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S Joseph

Publications and source records attributed to S Joseph.

At least 37 records · Page 2Linked to original sources
PubMed2001

Identification of molecular interactions between P-site tRNA and the ribosome essential for translocation.

Translocation of the tRNA-mRNA complex is a fundamental step in the elongation cycle of protein synthesis. Our studies show that the ribosome can translocate a P-site-bound tRNA(Met) with a break in the phosphodiester backbone between positions 56 and 57 in the TPsiC-loop. We have used this fragmented P-site-bound tRNA(Met) to identify two 2'-hydroxyl groups at positions 71 and 76 in the 3'-acceptor arm that are essential for translocation. Crystallographic data show that the 2'-hydroxyl group at positions 71 and 76 contacts the backbone of 23S rRNA residues 1892 and 2433-2434, respectively, in the ribosomal E site. These results establish a set of functional interactions between P-site tRNA and 23S rRNA that are essential for translocation.

Base Sequence↗
PubMed2001

Electrostatics of nanosystems: application to microtubules and the ribosome.

Evaluation of the electrostatic properties of biomolecules has become a standard practice in molecular biophysics. Foremost among the models used to elucidate the electrostatic potential is the Poisson-Boltzmann equation; however, existing methods for solving this equation have limited the scope of accurate electrostatic calculations to relatively small biomolecular systems. Here we present the application of numerical methods to enable the trivially parallel solution of the Poisson-Boltzmann equation for supramolecular structures that are orders of magnitude larger in size. As a demonstration of this methodology, electrostatic potentials have been calculated for large microtubule and ribosome structures. The results point to the likely role of electrostatics in a variety of activities of these structures.

Algorithms↗
PubMed2001

An attenuated herpes vaccine may protect Gyr hybrids from fatal inclusion body hepatitis. A preliminary report.

Four Gyr hybrids were used for this falcon herpes vaccine experiment. Three falcons were given 1 ml of an attenuated falcon herpesvirus vaccine (DuFaHe) subcutaneously twice within 14 days, whereas the fourth falcon was used as a control. Eighteen days after the booster vaccination, all four Gyr hybrids were intranasally and ocularly challenged with a virulent low-passage falcon herpesvirus. The control falcon died 9 days after challenge with typical lesions of herpesvirus inclusion body hepatitis. The three vaccinated falcons seroconverted and did not show any symptoms. Following the challenge their antibody titres to falcon herpesvirus increased. No herpesvirus was isolated from any of the cloacal swabs taken during this experiment, indicating that there was no danger for any other birds from DuFaHe. This experiment shows that falcons can be protected from herpesvirus infection by an attenuated herpesvirus vaccine. However, it should be stressed that only four falcons were used for this experiment.

Animals↗
PubMed2001

Convergent validity of the Depression-Happiness Scale with the Memorial University of Newfoundland Scale of Happiness.

The Depression-Happiness Scale and the Memorial University of Newfoundland Scale of Happiness were administered to 52 Northern Irish university students. Higher scores on the Depression-Happiness Scale were significantly associated with higher scores on the Memorial University of Newfoundland Scale and the subscale scores of Positive Affect and Positive Experiences and with lower scores on Negative Affect and Negative Experiences. These data provide further support for the convergent validity of the Depression-Happiness Scale.

Adult↗
PubMed2001

Selective intra arterial thrombolysis in acute carotid territory stroke.

The safety and efficacy of selective intraarterial administration of urokinase in five male patients, (age range 30 to 65 years, mean 41.2 years), with occlusive stroke involving the carotid territory and a normal cranial computed tomography scan was evaluated. The time elapsed before treatment ranged from one to 10 hours. Digital subtraction angiography disclosed distal internal carotid artery occlusion in one patient and occlusion of the middle cerebral artery or its branches in the others. The urokinase dose ranged from 120,000 to 500,000 units. In two patients who received thrombolytic treatment within three hours of the onset of symptoms, there was a 100% recanalisation associated with excellent neurological recovery. In the remaining three patients, recanalisation rate varied from 0 to 50% with partial recovery in two and no recovery in one patient. None had a haemorrhagic transformation of the infarct. Although no firm conclusions can be drawn because of the small number of patients studied, selective intraarterial urokinase therapy appears to be safe and useful in patients with carotid territory stroke if undertaken early. Only through a multicenter, randomized, controlled trial, enough number of patients can be recruited to verify these observations.

Acute Disease↗
PubMed2001

Neurocysticercosis: a clinical and radiological appraisal from Kerala State, South India.

OBJECTIVES: Little has been published on Neurocysticercosis (NCC) in the State of Kerala, South India. This study was conducted to describe the clinical and radiological features of NCC in Kerala and also to study the frequency of NCC as seen in a tertiary referral setting. MATERIALS AND METHODS: We evaluated retrospectively 11 patients who were admitted with a diagnosis of NCC from 1986 to 1998. A pre-abstracted proforma containing detailed demographic data, dietary habits, clinical features and history of travel outside Kerala and neuroimaging findings were obtained from patient records and the data was tabulated and analysed. Follow up assessment was made three months after treatment. RESULTS: There were a total of 11 patients, including nine males and two females in the age range of 24 to 62 years and a mean age of 35.2 years. All were nonvegans, only 36% were pork eaters while 18% claimed consumption of salads and uncooked vegetables. 55% of patients were migrants. Migrants were defined as those who lived outside the state of Kerala for more than six months. Seizure was the most common presenting complaint and occurred in all patients (100%). Multiple ring enhancing lesions were seen on computerised tomography (CT) and magnetic resonance imaging (MRI) scans in 60%. Calcified lesions were noted in two patients. An isolated instance of miliary or disseminated cysticercosis with subcutaneous nodules and multiple brain lesions in MRI scan was observed. All patients received anticysticercal therapy besides anticonvulsants. CONCLUSIONS: It appears that NCC is rather uncommon in Kerala. Better socioeconomic status, high literacy rate, improved sanitation and health care in the state of Kerala could be reasons for this observation. A prospective case-control study of NCC in Kerala is needed to study these factors.

Adult↗
PubMed2000

Conformational changes in the ribosome induced by translational miscoding agents.

Ribosomes are dynamic complexes responsible for translating the genetic information encoded in mRNAs to proteins. The accuracy of this process is vital to the survival of an organism, and is often compromised by translational miscoding agents. Aminoglycosides are a group of miscoding agents that bind to the ribosome and reduce the fidelity of translation. Previous studies have shown that aminoglycosides alter the higher order structure of the ribosome. Here, we used a toeprinting assay to how that streptomycin, neomycin, kanamycin, gentamycin, and hygromycin B trigger conformational changes within Escherichia coli ribosome. Miscoding agents viomycin and 30% ethanol also cause similar structural changes within the ribosome. In contrast, antibiotics that do not cause miscoding, such as tetracycline, chloramphenicol, erythromycin, fusidic acid and spectinomycin, do not induce the conformational changes triggered by miscoding agents. Furthermore, ribosomes isolated from strains that are either streptomycin resistant or dependent for growth do not show these conformational changes in the presence of streptomycin. These results correlate structural changes in the ribosome induced by miscoding agents in vitro with their in vivo phenotype.

Anti-Bacterial Agents↗
PubMed2000

Increased marine production of N2O due to intensifying anoxia on the Indian continental shelf.

Eutrophication of surface waters and hypoxia in bottom waters has been increasing in many coastal areas, leading to very large depletions of marine life in the affected regions. These areas of high surface productivity and low bottom-water oxygen concentration are caused by increasing runoff of nutrients from land. Although the local ecological and socio-economic effects have received much attention, the potential contribution of increasing hypoxia to global-change phenomena is unknown. Here we report the intensification of one of the largest low-oxygen zones in the ocean, which develops naturally over the western Indian continental shelf during late summer and autumn. We also report the highest accumulations yet observed of hydrogen sulphide (H2S) and nitrous oxide (N2O) in open coastal waters. Increased N2O production is probably caused by the addition of anthropogenic nitrate and its subsequent denitrification, which is favoured by hypoxic conditions. We suggest that a global expansion of hypoxic zones may lead to an increase in marine production and emission of N2O, which, as a potent greenhouse gas, could contribute significantly to the accumulation of radiatively active trace gases in the atmosphere.

Atmosphere↗
PubMed2000

HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells.

Non-classical MHC class I molecule HLA-E is the ligand for CD94/NKG2 NK cell receptors. Surface expression of HLA-E requires binding of specific HLA class I leader sequences. The uterine mucosa in early pregnancy (decidua) is infiltrated by large numbers of NK cells, which are closely associated with placental trophoblast cells. In this study we demonstrate that trophoblast cells express HLA-E on their cell surface in addition to the previously reported expression of HLA-G and HLA-C. Furthermore, we show that the vast majority of decidual NK cells bind to HLA-E tetrameric complexes and this binding is inhibited by mAb to CD94. Thus, recognition of fetal HLA-E by decidual NK cells may play a key role in regulation of placentation. The functional consequences of decidual NK cell interaction were investigated in cytotoxicity assays using polyclonal decidual NK cells. The overall effect of CD94/NKG2 interaction with HLA-E is inhibition of cytotoxicity by decidual NK cells. However, since decidual NK cells are unable to kill trophoblast even in the presence of mAb to MHC class I molecules and NK cell receptors, HLA-E interaction with CD94/NKG2 receptors may regulate other functions besides cytolysis during implantation.

Antigens, CD↗
PubMed2000

Immune responses during the acute stages of infection with the intestinal trematode Echinostoma caproni.

This study investigated the nature of the immune response of C57BL/6 mice infected with the trematode Echinostoma caproni. To determine the preferential development of either a Th1 or Th2 cytokine pattern during early stages of infection, cytokine production by spleen and mesenteric lymph node (MLN) cells during the first 3 weeks of infection was followed. Whereas spleen cells failed to respond to antigen stimulation, MLN cells produced IFN-gamma and to a lesser extent IL-4. IL-5 levels were elevated throughout the period studied. The humoral response was consistent with a Th1 cytokine pattern as antigen-specific IgG2a antibodies were preferentially developed. We investigated whether IFN-gamma is critical for establishment of E. caproni infection. Worm burden in infected mice treated with a single injection of anti-IFN-gamma mAb was significantly reduced compared to that of animals treated with a control antibody.

Animals↗
PubMed2000

Calculation of the relative geometry of tRNAs in the ribosome from directed hydroxyl-radical probing data.

The many interactions of tRNA with the ribosome are fundamental to protein synthesis. During the peptidyl transferase reaction, the acceptor ends of the aminoacyl and peptidyl tRNAs must be in close proximity to allow peptide bond formation, and their respective anticodons must base pair simultaneously with adjacent trinucleotide codons on the mRNA. The two tRNAs in this state can be arranged in two nonequivalent general configurations called the R and S orientations, many versions of which have been proposed for the geometry of tRNAs in the ribosome. Here, we report the combined use of computational analysis and tethered hydroxyl-radical probing to constrain their arrangement. We used Fe(II) tethered to the 5' end of anticodon stem-loop analogs (ASLs) of tRNA and to the 5' end of deacylated tRNA(Phe) to generate hydroxyl radicals that probe proximal positions in the backbone of adjacent tRNAs in the 70S ribosome. We inferred probe-target distances from the resulting RNA strand cleavage intensities and used these to calculate the mutual arrangement of A-site and P-site tRNAs in the ribosome, using three different structure estimation algorithms. The two tRNAs are constrained to the S configuration with an angle of about 45 degrees between the respective planes of the molecules. The terminal phosphates of 3'CCA are separated by 23 A when using the tRNA crystal conformations, and the anticodon arms of the two tRNAs are sufficiently close to interact with adjacent codons in mRNA.

Anticodon↗
PubMed2000

Psychometric evaluation of Horowitz's Impact of Event Scale: a review.

Despite being developed before the formal introduction of posttraumatic stress disorder (PTSD) within the diagnostic literature, the Impact of Event Scale (Horowitz, Wilner, & Alvarez, 1979) remains one of the most widely used self-report measures of posttraumatic stress. This paper presents an overview of research using the IES in an attempt to assess its psychometric status. It is concluded that the psychometric properties of the IES are satisfactory (although not as a PTSD diagnostic measure) and that continued use of the IES as a measure of intrusive and avoidant processes is warranted.

Defense Mechanisms↗
PubMed2000

Surface expression of HLA-C antigen by human extravillous trophoblast.

In this paper definitive evidence that the classical class I product, HLA-C, is expressed on the surface of normal trophoblast cells is provided. HLA-C transcripts were sequenced from cDNA isolated from first trimester trophoblast cells obtained by flow cytometric sorting. Both paternal and maternal alleles were transcribed. HLA-C proteins were demonstrated by biochemical analysis and found on the cell surface in association with beta(2)-microglobulin. Upregulation of cell surface HLA-C but not HLA-G expression after interferon (IFN)-gamma treatment was demonstrated by flow cytometric analysis. Immunohistology has confirmed HLA-C is expressed by all extravillous subpopulations in vivo. The question of whether trophoblast HLA-C molecules interact with decidual NK cells expressing killer Ig-like receptors (KIR) has also been addressed. Our results demonstrate that extravillous trophoblast expresses at least two HLA class I molecules, HLA-G and HLA-C on the cell surface.

Adult↗
PubMed2000

Evidence of functional somatotopy in GPi from results of pallidotomy.

The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian 'off' signs and levodopa-induced dyskinesias (LID). We found significant positive correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID. We also found a highly significant correlation (P: < 0.0001, r = 0.8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian 'off' signs. The volumes of the total lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian 'off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian 'off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian 'off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian 'off' signs and dyskinesias. Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPi could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable.

Dyskinesia, Drug-Induced↗
PubMed2000

The Herald of Free Enterprise disaster. Lessons from the first 6 years.

A substantial body of data has been collected on survivors of the Herald of Free Enterprise disaster over the first 6 years. These data show the psychological effects to be considerable, and although they appear to decrease over time, 6 years later there remains a substantial minority that remains highly distressed. Our research has also pointed to those factors that appear to be important in determining the severity and chronicity of symptoms. Levels of crisis support early on seem to be protective. Not everyone has access to supportive others, and these people would seem to be at increased risk of disturbance. But even if crisis support is potentially available from family and friends, not everyone is in a position to draw on these resources. Those individuals who possess negative attitudes toward emotional expression might be less likely to seek out support. Evidence would suggest that modifying such attitudes might be an important component of intervention. A further target for intervention would seem to be the causal attributions made by survivors. It was found that those who perceived the causes of events during the disaster as internal and controllable were at greatest risk of psychological disturbance. The data gathered in the wake of this disaster suggest that intervening early with respect to these three components (crisis support, attitude to emotional expression, and attributional style) is highly likely to mitigate against long-term distress.

Adaptation, Psychological↗
PubMed2000

Attitudes towards emotional expression, relational competence and psychological distress.

The association between life events and psychological distress was found to be mediated by attitudes towards emotional expression for those with low social support but not for those with high social support. Passive interpersonal behaviour significantly accounted for additional variance in psychological distress to that accounted for by life events and attitudes.

Adult↗
PubMed2000

Attitudes towards emotional expression: factor structure, convergent validity and associations with personality.

The aim of the present study was to investigate the structure of the Attitudes towards Emotional Expression scale (AEE), its convergent validity with the Ambivalence over Emotional Expressiveness Questionnaire (AEQ), and its association with the Big 5 personality dimensions. The AEE was found to consist of four clearly identifiable factors, which loaded together on a higher order single factor. Higher scores on the AEE were associated with higher scores on the AEQ. Regression of scores on the AEE onto the Big 5 personality dimensions showed that scores on the AEE were associated with agreeableness, extraversion, and openness to experience.

Adolescent↗