Publications

Monodisperse silicon nanowires were synthesized by exploiting well-defined gold nanoclusters as catalysts for one-dimensional growth via a vapor–liquid–solid mechanism. Transmission electron microscopy studies of the materials grown from 5, 10, 20, and 30 nm nanocluster catalysts showed that the nanowires had mean diameters of 6, 12, 20, and 31 nm, respectively, and were thus well defined by the nanocluster sizes. High-resolution transmission electron microscopy demonstrated that the nanowires have single-crystal silicon cores sheathed with 1–3 nm of amorphous oxide and that the cores remain highly crystalline for diameters as small as 2 nm.

Background: There has been intensive debate whether migraine with aura (MA) and migraine without aura (MO) should be considered distinct subtypes or part of the same disease spectrum. There is also discussion to what extent migraine cases collected in specialised headache clinics differ from cases from population cohorts, and how female cases differ from male cases with respect to their migraine. To assess the genetic overlap between these migraine subgroups, we examined genome-wide association (GWA) results from analysis of 23,285 migraine cases and 95,425 populationmatched controls. Methods: Detailed heterogeneity analysis of single-nucleotide polymorphism (SNP) effects (odds ratios) between migraine subgroups was performed for the 12 independent SNP loci significantly associated (p het <1.4×10-3) was observed between the MA and MO subgroups (for SNP rs9349379), and between the clinic- and population-based subgroups (for SNPs rs10915437, rs6790925 and rs6478241). However, for all 12 SNPs the risk-increasing allele was the same, and SECA found the majority of genomewide SNP effects to be in the same direction across the subgroups. Conclusions: Any differences in common genetic risk across these subgroups are outweighed by the similarities. Metaanalysis of additional migraine GWA datasets, regardless of their major subgroup composition, will identify new susceptibility loci for migraine.

Background: Smoking may lead to future cardiovascular events among those with CVD and may result in heart failure.The American Heart Association and the American College of Cardiology recommend complete cessation of smoking for patients with coronary and other vascular diseases.Little data on prevalence of smoking among people with CVD and CHF are available.Methods: We used data from the National Health and Nutrition Examination Survey 1999-2002 to examine the prevalence of current smoking by presence of CVD and CHF.The CVD was defined as self reported ischemic heart disease (IHD, [angina, coronary heart disease or heart attack]) or stroke.The prevalence data were adjusted for age, gender, race/ethnicity (white, black, Mexican American, other) and education (<high school, high school, >high school).We used SUDAAN to account for complex sampling design.Sampling weights were used to estimate weighted prevalence.Results: Of 10,105 participants aged !20 years included in these analysis, 1,027 reported CVD (785 IHD, 373 stroke) and 349 reported CHF.Current smoking was reported by 20.1% of participants with CVD and 25% of participants without CVD.Similarly 20.1% and 24.6% of participants with and without CHF were current smokers.After adjusting for demographic characteristics, the prevalence was 26.8% and 24.5% among those with and without CVD (p ¼ 0.38 for difference in prevalence) and 25.1% and 24.5% among those with and without CHF (p ¼ 0.86 for difference in prevalence).Conclusions: These data show no difference in the prevalence of current smoking by presence of CVD or CHF.The results call for additional efforts to promote smoking cessation, especially among people with CVD and CHF.Increased use of existing resources and cessation programs can be helpful.

Introduction: Emerging data from animal studies suggest that diet during pregnancy may affect fetal growth and metabolic programming of the offspring with long-term consequences. Epidemiologic data on transgenerational effects of maternal diet are sparse. Objective: We prospectively investigated the association of maternal diet, in particular, intake of grains during pregnancy with offspring growth and risk of obesity from birth through age 7 years among high risk populations, women complicated by gestational diabetes (GDM) and their children born from the index pregnancy. Methods: In the Danish National Birth Cohort (1996-2002), 918 women complicated by GDM and their singleton children were included in the study. Diet during pregnancy was measured by a validated food frequency questionnaire. Offspring body mass index z-scores (BMIZ) by WHO references were calculated using clinically measured weight and length/height at birth, 5 months, 12 months, and 7 years. Overweight/obese was defined by WHO cutoffs. Linear and Poisson regression with robust standard errors were applied, adjusting for maternal pre-pregnancy BMI and other demographic, lifestyle, and dietary factors. Results: Refined grain intake during pregnancy was significantly and positively associated with offspring growth at 7 years: adjusted β coefficient (95% CI) for a 1-serving per-day increment of refined grains associated with BMIZ at 7 years was 0.09 (0.02, 0.16). At 7 years, offspring born from women who consumed refined grains in the highest quartile (≥4.7 servings/day) experienced more than 1.7-fold increased risk of overweight/obesity as compared to those in the lowest quartile (&lt;2.2 servings/day) [adjusted relative risk (RR) (95% CI) = 1.74 (1.03, 2.93)]. Corresponding RR (95% CI) comparing the extremely high amount of refined grains (the highest 10th percentile, ≥5.9 servings/day) to the lowest quartile was 2.59 (1.28, 5.23). The associations appeared being modified by offspring diet and lifestyle factors during childhood: being more pronounced among children with less favorable lifestyle (i.e., who were breastfed &lt;6 months, physically inactive, or consumed more sugar sweetened beverages). Moreover, substitution of 1 serving/day of refined grains with an equal serving of whole grains among women was associated with an 11% (95% CI: 0.82, 0.98) reduced risk of overweight/obesity at 7 years among the offspring. Conclusions: Our findings suggest that higher intake of refined grains during pregnancy was significantly associated with greater offspring BMIZ and increased risk of overweight/obesity at 7 years. Such associations could be potentially modified by offspring diet and lifestyle factors during childhood.

Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed 2 genome-wide association studies on self-reported allergy and sensitization comprising a total of 62,330 subjects. These results were used to calculate enrichment for single nucleotide polymorphisms (SNPs) previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites and characterized commonalities in variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DNase-hypersensitive site data. Finally, we compared the allergy data with those of all known diseases. Results: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (P = 1.4e-17) encompassing 29 loci at a false discovery rate of less than 0.05. Such enrichment seemed to be a general characteristic for autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in patients with autoimmune diseases but not those with other diseases. Conclusion: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms. Further studies of these shared genetic mechanisms might help in understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.

This paper describes a method for the selective precipitation and purification of a monovalent protein (carbonic anhydrase is used as a demonstration) from cellular lysate using ammonium sulfate and oligovalent ligands. The oligovalent ligands induce the formation of protein–ligand aggregates, and at an appropriate concentration of dissolved ammonium sulfate, these complexes precipitate. The purification involves three steps: (i) the removal of high-molecular-weight impurities through the addition of ammonium sulfate to the crude cell lysate; (ii) the introduction of an oligovalent ligand and the selective precipitation of the target protein–ligand aggregates from solution; and (iii) the removal of the oligovalent ligand from the precipitate by dialysis to release the target protein. The increase of mass and volume of the proteins upon aggregate formation reduces their solubility, and results in the selective precipitation of these aggregates. We recovered human carbonic anhydrase, from crude cellular lysate, in 82% yield and 95% purity with a trivalent benzene sulfonamide ligand. This method provides a chromatography-free strategy of purifying monovalent proteins—for which appropriate oligovalent ligands can be synthesized—and combines the selectivity of affinity-based purification with the convenience of salt-induced precipitation.

The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear.The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness.In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P < 0.05). Genus.Coprococcus3 and genus.Anaerotruncus were validated in FinnGen datasets. Nine, twelve, and seven bacterial entities were identified for migraine, MA, and MO, respectively. The causal association still exists in family.Bifidobacteriaceae and order.Bifidobacteriales for migraine and MO after FDR correction. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results.Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them.