PKAR

INTRODUCTION: Gait dysfunction is common in people with Parkinson's disease (PD). Freezing of gait (FOG) is one such gait disturbance that significantly impacts mobility and quality of life in PD. Recent evidence suggests that cerebellar connectivity may differ in people with PD and FOG (PD+FOG) relative to those without FOG (PD-FOG). Investigation of gait adaptation, or the ability to change gait patterns in response to external perturbations, is cerebellum-dependent, is a practical means of probing cerebellar integrity and may provide additional insights regarding the FOG phenomenon...

The second messenger molecule cAMP regulates the activation phase of the cAMP signaling pathway through high-affinity interactions with the cytosolic cAMP receptor, the protein kinase A regulatory subunit (PKAR). Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis of cAMP to 5' AMP. It was recently shown that PDEs interact with PKAR to initiate the termination phase of the cAMP signaling pathway. While the steps in the activation phase are well understood, steps in the termination pathway are unknown...

Here, we chronologically analyzed age-associated changes of cAMP- and MAPK-signaling in Leydig cells (LCs) in relation with decreased testosterone (T) production. In Wistar rats, decreased serum T observed in 12 to 24-month-old rats was not related to decreased serum LH concentration but to reduced luteinizing hormone receptor (Lhr/LHR) and time-coordinated reduction of steroidogenic gene expression (decreased Cyp11a1, Cyp17a1 in 12-month-old rats followed by decreased Star/StAR, Hsd3b/HSD3B, Hsd17b4, and increased Cyp19a1 later in life)...

By using EST database from a full-length cDNA library of Curvularia lunata, we have isolated a 2.9 kb cDNA, termed PKAr. An ORF of 1,383 bp encoding a polypeptide of 460 amino acids with molecular weight 50.1 kDa, (GeneBank Acc. No. KF675744) was cloned. The deduced amino acid sequence of the PKAr shows 90 and 88 % identity with cAMP-dependent protein kinase A regulatory subunit from Alternaria alternate and Pyrenophora tritici-repentis Pt-1C-BFP, respectively. Database analysis revealed that the deduced amino acid sequence of PKAr shares considerable similarity with that of PKA regulatory subunits in other organisms, particularly in the conserved regions...

Pulses of insulin released from pancreatic β-cells maintain blood glucose in a narrow range, although the source of these pulses is unclear. We and others have proposed that positive feedback mediated by the glycolytic enzyme phosphofructokinase-1 (PFK1) enables β-cells to generate metabolic oscillations via autocatalytic activation by its product fructose 1,6-bisphosphate (FBP). Although much indirect evidence has accumulated in favor of this hypothesis, a direct measurement of oscillating glycolytic intermediates has been lacking...

Ammonium secreted by the post-harvest pathogen Colletotrichum gloeosporioides during host colonization accumulates in the host environment due to enhanced fungal nitrogen metabolism. Two types of ammonium transporter-encoding genes, AMET and MEP, are expressed during pathogenicity. Gene disruption of AMET, a gene modulating ammonia secretion, showed twofold reduced ammonia secretion and 45% less colonization on avocado fruit, suggesting a contribution to pathogenicity. MEPB, a gene modulating ammonium transport, is expressed by C...

After a period of stepping on a rotating platform, blindfolded subjects demonstrate a tendency to unconsciously turn when stepping in place, an after-effect known as podokinetic after-rotation (PKAR). Recent studies have also reported a change in postural orientation following the adaptive period and have suggested that this is causally related to PKAR. Here, we assess changes in trunk orientation following platform adaptation and determine their relationship to PKAR. Specifically, we determine whether a reorganized standing posture causes PKAR...

Podokinetic after-rotation (PKAR) is a phenomenon in which subjects inadvertently rotate when instructed to step in place after a period of walking on a rotating treadmill. PKAR has been shown to transfer between different forms of locomotion, but has not been tested in a non-locomotor task. We conducted two experiments to assess effects of PKAR on perception of subjective straight ahead and on quiet standing posture. Twenty-one healthy young right-handed subjects pointed to what they perceived as their subjective straight ahead with a laser pointer while they were recorded by a motion capture system both before and after a training period on the rotating treadmill...

Aspergillus fumigatus is an opportunistic pathogen that causes 90% of invasive aspergillosis (IA) due to Aspergillus genus, with a 50-95% mortality rate. It has been postulated that certain virulence factors are characteristic of A. fumigatus, but the "non-classical" virulence factors seem to be highly variable. Overall, published studies have demonstrated that the virulence of this fungus is multifactorial, associated with its structure, its capacity for growth and adaptation to stress conditions, its mechanisms for evading the immune system and its ability to cause damage to the host...

In this study, the applicability of fluorescently labeled adenosine analogue-oligoarginine conjugates (ARC-Photo probes) for monitoring of protein kinase A (PKA) activity in living cells was demonstrated. ARC-Photo probes possessing subnanomolar affinity towards the catalytic subunit of PKA (PKAc) and competitive with the regulatory subunit (PKAr), penetrate cell plasma membrane and associate with PKAc fused with yellow fluorescent protein (PKAc-YFP). Detection of inter-molecular Förster resonance energy transfer (FRET) efficiency between the fluorophores of the fusion protein and ARC-Photo probe can be used for both the evaluation of non-labeled inhibitors of PKAc and for monitoring of cAMP signaling via detection of changes in the activity of PKA as a cAMP downstream effector...

After stepping in place on a rotating treadmill, individuals exhibit involuntary turning in the direction opposite treadmill rotation when stepping in place on a stationary surface without vision. This response is called podokinetic after-rotation (PKAR). It remains unclear where the control center for PKAR is located and whether separate, independent podokinetic control centers exist for each lower limb. To better understand neural mechanisms underlying locomotor trajectory adaptation, this study asked whether PKAR transfers between lower limbs...

Active countercircling on a rotating platform for 15 min causes individuals to involuntarily circle in the same direction when they step in place on firm ground. This is referred to as podokinetic after-rotation (PKAR). It is unclear how interjecting brief periods of visual or haptic inputs for a stable orientation reference affects PKAR. The authors studied this issue in 16 healthy individuals who participated in three sessions each. Following active countercircling, participants attempted to step in place for 30 min on firm ground...

Proper regulation of the cyclic AMP-dependent protein kinase (PKA) pathway is required for normal growth and development in many fungi. We have reported that deletion of the PKA regulatory subunit gene, pkaR, in Aspergillus fumigatus leads to defects in germination and a hypersensitivity of conidia to oxidative stress. In this study, we further analyzed the defects of DeltapkaR conidia and found that a large proportion were abnormally larger than wild type. Because swelling and increased susceptibility to oxidative stress are characteristic of germinating conidia, we analyzed the metabolic activity of the conidia by mitochondrial staining...

Stepping in place on a rotating platform for a period of 15 minutes induces an adaptive response, podokinetic after-rotation (PKAR), which causes a blindfolded individual to inadvertently rotate when attempting to step in place on the floor. The purpose of this investigation was to determine whether lower extremity load receptors were involved in this adaptation. As load receptor input is critical for locomotion, we hypothesized that manipulating load via body weight support (BWS) would influence PKAR. Eleven healthy female volunteers performed 15 minutes of stepping in place on a rotating treadmill (stimulation), followed by 10 minutes of stepping in place (response) without vision on a stationary surface...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death. Smoking, diabetes, and pancreatitis are risk factors. It has been shown that the growth of PDAC and pancreatic duct epithelial cells is regulated by beta-adrenoreceptors (beta-ARs). The activity of beta-ARs in the central nervous system is counteracted by gamma-aminobutyric acid (GABA) via GABA B receptor-mediated inhibition of adenylyl cyclase. The aim of the study was to investigate if GABA B R inhibits beta-AR signaling in PDAC and pancreatic duct epithelial cells, thus blocking driving forces of cancer progression, such as cell proliferation and cell migration...

Following stepping in place on a rotating treadmill, subjects inadvertently rotate when asked to step in place without vision. This response is called podokinetic after-rotation (PKAR). The purpose of this study was to determine whether PKAR transfers across tasks with different lower limb configurations, that is, from kneeling to stepping. We hypothesized that PKAR would transfer from kneeling to stepping for two reasons. First, there have been several demonstrations of robust PKAR transfer from forward to backward walking, stepping to hopping, running to walking, and from one limb to another...

Walking on a rotating platform for 15 min causes healthy subjects to involuntarily turn when walking without vision. This adaptive response, called podokinetic after-rotation (PKAR), uses the same kinematic patterns as voluntary turning suggesting that PKAR and voluntary turning share common mechanisms. The purpose of this study is to determine whether people with Parkinson disease (PD), a condition that produces substantial disability from turning difficulties, can adapt to the rotating platform. Initial testing of people with PD revealed that most were unable to step on the rotating platform for 15 continuous minutes...

Aspergillus fumigatus is an important opportunistic fungal pathogen. The cAMP-dependent protein kinase (PKA) signaling pathway plays an important role in regulating morphology, growth, and virulence in a number of fungal pathogens of plants and animals. We have constructed a mutant of A. fumigatus that lacks the regulatory subunit of PKA, pkaR, and analyzed the growth and development, sensitivity to oxidative damage, and virulence of the mutant, along with those of the wild type and a complemented mutant. Both growth and germination rates of the mutant are reduced, and there are morphological abnormalities in conidiophores, leading to reduced conidiation...

We examined the kinematics of voluntary turning in place at three different speeds and of inadvertent turning in place during attempts to step in place following stepping on a rotating disc (podokinetic after-rotation, PKAR). We hypothesized that voluntary turning in place, like online turning during walking, would be characterized by a top-down sequence of yaw rotations in the direction of the turn, i.e. the head would rotate first, followed by the trunk and then the foot. We also hypothesized that in place PKAR would be characterized by a bottom-up sequence of yaw rotations, i...

After prolonged stepping in place relative to space over the center of a rotating turntable, blindfolded subjects cannot step on the stationary platform without unknowingly turning themselves relative to space, a phenomenon termed podokinetic after rotation (PKAR). We asked what role the resulting vestibular stimulation might play in the expression of this form of PKAR. A method of servo-stabilizing the body relative to space during PKAR was devised to compare PKAR expression with and without significant vestibular stimulation...