Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysosomal Phospholipase A2 and Phospholipidosis

ABSTRACT A lysosomal phospholipase A2, LPLA2, was recently characterized and shown to have substrate specificity for phosphatidylcholine and phosphatidylethanolamine. LPLA2 is ubiquitously expressed but is most highly expressed in alveolar macrophages. Double conditional gene targeting was employed to elucidate the function of LPLA2. LPLA2-deficient mice (Lpla2−/−) were generated by the systemic deletion of exon 5 of the Lpla2 gene, which encodes the lipase motif essential for the phospholipase A2 activity. The survival of the Lpla2−/− mice was normal. Lpla2−/− mouse mating pairs yielded normal litter sizes, indicating that the gene deficiency did not impair fertility or fecundity. Alveolar macrophages from wild-type but not Lpla2−/− mice readily degraded radiolabeled phosphatidylcholine. A marked accumulation of phospholipids, in particular phosphatidylethanolamine and phosphatidylcholine, was found in the alveolar macrophages, the peritoneal macrophages, and the spleens of Lpla2−/− mice. By 1 year of age, Lpla2−/− mice demonstrated marked splenomegaly and increased lung surfactant phospholipid levels. Ultrastructural examination of Lpla2−/− mouse alveolar and peritoneal macrophages revealed the appearance of foam cells with lamellar inclusion bodies, a hallmark of cellular phospholipidosis. Thus, a deficiency of lysosomal phospholipase A2 results in foam cell formation, surfactant lipid accumulation, splenomegaly, and phospholipidosis in mice.
Dual EGFR/HER2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Withdrawal by Suppressing ErbB3

Purpose: Patients with recurrent prostate cancer are commonly treated with androgen withdrawal therapy (AWT); however, almost all patients eventually progress to castration resistant prostate cancer (CRPC), indicating failure of AWT to eliminate androgen-sensitive prostate cancer. The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness of this treatment in prostate cancer. Experimental Design: We used androgen-dependent LNCaP cells and its CRPC sublines LNCaP-AI and C4-2. Additional data were collected in pRNS-1-1 cells stably expressing a mutant androgen receptor (AR-T877A), and in nude mice harboring CWR22 tumors. Studies utilized EGFR inhibitors erlotinib and AG1478, and HER2 inhibitors trastuzumab and AG879. Results: Dual EGFR/HER2 inhibition induced apoptosis selectively in androgen-sensitive prostate cancer cells undergoing AWT, but not in the presence of androgens, or in CRPC cells. We show that AWT alone failed to induce significant apoptosis in androgen-dependent cells, due to AWT-induced increase in HER2 and ErbB3, which promoted survival by increasing Akt phosphorylation. AWT-induced ErbB3 stabilized the AR and stimulated PSA, while it was inactivated only by inhibition of both its dimerization partners EGFR and HER2 (prostate cancer cells do not express ErbB4); but not the inhibition of any one receptor alone, explaining the success of dual EGFR/HER2 inhibition in sensitizing androgen-dependent cells to AWT. The effectiveness of the inhibitors in suppressing growth correlated with its ability to prevent Akt phosphorylation. Conclusion: These studies indicate that dual EGFR/HER2 inhibition, administered together with AWT, sensitize prostate cancer cells to apoptosis during AWT. Clin Cancer Res; 17(19); 6218–28. ©2011 AACR.
TM2-TM7 Interaction in Coupling Movement of Transmembrane Helices to Activation of the Angiotensin II Type-1 Receptor*

Agonist-induced rigid body motion of transmembrane (TM) helices has been established as a unifying mechanism in the activation of the G protein-coupled receptors. In attempts to measure specific conformational transitions during the activation of the type 1 receptor for angiotensin II (AT1), we found a decrease in accessibility of Cys76 in the second TM helix, suggesting that the orientation of TM2 is altered (Miura, S., and Karnik, S. S. (2002) J. Biol. Chem. 277, 24299–24305). Now we provide evidence that the TM2 helical movement plays a role in regulating the activated state of the AT1 receptor, and this role may involve an interaction between TM2 and TM7. Alanine substitution of native Cys296in TM7 leads to increased accessibility of Cys289 and diminished response to bound agonist. Both effects of the C296A mutation are suppressed when combined with F77A and N111G mutants. The TM7 conformation and the sensitivity of Cys289 altered by C296A mutation are suppressed by the F77A mutation in TM2 to salvage function. We show that the F77A mutant alters orientation of both TM2 and TM7 but does not induce constitutive activity in suppressing the C296A mutant effects. Thus, interaction of TM2 and TM7 is important for transmembrane signal transduction in the AT1 receptor.
Two modes of hair cell loss from the vestibular sensory epithelia of the guinea pig inner ear

In the vestibular and auditory neurosensory epithelia of poikilothermic vertebrates and of birds, damaged sensory “hair” cells are often deleted by extrusion from the apical surface. In contrast, in the adult mammalian auditory epithelium (the organ of Corti), the bodies of damaged hair cells degenerate within the epithelium. To determine whether this apparent difference is species related or is associated with the differing structural organisation of the epithelia, hair cell deletion in the mammalian vestibular end‐organs was examined. The structural organisation of these tissues is closer to that of the inner ear epithelia of lower vertebrates than to the organ of Corti. Hair cell loss was induced by chronic, systemic treatment of guinea pigs with the ototoxic aminoglycoside antibiotic gentamicin. The vestibular sensory epithelia were examined at various times after treatment via scanning electron microscopy, thin sectioning, and staining f‐actin with fluorescently labelled phalloidin. Two distinct modes of hair cell loss were identified: (1) degeneration of hair cells within the epithelium, which often showed morphological features consistent with those described for apoptosis, and (2) extrusion of intact cells from the apical surface. Neither process caused the formation of obvious lesions through the epithelial surfaces. Expansion of adjacent supporting cells during hair cell deletion resulted in repair that appeared to preserve permeability barriers. There was also no evidence of inflammation accompanying hair cell removal. Thus, with both modes of hair cell loss, it appeared that deletion of hair cells was achieved without disruption of tissue architecture or integrity. This may be important for subsequent repair and regeneration processes to operate.
Intraspecific Diversity of Vibrio vulnificus in Galveston Bay Water and Oysters as Determined by Randomly Amplified Polymorphic DNA PCR

ABSTRACT Randomly amplified polymorphic DNA (RAPD) PCR was used to analyze the temporal and spatial intraspecific diversity of 208 Vibrio vulnificus strains isolated from Galveston Bay water and oysters at five different sites between June 2000 and June 2001. V. vulnificus was not detected during the winter months (December through February). The densities of V. vulnificus in water and oysters were positively correlated with water temperature. Cluster analysis of RAPD PCR profiles of the 208 V. vulnificus isolates revealed a high level of intraspecific diversity among the strains. No correlation was found between the intraspecific diversity among the isolates and sampling site or source of isolation. After not being detected during the winter months, the genetic diversity of V. vulnificus strains first isolated in March was 0.9167. Beginning in April, a higher level of intraspecific diversity (0.9933) and a major shift in population structure were observed among V. vulnificus isolates. These results suggest that a great genetic diversity of V. vulnificus strains exists in Galveston Bay water and oysters and that the population structure of this species is linked to changes in environmental conditions, especially temperature.
Sudden infant death syndrome: after the “back to sleep” campaign

The incidence of sudden infant death syndrome in England and Wales fell by two thirds between 1989 and 1993. The decline in deaths followed the “back to sleep” health education campaign (started in 1991), which advised parents to place babies on their back or side to sleep, to avoid overheating and smoky environments, and to contact a doctor if their baby was unwell.1 Similar campaigns were conducted in Australia, New Zealand, and several other countries, with a decrease in the incidence of sudden infant death syndrome of 50% or more.2 In Tasmania a within-cohort analysis of more than 30 factors that might have contributed to the decline in incidence found that 70% of the decline could be attributed to the reduction in the proportion of infants who usually slept prone.3 Much of the research effort is now focused on understanding the mechanisms through which the prone position exerts its effect and on identifying the causal pathway for sudden infant death in infants who do not sleep in the prone position. Two papers in this week's …
Table ( 1 ) : Comparison between the mean anxiety scale according different study variables among patients attending outpatient clinics in King Abdulaziz University Hospital

Background: Anxiety is an emotion experienced by most of individuals at some time during their life. Oral health is an essential component of the overall public health, while dental anxiety can lead to deterioration of such health. The purpose of the study was to determine the prevalence and predictors of dental anxiety among patients attending outpatient clinics of King Abdulaziz University Hospital (KAUH), Jeddah. Methods: A cross-sectional study was conducted among a sample of 231 adult patients who attended the outpatient clinics of KAUH, Jeddah, during the year 2013/2014. A standardized interviewing questionnaire was used and contained Corah’s Dental Anxiety Scale (DAS) was included. Results: The prevalence dental anxiety among participants was 50.6%. Females obtained a significantly higher mean DAS compared to males (Student's t-test = 3.78, p < 0.001). Dental anxiety was also higher among younger participants. Multiple linear regression model revealed that predictors of dental anxiety were the previous cancellation of dental appointment (t-test =2.998, p < 0.001, B = 2.998), followed by memorizing poor dental practice, gender and age. The highest percentage of severe anxiety was related to dental extraction (46.0%). Sweaty hands (56.1 %), fast breathing (21.5 %) & increased heart rates (13.6 %) were the commonest reported somatic manifestations accompanying visiting dentists. Conclusions: Dental anxiety represents a common problem among Saudi adults attending KAUH. Dental anxiety was predicted by cancellation of dental appointment(s), memorization of poor dental practice, gender and age. Enhancing awareness of the community about oral health and how to avoid dental anxiety through educational campaigns is recommended.
Fruit quality and antioxidant properties of 'KluaiKhai' banana (Musa AA group) at different stages of harvest maturity.

This study was designed to determine the effects of harvest maturity and harvesting season on fruit quality and shelf life and evaluate the relationship between maturity and antioxidant properties in ‘KluaiKhai’ banana (Musa AA group) for export in Thailand. Three harvest season trials (cool, summer and rainy seasons) were conducted using fruit bunches of different ages (30-50 days from removal of the blossom when the last fruit hand emerged). Fruit samples were stored at 13oC for 2 weeks to simulate export shipment and holding. Fruits were ripened with ethylene for measuring total soluble solids (TSS) and shelf life of ripe fruits. Results showed that the degree of maturity of fruits from the same bunch age differed with harvest season; fruits matured the slowest in the cool season and fastest in the rainy season. Hand weight and finger diameter generally increased with increasing harvest maturity and were highest in the most mature fruits regardless of harvest season. Fruit length did not widely vary with maturity. Similarly, TSS and shelf life of ripe fruits were not significantly affected by harvest maturity and season. Fruits were 70-80% mature, the recommended maturity for export, at 45-50, 37-40, and 33-37 days from blossom removal during the cool, summer and rainy season, respectively. A fourth trial was conducted to determine fruit quality and antioxidant properties at table ripe and overripe stages. Firmness and TSS showed no significant variations due to maturity but starch content was comparably higher in fruits harvested at 35-40 days (75-90% mature) than those at 30-33 days (60-70% mature) from blossom removal. Ascorbic acid, phenolics, flavonoids and β-carotene contents at table ripe stage increased with increasing harvest maturity while lycopene content was low and was not clearly affected by maturity. Similar trend and amount of ascorbic acid were obtained in overripe fruits but phenolics, flavonoids and β-carotene contents decreased. Ferrous ion chelating ability and DPPH scavenging activity at the table ripe stage generally increased with harvest maturity while reducing power decreased with increasing maturity. These antioxidant activities decreased slightly in overripe fruits. Ferrous ion chelating ability was higher than DPPH scavenging activity in fruits at 35-45 days from blossom removal. The results indicate the nutritional advantage of harvesting fruit at the more mature stage. Considering both export requirement and nutritional potential, fruits could be harvested when 75-85% mature.
Indoor air pollution as a risk factor for lung cancer in women.

OBJECTIVES Tobacco smoking is the most common risk factor for lung cancer. But a significant proportion of lung cancer occurs in non-smokers. Indoor pollution due to domestic fuels has been recently implicated as a causative agent in lung cancer especially in women. We conducted a case control study to find out the role of indoor air pollution due to domestic cooking fuels in Indian women. METHODS In a case control study 67 women with proven lung cancer were recruited. Forty-six females having a non-malignant respiratory disease constituted the control group. The patients and controls were asked about the exposure in various cooking fuels using a questionnaire. RESULT There were 50 (74.6%) non-smokers and 17 (25.4%) smokers among the female cancer cases (p = 0.016). Adenocarcinoma was the commonest histological type of malignancy (n = 26, 38.8%) in the whole group and was the predominant form in the nonsmoking females. Tobacco smoking was the most important risk factor for lung cancer with OR of 4.87 (95% CI 1.34-17.76). Among non-smokers out of all the cooking fuels the risk of development of lung cancer was highest for biomass fuel exposure with an odds ratio of 5.33 (95% CI 1.7-16.7). Use of mixed fuels was associated with a lesser risk (OR = 3.04, 95% CI 1.1-8.38). ). In multivariate logistic regression analysis biomass fuel exposure was still significant with OR of 3.59 (95% CI 1.07-11.97) even after adjusting for smoking and passive smoking. CONCLUSION This study indicated that biomass fuel exposure is an important risk factor in the causation of lung cancer among women in addition of exposure to tobacco smoke.
Caregiving and Stress: Experience of People Taking Care of Elderly Relations in South-eastern Nigeria

Providing care especially to the elderly, takes a huge toll, both physically and emotionally on the caregiver. With the population of the elderly growing in Nigeria, one of the emerging issues is the care and support of elderly persons in years to come. Few people are prepared for the responsibilities and tasks involved in caring for the aged because of the stress involved. This study investigates the experiences of caregivers of elderly relatives. Questionnaires were distributed to 330 respondents. Result shows that there exists a significant relationship between caregiver’s age and level of stress (p=0.001). The sex of care receiver, the level of education of caregivers, level of education of care receiver are all significantly related to the level of stress. The role of social workers in future care and support of the elderly in Nigeria is discussed.
HI antibody to various influenza viruses and adenoviruses in individuals of blood groups A and O

SUMMARY Serum specimens collected in 1966 from individuals of different age groups were studied for the presence of haemagglutination inhibition (HI) antibody to four influenza viruses. All sera were from individuals of blood group A or O and in no instance was the incidence of antibody to a virus strain significantly greater for persons of blood group O compared with similar aged individuals of blood group A. This finding for HI antibody to A 2/Singapore/1/57 is different from similar studies of serum specimens collected in 1961–3. It is suggested that the change in the immune status of a population, with reference to blood-group status, is due to repeated exposure to infection; this changing pattern of immune status is discussed. Similar studies of HI antibody to adenovirus type 3 and 7 in human sera from persons of blood group A and O shows a changing pattern with increasing age. These results are consistent with the findings for influenza virus and are discussed. Repeated exposure of a population to infection results in obscuring genetically determined variations in susceptibility. I would like to thank Professor M. G. McEntegart, Professor of Medical Microbiology, and Professor C. H. Stuart-Harris, Professor of Medicine, for their advice and criticism, and Miss D. Coles, F.I. M.L. T. , and Mrs P. Robinson for expert technical assistance.
Neural Dysregulation in Posttraumatic Stress Disorder: Evidence for Disrupted Equilibrium Between Salience and Default Mode Brain Networks

Objective Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]). Methods Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain. Results Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected). Conclusions During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.
Mobile computing in medical education: opportunities and challenges

Purpose of review There is an increasing importance of incorporating mobile computing into the academic medical environment. A growing majority of physicians, residents and medical students currently use mobile devices for education, access to clinical information and to facilitate bedside care. Therefore, it is important to assess the current opportunities and challenges in the use of mobile computing devices in the academic medical environment. Recent findings Current research has found that a majority of physicians, residents and medical students either own or use mobile devices. In addition, studies have shown that these devices are effective as educational tools, resource guides and aids in patient care. Although there are opportunities for medical education, issues of deployment must still be addressed, such as privacy, connectivity, standardization and professionalism. Summary Understanding the opportunities and challenges of using mobile computing devices in the academic medical environment can help determine the feasibility and benefits of their use for individuals and institutions.
Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis

Background: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen.
The intersection of nonalcoholic fatty liver disease and obesity

New insights into the overlap and differences between obesity and nonalcoholic fatty liver disease (NAFLD) are contributing to advances in diagnosis and treatment of NAFLD. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD.
Dynamic‐SIMS imaging and quantification of inorganic ions in frozen‐hydrated plant samples

We present here SIMS images of the distribution of inorganic cations (Na, K, Mg and Ca) in frozen‐hydrated samples of three plant species, ivy, camomile, and flax. The samples were cryofixed using fast plunge‐freezing. Stigmatic images were obtained, at 100 K, under dynamic SIMS conditions by fast atom bombarding (FAB). Even though the images obtained with the frozen‐hydrated plant samples are still not of upper quality, they show that the method used to prepare these samples preserves existing ionic gradients between the outer and the inner part of the cells, between adjacent cells, including cells with the same type of differentiation, and between tissues. We also describe the quantification of the relative proportions of the ions in the vacuoles of flax. The reasonable accuracy achieved for quantification of the vacuole ion ratios permitted to show (i) that radial gradients of ion ratios in hypocotyls change when the plant is becoming older and (ii) that large differences may exist between adjacent cortical cells of the same type. The role of these substantial differences in vacuole ion balance ratios is a largely unexplored issue in plant physiology. Microsc. Res. Tech. 69:53–63, 2006. © 2006 Wiley‐Liss, Inc.