Progress toward the Definition of X-ray Computed Tomography Accuracy in the Characterization of Polymer-Based Lattice Structures.

Lattice structures have become an innovative solution for the improvement of part design, as they are able to substitute solid regions, maintain mechanical capabilities, and reduce material usage; however, dimensional quality control of these geometries is challenging. X-ray computed tomography (XCT) is the most suitable non-destructive metrological technique as it is capable of characterizing internal features and hidden elements. Uncertainty estimation of XCT is still in development, and studies typically use high-resolution calibrated devices such as focal variation microscopes (FVMs) as a reference, focusing on certain parts of the lattice but not the whole structure. In this paper, an estimation of the accuracy of XCT evaluation of a complete lattice structure in comparison to a higher-resolution reference device (FVM) is presented. Experimental measurements are taken on ad hoc designed test objects manufactured in polyamide 12 (PA12) using selective laser sintering (SLS), optimized for the evaluation on both instruments using different cubic-based lattice typologies. The results confirm higher precision on XCT evaluation in both qualitative and quantitative analysis. Even with a lower resolution, XCT is able to characterize details of the surface such as re-entrant features; as well, standard deviations and uncertainties in strut diameter evaluation remain more stable in all cells in XCT, identifying on the other hand reconstruction problems on FVM measurements. Moreover, it is shown that, using XCT, no additional evaluation errors were found in inner cells, suggesting that the measurement of external elements could be representative of the whole structure for metrological purposes.

Optimizing pediatric periprocedural pain management part I-Evolving ethics and topical anesthetics.

Pediatric procedure-related pain management is often incompletely understood, inadequately addressed, and critical in influencing a child's lifelong relationship with the larger health care community. We highlight the evolution of ethics and expectations around optimizing periprocedural pain management as a fundamental human right. We investigate the state-of-the-art of topical anesthetics, reviewing their mechanisms of action and providing comparisons of their relative safety and efficacy data to help guide clinical selection. In total, this two-part review offers a combination of conventional approaches and innovative techniques that should be used multimodally-in series and in parallel-to help optimize pain management and provide alternatives to sedation medication and general anesthesia.

Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter.

Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral heteromeric amino acid transporter that can function through facilitated diffusion, and the only one that efficiently transports glycine and D-serine, and thus has a regulatory role in the central nervous system. Here we use cryoEM, ligand-binding simulations, mutagenesis, transport assays, and molecular dynamics to define human Asc1/CD98hc determinants for substrate specificity and gain insights into the mechanisms that govern substrate translocation by exchange and facilitated diffusion. The cryoEM structure of Asc1/CD98hc is determined at 3.4-3.8 Å resolution, revealing an inward-facing semi-occluded conformation. We find that Ser 246 and Tyr 333 are essential for Asc1/CD98hc substrate selectivity and for the exchange and facilitated diffusion modes of transport. Taken together, these results reveal the structural bases for ligand binding and transport features specific to human Asc1.

Novel Lactobacillaceae strains and consortia to produce propionate-containing fermentates as biopreservatives.

Biopreservation refers to the use of natural or controlled microbial single strains or consortia, and/or their metabolites such as short-chain carboxylic acids (SCCA), to improve the shelf-life of foods. This study aimed at establishing a novel Lactobacillaceae-driven bioprocess that led to the production of the SCCA propionate through the cross-feeding on 1,2-propanediol (1,2-PD) derived from the deoxyhexoses rhamnose or fucose. When grown as single cultures in Hungate tubes, strains of Lacticaseibacillus rhamnosus preferred fucose over rhamnose and produced 1,2-PD in addition to lactate, acetate, and formate, while Limosilactobacillus reuteri metabolized 1,2-PD into propionate, propanol and propanal. Loigolactobacillus coryniformis used fucose to produce 1,2-PD and only formed propionate when supplied with 1,2-PD. Fermentates collected from batch fermentations in bioreactor using two-strain consortia (L. rhamnosus and L. reuteri) or fed-batch fermentations of single strain cultures of L. coryniformis with rhamnose contained mixtures of SCCA consisting of mainly lactate and acetate and also propionate. Synthetic mixtures that contained SCCA at concentrations present in the fermentates were more antimicrobial against Salmonella enterica if propionate was present. Together, this study (i) demonstrates the potential of single strains and two-strain consortia to produce propionate in the presence of deoxyhexoses extending the fermentation metabolite profile of Lactobacillaceae, and (ii) emphasizes the potential of applying propionate-containing fermentates as biopreservatives.

Underrepresented Groups and Perceived Educational Barriers for Residency and Fellowship Success.

BACKGROUND: The study aimed to compare barriers perceived by medical students and resident physicians identifying as of underrepresented groups in medicine (UIM) and/or as sexual and gender minorities (SGM) to individuals not identifying with these groups, especially for trainees with an interest in dermatology. METHODS: Cross-sectional survey of medical students and resident physicians based in the United States from February 2021 to July 2021, with subgroup analysis of trainees with interest in dermatology. FINDINGS: Among trainees interested in dermatology, the most notable barriers for the UIM group were 1) lack of home program in specialty/fellowship of interest (4.71±1.73); 2) lack of connections/networking opportunities (4.14±1.29); 3) lack of opportunity to obtain AOA membership (4.00±1.96); 4) obtaining mentorship (4.00±1.47); and lack of diversity in specialty/fellowship of interest (3.93±1.14). CONCLUSIONS AND RELEVANCE: Increasing focused mentorship programs and fostering environments that embrace diversity are key to reducing perceived barriers for minority candidates. J Drugs Dermatol. 2023;22(12):1210-1215. doi:10.36849/JDD.7528R1.

Manifestaciones otorrinolaringológicas del Síndrome VEXAS. Revisión sistemática / Ear, nose, and throat manifestations of VEXAS Syndrome. Systematic review

Introducción y objetivo: El síndrome VEXAS (SV) es una entidad de descripción reciente que afecta fundamentalmente a varones, y se debe a una mutación somática en el gen UBA1. Puede cursar con múltiples manifestaciones sistémicas, siendo la afectación de cabeza y cuello muy frecuente. El objetivo de este estudio fue describir las manifestaciones otorrinolaringológicas del SV, que contribuyan a un diagnóstico y tratamiento temprano de la enfermedad. Método: Se realizó una revisión de la literatura médica, utilizando los criterios PRISMA adaptados al tipo de estudio, de las manifestaciones otorrinolaringológicas del SV, utilizando la base de datos PubMed. Resultados: Fueron incluidos en nuestro trabajo 81 artículos que cumplían los criterios de inclusión del mismo, los cuales describían 133 casos. Los resultados mostraron que el SV se produce, sobre todo, en varones mayores de 50 años de edad, presentando en más de la mitad de los casos, manifestaciones de cabeza y cuello, entre las que destacan la CA, la condritis nasal y el edema periorbitario. Conclusiones: Con frecuencia el SV es confundido, en los pacientes con manifestaciones otorrinolaringológicas, con la policondritis recurrente. El conocimiento por parte del otorrinolaringólogo de las manifestaciones de cabeza y cuello asociadas al mismo, puede contribuir a un diagnóstico y tratamiento temprano mejorando el pronóstico de la enfermedad. (AU)

Introduction and objectives: VEXAS syndrome (VS) is a recently described clinical entity that mainly affects males, and is due to a somatic mutation in the UBA1 gene. It can present with multiple systemic manifestations, especially hematological and dermatological, being the affectation of the head and neck very frequent, especially, auricular chondritis (AC). The objective of this study was to describe the otorhinolaryngological manifestations of VS, knowledge of which by the otolaryngologist could contribute to early diagnosis and treatment of the disease. Methods: A review of the medical literature was carried out, using the PRISMA criteria adapted to the type of study, of the otorhinolaryngological manifestations of VS, from its description in the year 2020 to December 2022, using the Pubmed database. Results: 81 articles that met the inclusion criteria were included in our work, which described 133 cases in detail. The results showed that VS occurs mainly in men over 50 years of age, presenting in more than half of the cases head and neck manifestations, among which AC, nasal chondritis and periorbital edema stand out. Conclusions: Since VS can affect any part of the body, mimicking the clinical pictures of other diseases, it has often been confused, in patients with otorhinolaryngological manifestations, especially with recurrent polychondritis. Knowledge by the otolaryngologist of the head and neck manifestations associated with it can contribute to early diagnosis and treatment, improving the prognosis of the disease. (AU)

Virtual reality and noise canceling headphone distraction during pediatric dermatologic procedures.

Pain and anxiety related to medical procedures have long been recognized as a significant healthcare concern. If a patient's procedural pain and anxiety are not addressed, long-term physical and psychological sequelae including increased perceived pain, anxiety, disruptive behavior, trauma reactions, or refusal of future procedures can occur. The objective of our study was to assess the utility of a virtual reality (VR) headset or noise-canceling headphones (HP) compared to treatment as usual (TAU) in reducing pain and anxiety during pediatric dermatology procedures. Results indicated a significant difference between pre- versus post-procedure anxiety in the VR and HP groups but not the TAU group suggesting non-pharmacologic technology-based interventions such as VR and headphones may reduce patients' anxiety during pediatric dermatology procedures.

Asociación de la gamma glutamil transferasa con la presencia y progresión de calcificaciones aórticas abdominales y con cambios en densidad mineral ósea / Association of gamma glutamyl transferase in the presence and progression of abdominal aortic calcifications and changes to bone mineral density

Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)

Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)

Improving Diagnostic Accuracy in Skin of Color Using an Educational Module.

Dermatologic disparities disproportionately affect patients with skin of color (SOC). This study evaluated the effectiveness of a focused educational module for improving diagnostic accuracy and confidence in the treatment of patients with SOC among interprofessional health care providers. An SOC educational module involving a pretest, 15-minute lecture, immediate posttest, and 3-month posttest was created. One hundred participants completed the pretest and immediate posttest; 36 of them also completed the 3-month post-test. Our results suggest that a focused educational module may provide long-term improvements in diagnostic accuracy and confidence for conditions presenting in patients with SOC.

Breastfeeding and the major fermentation metabolite lactate determine occurrence of Peptostreptococcaceae in infant feces.

Previous studies indicated an intrinsic relationship between infant diet, intestinal microbiota composition and fermentation activity with a strong focus on the role of breastfeeding on microbiota composition. Yet, microbially formed short-chain fatty acids acetate, propionate and butyrate and other fermentation metabolites such as lactate not only act as substrate for bacterial cross-feeding and as mediators in microbe-host interactions but also confer antimicrobial activity, which has received considerably less attention in the past research. It was the aim of this study to investigate the nutritional-microbial interactions that contribute to the development of infant gut microbiota with a focus on human milk oligosaccharide (HMO) fermentation. Infant fecal microbiota composition, fermentation metabolites and milk composition were analyzed from 69 mother-infant pairs of the Swiss birth cohort Childhood AlleRgy nutrition and Environment (CARE) at three time points depending on breastfeeding status defined at the age of 4 months, using quantitative microbiota profiling, HPLC-RI and 1H-NMR. We conducted in vitro fermentations in the presence of HMO fermentation metabolites and determined the antimicrobial activity of lactate and acetate against major Clostridiaceae and Peptostreptococcaceae representatives. Our data show that fucosyllactose represented 90% of the HMOs present in breast milk at 1- and 3-months post-partum with fecal accumulation of fucose, 1,2-propanediol and lactate indicating fermentation of HMOs that is likely driven by Bifidobacterium. Concurrently, there was a significantly lower absolute abundance of Peptostreptococcaceae in feces of exclusively breastfed infants at 3 months. In vitro, lactate inhibited strains of Peptostreptococcaceae. Taken together, this study not only identified breastfeeding dependent fecal microbiota and metabolite profiles but suggests that HMO-derived fermentation metabolites might exert an inhibitory effect against selected gut microbes.

Characteristics and treatment pathways in pediatric and adult hidradenitis suppurativa: An examination using real world data.

Background: Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory disease. Contemporaneous real-world data can be used to elucidate the clinical treatment of pediatric patients and how treatment strategies compare with adult hidradenitis suppurativa patients. Objective: The objective of this study is to evaluate clinical and treatment characteristics of pediatric and adult HS patients. Methods: HS adult and pediatric patients were identified in 3 the United States administrative claims databases during the study period between 2016 to 2021. Patients were required to have 2 diagnostic codes for HS and have at least 365 days of prior observation time to the first HS diagnosis. Results: Pediatric and adult HS treatments were similar. The proportions of subjects treated with topical and oral antibiotic or oral antibiotic alone or topical medication alone or surgery alone covered 90% of the treated pediatric subjects and 91% of treated adult subjects. The remaining proportion of subjects received other treatment combinations. Limitations: The databases represent subjects with commercial or government insurance coverage and thus do not necessarily represent the broader US population. The databases do not capture information about medications obtained without insurance. Conclusions: Although subtle differences exist, this study confirms that topical and systemic therapeutic treatment of HS in adults and adolescents is very similar.

Characterization of p38α autophosphorylation inhibitors that target the non-canonical activation pathway.

p38α is a versatile protein kinase that can control numerous processes and plays important roles in the cellular responses to stress. Dysregulation of p38α signaling has been linked to several diseases including inflammation, immune disorders and cancer, suggesting that targeting p38α could be therapeutically beneficial. Over the last two decades, numerous p38α inhibitors have been developed, which showed promising effects in pre-clinical studies but results from clinical trials have been disappointing, fueling the interest in the generation of alternative mechanisms of p38α modulation. Here, we report the in silico identification of compounds that we refer to as non-canonical p38α inhibitors (NC-p38i). By combining biochemical and structural analyses, we show that NC-p38i efficiently inhibit p38α autophosphorylation but weakly affect the activity of the canonical pathway. Our results demonstrate how the structural plasticity of p38α can be leveraged to develop therapeutic opportunities targeting a subset of the functions regulated by this pathway.

Characterization of wound microbes in epidermolysis bullosa: A focus on Pseudomonas aeruginosa.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

Are Deep Learning Structural Models Sufficiently Accurate for Virtual Screening? Application of Docking Algorithms to AlphaFold2 Predicted Structures.

Machine learning-based protein structure prediction algorithms, such as RosettaFold and AlphaFold2, have greatly impacted the structural biology field, arousing a fair amount of discussion around their potential role in drug discovery. While there are few preliminary studies addressing the usage of these models in virtual screening, none of them focus on the prospect of hit-finding in a real-world virtual screen with a model based on low prior structural information. In order to address this, we have developed an AlphaFold2 version where we exclude all structural templates with more than 30% sequence identity from the model-building process. In a previous study, we used those models in conjunction with state-of-the-art free energy perturbation methods and demonstrated that it is possible to obtain quantitatively accurate results. In this work, we focus on using these structures in rigid receptor-ligand docking studies. Our results indicate that using out-of-the-box Alphafold2 models is not an ideal scenario for virtual screening campaigns; in fact, we strongly recommend to include some post-processing modeling to drive the binding site into a more realistic holo model.

A framework for meta-learning in science education for a time of crisis and beyond.

Science education has an important role in educating the public on learning strategies that will generate a scientific literate population. The challenges encountered in this time of crisis calls for individuals to make well-informed decisions, based on reliable information. Understanding scientific basic concepts can inform the population on making informed decisions that will protect and prosper their communities. This study applied a grounded theory approach to propose a framework for meta-learning as a strategy that enhances science understanding and cultivates trust toward science. Meta-learning in science education is contextualized during a time of crisis and four stages are suggested for the meta-learning process. In the first stage, the learner becomes aware of a situation and activates prior knowledge. In the second stage, the learner searches and evaluates reliable information. In the third stage, the learner adjusts their behavior based on the new knowledge. Finally, in the fourth stage, the learner embraces learning as an everlasting process and re-adjusts behavior accordingly. Through meta-learning practices in science education, learners can claim agency of their learning processes and embrace a lifelong learning endeavor that will benefit themselves and those around them.

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial.

BACKGROUND: Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke. METHODS: The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18-80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1-7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6-20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed. FINDINGS: Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9-15), with intra-arterial BMMNC injection done a median of 6 days (4-7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55-7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52-6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72-6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group. INTERPRETATION: Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints. FUNDING: Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.

Transition of care in patients with epidermolysis bullosa: A survey study.

There are little published data on the transition of care in EB. We conducted a survey study recruiting EB patients from the Dystrophic EB Research Association (debra) website and centers caring for high numbers of EB patients in the United States and internationally from Sept 17, 2019 to Nov 3, 2021. The majority of participants had not discussed the transition of care with their healthcare providers, nor the healthcare needs to be required as an adult. Ongoing pediatric subspecialty care was reported by 12% of adults, most commonly in pediatric dermatology. Identified barriers to transition included the perceived lack of adult providers' knowledge about EB patient healthcare needs. The results suggest the need for transition guidelines, early discussions with families about transition, and practical information for the adult providers accepting care.

Ichthyosis, petechiae, and arthrogryposis in a neonate.

Gaucher disease is a rare lysosomal storage disorder caused by a deficiency in glucocerebrosidase. This enzyme deficiency leads to the accumulation of toxic metabolites in various organs. Multiple subtypes of this disease have been described; however, the perinatal-lethal form is extremely rare and challenging to diagnose. We present a case of a newborn girl with ichthyosis, petechiae, and arthrogryposis, later found to be homozygous for a pathogenic variant of the glucocerebrosidase gene. This case highlights the potential role of dermatologists in the recognition of this rare disease.

MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply.

Isoprenoids are a very large and diverse family of metabolites required by all living organisms. All isoprenoids derive from the double-bond isomers isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are produced by the methylerythritol 4-phosphate (MEP) pathway in bacteria and plant plastids. It has been reported that IPP and DMAPP feedback-regulate the activity of deoxyxylulose 5-phosphate synthase (DXS), a dimeric enzyme that catalyzes the main flux-controlling step of the MEP pathway. Here we provide experimental insights into the underlying mechanism. Isothermal titration calorimetry and dynamic light scattering approaches showed that IPP and DMAPP can allosterically bind to DXS in vitro, causing a size shift. In silico ligand binding site analysis and docking calculations identified a potential allosteric site in the contact region between the two monomers of the active DXS dimer. Modulation of IPP and DMAPP contents in vivo followed by immunoblot analyses confirmed that high IPP/DMAPP levels resulted in monomerization and eventual aggregation of the enzyme in bacterial and plant cells. Loss of the enzymatically active dimeric conformation allows a fast and reversible reduction of DXS activity in response to a sudden increase or decrease in IPP/DMAPP supply, whereas aggregation and subsequent removal of monomers that would otherwise be available for dimerization appears to be a more drastic response in the case of persistent IPP/DMAPP overabundance (e.g., by a blockage in their conversion to downstream isoprenoids). Our results represent an important step toward understanding the regulation of the MEP pathway and rational design of biotechnological endeavors aimed at increasing isoprenoid contents in microbial and plant systems.