“Pigment epithelium-derived factor (PEDF) has roles in ant

“Pigment epithelium-derived factor (PEDF) has roles in antiangiogenesis and antitumourigenesis that are intimately entwined and is showing promise as a potential anticancer agent. However, the function of PEDF in the deregulated

apoptotic pathways of malignant cells must first be fully characterized. Here, we review the currently known apoptotic pathways that are relevant to PEDF and cancer. Recently, a pathway that includes the PEDF receptor, PPAR gamma and p53 has emerged. It is hoped that further characterization of this and other pathways involved in cancer will bring to light potential new therapeutic targets and approaches, which due to their specificity might be free of the Flavopiridol molecular weight morbidity associated with conventional chemotherapy.”
“We develop a model to describe the effect of cell wall ageing on the local expansion

rate of tip-growing cells. Starting from an exact equation for the stationary age-distribution of the wall material, we propose find more a generic measure for the local expansion propensity of the wall if the ageing process is described by a constant rate Poissonian decay process. This ageing process may be either interpreted as biochemical in nature describing the finite lifetime of regulatory proteins, or as mechanical in nature describing the gradual “”hardening”" of the wall through cross-linking or gelation of the wall polymers. In this way we can construct models for tip-growth in which material deposition, evolving wall properties and surface expansion are self-consistently intertwined. As a proof of principle, we implement our ageing approach in two different idealised models

of tip-growth, obtaining the stationary tip shapes as a function of the ageing parameter. In the first, the spatial distribution of delivery of growth material is determined by the local curvature of the cell and the growth mode is orthogonal. In the second, the growth material originates from a Vesicle Supply Center, a point-like representation of the Spitzenkorper as found in fungal selleck hyphae, and the growth mode is isometric. (C) 2011 Elsevier Ltd. All rights reserved.”
“We developed a novel thermoelectric cooling device using Peltier modules for the treatment of spinal cord injury in rats. The extracorporeal electrically cooling component was attached to the aluminum arched plate which was placed on the surface of the spinal cord after the contusion injury in the 11th thoracic spinal cord. During the hypothermic treatment, rats were awake and could move in the cage. Hind limb motor function, evaluated using a BBB scale, in the hypothermic animals (33 degrees C for 48 h) was significantly higher than that in the normothermic animals from 2 weeks to 8 weeks after the injury. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Therefore, it is also crucial to determine the tumorgenicity of t

Therefore, it is also crucial to determine the tumorgenicity of the cells derived from iPSCs for any future Nutlin-3 cost therapeutic use.”
“Each postnatal hair follicle (HF) perpetually goes through three phases: anagen, catagen, and telogen. The molecular signals that orchestrate the follicular transition between phases are still largely unknown. Our previous study shows that the keratinocyte specific Smad4 knockout mice exhibit progressive alopecia due to the mutant HFs failure to undergo programmed regression. To investigate the detailed molecular events controlling

this process, the protein profiles of Smad4 mutant and control epidermal and HF keratinocytes were compared using 2-D difference gel electrophoresis (2-D DIGE) proteomic analysis. Eighty-six differentially expressed protein spots were identified by MALDI-TOF/TOF MS or ESI-MS/MS as 72 proteins, of which 29 proteins were found to be changed during the anagen-catagen transition of HFs in Smad4 mutants compared with the controls. The differentially expressed proteins represent a wide spectrum of functional

classes such as keratin, the cytoskeleton, cellular growth and differentiation, ion combination and transfer, protein enzymes. Notably, we found that the 14-3-3 sigma protein together with the 14-3-3 zeta and 14-3-3 beta proteins were significantly Romidepsin down-regulated only in wild-type keratinocytes but not in Smad4 mutant keratinocytes during the catagen phase, suggesting that increased expression of 14-3-3 proteins might contribute to the blockade of catagen initiation in Smad4 deficient HFs.”
“Aims: To establish PCR-based assays for the A-769662 mouse rapid identification and differentiation of each of four known biotype 2 (BT2) phenotype-causing alleles in Yersinia ruckeri strains currently circulating in Europe and the United States.

Methods and Results: Novel assays were developed relying on detection of mutant allele-specific changes in restriction enzyme

cleavage sites within targeted PCR products. The developed assays were validated against isolates previously genotyped by DNA sequencing.

Conclusions: The described methods were specific, rapid and simple to perform and interpret.

Significance and Impact of the Study: The developed genotyping assays provide a valuable tool for identification and differentiation of specific BT2 strains of Y. ruckeri. These assays will be critical for the design and validation of new vaccines or other measures meant to control BT2 strains.”
“A sense of motion can be elicited by the movement of both luminance- and texture-defined patterns, what is commonly referred to as first- and second-order, respectively.

These observations provide evidence that AHN-1055 does not behave

These observations provide evidence that AHN-1055 does not behave as a classical psychomotor stimulant and that some of its properties, including attenuation of cocaine-induced striatal c-Fos expression, locomotor stimulation, and CPP, support its candidacy, and that of structurally related molecules, as possible pharmacotherapies in cocaine addiction. Neuropsychopharmacology (2009) 34, 2497-2507; doi:10.1038/npp.2009.78; published online 15 July 2009″
“The kidney and brain expressed protein gene (KIBRA) and the calsyntenin 2 gene (CLSTN2) are reportedly involved in synaptic plasticity.

Single nucleotide polymorphisms (SNPs) rs17070145 (KIBRA) and rs6439886 (CLSTN2) have been found VE-821 nmr to affect memory performance measures. This study examined the association of KIBRA SNP rs17070145 and CLSTN2 SNPs rs6439886 and rs17348572 (a nonsynonymous variant) with cognitive flexibility in 674 African Americans (AAs; 526 current smokers) and 419 European Americans (EAs; 318 current smokers). The subjects’ cognitive flexibility was assessed using the Wisconsin Card Sorting Test. The effects on cognitive flexibility of sex, age, education,

and tobacco recency (a possible mediator of gene effects in smokers), the three SNPs, and the interaction of each SNP with tobacco recency were analyzed using multivariate analysis of variance. In AAs, there were no main or interaction effects of the SNPs on cognitive flexibility. In EAs, the two CLSTN2 SNPs showed no main effect on cognitive flexibility. phosphatase inhibitor However, among EAs, individuals with the KIBRA rs17070145 T allele made significantly more perseverative responses (P = 0.002) and perseverative errors (P = 0.002) than those with no T allele. Furthermore, among EAs with the rs17070145 T allele, current smokers made significantly fewer perseverative responses (P < 0.001) and perseverative errors (P < 0.001) than past smokers. Nongenetic factors (age, education, and tobacco recency) had substantial effects to on cognitive flexibility in both AAs and EAs. We conclude that variation in KIBRA influences cognitive flexibility in a population-specific way, and that current smoking

status moderates this effect. Neuropsychopharmacology (2009) 34, 2508-2516; doi:10.1038/npp.2009.80; published online 15 July 2009″
“The aim of this study was to investigate genetic predictors of an increase in suicidal ideation during treatment with a selective serotonin reuptake inhibitor or a tricyclic antidepressant. A total of 796 adult patients with major depressive disorder who were treated with a flexible dosage of escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP) were included in the sample and provided data on suicidal ideation. Nine candidate genes involved in neurotrophic, serotonergic, and noradrenergic pathways were selected based on previous association studies with suicidal ideation or behavior.

3,3′,4′-Trihydroxyflavone and 3′,4′-dihydroxyflavone inhibited A

3,3′,4′-Trihydroxyflavone and 3′,4′-dihydroxyflavone inhibited A beta fibril formation more potently than fisetin or

3′,4′,7-trihydroxyflavone, suggesting that the 7-hydroxy group is not necessary for anti-amyloidogenic activity. 3,3′,4′,5′-Tetrahydroxyflavone and 3′,4′,5′-trihydroxyflavone inhibited A beta fibril formation far more potently than 3,3′,4′-trihydroxyflavone and 3′,4′-dihydroxyflavone, suggesting that 3′,4′,5′-trihydroxyl group of the B ring is crucial for the anti-amyloidogenic activity of flavonoids. Based on the structure-activity relationship, we synthesized 3,3′,4′,5,5′-pentahydroxyflavone, and confirmed that this compound is the most potent inhibitor of A beta fibril formation among fisetin analogues that have been tested. Cytotoxicity Quizartinib chemical structure assay using rat hippocampal neuron cultures demonstrated that A beta preincubated with 3,3′,4′,5,5′-pentahydroxyflavone GSK2118436 in vitro was significantly less toxic than A beta preincubated with vehicle. 3,3′,4′,5,5′-Pentahydroxyflavone could be a new therapeutic drug candidate for the treatment of Alzheimer’s disease. (c) 2012 Elsevier Ireland Ltd. All rights reserved.”

inherited polyglutamine disorders are chronic neurodegenerative diseases therapeutically amenable to gene-specific silencing strategies. Several compelling nucleic acid-based approaches have recently been developed to block the expression of mutant proteins and prevent toxic LCL161 mouse neurodegenerative sequelae. With such approaches, avoiding potential side effects caused by the concomitant ablation of the normal protein is an important objective. Therefore, allele-specific gene silencing is highly desirable; however, retaining wild type function is complex given that the common CAG mutation cannot be directly targeted, and might not be necessary or justifiable in all cases. Insights from polyglutamine gene function studies and the further development of allele-specific and other gene silencing methodologies will be important to determine

the optimal therapeutic strategy for each polyglutamine disorder.”
“Childhood trauma is a potent risk factor for developing depression in adulthood, particularly in response to additional stress. We here summarize results from a series of. clinical studies suggesting that childhood trauma in humans is associated with sensitization of the neuroendocrine stress response, glucocorticoid resistance, increased central corticotropin-releasing factor (CRF) activity, immune activation, and reduced hippocampal volume, closely paralleling several of the neuroendocrine features of depression. Neuroendocrine changes secondary to early-life stress likely reflect risk to develop depression in response to stress, potentially due to failure of a connected neural circuitry implicated in emotional, neuroendocrine and autonomic control to compensate in response to challenge.

Thus, while a strong genetic bottleneck was detected during MCTC,

Thus, while a strong genetic bottleneck was detected during MCTC, with click here viruses of shorter and fewer glycosylation sites in env present in IP transmission, our data do not support this bottleneck being driven by selective resistance to antibodies.”
“Post-translational modification (PTM) of a protein is an important event in regulating cellular functions. An algorithm, MAPRes, has been developed for mining associations among PTM sites and the preferred amino acids in their vicinity. The

algorithm has been implemented to O-glycosylation and O-phosphorylation data (phosphorylated/glycosylated Ser/Thr/Tyr). The association patterns mined by MAPRes demonstrate significant correlations and the results are in conformity with the existing methods. These association rules/patterns will be helpful in predicting the sequences/motifs involved for specific PTMs in proteins.”
“Decades of controversy regarding ribosome occurrence in axons are finally coalescing to a realization that the protein synthesis machinery is recruited and activated in both central and peripheral axons during development and in adult peripheral axons upon injury. Exciting recent findings indicate that ribosome recruitment to axons learn more occurs via lateral transfer from glial cells, a mechanism that could be part of a continuum of intercellular communication systems including

tunneling nanotubes and exosomes. Such transcellular interactions could have crucial roles in nervous system functions and will provide new avenues for research into long-standing problems.”
“Substance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved

in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. lmmunofluorescence analysis of the co-expression of NK1 with calcium binding proteins in www.selleck.cn/products/defactinib.html LA revealed that similar to 35% of NK1-containing neurons co-expressed parvalbumin (PV), whereas no co-localization was detected in the basal amygdaloid nucleus. We also show that neurons expressing NK1 receptors in LA did not contain detectable levels of calcium/calmodulin kinase II alpha, thus suggesting that NK1 receptors are expressed by interneurons. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, we found that in LA similar to 75% of glutamatergic synapses onto NK1-expressing neurons were labeled for the vesicular glutamate transporter 1 indicating that they most likely are of cortical, hippocampal, or intrinsic origin. The remaining similar to 25% were immunoreactive for the vesicular glutamate transporter 2 (VGIuT2), and may then originate from subcortical areas.

Gli2 was the only hedgehog signaling molecule of which expression

Gli2 was the only hedgehog signaling molecule of which expression correlated with stratification. Manipulation of Gli2 expression or activity significantly affected cell invasiveness.

Conclusions: Weak

growth suppression by cyclopamine suggests that hedgehog signaling is not involved in bladder cancer cell proliferation TPCA-1 cost but Gli2 expression strongly correlated with invasive behavior. Increased Gli2 expression increased low Gli2 cell invasiveness while Gli inhibition by GANT61 decreased high Gli2 cell invasiveness. Results suggest that Gli2 expression by noncanonical signaling contributes to bladder cancer cell invasiveness.”
“Animals are known to recognize a specific odorant informing conspecific health condition, which plays a significant role in regulating their social communication Here, we assess neural mechanisms regulating

innate approach/avoidance response toward such conspecific odor cues in rats Odor scent from healthy conspecifics induced approach behavior, while those from sick conspecifics produced avoidance response in odor recipient male rats Analysis of mRNA expression in several brain sites of odor recipient rats illustrated that Torin 1 induction of c-fos mRNA expression was found in the olfactory bulb (OB), the medial amygdala (MeA), the bed nucleus of stria terminalis (BnST), and the paraventricular nucleus of the hypothalamus (PVN), when exposed to conspecific odor Moreover, in the MeA, expression of oxytocin (OT) receptor mRNA was increased when rats were exposed to healthy conspecific odor, while induction of arginine

vasopressin (AVP) receptor 1a and 1b mRNA were found only when exposed to sick conspecific odor Bilateral infusion of OT receptor (OTR) antagonist, (d(CH2)5(1),Tyr(Me)(2),Thr(4),Orn(8),des Gly NH2(9))-Vasotocin, into the MeA blocked approach behavior to healthy odor, while those of AVP receptor antagonists, Via selective (Phenylac(1),D Tyr(Me)(2),Arg(6) tuclazepam (8),Lys NH2(8))-Vasopressin and type 1 receptor antagonist (Deamino Pen(1) Try(Me)(2), Arg(8)) Vasopressin into the MeA inhibited avoidance response to sick odor These findings provide evidence for an essential role of OT and AVP receptors especially type la in the MeA in regulating approach/avoidance behaviors respectively in social odorant communication (C) 2010 IBRO Published by Elsevier Ltd All rights reserved”
“Purpose: Focal therapy using lasers is emerging as an alternative strategy for prostate cancer treatment. However, to our knowledge no anatomically correct models are available to test imaging and ablation techniques. Animal models present ethical, anatomical and cost challenges. We designed and validated an inexpensive but anatomically correct prostate phantom incorporating tumor, rectum and urethra that can be used for simulated and experimental magnetic resonance guided focal intervention. Our secondary aim was to asses the phantom using other imaging modalities.

In the second study, 31 diabetic patients were divided into two g

In the second study, 31 diabetic patients were divided into two groups, having normal or diminished (< 6 ms/mmHg) baroreflex DMH1 molecular weight sensitivity (BRS). Patients with normal BRS showed the same results found in healthy volunteers. Diabetic patients with diminished BRS did not show this pattern. Because diminished BRS is an indicator of impaired baro-afferent signal transmission, it is concluded that cardiac modulation of startle is associated with intact baro-afferent feedback. Thus, pre-attentive startle methodology is feasible to study visceral

afferent processing originating from the cardiovascular system.”
“The evolution of the human brain has resulted in the emergence of higher-order cognitive abilities, such as reasoning, planning and social awareness. Although there has been a concomitant increase in brain size and complexity, and component diversification, we argue that RNA regulation of epigenetic processes, RNA editing, and the controlled mobilization of transposable elements have provided the major substrates for cognitive advance. We also suggest that these expanded capacities and flexibilities have led

to the collateral GSK621 mw emergence of psychiatric fragilities and conditions.”
“The host immune response is believed to tightly control viral replication of deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV). However, this assumption has not been definitely proven in vivo. In order to further evaluate the importance of

the immune response in the BLV model, we studied the fate of cells in which viral expression was transiently induced. Using a dual fluorochrome labeling approach, we showed that ex vivo induction of viral expression induces higher death rates of B cells in vivo. Furthermore, cyclosporine treatment of these animals indicated that an efficient immune response is required to control virus-expressing cells.”
“MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, LGX818 functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading.

We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences.

TORCs (transducers of regulated CREB) represent a new family of c

TORCs (transducers of regulated CREB) represent a new family of conserved CREB coactivators that function as intracellular calcium- and cAMP-sensitive coincidence detectors, controlling the kinetics of CRE-mediated responses and long-term potentiation of synaptic transmission. Here we examined the expression and activity-dependent translocaition of TORCs in adult retinal ganglion cells (RGCs), the primary target of acute retinal ischemic injury as well as chronic: retinal degenerative diseases. We found that both mRNAs of TORC1 and TORC2, but not TORC3, were enriched in adult rat retina. Comparing with TORC2, TORC1 protein was highly and

selectively expressed in RGCs. At resting condition, TORC1 protein was localized in the cytoplasm

but not nucleus of RGCs. Activation of N-methyl-D-aspartate (NMDA) receptors by intravitreous injection of NMDA or increase of cAMP signaling by administration of forskolin triggered nuclear accumulation BAY 11-7082 solubility dmso of TORC1. Furthermore, transient retinal ischemic injury resulted in peri-nuclear and nuclear accumulation of TORC1 as well as transcription of BDNF in RGCs. Our results demonstrate that TORC1 is enriched in RGCs and its subcellular location could be regulated by Ca(2+) and cAMP, suggesting that manipulation of TORC1 activity may promote survival of IRGCs in some optic disease conditions. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Sensory gating refers to the ability of cerebral networks to inhibit responding to irrelevant environmental stimuli, a mechanism that protects this website the brain from information overflow.

PSI-7977 cost The reduction of the P50 amplitude (an early component of the event-related potential/ERP in electrophysiological recordings) after repeated occurrence of a particular acoustic stimulus is one means to quantitatively assess gating mechanisms. Even though P50 suppression has been extensively investigated, neuroimaging studies on the cortical correlates of auditory sensory gating are so far very sparse. Near-infrared spectroscopy (NIRS) is an optical imaging technique perfectly suitable for the investigation of auditory paradigms, since it involves virtually no noise. We conducted a simultaneous NIRS-ERP measurement to assess cortical correlates of auditory sensory gating in humans. The multi-channel NIRS recording indicated a specific activation of prefrontal and temporo-parietal cortices during conditions of increased sensory gating (dual-click trials). Combining the hemodynamic data with an electrophysiological index of the “”gating quality”" (gating quotient Q) revealed a positive correlation between the amount of sensory gating and the strength of the hemodynamic response during dual-clicks in the left prefrontal and temporal cortices. The results are in line with previous findings and confirm a possible inhibitory influence of the prefrontal cortex on primary auditory cortices. (C) 2009 IBRO.

The authors describe the most direct trajectory to the ventricula

The authors describe the most direct trajectory to the ventricular trigone using this approach and propose a point of entry that transects the cingulate gyrus at a point 5 mm superior and 5 mm posterior to the falco-tentorial junction.”
“Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied

utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to addiction treatment. Data suggest a major role for the noradrenergic system in extinction of fear-based learning. Employing both pharmacological and genetic approaches, we investigated DAPT in vivo the role of the alpha(2)-adrenergic receptor (alpha(2)-AR) in extinction of cocaine-conditioned CH5183284 solubility dmso place preference (CPP) and glutamatergic transmission in the bed nucleus of the stria terminalis (BNST). We found

that pre-extinction systemic treatment with the alpha(2)-AR antagonist yohimbine impaired cocaine CPP extinction in C57BL/6J mice, an effect that was not mimicked by the more selective alpha(2)-AR antagonist, atipamezole. Moreover, alpha(2)A-AR knockout mice exhibited similar cocaine CPP extinction and exacerbated extinction impairing effects of yohimbine. Using acute brain slices and electrophysiological approaches, we found that yohimbine produces a slowly evolving depression of glutamatergic transmission in the BNST that was

not mimicked by atipamezole. Further, this action was extant in slices from alpha(2)A-AR knockout mice. Our data strongly suggest that extinction-modifying effects of yohimbine are unlikely to be due to actions at alpha(2)A-ARs.”
“OBJECTIVE: GW4869 Surgical approaches to the orbit require great precision and care because of the functional and aesthetic importance of this region. Conventional approaches to the posterior orbit often require bone removal, may disrupt extraocular muscles, and may create external surgical scars. We conceived a transconjunctival surgical approach to the medial intraconal space that is aided by a minimally invasive endoscopic technique and avoids muscle transection.

METHODS: Assisted by a rigid endoscope measuring 2.7 mm in diameter, with 0- and 30-degree lenses, we made a medial conjunctival incision along the limbus to approach the medial intraconal space and optic nerve in 7 fresh cadaver heads (a total of 9 procedures).

RESULTS: This approach provided direct and quick access to the medial intraconal space and intraorbital optic nerve with the use of endoscopes via an aesthetically acceptable conjunctival incision, and it provided an excellent view of the operative area. Unlike conventional techniques, this approach left the anatomy relatively undisturbed and did not require detachment of the medial rectus muscle.

When rare, assessment rules which positively judge a refusal to h

When rare, assessment rules which positively judge a refusal to help bad people produce a poor correlation between reputation and behavior. It is this correlation that generates the assortment crucial in sustaining

cooperation through indirect reciprocity. Only assessment rules that require good deeds to achieve a good reputation guarantee a strong correlation between behavior and reputation. (C) 2011 Elsevier Ltd. All rights reserved.”
“Background: Many patients with Parkinson’s disease (PD) develop freezing of gait (FOG), which may manifest as a hesitation or “”getting stuck”" when they attempt to pass through a doorway. In ISRIB chemical structure two experiments, we asked whether FoG is associated with (1) a deficit in internal representation of one’s body size with respect to a doorway and (2) a mismatch between imagined and actual walking times when passing through a doorway.

Methods: Apoptosis inhibitor 23 subjects with PD (11 with and 13 without FoG) and 10 control subjects of similar age completed

two experiments. In the Passability experiment, subjects judged the passability of doorways with different apertures scaled to their body widths. We compared passability estimates across groups. In the Imagery experiment, subjects timed themselves while: (1) imagining walking through doorways of different apertures and from different distances and (2) actually walking in the same conditions they had just imagined. We compared imagined and actual walking durations across groups and conditions.

Results: In the Passability experiment, the estimated just-passable doorway was wider, relative to body width, in PD subjects than in control subjects, but there was no difference between PD subjects with and without FoG. In the Imagery experiment, subjects in all groups walked more slowly through narrow doorways than though wide doorways, and subjects with FoG walked much more slowly through Akt inhibitor the narrowest

doorways. PD subjects with FoG showed a large discrepancy between actual and imagined time to pass through narrow doorways, unlike PD subjects without FoG and control subjects.

Conclusions: The equivalent passability judgments in PD subjects with and without FoG indicate that FoG is not specifically associated with a deficit in ability to internally represent space with reference to body size. However, the large difference in duration between actual and imagined walking through narrow doorways in subjects with FoG suggests that PD subjects with FoG did not know how much they would slow down to pass through narrow doorways. The observed discrepancy between imagined and actual walking times may point to a specific problem that contributes to the occurrence of FoG.