CRISPR-based editing of the ω- and γ-gliadin gene clusters reduces wheat immunoreactivity without affecting grain protein quality.

Wheat immunotoxicity is associated with abnormal reaction to gluten-derived peptides. Attempts to reduce immunotoxicity using breeding and biotechnology often affect dough quality. Here, the multiplexed CRISPR-Cas9 editing of cultivar Fielder was used to modify gluten-encoding genes, specifically focusing on ω- and γ-gliadin gene copies, which were identified to be abundant in immunoreactive peptides based on the analysis of wheat genomes assembled using the long-read sequencing technologies. The whole-genome sequencing of an edited line showed mutation or deletion of nearly all ω-gliadin and half of the γ-gliadin gene copies and confirmed the lack of editing in the α/ß-gliadin genes. The estimated 75% and 64% reduction in ω- and γ-gliadin content, respectively, had no negative impact on the end-use quality characteristics of grain protein and dough. A 47-fold immunoreactivity reduction compared to a non-edited line was demonstrated using antibodies against immunotoxic peptides. Our results indicate that the targeted CRISPR-based modification of the ω- and γ-gliadin gene copies determined to be abundant in immunoreactive peptides by analysing high-quality genome assemblies is an effective mean for reducing immunotoxicity of wheat cultivars while minimizing the impact of editing on protein quality.

Fatal Food: Silver-Coated Grain Particles Display Larvicidal Activity in Culex quinquefasciatus.

Mosquitoes pose a significant risk to millions of people worldwide since they can transmit pathogens. Current methods to control mosquito populations include the use of synthetic pesticides. Nanotechnology may be a solution to develop new mosquito control. However, one barrier to expanding the impact of nanomaterials is the ability to mass-produce the particles. Here, we report a novel hybrid particle synthesis combining micro- and nanoparticles using the coprecipitation technique with the potential for mass production. These particles may have applications as a mosquito larvacide. The particles reported here were designed using a microparticle zein polymer as the core and a nanoparticle silver as the active ingredient. The hybrid NPs reported here targeted a late-stage mosquito larvae and that resulted in a high larval mortality concentration (1.0 ppm, LC90) and suppression of pupal emergence at 0.1 ppm. This research demonstrates the efficacy of a plant-based core with a metal-based AI coating (AgNPs) against larval mosquitoes.

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder.

Environmental and genetic factors contribute to the etiology of autism spectrum disorder (ASD), but their interaction is less well understood. Mothers that are genetically more stress-susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, the presence of maternal antibodies for the fetal brain is associated with a diagnosis of ASD in children. However, the relationship between prenatal stress exposure and maternal antibodies in the mothers of children diagnosed with ASD has not yet been addressed. This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in children. Blood samples from 53 mothers with at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress levels during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. While high incidences of prenatal stress and maternal antibodies were found in the sample, they were not associated with each other (p = 0.709, Cramér's V = 0.051). Furthermore, the results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (p = 0.729, Cramér's V = 0.157). Prenatal stress was not found to be associated with the presence of maternal antibodies in the context of ASD, at least in this initial exploratory sample. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. However, this would need to be confirmed in a larger sample.

Bread-making properties of different pulse flours in composites with refined wheat flour.

There has been a growing demand for pulses due to the nutrition, health benefits, and agronomical advantages, along with the recommendation of international organizations to diversify the use of pulses. Lentil, yellow pea, and chickpea were studied for their effect on the quality of the bread when incorporated into refined wheat flour. The pulse grains were roller milled into different particle sizes (small: 44-59 µm, medium: 70-85 µm, and large: 95-104 µm) with similar composition, and each refined pulse flour was incorporated in refined wheat flour at levels of 5, 12.5, and 20% (wt/wt). The flours were characterized for particle size distribution, starch damage, proximate composition, water retention, and dough mixing properties, followed by baking test and texture analysis. The particle size of the pulse flours did not significantly affect the bread volume or the texture, while increasing the pulse flour incorporation decreased the bread specific volume from 5.0 to 3.4 cm3 /g and the hardness of the bread increased from 3.9 to 9.9 N at the maximum incorporation level. The crust color darkened as pulse flour incorporation was increased, while the effect on crumb color was marginable. Among the three pulses, chickpea performed better compared to lentil and yellow pea, and yellow pea resulted in bread with lower volume at all levels of incorporation. Enriched bread can be produced by incorporating pulse flours at up to 12.5% (wt/wt) without significant effect on the quality of bread, with chickpeas possessing better baking properties than yellow pea or lentil.

A comprehensive review of wheat phytochemicals: From farm to fork and beyond.

The health benefits of whole wheat consumption can be partially attributed to wheat's phytochemicals, including phenolic acids, flavonoids, alkylresorcinols, carotenoids, phytosterols, tocopherols, and tocotrienols. It is of increasing interest to produce whole wheat products that are rich in bioactive phytochemicals. This review provides the fundamentals of the chemistry, extraction, and occurrence of wheat phytochemicals and includes critical discussion of several long-lasting issues: (1) the commonly used nomenclature on distribution of wheat phenolic acids, namely, soluble-free, soluble-conjugated, and insoluble-bound phenolic acids; (2) different extraction protocols for wheat phytochemicals; and (3) the chemistry and application of in vitro antioxidant assays. This review further discusses recent advances on the effects of genotypes, environments, field management, and processing techniques including ultrafine grinding, germination, fermentation, enzymatic treatments, thermal treatments, and food processing. These results need to be interpreted with care due to varied sample preparation protocols and limitations of in vitro assays. The bioaccessibility, bioavailability, metabolism, and potential health benefits of wheat phytochemicals are also reviewed. This comprehensive and critical review will benefit scientific researchers in the field of bioactive compounds of cereal grains and also those in the cereal food industry to produce high-quality functional foods.

Quantitative assessment of wheat quality using near-infrared spectroscopy: A comprehensive review.

Wheat is one of the most widely cultivated crops throughout the world. A great need exists for wheat quality assessment for breeding, processing, and products production purposes. Near-infrared spectroscopy (NIRS) is a rapid, low-cost, simple, and nondestructive assessment method. Many advanced studies associated with NIRS for wheat quality assessment have been published recently, either introducing new chemometrics or attempting new assessment parameters to improve model robustness and accuracy. This review provides a comprehensive overview of NIRS methodology including its principle, spectra pretreatments, spectral wavelength selection, outlier disposal, dataset division, regression methods, and model evaluation. More importantly, the applications of NIRS in the determination of analytical parameters, rheological parameters, and end product quality of wheat are summarized. Although NIRS showed great potential in the quantitative determination of analytical parameters, there are still challenges in model robustness and accuracy in determining rheological parameters and end product quality for wheat products. Future model development needs to incorporate larger databases, integrate different spectroscopic techniques, and introduce cutting-edge chemometrics methods. In addition, calibration based on external factors should be considered to improve the predicted results of the model. The NIRS application in micronutrients needs to be extended. Last, the idea of combining standard product sensory attributes and spectra for model development deserves further study.

Chemical Composition, Fatty Acid and Mineral Content of Food-Grade White, Red and Black Sorghum Varieties Grown in the Mediterranean Environment.

Grain sorghum (Sorghum bicolor) is a gluten-free cereal grown around the world and is a food staple in semi-arid and subtropical regions. Sorghum is a diverse crop with a range of pericarp colour including white, various shades of red, and black, all of which show health-promoting properties as they are rich sources of antioxidants such as polyphenols, carotenoids, as well as micro- and macro-nutrients. This work examined the grain composition of three sorghum varieties possessing a range of pericarp colours (white, red, and black) grown in the Mediterranean region. To determine the nutritional quality independent of the contributions of phenolics, mineral and fatty acid content and composition were measured. Minor differences in both protein and carbohydrate were observed among varieties, and a higher fibre content was found in both the red and black varieties. A higher amount of total saturated fats was found in the white variety, while the black variety had a lower amount of total unsaturated and polyunsaturated fats than either the white or red varieties. Oleic, linoleic, and palmitic were the primary fatty acids in all three analysed sorghum varieties. Significant differences in mineral content were found among the samples with a greater amount of Mg, K, Al, Mn, Fe, Ni, Zn, Pb and U in both red and black than the white sorghum variety. The results show that sorghum whole grain flour made from grain with varying pericarp colours contains unique nutritional properties.

microRNAs and Gene-Environment Interactions in Autism: Effects of Prenatal Maternal Stress and the SERT Gene on Maternal microRNA Expression.

Background: Genetics and environment both are critical in autism spectrum disorder (ASD), but their interaction (G × E) is less understood. Numerous studies have shown higher incidence of stress exposures during pregnancies with children later diagnosed with ASD. However, many stress-exposed mothers have unaffected children. The serotonin transporter (SERT) gene affects stress reactivity. Two independent samples have shown that the association between maternal stress exposure and ASD is greatest with maternal presence of the SERT short (S)-allele (deletion in the promoter region). MicroRNAs play a regulatory role in the serotonergic pathway and in prenatal stress and are therefore potential mechanistic targets in this setting. Design/methods: We profiled microRNA expression in blood from mothers of children with ASD, with known stress exposure during pregnancy. Samples were divided into groups based on SERT genotypes (LL/LS/SS) and prenatal stress level (high/low). Results: Two thousand five hundred mature microRNAs were examined. The ANOVA analysis showed differential expression (DE) of 119 microRNAs; 90 were DE in high- vs. low-stress groups (stress-dependent). Two (miR-1224-5p, miR-331-3p) were recently reported by our group to exhibit stress-dependent expression in rodent brain samples from embryos exposed to prenatal stress. Another, miR-145-5p, is associated with maternal stress. Across SERT genotypes, with high stress exposure, 20 significantly DE microRNAs were detected, five were stress-dependent. These microRNAs may be candidates for stress × SERT genotype interactions. This is remarkable as these changes were from mothers several years after stress-exposed pregnancies. Conclusions: Our study provides evidence for epigenetic alterations in relation to a G × E model (prenatal maternal stress × SERT gene) in ASD.

High-resolution spectral information enables phenotyping of leaf epicuticular wax in wheat.

BACKGROUND: Epicuticular wax (EW) is the first line of defense in plants for protection against biotic and abiotic factors in the environment. In wheat, EW is associated with resilience to heat and drought stress, however, the current limitations on phenotyping EW restrict the integration of this secondary trait into wheat breeding pipelines. In this study we evaluated the use of light reflectance as a proxy for EW load and developed an efficient indirect method for the selection of genotypes with high EW density. RESULTS: Cuticular waxes affect the light that is reflected, absorbed and transmitted by plants. The narrow spectral regions statistically associated with EW overlap with bands linked to photosynthetic radiation (500 nm), carotenoid absorbance (400 nm) and water content (~ 900 nm) in plants. The narrow spectral indices developed predicted 65% (EWI-13) and 44% (EWI-1) of the variation in this trait utilizing single-leaf reflectance. However, the normalized difference indices EWI-4 and EWI-9 improved the phenotyping efficiency with canopy reflectance across all field experimental trials. Indirect selection for EW with EWI-4 and EWI-9 led to a selection efficiency of 70% compared to phenotyping with the chemical method. The regression model EWM-7 integrated eight narrow wavelengths and accurately predicted 71% of the variation in the EW load (mg·dm-2) with leaf reflectance, but under field conditions, a single-wavelength model consistently estimated EW with an average RMSE of 1.24 mg·dm-2 utilizing ground and aerial canopy reflectance. CONCLUSIONS: Overall, the indices EWI-1, EWI-13 and the model EWM-7 are reliable tools for indirect selection for EW based on leaf reflectance, and the indices EWI-4, EWI-9 and the model EWM-1 are reliable for selection based on canopy reflectance. However, further research is needed to define how the background effects and geometry of the canopy impact the accuracy of these phenotyping methods.

Identification of gluten-like proteins in selected pod bearing leguminous tree seeds.

The protein composition, molecular weight distribution, and rheological properties of honey locust, mesquite, Kentucky coffee tree, and carob seed germs were compared against wheat gluten. Polymeric and Osborne fractionation protocols were used to assess biochemical properties. Dynamic oscillatory shear tests were performed to evaluate protein functionality. All samples had similar ratios of protein fractions as well as high molecular weight disulfide linked proteins except for the Kentucky coffee tree germ proteins, which were found to have lower molecular weight proteins with little disulfide polymerization. Samples were rich in acidic and polar amino acids (glutamic acid and arginine,). Rheological analyses showed that vital wheat gluten had the most stable network, while Kentucky coffee seed proteins had the weakest. High molecular weight disulfide linked glutenous proteins are a common, but not universal feature of pod bearing leguminous trees.

Analysis of corn and sorghum flour mixtures using laser-induced breakdown spectroscopy.

BACKGROUND: In a world constantly challenged by climate change, corn and sorghum are two important grains because of their high productivity and adaptability, and their multifunctional use for different purposes such as human food, animal feed, and feedstock for many industrial products and biofuels. Corn and sorghum can be utilized interchangeably in certain applications; one grain may be preferred over the other for several reasons. The determination of the composition corn and sorghum flour mixtures may be necessary for economic, regulatory, environmental, functional, or nutritional reasons. RESULTS: Laser-induced breakdown spectroscopy (LIBS) in combination with chemometrics, was used for the classification of flour samples based on the LIBS spectra of flour types and mixtures using partial least squares discriminant analysis (PLS-DA) and the determination of the sorghum ratio in sorghum / corn flour mixture based on their elemental composition using partial least squares (PLS) regression. Laser-induced breakdown spectroscopy with PLS-DA successfully identified the samples as either pure corn, pure sorghum, or corn-sorghum mixtures. Moreover, the addition of various levels of sorghum flour to mixtures of corn-sorghum flour were used for PLS analysis. The coefficient of determination values of calibration and validation PLS models are 0.979 and 0.965, respectively. The limit of detection of the PLS models is 4.36%. CONCLUSION: This study offers a rapid method for the determination of the sorghum level in corn-sorghum flour mixtures and the classification of flour samples with high accuracy, a short analysis time, and no requirement for time-consuming sample preparation procedures. © 2020 Society of Chemical Industry.

Changes in phenolic profiles and antioxidant activities during the whole wheat bread-making process.

Health benefits of whole wheat products are partially attributed to their unique phenolic profiles. This study investigated the effect of bread-making processes on the phenolic profiles and antioxidant activities of four different varieties of hard red winter wheat. The fermentation process generally increased soluble phenolic content, flavonoid content, antioxidant activities, and soluble ferulic acid of whole wheat products. The baking process increased the soluble phenolic content and antioxidant activities. Some phenolic acids were incorporated into Maillard reaction products during baking. For the insoluble fraction, fermentation and baking slightly increased phenolic content, flavonoid content, and antioxidant activities of certain wheat varieties. Ferulic acid and isomers of di-ferulic acid (DFA) were not significantly affected by the baking process. Overall, the bread-making process demonstrated positive effects on the potential health benefits of whole wheat products.

Rapid determination of total phenolic content of whole wheat flour using near-infrared spectroscopy and chemometrics.

Phenolics in whole wheat products provide many health benefits. Wheat breeders, producers, and end-users are becoming increasingly interested in wheats with higher total phenolic content (TPC). Whole wheat flour with higher phenolics may have greater marketing value in the future. However, conventional methods determining TPC are costly and labor-intensive, which are not practical for wheat breeders to analyze several thousands of lines within a limited timeframe. We presented a novel application of near-infrared spectroscopy for TPC prediction in whole wheat flour. The optimal regression model demonstrated R2 values of 0.92 and 0.90 for the calibration and validation sets, and a residual prediction deviation value of 3.4. The NIR method avoids the tedious extraction and TPC assay procedures, making it more convenient and cost-effective. Our result also demonstrated that NIR can accurately quantify phenolics even at low concentration (less than 0.2%) in the food matrix such as whole wheat flour.

Individual effects of enzymes and vital wheat gluten on whole wheat dough and bread properties.

The objective of this research was to determine effects of five enzymes on whole wheat bread properties, particularly loaf volume, bread texture, and staling. Enzymes containing conventional α-amylase (α-amyl), cellulase (cel), glucose oxidase, maltogenic α-amylase (m amyl), and xylanase (xyl) were added at three levels. Vital wheat gluten (VWG) was added as an additional, separate treatment at 2.5% (flour weight basis). Enzymes had minimal effect on water absorption and mixing time. Each enzyme increased specific loaf volume for at least one of the usage levels tested (P < 0.01). Among the enzyme treatments, the greatest loaf volume was seen for xyl at the medium and high levels. No enzyme was as effective as VWG at increasing loaf volume. Overall, enzymes did not significantly change cell structure. The greatest reduction in fresh bread hardness was obtained for the high level of xyl. VWG, m amyl, and xyl reduced the rate of bread firming over 7 days. α-Amyl, cel, and m amyl decreased starch retrogradation at day 7 as measured by differential scanning calorimetry (P < 0.01). M amyl nearly eliminated the endothermic peak for recrystallized amylopectin. This study demonstrated the specific application of enzymes in whole wheat bread to increase loaf volume and decrease initial crumb hardness and bread staling. PRACTICAL APPLICATION: This study will provide guidance for practical uses of enzymes in improving whole wheat dough and bread quality.

Traumatic Arthrotomy.

Evaluation of periarticular traumatic wounds for joint penetration is a common clinical concern for orthopaedic surgeons. Wounds that violate the joint capsule can result in deep infection and sepsis. Understanding the anatomic landmarks and capsular extensions of the major joints is key to proper evaluation. Initial evaluation of periarticular wounds includes thorough examination of the wound and plain radiographs. Historically, the saline load test has been the diagnostic test of choice for assessing traumatic arthrotomy; however, CT has recently been shown to have excellent sensitivity and specificity for detecting open knee joint injuries. Current treatment of traumatic arthrotomy includes intravenous antibiotics and surgical irrigation and débridement. Future areas of research must focus on further validation of CT evaluation and its use in other major joints, standardizing antibiotic treatment, and further delineating the role of nonsurgical management in minor injuries.

Ipsilateral rotational double-barrel fibula autograft for limb salvage in a pediatric patient with lower extremity intramedullary osteosarcoma: A case report.

Osteosarcoma is a relatively uncommon diagnosis that often requires limb salvage techniques in young patients. Due to the potential long-life expectancy of these patients, techniques which avoid prostheses are preferred to limit the need for future revision surgeries. This case report presents a 9-year-old male diagnosed with intramedullary well-differentiated osteosarcoma of the tibial diaphysis. This limb salvage procedure utilized a rotational ipsilateral vascularized double barrel fibula autograft measuring a total of 24.5 cm when harvested but osteotomized to lengths of 11 and 12.5 cm limbs to reconstruct an 11 cm tibial shaft defect. Anterior chamfer cuts were performed on one limb allowing it to be inserted intramedullary while the second limb was then placed with an inlay technique posterolaterally and then compressed with a carbon fiber plate. The patient recovered well initially postoperatively but was taken back for revision of the carbon fiber plate 10 weeks postoperatively secondary to asymptomatic loosening of the proximal screws. The patient subsequently healed and experienced full graft incorporation with expected hypertrophy of the graft. At most recent follow-up at 19 months, the patient reported no pain and was utilizing the extremity in a normal fashion with no activity limitations. In this report, we present a case of the use of an ipsilateral rotational double-barrel fibula autograft for limb salvage in a pediatric patient with lower extremity intramedullary osteosarcoma.

Effects of stress on functional connectivity during problem solving.

AIM: Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect. METHODS: Forty-five healthy participants (Mean age: 19.6 â€‹± â€‹1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task. RESULTS: There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene â€‹× â€‹stress interaction on solution latency was also observed. DISCUSSION: Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.

Effects of stress on functional connectivity during verbal processing.

Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6 ± 1.6 years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.

Factors Influencing Zein-Whole Sorghum Flour Dough Formation and Bread Quality.

Zein is known to able to form viscoelastic dough with wheat-like properties under certain conditions. Several studies have been conducted to explain the mechanism behind this ability and to improve the functionality and end-use quality of zein-based dough systems. However, most of this research has been conducted using zein in combination with isolated starches or high-starch flours. To investigate the production of additional zein-whole sorghum flour breads, experiments were conducted to determine factors impacting zein-whole sorghum flour dough and bread quality. Optimizing water levels, using defatted zein and/or sorghum flour, and increasing zein content in dough formulas were investigated as initial formulation steps. Of these factors, increasing zein content from 20% to 30% (flour weight basis) had the greatest impact, resulting in stronger zein-based dough and improved bread quality. Additives and zein treatments shown to impact zein functionality were then investigated for their effect of zein-whole sorghum flour breads. Mixing zein and whole sorghum flour with 0.5% hydrogen peroxide, 5% ethanol, or 3% hydroxypropyl methylcellulose resulted in improved dough strength and bread quality. Breads made from whole white sorghum flour had improved quality compared to zein-based breads made with black or high-tannin whole sorghum flour. PRACTICAL APPLICATION: Zein is known to be able to form wheat-like dough when mixed under the right conditions. Most of the research on zein-based dough and food products has used high-starch flours. This project investigated optimizing the production of zein-whole sorghum flour dough and bread as an alternative. Increasing the zein content in the formula and using additives including ethanol and HPMC produced breads from zein-whole sorghum flour that were like those made with zein and pure starch.

Influence of Serotonin Transporter SLC6A4 Genotype on the Effect of Psychosocial Stress on Cognitive Performance: An Exploratory Pilot Study.

BACKGROUND AND OBJECTIVE: Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams. METHODS: In this exploratory pilot study, 28 healthy young adults were genotyped for long (L)-allele versus S-allele promoter region polymorphism of the 5-HTT gene, SLC6A4. Participants solved anagrams during the Trier Social Stress Test, which included public speaking and mental arithmetic stressors. We compared the participants' cognitive response to stress across genotypes. RESULTS: A Gene×Stress interaction effect was observed in this small sample. Comparisons revealed that participants with at least one S-allele performed worse during the Stress condition. CONCLUSIONS: Genetic susceptibility to stress conferred by SLC6A4 appeared to modulate unconstrained cognitive flexibility during psychosocial stress in this exploratory sample. If confirmed, this finding may have implications for conditions associated with increased stress response, including performance anxiety and cocaine withdrawal. Future work is needed both to confirm our findings with a larger sample and to explore the mechanisms of this proposed effect.