Thermoanalytical study of the minerals apophyllite-(KF) KCa4Si8O20F·8H2O and apophyllite-(KOH) KCa4Si8O20(F,OH)·8H2O

The name apophyllite refers to a specific group of phyllosilicates, a class of minerals that also includes the micas and are a class of minerals of similar chemical makeup that comprise a solid solution series, and includes the members apophyllite-(KF), apophyllite-(KOH) and apophyllite-(NaF). Fluorapophyllite apophyllite-(KF) and hydroxyapophyllite apophyllite-(KOH) are different minerals only because of the difference in percentages of fluorine to hydroxyl ions. Three apophyllite minerals have been characterised by thermogravimetric analysis and infrared spectroscopy. Dehydration takes place in several steps. Major mass losses occur at around 205–220 °C and at 400–429 °C. Minor mass losses are observed around 242–292 °C. It is proposed that dehydration occurs in the first decomposition step. Water is lost over the temperature range 125–250, 250–325 and 325–525 °C with the loss of 4.5, 0.5 and 3.0 mol of water. Water functions as zeolitic water and is also coordinated to the silica surfaces.

Characterization of inflammatory responses to eccentric exercise in humans

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

Meal induced thermogenesis and appetite : methodological issues and responses to energy restriction

Diet Induced Thermogenesis (DIT) is the energy expended consequent to meal consumption, and reflects the energy required for the processing and digestion of food consumed throughout each day. Although DIT is the total energy expended across a day in digestive processes to a number of meals, most studies measure thermogenesis in response to a single meal (Meal Induced Thermogenesis: MIT) as a representation of an individual’s thermogenic response to acute food ingestion. As a component of energy expenditure, DIT may have a contributing role in weight gain and weight loss. While the evidence is inconsistent, research has tended to reveal a suppressed MIT response in obese compared to lean individuals, which identifies individuals with an efficient storage of food energy, hence a greater tendency for weight gain. Appetite is another factor regulating body weight through its influence on energy intake. Preliminary research has shown a potential link between MIT and postprandial appetite as both are responses to food ingestion and have a similar response dependent upon the macronutrient content of food. There is a growing interest in understanding how both MIT and appetite are modified with changes in diet, activity levels and body size. However, the findings from MIT research have been highly inconsistent, potentially due to the vastly divergent protocols used for its measurement. Therefore, the main theme of this thesis was firstly, to address some of the methodological issues associated with measuring MIT. Additionally this thesis aimed to measure postprandial appetite simultaneously to MIT to test for any relationships between these meal-induced variables and to assess changes that occur in MIT and postprandial appetite during periods of energy restriction (ER) and following weight loss. Two separate studies were conducted to achieve these aims. Based on the increasing prevalence of obesity, it is important to develop accurate methodologies for measuring the components potentially contributing to its development and to understand the variability within these variables. Therefore, the aim of Study One was to establish a protocol for measuring the thermogenic response to a single test meal (MIT), as a representation of DIT across a day. This was done by determining the reproducibility of MIT with a continuous measurement protocol and determining the effect of measurement duration. The benefit of a fixed resting metabolic rate (RMR), which is a single measure of RMR used to calculate each subsequent measure of MIT, compared to separate baseline RMRs, which are separate measures of RMR measured immediately prior to each MIT test meal to calculate each measure of MIT, was also assessed to determine the method with greater reproducibility. Subsidiary aims were to measure postprandial appetite simultaneously to MIT, to determine its reproducibility between days and to assess potential relationships between these two variables. Ten healthy individuals (5 males, 5 females, age = 30.2 ± 7.6 years, BMI = 22.3 ± 1.9 kg/m2, %Fat Mass = 27.6 ± 5.9%) undertook three testing sessions within a 1-4 week time period. During the first visit, participants had their body composition measured using DXA for descriptive purposes, then had an initial 30-minute measure of RMR to familiarise them with the testing and to be used as a fixed baseline for calculating MIT. During the second and third testing sessions, MIT was measured. Measures of RMR and MIT were undertaken using a metabolic cart with a ventilated hood to measure energy expenditure via indirect calorimetry with participants in a semi-reclined position. The procedure on each MIT test day was: 1) a baseline RMR measured for 30 minutes, 2) a 15-minute break in the measure to consume a standard 576 kcal breakfast (54.3% CHO, 14.3% PRO, 31.4% FAT), comprising muesli, milk toast, butter, jam and juice, and 3) six hours of measuring MIT with two, ten-minute breaks at 3 and 4.5 hours for participants to visit the bathroom. On the MIT test days, pre and post breakfast then at 45-minute intervals, participants rated their subjective appetite, alertness and comfort on visual analogue scales (VAS). Prior to each test, participants were required to be fasted for 12 hours, and have undertaken no high intensity physical activity for the previous 48 hours. Despite no significant group changes in the MIT response between days, individual variability was high with an average between-day CV of 33%, which was not significantly improved by the use of a fixed RMR to 31%. The 95% limits of agreements which ranged from 9.9% of energy intake (%EI) to -10.7%EI with the baseline RMRs and between 9.6%EI to -12.4%EI with the fixed RMR, indicated very large changes relative to the size of the average MIT response (MIT 1: 8.4%EI, 13.3%EI; MIT 2: 8.8%EI, 14.7%EI; baseline and fixed RMRs respectively). After just three hours, the between-day CV with the baseline RMR was 26%, which may indicate an enhanced MIT reproducibility with shorter measurement durations. On average, 76, 89, and 96% of the six-hour MIT response was completed within three, four and five hours, respectively. Strong correlations were found between MIT at each of these time points and the total six-hour MIT (range for correlations r = 0.990 to 0.998; P < 0.01). The reproducibility of the proportion of the six-hour MIT completed at 3, 4 and 5 hours was reproducible (between-day CVs ≤ 8.5%). This indicated the suitability to use shorter durations on repeated occasions and a similar percent of the total response to be completed. There was a lack of strong evidence of any relationship between the magnitude of the MIT response and subjective postprandial appetite. Given a six-hour protocol places a considerable burden on participants, these results suggests that a post-meal measurement period of only three hours is sufficient to produce valid information on the metabolic response to a meal. However while there was no mean change in MIT between test days, individual variability was large. Further research is required to better understand which factors best explain the between-day variability in this physiological measure. With such a high prevalence of obesity, dieting has become a necessity to reduce body weight. However, during periods of ER, metabolic and appetite adaptations can occur which may impede weight loss. Understanding how metabolic and appetite factors change during ER and weight loss is important for designing optimal weight loss protocols. The purpose of Study Two was to measure the changes in the MIT response and subjective postprandial appetite during either continuous (CONT) or intermittent (INT) ER and following post diet energy balance (post-diet EB). Thirty-six obese male participants were randomly assigned to either the CONT (Age = 38.6 ± 7.0 years, weight = 109.8 ± 9.2 kg, % fat mass = 38.2 ± 5.2%) or INT diet groups (Age = 39.1 ± 9.1 years, weight = 107.1 ± 12.5 kg, % fat mass = 39.6 ± 6.8%). The study was divided into three phases: a four-week baseline (BL) phase where participants were provided with a diet to maintain body weight, an ER phase lasting either 16 (CONT) or 30 (INT) weeks, where participants were provided with a diet which supplied 67% of their energy balance requirements to induce weight loss and an eight-week post-diet EB phase, providing a diet to maintain body weight post weight loss. The INT ER phase was delivered as eight, two-week blocks of ER interspersed with two-week blocks designed to achieve weight maintenance. Energy requirements for each phase were predicted based on measured RMR, and adjusted throughout the study to account for changes in RMR. All participants completed MIT and appetite tests during BL and the ER phase. Nine CONT and 15 INT participants completed the post-diet EB MIT and 14 INT and 15 CONT participants completed the post-diet EB appetite tests. The MIT test day protocol was as follows: 1) a baseline RMR measured for 30 minutes, 2) a 15-minute break in the measure to consume a standard breakfast meal (874 kcal, 53.3% CHO, 14.5% PRO, 32.2% FAT), and 3) three hours of measuring MIT. MIT was calculated as the energy expenditure above the pre-meal RMR. Appetite test days were undertaken on a separate day using the same 576 kcal breakfast used in Study One. VAS were used to assess appetite pre and post breakfast, at one hour post breakfast then a further three times at 45-minute intervals. Appetite ratings were calculated for hunger and fullness as both the intra-meal change in appetite and the AUC. The three-hour MIT response at BL, ER and post-diet EB respectively were 5.4 ± 1.4%EI, 5.1 ± 1.3%EI and 5.0 ± 0.8%EI for the CONT group and 4.4 ± 1.0%EI, 4.7 ± 1.0%EI and 4.8 ± 0.8%EI for the INT group. Compared to BL, neither group had significant changes in their MIT response during ER or post-diet EB. There were no significant time by group interactions (p = 0.17) indicating a similar response to ER and post-diet EB in both groups. Contrary to what was hypothesised, there was a significant increase in postprandial AUC fullness in response to ER in both groups (p < 0.05). However, there were no significant changes in any of the other postprandial hunger or fullness variables. Despite no changes in MIT in both the CONT or INT group in response to ER or post-diet EB and only a minor increase in postprandial AUC fullness, the individual changes in MIT and postprandial appetite in response to ER were large. However those with the greatest MIT changes did not have the greatest changes in postprandial appetite. This study shows that postprandial appetite and MIT are unlikely to be altered during ER and are unlikely to hinder weight loss. Additionally, there were no changes in MIT in response to weight loss, indicating that body weight did not influence the magnitude of the MIT response. There were large individual changes in both variables, however further research is required to determine whether these changes were real compensatory changes to ER or simply between-day variation. Overall, the results of this thesis add to the current literature by showing the large variability of continuous MIT measurements, which make it difficult to compare MIT between groups and in response to diet interventions. This thesis was able to provide evidence to suggest that shorter measures may provide equally valid information about the total MIT response and can therefore be utilised in future research in order to reduce the burden of long measurements durations. This thesis indicates that MIT and postprandial subjective appetite are most likely independent of each other. This thesis also shows that, on average, energy restriction was not associated with compensatory changes in MIT and postprandial appetite that would have impeded weight loss. However, the large inter-individual variability supports the need to examine individual responses in more detail.

The knock-on from the knock-off : recent shifts within Australian mass market fashion design practice

Australia's mass market fashion labels have traditionally benefitted from their peripheral location to the world's fashion centres. Operating a season behind, Australian mass market designers and buyers were well-placed to watch trends play out overseas before testing them in the Australian marketplace. For this reason, often a designer's role was to source and oversee the manufacture of 'knock-offs', or close copies of northern hemisphere mass market garments. Both Weller and Walsh have commented on this practice.12 The knock-on effect from this continues to be a cautious, derivative fashion sensibility within Australian mass market fashion design, where any new trend or product is first tested and proved overseas months earlier. However, there is evidence that this is changing. The rapid online dissemination of global fashion trends, coupled with the Australian consumer’s willingness to shop online, has meant that the ‘knock-off’ is less viable. For this reason, a number of mass market companies are moving away from the practice of direct sourcing and are developing product in-house under a northern hemisphere model. This shift is also witnessed in the trend for mass market companies to develop collections in partnership with independent Australian designers. This paper explores the current and potential effects of these shifts within Australian mass market design practice, and discusses how they may impact on both consumers and on the wider culture of Australian fashion.

Malnutrition and chemotherapy : implications for nursing practice

Background: Malnutrition before and during chemotherapy is associated with poor treatment outcomes. The risk of cancer-related malnutrition is exacerbated by common nutrition impact symptoms during chemotherapy, such as nausea, diarrhoea and mucositis. Aim of presentation: To describe the prevalence of malnutrition/ malnutrition risk in two samples of patients treated in a quaternary-level chemotherapy unit. Research design: Cross sectional survey. Sample 1: Patients ≥ 65 years prior to chemotherapy treatment (n=175). Instrument: Nurse-administered Malnutrition Screening Tool to screen for malnutrition risk and body mass index (BMI). Sample 2: Patients ≥ 18 years receiving chemotherapy (n=121). Instrument: Dietitian-administered Patient Generated Subjective Global Assessment to assess malnutrition, malnutrition risk and BMI. Findings Sample 1: 93/175 (53%) of older patients were at risk of malnutrition prior to chemotherapy. 27 (15%) were underweight (BMI <21.9); 84 (48%) were overweight (BMI >27). Findings Sample 2: 31/121 patients (26%) were malnourished; 12 (10%) had intake-limiting nausea or vomiting; 22 (20%) reported significant weight loss; and 20 (18%) required improved nutritional symptom management during treatment. 13 participants with malnutrition/nutrition impact symptoms (35%) had no dietitian contact; the majority of these participants were overweight. Implications for nursing: Patients with, or at risk of, malnutrition before and during chemotherapy can be overlooked, particularly if they are overweight. Older patients seem particularly at risk. Nurses can easily and quickly identify risk with the regular use of the Malnutrition Screening Tool, and refer patients to expert dietetic support, to ensure optimal treatment outcomes.

Nutritional status of Ugandan women living with HIV/AIDS : anthropometry and body composition assessment

Human immunodeficiency virus (HIV) that leads to acquired immune deficiency syndrome (AIDs) reduces immune function, resulting in opportunistic infections and later death. Use of antiretroviral therapy (ART) increases chances of survival, however, with some concerns regarding fat re-distribution (lipodystrophy) which may encompass subcutaneous fat loss (lipoatrophy) and/or fat accumulation (lipohypertrophy), in the same individual. This problem has been linked to Antiretroviral drugs (ARVs), majorly, in the class of protease inhibitors (PIs), in addition to older age and being female. An additional concern is that the problem exists together with the metabolic syndrome, even when nutritional status/ body composition, and lipodystrophy/metabolic syndrome are unclear in Uganda where the use of ARVs is on the increase. In line with the literature, the overall aim of the study was to assess physical characteristics of HIV-infected patients using a comprehensive anthropometric protocol and to predict body composition based on these measurements and other standardised techniques. The other aim was to establish the existence of lipodystrophy, the metabolic syndrome, andassociated risk factors. Thus, three studies were conducted on 211 (88 ART-naïve) HIV-infected, 15-49 year-old women, using a cross-sectional approach, together with a qualitative study of secondary information on patient HIV and medication status. In addition, face-to-face interviews were used to extract information concerning morphological experiences and life style. The study revealed that participants were on average 34.1±7.65 years old, had lived 4.63±4.78 years with HIV infection and had spent 2.8±1.9 years receiving ARVs. Only 8.1% of participants were receiving PIs and 26% of those receiving ART had ever changed drug regimen, 15.5% of whom changed drugs due to lipodystrophy. Study 1 hypothesised that the mean nutritional status and predicted percent body fat values of study participants was within acceptable ranges; different for participants receiving ARVs and the HIV-infected ART-naïve participants and that percent body fat estimated by anthropometric measures (BMI and skinfold thickness) and the BIA technique was not different from that predicted by the deuterium oxide dilution technique. Using the Body Mass Index (BMI), 7.1% of patients were underweight (<18.5 kg/m2) and 46.4% were overweight/obese (≥25.0 kg/m2). Based on waist circumference (WC), approximately 40% of the cohort was characterized as centrally obese. Moreover, the deuterium dilution technique showed that there was no between-group difference in the total body water (TBW), fat mass (FM) and fat-free mass (FFM). However, the technique was the only approach to predict a between-group difference in percent body fat (p = .045), but, with a very small effect (0.021). Older age (β = 0.430, se = 0.089, p = .000), time spent receiving ARVs (β = 0.972, se = 0.089, p = .006), time with the infection (β = 0.551, se = 0.089, p = .000) and receiving ARVs (β = 2.940, se = 1.441, p = .043) were independently associated with percent body fat. Older age was the greatest single predictor of body fat. Furthermore, BMI gave better information than weight alone could; in that, mean percentage body fat per unit BMI (N = 192) was significantly higher in patients receiving treatment (1.11±0.31) vs. the exposed group (0.99±0.38, p = .025). For the assessment of obesity, percent fat measures did not greatly alter the accuracy of BMI as a measure for classifying individuals into the broad categories of underweight, normal and overweight. Briefly, Study 1 revealed that there were more overweight/obese participants than in the general Ugandan population, the problem was associated with ART status and that BMI broader classification categories were maintained when compared with the gold standard technique. Study 2 hypothesized that the presence of lipodystrophy in participants receiving ARVs was not different from that of HIV-infected ART-naïve participants. Results showed that 112 (53.1%) patients had experienced at least one morphological alteration including lipohypertrophy (7.6%), lipoatrophy (10.9%), and mixed alterations (34.6%). The majority of these subjects (90%) were receiving ARVs; in fact, all patients receiving PIs reported lipodystrophy. Period spent receiving ARVs (t209 = 6.739, p = .000), being on ART (χ2 = 94.482, p = .000), receiving PIs (Fisher’s exact χ2 = 113.591, p = .000), recent T4 count (CD4 counts) (t207 = 3.694, p = .000), time with HIV (t125 = 1.915, p = .045), as well as older age (t209 = 2.013, p = .045) were independently associated with lipodystrophy. Receiving ARVs was the greatest predictor of lipodystrophy (p = .000). In other analysis, aside from skinfolds at the subscapular (p = .004), there were no differences with the rest of the skinfold sites and the circumferences between participants with lipodystrophy and those without the problem. Similarly, there was no difference in Waist: Hip ratio (WHR) (p = .186) and Waist: Height ratio (WHtR) (p = .257) among participants with lipodystrophy and those without the problem. Further examination showed that none of the 4.1% patients receiving stavudine (d4T) did experience lipoatrophy. However, 17.9% of patients receiving EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI) had lipoatrophy. Study 2 findings showed that presence of lipodystrophy in participants receiving ARVs was in fact far higher than that of HIV-infected ART-naïve participants. A final hypothesis was that the prevalence of the metabolic syndrome in participants receiving ARVs was not different from that of HIV-infected ART-naïve participants. Moreover, data showed that many patients (69.2%) lived with at least one feature of the metabolic syndrome based on International Diabetic Federation (IDF, 2006) definition. However, there was no single anthropometric predictor of components of the syndrome, thus, the best anthropometric predictor varied as the component varied. The metabolic syndrome was diagnosed in 15.2% of the subjects, lower than commonly reported in this population, and was similar between the medicated and the exposed groups (χ 21 = 0.018, p = .893). Moreover, the syndrome was associated with older age (p = .031) and percent body fat (p = .012). In addition, participants with the syndrome were heavier according to BMI (p = .000), larger at the waist (p = .000) and abdomen (p = .000), and were at central obesity risk even when hip circumference (p = .000) and height (p = .000) were accounted for. In spite of those associations, results showed that the period with disease (p = .13), CD4 counts (p = .836), receiving ART (p = .442) or PIs (p = .678) were not associated with the metabolic syndrome. While the prevalence of the syndrome was highest amongst the older, larger and fatter participants, WC was the best predictor of the metabolic syndrome (p = .001). Another novel finding was that participants with the metabolic syndrome had greater arm muscle circumference (AMC) (p = .000) and arm muscle area (AMA) (p = .000), but the former was most influential. Accordingly, the easiest and cheapest indicator to assess risk in this study sample was WC should routine laboratory services not be feasible. In addition, the final study illustrated that the prevalence of the metabolic syndrome in participants receiving ARVs was not different from that of HIV-infected ART-naïve participants.

Pregnancy loss and psychiatric disorders in young women : an Australian birth cohort study

Background Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Aims To examine whether abortion or miscarriage are associated with subsequent psychiatric and substance use disorders. Method A sample (n=1223) of women from a cohort born between 1981 and 1984 in Australia were assessed at 21 years for psychiatric and substance use disorders and lifetime pregnancy histories. Results Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis): abortion odds ratio (OR)=3.6 (95% CI 2.0–6.7) and miscarriage OR=2.6 (95% CI 1.2–5.4). Abortion was associated with alcohol use disorder (OR=2.1, 95% CI 1.3–3.5) and 12-month depression (OR=1.9, 95% CI 1.1–3.1). Conclusions These findings add to the growing body of evidence suggesting that pregnancy loss per se, whether abortion or miscarriage, increases the risk of a range of substance use disorders and affective disorders in young women.

Pregnancy loss and mental health

Between 8 and 20 percent of depression in young men and women aged 18-23 is associated with pregnancy loss, according to a recent analysis of the 30 year Mater Hospital longitudinal study of mothers and children. Dr Kaeleen Dingle from the University of Queensland explains the study and discusses the implications for both men and women.

FP01-5 Pregnancy loss and psychiatric disorders in young men and women : results from Australian longitudinal cohort study

Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Little is known about later adverse psychiatric outcomes in young men whose partners have fallen pregnant and either go on to have a child, have an abortion or miscarry. 1223 women and 1159 men, from an Austrailan cohort born between 1981 and 1984, were assessed at 21 years for psychiatric and substance misuse and lifetime pregnancy histories. Young women reporting a pregnancy loss (either miscarriage or abortion) had nearly three times the odds of experiencing a illicit drug disorder (excluding cannabis), and nearly twice the odds of an alcohol misuse compared to never pregnant women. Young men whose partner had an abortion, but not a miscarriage, had nearly twice the odds of cannabis disorder, illicit drug disorder, and mood disorder compared to men that had never fathered a pregnancy. Young women who have lost a pregnancy have an increased risk of developing alcohol or substance abuse in later life. Young men whose partner aborted a pregnancy only had an increased of substance abuse and mood disorder in later life. These findings add to the growing body of evidence suggesting that pregnancy loss per se increases the risk of a range of substance use disorders in young women. The findings for young men are novel and raise the possibility that the associations measured may be due to common unmeasured factors associated with early pregnancy in young people rather than pregnancy loss.

Design, sustainability and Australian mass-market fashion : three case studies

The production of fashion garments has negative environmental and social impacts that can potentially be reduced through decisions made in the design process. This research explores to what extent Australian mass-market fashion designers consider environmental sustainability within product design. The study presents three case studies from different market levels, assembled through interviews with designers, along with an analysis of the Australian mass-market fashion industry. The project provides insights into the workings of the fashion design process within mid and high volume companies, and identifies opportunities and barriers for consideration of sustainability.

Mass spectrometry-based metabolomics towards understanding of gene functions with a diversity of biological contexts

Currently, mass spectrometry-based metabolomics studies extend beyond conventional chemical categorization and metabolic phenotype analysis to understanding gene function in various biological contexts (e.g., mammalian, plant, and microbial). These novel utilities have led to many innovative discoveries in the following areas: disease pathogenesis, therapeutic pathway or target identification, the biochemistry of animal and plant physiological and pathological activities in response to diverse stimuli, and molecular signatures of host-pathogen interactions during microbial infection. In this review, we critically evaluate the representative applications of mass spectrometry-based metabolomics to better understand gene function in diverse biological contexts, with special emphasis on working principles, study protocols, and possible future development of this technique. Collectively, this review raises awareness within the biomedical community of the scientific value and applicability of mass spectrometry-based metabolomics strategies to better understand gene function, thus advancing this application's utility in a broad range of biological fields

Metabolic urinary profiling of alcohol hepatotoxicity and intervention effects of Yin Chen Hao Tang in rats using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

This paper was designed to study metabonomic characters of the hepatotoxicity induced by alcohol and the intervention effects of Yin Chen Hao Tang (YCHT), a classic traditional Chinese medicine formula for treatment of jaundice and liver disorders in China. Urinary samples from control, alcohol- and YCHT-treated rats were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) in positive ionization mode. The total ion chromatograms obtained from the control, alcohol- and YCHT-treated rats were easily distinguishable using a multivariate statistical analysis method such as the principal components analysis (PCA). The greatest difference in metabolic profiling was observed from alcohol-treated rats compared with the control and YCHT-treated rats. The positive ions m/z 664.3126 (9.00 min) was elevated in urine of alcohol-treated rats, whereas, ions m/z 155.3547 (10.96 min) and 708.2932 (9.01 min) were at a lower concentration compared with that in urine of control rats, however, these ions did not indicate a statistical difference between control rats and YCHT-treated rats. The ion m/z 664.3126 was found to correspond to ceramide (d18:1/25:0), providing further support for an involvement of the sphingomyelin signaling pathway in alcohol hepatotoxicity and the intervention effects of YCHT.

Development of a rapid and validated method for investigating the metabolism of scoparone in rat using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

Scoparone (6,7-dimethoxycoumarin) is known to have a wide range of pharmacological properties. In this study, a rapid and validated ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTof-MS) method was developed to investigate the metabolism of scoparone in rat for the first time. The new method reduced the sample handling and analytical time by three- to six-fold, and the detection limit by five- to 1000-fold, compared to published methods. Far more metabolites were detected and identified compared to published data, which were preliminarily identified as scopoletin, isoscopoletin, isofraxidin, and fraxidin, respectively, when subjected to tandem mass spectrometry analyses. It is found that the metabolic trajectory of scoparone in rat focused on phase I metabolism which is obviously different from published results, and revealed a wide range of pharmacological properties of scoparone partly attributed to the bioactivities of its metabolites.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Timing, origin and emplacement dynamics of mass flows offshore of SE Montserrat in the last 110 ka : implications for landslide and tsunami hazards, eruption history, and volcanic island evolution

Mass flows on volcanic islands generated by volcanic lava dome collapse and by larger-volume flank collapse can be highly dangerous locally and may generate tsunamis that threaten a wider area. It is therefore important to understand their frequency, emplacement dynamics, and relationship to volcanic eruption cycles. The best record of mass flow on volcanic islands may be found offshore, where most material is deposited and where intervening hemipelagic sediment aids dating. Here we analyze what is arguably the most comprehensive sediment core data set collected offshore from a volcanic island. The cores are located southeast of Montserrat, on which the Soufriere Hills volcano has been erupting since 1995. The cores provide a record of mass flow events during the last 110 thousand years. Older mass flow deposits differ significantly from those generated by the repeated lava dome collapses observed since 1995. The oldest mass flow deposit originated through collapse of the basaltic South Soufriere Hills at 103-110 ka, some 20-30 ka after eruptions formed this volcanic center. A ∼1.8 km3 blocky debris avalanche deposit that extends from a chute in the island shelf records a particularly deep-seated failure. It likely formed from a collapse of almost equal amounts of volcanic edifice and coeval carbonate shelf, emplacing a mixed bioclastic-andesitic turbidite in a complex series of stages. This study illustrates how volcanic island growth and collapse involved extensive, large-volume submarine mass flows with highly variable composition. Runout turbidites indicate that mass flows are emplaced either in multiple stages or as single events.