Biomedical subjects

Mohammad Ghafouri

Publications and source records attributed to Mohammad Ghafouri.

6 recordsLinked to original sources

PubMed2006

The role of Vpr in the regulation of HIV-1 gene expression.

Expression of the viral protein R, Vpr, of HIV-1 affects many biological events in host cells including cell cycle progression, and modulates HIV-1 gene transcription. Earlier studies implicating the cellular protein p21(WAF1) (p21) in regulation of HIV-1 transcription, led us to investigate the functional and physical interaction of Vpr and p21. Our results show that Vpr modestly activated HIV-LTR in cells lacking p21 gene. Here, we describe the mechanisms by which p21 and Vpr leading to stimulation of HIV-1 transcription. Data from the protein-protein interaction experiments revealed the ability of Vpr, p21 and p300 to form a complex. Further, we show that, Vpr interacts with the N- and the C-terminal domains of p21. Furthermore, in cells expressing Vpr, p21 localizes to both the cytoplasm and the nucleus. Interestingly, expression of Vpr alleviates p21-mediated inhibition of cell departure from G1 phase. Expression of a mutant Vpr, with arginine 73 altered to serine, did not affect the ability of p21 to cause cells arrest or its sub-cellular localization. These observations reveal a new cellular partner for Vpr, and provide a new therapeutic avenue for controlling HIV-1 expression.

Binding Sites↗

PubMed2006

HIV-1 associated dementia: symptoms and causes.

Despite the use of highly active antiretroviral therapy (HAART), neuronal cell death remains a problem that is frequently found in the brains of HIV-1-infected patients. HAART has successfully prevented many of the former end-stage complications of AIDS, however, with increased survival times, the prevalence of minor HIV-1 associated cognitive impairment appears to be rising among AIDS patients. Further, HIV-1 associated dementia (HAD) is still prevalent in treated patients as well as attenuated forms of HAD and CNS opportunistic disorders. HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV-1. In this review, we discussed the symptoms and causes leading to HAD. Outcome from this review will provide new information regarding mechanisms of neuronal loss in AIDS patients.

AIDS Dementia Complex↗

PubMed2006

Cdk9 phosphorylates p53 on serine 392 independently of CKII.

The tumor suppressor p53 is an important cellular protein, which controls cell cycle progression. Phosphorylation is one of the mechanisms by which p53 is regulated. Here we report the interaction of p53 with another key regulator, cdk9, which together with cyclin T1 forms the positive transcription elongation complex, p-TEFb. This complex cooperates with the HIV-1 Tat protein to cause the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II and this facilitates the elongation of HIV-1 transcription. We demonstrate that cdk9 phosphorylates p53 on serine 392 through their direct physical interaction. Results from protein-protein interaction assays revealed that cdk9 interacts with the C-terminal domain (aa 361-393) of p53, while p53 interacts with the N-terminal domain of cdk9. Transfection and protein binding assays (EMSA and ChIP) demonstrated the ability of p53 to bind and activate the cdk9 promoter. Interestingly, cdk9 phosphorylates serine 392 of p53, which could be also phosphorylated by casein kinase II. Kinase assays demonstrated that cdk9 phosphorylates p53 independently of CKII. These studies demonstrate the existence of a feedback-loop between p53 and cdk9, pinpointing a novel mechanism by which p53 regulates the basal transcriptional machinery.

Brain Neoplasms↗

PubMed2005

Contribution of reference frames for movement planning in peripersonal space representation.

The principal goal of our study is to gain an insight into the representation of peripersonal space. Two different experiments were conducted in this study. In the first experiment, subjects were asked to represent principal anatomical reference planes by drawing ellipses in the sagittal, frontal and horizontal planes. The three-dimensional hand-drawing movements, which were achieved with and without visual guidance, were considered as the expression of a cognitive process per se: the peripersonal space representation for action. We measured errors in the spatial orientation of ellipses with regard to the requested reference planes. For ellipses drawn without visual guidance, with eyes open and eyes closed, orientation errors were related to the reference planes. Errors were minimal for sagittal and maximal for horizontal plane. These disparities in errors were considerably reduced when subjects drew using a visual guide. These findings imply that different planes are centrally represented, and are characterized, by different errors when subjects use a body-centered frame for performing the movement and suggest that the representation of peripersonal space may be anisotropic. However, this representation can be modified when subjects use an environment-centered reference frame to produce the movement. In the second experiment, subjects were instructed to represent, with eyes open and eyes closed, sagittal, frontal and horizontal planes by pointing to virtual targets located in these planes. Disparities in orientation errors measured for pointing were similar to those found for drawing, implying that the sensorimotor representation of reference planes was not constrained by the type of motor tasks. Moreover, arm postures measured at pointing endpoints and at comparable spatial locations in drawing are strongly correlated. These results suggest that similar patterns of errors and arm posture correlation, for drawing and pointing, can be the consequence of using a common space representation and reference frame. These findings are consistent with the assumption of an anisotropic action-related representation of peripersonal space when the movement is performed in a body-centered frame.

Adult↗

PubMed2004

Initiation of rapid reach-and-grasp balance reactions: is a pre-formed visuospatial map used in controlling the initial arm trajectory?

In order to recover balance by grasping an object for support, the CNS must rapidly move the hand toward a specific target (handhold) in the environment. The early latency (80-140 ms) of these grasping reactions would seem to preclude a role for online visual feedback in the control of the initial limb movement; however, some studies have shown that vision can influence initiation of lower-limb postural reactions at similar latency. This study explored the role of vision in controlling the initial trajectory of grasping reactions triggered by sudden unpredictable medio-lateral platform translation. Healthy young adults were instructed to recover balance by grasping a marked section of a handrail, located to their right. To reinforce a dependence on arm reactions, movement of the feet was prevented by barriers. Liquid-crystal goggles were used to occlude vision during response initiation (200 ms interval starting at perturbation onset, PO). Results showed that the initial grasping trajectory (first 100 ms) and associated muscle activation were heavily modulated to take into account the direction and speed of the perturbation-induced body motion in relation to the handrail. This modulation was unaffected by occlusion of vision at PO, indicating that information about the rail location obtained prior to PO was incorporated into the control. These findings are consistent with the view that the CNS tunes the initial arm trajectory by combining an egocentric spatial map, formed prior to PO, with online feedback about the body motion from non-visual inputs (somatosensory and/or vestibular). This prevents potential delays associated with visual processing and ensures very rapid onset of arm movement that is directed appropriately even though the position of the body is perturbed unpredictably with respect to the target.

Adult↗

PubMed2002

Pointing movements may be produced in different frames of reference depending on the task demand.

Movements are likely guided by the nervous system in task-specific spatial frames of reference (FRs). We tested this hypothesis by analyzing fast arm pointing movements involving the trunk made to targets located within the reach of the arm. In the first experiment, subjects pointed to a motionless target and, in the second experiment, to a target moving synchronously with the trunk. Vision of the arm and targets was prevented before movement onset. Each experiment started after three to five training trials. In randomly selected trials of both experiments, an electromagnet device unexpectedly prevented the trunk motion. When the trunk was arrested, the hand trajectory and velocity profile remained invariant in an FR associated with the experimental room in the first or in an FR moving with the trunk in the second experiment. Substantial changes in the arm interjoint coordination in response to the trunk arrest were observed in the first but not in the second experiment. The results demonstrate the ability of the nervous system to rapidly adapt behavior at the joint level to transform motor performance from a spatial FR associated with the environment to one associated with the body. A theoretical framework is suggested in which FRs are considered as pre-existing neurophysiological structures permitting switching between different FRs and guiding multiple joints and muscles without redundancy problems.

Adult↗