Publications

A detailed understanding of the interaction of proteins with artificial surfaces is essential for many applications in medicine and biochemistry. The affinity of surfaces toward proteins may, for instance, remove pharmacological proteins from media or control the adherence of pathogenic bacteria to protheses. Only a few analytical techniques now exist that can be used to study the binding process in real time, using unlabeled proteins. By investigating the adsorption kinetics of fibrinogen at differently terminated self-assembled monolayers (SAMs) of alkanethiols on thin gold films, it is demonstrated that acoustic plate-mode sensors are a promising analytical tool for studying the adsorption of proteins. In agreement with previous studies for fibrinogen, it is shown in situ that hexa(ethylene glycol)-terminated SAMs (HS(CH2)11(OCH2CH2)6OH) exhibit very low protein adsorption and that methyl-terminated SAMs (HS(CH2)11CH3) tend to adsorb large amounts of protein nonspecifically. The observed adsorption kinetics deviate from classical Langmuir behavior; these kinetics are compatible with a mechanism that involves an unfolding of fibrinogen after adsorption. Film quality is controlled by IR, XPS, and contact angle measurements.

This paper describes the spontaneous formation of patterns of aligned buckles in a thin film of gold deposited on the surface of an elastomer [poly(dimethylsiloxane), PDMS]. The surface of the elastomer is patterned photochemically into areas differing in stiffness and coefficient of thermal expansion. The gold is deposited while the surface of the patterned elastomer is warm (T ∼ 100 °C). On cooling, shrinkage in the elastomer places the gold film under compressive stress. The buckles relieve this compressive stress. The distribution of stresses and buckle patterns is described during the pre- and postbuckling regimes using solutions from calculations describing a model comprising a thin stiff plate resting on a thick elastic foundation.

marv_chr1-5.result. Original results files outputted from MARV from the case study using NFBC1966 data. (RESULT 17825Â kb)

Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 10 6 ) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10 −8 ) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10 −8 ) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10 −8 ) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10 −7 ) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.

This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding. The array is coupled to a tree-like arrangement of distribution channels that automatically delivers one nematode to each recording module. The same channels are then used to perfuse the recording modules with test solutions while recording the electropharyngeogram (EPG) from each worm with sufficient sensitivity to detect each pharyngeal contraction. The device accurately reported the acute effects of known anthelmintics (anti-nematode drugs) and also correctly distinguished a specific drug-resistant mutant strain of C. elegans from wild type. The approach described here is readily adaptable to parasitic species for the identification of novel anthelmintics. It is also applicable in toxicology and drug discovery programs for human metabolic and degenerative diseases for which C. elegans is used as a model.

Background: Olive oil intake has been associated with lower risk of cardiometabolic risk factors in Mediterranean populations, but little is known about these associations in the U.S. population, where olive oil intake is relatively low. Objectives: To examine whether olive oil intake is associated with total Cardiovascular Disease (CVD), coronary heart disease (CHD) and stroke risk. Methods: We included 63,867 women from the Nurses’ Health Study (1990 to 2014) and 35,512 men from the Health Professionals Follow-up Study (1990 to 2014) who were free of cancer, heart disease, and stroke at baseline. Diet was assessed using food frequency questionnaires at baseline and then every 4 years. Cumulative average of intake was used in the primary analysis. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. Results: During 24 years of follow-up, we documented 10,240 incident cases of CVD, including 6,270 CHD cases and 3,970 stroke cases. After adjusting for major diet and lifestyle factors, compared with non-consumers, those with higher olive oil intake (>1/2 tablespoon/d or > 7g/d) had 15% lower risk of total CVD [pooled hazard ratio (95% confidence interval): 0.85 (0.77, 0.93)] and 21% lower risk of CHD [pooled hazard ratio (95% confidence interval): 0.79 (0.70, 0.89)]. No significant associations were observed for total stroke or ischemic stroke. We estimated that replacing 5g of margarine, butter, mayonnaise, or dairy fat with the equivalent amount of olive oil was associated with 5-7% lower risk of total CVD and CHD. No significant associations were observed when olive oil was compared with other plant oils combined (corn, safflower, soybean and canola oil). Conclusions: Higher olive oil intake was associated with a lower risk of CHD and total CVD in two large prospective cohorts of U.S. men and women. The substitution of margarine, butter, mayonnaise, and dairy fat with olive oil might lead to a lower risk for CHD and CVD.

Background Studies mainly relied on hospital or case-control data have well documented that individuals with psychoses, and especially with schizophrenia have increased rates of physical illnesses. They have two to four-fold higher mortality risk, and about 10 to 25 years shorter life expectancy compared with the general population. The aim of this study is to evaluate the prevalence of physical illnesses in individuals with schizophrenia or with other psychoses and among people without psychoses until the age of 46 years using complete outpatient and inpatient data from birth cohort. Methods The study is based on The Northern Finland 1966 Birth Cohort (NFBC, 1966), which is a population-based prospective cohort concerning 12.058 live-born children in 1966 in the provinces of Lapland and Oulu. The study population consisted of 10,933 individuals, who were alive at the age of 16-years, and followed serially until the age of 46-years The study population was divided into three groups: those having schizophrenia ( n = 228) and those with other psychoses ( n = 240) while individuals without psychosis ( n = 10,465) formed the control group. The data was obtained from various national registers. Results Diseases of the blood and blood forming organs (prevalence in SCZ was 17% versus 10% in controls, P < 0.001), endocrine, nutritional and metabolic diseases (45% vs. 27%, P < 0.001), diabetes mellitus (7% vs. 3%, P < 0.001) and nervous diseases (33% vs. 25%, P = 0.018) were more common among individuals with SCZ compared with controls. Diseases of musculoskeletal system and connective tissue were less common in SCZ than among controls (28% vs. 41%, P < 0.001). People with other psychoses than SCZ had statistically significant association with all the diagnostic groups classified in ICD-10 except with neoplasms. Infections and parasitic diseases (prevalence in other psychoses was 44% versus 32% in controls, P < 0.001), diseases of the blood and blood forming organs (18% vs. 10%, P < 0.001), endocrine, nutritional and metabolic diseases (42% vs. 27%, P < 0.001) including diabetes mellitus (9% vs. 3%, P < 0.001), nervous diseases (40% vs. 25%, P < 0.001), diseases of the eye and adnexa (32% vs. 21%, P < 0.001), diseases of the ear and mastoid process (58% vs. 44%, P < 0.001), diseases of circulatory (50% vs. 37%, P < 0.001), respiratory (70% vs. 60%, P < 0.001) and digestive system (77% vs. 68%, P = 0.004), diseases of skin and subcutaneous tissue (23% vs. 16%, P = 0.006), diseases of musculoskeletal system and connective tissue (51% vs. 40%, P = 0.004) and diseases of genitourinary system (41% vs. 31%, P = 0.003) were more common among people with other psychoses than SCZ compared with controls. Discussion A new finding is that not only people with schizophrenia but especially those with other psychoses show a greater occurrence of somatic diseases compared with those without psychosis. The increased occurrence of somatic comorbidity in other psychoses should be noted by medical professional, and further longitudinal studies are warranted to study its possible risk factors during lifespan. Disclosure of interest The authors have not supplied their declaration of competing interest.

Introduction: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies, usually with exposure assessment limited to baseline values. As BMI is a proxy for adiposity but does not capture fat tissue or its metabolically relevant distribution, precise measurements of distinct adipose tissues are needed, so the cardiometabolic impact of an anti-obesity effect can be assessed. Hypothesis: We assessed the hypothesis that an increase in coffee consumption is associated with a reduction in body fat, in particular with trunk fat and visceral adipose tissue (VAT). Methods: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome. Changes in the consumption of caffeinated and decaffeinated coffee were derived from validated food frequency questionnaires at baseline, 6 months and yearly during follow-up. Fat tissue was measured with dual x-ray absorptiometry at baseline and after 6, 12 months and three years. Linear multilevel mixed effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue over three years. Results: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤ 3 cups/ month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95 % CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95 % CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95 % CI: -0.13 to -0.01). However, changes to even higher levels (> 1 cup/day) showed no significant association. Conclusions: Moderate consumption of caffeinated coffee, but not high consumption, was associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with metabolic syndrome. Decaffeinated coffee was not linked to adiposity indicators. In conclusion, moderate consumption of caffeinated coffee may be part of a weight management strategy.

Nanowire nanoelectronic devices have been exploited as highly sensitive subcellular resolution detectors for recording extracellular and intracellular signals from cells, as well as from natural and engineered/cyborg tissues, and in this capacity open many opportunities for fundamental biological research and biomedical applications. Here we demonstrate the capability to take full advantage of the attractive capabilities of nanowire nanoelectronic devices for long term physiological studies by passivating the nanowire elements with ultrathin metal oxide shells. Studies of Si and Si/aluminum oxide (Al2O3) core/shell nanowires in physiological solutions at 37 °C demonstrate long-term stability extending for at least 100 days in samples coated with 10 nm thick Al2O3 shells. In addition, investigations of nanowires configured as field-effect transistors (FETs) demonstrate that the Si/Al2O3 core/shell nanowire FETs exhibit good device performance for at least 4 months in physiological model solutions at 37 °C. The generality of this approach was also tested with in studies of Ge/Si and InAs nanowires, where Ge/Si/Al2O3 and InAs/Al2O3 core/shell materials exhibited stability for at least 100 days in physiological model solutions at 37 °C. In addition, investigations of hafnium oxide-Al2O3 nanolaminated shells indicate the potential to extend nanowire stability well beyond 1 year time scale in vivo. These studies demonstrate that straightforward core/shell nanowire nanoelectronic devices can exhibit the long term stability needed for a range of chronic in vivo studies in animals as well as powerful biomedical implants that could improve monitoring and treatment of disease.