple training sessions, small changes in MI within the neuronal network suddenly produce a big change in ensemble MI during the task acquisition phase. This phase represents the "tipping point" in the neuronal network where the MI growth builds habits during motor learning in the striatum.

Action Potentials↗

Visual inspection time in Parkinson's disease: deficits in early stages of cognitive processing.

Inspection time (IT) is a simple information processing paradigm dependent on a participant's ability to identify physical properties of a stimulus presented for a specified time interval. In contrast with reaction time (RT) studies, the dependent variable of interest in IT is not related to the motoric speed with which the individual is able to respond, but rather the minimum presentation time necessary for participants to reliably identify physical properties of the stimulus. It is well documented that individuals with Parkinson's disease (PD) experience significant impairment on tests of simple RT, but it is unclear whether such deficits can be interpreted as 'pure' slowness of information processing, or a delay in the selection and output of a motor response. In the first experiment described here, a sample of 'optimally medicated' PD patients was compared with an age-matched control group, on an IT task. Results of this experiment suggested that individuals with PD required significantly longer stimulus presentation times than healthy participants. The second experiment compared a sample of PD patients (tested both "ON" and "OFF" their typical dopaminergic medications), with an age-matched control group, on the same test of IT. Results again indicated a significant IT deficit in participants with PD, and suggested that these deficits do not significantly resolve with levodopa treatment. Overall, the results of these two experiments suggest that information processing deficits associated with PD are distinct from motor impairment. These findings are further discussed in terms of existing neurochemical models of information processing ability.

Adult↗

An evaluation of sensorimotor integration during locomotion toward a target in Parkinson's disease.

Recent research suggests that basal ganglia dysfunction may result in problems integrating concurrent vision and proprioception during movement. We evaluated dopaminergic system involvement in this sensorimotor process during locomotion within a large sample of Parkinson's disease (PD) patients while "On" and "Off" their dopaminergic medications (n=25), in conditions that selectively manipulated the availability of proprioception, vision or both. The present experiment focused on two main objectives: i) to examine the relative influence of visual and proprioceptive inputs on locomotion and target accuracy in patients with PD; and ii) to examine the influence of dopamine replacement therapy on sensorimotor integration while moving toward the target. All participants walked at a self-selected pace on a GAITRite carpet in two baseline conditions (light and dark), as well as four experimental darkness conditions: a) to a remembered target (i.e. proprioception only), b) to a remembered target with light on chest for body position awareness (proprioception plus), c) with vision of a lit target, also with light on chest (vision and proprioception), d) pushed in wheelchair to remembered target (no proprioception or vision). Final position was measured by 2-D radial error, and revealed a group by condition interaction, suggesting that PD patients "Off" their medications move to targets with less accuracy, but approach the accuracy of healthy participants when in the "On" state. Both PD and healthy improved their accuracy with availability of concurrent vision and proprioception (condition c). Interestingly, our results demonstrate that PD "Off" performed the task with greater difficulty than when "On" medication, but only when proprioception was the sole source of feedback. Since PD, whether medicated or unmedicated were even more affected when proprioception was removed (wheelchair), a memory-related explanation can be ruled out. Our results suggest that the basal ganglia are not specifically involved in visuoproprioceptive integration; however, assimilation of proprioceptive feedback to guide an ongoing movement may be a critical function of the basal ganglia.

Adult↗

Memory perception and strategy use in Parkinson's disease.

Although there is growing support for the existence of memory deficits within Parkinson's disease (PD), little has been done to evaluate the extent to which PD patients demonstrate differences in their use of metacognitive strategies. In the present study, 79 PD patients (46 men and 33 women) and 49 age-matched healthy participants (19 men and 30 women) were compared on a metamemory questionnaire. PD patients reported significantly less strategy-use than age-matched controls, particularly with regards to external memory strategies (such as making lists). This suggests that auxiliary treatments such as memory strategy training might be effective in this population.

Adaptation, Psychological↗

Alkaline phytase from Lilium longiflorum: purification and structural characterization.

Phytases catalyze the hydrolysis of phytic acid (myo-inositol hexakisphosphate), the most abundant inositol phosphate in cells. Phytases are of great commercial importance because their use as food and animal feed supplement has been approved by many countries to alleviate environmental and nutritional problems. Although acid phytases have been extensively studied, information regarding alkaline phytases is limited. Alkaline phytases with unique catalytic properties have been identified in plants, however, there is no report on the purification or structural properties. In this paper, we describe the purification of alkaline phytase from plant tissue. The purification was challenging because of contamination from non-specific phosphatases and acid phytases and low endogenous concentration. The purification of alkaline phytase from pollen grains of Lilium longiflorum involved selective precipitation by heat and ammonium sulfate followed by anion exchange and chromatofocusing chromatography and, finally, gel electrophoresis. Alkaline phytase was purified approximately 3000-fold with an overall recovery of 4.2%. The native molecular mass was estimated to be in the range of 118+/-7 kDa by Ferguson plot analysis and Mr of denatured protein in the range of 52-55 kDa by SDS-PAGE suggesting that the enzyme is a homodimer. Separation by 2-D gel and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometric analysis of separated proteins indicates the presence of multiple mass and charge isoforms with pI values between 7.3 and 8.3. To our knowledge, this is the first alkaline phytase to be purified from plant sources. The unique properties suggest that the enzyme has the potential to be useful as a feed and food supplement.

6-Phytase↗

Lily pollen alkaline phytase is a histidine phosphatase similar to mammalian multiple inositol polyphosphate phosphatase (MINPP).

Phytic acid is the most abundant inositol phosphate in cells; it constitutes 1-5% of the dry weight of cereal grains and legumes. Phytases are the primary enzymes responsible for the hydrolysis of phytic acid and thus play important roles in inositol phosphate metabolism. A novel alkaline phytase in lily pollen (LlALP) was recently purified in our laboratory. In this paper, we describe the cloning and characterization of LlALP cDNA from lily pollen. Two isoforms of alkaline phytase cDNAs, LlAlp1 and LlAlp2, which are 1467 and 1533 bp long and encode proteins of 487 and 511 amino acids, respectively, were identified. The deduced amino acid sequences contains the signature heptapeptide of histidine phosphatases, -RHGXRXP-, but shares < 25% identity to fungal histidine acid phytases. Phylogenetic analysis reveals that LlALP is most closely related to multiple inositol polyphosphate phosphatase (MINPP) from humans (25%) and rats (23%). mRNA corresponding to LlAlp1 and LlAlp2 were expressed in leaves, stem, petals and pollen grains. The expression profiles of LlAlp isoforms in anthers indicated that mRNA corresponding to both isoforms were present at all stages of flower development. The expression of LlAlp2 cDNA in Escherichia coli revealed the accumulation of the active enzyme in inclusion bodies and confirmed that the cDNA encodes an alkaline phytase. In summary, plant alkaline phytase is a member of the histidine phosphatase family that includes MINPP and exhibits properties distinct from bacterial and fungal phytases.

6-Phytase↗

Induction of ovulation with subcutaneous pulsatile gonadotropin-releasing hormone: correlation with body weight and other parameters.

We treated 21 anovulatory infertile patients with subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administered via a syringe pump. Response to treatment was assessed by urinary estrogen excretion and ultrasound measurement of follicular growth. Ten patients ovulated and 8 subsequently conceived, for a total of 10 pregnancies. Human chorionic gonadotropin (hCG) was not administered routinely, but two patients required hCG to induce follicular rupture. The majority of the patients who conceived had a body mass index (BMI) of less than 21 and a luteinizing hormone (LH)/follicle-stimulating hormone ratio of less than 1. Conversely, those patients with either elevated BMI or LH or both generally failed to respond satisfactorily to this treatment. It is suggested that pulsatile GnRH is most likely to succeed in inducing ovulation if the BMI is less than 21 and the LH is normal, but is unlikely to be successful if there is both an elevated LH and a BMI of greater than 25. Between these two extremes, the response is variable and a therapeutic trial may be appropriate.

Anovulation↗

Mechanical properties of the tendinous equine interosseus muscle are affected by in vivo transducer implantation.

Liquid metal strain gauges (LMSGs) were implanted in the tendinous interosseous muscle, also called suspensory ligament (SL), in the forelimbs of 6 ponies in order to quantify in vivo strains and forces. Kinematics and ground reaction forces were recorded simultaneously with LMSG signals at the walk and the trot prior to implantation, and 3 and 4 days thereafter. The ponies were euthanised and tensile and failure tests were performed on the instrumented tendons and on the tendons of the contra lateral limb, which were instrumented post mortem. The origo-insertional (OI) strain of the SL was computed from pre- and post-operative kinematics, using a 2D geometrical model. The LMSG-recorded peak strain of the SL was 5.4+/-0.9% at the walk and 9.1+/-1.3% at the trot. Failure occurred at 15.4+/-2.1% (mean+/-S.D.). The LMSG strain was higher than the simultaneously recorded OI strain 0.5+/-0.7% strain at the walk and 2.2+/-1.1% strain at the trot. Post-operative OI strains were only slightly higher than pre-operative values. Failure strains of in vivo instrumented SLs were 2.0+/-1.2% strain higher, and failure forces were slightly lower, than those of the contra lateral SLs that were instrumented post mortem. SL strains appeared to be considerably higher than those found in earlier acute experiments. Differences between in vivo LMSG and OI strains, supported by lower failure strains comparing in vivo and post mortem instrumented SLs, revealed that local changes in tendon mechanical properties occurred within 3 to 4 days after transducer implantation. Therefore, measurements of normal physiological tendon strains should be performed as soon as possible after transducer implantation.

Animals↗

Preparation, characterization and in vitro biocompatibility evaluation of poly(butylene terephthalate)/wollastonite composites.

The aim of the study was to prepare composites of poly(butylene terepthalate)/wollastonite (PBT/W), evaluate their properties and in vitro biocompatibility. Composites of PBT with wollastonite in two different proportions, viz. 70/30 (PW-30), 50/50 (PW-50) were prepared. The DSC studies indicate marginal changes in the melting behavior and enhanced crystallization in PBT/W composites. The mechanical properties of the composites such as tensile modulus shows remarkable improvement as a result of incorporation of wollastonite. SEM studies of fractured surfaces of impact samples showed no evidence of bonding between PBT and wollastonite. Water contact angle of PW30 and PW50 was 73.7 and 78.7, respectively. In vitro biocompatibility of PW-30 was evaluated as a representative composite. Direct cell contact test did not show deleterious effects on NIH3T3 fibroblast morphology and DNA integrity indicating its compatibility. Leach out products (LOP) of PW-30 were evaluated non-toxic as tested by MTT assay. Mouse peritoneal macrophages in contact with PW-30 showed comparable expression of CD 11b/18, CD45, CD14 and B7.2 to macrophages in contact with PTFE control indicating its non-activating nature. LOP did not induce proliferation of mouse splenic lymphocytes suggesting its immuno-tolerance. PW-30 also exhibited preliminary blood compatibility. These physical properties and biocompatibility of PBT/W composites show their suitability as potential biomaterials.

3T3 Cells↗

The effect of exercise on non-restricted caloric intake in male joggers.

This study examined the effects of both increasing and decreasing normal energy expenditure over periods of one week on the self-reported caloric intake of seven male joggers (22-27 years). The three levels of energy expenditure were: no exercise, regular exercise and double exercise. Despite significant difference in energy expenditure across conditions, self-reported caloric intake did not differ significantly, suggesting that energy intake was not affected by short-term changes in energy expenditure.

Adult↗

Observations on sleeping position and essential hypertension.

A hypertensive black male, at risk for episodic attacks of pseudo-malignant hypertension and self-induced atrial fibrillation, seeks to discover possible clues to the pathogeneses of these strange disorders through self-study and concludes they might be associated with impaired oxygen intake, secondary to sleeping position in bed.

Adult↗

Rapid cooling techniques in joggers experiencing heat strain.

This study examined subjects that exercised on three occasions in a heated environment (WBGT = 39 degrees C] until they experienced heat strain. Since morbidity and mortality due to heat injury increase with the duration of elevated core temperature, it is important that techniques to lower core temperature be evaluated. Following three exercise sessions, subjects underwent each of three core cooling treatments in random order: 1) Torso immersion in cool water, 2) Hands and feet immersion in cool water, and 3) Sit-in-shade with a 1.5mph breeze provided. Subjects (n=5) consistently reached peak rectal temperatures of 38.8 (+/-0.1) degrees C following each exercise bout in the heated environment. Torso immersion produced a significantly (p<0.05) greater rate of decline in rectal temperature (0.25+/-0.10 degrees C/min) than the hands and feet immersion technique (0.16+/-0.05 degrees C/min) and the sit in the shade technique (0.11+/-0.04 degrees C/min). After only 10 minutes of cooling, the differences among cooling techniques were evident. Similar trends were observed for mean heart rate readings, albeit not significant (p>0.05). It was concluded that rectal temperatures can be reduced rapidly through the use of a cool water torso-immersion technique.

Abdomen↗