Contrasting the conformational effects of α-O-GalNAc and α-O-Man glycan protein modifications and their impact on the mucin-like region of alpha-dystroglycan.

We have carried out a comparative study of the conformational impact of modifications to threonine residues of either α-O-Man or α-O-GalNAc in the context of a sequence from the mucin-like region of α-dystroglycan. Both such modifications can coexist in this domain of the glycoprotein. Solution NMR experiments and molecular dynamics calculations were employed. Comparing the results for an unmodified peptide Ac- PPTTTTKKP-NH2 sequence from α-dystroglycan, and glycoconjugates with either modification on the Ts, we find that the impact of the α-O-Man modification on the peptide scaffold is quite limited, while that of the α-O-GalNAc is more profound. The results for the α-O-GalNAc glycoconjugate are consistent with what has been seen earlier in other systems. Further examination of the NMR-based structure and the MD results suggest a more extensive network of hydrogen bond interactions within the α-O-GalNAc-threonine residue than has been previously appreciated, which influences the properties of the protein backbone. The conformational effects are relevant to the mechanical properties of α-dystroglycan.

Reducing financial barriers through the implementation of voucher incentives to promote children's participation in community sport in Australia.

BACKGROUND: Participation in organised sport and physical activity contributes to health-enhancing levels of leisure time physical activity. In Australia, 58% of children aged 0-14 years participated at least once a week in October 2015 - December 2017. To overcome the frequently cited cost barrier, sports voucher incentives have been widely implemented across Australia. METHOD: The financial value of jurisdictional vouchers and the National median financial value were used to calculate the proportion of total annual expenditure on children's participation in sport supported by sports vouchers. Participation rates using AusPlay data were estimated by age, sex and socio-economic index (SEIFA) at state and national level for children aged 0-14 years. RESULTS: Five States and Territories implemented sports vouchers from 2011 to 2018, with a median value of AU$150. Nationally, median annual expenditure for children's sport participation was AU$447 (IQR $194.2-936), with 27% reported expenditure supported by a sports voucher. The proportion of financial support from sports vouchers increased considerably with social disadvantage, rising to over 60% of total expenditure in the most disadvantaged populations. CONCLUSIONS: Socio-economic status was associated with sports-related expenditure and sports participation amongst children. Sport vouchers should target children in the most disadvantaged areas to promote participation in organised sport and physical activity.

Evaluation of a peer education program on student leaders' energy balance-related behaviors.

BACKGROUND: Few studies have reported energy balance-related behavior (EBRB) change for peer leaders delivering health promotion programs to younger students in secondary schools. Our study assessed the impact of the Students As LifeStyle Activists (SALSA) program on SALSA peer leaders' EBRBs, and their intentions regarding these behaviors. METHODS: We used a pre-post study design to assess changes in EBRBs and intentions of Year 10 secondary school students (15-16 year olds) who volunteered to be peer leaders to deliver the SALSA program to Year 8 students (13-14 year olds). This research is part of a larger study conducted during 2014 and 2015 in 23 secondary schools in Sydney, Australia. We used an online questionnaire before and after program participation to assess Year 10 peer leaders' fruit and vegetable intake, daily breakfast eating, sugar sweetened beverage (SSB) intake, moderate-to-vigorous physical activity (MVPA) participation and school-day recreational screen time behaviors and intentions regarding these EBRBs. Generalized estimating equations with a robust variance structure and exchangeable correlation structure were used to estimate the individual-level summary statistics and their 95% CIs, adjusted for clustering. We further assessed the effect of covariates on EBRB changes. RESULTS: There were significant increases in the proportion of Year 10 peer leaders (n = 415) who reported eating ≥2 serves fruit/day fruit from 54 to 63% (P < 0.01); eating ≥5 serves vegetables/day from 8 to 12% (P < 0.01); and drinking <1 cup/day of SSBs from 56 to 62% (P < 0.01). Change in ≥60 min MVPA participation/day depended on gender (P < 0.01): Boys increased 14% while girls decreased -2%. Changes in eating breakfast daily also depended on gender (P < 0.004): Boys increased 13% while girls decreased -0.4%. The change in peer leaders recreational screen time differed by socio-economic status (P < 0.05): above average communities decreased by -2.9% while below average communities increased 6.0%. Significant shifts were seen in peer leaders' intentions, except MVPA which remained stable. CONCLUSIONS: The SALSA program had a positive impact on peer leaders' EBRBs, with gender and socio-economic status moderating some outcomes. TRIAL REGISTRATION: ACTRN12617000712303 retrospectively registered.

The Dependence of Carbohydrate-Aromatic Interaction Strengths on the Structure of the Carbohydrate.

Interactions between proteins and carbohydrates are ubiquitous in biology. Therefore, understanding the factors that determine their affinity and selectivity are correspondingly important. Herein, we have determined the relative strengths of intramolecular interactions between a series of monosaccharides and an aromatic ring close to the glycosylation site in an N-glycoprotein host. We employed the enhanced aromatic sequon, a structural motif found in the reverse turns of some N-glycoproteins, to facilitate face-to-face monosaccharide-aromatic interactions. A protein host was used because the dependence of the folding energetics on the identity of the monosaccharide can be accurately measured to assess the strength of the carbohydrate-aromatic interaction. Our data demonstrate that the carbohydrate-aromatic interaction strengths are moderately affected by changes in the stereochemistry and identity of the substituents on the pyranose rings of the sugars. Galactose seems to make the weakest and allose the strongest sugar-aromatic interactions, with glucose, N-acetylglucosamine (GlcNAc) and mannose in between. The NMR solution structures of several of the monosaccharide-containing N-glycoproteins were solved to further understand the origins of the similarities and differences between the monosaccharide-aromatic interaction energies. Peracetylation of the monosaccharides substantially increases the strength of the sugar-aromatic interaction in the context of our N-glycoprotein host. Finally, we discuss our results in light of recent literature regarding the contribution of electrostatics to CH-π interactions and speculate on what our observations imply about the absolute conservation of GlcNAc as the monosaccharide through which N-linked glycans are attached to glycoproteins in eukaryotes.

Utilization of mechanical diagnosis and therapy (MDT) for the treatment of lumbar pain in the presence of known lumbar transverse process fractures: a case study.

BACKGROUND: Spinal fractures are typically considered a contraindication to mechanical diagnosis and therapy (MDT). OBJECTIVE AND IMPORTANCE: The purpose of this case study is to illustrate how MDT was used safely and effectively to treat lumbar pain in a patient with multiple lumbar transverse process fractures. CLINICAL PRESENTATION: The subject was a 24-year-old female with left L2-5 transverse process fractures, sustained 10 weeks prior in a pedestrian versus motor vehicle accident. INTERVENTION AND TECHNIQUE: After collaboration with her physiatrist, an MDT examination revealed a presentation consistent with the lumbar derangement syndrome. CONCLUSION: After three visits, utilizing patient generated forces with the extension principle of treatment, her pain, Oswestry disability index (ODI) score, and function all improved.

Connecting thermal performance curve variation to the genotype: a multivariate QTL approach.

Thermal performance curves (TPCs) are continuous reaction norms that describe the relationship between organismal performance and temperature and are useful for understanding trade-offs involved in thermal adaptation. Although thermal trade-offs such as those between generalists and specialists or between hot- and cold-adapted phenotypes are known to be genetically variable and evolve during thermal adaptation, little is known of the genetic basis to TPCs - specifically, the loci involved and the directionality of their effects across different temperatures. To address this, we took a multivariate approach, mapping quantitative trait loci (QTL) for locomotor activity TPCs in the fly, Drosophila serrata, using a panel of 76 recombinant inbred lines. The distribution of additive genetic (co)variance in the mapping population was remarkably similar to the distribution of mutational (co)variance for these traits. We detected 11 TPC QTL in females and 4 in males. Multivariate QTL effects were closely aligned with the major axes genetic (co)variation between temperatures; most QTL effects corresponded to variation for either overall increases or decreases in activity with a smaller number indicating possible trade-offs between activity at high and low temperatures. QTL representing changes in curve shape such as the 'generalist-specialist' trade-off, thought key to thermal adaptation, were poorly represented in the data. We discuss these results in the light of genetic constraints on thermal adaptation.

BFMP: a method for discretizing and visualizing pyranose conformations.

We report a new classification method for pyranose ring conformations called Best-fit, Four-Membered Plane (BFMP), which describes pyranose ring conformations based on reference planes defined by four atoms. The method is able to characterize all asymmetrical and symmetrical shapes of a pyran ring, is readily automated, easy to interpret, and maps trivially to IUPAC definitions. It also provides a qualitative measurement of the distortion of the ring. Example applications include the analysis of data from crystal structures and molecular dynamics simulations.

Postzygotic isolation involves strong mitochondrial and sex-specific effects in Tigriopus californicus, a species lacking heteromorphic sex chromosomes.

Detailed studies of the genetics of speciation have focused on a few model systems, particularly Drosophila. The copepod Tigriopus californicus offers an alternative that differs from standard animal models in that it lacks heteromorphic chromosomes (instead, sex determination is polygenic) and has reduced opportunities for sexual conflict, because females mate only once. Quantitative trait loci (QTL) mapping was conducted on reciprocal F2 hybrids between two strongly differentiated populations, using a saturated linkage map spanning all 12 autosomes and the mitochondrion. By comparing sexes, a possible sex ratio distorter was found but no sex chromosomes. Although studies of standard models often find an excess of hybrid male sterility factors, we found no QTL for sterility and multiple QTL for hybrid viability (indicated by non-Mendelian adult ratios) and other characters. Viability problems were found to be stronger in males, but the usual explanations for weaker hybrid males (sex chromosomes, sensitivity of spermatogenesis, sexual selection) cannot fully account for these male viability problems. Instead, higher metabolic rates may amplify deleterious effects in males. Although many studies of standard speciation models find the strongest genetic incompatibilities to be nuclear-nuclear (specifically X chromosome-autosome), we found the strongest deleterious interaction in this system was mito-nuclear. Consistent with the snowball theory of incompatibility accumulation, we found that trigenic interactions in this highly divergent cross were substantially more frequent (>6×) than digenic interactions. This alternative system thus allows important comparisons to studies of the genetics of reproductive isolation in more standard model systems.

Safety of therapeutic hypothermia in post VF/VT cardiac arrest patients.

Therapeutic hypothermia (TH) is a process of cooling a patient post ventricular tachycardia/ventricular fibrillation (VT/VF) cardiac arrest to 32-34 degrees C for 24 hours. This improves neurological outcome and is part of current guidelines. Hypothermia prolongs QT interval, which can precipitate torsades de pointes (TdP). We performed a retrospective review of all patients who received TH in our hospital over a period of 2 years to assess the effect of TH on the corrected OT interval (QTc) and any possible pro-arrhythmia. A total of 13 patients received TH. QTc prolonged in all patients with an average of 80.3 + 57.2 ms., and up to 109.8 + 80.4 ms in patients who received Amiodarone concurrently. No TdP was seen in any patient. We conclude that TH is safe, though careful monitoring of the OTc interval is advisable especially with concurrent use of QT prolonging drugs.

Molecular evidence of HIV-1 transmission in 20 Korean individuals with haemophilia: phylogenetic analysis of the vif gene.

To assess whether a genetic relationship exists between the viruses infecting HIV-positive patients with haemophilia and those infecting plasma donors, we determined the vif sequences in 169 individuals, including 20 haemophilia patients, 3 plasma donors, and 146 local controls. Twenty haemophilia patients were diagnosed with HIV-1 at 1-2 years after exposure to factor IX (FIX) manufactured in Korea, beginning in 1989-1990. Plasma samples from donors O and P were used to manufacture clotting factors including FIX used to treat the 20 haemophiliacs. The vif gene from frozen stored serum samples obtained 1-3 years after diagnosis was amplified by RT-PCR, and subjected to direct sequencing. Phylogenetic analysis revealed that vif sequences from 128 of the samples (including haemophilia patients and donors) belonged to the Korean subclade of HIV-1 subtype B (KSB). Sequences from 41 other participants were identified as subtype B, but outside the Korean subclade. Sequences of the vif gene from donors O and P plus the 20 individuals with haemophilia comprised two subclusters within KSB. In addition, signature pattern analysis disclosed the presence of conserved nucleotides at two positions in donors and haemophiliacs only. Together with information on KSB, dates of plasma donations and seroconversion of haemophilia patients, our results suggest that the haemophiliacs examined here became infected by viruses in the domestic clotting factor used for treatment.

Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity.

HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol.

Quantitative genetic analysis suggests causal association between cuticular hydrocarbon composition and desiccation survival in Drosophila melanogaster.

Survival to low relative humidity is a complex adaptation, and many repeated instances of evolution to desiccation have been observed among Drosophila populations and species. One general mechanism for desiccation resistance is Cuticular Hydrocarbon (CHC) melting point. We performed the first Quantitative Trait Locus (QTL) map of population level genetic variation in desiccation resistance in D. melanogaster. Using a panel of Recombinant Inbred Lines (RILs) derived from a single natural population, we mapped QTL in both sexes throughout the genome. We found that in both sexes, CHCs correlated strongly with desiccation resistance. At most desiccation resistance loci there was a significant association between CHCs and desiccation resistance of the sort predicted from clinal patterns of CHC variation and biochemical properties of lipids. This association was much stronger in females than males, perhaps because of greater overall abundance of CHCs in females, or due to correlations between CHCs used for waterproofing and sexual signalling in males. CHC evolution may be a common mechanism for desiccation resistance in D. melanogaster. It will be interesting to compare patterns of CHC variation and desiccation resistance in species which adapt to desiccation, and rainforest restricted species which cannot.

Gender inclusive sporting environments: the proportion of women in non-player roles over recent years.

BACKGROUND: Throughout the ecosystem of sport, women have been and continue to be underrepresented at all levels compared to men. The capacity of community-level sport is heavily reliant on the many non-player roles including governance, as well as administration, coaching and officiating. Recently there has been increased attention to improving the gender balance in sport. The aim of this study is to investigate the proportions of women engaged in non-playing roles in sport (2016-2018). METHODS: This study involved secondary analysis of the AusPlay survey, a national population survey, funded by Sport Australia. This study utilised data from people aged 15-years or older about their involvement in non-playing roles in sport, and their demographic data. Survey respondents were asked "During the last 12 months, have you been involved with any sports in a nonplaying role, such as official, coach, referee, administrator, etc?" Analysis of non-player role responses focussed specifically on the top four non-player role categories; coach, official, administrator and manager. Frequency analysis concentrated on the distribution of men and women involvement in a non-player capacity for the three years, with detailed analysis of the most recent year (2018). RESULTS: In this study of 61,578 Australians there was a higher proportion of men in non-player roles in sport compared to women, across each of the three years (2018: men 55 %, women 46 %). Involvement of women in coaching increased significantly from 38 % to 2016 to 44 % in 2018 (p < 0.001). The proportion of women involved in administration roles significantly decreased from a peak of 51 % in 2017 to 46 % in 2018 (p < 0.001). CONCLUSIONS: Aligned with strategic policy and investment strategies, there are gradual increased representation of women in non-playing sport, coaching roles. Women are still underrepresented in terms of coaches, officials and administrators, but are more likely to be managers. It is recommended that there is continued mentoring, identification and emphasising of female role models, and further strategies to increase female presence in non-playing roles. We recommend that future research, in line with appropriate gender and cultural-change theories, investigates and discusses the progress of gender equality throughout playing and non-playing role in sport.

Risk factors for sporadic Campylobacter infection: an all-Ireland case-control study.

We report the findings of the first case-control study conducted in both the Republic of Ireland and Northern Ireland to determine risk factors for sporadic Campylobacter infections. A total of 197 cases and 296 case-nominated controls matched for age, were included. Based on Population Attributable Fraction (PAF), the most important risk factors were consuming chicken [adjusted matched (am) OR 6.8; 95%CI 2.1-21.9], consuming lettuce (amOR 3.3; 95%CI 1.5-7.1) and eating in takeaways (amOR=3.1; 95%CI 1.4-6.6). Contact with sheep (amOR=11; 95%CI 1.6-78), peptic ulcer (amOR=19; 95%CI 3.8-93.7), hiatus hernia (amOR=20.3; 95%CI 2.3-183.3), lower bowel problems (amOR=4.5; 95%CI 1.2-16.8) were also independently associated with infection. Mains water supply showed protective effect (amOR=0.2; 95 CI 0.1-0.9). The findings highlight the continued need for consumer food safety education and further control measures throughout the food chain on the island of Ireland.

Infective endocarditis: a retrospective cohort study.

BACKGROUND: Infective endocarditis (IE) is a potentially life-threatening infection of the heart's endocardial surface. Despite advances in the diagnosis and management of IE, morbidity and mortality remain high. AIM: To characterize the demographics, bacteriology and outcomes of IE cases presenting to an Irish tertiary referral centre. DESIGN: Retrospective cohort study. METHODS: Patients were identified using Hospital Inpatient Enquiry and Clinical Microbiology inpatient consult data, from January 2005 to January 2014. Patients were diagnosed with IE using Modified Duke Criteria. Standard Bayesian statistics were employed for analysis and cases were compared to contemporary international registries. RESULTS: Two hundred and two patients were diagnosed with IE during this period. Mean age 54 years. Of these, 136 (67%) were native valve endocarditis (NVE), 50 (25%) were prosthetic valve endocarditis (PVE) and 22 (11%) were cardiovascular implantable electronic device-associated endocarditis. Culprit organism was identified in 176 (87.1%) cases and Staphylococcal species were the most common (57.5%). Fifty-nine per cent of NVE required surgery compared to 66% of PVE. Mean mortality rate was 17.3%, with NVE being the lowest (12.5%) and PVE the highest (32%). Increasing age was also associated with increased mortality. Fifty-three (26.2%) patients had embolic complications. CONCLUSIONS: This Irish cohort exhibited first-world demographic patterns comparable to those published in contemporary international literature. PVE required surgery more often and was associated with higher rates of mortality than NVE. Embolic complications were relatively common and represent important sequelae, especially in the intravenous drug user population. It is also pertinent to aggressively treat older cohorts as they were associated with increased mortality.

Involvement of water in carbohydrate-protein binding: concanavalin A revisited.

Ordered water molecules bound to protein surfaces, or in protein-ligand interfaces, are frequently observed by crystallography. The investigation of the impact of such conserved water molecules on protein stability and ligand affinity requires detailed structural, dynamic, and thermodynamic analyses. Several crystal structures of the legume lectin concanavalin A (Con A) bound to closely related carbohydrate ligands show the presence of a conserved water molecule that mediates ligand binding. Experimental thermodynamic and theoretical studies have examined the role of this conserved water in the complexation of Con A with a synthetic analog of the natural trisaccharide, in which a hydroxyethyl side chain replaces the hydroxyl group at the C-2 position in the central mannosyl residue. Molecular modeling earlier indicated (Clarke, C.; Woods, R. J.; Glushka, J.; Cooper, A.; Nutley, M. A.; Boons, G.-J. J. Am. Chem. Soc. 2001, 123, 12238-12247) that the hydroxyl group in this synthetic side chain could occupy a position equivalent to that of the conserved water, and thus might displace it. An interpretation of the experimental thermodynamic data, which was consistent with the displacement of the conserved water, was also presented. The current work reports the crystal structure of Con A with this synthetic ligand and shows that even though the position and interactions of the conserved water are distorted, this key water is not displaced by the hydroxyethyl moiety. This new structural data provides a firm basis for molecular dynamics simulations and thermodynamic integration calculations whose results indicate that differences in van der Waals contacts (insertion energy), rather than electrostatic interactions (charging energy) are fundamentally responsible for the lower affinity of the synthetic ligand. When combined with the new crystallographic data, this study provides a straightforward interpretation for the lower affinity of the synthetic analog; specifically, that it arises primarily from weaker interactions with the protein via the positionally perturbed conserved water. This interpretation is fully consistent with the experimental observations that the free energy of binding is enthalpy driven, that there is both less enthalpic gain and less entropic penalty for binding the synthetic ligand, relative to the natural trisaccharide, and that the entropic component does not arise from releasing an ordered water molecule from the protein surface to the bulk solvent.

GLYCAM06: a generalizable biomolecular force field. Carbohydrates.

A new derivation of the GLYCAM06 force field, which removes its previous specificity for carbohydrates, and its dependency on the AMBER force field and parameters, is presented. All pertinent force field terms have been explicitly specified and so no default or generic parameters are employed. The new GLYCAM is no longer limited to any particular class of biomolecules, but is extendible to all molecular classes in the spirit of a small-molecule force field. The torsion terms in the present work were all derived from quantum mechanical data from a collection of minimal molecular fragments and related small molecules. For carbohydrates, there is now a single parameter set applicable to both alpha- and beta-anomers and to all monosaccharide ring sizes and conformations. We demonstrate that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms. However, we note that there are cases where this approach is inadequate. Reported here are the basic components of the new force field as well as an illustration of its extension to carbohydrates. In addition to reproducing the gas-phase properties of an array of small test molecules, condensed-phase simulations employing GLYCAM06 are shown to reproduce rotamer populations for key small molecules and representative biopolymer building blocks in explicit water, as well as crystalline lattice properties, such as unit cell dimensions, and vibrational frequencies.

Analysis of integrated virological and epidemiological reports of norovirus outbreaks collected within the Foodborne Viruses in Europe network from 1 July 2001 to 30 June 2006.

The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.

Quantifying protein interface footprinting by hydroxyl radical oxidation and molecular dynamics simulation: application to galectin-1.

Biomolecular surface mapping methods offer an important alternative method for characterizing protein-protein and protein-ligand interactions in cases in which it is not possible to determine high-resolution three-dimensional (3D) structures of complexes. Hydroxyl radical footprinting offers a significant advance in footprint resolution compared with traditional chemical derivatization. Here we present results of footprinting performed with hydroxyl radicals generated on the nanosecond time scale by laser-induced photodissociation of hydrogen peroxide. We applied this emerging method to a carbohydrate-binding protein, galectin-1. Since galectin-1 occurs as a homodimer, footprinting was employed to characterize the interface of the monomeric subunits. Efficient analysis of the mass spectrometry data for the oxidized protein was achieved with the recently developed ByOnic (Palo Alto, CA) software that was altered to handle the large number of modifications arising from side-chain oxidation. Quantification of the level of oxidation has been achieved by employing spectral intensities for all of the observed oxidation states on a per-residue basis. The level of accuracy achievable from spectral intensities was determined by examination of mixtures of synthetic peptides related to those present after oxidation and tryptic digestion of galectin-1. A direct relationship between side-chain solvent accessibility and level of oxidation emerged, which enabled the prediction of the level of oxidation given the 3D structure of the protein. The precision of this relationship was enhanced through the use of average solvent accessibilities computed from 10 ns molecular dynamics simulations of the protein.