Showing papers by "University of Zagreb published in 2008"

Complementary Feeding: A Commentary by the ESPGHAN Committee on Nutrition

Abstract: This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early ( or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.

Runs of Homozygosity in European Populations

Abstract: Estimating individual genome-wide autozygosity is important both in the identification of recessive disease variants via homozygosity mapping and in the investigation of the effects of genome-wide homozygosity on traits of biomedical importance. Approaches have tended to involve either single-point estimates or rather complex multipoint methods of inferring individual autozygosity, all on the basis of limited marker data. Now, with the availability of high-density genome scans, a multipoint, observational method of estimating individual autozygosity is possible. Using data from a 300,000 SNP panel in 2618 individuals from two isolated and two more-cosmopolitan populations of European origin, we explore the potential of estimating individual autozygosity from data on runs of homozygosity (ROHs). Termed Froh, this is defined as the proportion of the autosomal genome in runs of homozygosity above a specified length. Mean Froh distinguishes clearly between subpopulations classified in terms of grandparental endogamy and population size. With the use of good pedigree data for one of the populations (Orkney), Froh was found to correlate strongly with the inbreeding coefficient estimated from pedigrees (r = 0.86). Using pedigrees to identify individuals with no shared maternal and paternal ancestors in five, and probably at least ten, generations, we show that ROHs measuring up to 4 Mb are common in demonstrably outbred individuals. Given the stochastic variation in ROH number, length, and location and the fact that ROHs are important whether ancient or recent in origin, approaches such as this will provide a more useful description of genomic autozygosity than has hitherto been possible.

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Abstract: Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200?500 lM) compared with other mammals (3?120 lM)1. About 70% of daily urate disposal occurs via the kidneys, and in 5?25% of the human population, impaired renal excretion leads to hyperuricemia2. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7?5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter3, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.

Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial Versus Microfracture

Abstract: BackgroundAs the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo.PurposeTo determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture.Study DesignRandomized controlled trial; Level of evidence, 1.MethodsCharacterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometr...

Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial.

Abstract: In this 3-yr, randomized, double-blind, placebo- and active-controlled study, healthy postmenopausal women with osteoporosis (55–85 yr of age) were treated with bazedoxifene 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. The primary endpoint was incidence of new vertebral fractures after 36 mo; secondary endpoints included nonvertebral fractures, BMD, and bone turnover markers. Among 6847 subjects in the intent-to-treat population, the incidence of new vertebral fractures was significantly lower (p < 0.05) with bazedoxifene 20 mg (2.3%), bazedoxifene 40 mg (2.5%), and raloxifene 60 mg (2.3%) compared with placebo (4.1%), with relative risk reductions of 42%, 37%, and 42%, respectively. The treatment effect was similar among subjects with or without prevalent vertebral fracture (p = 0.89 for treatment by baseline fracture status interaction). The incidence of nonvertebral fractures with bazedoxifene or raloxifene was not significantly different from placebo. In a posthoc analysis of a subgroup of women at higher fracture risk (femoral neck T-score ≤ –3.0 and/or ≥1 moderate or severe vertebral fracture or multiple mild vertebral fractures; n = 1772), bazedoxifene 20 mg showed a 50% and 44% reduction in nonvertebral fracture risk relative to placebo (p = 0.02) and raloxifene 60 mg (p = 0.05), respectively. Bazedoxifene significantly improved BMD and reduced bone marker levels (p < 0.001 versus placebo). The incidence of vasodilatation, leg cramps, and venous thromboembolic events was higher with bazedoxifene and raloxifene compared with placebo. In conclusion, bazedoxifene significantly reduced the risk of new vertebral fracture in postmenopausal women with osteoporosis and decreased the risk of nonvertebral fracture in subjects at higher fracture risk.

Flavor physics of leptons and dipole moments

Abstract: This chapter of the report of the “Flavor in the era of the LHC” Workshop discusses the theoretical, phenomenological and experimental issues related to flavor phenomena in the charged lepton sector and in flavor conserving CP-violating processes. We review the current experimental limits and the main theoretical models for the flavor structure of fundamental particles. We analyze the phenomenological consequences of the available data, setting constraints on explicit models beyond the standard model, presenting benchmarks for the discovery potential of forthcoming measurements both at the LHC and at low energy, and exploring options for possible future experiments.

Mapping the spatial distribution of charge carriers in LaAlO3/SrTiO3 heterostructures

Abstract: At the interface between complex insulating oxides, novel phases with interesting properties may occur, such as the metallic state reported in the LaAlO(3)/SrTiO(3) system . Although this state has been predicted and reported to be confined at the interface, some studies indicate a much broader spatial extension, thereby questioning its origin. Here, we provide for the first time a direct determination of the carrier density profile of this system through resistance profile mappings collected in cross-section LaAlO(3)/SrTiO(3) samples with a conducting-tip atomic force microscope (CT-AFM). We find that, depending on specific growth protocols, the spatial extension of the high-mobility electron gas can be varied from hundreds of micrometres into SrTiO(3) to a few nanometres next to the LaAlO(3)/SrTiO(3) interface. Our results emphasize the potential of CT-AFM as a novel tool to characterize complex oxide interfaces and provide us with a definitive and conclusive way to reconcile the body of experimental data in this system.

Relativistic nuclear energy density functionals: Adjusting parameters to binding energies

Abstract: We study a particular class of relativistic nuclear energy density functionals in which only nucleon degrees of freedom are explicitly used in the construction of effective interaction terms. Short-distance (high-momentum) correlations, as well as intermediate- and long-range dynamics, are encoded in the medium (nucleon-density) dependence of the strength functionals of an effective interaction Lagrangian. Guided by the density dependence of microscopic nucleon self-energies in nuclear matter, a phenomenological ansatz for the density-dependent coupling functionals is accurately determined in self-consistent mean-field calculations of binding energies of a large set of axially deformed nuclei. The relationship between the nuclear matter volume, surface, and symmetry energies and the corresponding predictions for nuclear masses is analyzed in detail. The resulting best-fit parametrization of the nuclear energy density functional is further tested in calculations of properties of spherical and deformed medium-heavy and heavy nuclei, including binding energies, charge radii, deformation parameters, neutron skin thickness, and excitation energies of giant multipole resonances.

Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

Abstract: Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965–2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07–1.60] and in the high (RR = 1.41; 95% CI = 1.16–1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34–3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37–3.70), RRhigh = 3.13 (95% CI = 1.17–8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.

The academic environment: the students' perspective

Abstract: Dental education is regarded as a complex, demanding and often stressful pedagogical procedure. Undergraduates, while enrolled in programmes of 4-6 years duration, are required to attain a unique and diverse collection of competences. Despite the major differences in educational systems, philosophies, methods and resources available worldwide, dental students' views regarding their education appear to be relatively convergent. This paper summarizes dental students' standpoint of their studies, showcases their experiences in different educational settings and discusses the characteristics of a positive academic environment. It is a consensus opinion that the 'students' perspective' should be taken into consideration in all discussions and decisions regarding dental education. Moreover, it is suggested that the set of recommendations proposed can improve students' quality of life and well-being, enhance their total educational experience and positively influence their future careers as oral health physicians. The 'ideal' academic environment may be defined as one that best prepares students for their future professional life and contributes towards their personal development, psychosomatic and social well-being. A number of diverse factors significantly influence the way students perceive and experience their education. These range from 'class size', 'leisure time' and 'assessment procedures' to 'relations with peers and faculty', 'ethical climate' and 'extra-curricular opportunities'. Research has revealed that stress symptoms, including psychological and psychosomatic manifestations, are prevalent among dental students. Apparently some stressors are inherent in dental studies. Nevertheless, suggested strategies and preventive interventions can reduce or eliminate many sources of stress and appropriate support services should be readily available. A key point for the Working Group has been the discrimination between 'teaching' and 'learning'. It is suggested that the educational content should be made available to students through a variety of methods, because individual learning styles and preferences vary considerably. Regardless of the educational philosophy adopted, students should be placed at the centre of the process. Moreover, it is critical that they are encouraged to take responsibility for their own learning. Other improvements suggested include increased formative assessment and self-assessment opportunities, reflective portfolios, collaborative learning, familiarization with and increased implementation of information and communication technology applications, early clinical exposure, greater emphasis on qualitative criteria in clinical education, community placements, and other extracurricular experiences such as international exchanges and awareness of minority and global health issues. The establishment of a global network in dental education is firmly supported but to be effective it will need active student representation and involvement.

A cis -acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse

Abstract: In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.

The impact of business process orientation on financial and non‐financial performance

Abstract: Purpose – Extensive literature on business process management suggests that organizations could enhance their overall performance by adopting a process view of business. However, there is a lack of empirical research in this field. The purpose of this paper is to investigate the understanding of the process view and process maturity levels in a transition economy and to test the impact of process orientation maturity level on organizational performance.Design/methodology/approach – Empirical investigation combined an exploratory‐confirmatory approach using factor analysis and structural equation modeling.Findings – The investigation confirms the impact of business process orientation on organizational performance in a transition economy. The link is even stronger than in the original investigation. The results show that business process orientation leads to better non‐financial performance and indirectly to better financial performance.Practical implications – The research confirms that business process o...

Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study

Abstract: Results: Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance.Streptococcusbovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P.001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P.001), and age older than 65 years was an independent predictor of mortality. Conclusions: In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care–associated acquisition and improve outcomes in this major subgroup of patients with IE.

Analytical Solution for Cogging Torque in Surface Permanent-Magnet Motors Using Conformal Mapping

Abstract: We present an analytical method for the calculation of cogging torque in surface permanent-magnet (PM) motors. The cogging torque is calculated by integrating the Maxwell stress tensor inside the air gap. The principle of complex relative air-gap permeance derived from conformal transformation of the slot geometry is used to take into account the effect of slotting and to calculate the radial and tangential components of the air-gap flux density required for integration of the tangential component of the Maxwell stress tensor. We implemented the proposed analytical solution on a 7-kW four-pole surface PM motor and compared the results with finite-element solutions. We present an example of finding the optimal magnet angular span to yield minimum cogging torque as an example of the effectiveness of the method.

Lifespan Alterations of Basal Dendritic Trees of Pyramidal Neurons in the Human Prefrontal Cortex: A Layer-Specific Pattern

Abstract: The postnatal development and lifespan alterations in basal dendrites of large layer IIIC and layer V pyramidal neurons were quantitatively studied. Both classes of neurons were characterized by rapid dendritic growth during the first postnatal months. At birth, layer V pyramidal neurons had larger and more complex dendritic trees than those of layer IIIC; however, at 1 postnatal month both classes of neurons displayed a similar extent of dendritic outgrowth. In addition, after a more than year-long ‘‘dormant’’ period of only fine dendritic rearrangement, layer IIIC pyramidal neurons displayed a second period of dendritic growth, starting at the end of the second year and continuing in the third year. During that period, the dendritic tree of layer IIIC pyramidal neurons became more extensive than that of layer V pyramidal neurons. Thus, layer IIIC pyramidal neurons appear to show a biphasic pattern of postnatal dendritic development. Furthermore, the childhood period was characterized by transient increase in size of pyramidal cell somata, which was more pronounced for neurons in layer IIIC. These structural changes occurred during both the period of rapid cognitive development in preschool children and the period of protracted cognitive maturation during the childhood, puberty, and adolescence.

Measuring depression: Comparison and integration of three scales in the GENDEP study

Abstract: BACKGROUND: A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales. METHOD: The 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores. RESULTS: The MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely 'observed mood and anxiety', 'cognitive' and 'neurovegetative', provided a more detailed description of depression severity. CONCLUSIONS: The MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.

ACCELERATION IN FAST HALO CMEs AND SYNCHRONIZED FLARE HXR BURSTS

Abstract: We study two well-observed, fast halo CMEs, covering the full CME kinematics including the initiation and impulsive acceleration phase, and their associated flares. We find a close synchronization between the CME acceleration profile and the flare energy release as indicated by the RHESSI hard X-ray flux onsets, as well as peaks occur simultaneously within 5 minutes. These findings indicate a close physical connection between both phenomena and are interpreted in terms of a feedback relationship between the CME dynamics and the reconnection process in the current sheet beneath the CME.

Isostructural materials achieved by using structurally equivalent donors and acceptors in halogen-bonded cocrystals.

Abstract: We demonstrate the supramolecular and structural equivalence of two halogen-bond donors (I and Br) and three acceptors (O, NH and S) through the synthesis of seven isostructural halogen-bonded cocrystals, involving six different molecules: 1,4-dibromo- and 1,4-diiodotetrafluorobenzene (donors) and thiomorpholine, thioxane, morpholine, and piperazine (acceptors) The formation of isostructural cocrystals indicates how cocrystallization may be used to overcome shape and functional group dissimilarities that control molecular arrangement in the solid state The differences in composition between the seven isostructural cocrystals directly affect the strength and nature of halogen bonds between their constituents, allowing the systematic variation of cocrystal physical properties, in particular the melting point, without affecting their crystal structure Replacement of each O or S halogen-bond acceptor with an NH group provided an approximate 70 degrees C increase in melting point, whereas the replacement of I with Br as the halogen-bond donor lowered the melting point of the resulting solid by a similar amount

Glycosylation of serum proteins in inflammatory diseases.

Abstract: Inflammatory diseases are accompanied by numerous changes at the site of inflammation as well as many systemic physiological and biochemical changes In the past two decades more and more attention is being paid to changes in glycosylation and in this review we describe some of the changes found on main serum proteins (α1-acid glycoprotein, immunoglobulin G, immunoglobulin A, transferrin, haptoglobin, α2-macroglobulin, C-reactive protein, and others) Molecular background and physiological importance of most of these changes are yet to be discovered, but it is evident that glycosylation plays an important role in the inflammatory response Maybe the greatest value of these changes currently lays in their potential diagnostic and prognostic usage, either in combination with current diagnostic markers or on their own However, determining glycan structures is still technically too complex for most clinical laboratories and further efforts have to be made to develop simple analytical tools to study changes in glycosylation

Metals in proteins: correlation between the metal-ion type, coordination number and the amino-acid residues involved in the coordination

Abstract: Metal ions are constituents of many metalloproteins, in which they have either catalytic (metalloenzymes) or structural functions. In this work, the characteristics of various metals were studied (Cu, Zn, Mg, Mn, Fe, Co, Ni, Cd and Ca in proteins with known crystal structure) as well as the specificity of their environments. The analysis was performed on two data sets: the set of protein structures in the Protein Data Bank (PDB) determined with resolution <1.5 A and the set of nonredundant protein structures from the PDB. The former was used to determine the distances between each metal ion and its electron donors and the latter was used to assess the preferred coordination numbers and common combinations of amino-acid residues in the neighbourhood of each metal. Although the metal ions considered predominantly had a valence of two, their preferred coordination number and the type of amino-acid residues that participate in the coordination differed significantly from one metal ion to the next. This study concentrates on finding the specificities of a metal-ion environment, namely the distribution of coordination numbers and the amino-acid residue types that frequently take part in coordination. Furthermore, the correlation between the coordination number and the occurrence of certain amino-acid residues (quartets and triplets) in a metal-ion coordination sphere was analysed. The results obtained are of particular value for the identification and modelling of metal-binding sites in protein structures derived by homology modelling. Knowledge of the geometry and characteristics of the metal-binding sites in metalloproteins of known function can help to more closely determine the biological activity of proteins of unknown function and to aid in design of proteins with specific affinity for certain metals.

Antibiotic resistance mechanisms in bacteria: biochemical and genetic aspects.

Abstract: Summary Since the discovery and subsequent widespread use of antibiotics, a variety of bacterial species of human and animal origin have developed numerous mechanisms that render bacteria resistant to some, and in certain cases to nearly all antibiotics. There are many important pathogens that are resistant to multiple antibiotic classes, and infections caused by multidrug resistant (MDR) organisms are limiting treatment options and compromising effective therapy. So the emergence of antibiotic-resistant pathogens in bacterial populations is a relevant field of study in molecular and evolutionary biology, and in medical practice. There are two main aspects to the biology of antimicrobial resistance. One is concerned with the development, acquisition and spread of the resistance gene itself. The other is the specific biochemical mechanism conveyed by this resistance gene. In this review we present some recent data on molecular mechanisms of antibiotic resistance.

Centrality dependence of charged hadron and strange hadron elliptic flow from √SNN = 200 GeV Au+Au collisions

Abstract: We present STAR results on the elliptic flow upsilon(2) Of charged hadrons, strange and multistrange particles from,root s(NN) = 200 GeV Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC). The detailed study of the centrality dependence of upsilon(2) over a broad transverse momentum range is presented. Comparisons of different analysis methods are made in order to estimate systematic uncertainties. To discuss the nonflow effect, we have performed the first analysis Of upsilon(2) with the Lee-Yang zero method for K(S)(0) and A. In the relatively low PT region, P(T) <= 2 GeV/c, a scaling with m(T) - m is observed for identified hadrons in each centrality bin studied. However, we do not observe nu 2(p(T))) scaled by the participant eccentricity to be independent of centrality. At higher PT, 2 1 <= PT <= 6 GeV/c, V2 scales with quark number for all hadrons studied. For the multistrange hadron Omega, which does not suffer appreciable hadronic interactions, the values of upsilon(2) are consistent with both m(T) - m scaling at low p(T) and number-of-quark scaling at intermediate p(T). As a function ofcollision centrality, an increase of p(T)-integrated upsilon(2) scaled by the participant eccentricity has been observed, indicating a stronger collective flow in more central Au+Au collisions.

ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures

Abstract: The program package ‘ClustScan’ (Cluster Scanner) is designed for rapid, semi-automatic, annotation of DNA sequences encoding modular biosynthetic enzymes including polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS) and hybrid (PKS/NRPS) enzymes. The program displays the predicted chemical structures of products as well as allowing export of the structures in a standard format for analyses with other programs. Recent advances in understanding of enzyme function are incorporated to make knowledge-based predictions about the stereochemistry of products. The program structure allows easy incorporation of additional knowledge about domain specificities and function. The results of analyses are presented to the user in a graphical interface, which also allows easy editing of the predictions to incorporate user experience. The versatility of this program package has been demonstrated by annotating biochemical pathways in microbial, invertebrate animal and metagenomic datasets. The speed and convenience of the package allows the annotation of all PKS and NRPS clusters in a complete Actinobacteria genome in 2–3 man hours. The open architecture of ClustScan allows easy integration with other programs, facilitating further analyses of results, which is useful for a broad range of researchers in the chemical and biological sciences.