While the vast majority of well-structured single protein chains can now be predicted to high accuracy due to the recent AlphaFold [1] model, the prediction of multi-chain protein complexes remains a challenge in many cases. In this work, we demonstrate that an AlphaFold model trained specifically for multimeric inputs of known stoichiometry, which we call AlphaFold-Multimer, significantly increases accuracy of predicted multimeric interfaces over input-adapted single-chain AlphaFold while maintaining high intra-chain accuracy. On a benchmark dataset of 17 heterodimer proteins without templates (introduced in [2]) we achieve at least medium accuracy (DockQ [3]≥0.49) on 14 targets and high accuracy (DockQ≥0.8) on 6 targets, compared to 9 targets of at least medium accuracy and 4 of high accuracy for the previous state of the art system (an AlphaFold-based system from [2]). We also predict structures for a large dataset of 4,433 recent protein complexes, from which we score all non-redundant interfaces with low template identity. For heteromeric interfaces we successfully predict the interface (DockQ≥0.23) in 67% of cases, and produce high accuracy predictions (DockQ≥0.8) in 23% of cases, an improvement of +25 and +11 percentage points over the flexible linker modification of AlphaFold [4] respectively. For homomeric interfaces we successfully predict the interface in 69% of cases, and produce high accuracy predictions in 34% of cases, an improvement of +5 percentage points in both instances.

BackgroundThe estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200–64,500). We updated the 2006 estimate and calculated incidence for 2007–2009 using improved methodology.MethodologyWe estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups.Principal FindingsEstimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400–54,700) in 2006, 56,000 (95% CI: 49,100–62,900) in 2007, 47,800 (95% CI: 41,800–53,800) in 2008 and 48,100 (95% CI: 42,200–54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%–39.8%; p = 0.017) increase in incidence for people aged 13–29 years, driven by a 34% (95% CI: 8.4%–60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%–83.0%; p<0.001). Among people aged 13–29, only MSM experienced significant increases in incidence, and among 13–29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%.Conclusions/SignificanceOverall, HIV incidence in the United States was relatively stable 2006–2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence.

We have devised a simple enzyme immunoassay (EIA) that detects increasing levels of anti-HIV IgG after seroconversion and can be used for detecting recent HIV-1 infection. Use of a branched peptide that included gp41 immunodominant sequences from HIV-1 subtypes B, E, and D allowed similar detection of HIV-specific antibodies among various subtypes. Because of the competitive nature of the capture EIA, a gradual increase in the proportion of HIV-1-specific IgG in total IgG was observed for 2 years after seroconversion. This was in contrast to results obtained with the conventional EIA using the same antigen in solid phase, which plateaus soon after seroconversion. The assay was used to test 622 longitudinal specimens from 139 incident infections in the United States (subtype B) and in Thailand (subtypes B and E). The assay was also performed with an additional 8 M urea incubation step to assess the contribution of high-avidity antibodies. Normalized optical density (OD-n) was calculated (ODspecimen/ODcalibrator), using a calibrator specimen. An incremental analysis indicated that a cutoff of 1.0 OD-n and a seroconversion period of 160 days offered the best combination of sensitivity and specificity for classifying incident or long-term infections. The urea step increased the seroconversion period to 180 days with similar sensitivity and specificity. Separate analysis of B and E subtype specimens yielded the same optimal OD-n threshold and similar seroconversion periods. The assay was further validated in African specimens (subtypes A, C, and D) where the observed incidence was within 10% of the expected incidence. This assay should be useful for detecting recent HIV-1 infection and for estimating incidence among diverse HIV-1 subtypes worldwide.

Glycemic index (GI) describes the blood glucose response after consumption of a carbohydrate containing test food relative to a carbohydrate containing reference food, typically glucose or white bread. GI was originally designed for people with diabetes as a guide to food selection, advice being given to select foods with a low GI. The amount of food consumed is a major determinant of postprandial hyperglycemia, and the concept of glycemic load (GL) takes account of the GI of a food and the amount eaten. More recent recommendations regarding the potential of low GI and GL diets to reduce the risk of chronic diseases and to treat conditions other than diabetes, should be interpreted in the light of the individual variation in blood glucose levels and other methodological issues relating to measurement of GI and GL. Several factors explain the large inter-and intra-individual variation in glycemic response to foods. More reliable measurements of GI and GL of individual foods than are currently available can be obtained by studying, under standard conditions, a larger number of subjects than has typically been the case in the past. Meta-analyses suggest that foods with a low GI or GL may confer benefit in terms of glycemic control in diabetes and lipid management. However, low GI and GL foods can be energy dense and contain substantial amounts of sugars or undesirable fats that contribute to a diminished glycemic response. Therefore, functionality in terms of a low glycemic response alone does not necessarily justify a health claim. Most studies, which have demonstrated health benefits of low GI or GL involved naturally occurring and minimally processed carbohydrate containing cereals, vegetables and fruit. These foods have qualities other than their immediate impact on postprandial glycemia as a basis to recommend their consumption. When the GI or GL concepts are used to guide food choice, this should be done in the context of other nutritional indicators and when values have been reliably measured in a large group of individuals.

The results of this trial do not support the hypothesis that homocysteine lowering with B vitamins improves cognitive performance. (Australian Clinical Trials registry number, ACTR NO 12605000030673.).

New Zealand children, particularly those of Māori and Pacific ethnicity, may be at risk for low vitamin D status because of low vitamin D intakes, the country's latitude (35-46 degrees S), and skin color. The aim of this study was to determine 25-hydroxyvitamin D concentrations and their determinants in a national sample of New Zealand children aged 5-14 y. The 2002 National Children's Nutrition Survey was designed to survey New Zealand children, including oversampling of Māori and Pacific children to allow ethnic-specific analyses. A 2-stage recruitment process occurred using a random selection of schools, and children within each school. Serum 25-hydroxyvitamin D concentration [mean (99% CI) nmol/L] in Māori children (n = 456) was 43 (38,49), in Pacific (n = 646) 36 (31,42), and in New Zealand European and Others (NZEO) (n = 483) 53 (47,59). Among Māori, Pacific, and NZEO, the prevalence (%, 99% CI) of serum 25-hydroxyvitamin D deficiency (<17.5 nmol/L) was 5 (2,12), 8 (5,14), and 3 (1,7), respectively. The prevalence of insufficiency (<37.5 nmol/L) was 41 (29,53), 59 (42,75), and 25 (15,35), respectively. Multiple regression analysis found that 25-hydroxyvitamin D concentrations were lower in winter than summer [adjusted mean difference (99% CI) nmol/L; 15 (8,22)], lower in girls than boys [5 (1,10)], and lower in obese children than in those of "normal" weight [6 (1,11)]. Relative to NZEO, 25-hydroxyvitamin D concentrations were lower in Māori [9 (3,15)] and Pacific children [16 (10,22)]. Ethnicity and season are major determinants of serum 25-hydroxyvitamin D. There is a high prevalence of vitamin D insufficiency in New Zealand children, which may or may not contribute to increased risk of osteoporosis and other chronic disease. There is a pressing need for more convincing evidence concerning the health risks associated with the low vitamin D status in New Zealand children.

Objective To determine in a group of pregnant women if vitamin D status, based on serum 25-hydroxyvitamin D (25OHD) concentration, was associated with a subsequent risk of pre-eclampsia or adverse pregnancy outcomes.Design Prospective cohort study.Setting Vancouver, British Columbia, Canada (49°N).Population Women attending a specialist antenatal clinic because of clinical or biochemical risk factors for pre-eclampsia (n = 221).Methods Serum 25OHD concentration measured between 10 and 20 weeks of gestation.Main outcome measures Pre-eclampsia and composite adverse pregnancy outcomes.Results Of the women, 78% were vitamin D insufficient (25OHD <75 nmol/l) and 53% were vitamin D deficient (25OHD <50 nmol/l). There was no difference in the rates of pre-eclampsia, gestational hypertension, preterm birth or composite adverse pregnancy outcomes by 25OHD concentration.Conclusions Vitamin D deficiency and insufficiency were common in a group of women at high risk of pre-eclampsia; however, it was not associated with subsequent risk of an adverse pregnancy outcome.

Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid-soluble (e.g., phosphatidylcholine and sphingomyelin). Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form, versus lipid-soluble forms for foods consumed later on. This review summarizes the current knowledge on dietary recommendations and assessment methods, and dietary choline intake from food sources across the life cycle.