Apical-basal polarity in the gut.

Apical-Basal polarity is a fundamental property of all epithelial cells that underlies both their form and function. The gut is made up of a single layer of intestinal epithelial cells, with distinct apical, lateral and basal domains. Occluding junctions at the apical side of the lateral domains create a barrier between the gut lumen and the body, which is crucial for tissue homeostasis, protection against gastrointestinal pathogens and for the maintenance of the immune response. Apical-basal polarity in most epithelia is established by conserved polarity factors, but recent evidence suggests that the gut epithelium in at least some organisms polarises by novel mechanisms. In this review, we discuss the recent advances in understanding polarity factors by focussing on work in C. elegans, Drosophila, Zebrafish and Mouse.

Applications of Capacitive Micromachined Ultrasonic Transducers: A Comprehensive Review.

Capacitive micromachined ultrasonic transducer (CMUT) was introduced as an alternative to the piezoelectric thick-film-based transducers in medical imaging applications. Gradually, CMUTs have been investigated in almost all the applications in acoustics due to their superior transduction properties. CMOS compatible process flow and limitless possibilities of miniaturization made CMUT a preferred choice for the ultrasound industry. This article comprehensively reviews all the applications in which CMUT was used until now. Such a complete review of the practical applications of CMUT has not been reported elsewhere. A topicwise presentation approach is adopted, and wherever possible, the necessary details of the device properties and experimental niceties were briefly covered.

A miniaturized electrochemical platform with an integrated PDMS reservoir for label-free DNA hybridization detection using nanostructured Au electrodes.

We report the fabrication and characterization of a miniaturized electrochemical platform for the label-free detection of DNA hybridization. The proposed platform is fabricated using microfabrication and electrodeposition techniques. Comprising a Ti working electrode with electrodeposited Au nanostructures, and Pt/Au pseudo-reference and counter electrodes, the device accounts for a limit of detection of 0.97 fM and a sensitivity of 20.78 (µA µM-1) cm-2 with respect to Dengue virus specific consensus primer detection in the range of 10 fM-1 µM. Here, the incorporation of nanostructured Au in the active sensing area not only enhances the current response by increasing the overall surface area, but it also facilitates facile probe DNA immobilization by gold-thiol self-assembly. We have used differential pulse voltammetry analysis in this study to monitor the changes in reaction kinetics with respect to target hybridization. Furthermore, the evaluation of reproducibility of the biosensor and its selectivity against interference has yielded acceptable outcomes. Additionally, in order to evaluate the system's selectivity, we have successfully distinguished PCR amplified wild type and mutant target DNAs corresponding to the BRCA1 specific gene. Here, the mutant and the wild type target DNAs differ by a two base deletion, and the fact that the system is able to differentiate even such minute dissimilarities under hybridization conditions is indicative of its superior performance.

Spoiled for Choice: Diverse Endocytic Pathways Function at the Cell Surface.

Endocytosis has long been identified as a key cellular process involved in bringing in nutrients, in clearing cellular debris in tissue, in the regulation of signaling, and in maintaining cell membrane compositional homeostasis. While clathrin-mediated endocytosis has been most extensively studied, a number of clathrin-independent endocytic pathways are continuing to be delineated. Here we provide a current survey of the different types of endocytic pathways available at the cell surface and discuss a new classification and plausible molecular mechanisms for some of the less characterized pathways. Along with an evolutionary perspective of the origins of some of these pathways, we provide an appreciation of the distinct roles that these pathways play in various aspects of cellular physiology, including the control of signaling and membrane tension.

Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.

Correction: Population Distribution Analyses Reveal a Hierarchy of Molecular Players Underlying Parallel Endocytic Pathways.

[This corrects the article DOI: 10.1371/journal.pone.0100554.].

Prevalence of depression among middle aged women in the rural area of Kerala.

AIMS: The aim of this study was to determine the prevalence of Depression among women aged 40-60 years in the rural area of Kerala using Patient Health Questionnaire 9 (PHQ-9). SETTINGS AND DESIGN: Ambalappuzha is an area of rural background under the District of Alappuzha. The study was conducted by Preventive and Social Medicine department of Govt. T. D. Medical College, Kerala in collaboration with the department of Psychiatry with the help of Ambalappuzha health centre. METHODS AND MATERIAL: A cross-sectional survey was carried out among 594 women from 18 wards of Amabalappuzha North Panchayat using cluster sampling technique. Data on sociodemographic factors, health factors, and behavioral factors were collected from the women by investigator administered the semi-structured questionnaire. Patient Health Questionnaire9 (PHQ-9), was used for diagnosing Major Depression. RESULTS: The prevalence of Major Depression among middle aged women was 26.09% using the PHQ-9 diagnostic criteria and 24.2% using a PHQ-9 cut off score ≥ 10. With increasing age, there was an increasing trend in the prevalence of Depression up to the age of 55years followed by a small decline. A higher prevalence of Depression was observed among widows (43.37%), women not in a marital relation (41.38%), a woman with a history of postpartum Depression (OR 3.471), with peri-menopausal symptoms (40.28%, OR 2.86). CONCLUSIONS: One fourth of the women screened positive for Depression in Ambalappuzha North Panchayat (26.09%). This study highlights the need for understanding the high prevalence and myriad determinants of depression among women living in villages.

Physical principles of membrane remodelling during cell mechanoadaptation.

Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope--the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell-substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes.

Fabrication of SU-8 based Capacitive Micromachined Ultrasonic Transducer for low frequency therapeutic applications.

In this paper we present a simple post-CMOS compatible sacrificial release method of fabricating SU-8 based Capacitive Micromachined Ultrasonic Transducer (CMUT) for low frequency therapeutic applications. CMUTs fabricated with Silicon Nitride and Silicon Dioxide lay constraints in terms of area and power consumption especially in the low frequency range. Fabrication of these devices need complex high temperature processes that makes them incompatible for post-CMOS processing. Analytical modeling shows that SU-8 based CMUT consumes less area (below 25%) and power compared to Silicon Nitride and Silicon Dioxide based CMUTs. The proposed fabrication method overcomes inherent disadvantages of sacrificial release method by providing uniformity in air gap and reducing the possibility of stiction.

A low power, area efficient fpga based beamforming technique for 1-D CMUT arrays.

A low power area efficient digital beamformer targeting low frequency (2MHz) 1-D linear Capacitive Micromachined Ultrasonic Transducer (CMUT) array is developed. While designing the beamforming logic, the symmetry of the CMUT array is well exploited to reduce the area and power consumption. The proposed method is verified in Matlab by clocking an Arbitrary Waveform Generator(AWG). The architecture is successfully implemented in Xilinx Spartan 3E FPGA kit to check its functionality. The beamforming logic is implemented for 8, 16, 32, and 64 element CMUTs targeting Application Specific Integrated Circuit (ASIC) platform at Vdd 1.62V for UMC 90nm technology. It is observed that the proposed architecture consumes significantly lesser power and area (1.2895 mW power and 47134.4 µm(2) area for a 64 element digital beamforming circuit) compared to the conventional square root based algorithm.

How good are ensembles in improving QSAR models? The case with eCoRIA.

A conceptually new idea in quantitative structure-activity relationships (QSAR) which makes use of ensembles from molecular dynamics (MD) trajectories and information retrieved from enzyme-inhibitor binding thermodynamics is presented in this study. This new methodology, termed ensemble comparative residue interaction analysis (eCoRIA), attempts to overcome the current one chemical-one structure-one parameter value dogma in computational chemistry by modeling the biological activity as a function of molecular descriptors derived from an ensemble of conformers of enzyme-inhibitor complexes. The approach is distinctly different from the standard QSAR methodology which uses a single low-energy conformation or the properties averaged over a set of conformers to correlate with the activity. Each conformational ensemble derived from MD simulations is analyzed for the distribution of the non-bonded interaction energies (steric, electrostatic, and hydrophobic) along with solvation, strain, and entropic energy of the inhibitors with the individual amino acid residues in the receptor and these are correlated to the activity through a QSAR model. The scope of the new method is demonstrated with three diverse enzyme-inhibitor data-sets - glycogen phosphorylase b, human immunodeficiency virus-1 protease and cyclin-dependent kinase 2. The QSAR equations derived from the methodology have revealed all the structure activity relationships previously reported for these classes of molecules as well as uncovered some features that were hitherto unknown and may have a hidden role in driving the ligand-receptor-binding process. Impressive improvements in the predictions of affinity have been achieved compared to other QSAR formalisms namely CoMFA, CoMSIA (receptor-independent QSAR techniques), and CoRIA (a receptor-dependent QSAR technique). eCoRIA could provide an understanding of the thermodynamic properties influencing the ligand-receptor binding over a time scale as sampled by the MD simulation. The advantage of analyzing enzyme-inhibitor interaction energies in a statistical domain is that the noise due to inaccuracies in the potential energy functions can be reduced and mechanistically important interaction terms related to protein-ligand binding specificity can be identified which can assist the medicinal chemists in designing new molecules and biologists in studying the influence of position-specific mutations in the receptor on ligand binding.

A comparative study on the physical, chemical and functional properties of carp skin and mammalian gelatins.

Carp species forms the bulk of the aquaculture production in India and studies have shown that the filleting waste of these species, particularly skin can be a good source of gelatin. This study is a comparison of the gelatins from these unexploited sources with that of mammalian gelatins to get a better understanding of their physicochemical and functional properties with respect to mammalian gelatins. The study showed that mammalian gelatins had significantly superior physical properties viz., higher viscosity, melting & setting temperature and faster setting time. The odour scores were significantly higher (P < 0.05) for bovine and porcine skin gelatins (3.1-3.12), indicating that they had a distinguishable odour and hence can be considered as inferior to fish skin gelatins in organoleptic qualities. The gel strengths of rohu and common carp skin gelatins were significantly lower than mammalian gelatins. Among the carp skin gelatins, grass carp skin gelatin was found to have better compatibility with gelatin from bovine and porcine skins.

Population distribution analyses reveal a hierarchy of molecular players underlying parallel endocytic pathways.

Single-cell-resolved measurements reveal heterogeneous distributions of clathrin-dependent (CD) and -independent (CLIC/GEEC: CG) endocytic activity in Drosophila cell populations. dsRNA-mediated knockdown of core versus peripheral endocytic machinery induces strong changes in the mean, or subtle changes in the shapes of these distributions, respectively. By quantifying these subtle shape changes for 27 single-cell features which report on endocytic activity and cell morphology, we organize 1072 Drosophila genes into a tree-like hierarchy. We find that tree nodes contain gene sets enriched in functional classes and protein complexes, providing a portrait of core and peripheral control of CD and CG endocytosis. For 470 genes we obtain additional features from separate assays and classify them into early- or late-acting genes of the endocytic pathways. Detailed analyses of specific genes at intermediate levels of the tree suggest that Vacuolar ATPase and lysosomal genes involved in vacuolar biogenesis play an evolutionarily conserved role in CG endocytosis.

A low pull-in SU-8 based Capacitive Micromachined Ultrasonic Transducer for medical imaging applications.

In this paper we present a thorough analysis of a low pull-in voltage Capacitive Micromachined Ultrasonic Transducer (CMUT) using SU-8 as the membrane material. It is designed to operate at 1 MHz frequency that has a wide range of applications including the imaging of deeper organs. We also propose a simple state-of-the-art fabrication methodology for the same. As compared to the standard Silicon Nitride CMUTs, the proposed structure gives the same electromechanical coupling coefficient with lower membrane dimensions and low pull-in voltage which in turn results in reduced area and power consumption. Moreover the proposed fabrication methodology is a low temperature process which makes it CMOS compatible.

Thoracic endometriosis: revisiting the association between clinical presentation and thoracic pathology based on thoracoscopic findings in 110 patients.

Thoracic endometriosis (TE) is a rare disorder affecting women during their reproductive years. The etiopathogenesis of this disease is not well understood; the prevailing opinion is based on analysis obtained from case reports and small case series. A 1996 review of TE was not able to address the association between clinical presentation and thoracic pathology due to a paucity of thoracoscopic findings in these earlier cases. Since the year 2001, most published cases and series have included thoracoscopic findings. Therefore, we compiled data from case reports and case series published in English from January 2001 to July 2007 to analyze the demographics, clinical characteristics, and thoracoscopic findings, and to study the relationship between thoracoscopic findings and clinical presentation in patients with thoracic endometriosis. The clinical presentations in 110 patients were as follows: pneumothorax in 79 (72%), hemoptysis in 16 (14%), hemothorax in 13 (12%), and lung mass in 2 (2%). Ninety-one of the 110 (85%) patients underwent thoracotomy or thoracoscopy. The right hemithorax was more often affected (85%) than the left side (p = 0.008). The mean (standard deviation [SD]) age of all patients was 34 (7.6 yr). The mean age of patients presenting with hemoptysis (25.9 +/- 4.6 yr) was significantly lower than the age of those presenting with pneumothorax and hemothorax (p < 0.01). There was no significant association between the presence of diaphragmatic defects and pneumothorax (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.05-1.58; p = 0.23). The presence of parietal and visceral pleural implants was associated with a fivefold increase in hemothorax (OR, 5.55; 95% CI, 1.20-25.53; p < 0.01).Hemoptysis occurring in younger subjects may be the earliest manifestation of parenchymal lung involvement in TE. Diaphragmatic defects do not increase the risk for pneumothorax. Hemothorax reflects an increased burden of pleural implants in TE.

Physical, mechanical, and barrier properties of carp and mammalian skin gelatin films.

Films of 0.11 to 0.13 mm thickness were prepared using gelatins from the skins of cultured freshwater carp species and mammalian gelatins viz., porcine and bovine skin gelatin. A comparative study was made on the physical, mechanical, and barrier properties of these films. The amino acid composition, gel strength, clarity, and gel setting point of the gelatins were also determined. Carp skin gelatins had a lower imino acid content (19.16% to 20.86%) than mammalian skin gelatins (22.91% to 23.7%). Grass carp gelatin had gel strength of 230.2 B that is comparable to the reported value for bovine skin gelatin (227.2 B). The bloom values of rohu and common carp skin gelatins were 188.6 B and 181.3 B, respectively, which were significantly lower than mammalian gelatins. Mammalian gels have significantly higher (P < 0.05) setting temperatures (23.7 to 24.2 °C) than carp skin gelatins. Tensile strength (TS) was lowest for films from common carp and rohu skin gelatin (490 and 497 kg/cm(2), respectively) and highest for porcine skin gelatin film. The degree of transparency (L*) was significantly higher for films from grass carp, bovine hide, and pork skin gelatin films. Carp skin gelatin films had significantly lower water vapor permeability (WVP) and oxygen permeability (OP) than mammalian skin gelatin films, which indicated that carp skin gelatin based films have superior barrier properties than mammalian skin gelatin films.

Paternal asthma is a predictor for childhood asthma in the consanguineous families from the United Arab Emirates.

Consanguinity is known to increase the burden of genetic disorders among offspring. However, the effect of consanguinity on a complex disorder like childhood asthma has not been studied previously. Therefore, we explored this relationship by studying the asthma prevalence in children between 6 and 14 years of age among the local Arab families of the United Arab Emirates (UAE) where consanguinity is known to be highly prevalent. A total of 1136 children from 295 families met our inclusion criteria. The prevalence of childhood asthma was higher among children in consanguineous families (43.3%) compared to non-consanguineous (22.6%, p < 0.001). There was a significant correlation between the degree of consanguinity and the number of asthmatic children per family (p = 0.0002). Girls from consanguineous families had proportionately more asthma (42.9%, p < 0.001) compared to boys (23.1%, p = 0.539). Paternal asthma in consanguineous families increased asthma risk for both boys and girls (p = 0.021 for boys, p < 0.001 for girls), while maternal asthma had no significant impact on asthma in offspring. Prevalence of childhood asthma was significantly higher in consanguineous families. The significant asthma predictors for girls from the consanguineous families were the degree of consanguinity and paternal asthma. The only predictor for boys was paternal asthma. These interesting observations merit further studies on both larger samples and in other consanguineous communities for confirmation.

Pleural effusion in hospitalized patients with Coccidioidomycosis.

INTRODUCTION: Coccidioidomycosis is a common fungal infection primarily affecting the lungs. The prevalence and the characteristics of pleural effusion in Coccidioidomycosis are not well described. Therefore, a retrospective analysis of data from patients admitted to a teaching hospital with a diagnosis of Coccidioidomycosis and pleural effusion was done. METHODS: All patients admitted with a diagnosis of Coccidioidomycosis were identified using ICD 9 from 114 to 114.9 from computerized medical records. Epidemiological, clinical and laboratory data were transcribed from medical records of all inpatients. Pleural effusion was identified using reports of chest radiography, ultrasound and CT scan of chest. RESULTS: Pleural effusion occurred in 22 of 146 (15%) patients hospitalized for Coccidioidomycosis. The proportion of patients with pleuritic chest pain, cough and dyspnea were significantly higher in patients with effusion than without effusion (p<0.01). There was a tendency for pleural effusions to occur more often on the left side (p=0.064). Empyema occurred in 22.7% of pleural effusions. Pleural fluid chemistry showed that all effusions were exudates with a mean (+/-S.E.M.) pleural fluid eosinophil count of 10.3+/-4.65. CONCLUSION: Pleural effusions are common in hospitalized patients with Coccidioidomycosis. Pleural fluid eosinophilia should alert clinician to Coccidioides immitis as a possible etiological agent especially in an endemic area. Empyema occurred in a quarter of pleural effusions and resolution required thoracotomy.

An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy.

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.

Risk factors predicting outcome in patients with pneumonia in Al-Ain, United Arab Emirates.

OBJECTIVE: To determine the predictive value of commonly used clinical and laboratory factors for mortality in patients with pneumonia in the Arab world. METHODS: We retrospectively analyze the data collected from all inpatients over the age of 16 years with a diagnosis of pneumonia in Tawam Hospital, Al-Ain, United Arab Emirates between the years 1997 and 2002. Patients were grouped into those who survived and those who died in the hospital. Clinical and laboratory factors on admission were used to predict outcome using simple, and multiple logistic regression analyses. RESULTS: Among the 236 patients admitted, 122 were females (age 56.9 +/- 23 years), and 114 males (age 58.5 +/- 23 years). The 30-day mortality rate was 10%. The most common comorbid risk factors were diabetes mellitus in 23.7% and chronic obstructive pulmonary disease in 19.5%. Of the 236 patients, 145 had sputum culture on admission. Simple logistic regression analysis showed increasing age, presence of comorbidity, low systolic blood pressure, confused mental status, low serum albumin, high serum creatinine, raised blood urea nitrogen and raised partial pressure of carbon dioxide at the time of admission were associated with higher mortality. On the Stepwise-multilogistic regression analysis, the most significant factors influencing mortality were: older age, altered mental status, low systolic blood pressure, low serum albumin and raised serum creatinine. Using a scoring system developed in the presence or absence of these risk factors, a score of >=100 predicted high risk for mortality. CONCLUSION: The in-hospital mortality rate for pneumonia was 10%. Older age, altered mental status, low systolic blood pressure, low serum albumin concentration and raised serum creatinine at admission were predictive of poor outcome in this cohort of patients.