Decreased oral function in Japanese inpatients with schizophrenia.

AIM: Oral function in patients with schizophrenia has not been well-characterized. To address this, we performed a cross-sectional study of oral function in Japanese inpatients with schizophrenia. METHODS: We measured oral function, including occlusal force, tongue-lip motor function, tongue pressure, and masticatory function in 130 Japanese inpatients with schizophrenia. We then compared the frequency of clinical signs of oral hypofunction among 63 non-elderly and 67 elderly inpatients with schizophrenia, as well as data from 98 elderly control participants from a previous Japanese study. RESULTS: The frequency of reduced occlusal force was significantly higher in the elderly inpatients (76.2%) than in the non-elderly inpatients (43.9%) and elderly controls (43.9%). The frequency of decreased tongue-lip motor function in non-elderly inpatients (96.8%) and elderly inpatients (97.0%) was significantly higher than that in elderly controls (56.1%). The frequency of decreased tongue pressure in non-elderly inpatients (66.1%) and elderly inpatients (80.7%) was significantly higher than that in elderly controls (43.9%). Finally, the frequency of decreased masticatory function was highest in elderly inpatients (76.5%), followed by non-elderly inpatients (54.8%) and elderly controls (15.3%). CONCLUSION: Oral function was decreased in both non-elderly and elderly Japanese inpatients with schizophrenia compared with elderly controls.

Accumulation of Phosphorylated SnRK2 Substrate 1 Promotes Drought Escape in Arabidopsis.

Plants adopt optimal tolerance strategies depending on the intensity and duration of stress. Retaining water is a priority under short-term drought conditions, whereas maintaining growth and reproduction processes takes precedence over survival under conditions of prolonged drought. However, the mechanism underlying changes in the stress response depending on the degree of drought is unclear. Here, we report that SNF1-related protein kinase 2 (SnRK2) substrate 1 (SNS1) is involved in this growth regulation under conditions of drought stress. SNS1 is phosphorylated and stabilized by SnRK2 protein kinases reflecting drought conditions. It contributes to the maintenance of growth and promotion of flowering as drought escape by repressing stress-responsive genes and inducing FLOWERING LOCUS T (FT) expression, respectively. SNS1 interacts with the histone methylation reader proteins MORF-related gene 1 (MRG1) and MRG2, and the SNS1-MRG1/2 module cooperatively regulates abscisic acid response. Taken together, these observations suggest that the phosphorylation and accumulation of SNS1 in plants reflect the intensity and duration of stress and can serve as a molecular scale for maintaining growth and adopting optimal drought tolerance strategies under stress conditions.

Usefulness of the autism spectrum quotient (AQ) in screening for autism spectrum disorder and social communication disorder.

BACKGROUND: In the Diagnostic and Statistical Manual and Mental Disorders, Fifth Edition (DSM-5), autism spectrum disorder (ASD) and social (pragmatic) communication disorder (SCD) were described as a new category of psychiatry nosography. SCD involves impairments in social communication and social interaction but not restricted, repetitive patterns of behavior, interests, or activities. The autism spectrum quotient (AQ) was developed to screen for autism tendencies in adults with normal intelligence. However, AQ cutoff scores for screening ASD and SCD in the DSM-5 have not been established. This study examined whether the Japanese version of the AQ (AQ-J) total scores could discriminate between an ASD group, an SCD group, and a neurotypical (NT) group. METHODS: Participants were 127 ASD patients, 52 SCD patients, and 49 NT individuals. Receiver operating characteristic (ROC) analyses were used to examine AQ-J total score cutoff values to distinguish between ASD and NT groups, SCD and NT groups, and ASD and SCD groups. RESULTS: In the ROC analysis for the ASD and NT groups, the area under the curve (AUC) was 0.96, and the optimum cutoff value was 23 points (sensitivity 92.9%, specificity 85.7%). The AUC for the SCD and NT groups was 0.89, and the optimum cutoff value was 22 points (sensitivity 84.6%, specificity 85.7%). The AUC for the ASD and SCD groups was 0.75; the optimum cutoff value was 32 points (sensitivity 67.7%, specificity 71.2%). CONCLUSION: Our findings suggest the usefulness of the AQ-J in screening for ASD and SCD.

Genetic Interaction between Arabidopsis SUR2/CYP83B1 and GNOM Indicates the Importance of Stabilizing Local Auxin Accumulation in Lateral Root Initiation.

Lateral root (LR) formation is an important developmental event for the establishment of the root system in most vascular plants. In Arabidopsis thaliana, the fewer roots (fwr) mutation in the GNOM gene, encoding a guanine nucleotide exchange factor of ADP ribosylation factor that regulates vesicle trafficking, severely inhibits LR formation. Local accumulation of auxin response for LR initiation is severely affected in fwr. To better understand how local accumulation of auxin response for LR initiation is regulated, we identified a mutation, fewer roots suppressor1 (fsp1), that partially restores LR formation in fwr. The gene responsible for fsp1 was identified as SUPERROOT2 (SUR2), encoding CYP83B1 that positions at the metabolic branch point in the biosynthesis of auxin/indole-3-acetic acid (IAA) and indole glucosinolate. The fsp1 mutation increases both endogenous IAA levels and the number of the sites where auxin response locally accumulates prior to LR formation in fwr. SUR2 is expressed in the pericycle of the differentiation zone and in the apical meristem in roots. Time-lapse imaging of the auxin response revealed that local accumulation of auxin response is more stable in fsp1. These results suggest that SUR2/CYP83B1 affects LR founder cell formation at the xylem pole pericycle cells where auxin accumulates. Analysis of the genetic interaction between SUR2 and GNOM indicates the importance of stabilization of local auxin accumulation sites for LR initiation.

Association Between the Number of Remaining Teeth and Body Mass Index in Japanese Inpatients with Schizophrenia.

Purpose: There is little evidence regarding the effects of dental status on body mass index (BMI) in inpatients with schizophrenia. Thus, we performed a cross-sectional study to explore the associations between the number of remaining teeth and BMI in Japanese inpatients with schizophrenia. Patients and Methods: We performed multiple regression analysis to assess the effects of potential predictors (age, sex, number of remaining teeth, number of antipsychotics prescribed, chlorpromazine equivalent dose, and antipsychotic type) on BMI in 212 inpatients with schizophrenia. We then compared the number of remaining teeth between inpatients with schizophrenia and the Japanese general population (3283 individuals) from the Japan Dental Diseases Survey 2016, using an analysis of covariance with age and sex as covariates. Results: Multiple regression analysis showed that the number of remaining teeth and the number of antipsychotics prescribed were significantly correlated with BMI (standardized regression coefficient = 0.201 and 0.235, respectively). In the analysis of covariance, inpatients with schizophrenia had significantly fewer remaining teeth compared with the Japanese general population (mean 14.8 [standard deviation: 10.9] vs mean 23.0 [standard deviation: 8.1]). Conclusion: These results suggested that tooth loss and antipsychotic polypharmacy affect BMI in inpatients with schizophrenia, and that inpatients with schizophrenia lose more teeth compared with the general population.

Chemical inhibition of the auxin inactivation pathway uncovers the roles of metabolic turnover in auxin homeostasis.

The phytohormone auxin, indole-3-acetic acid (IAA), plays a prominent role in plant development. Auxin homeostasis is coordinately regulated by auxin synthesis, transport, and inactivation; however, the physiological contribution of auxin inactivation to auxin homeostasis has not been determined. The GH3 IAA-amino acid conjugating enzymes play a central role in auxin inactivation. Chemical inhibition of GH3 proteins in planta is challenging because the inhibition of these enzymes leads to IAA overaccumulation that rapidly induces GH3 expression. Here, we report the characterization of a potent GH3 inhibitor, kakeimide, that selectively targets IAA-conjugating GH3 proteins. Chemical knockdown of the auxin inactivation pathway demonstrates that auxin turnover is very rapid (about 10 min) and indicates that both auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.

Enhancement of shoot regeneration by treatment with inhibitors of auxin biosynthesis and transport during callus induction in tissue culture of Arabidopsis thaliana.

In two-step culture systems for efficient shoot regeneration, explants are first cultured on auxin-rich callus-inducing medium (CIM), where cells are activated to proliferate and form calli containing root-apical meristem (RAM)-type stem cells and stem cell niche, and then cultured on cytokinin-rich shoot-inducing medium (SIM), where stem cells and stem cell niche of the shoot apical meristem (SAM) are established eventually leading to shoot regeneration. In the present study, we examined the effects of inhibitors of auxin biosynthesis and polar transport in the two-step shoot regeneration culture of Arabidopsis and found that, when they were applied during CIM culture, although callus growth was repressed, shoot regeneration in the subsequent SIM culture was significantly increased. The regeneration-stimulating effect of the auxin biosynthesis inhibitor was not linked with the reduction in the endogenous indole-3-acetic acid (IAA) level. Expression of the auxin-responsive reporter indicated that auxin response was more uniform and even stronger in the explants cultured on CIM with the inhibitors than in the control explants. These results suggested that the shoot regeneration competence of calli was enhanced somehow by the perturbation of the endogenous auxin dynamics, which we discuss in terms of the transformability between RAM and SAM stem cell niches.

4-Phenylbutyric acid promotes plant regeneration as an auxin by being converted to phenylacetic acid via an IBR3-independent pathway.

4-Phenylbutyric acid (4PBA) is utilized as a drug to treat urea cycle disorders and is also being studied as a potential anticancer drug that acts via its histone deacetylase (HDAC) inhibitor activity. During a search to find small molecules that affect plant regeneration in Arabidopsis, we found that 4PBA treatment promotes this process by mimicking the effect of exogenous auxin. Specifically, plant tissue culture experiments revealed that a medium containing 4PBA enhances callus formation and subsequent shoot regeneration. Analyses with auxin-responsive or cytokinin-responsive marker lines demonstrated that 4PBA specifically enhances AUXIN RESPONSE FACTOR (ARF)-dependent auxin responses. Our western blot analyses showed that 4PBA treatment does not enhance histone acetylation in Arabidopsis, in contrast to butyric acid and trichostatin A, other chemicals often used as HDAC inhibitors, suggesting this mechanism of action does not explain the observed effect of 4PBA on regeneration. Finally, mass spectroscopic analysis and genetic approaches uncovered that 4PBA in Arabidopsis plants is converted to phenylacetic acid (PAA), a known natural auxin, in a manner independent of peroxisomal IBR3-related ß-oxidation. This study demonstrates that 4PBA application promotes regeneration in explants via its auxin activity and has potential applications to not only plant tissue culture engineering but also research on the plant ß-oxidation pathway.

The heterogeneous effects of COVID-19 on labor markets: People's movement and non-pharmaceutical interventions.

The paper investigates the heterogeneous effect of a policy-induced decline in people's mobility on the Japanese labor market outcome during the early COVID-19 period. Regressing individual-level labor market outcomes on prefecture-level mobility changes using policy stringency index as an instrument, our two-stage least squares estimator presents the following findings. First, the number of people absent from work increased for all groups of individuals, but the magnitude was greater for workers with non-regular employment status, low-educated people, females especially with children, and those aged 31 to 45 years. Second, while work hours decreased for most groups, the magnitude was especially greater for business owners without employees and those aged 31 to 45. Third, the negative effect on unemployment was statistically significant for older males who worked as regular workers in the previous year. The impact was particularly considerable for those aged 60 and 65, thus suggesting that they lost their re-employment opportunity due to COVID-19. Fourth, all these adverse effects were greater for people working in service and sales occupations. Fifth, a counterfactual experiment of more stringent policies indicates that while an average worker would lose JPY 3857 in weekly earnings by shortening their work hours, the weekly loss for those aged 31 to 45 years and working in service and sales occupations would be about JPY 13,842.

Local conjugation of auxin by the GH3 amido synthetases is required for normal development of roots and flowers in Arabidopsis.

Gretchen Hagen 3 (GH3) amido synthetases conjugate amino acids to a carboxyl group of small molecules including hormones auxin, jasmonate, and salicylic acid. The Arabidopsis genome harbors 19 GH3 genes, whose exact roles in plant development have been difficult to define because of genetic redundancy among the GH3 genes. Here we use CRISPR/Cas9 gene editing technology to delete the Arabidopsis group II GH3 genes, which are able to conjugate indole-3-acetic acid (IAA) to amino acids. We show that plants lacking the eight group II GH3 genes (gh3 octuple mutants) accumulate free IAA and fail to produce IAA-Asp and IAA-Glu conjugates. Consequently, gh3 octuple mutants have extremely short roots, long and dense root hairs, and long hypocotyls. Our characterization of gh3 septuple mutants, which provide sensitized backgrounds, reveals that GH3.17 and GH3.9 play prominent roles in root elongation and seed production, respectively. We show that GH3 functions correlate with their expression patterns, suggesting that local deactivation of auxin also contributes to maintaining auxin homeostasis. Moreover, this work provides a method for elucidating functions of individual members of a gene family, whose members have overlapping functions.

The main oxidative inactivation pathway of the plant hormone auxin.

Inactivation of the phytohormone auxin plays important roles in plant development, and several enzymes have been implicated in auxin inactivation. In this study, we show that the predominant natural auxin, indole-3-acetic acid (IAA), is mainly inactivated via the GH3-ILR1-DAO pathway. IAA is first converted to IAA-amino acid conjugates by GH3 IAA-amidosynthetases. The IAA-amino acid conjugates IAA-aspartate (IAA-Asp) and IAA-glutamate (IAA-Glu) are storage forms of IAA and can be converted back to IAA by ILR1/ILL amidohydrolases. We further show that DAO1 dioxygenase irreversibly oxidizes IAA-Asp and IAA-Glu into 2-oxindole-3-acetic acid-aspartate (oxIAA-Asp) and oxIAA-Glu, which are subsequently hydrolyzed by ILR1 to release inactive oxIAA. This work established a complete pathway for the oxidative inactivation of auxin and defines the roles played by auxin homeostasis in plant development.

The association of opening K-12 schools with the spread of COVID-19 in the United States: County-level panel data analysis.

This paper empirically examines how the opening of K-12 schools is associated with the spread of COVID-19 using county-level panel data in the United States. As preliminary evidence, our event-study analysis indicates that cases and deaths in counties with in-person or hybrid opening relative to those with remote opening substantially increased after the school opening date, especially for counties without any mask mandate for staff. Our main analysis uses a dynamic panel data model for case and death growth rates, where we control for dynamically evolving mitigation policies, past infection levels, and additive county-level and state-week "fixed" effects. This analysis shows that an increase in visits to both K-12 schools and colleges is associated with a subsequent increase in case and death growth rates. The estimates indicate that fully opening K-12 schools with in-person learning is associated with a 5 (SE = 2) percentage points increase in the growth rate of cases. We also find that the association of K-12 school visits or in-person school openings with case growth is stronger for counties that do not require staff to wear masks at schools. These findings support policies that promote masking and other precautionary measures at schools and giving vaccine priority to education workers.

Trade-off between job losses and the spread of COVID-19 in Japan.

This paper quantitatively analyzes the trade-off between job losses and the spread of COVID-19 in Japan. We derive an empirical specification from the social planner's resource constraint under the susceptible, infected, recovered, and deaths (SIRD) model and estimate how job losses and the case growth rate are related to people's mobility using the Japanese prefecture-level panel data on confirmed cases, involuntary job losses, people's mobility, and teleworkability. Our findings are summarized as follows. First, we find that a decrease in mobility driven by containment policies is associated with an increase in involuntary job separations, but the high teleworkability mitigates the negative effect of decreased mobility on job losses. Second, estimating how the case growth is related to people's mobility and past cases, we find that the case growth rate is positively related to an increase in people's mobility but negatively associated with past confirmed cases. Third, using these estimates, we provide a quantitative analysis of the trade-off between job losses and the number of confirmed cases. Taking Tokyo in July 2020 as a benchmark, we find that the cost of saving 1 job per month is 2.3 more confirmed cases per month in the short run of 1 month. When we consider a trade-off for 3 months from July to September of 2020, protecting 1 job per month requires 6.6 more confirmed cases per month. Therefore, the trade-off becomes worse substantially in the longer run of 3 months, reflecting the exponential case growth when the people's mobility is high.

Causal impact of masks, policies, behavior on early covid-19 pandemic in the U.S.

The paper evaluates the dynamic impact of various policies adopted by US states on the growth rates of confirmed Covid-19 cases and deaths as well as social distancing behavior measured by Google Mobility Reports, where we take into consideration people's voluntarily behavioral response to new information of transmission risks in a causal structural model framework. Our analysis finds that both policies and information on transmission risks are important determinants of Covid-19 cases and deaths and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our main counterfactual experiments suggest that nationally mandating face masks for employees early in the pandemic could have reduced the weekly growth rate of cases and deaths by more than 10 percentage points in late April and could have led to as much as 19 to 47 percent less deaths nationally by the end of May, which roughly translates into 19 to 47 thousand saved lives. We also find that, without stay-at-home orders, cases would have been larger by 6 to 63 percent and without business closures, cases would have been larger by 17 to 78 percent. We find considerable uncertainty over the effects of school closures due to lack of cross-sectional variation; we could not robustly rule out either large or small effects. Overall, substantial declines in growth rates are attributable to private behavioral response, but policies played an important role as well. We also carry out sensitivity analyses to find neighborhoods of the models under which the results hold robustly: the results on mask policies appear to be much more robust than the results on business closures and stay-at-home orders. Finally, we stress that our study is observational and therefore should be interpreted with great caution. From a completely agnostic point of view, our findings uncover predictive effects (association) of observed policies and behavioral changes on future health outcomes, controlling for informational and other confounding variables.

The Arabidopsis NRT1/PTR FAMILY protein NPF7.3/NRT1.5 is an indole-3-butyric acid transporter involved in root gravitropism.

Active membrane transport of plant hormones and their related compounds is an essential process that determines the distribution of the compounds within plant tissues and, hence, regulates various physiological events. Here, we report that the Arabidopsis NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY 7.3 (NPF7.3) protein functions as a transporter of indole-3-butyric acid (IBA), a precursor of the major endogenous auxin indole-3-acetic acid (IAA). When expressed in yeast, NPF7.3 mediated cellular IBA uptake. Loss-of-function npf7.3 mutants showed defective root gravitropism with reduced IBA levels and auxin responses. Nevertheless, the phenotype was restored by exogenous application of IAA but not by IBA treatment. NPF7.3 was expressed in pericycle cells and the root tip region including root cap cells of primary roots where the IBA-to-IAA conversion occurs. Our findings indicate that NPF7.3-mediated IBA uptake into specific cells is required for the generation of appropriate auxin gradients within root tissues.

Molecular and Biochemical Differences in Leaf Explants and the Implication for Regeneration Ability in Rorippa aquatica (Brassicaceae).

Plants have a high regeneration capacity and some plant species can regenerate clone plants, called plantlets, from detached vegetative organs. We previously outlined the molecular mechanisms underlying plantlet regeneration from Rorippa aquatica (Brassicaceae) leaf explants. However, the fundamental difference between the plant species that can and cannot regenerate plantlets from vegetative organs remains unclear. Here, we hypothesized that the viability of leaf explants is a key factor affecting the regeneration capacity of R. aquatica. To test this hypothesis, the viability of R. aquatica and Arabidopsis thaliana leaf explants were compared, with respect to the maintenance of photosynthetic activity, senescence, and immune response. Time-course analyses of photosynthetic activity revealed that R. aquatica leaf explants can survive longer than those of A. thaliana. Endogenous abscisic acid (ABA) and jasmonic acid (JA) were found at low levels in leaf explant of R. aquatica. Time-course transcriptome analysis of R. aquatica and A. thaliana leaf explants suggested that senescence was suppressed at the transcriptional level in R. aquatica. Application of exogenous ABA reduced the efficiency of plantlet regeneration. Overall, our results propose that in nature, plant species that can regenerate in nature can survive for a long time.

UDP-glucosyltransferase UGT84B1 regulates the levels of indole-3-acetic acid and phenylacetic acid in Arabidopsis.

Auxin is a key plant growth regulator for diverse developmental processes in plants. Indole-3-acetic acid (IAA) is a primary plant auxin that regulates the formation of various organs. Plants also produce phenylacetic acid (PAA), another natural auxin, which occurs more abundantly than IAA in various plant species. Although it has been demonstrated that the two auxins have distinct transport characteristics, the metabolic pathways and physiological roles of PAA in plants remain unsolved. In this study, we investigated the role of Arabidopsis UDP-glucosyltransferase UGT84B1 in IAA and PAA metabolism. We demonstrated that UGT84B1, which converts IAA to IAA-glucoside (IAA-Glc), can also catalyze the conversion of PAA to PAA-glucoside (PAA-Glc), with a higher catalytic activity in vitro. Furthermore, we showed a significant increase in both the IAA and PAA levels in the ugt84b1 null mutants. However, no obvious developmental phenotypes were observed in the ugt84b1 mutants under laboratory growth conditions. Moreover, the overexpression of UGT84B1 resulted in auxin-deficient root phenotypes and changes in the IAA and PAA levels. Our results indicate that UGT84B1 plays an important role in IAA and PAA homeostasis in Arabidopsis.

An Evolutionarily Primitive and Distinct Auxin Metabolism in the Lycophyte Selaginella moellendorffii.

Auxin is a key regulator of plant growth and development. Indole-3-acetic acid (IAA), a plant auxin, is mainly produced from tryptophan via indole-3-pyruvate (IPA) in both bryophytes and angiosperms. Angiosperms have multiple, well-documented IAA inactivation pathways, involving conjugation to IAA-aspartate (IAA-Asp)/glutamate by the GH3 auxin-amido synthetases, and oxidation to 2-oxindole-3-acetic acid (oxIAA) by the DAO proteins. However, IAA biosynthesis and inactivation processes remain elusive in lycophytes, an early lineage of spore-producing vascular plants. In this article, we studied IAA biosynthesis and inactivation in the lycophyte Selaginella moellendorffii. We demonstrate that S. moellendorffii mainly produces IAA from the IPA pathway for the regulation of root growth and response to high temperature, similar to the angiosperm Arabidopsis. However, S. moellendorffii exhibits a unique IAA metabolite profile with high IAA-Asp and low oxIAA levels, distinct from Arabidopsis and the bryophyte Marchantia polymorpha, suggesting that the GH3 family is integral for IAA homeostasis in the lycophytes. The DAO homologs in S. moellendorffii share only limited similarity to the well-characterized rice and Arabidopsis DAO proteins. We therefore suggest that these enzymes may have a limited role in IAA homeostasis in S. moellendorffii compared to angiosperms. We provide new insights into the functional diversification of auxin metabolic genes in the evolution of land plants.

Role of Arabidopsis INDOLE-3-ACETIC ACID CARBOXYL METHYLTRANSFERASE 1 in auxin metabolism.

The phytohormone auxin regulates a wide range of developmental processes in plants. Indole-3-acetic acid (IAA) is the main auxin that moves in a polar manner and forms concentration gradients, whereas phenylacetic acid (PAA), another natural auxin, does not exhibit polar movement. Although these auxins occur widely in plants, the differences between IAA and PAA metabolism remain largely unknown. In this study, we investigated the role of Arabidopsis IAA CARBOXYL METHYLTRANSFERASE 1 (IAMT1) in IAA and PAA metabolism. IAMT1 proteins expressed in Escherichia coli could convert both IAA and PAA to their respective methyl esters. Overexpression of IAMT1 caused severe auxin-deficient phenotypes and reduced the levels of IAA, but not PAA, in the root tips of Arabidopsis, suggesting that IAMT1 exclusively metabolizes IAA in vivo. We generated iamt1 null mutants via CRISPR/Cas9-mediated genome editing and found that the single knockout mutants had normal auxin levels and did not exhibit visibly altered phenotypes. These results suggest that other proteins, namely the IAMT1 homologs in the SABATH family of carboxyl methyltransferases, may also regulate IAA levels in Arabidopsis.

Two homologous INDOLE-3-ACETAMIDE (IAM) HYDROLASE genes are required for the auxin effects of IAM in Arabidopsis.

Indole-3-acetamide (IAM) is the first confirmed auxin biosynthetic intermediate in some plant pathogenic bacteria. Exogenously applied IAM or production of IAM by overexpressing the bacterial iaaM gene in Arabidopsis causes auxin overproduction phenotypes. However, it is still inconclusive whether plants use IAM as a key precursor for auxin biosynthesis. Herein, we reported the isolation IAMHYDROLASE1 (IAMH1) gene in Arabidopsis from a forward genetic screen for IAM-insensitive mutants that display normal auxin sensitivities. IAMH1 has a close homolog named IAMH2 that is located right next to IAMH1 on chromosome IV in Arabidopsis. We generated iamh1 iamh2 double mutants using our CRISPR/Cas9 gene editing technology. We showed that disruption of the IAMH genes rendered Arabidopsis plants resistant to IAM treatments and also suppressed the iaaM overexpression phenotypes, suggesting that IAMH1 and IAMH2 are the main enzymes responsible for converting IAM into indole-3-acetic acid (IAA) in Arabidopsis. The iamh double mutants did not display obvious developmental defects, indicating that IAM does not play a major role in auxin biosynthesis under normal growth conditions. Our findings provide a solid foundation for clarifying the roles of IAM in auxin biosynthesis and plant development.