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1.  Carbohydrate force fields 
Carbohydrates present a special set of challenges to the generation of force fields. First, the tertiary structures of monosaccharides are complex merely by virtue of their exceptionally high number of chiral centers. In addition, their electronic characteristics lead to molecular geometries and electrostatic landscapes that can be challenging to predict and model. The monosaccharide units can also interconnect in many ways, resulting in a large number of possible oligosaccharides and polysaccharides, both linear and branched. These larger structures contain a number of rotatable bonds, meaning they potentially sample an enormous conformational space. This article briefly reviews the history of carbohydrate force fields, examining and comparing their challenges, forms, philosophies, and development strategies. Then it presents a survey of recent uses of these force fields, noting trends, strengths, deficiencies, and possible directions for future expansion.
doi:10.1002/wcms.89
PMCID: PMC4270206  PMID: 25530813
2.  Postzygotic isolation involves strong mitochondrial and sex-specific effects in Tigriopus californicus, a species lacking heteromorphic sex chromosomes 
Heredity  2013;111(5):391-401.
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.
doi:10.1038/hdy.2013.61
PMCID: PMC3806025  PMID: 23860232
QTL; reproductive isolation; speciation; copepod; nuclear–mitochondrial interaction
3.  On Achieving Experimental Accuracy from Molecular Dynamics Simulations of Flexible Molecules: Aqueous Glycerol 
The journal of physical chemistry. A  2008;112(12):2634-2639.
The rotational isomeric states (RIS) of glycerol at infinite dilution have been characterized in the aqueous phase via a 1 μs conventional molecular dynamics (MD) simulation, a 40 ns enhanced sampling replica exchange molecular dynamics (REMD) simulation, and a reevaluation of the experimental NMR data. The MD and REMD simulations employed the GLYCAM06/AMBER force field with explicit treatment of solvation. The shorter time scale of the REMD sampling method gave rise to RIS and theoretical scalar 3JHH coupling constants that were comparable to those from the much longer traditional MD simulation. The 3JHH coupling constants computed from the MD methods were in excellent agreement with those observed experimentally. Despite the agreement between the computed and the experimental J-values, there were variations between the rotamer populations computed directly from the MD data and those derived from the experimental NMR data. The experimentally derived populations were determined utilizing limiting J-values from an analysis of NMR data from substituted ethane molecules and may not be completely appropriate for application in more complex molecules, such as glycerol. Here, new limiting J-values have been derived via a combined MD and quantum mechanical approach and were used to decompose the experimental 3JHH coupling constants into population distributions for the glycerol RIS.
doi:10.1021/jp710544s
PMCID: PMC4201037  PMID: 18311953
4.  Molecular evidence of HIV-1 transmission in 20 Korean individuals with haemophilia: phylogenetic analysis of the vif gene 
Summary
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.
doi:10.1111/j.1365-2516.2011.02620.x
PMCID: PMC3471993  PMID: 21787373
AIDS; haemophilia; HIV-1; phylogenetic analysis; signature pattern analysis; vif
5.  Quantitative genetic analysis suggests causal association between cuticular hydrocarbon composition and desiccation survival in Drosophila melanogaster 
Heredity  2010;106(1):68-77.
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.
doi:10.1038/hdy.2010.40
PMCID: PMC2905492  PMID: 20389309
D. melanogaster; QTL; pleiotropy; desiccation; CHCs
6.  Quantitative genetic analysis suggests causal association between cuticular hydrocarbon composition and desiccation survival in Drosophila melanogaster 
Heredity  2010;106(1):68-77.
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.
doi:10.1038/hdy.2010.40
PMCID: PMC2905492  PMID: 20389309
D. melanogaster; QTL; pleiotropy; desiccation; CHCs
7.  Involvement of Water in Carbohydrate-Protein Binding: Concanavalin A Revisited 
Journal of the American Chemical Society  2008;130(50):16933-16942.
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.
doi:10.1021/ja8039663
PMCID: PMC2626182  PMID: 19053475
AMBER; binding free energy; carbohydrate binding; conserved water; enthalpy-entropy compensation; Gaussian quadrature; GLYCAM; ligand binding; splined integration; thermodynamic integration
8.  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 3D structures of complexes. Hydroxyl radical footprinting offers a significant advance in footprint resolution compared to traditional chemical derivatization. Here we present results of footprinting performed with hydroxyl radicals generated on the nanosecond time scale by a 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 MS data for the oxidized protein was achieved with the recently developed ByOnic 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 that 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.
doi:10.1016/j.jasms.2008.07.013
PMCID: PMC2607067  PMID: 18707901
AMBER; ByOnic; galectin-1; MD simulations; oxidative surface mapping; solvent accessible surface area; SASA
9.  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▿  
Journal of Clinical Microbiology  2008;46(9):2959-2965.
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.
doi:10.1128/JCM.00499-08
PMCID: PMC2546741  PMID: 18650354
10.  Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia 
Objectives
To explore the extent to which commonly used measures of specific outcomes in dementia are an appropriate proxy for quality of life in dementia.
Methods
This was a cross sectional study set in communities in London and Nottingham, comprising 101 people with dementia and their 99 main family caregivers. The main outcome measures were health related quality of life in dementia (measured by the DEMQOL‐Proxy), cognition (Mini Mental State Examination), functional impairment (Barthel Index), behavioural and psychological symptoms in dementia (Neuropsychiatric Inventory; NPI), and carer mental health (General Health Questionnaire).
Results
On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer. Quality of life was not statistically significantly associated with cognition or carer age. In a multivariate model, psychological and behavioural disturbance and patient age remained statistically significantly associated with quality of life. Carer mental health was no longer statistically significantly associated, and cognition and functional limitation remained statistically insignificant.
Conclusions
These data suggest that quality of life in dementia is complex, and that simple proxy substitutions of discrete measures such as cognition or function are likely to miss important factors.
doi:10.1136/jnnp.2005.072983
PMCID: PMC2077592  PMID: 16421113
quality of life; dementia; cognition; measurement; behavioural and psychological symptoms of dementia
11.  Genetic Diversity among Botulinum Neurotoxin-Producing Clostridial Strains▿  
Journal of Bacteriology  2006;189(3):818-832.
Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore-forming rod-shaped bacteria that have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and death in humans and other animal species. A collection of 174 C. botulinum strains was examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine the genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT/A to BoNT/G). Analysis of the16S rRNA gene sequences confirmed previous identifications of at least four distinct genomic backgrounds (groups I to IV), each of which has independently acquired one or more BoNT genes through horizontal gene transfer. AFLP analysis provided higher resolution and could be used to further subdivide the four groups into subgroups. Sequencing of the BoNT genes from multiple strains of serotypes A, B, and E confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven toxin genes of the serotypes were compared and showed various degrees of interrelatedness and recombination, as was previously noted for the nontoxic nonhemagglutinin gene, which is linked to the BoNT gene. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for the treatment of botulism.
doi:10.1128/JB.01180-06
PMCID: PMC1797315  PMID: 17114256
12.  Predictors of institutionalisation in people with dementia 
Method: Longitudinal study of a cohort of people with dementia and their carers in contact with old age psychiatric services in south London.
Results: 100 people with dementia and their main family carer were recruited. At six month follow up 22 were in residential care, 63 in the community, 8 had died, and for 7 there were missing data. Between six and 12 months, 7 of the 63 in the community went into residential care, 4 died, and 12 were lost to follow up. The most striking finding is the 20-fold protective effect of having a co-resident carer (odds ratio 0.05, 95% confidence intervals 0.01 to 0.42, p=0.006). Higher ratings of behavioural problems in the person with dementia were also statistically significantly associated with transition into residential care as was the psychological domain of quality of life of the carer.
Conclusion: These findings powerfully illustrate the pivotal role carried out by carers of people with dementia; interventions directly targeted at helping them to maintain this role would be supported by these data. These data also suggest that strategies directed at improving carer quality of life and at the resolution of behavioural disorder in the person with dementia may also have particular value.
doi:10.1136/jnnp.74.9.1315
PMCID: PMC1738636  PMID: 12933944
13.  Consistent Patterns of Change during the Divergence of Human Immunodeficiency Virus Type 1 Envelope from That of the Inoculated Virus in Simian/Human Immunodeficiency Virus-Infected Macaques 
Journal of Virology  2006;80(2):999-1014.
We have analyzed changes to proviral Env gp120 sequences and the development of neutralizing antibodies (NAbs) during 1 year of simian/human immunodeficiency virus SHIV-89.6P infection in 11 Macaca nemestrina macaques. Seven macaques had significant env divergence from that of the inoculum, and macaques with greater divergence had higher titers of homologous NAbs. Substitutions in sequons encoding potential N-linked glycosylation sites (PNGs) were among the first to be established, although overall the total number of sequons did not increase significantly. The majority (19 of 23) of PNGs present in the inoculum were conserved in the sequences from all macaques. Statistically significant variations in PNGs occurred in multiple macaques within constrained regions we term “hot spots,” resulting in the selection of sequences more similar to the B consensus. These included additions on V1, the N-terminal side of V4, and the outer region of C2. Complex mutational patterns resulted in convergent PNG shifts in V2 and V5. Charge changes in Env V1V2, resulting in a net acidic charge, and a proline addition in V5 occurred in several macaques. Molecular modeling of the 89.6P sequence showed that the conserved glycans lie on the silent face of Env and that many are proximal to disulfide bonds, while PNG additions and shifts are proximal to the CD4 binding site. Nonsynonymous-to-synonymous substitution ratios suggest that these changes result from selective pressure. This longitudinal and cross-sectional study of mutations in human immunodeficiency virus (HIV) env in the SHIV background provides evidence that there are more constraints on the configuration of the glycan shield than were previously appreciated.
doi:10.1128/JVI.80.2.999-1014.2006
PMCID: PMC1346845  PMID: 16379001
14.  Human Immunodeficiency Virus Type 1 Subtype C Molecular Phylogeny: Consensus Sequence for an AIDS Vaccine Design? 
Journal of Virology  2002;76(11):5435-5451.
An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence of HIV-1C infection in the southern African countries and with an expanding epidemic in India and China. Understanding the molecular phylogeny and genetic diversity of HIV-1C viruses may be important for the design and evaluation of an HIV vaccine for ultimate use in the developing world. In this study we analyzed the phylogenetic relationships (i) between 73 nonrecombinant HIV-1C near-full-length genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C consensus sequences that represent different geographic subsets; and (iii) between specific isolates and consensus sequences. Based on the phylogenetic analyses of 73 near-full-length genomes, 16 “lineages” (a term that is used hereafter for discussion purposes and does not imply taxonomic standing) were identified within HIV-1C. The lineages were supported by high bootstrap values in maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum-likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to 7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence were significantly lower than distances between samples within all HIV-1C proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid frequencies were presented (that of Gag is presented in this work; those of Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm]). Additionally, in the promoter region three NF-κB sites (GGGRNNYYCC) were identified within the consensus sequences of the entire set or any subset of HIV-1C isolates. This study suggests that the consensus sequence approach could overcome the high genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly if the assumption that an HIV-1C antigen with a more extensive match to the circulating viruses is likely to be more efficacious is proven in efficacy trials.
doi:10.1128/JVI.76.11.5435-5451.2002
PMCID: PMC137027  PMID: 11991972
15.  Identification of Human Immunodeficiency Virus Type 1 Subtype C Gag-, Tat-, Rev-, and Nef-Specific Elispot-Based Cytotoxic T-Lymphocyte Responses for AIDS Vaccine Design 
Journal of Virology  2001;75(19):9210-9228.
The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. CTLs were shown to be an important component of the immune response to control HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The enzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well with other methods, such as intracellular staining, tetramer staining, and the classical chromium release assay. Using Elispot with overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide an additional characterization of immunodominant regions across the HIV-1C genome. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant CTL epitopes across the viral genome, derived from predominant HIV-1 viruses, might be a logical approach to the design of a vaccine against AIDS.
doi:10.1128/JVI.75.19.9210-9228.2001
PMCID: PMC114489  PMID: 11533184
16.  Maintaining the integrity of human immunodeficiency virus sequence databases. 
Journal of Virology  1996;70(8):5720-5730.
Human immunodeficiency virus type 1 (HIV-1) sequences are accumulating in the literature at a rapid pace. For this ever-expanding resource to be maximally useful, it is critical that researchers strive to maintain a high level of quality assurance, both in experimental design and conduct and in analyses. Here we present detailed analyses of problematic sets of HIV-1 sequences in the database that include sequence anomalies suggestive of mislabeling or sample contamination problems. These data are examined in the context of currently available HIV-1 sequence information to provide an example of how to identify potentially flawed data. Indicators of potential problems with sequences are (i) sequences that are nearly identical that are supposed to be derived from unlinked individuals and that are markedly distinct from other sequences from the putative source or (ii) sequences that are nearly identical to those of laboratory strains. We provide an outline of methods that researchers can use to perform preliminary laboratory and computational analyses that could help identify problematic data and thus help ensure the integrity of sequence databases.
PMCID: PMC190542  PMID: 8764096
17.  Brucellosis in South West Eire. 
Journal of Clinical Pathology  1972;25(6):551-552.
PMCID: PMC477388  PMID: 5043388
18.  RT-PCR with affinity-captured mRNA. 
Nucleic Acids Research  1993;21(9):2281.
Images
PMCID: PMC309514  PMID: 7684840

Results 1-18 (18)