Micromechanics of Biomembranes.

Micromechanics techniques are playing an increasing role in characterization of biomembranes. The mechanical properties of membranes play an important role for a whole range of cellular processes. Lipid-protein biomembranes display lateral heterogeneity, domain formation, and morphological changes at mesoscopic and nanoscopic length scales. An attempt is made to introduce how membrane's material properties can be measured. Both fluctuation analysis and micro-pipette aspiration experiments have been used to quantify the micromechanics of membranes. The relationship between the structure and function of biomembranes is a critical concern in modern biology. This overview calls for a deeper understanding of how the cell complexity might be related to the mechanical properties of the lipid-protein membrane. Mechanical properties can influence cellular response to processes like adhesion, transport, differentiation, proliferation and migration.

Tubules, beads, discs and junctions - Morphologies and dynamics of dispersed multilamellar lipid phases in excess water.

In this paper, experimental results on the swelling, dispersion and disintegration of the lamellae composed of the lipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in contact with excess water are described. Multilamellar structures nucleate and grow at the interface between the pure solvent and the lipid. The system evolves slowly via flow and coalescence of lamellae through a variety of non-equilibrium morphologies demonstrating that their dynamics is complex and non-universal, with no unique kinetic pathway. The tubular structures disintegrate slowly into the bulk water phase, inside the sealed sample chamber.

Exploring the raft-hypothesis by probing planar bilayer patches of free-standing giant vesicles at nanoscale resolution, with and without Na,K-ATPase.

The structure of functional lipid domains (rafts) in biological membranes has for long time been unresolved due to their small length scales and transient nature. These cooperative properties of the lipid bilayer matrix are modelled by free-standing giant unilammellar vesicles (GUVs) with well-characterized lipid composition. We review a series of recent advances in preparation and analysis of GUVs, which allows for characterization of small domains by high-resolution imaging techniques. These includes a new GUV preparation method with a desired overall lipid composition achieved by mixing small unilammellar vesicles (SUVs), test of the lipids compositional uniformity in GUVs and swift adsorption of GUVs to solid support by kinetically arresting the lateral structure of membrane prior to collapse for subsequent imaging. The techniques are applied to the analysis of membrane domains in GUVs formed from mixtures of DOPC/DPPC/cholesterol with and without Na,K-ATPase (NKA), a transmembrane protein known to be associated with rafts. Two mechanisms of domain formation are revealed: 1) close to lo/ld phase coexistence, domains in size up to 100nm appear as thermally induced droplet fluctuations, 2) NKA shows interfacial activity and cluster in lo/ld micro-emulsion droplets. Some perspectives for the application of the techniques and the understanding of the nature of raft domains are outlined.

Spigelian hernia.

A Spigelian hernia (or lateral ventral hernia) is a hernia through the spigelian fascia, which is the aponeurotic layer between the rectus abdominis muscle medially, and the semilunar line laterally. So far, about 1000 cases have been reported worldwide. These hernias are difficult to diagnose as they do not present with a subcutaneous swelling and have high risk of going for strangulation. We discuss the case of a 36 year old female who presented with history of pain and lumpiness in left lower abdomen, both of which decreased on lying down. She presented to emergency with an episode severe pain at same site which subsided spontaneously. Diagnosis was confirmed on CT scan, plication and onlay prolene mesh repair performed. Spigelian hernias are rare, interparietal type of hernias which have high risk undergoing strangulation. Knowledge of symptoms and signs is vital to diagnosis and treatment of these rare type of hernias.

Executive functions and cognitive deficits in schizophrenia: comparisons between probands, parents and controls in India.

BACKGROUND: Cognitive impairment is said to be a core feature of schizophrenia. Executive function is an important cognitive domain. AIM: This study was undertaken to assess cognitive impairment among Indian patients with schizophrenia (Sz) or schizoaffective disorder (SzA), compared with their parents and unaffected individuals (controls). SETTINGS AND DESIGN: Executive functions as measured by Trail-making Test (TMT), of patients and their parents were compared with controls. The patients were recruited from the Outpatients' Department (OPD) of a government hospital. MATERIALS AND METHODS: Patients diagnosed as Sz or SzA (n=172) and their parents (n=196: families n=132, 119 fathers and 77 mothers) participated. We also included 120 persons with no history of psychiatric illness. Cognitive function was assessed with the TMT. The Information Score of the Post Graduate Institute Battery of Brain Dysfunction test, developed in India for Indian subjects was used as a proxy for general fixed knowledge. STATISTICAL ANALYSIS: Logistic and linear regression was used to compare cognitive deficits of cases, parents and controls. RESULTS: Cases and their parents took significantly more time than controls on Part B of the TMT. There were no statistically significant differences between cases and parents on any of the TMT parameters. Using regression analysis, the most significant correlates of all TMT parameters among cases were with occurrence of auditory hallucinations and current age. CONCLUSION: Cases, as well as their parents showed more cognitive impairment than controls on the TMT.

Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism.

Understanding the pharmacogenetic basis of developing iatrogenic disorders such as Tardive Dyskinesia (TD) has significant clinical implications. CYP1A2, an inducible gene of the cytochrome P450 family of genes, has been suggested to contribute to the metabolism of typical antipsychotics in subjects with schizophrenia on long-term treatment, and has been considered as a potential candidate gene for development of TD. In this study, we have investigated the significance of CYP1A2 gene polymorphisms in TD susceptibility among chronic schizophrenia sufferers (n=335) from north India. TD was diagnosed in approximately 29% (96/335) of these subjects. Of the 96 TD positives, 28 had been treated with typical antipsychotics alone, 23 with atypical antipsychotics alone and 45 patients had received both classes of drugs during the course of their illness. Out of the six SNPs tested, CYP1A2(*)2, (*)4, (*)5, (*)6 were found to be monomorphic in our population. CYP1A2(*)1C and CYP1A2(*)1F were polymorphic and were analyzed in the study sample. Since these two allelic variants lead to lesser inducibility among smokers, the smoking status of TD patients was also considered for all subsequent analysis. We observed increased severity of TD among TD-Y smokers, who were carriers of CYP1A2(*)1C (G>A) variant allele and had received only typical antipsychotic drugs (F(1,8)=9.203, P=0.016). No significant association of CYP1A2(*)1F with TD was observed irrespective of the class of drug they received or their smoking status. However, we found a significant association of CYP1A2(*)1F with schizophrenia (chi(2)=6.572, df=2, P=0.037).

Association analysis of NOTCH 4 polymorphisms with schizophrenia among two independent family based samples.

The present study investigated polymorphisms of the NOTCH 4 gene in two independent samples from India and USA, consisting of patients with schizophrenia and their parents (n = 182, and n = 148 'trios,' respectively). Five DNA markers, namely (GAAG)(n), (TAA)(n), SNP1, SNP2, and (CTG)(n) were evaluated. Transmission distortion, consistent with a modest association was detected among both samples. Additional association studies at this locus are warranted.

Clinical and familial correlates of tardive dyskinesia in India and Israel.

BACKGROUND: Antipsychotic drugs are widely used for the treatment of psychosis, especially schizophrenia. Their long-term use can result at times in serious side-effects such as Tardive Dyskinesia (TD). Since over 80% of schizophrenia sufferers (lifetime prevalence 1%) receive long-term antipsychotic drug treatment, the extent of the problem is potentially large. Increasing age is the most consistently demonstrated risk factor for TD. AIMS: To assess effect of different clinical factors and demographic variables in India and Israel and sib pair concordance of Tardive Dyskinesia (TD) in India. SETTINGS AND DESIGN: The study was conducted simultaneously among Indian and Israeli subjects: ascertainment was family-based in India and hospital-based in Israel. METHODS AND MATERIAL: In India the instruments used were: Diagnostic Interview for Genetic Studies (DIGS), Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and Simpson Angus Scale (SAS). The last three instruments were also used in Israel. STATISTICAL ANALYSIS: Regression analysis and Pearson's correlation. RESULTS AND CONCLUSIONS: TD symptoms were present in 40.4% of 151 Israeli subjects and 28.7% of 334 Indian subjects. While age at onset and total scores on PANSS were significant predictors of TD in both the samples, lower scores on the Global Assessment of Functioning Scale (GAF), diagnostic sub-group and male gender were significant predictors among Indians. There was no concordance of TD symptoms among 33 affected sib-pairs from India.

Gender and procreation among patients with schizophrenia.

OBJECTIVE: Reduced procreation among men with schizophrenia has been reported consistently when compared with female patients, but the cause is unknown. Reports on Caucasian individuals predominate in the published literature. Therefore, analyses were conducted concurrently among independent Indian and US samples in the present study. METHOD: Individuals with schizophrenia or schizoaffective disorder (DSM-IV criteria) were ascertained and interviewed at New Delhi and in the northeastern United States using identical procedures (n=224 and 144, respectively). Selected indices of fertility and fecundity were compared among men and women at each site. RESULTS: In the smaller US sample, male cases were significantly more likely to be single and childless compared with female cases. They also had fewer children. In contrast, there were no significant gender differences in the larger Indian sample with regard to the reproductive indices. Multivariate analyses revealed that the indices of reproduction were associated with different variables in the US and Indian samples. Fertility (the presence or absence of offspring) was associated with gender and age in the US sample while in the Indian sample conjugal status and age were significant predictors. Fecundity (the number of offspring) was associated with gender, conjugal status and educational status in the US sample while in the Indian sample conjugal status and educational status were both significant. CONCLUSIONS: The reproductive deficit observed among US males was not observed among the Indian men. Conjugal status was a significant covariate for reproduction in both samples. The reproductive deficit may be due to difficulties in establishing long-term conjugal relationships among the US men. The differences may also reflect underlying cultural variations related to marital practices in these two countries. Our analyses suggest that the male reproductive deficit in schizophrenia is variable and may be overcome.

Family-based association studies of monoaminergic gene polymorphisms among North Indians with schizophrenia.

Associations between schizophrenia and four candidate genes were tested among Indian patients with schizophrenia and their parents (DSM-IV criteria, n = 179 families). Polymorphisms within the genes encoding the serotonin 2A receptor (HT2A), tryptophan hydroxylase (TPH), catechol-O-methyl transferase (COMT) and dopamine transporter (DAT) were thus investigated. Two polymorphisms each were analyzed at HT2A and TPH, enabling haplotype-based analyses using the transmission disequilibrium test (TDT) for these genes. No significant associations were detected. Pooled analysis of samples like ours may be necessary to definitively exclude putative allelic associations at these loci.

Association studies of cytosolic phospholipase A2 polymorphisms and schizophrenia among two independent family-based samples.

An association between the cytosolic phospholipase A2 locus (cPLA2) and schizophrenia has been reported using two polymorphic DNA markers. In an attempt to replicate these results, two independent family-based samples were ascertained from the United States and India (86 and 159 families, respectively). No significant associations were detected in either sample.

Association study of schizophrenia among Indian families.

A putative association of schizophrenia with a Msc I restriction fragment length polymorphism at the dopamine D3 receptor gene locus (DRD3) was tested among Indian families, using haplotype relative risk analysis and the transmission disequilibrium test (n=66 families and 58 sets of transmissions, respectively). A significant association either with homozygosity or with allele 1 at the biallelic polymporphism could not be detected.

A Hindi version of the Diagnostic Interview for Genetic Studies.

The validity of a Hindi version of the Diagnostic Interview for Genetic Studies (DIGS) was investigated. The original English version was initially translated into Hindi. The Hindi version was then back-translated and compared with the original. Next, a group of psychiatric inpatients and outpatients were interviewed using the Hindi version. The resultant diagnoses were compared with those obtained for the same patients using a Hindi version of the Present State Examination (PSE), and the clinical diagnoses given by the treating psychiatrists. The DIGS diagnoses were significantly correlated with both the PSE diagnoses (Cohen's kappa = 0.80) and the clinical diagnoses (kappa = 0.56). Interrater reliability between three interviewers for diagnoses obtained using the Hindi version of the DIGS varied (kappa = 0.45-1.00). Possible causes for this variability are discussed. The Hindi version of the DIGS fulfills the need for a current comprehensive interview schedule not only for psychiatric genetic research in India, but also for nongenetic research.

Dissemination of Salmonella in broiler-chicken operations.

Dissemination of Salmonella from hatchery to broiler farm and from broiler farm to processing plant was assessed. Bacteriological examination of fluff and meconium at the hatchery, feed and litter at the farm, and carcass rinsing at the plant level was conducted. When fluff and/or meconium were contaminated with Salmonella, litter and carcasses were contaminated with the same serotypes. Properly pelleted feed does not seem to be an important source of infection. Stress (feed and water deprivation) and some effect on shedding of Salmonella. Fluff and meconium at hatchery, feces from 3-to-7-day-old chicks, and litter at 3 and 6 weeks can be used as an indicator of flock infection and thus carcass contamination.

Hindi stop consonants: an acoustic and fiberscopic study.

Fiberscopic films and audio recordings were made of two native speakers of Hindi, producing # Ci, iCi, iC # utterances where C was one of the four types of stops and affricates. The voiced unaspirated type showed voicing through the whole consonant and no ab-/adduction gesture. The other three types, in the intervocalic case, all showed an ab-/adduction gesture, but the timing and the amplitude of this gesture differed for the three types. For the voiceless unaspirated type, the gesture started at the beginning of the consonant and ended at the release, whereas for the voiced aspirated type, it started at the release and ended at the end of the consonant. For the voiceless aspirated type, it started and ended with the consonant, reaching a glottal width approximately double of the latter two types. Similar results were obtained in initial and final position. Voice onset time values and durations of oral closure are examined. Pros and cons of the terms 'voiced aspirated', 'murmured aspirated', and 'voiced phonoaspirated' are discussed. Finally a mechanism underlying stop production is suggested.

Salmonella isolation from litter as an indicator of flock infection and carcass contamination.

The Salmonella status of 15 different farm flocks was assessed at the farm level and at processing plants. Bacteriological examination for Salmonella was made of litter, dust, feed, 5-day-old culled chicks, and chicken carcasses. Fresh straw litter was found contaminated with Salmonella and may be a source of flock infection. Culture of floor litter can be a practical method for detecting flock infection, and culture of 6-weeks litter in particular would be a good indicator of carcass contamination at processing plants. Properly pelleted feed did not contain Salmonella. Processing did not render carcasses free of Salmonella.

Phage typing of Escherichia coli isolated from chickens.

Ten different bacteriophages were isolated from untreated city sewage water. These phages were stable at 57 degrees C for 40 min. A modified agar layer technique was used to obtain high titre phages. Ninety-four of a stock of 101 cultures of Escherichia coli, which were isolated from inflamed portions of intestines of chickens, were lysed by one or more of these phages. The E. coli of a known serological grouping were phage typed.

On the predictive role of the recent theories of aspiration.

The purpose of this study is to examine the predictive power of recent theories of aspiration. These theories (lag of voicing) predict that aspirated sounds will be perceived as unaspirated in word-final position, as in the case of Korean stops. Contrary to the predictions of these theories, our experiment showed that in final position in Hindi stops, such a neutralization between unaspirated and aspirated stops was absent. What is even more interesting is that the intelligibility of aspirated sounds in Hindi was the highest on the perception scale while unaspirated had a lower rank.