Identification and Characterisation of a Novel Acylpeptide Hydrolase from Sulfolobus Solfataricus: Structural and Functional Insights

A novel acylpeptide hydrolase, named APEH-3Ss, was isolated from the hypertermophilic archaeon Sulfolobus solfataricus. APEH is a member of the prolyl oligopeptidase family which catalyzes the removal of acetylated amino acid residues from the N terminus of oligopeptides. The purified enzyme shows a homotrimeric structure, unique among the associate partners of the APEH cluster and, in contrast to the archaeal APEHs which show both exo/endo peptidase activities, it appears to be a “true” aminopeptidase as exemplified by its mammalian counterparts, with which it shares a similar substrate specificity. Furthermore, a comparative study on the regulation of apeh gene expression, revealed a significant but divergent alteration in the expression pattern of apeh-3Ss and apehSs (the gene encoding the previously identified APEHSs from S. solfataricus), which is induced in response to various stressful growth conditions. Hence, both APEH enzymes can be defined as stress-regulated proteins which play a complementary role in enabling the survival of S. solfataricus cells under different conditions. These results provide new structural and functional insights into S. solfataricus APEH, offering a possible explanation for the multiplicity of this enzyme in Archaea

Protoporphyrin IX enhancement by 5-aminolaevulinic acid peptide derivatives and the effect of RNA silencing on intracellular metabolism

Intracellular generation of the photosensitiser, protoporphyrin IX, from a series of dipeptide derivatives of the haem precursor, 5-aminolaevulinic acid (ALA), was investigated in transformed PAM212 murine keratinocytes, together with studies of their intracellular metabolism. Porphyrin production was substantially increased compared with equimolar ALA using N-acetyl terminated phenylalanyl, leucinyl and methionyl ALA methyl ester derivatives in the following order: Ac-L-phenylalanyl-ALA-Me, Ac-L-methionyl-ALA-Me and Ac-L-leucinyl-ALA-Me. The enhanced porphyrin production was in good correlation with improved photocytotoxicity, with no intrinsic dark toxicity apparent. However, phenylalanyl derivatives without the acetyl/acyl group at the N terminus induced significantly less porphyrin, and the replacement of the acetyl group by a benzyloxycarbonyl group resulted in no porphyrin production. Porphyrin production was reduced in the presence of class-specific protease inhibitors, namely serine protease inhibitors. Using siRNA knockdown of acylpeptide hydrolase (ACPH) protein expression, we showed the involvement of ACPH, a member of the prolyl oligopeptidase family of serine peptidases, in the hydrolytic cleavage of ALA from the peptide derivatives. In conclusion, ALA peptide derivatives are capable of delivering ALA efficiently to cells and enhancing porphyrin synthesis and photocytotoxicity; however, the N-terminus state, whether free or substituted, plays an important role in determining the biological efficacy of ALA peptide derivatives

Effects of gymnastics expertise on the perception of body orientation in the pitch dimension.

The purpose of this study was to investigate how experts in motor skills requiring a fine postural control perceive their body orientation with few gravity based sensory cues. In Experiment 1, expert gymnasts and controls had to detect their body tilt when pitching at a velocity of 0.05 deg.s(-1), in two conditions of body restriction (strapped and body cast altering the somatosensory cues). Contrary to the experts, the controls exhibited a larger body tilt when totally restrained in the body cast. In Experiment 2, subjects had to estimate their Subjective Postural Vertical (SPV) starting from different angles of pitch tilt. The controls exhibited significant errors of SPV judgement whereas the experts were very precise. These results suggest that 1) somatosensory cues are more informative than otolithic cues for the perception of body orientation, and 2) the efficiency of otolithic and/or interoceptive inputs can be improved through a specific training to compensate for the lack of somatosensory cues

Effects of gymnastics expertise on the perception of body orientation in the pitch dimension.

The purpose of this study was to investigate how experts in motor skills requiring a fine postural control perceive their body orientation with few gravity based sensory cues. In Experiment 1, expert gymnasts and controls had to detect their body tilt when pitching at a velocity of 0.05 deg.s(-1), in two conditions of body restriction (strapped and body cast altering the somatosensory cues). Contrary to the experts, the controls exhibited a larger body tilt when totally restrained in the body cast. In Experiment 2, subjects had to estimate their Subjective Postural Vertical (SPV) starting from different angles of pitch tilt. The controls exhibited significant errors of SPV judgement whereas the experts were very precise. These results suggest that 1) somatosensory cues are more informative than otolithic cues for the perception of body orientation, and 2) the efficiency of otolithic and/or interoceptive inputs can be improved through a specific training to compensate for the lack of somatosensory cues

Effects of gymnastics expertise on the perception of body orientation in the pitch dimension.

The purpose of this study was to investigate how experts in motor skills requiring a fine postural control perceive their body orientation with few gravity based sensory cues. In Experiment 1, expert gymnasts and controls had to detect their body tilt when pitching at a velocity of 0.05 deg.s(-1), in two conditions of body restriction (strapped and body cast altering the somatosensory cues). Contrary to the experts, the controls exhibited a larger body tilt when totally restrained in the body cast. In Experiment 2, subjects had to estimate their Subjective Postural Vertical (SPV) starting from different angles of pitch tilt. The controls exhibited significant errors of SPV judgement whereas the experts were very precise. These results suggest that 1) somatosensory cues are more informative than otolithic cues for the perception of body orientation, and 2) the efficiency of otolithic and/or interoceptive inputs can be improved through a specific training to compensate for the lack of somatosensory cues

Perception of slow pitch and roll body tilts in bilateral labyrinthine-defective subjects

The aim of the present study was to examine whether the perception of slow body tilts in total darkness was affected by a complete loss of vestibular function. Four blindfolded bilateral labyrinthine-defective subjects (LDs) and 12 normal subjects (Normals) were seated and immobilized with large straps against the back of a rotating L-shaped platform, and were passively displaced from the upright at 0.05 degrees x s(-1) in the pitch and roll dimensions. Subjects were asked to detect the slow change in their body orientation, by indicating as soon as possible the direction of tilt. After a brief period of practice observed for all LDs at the beginning of the session, results showed no significant difference between LDs and Normals in the mean detection threshold recorded for each direction of tilt. The mean perceptual threshold was 4.4 versus 5.1 degrees in the roll dimension, and 6.1 versus 6.1 degrees in the pitch dimension, for the LDs and Normals, respectively. These findings indicate that the accurate perception of body orientation in quasi-static conditions is mainly allowed by somatosensory information rather than by otolithic input

Accuracy level of pointing movements performed during slow passive whole-body rotations.

Seated observers requested to detect low-velocity passive rotations show a high motion-detection threshold. However, when standing on a slowly rotating platform, their equilibrium is preserved, suggesting that cognitive sensing and sensorimotor reactions do not share the same central processes. The present experiments investigated the ability of observers seated on a slowly rotating chair in total darkness to indicate with their hand the position of briefly flashed targets (Experiment 1) and to indicate the subjective horizon with an outstretched arm (Experiment 2) or with a target driven by a joystick (Experiment 3). The overall hypothesis stated that egocentric coding of the position of a target should not be affected by sensing or not-sensing body rotation (Experiment 1), while geocentric positioning may (Experiments 2 and 3). Our data partially supported the hypothesis. Subjects pointed accurately to the memorized targets (Experiment 1), whereas misperception of body orientation was a source of inaccuracy for actions referred to a geocentric frame (Experiments 2 and 3). More interestingly, subjects' perceptions changed as a single, smooth, and monotonic function of tilt, independent of whether the perception of body orientation was present or not

Contribution of ankle, knee, and hip joints to the perception threshold for support surface rotation.

The purpose of the present experiment was to investigate the extent to which subjects can perceive, at very slow velocities, an angular rotation of the support surface about the medio-lateral axis of the ankle, knee, hip, or neck joint when visual cues are not available. Subjects were passively displaced on a slowly rotating platform at .01, .03, and .05 deg/sec. The subjects' task was to detect movements of the platform in four different postural conditions allowing body oscillations about the ankle, knee, hip, or neck joint. In Experiment 1, subjects had to detect backward and forward rotation (pitching). In Experiment 2, they had to detect left and right rotations of the platform (rolling). In Experiment 3, subjects had to detect both backward/forward and left/right rotations of the platform, with the body fixed and the head either fixed or free to move. Overall, when the body was free to oscillate about the ankle, knee, or hip joints, a similar threshold for movement perception was observed. This threshold was lower for rolling than for pitching. Interestingly, in these postural conditions, an unconscious compensation in the direction opposite to the platform rotation was observed on most trials. The threshold for movement perception was much higher when the head was the only segment free to oscillate about the neck joint. These results suggest that, in static conditions, the otoliths are poor detectors of the direction of gravity forces. They also suggest that accurate perception of body orientation is improved when proprioceptive information can be dynamically integrated

Knowledge Regarding Prevention and Management of Cervical Cancer Among Women in Amala Institute of Medical Sciences, Thrissur

These days cervical cancer is the most common cancer among Indian women of reproductive age. Unfortunately, despite the availability of methods for prevention, most of the women remain unscreened. More than 60-70% of cancers are diagnosed in later stages with poor survival rate. Reasons for unscreening include lack of awareness of risk factors, symptoms and prevention, stigma and misconceptions about gynecological diseases and lack of national cervical cancer screening guidelines and policies. In order to reduce the incidence women should possess adequate knowledge and understanding about cervical cancer, its causes, signs and symptoms, early diagnostic measures, management and the preventive measures. The present study was aimed to assess the knowledge regarding prevention and management of cervical cancer among women in Amala Institute of Medical Sciences, Thrissur. The objectives of study were to assess the knowledge regarding prevention and management of cervical cancer among women, to determine the association of level of knowledge with selected baseline variables, and to prepare a pamphlet on prevention and management of cervical cancer. The research approach was quantitative and the research design adopted was descriptive design. Fifty women were selected by convenience sampling technique. Data was collected using structured questionnaire to assess the knowledge on prevention and management of cervical cancer and to assess the baseline line variables. The results showed that out of total 50 samples, 28 (56%) had poor knowledge level, 15 (30%) had average knowledge level, 6 (12%) had very poor knowledge level, 1 (2%) had good knowledge level and nobody had very good knowledge level