The predictability of a lake phytoplankton community, over time-scales of hours to years.

Forecasting changes to ecological communities is one of the central challenges in ecology. However, nonlinear dependencies, biotic interactions and data limitations have limited our ability to assess how predictable communities are. Here, we used a machine learning approach and environmental monitoring data (biological, physical and chemical) to assess the predictability of phytoplankton cell density in one lake across an unprecedented range of time-scales. Communities were highly predictable over hours to months: model R2 decreased from 0.89 at 4 hours to 0.74 at 1 month, and in a long-term dataset lacking fine spatial resolution, from 0.46 at 1 month to 0.32 at 10 years. When cyanobacterial and eukaryotic algal cell densities were examined separately, model-inferred environmental growth dependencies matched laboratory studies, and suggested novel trade-offs governing their competition. High-frequency monitoring and machine learning can set prediction targets for process-based models and help elucidate the mechanisms underlying ecological dynamics.

Ecology under lake ice.

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer 'growing seasons'. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.

Who Smells? Forecasting Taste and Odor in a Drinking Water Reservoir.

Taste and odor problems can impede public trust in drinking water and impose major costs on water utilities. The ability to forecast taste and odor events in source waters, in advance, is shown for the first time in this paper. This could allow water utilities to adapt treatment, and where effective treatment is not available, consumers could be warned. A unique 24-year time series, from an important drinking water reservoir in Saskatchewan, Canada, is used to develop forecasting models of odor using chlorophyll a, turbidity, total phosphorus, temperature, and the following odor producing algae taxa: Anabaena spp., Aphanizemenon spp., Oscillatoria spp., Chlorophyta, Cyclotella spp., and Asterionella spp. We demonstrate, using linear regression and random forest models, that odor events can be forecast at 0-26 week time lags, and that the models are able to capture a significant increase in threshold odor number in the mid-1990 s. Models with a fortnight time-lag show a high predictive capacity (R(2) = 0.71 for random forest; 0.52 for linear regression). Predictive skill declines for time lags from 0 to 15 weeks, then increases again, to R(2) values of 0.61 (random forest) and 0.48 (linear regression) at a 26-week lag. The random forest model is also able to provide accurate forecasting of TON levels requiring treatment 12 weeks in advance-93% true positive rate with a 0% false positive rate. Results of the random forest model demonstrate that phytoplankton taxonomic data outperform chlorophyll a in terms of predictive importance.

Cannabis psychosis: examining the evidence for a distinctive psychopathology in a systematic and narrative review.

BACKGROUND: The term "cannabis psychosis" has become ubiquitous in the psychiatric literature. Few authors have described the precise psychopathology of this potentially distinct subtype of psychosis. Specifically, little attention has been paid to exploring whether cannabis psychosis is characterized by a psychopathology which is different from that of other types of psychosis. OBJECTIVE: The purpose of this paper was to systematically review the literature for evidence of a specific constellation of symptoms which are consistently characteristic of cannabis psychosis within an inpatient psychiatric setting and to determine whether these combine to create a psychopathology which is distinct from that of other types of psychosis. METHOD: Systematic review using Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. RESULTS: 13 studies of the 439 identified met the inclusion criteria. Only eight studies had sufficient internal and external validity to allow comparison in a narrative format of the psychopathology present, compared with controls. Of these eight selected studies, seven reported at least one significant difference (p < .05) in the psychopathology of the cannabis group to the control group used as a comparator. DISCUSSION AND CONCLUSION: This study should be interpreted with great caution and conclusions should not be generalized. These findings do not suggest that "cannabis psychosis" does not exist, only that from a psychopathological perspective it may not be qualitatively any different from other forms of psychosis. Future research in this area needs to focus on clarifying the definition or description of "cannabis psychosis" and the use of standardized robust experimental and/or observational designs to eliminate heterogeneity that may lead to inconclusive results.

A highly unusual thioester bond in a pilus adhesin is required for efficient host cell interaction.

Many bacterial pathogens present adhesins at the tips of long macromolecular filaments known as pili that are often important virulence determinants. Very little is known about how pili presented by Gram-positive pathogens mediate host cell binding. The crystal structure of a pilus adhesin from the important human pathogen Streptococcus pyogenes reveals an internal thioester bond formed between the side chains of a cysteine and a glutamine residue. The presence of the thioester was verified using UV-visible spectroscopy and mass spectrometry. This unusual bond has only previously been observed in thioester domains of complement and complement-like proteins where it is used to form covalent attachment to target molecules. The structure also reveals two intramolecular isopeptide bonds, one of these formed through a Lys/Asp residue pair, which are strategically positioned to confer protein stability. Removal of the internal thioester by allele-replacement mutagenesis in S. pyogenes severely compromises bacterial adhesion to model host cells. Although current paradigms of bacterial/host cell interaction envisage strong non-covalent interactions, the present study suggests cell adhesion could also involve covalent bonds.

Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2) toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

Roles of minor pilin subunits Spy0125 and Spy0130 in the serotype M1 Streptococcus pyogenes strain SF370.

Adhesive pili on the surface of the serotype M1 Streptococcus pyogenes strain SF370 are composed of a major backbone subunit (Spy0128) and two minor subunits (Spy0125 and Spy0130), joined covalently by a pilin polymerase (Spy0129). Previous studies using recombinant proteins showed that both minor subunits bind to human pharyngeal (Detroit) cells (A. G. Manetti et al., Mol. Microbiol. 64:968-983, 2007), suggesting both may act as pilus-presented adhesins. While confirming these binding properties, studies described here indicate that Spy0125 is the pilus-presented adhesin and that Spy0130 has a distinct role as a wall linker. Pili were localized predominantly to cell wall fractions of the wild-type S. pyogenes parent strain and a spy0125 deletion mutant. In contrast, they were found almost exclusively in culture supernatants in both spy0130 and srtA deletion mutants, indicating that the housekeeping sortase (SrtA) attaches pili to the cell wall by using Spy0130 as a linker protein. Adhesion assays with antisera specific for individual subunits showed that only anti-rSpy0125 serum inhibited adhesion of wild-type S. pyogenes to human keratinocytes and tonsil epithelium to a significant extent. Spy0125 was localized to the tip of pili, based on a combination of mutant analysis and liquid chromatography-tandem mass spectrometry analysis of purified pili. Assays comparing parent and mutant strains confirmed its role as the adhesin. Unexpectedly, apparent spontaneous cleavage of a labile, proline-rich (8 of 14 residues) sequence separating the N-terminal approximately 1/3 and C-terminal approximately 2/3 of Spy0125 leads to loss of the N-terminal region, but analysis of internal spy0125 deletion mutants confirmed that this has no significant effect on adhesion.

Stray light characterization of an InGaAs anamorphic hyperspectral imager.

Compact hyperspectral sensors potentially have a wide range of applications, including machine vision, quality control, and surveillance from small Unmanned Aerial Vehicles (UAVs). With the development of Indium Gallium Arsenide (InGaAs) focal plane arrays, much of the Short Wave Infra-Red (SWIR) spectral regime can be accessed with a small hyperspectral imaging system, thereby substantially expanding hyperspectral sensing capabilities. To fully realize this potential, system performance must be well-understood. Here, stray light characterization of a recently-developed push-broom hyperspectral sensor sensitive in the 1 microm -1.7 microm spectral regime is described. The sensor utilizes anamorphic fore-optics that partially decouple image formation along the spatial and spectral axes of the instrument. This design benefits from a reduction in complexity over standard high-performance spectrometer optical designs while maintaining excellent aberration control and spatial and spectral distortion characteristics. The stray light performance characteristics of the anamorphic imaging spectrometer were measured using the spectral irradiance and radiance responsivity calibrations using uniform sources (SIRCUS) facility at the National Institute of Standards and Technology (NIST). A description of the measurements and results are presented. Additionally, a stray-light matrix was assembled for the instrument to improve the instrument's spectral accuracy. Transmittance of a silicon wafer was measured to validate this approach.

Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes.

Adhesion of the serotype M1 Streptococcus pyogenes strain SF370 to human tonsil explants and cultured keratinocytes requires extended polymeric surface structures called pili. In this important human pathogen, pili are assembled from three protein subunits: Spy0125, Spy0128 and Spy0130 through the action of sortase enzymes. For this study, the structural properties of these pili proteins have been investigated in solution. Spy0125 and Spy0128 display characteristics of globular, folded proteins. Circular dichroism suggests a largely beta-sheet composition for Spy0128 and Spy0125; Spy0130 appears to contain little secondary structure. Each of the proteins adopts a monodisperse, monomeric state in solution as assessed by analytical ultracentrifugation. Further, small-angle X-ray scattering curves for Spy0125, Spy0128 and Spy0130 suggest each protein adopts an elongated shape, likely comprised of two domains, with similar maximal dimensions. Based on the scattering data, dummy atom models of each of the pili subunits have been reconstructed ab initio. This study provides the first insights into the structure of Streptococcus pyogenes minor pili subunits, and possible implications for protein function are discussed.

Evidence for niche adaptation in the genome of the bovine pathogen Streptococcus uberis.

BACKGROUND: Streptococcus uberis, a Gram positive bacterial pathogen responsible for a significant proportion of bovine mastitis in commercial dairy herds, colonises multiple body sites of the cow including the gut, genital tract and mammary gland. Comparative analysis of the complete genome sequence of S. uberis strain 0140J was undertaken to help elucidate the biology of this effective bovine pathogen. RESULTS: The genome revealed 1,825 predicted coding sequences (CDSs) of which 62 were identified as pseudogenes or gene fragments. Comparisons with related pyogenic streptococci identified a conserved core (40%) of orthologous CDSs. Intriguingly, S. uberis 0140J displayed a lower number of mobile genetic elements when compared with other pyogenic streptococci, however bacteriophage-derived islands and a putative genomic island were identified. Comparative genomics analysis revealed most similarity to the genomes of Streptococcus agalactiae and Streptococcus equi subsp. zooepidemicus. In contrast, streptococcal orthologs were not identified for 11% of the CDSs, indicating either unique retention of ancestral sequence, or acquisition of sequence from alternative sources. Functions including transport, catabolism, regulation and CDSs encoding cell envelope proteins were over-represented in this unique gene set; a limited array of putative virulence CDSs were identified. CONCLUSION: S. uberis utilises nutritional flexibility derived from a diversity of metabolic options to successfully occupy a discrete ecological niche. The features observed in S. uberis are strongly suggestive of an opportunistic pathogen adapted to challenging and changing environmental parameters.

Impact of a multimedia e-learning module on colon cancer literacy: a community-based pilot study.

BACKGROUND: We aimed to determine if an e-learning module could improve colon cancer literacy in a community-based cohort, while obtaining variability estimates for subsequent study. METHODS: A convenience sample of subjects attending a health-education fair was surveyed to determine colon cancer literacy before-and-after viewing a colon cancer e-learning module. The difference in cancer literacy scores was assessed for significance using univariate analysis. RESULTS: Twenty-two eligible subjects completed the survey: mean age 77.2+/-7.5 y, 55% women; 67% had at least some graduate-level education. Baseline colon cancer literacy was 72.6% +/- 11.6%; after the e-learning module, the mean colon cancer literacy score was 75.5% +/- 12.2%, representing a 3% improvement (P=0.33). After excluding a single problematic item identified by item analysis, the adjusted improvement was 7% (P=0.04). Invasiveness, malignant, and metastatic remained poorly understood concepts, while a large improvement (45%) was seen regarding the role of routine lymphadenectomy. Subject satisfaction with the module was universally (100%) high or very high. CONCLUSIONS: Use of an e-learning module is associated with high patient satisfaction, and has potential to improve colon cancer literacy in laypersons. Randomized study is warranted to determine the incremental impact of this and other multimedia educational interventions.

Low frequency fatigue in human quadriceps is fatigue dependent and not task dependent.

It is well accepted that a low intensity/long duration isometric contraction induces more low frequency fatigue (LFF) compared to a high-intensity/short-duration contraction. However, previous reports examined the intensity/duration of the contraction but did not control the level of fatigue when concluding fatigue is task dependent. The purpose of this study was to determine whether a long duration/low intensity fatiguing contraction would induce greater LFF than a short duration/high-intensity contraction when the quadriceps muscle was fatigued to similar levels. Eighteen healthy male subjects performed quadriceps contractions sustained at 35% and 65% of maximal voluntary contraction (MVC) on separate days, until the tasks induced a similar amount of fatigue (force generating capacity=45% MVC). Double pulse torque to single pulse torque ratio (D/S ratio) was obtained before, immediately and 5min after fatigue along with the electromyographic (EMG) signal from vastus medialis (VM) and rectus femoris (RF). The D/S ratio significantly (p<0.05) increased by 8.7+/-8.5% (mean+/-SD) and 10.2+/-9.2% after 35% and 65% tasks, respectively, and remained elevated 5min into recovery; however, there was no significant difference in ratio between the two sessions immediately or 5min post-fatigue (p>0.05) even though the endurance time for the 35% fatigue task (124+/-39.68s) was significantly longer (p=0.05) than that of the 65% task (63+/-17.73s). EMG amplitude and median power frequency (MPF) analysis also did not reveal any significant differences between these two sessions after fatigue. These findings indicate that LFF fatigue is fatigue dependent as well as task intensity/duration dependent. These findings assist us in understanding task dependency and muscle fatigue.

Identification of patients with Cushing's disease with negative pituitary adrenocorticotropin gradients during inferior petrosal sinus sampling: prolactin as an index of pituitary venous effluent.

Inferior petrosal sinus sampling for ACTH differentiates pituitary ACTH-dependent Cushing's (CD) from the ectopic ACTH syndrome (EAS). Petrosal sinus to peripheral (IPS:P) ACTH ratios greater than 2.0 in the basal state or a peak greater than 3.0 after CRH are diagnostic of CD. However, false-negative rates of 1-10% have been reported. We report three patients with features of CD with peak IPS:P ACTH ratios less than 3.0 after CRH suggesting EAS. We compared IPS:P prolactin (PRL) as an index of pituitary venous effluent in these three index cases with 44 patients with CD and five with EAS. The dominant basal IPS:P PRL ratio was greater than 1.8 in all 49 patients but was less than 1.2 in the three index cases. The IPS:P ACTH ratio normalized to IPS:P PRL was greater than 0.8 in all CD patients but was less than 0.6 in EAS patients. The IPS:P ACTH ratios normalized to IPS:P PRL were greater than 1.2 in the index cases, which was similar to those with CD. The three index cases had clinical and biochemical remissions after pituitary surgery.PRL is an index of pituitary venous effluent during inferior petrosal sinus sampling in patients with CD who fail to have a peak IPS:P ACTH ratio greater than 3.0 after CRH. IPS:P PRL should be measured when results indicate EAS.

Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism.

Sortases are a family of Gram-positive bacterial transpeptidases that anchor secreted proteins to bacterial cell surfaces. These include many proteins that play critical roles in the virulence of Gram-positive bacterial pathogens such that sortases are attractive targets for development of novel antimicrobial agents. All Gram-positive pathogens express a "housekeeping" sortase that recognizes the majority of secreted proteins containing an LPXTG wall-sorting motif and covalently attaches these to bacterial cell wall peptidoglycan. Many Gram-positive pathogens also express additional sortases that link a small number of proteins, often with variant wall-sorting motifs, to either other surface proteins or peptidoglycan. To better understand the mechanisms of catalysis and substrate recognition by the housekeeping sortase produced by the important human pathogen Streptococcus pyogenes, the crystal structure of this protein has been solved and its transpeptidase activity established in vitro. The structure reveals a novel arrangement of key catalytic residues in the active site of a sortase, the first that is consistent with kinetic analysis. The structure also provides a complete description of residue positions surrounding the active site, overcoming the limitation of localized disorder in previous structures of sortase A-type proteins. Modification of the active site Cys through oxidation to its sulfenic acid form or by an alkylating reagent supports a role for a reactive thiol/thiolate in the catalytic mechanism. These new insights into sortase structure and function could have important consequences for inhibitor design.

Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis.

BACKGROUND: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. CONCLUSIONS/SIGNIFICANCE: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.

Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin.

Very little is known about the biological functions of pili that have recently been found to be expressed by important Gram-positive pathogens such as Corynebacterium diphtheriae, Streptococcus agalacticae, S. pneumoniae and S. pyogenes. Using various ex vivo tissue and cellular models, here we show that pili mediate adhesion of serotype M1 S. pyogenes strain SF370 to both human tonsil epithelium and primary human keratinocytes, which represent the two main sites of infection by this human-specific pathogen. Mutants lacking minor pilus subunits retained the ability to express cell-surface pili, but these were functionally defective. In contrast to above, pili were not required for S. pyogenes adhesion to either immortalized HEp-2 or A549 cells, highlighting an important limitation of these extensively used adhesion/invasion models. Adhering bacteria were internalized very effectively by both HEp-2 and A549 cells, but not by tonsil epithelium or primary keratinocytes. While pili acted as the primary adhesin, the surface M1 protein clearly enhanced adhesion to tonsil, but surprisingly, had the opposite effect on adhesion to keratinocytes. These studies provide clear evidence that S. pyogenes pili display an adhesive specificity for clinically relevant human tissues and are likely to play a critical role in the initial stages of infection.

Complete genome of acute rheumatic fever-associated serotype M5 Streptococcus pyogenes strain manfredo.

Comparisons of the 1.84-Mb genome of serotype M5 Streptococcus pyogenes strain Manfredo with previously sequenced genomes emphasized the role of prophages in diversification of S. pyogenes and the close relationship between strain Manfredo and MGAS8232, another acute rheumatic fever-associated strain.

An assessment of risk associated with the photography of microbiological materials.

This study investigated risks associated with the photography of materials that are a potential source of infection, the extent to which medical illustrators are aware of these risks, the relevant government regulations and guidance, and whether recommended control measures are adopted. To seek information about current practice, a questionnaire was sent to randomly selected Medical Illustration Units across the United Kingdom. The data indicated that a significant proportion of medical illustrators routinely photograph materials that could be a source of infection, but that a high percentage know little about the specific regulations and guidance which govern the handling of such materials. Apparent deficiencies in safety procedures currently applied in photographing microbiological materials were identified; recommendations that address these problems at little or no cost are proposed.

Combined contributions of streptolysin O and streptolysin S to virulence of serotype M5 Streptococcus pyogenes strain Manfredo.

Streptolysin O (SLO) and streptolysin S (SLS) are potent cytolytic toxins produced by almost all clinical isolates of group A streptococci (GAS). Allele-replacement mutagenesis was used to construct nonpolar (in-frame) deletion mutations in the slo and sagB genes of the serotype M5 GAS strain Manfredo, producing isogenic single and double SLO- and SLS-defective mutants. In contrast to recent reports on SLS-defective insertion mutants (I. Biswas, P. Germon, K. McDade, and J. Scott, Infect. Immun. 69:7029-7038, 2001; Z. Li, D. Sledjeski, B. Kreikemeyer, A.Podbielski, and M. Boyle, J. Bacteriol. 181:6019-6027, 1999), none of the mutants described here had notable pleiotropic effects on the expression of other virulence factors examined. Comparison of isogenic parent and mutant strains in various virulence models revealed no differences in their abilities to multiply in human blood or in their 50% lethal doses (LD(50)s) upon intraperitoneal infection of BALB/c mice. A single log unit difference in the LD(50)s of the parent and SLS-defective mutant strains was observed upon infection by the subcutaneous (s.c.) route. Comparisons over a range of infective doses showed that both SLO and SLS contributed to the early stages of infection and to the induction of necrotic lesions in the murine s.c. model. Individually, each toxin made an incremental contribution to virulence that was not apparent at higher infective doses, although the absence of both toxins reduced virulence over the entire dose range examined. Interestingly, in some cases, the contribution of SLO to virulence was clear only from an analysis of the double-mutant strain, highlighting the value of not confining virulence studies to mutant strains defective in the expression of only single virulence factors.

Structural and functional role of threonine 112 in a superantigen Staphylococcus aureus enterotoxin B.

Bacterial superantigens are potent T-cell stimulatory protein molecules produced by Staphylococcus aureus and Streptococcus pyogenes. Their superantigenic activity can be attributed to their ability to cross-link major histocompatibility complex class II molecules with T-cell receptors (TCRs) to form a tri-molecular complex. Each superantigen is known to interact with a specific V(beta) element of TCR. Staphylococcal enterotoxin B (SEB, a superantigen), a primary cause of food poisoning, is also responsible for a significant percentage of non-menstrual associated toxic shock syndrome in patients with a variety of staphylococcal infections. Structural studies have elucidated a binding cavity on the toxin molecule essential for TCR binding. To understand the crucial residues involved in binding, mutagenesis analysis was performed. Our analysis suggest that mutation of a conserved residue Thr(112) to Ser (T112S) in the binding cavity induces a selective reduction in the affinity for binding one TCR V(beta) family and can be attributed to the structural differences in the native and mutant toxins. We present a detailed comparison of the mutant structure determined at 2.0 A with the previously reported native SEB and SEB-TCR V(beta) complex structures.