Molecular transduction in receptor-ligand systems by planar electromagnetic fields / Transdução molecular em sistemas receptor-ligante por campos electromagnéticos planares

The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptor ligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.

A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução – a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.

Molecular transduction in receptor-ligand systems by planar electromagnetic fields

Abstract The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptor-ligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.

Resumo A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.

Molecular transduction in receptor-ligand systems by planar electromagnetic fields / Transdução molecular em sistemas receptor-ligante por campos electromagnéticos planares

The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptorligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.

A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução ­ a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.

Adverse effects and duration of treatment of TB in Canterbury, New Zealand.

BACKGROUND Treatment of TB is often extended beyond the recommended duration. The aim of this study was to assess prevalence of extended treatment and to identify associated risk factors. We also aimed to determine the frequency and type of adverse drug reactions (ADR) experienced by this study population.METHODS We performed a retrospective cohort study of all patients treated for active TB at Christchurch Hospital, Christchurch, New Zealand, between 1 March 2012 and 31 December 2018. Data for 192 patients were collected on patient demographics, disease characteristics and treatment characteristics, including planned and actual duration of treatment and ADRs.RESULTS Of 192 patients, 35 (18.2%) had treatment extended, and 85 (46.5%) of 183 with fully drug-susceptible TB received ≥9 months treatment. The most common reasons for extension were persistent or extensive disease and ADR. Extended treatment duration was not associated with any patient or disease characteristics. We found 35 (18.2%) patients experienced at least one ADR. The most common ADRs were hepatitis, rash and peripheral neuropathy.CONCLUSION TB treatment extension beyond WHO guidelines is common. Further research is needed to guide management of those with slow response to treatment. Methods for early detection of ADR, systems to improve adherence and therapeutic drug monitoring are potentially useful strategies.

Molecular transduction in receptor-ligand systems by planar electromagnetic fields.

The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptor-ligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.

Machine learning based deconvolution of microarray atrial samples from atrial fibrillation patients reveals increased fractions of follicular CD4+ T lymphocytes and gamma-delta T cells.

A potential relationship between T cell immunity and development of atrial fibrillation (AF) has been proposed. Historically in AF patients it has been reported that peripheral blood had elevated CD4+ T cells. However few studies have explored whether there is a direct increase of CD4+ T cells in atrial tissues with AF. In this study, public domain micro-array dataset of cardiac surgery patients with atrial tissue biopsies in AF and non-AF patients have been used to explore immune cell subsets. Machine learning based deconvolution of permanent atrial fibrillation microarray atrial samples was applied using Cibersort to enumerate the relative fractions of twenty-two different leukocyte sub-populations. Cibersort enumerated significantly increased fractions of follicular CD4+ T lymphocytes and gamma-delta T cells in the atria of permanent AF subjects. Gene expression analysis of permanent AF microarray tissue samples with elevated follicular CD4+ T cell fractions with gene pathways associated with myocardial substrate remodelling. That is both integrin and non-integrin mediated gene interactions between inflammatory cells and the extra cellular matrix, including infiltrating follicular CD4+ T cells that trafficked to the atria by virtue of the repertoire of cell surfaced expressed adhesion molecules. Additionally, IL-17 and other interleukin inflammatory gene heat maps were associated with enhanced CD4+ follicular T cell expression in our profiled atrial tissues with AF. These observations suggest that atrial structural remodelling was associated with the presence of pathogenic T cell mediated inflammation, present in AF atria but not in non-AF atria.

RUNX1T1 rs34269950 is associated with obesity and metabolic syndrome.

BACKGROUND: Runt-related transcription factor 1 (RUNX1T1) isoforms are involved in adipogenesis. RUNX1T1 is mediated by the fat mass and obesity-associated (FTO). However, the extent to which RUNX1T1 single-nucleotide polymorphisms (SNPs) are associated with obesity risk or metabolic abnormalities in a community population basis is unknown. METHODS: Samples were obtained from the Australian Crossroads study bio-bank. SNPs located in the coding region and 3'untranslated regions of RUNX1T1 with minor allele frequency ≥0.05 were analysed using Taqman genotyping assays. RESULTS: Eight candidate SNPs were genotyped successfully in 1440 participants. Of these SNPs only rs34269950 located in the 'RRACH' motif, the most common N6-methyladenosine (m6A) methylation modification site (recognized by FTO), was significantly associated with obesity risk and metabolic abnormalities. Specifically, compared to AA genotype, rs34269950 del/del genotype was associated with a 1.47 [95% confidence interval (CI): 1.01-2.14, P = 0.042] fold higher rate of obesity risk. Additionally, the del/del genotype was associated with a 60% increased risk of metabolic syndrome (MetS) [odds ratio (OR) = 1.60, 95% CI: 1.10-2.32, P = 0.015], in comparison to the AA genotype. Finally, rs34269950 del/del increased the risk of a larger waist circumference (OR = 1.65, 95% CI: 1.15-2.36, P = 0.007), but not other components of MetS. CONCLUSION: Our study demonstrates that RUNX1T1 rs34269950, located in a potential FTO recognition motif, is significantly associated with waist circumference. This provides novel evidence to suggest SNPs located in RRACH motif may be involved in RNA m6A modification and mechanistic pathways that influence abdominal obesity.

Sex-specific educational attainment is associated with telomere length in an Australian rural population.

BACKGROUND: There is limited understanding on whether and how socioeconomic status (SES), particularly educational attainment and household income, impacts on telomere length in an Australian rural context. Additionally, it is unknown whether access to health services via the Australian public or private health system influences telomere length. AIM: This study investigates whether there is a relationship between telomere length and SES indicators (income, education) as well as health insurance status in a rural Australian population. METHODS: Samples were drawn from the Australian Rural Victoria cross-sectional Crossroads Study. Leucocyte telomere length (LTL) was measured using a multiplex quantitative polymerase chain reaction method. RESULTS: Among 1424 participants, we did not find a significant main effect association with LTL across education, income level and health insurance. An exploratory finding was sex may influence the relationship between educational attainment and LTL (P = 0.021). In males, but not females, higher education was associated with longer LTL by 0.033 [95% confidence interval (CI) 0.002-0.063, P = 0.035]; in those with low education attainment, male participants had shorter LTL by 0.058 (95% CI -0.086 to -0.029) than female participants (P < 0.0001). CONCLUSION: Being male and having lower education attainment was associated with shorter telomere length in our rural population. Evidence from our study supports the importance of education on LTL in males in rural Australia. Our studies also support previous findings that LTL in later life may not be closely associated with indicators of SES.

Engaging stakeholders in research to address water-energy-food (WEF) nexus challenges.

The water-energy-food (WEF) nexus has become a popular, and potentially powerful, frame through which to analyse interactions and interdependencies between these three systems. Though the case for transdisciplinary research in this space has been made, the extent of stakeholder engagement in research remains limited with stakeholders most commonly incorporated in research as end-users. Yet, stakeholders interact with nexus issues in a variety of ways, consequently there is much that collaboration might offer to develop nexus research and enhance its application. This paper outlines four aspects of nexus research and considers the value and potential challenges for transdisciplinary research in each. We focus on assessing and visualising nexus systems; understanding governance and capacity building; the importance of scale; and the implications of future change. The paper then proceeds to describe a novel mixed-method study that deeply integrates stakeholder knowledge with insights from multiple disciplines. We argue that mixed-method research designs-in this case orientated around a number of cases studies-are best suited to understanding and addressing real-world nexus challenges, with their inevitable complex, non-linear system characteristics. Moreover, integrating multiple forms of knowledge in the manner described in this paper enables research to assess the potential for, and processes of, scaling-up innovations in the nexus space, to contribute insights to policy and decision making.

[Planar molecular arrangements aid the design of MHC class II binding peptides].

The coupling between peptides and MHC-II proteins in the human immune system is not well understood. This work presents an evidence-based hypothesis of a guiding intermolecular force present in every human MHC-II protein (HLA-II). Previously, we examined the spatial positions of the fully conserved residues in all HLA-II protein types. In each one, constant planar patterns were revealed. These molecular planes comprise of amino acid groups of the same chemical species (for example, Gly) distributed across the protein structure. Each amino acid plane has a unique direction and this directional element offers spatial selectivity. Constant within all planes, too, is the presence of an aromatic residue possessing electrons in movement, leading the authors to consider that the planes generate electromagnetic fields that could serve as an attractive force in a single direction. Selection and attraction between HLA-II molecules and antigen peptides would, therefore, be non-random, resulting in a coupling mechanism as effective and rapid as is clearly required in the immune response. On the basis of planar projections onto the HLA-II groove, modifications were made by substituting the key residues in the class II-associated invariant chain peptide-a peptide with a universal binding affinity-resulting in eight different modified peptides with affinities greater than that of the unmodified peptide. Accurate and reliable prediction of MHC class II-binding peptides may facilitate the design of universal vaccine-peptides with greatly enhanced binding affinities. The proposed mechanisms of selection, attraction and coupling between HLA-II and antigen peptides are explained further in the paper.

rs9939609 FTO genotype associations with FTO methylation level influences body mass and telomere length in an Australian rural population.

BACKGROUND: The fat mass- and obesity-associated (FTO) gene influences energy homeostasis in humans. Although the obesity-related variant, rs9939609 has been replicated across a number of cohort studies, there remains significant variance and a low to modest association. Telomere length is another commonly reported obesity risk factor. We hypothesize understanding the associations between FTO rs9939609 with FTO methylation and telomere length will provide a more accurate assessment of obesity risk. METHODS: Overall, 942 participants free of diabetes or pre-diabetes were included in the retrospective study. Leukocyte genomic DNA was analyzed for rs9939609 genotyping, FTO gene methylation and leukocyte telomere length (LTL) measurement. RESULTS: In general linear models, rs9939609 AA genotypes were associated with increased fat percentage (3.15%, P=0.001), fat mass (4.16 kg, P=0.001), body mass index (BMI) (1.38, P=0.006) and waist circumference (3.35 cm, P=0.006), but not with FTO methylation or LTL in this overall population. However, when participants were stratified into higher and lower FTO methylation groups, the AA genotype possesses a 2.04-fold increased obesity risk in comparison to TT genotype (95%CI, 1.07-3.89, P=0.031) in participants with a higher FTO methylation level, but this association was absent in the lower FTO methylation sub-group. Moreover, AT and AA genotype carriers were associated with shorter LTL compared to TT carriers (P=0.020 and P=0.111, respectively) in the higher FTO methylation level group. However, this association was absent in the lower methylation group. Furthermore, FTO gene methylation level was significantly associated with LTL in the 942 samples (P=0.017). CONCLUSIONS: FTO rs9939609 is associated with obesity risk and LTL in this study, where this association is only observed at higher, but not lower, FTO methylation levels of participants. Our data suggest association of multiple factors, including FTO methylation level, may be involved in one of several mechanisms underlying the commonly reported obesity risk of this FTO polymorphism.

Cognitive impairment and reduced quality of life among old-age groups in Southern Urban India: home-based community residents, free and paid old-age home residents.

AIM: The purpose of the study were (i) to screen for cognitive impairment using Mini-Mental Status Examination among three old-age groups based on dwelling types in Chennai, India i.e. residential paid old-age homes, residential free (charitable) homes and home-based community-dwelling residents; (ii) secondly to investigate factors (demographic, psychological, medical and disability) associated with cognitive impairment in the these old-age; (iii) third, to investigate the independent association between cognitive impairment and health-related quality of life (QOL) among elderly across aged care dwelling types. METHODS: A total of 499 elderly from three old-age groups were interviewed in this cross-sectional study (173 elderly home-based community-dwellers, 176 paid-home and 150 free-home residents). All the participants were interviewed for their socio-economic condition, medical morbidity, self-reported worry and anxiety, disability and QOL. RESULTS: 42.7% free-home elderly residents were found to have cognitive impairment, whereas 32.4% of paid-home and 21.9% of community-dwelling elderly had cognitive impairment. The residents of free-home were less educated, had lower income and reported higher incidence of worry, anxiety, disability and poor QOL than community-dwelling or paid-home residents. Increasing age, low education, female gender, high blood pressure and disability were associated with cognitive impairment. Cognitive impairment had significant negative effect on their health-related QOL (b = -0.10, P = 0.01), independent of age, gender, education, chronic illness and dwelling type. CONCLUSION: The burden of cognitive impairment was high in all aged-care dwelling types in urban India; with free charitable home residents being worse affected. Cognitive impairment was associated with disability and poor health-related QOL in these age-care settings.

Adverse drug events are a major cause of acute medical admission.

BACKGROUND: Adverse drug events (ADE) contribute significantly to hospital admissions. Prospective New Zealand data are scant, and the ability of clinical coding to identify ADE associated admissions is uncertain. Outcomes after cessation of causative medications are unknown. AIMS: To assess the frequency, nature and causality of ADE associated with acute admissions to General Medicine at Christchurch Hospital. METHODS: Prospective observational study of patients admitted to our medical team over 20 weeks. RESULTS: Of 336 admissions, 96 (28.6%) were ADE related. Sixty-five (19.3%) were caused by an ADE, and 31 (9.2%) were contributed to by an ADE. The mean age of non-ADE patients was 64.3 years (range 16-91), which was similar to the mean age of ADE patients (65.9 years; 21-92). However, if intentional overdoses and recreational drug use were excluded, ADE patients were significantly older at 72.4 years (21-92) (P = 0.0007). ADE patients took more regular medications on admission (mean 6.6, range 0-22) than non-ADE patients (mean 5.0, 0-18), (P = 0.003). The average length of stay was similar. The commonest medications implicated were vasodilators, psychotropics and diuretics. The most common adverse effects were postural hypotension and/or vasovagal syncope (29% of ADE), intentional overdoses and recreational drug use (15%) and acute renal failure and/or clinical dehydration (10%). Seventy-six patients had culprit medications stopped or reduced, and this potentially contributed to six readmissions. Coding identified 61% of ADE associated admissions. CONCLUSION: ADE are a common cause of hospital admission. The most frequent problems are postural hypotension and vasovagal syncope, intentional drug misuse and dehydration.

Chronic NG-nitro-l-arginine methyl ester (L-NAME) administration in C57BL/6J mice induces a sustained decrease in c-kit positive cells during development of cardiac hypertrophy.

Chronic NG-nitro-l-arginine methyl ester (L-NAME) administration induces cardiac hypertrophy in rodent models. Our aims is to determine the role of c-kit expression in L-NAME induced cardiac hypertrophy. 12-20 week old C57BL/6J mice (5 per group) were administered L-NAME (0.325mg/ml) in the drinking water. Hearts were excised at 1-day, 2-days, 5-days, 2-weeks or 6-weeks; or controls which received no L-NAME. Ventricular cross-sectional wall thickness and individual cardiac myocytes cross-sectional area and cardiomyocyte/nuclear ratio to determine cardiac hypertrophy. Immuno-histochemical staining for c-kit, sca-1 and BCRP undertaken. Six weeks L-NAME administration induced significant cardiac hypertrophy compared to control hearts, evidenced by an increase in the thickness of the cross-sectional free ventricular wall (p<0.05) and an increase in mean individual cross-sectional area of cardiac myocytes in the LV wall (p<0.007). We observed c-kit(+) cells (predominately non-mast cell sub-types) in both healthy mice and in the L-NAME treated mice. C-kit staining in the left ventricular cross sections following L-NAME remained stable at 1 and 2 days compared to controls (p=NS). After 5 days of L-NAME we observed c-kit expression to decrease below control levels (p<0.05) and these lower levels were sustained at 2 and 6 weeks. C-kit expression does not decrease during two days of L-NAME administration, suggesting, firstly, that the later decrease in c-kit is not due to NOS inhibition directly and, secondly, there is the possibility for c-kit(+) cell differentiation into other cell types, possibly inducing myocardial cellular hyperplasia, without significant replacement of the original pool of c-kit(+) cells.

Effects of cannabis on lung function: a population-based cohort study.

The effects of cannabis on lung function remain unclear and may be different from those of tobacco. We compared the associations between use of these substances and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco use were reported at ages 18, 21, 26 and 32 yrs. Spirometry, plethysmography and carbon monoxide transfer factor were measured at 32 yrs. Associations between lung function and exposure to each substance were adjusted for exposure to the other substance. Cumulative cannabis use was associated with higher forced vital capacity, total lung capacity, functional residual capacity and residual volume. Cannabis was also associated with higher airway resistance but not with forced expiratory volume in 1 s, forced expiratory ratio or transfer factor. These findings were similar among those who did not smoke tobacco. In contrast, tobacco use was associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio, lower transfer factor and higher static lung volumes, but not with airway resistance. Cannabis appears to have different effects on lung function from those of tobacco. Cannabis use was associated with higher lung volumes, suggesting hyperinflation and increased large-airways resistance, but there was little evidence for airflow obstruction or impairment of gas transfer.

Chronic high dose captopril decreases total heart rate variability and increases heart rate in C57BL/6J mice.

The effects of high dose captopril, within the therapeutic range, on autonomic activity are unknown in those with normal cardiovascular function. Thus the study aims were to assess the effects of high dose captopril on autonomic function in mice. Autonomic activity was measured using heart rate variability (HRV). ECG recordings were obtained from 18 Male C57BL/6J mice (20-25 g) subdivided into control (N=8) or mice receiving oral captopril (0.688 mg/ml captopril in the drinking water for 6 weeks, N=10). HRV results for linear and non-linear parameters were attenuated following chronic captopril for 6 weeks compared to control. Captopril was associated with a trend for an increase in average heart rate and approximate entropy (ApEn), a non-linear measure of HRV decreased significantly compared to control (p<0.05). In conclusion high dose captopril reduces total HRV and increases heart rate in normotensive mice with normal cardiac function.

Associations between birth weight, early childhood weight gain and adult lung function.

BACKGROUND: Low birth weight is associated with lower values for spirometry in adults but it is not known if birth weight influences other measures of pulmonary function. It is also unclear whether postnatal growth affects adult lung function. The associations between birth weight, postnatal growth and adult lung function were assessed in an unselected birth cohort of 1037 children. METHODS: Birth weight, weight gain between birth and age 3 years, and lung function at age 32 years were measured. Analyses were adjusted for adult height and sex and further adjusted for multiple other potential confounding factors. RESULTS: Birth weight was positively correlated with spirometric (forced expiratory volume in 1 s and forced vital capacity) and plethysmographic (total lung capacity and functional residual capacity) lung function and with lung diffusing capacity. These associations persisted after adjustment for confounding factors including adult weight, exposure to cigarette smoke in utero and during childhood, personal smoking, socioeconomic status, asthma and gestational age. Weight gain between birth and age 3 years was also positively associated with lung diffusing capacity, and with higher values of lung volumes in men after adjustment for covariates. Neither birth weight nor postnatal weight gain was associated with airflow obstruction. CONCLUSIONS: Low birth weight and lower weight gain in early childhood are associated with modest reductions in adult lung function across a broad range of measures of lung volumes and with lower diffusing capacity. These findings are independent of a number of potential confounding factors and support the hypothesis that fetal and infant growth is a determinant of adult lung function.

Simultaneous widefield single molecule orientation and FRET microscopy in cells.

We combine single molecule fluorescence orientation imaging with single-pair fluorescence resonance energy transfer microscopy, using a total internal reflection microscope. We show how angles and FRET efficiencies can be determined for membrane proteins at the single molecule level and provide data from the epidermal growth factor receptor system in cells.