Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status. Key words: Vitamin D: Populations: Public healthVitamin D plays an important role in bone mineralisation and other metabolic processes in the human body such as Ca and phosphate homeostasis and skeletal growth (1,2) . Vitamin D deficiency, for example, causes rickets in children, leading to skeletal abnormalities, short stature, delayed development or failure to thrive (3) . In adults, low values of vitamin D are associated with osteomalacia, osteopenia, osteoporosis and subsequent risk of fractures (1) . In addition to beneficial effects on musculoskeletal health, observational studies have suggested that low 25-hydroxyvitamin D (25(OH)D) values are associated with an increased risk for several extraskeletal diseases including cancer, infections, autoimmune diseases and CVD (4) . In light of the global ageing population (5) ,an almost fourfold increase in osteoporotic hip fractures since 1990 (6) and the possible risk of other chronic diseases, patterns of low 25(OH)D levels are of substantial public health interest. Vitamin D status is traditionally measured through assays of 25(OH)D, the major circulating form of vitamin D (7) . Although 25(OH)D levels below 25 nmol/l have been associated with disorders of bone metabolism (8) and are used to indicate severe vitamin D deficiency, the threshold for defining adequate stores of vitamin D in humans has not been established clearly (9) . The Institute of Medicine has suggested, for example, that approximately 97·5 % of t...

The unified global efforts to mitigate the high burden of vitamin and mineral deficiency, known as hidden hunger, in populations around the world are crucial to the achievement of most of the Millennium Development Goals (MDGs). We developed indices and maps of global hidden hunger to help prioritize program assistance, and to serve as an evidence-based global advocacy tool. Two types of hidden hunger indices and maps were created based on i) national prevalence data on stunting, anemia due to iron deficiency, and low serum retinol levels among preschool-aged children in 149 countries; and ii) estimates of Disability Adjusted Life Years (DALYs) attributed to micronutrient deficiencies in 136 countries. A number of countries in sub-Saharan Africa, as well as India and Afghanistan, had an alarmingly high level of hidden hunger, with stunting, iron deficiency anemia, and vitamin A deficiency all being highly prevalent. The total DALY rates per 100,000 population, attributed to micronutrient deficiencies, were generally the highest in sub-Saharan African countries. In 36 countries, home to 90% of the world’s stunted children, deficiencies of micronutrients were responsible for 1.5-12% of the total DALYs. The pattern and magnitude of iodine deficiency did not conform to that of other micronutrients. The greatest proportions of children with iodine deficiency were in the Eastern Mediterranean (46.6%), European (44.2%), and African (40.4%) regions. The current indices and maps provide crucial data to optimize the prioritization of program assistance addressing global multiple micronutrient deficiencies. Moreover, the indices and maps serve as a useful advocacy tool in the call for increased commitments to scale up effective nutrition interventions.

Vitamin D is a micronutrient that is needed for optimal health throughout the whole life. Vitamin D3 (cholecalciferol) can be either synthesized in the human skin upon exposure to the UV light of the sun, or it is obtained from the diet. If the photoconversion in the skin due to reduced sun exposure (e.g., in wintertime) is insufficient, intake of adequate vitamin D from the diet is essential to health. Severe vitamin D deficiency can lead to a multitude of avoidable illnesses; among them are well-known bone diseases like osteoporosis, a number of autoimmune diseases, many different cancers, and some cardiovascular diseases like hypertension are being discussed. Vitamin D is found naturally in only very few foods. Foods containing vitamin D include some fatty fish, fish liver oils, and eggs from hens that have been fed vitamin D and some fortified foods in countries with respective regulations. Based on geographic location or food availability adequate vitamin D intake might not be sufficient on a global scale. The International Osteoporosis Foundation (IOF) has collected the 25-hydroxy-vitamin D plasma levels in populations of different countries using published data and developed a global vitamin D map. This map illustrates the parts of the world, where vitamin D did not reach adequate 25-hydroxyvitamin D plasma levels: 6.7% of the papers report 25-hydroxyvitamin D plasma levels below 25 nmol/L, which indicates vitamin D deficiency, 37.3% are below 50 nmol/Land only 11.9% found 25-hydroxyvitamin D plasma levels above 75 nmol/L target as suggested by vitamin D experts. The vitamin D map is adding further evidence to the vitamin D insufficiency pandemic debate, which is also an issue in the developed world. Besides malnutrition, a condition where the diet does not match to provide the adequate levels of nutrients including micronutrients for growth and maintenance, we obviously have a situation where enough nutrients were consumed, but lacked to reach sufficient vitamin D micronutrient levels. The latter situation is known as hidden hunger. The inadequate vitamin D status impacts on health care costs, which in turn could result in significant savings, if corrected. Since little is known about the effects on the molecular level that accompany the pandemic like epigenetic imprinting, the insufficiency-triggered gene regulations or the genetic background influence on the body to maintain metabolic resilience, future research will be needed. The nutrition community is highly interested in the molecular mechanism that underlies the vitamin D insufficiency caused effect. In recent years, novel large scale technologies have become available that allow the simultaneous acquisition of transcriptome, epigenome, proteome, or metabolome data in cells of organs. These important methods are now used for nutritional approaches summarized in emerging scientific fields of nutrigenomics, nutrigenetics, or nutriepigenetics. It is believed that with the help of these novel concepts further understanding can be generated to develop f...

De novo sequencing of peptides poses one of the most challenging tasks in data analysis for proteome research. In this paper, a generative hidden Markov model (HMM) of mass spectra for de novo peptide sequencing which constitutes a novel view on how to solve this problem in a Bayesian framework is proposed. Further extensions of the model structure to a graphical model and a factorial HMM to substantially improve the peptide identification results are demonstrated. Inference with the graphical model for de novo peptide sequencing estimates posterior probabilities for amino acids rather than scores for single symbols in the sequence. Our model outperforms state-of-the-art methods for de novo peptide sequencing on a large test set of spectra.

Selection experiments and protein engineering were used to identify an amino acid position in integral membrane alkane hydroxylases (AHs) that determines whether long-chain-length alkanes can be hydroxylated by these enzymes. First, substrate range mutants of the Pseudomonas putida GPo1 and Alcanivorax borkumensis AP1 medium-chain-length AHs were obtained by selection experiments with a specially constructed host. In all mutants able to oxidize alkanes longer than C 13 , W55 (in the case of P. putida AlkB) or W58 (in the case of A. borkumensis AlkB1) had changed to a much less bulky amino acid, usually serine or cysteine. The corresponding position in AHs from other bacteria that oxidize alkanes longer than C 13 is occupied by a less bulky hydrophobic residue (A, V, L, or I). Site-directed mutagenesis of this position in the Mycobacterium tuberculosis H37Rv AH, which oxidizes C 10 to C 16 alkanes, to introduce more bulky amino acids changed the substrate range in the opposite direction; L69F and L69W mutants oxidized only C 10 and C 11 alkanes. Subsequent selection for growth on longer alkanes restored the leucine codon. A structure model of AHs based on these results is discussed. The alkane hydroxylases (AHs) of Pseudomonas putidaGPo1 and other eubacteria are of great interest for biocatalytic (37) and environmental studies (35) and as prototypes of a large family of integral membrane non-heme iron oxygenases which includes desaturases and xylene monooxygenases (24). In addition, AHs occur in pathogens such as Mycobacterium tuberculosis and Legionella pneumophila, in which they have unknown roles.The P. putida GPo1 AH catalyzes the hydroxylation of linear and branched aliphatic, alicyclic, and alkylaromatic compounds (7,20,31); oxidation of terminal alcohols to the corresponding aldehydes; demethylation of branched methyl ethers; sulfoxidation of thioethers; and epoxidation of terminal olefins (12,13,18,19) and allyl alcohol derivatives (6). One of the substrate range studies was used to estimate the approximate dimensions of the substrate-binding site (31). However, our attempts to determine the three-dimensional structure of the integral membrane AH failed, and three-dimensional structures of related proteins are not available, either. Figure 1 shows a schematic topology model of P. putida GPo1 AlkB based on an analysis of the hydrophobicity and gene fusions with alkaline phosphatase and ␤-galactosidase (34). Transmembrane (TM) helices 1 and 2, 3 and 4, and 5 and 6 are likely to form pairs because the loops connecting the three helix pairs on the periplasmic side are very short. However, nothing is known about the spatial arrangement and relative angles of the TM helices or the presence or absence of kinks. AlkB contains two iron atoms that are liganded to histidine residues located in four highly conserved, short sequence motifs (26, 28). The four sequence motifs are indicated in Fig. 1 and are located near the ends of TM helices 4 and 6. Alanine scanning has shown that the eight conserved histidines in mot...