Children's attitudes about transgender identity disclosure and concealment.

Supportive peers are crucial for transgender children's well-being. Transgender children who live in their affirmed gender face decisions surrounding concealment and disclosure of their transgender identity. We sought to understand how cisgender (N = 115) and gender-diverse children (N = 127), and siblings of gender-diverse children (N = 63) think about transition disclosure and concealment. All groups viewed transition disclosure and concealment positively. However, gender-diverse children showed greater acceptance of transition concealment and had stronger liking of transition concealers (relative to non-transition concealers). Additionally, children generally expected transgender peers to be selective about who they disclose to, valuing trustworthiness and diverse friend groups in such decisions. Our findings suggest that regardless of gender identity, children are sensitive to the potential costs of disclosure and may support trans children however they choose to navigate these decisions.

Where Have All the Rhinoplasties Gone? A Call to Action for Academic Plastic Surgeons to Focus on Increasing Rhinoplasty Procedures Before It Is Too Late.

BACKGROUND: The armamentarium of a plastic surgeon is vast, consisting of an array of surgical procedures from head to toe. Unfortunately, plastic surgeons have been losing portions of their operative domain to other surgical subspecialties for years. The number of subspecialties invading our niche is bothersome, but more concerning is the fact that losing the reins of these core procedures results in less surgical exposure and competency for plastic surgery residents.Lately, in academic institutions, otolaryngologists seem to be performing most rhinoplasty procedures, resulting in fewer surgeries performed by plastic surgeons. Trainees must perform 10 rhinoplasties to fulfill graduation requirements but, more importantly, residents should graduate feeling competent and confident performing rhinoplasties. The aims of this study are to determine the number of rhinoplasties being performed at academic centers each year and to evaluate the trend with regard to which specialties are performing these procedures. METHODS: Three academic institutions with plastic surgery and otolaryngology residency programs searched medical records for rhinoplasty Current Procedural Terminology codes from January 1, 2009, to December 31, 2019. The total numbers of rhinoplasties performed each year, by each specialty, were tallied. RESULTS: Growth rate in rhinoplasty volume among participating institutions ranged from 27% to 149%. At these institutions, plastic surgeons performed less than one third of all rhinoplasties. In 2009, 10% of rhinoplasties were performed by plastic surgeons at institution 1, 22% at institution 2, and 18% at institution 3. In 2019, the volume of rhinoplasties performed by plastic surgeons was 5%, 12%, and 27%, respectively. The 3 ENT departments had statistically significant increasing trends in rhinoplasty volume. Institutions 1 and 2's plastic surgery departments showed that negative volume trends, however, were not statistically significant. Institution 3's plastic surgery department has had an increasing trend, which was statistically significant. CONCLUSIONS: Otolaryngology is performing most rhinoplasties at several academic institutions. This is concerning for the education of plastic surgery trainees. Academic plastic surgeons must focus on increasing the number of rhinoplasties performed to adequately train residents this core procedure. If rhinoplasties are not made a priority now, this surgery may become a historic operation instead of a vital skill in plastic surgeons' armamentarium.

Young children apply the homophily principle to their reasoning about social relationships.

People who are in close relationships tend to do and like the same things, a phenomenon termed the "homophily principle." The present research probed for evidence of the homophily principle in 4- to 6-year-old children. Across two experiments, participants (N = 327; 166 girls, 161 boys; located in the Midwestern United States) were asked to predict the closeness of two people based on their preferences. Participants in Experiment 1 indicated that people with a shared preference or a shared dispreference were more closely affiliated than people whose preferences diverged, suggesting inferences of homophily. Furthermore, children were not only relying on the emotional valences expressed: They expected people with a shared preference to be closer than people who expressed positive emotions about different items and expected people with a shared dispreference to be closer than people who expressed negative emotions about different items. Experiment 2 replicated and extended the main findings of Experiment 1 with more naturalistic stimuli. The present studies provide strong evidence that young children apply the homophily principle to their reasoning about social relationships. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Retransitioning: The experiences of youth who socially transition genders more than once.

Background: Retransitions in youth are critical to understand, as they are an experience about which little is known and about which families and clinicians worry. Aims: This study aims to qualitatively describe the experiences of youth who made binary social transitions (came to live as the binary gender different from the one assigned at birth) in childhood by the age of 12, and who later socially transitioned genders again (here, called "retransitioning"). Methods: Out of 317 participants in an ongoing longitudinal study of (initially) binary transgender youth, 23 participants had retransitioned at least once and were therefore eligible for this study. Of those youth, 8 were cisgender at the time of data collection, 11 were nonbinary, and 4 were binary transgender youth (after having retransitioned to nonbinary identities for a period). Fifteen youth and/or their parent(s) participated in semi-structured interviews (MYouthA ge = 11.3 years; 9 non-Hispanic White; 3 Hispanic White; 3 Multiracial; 10 assigned male; 5 assigned female). Interviews gauged antecedents of transitions, others' reactions to transitions, and participants' general reflections. Responses were coded and thematically analyzed. Results: Participants described various paths to retransitions, including that some youth identified differently over time, and that some youth learned about a new identity (e.g., nonbinary) that fit them better. Social environments' responses to retransitions varied but were often neutral or positive. No participants spontaneously expressed regret over initial transitions. Conclusions: These findings largely do not support common concerns about retransitions. In supportive environments, gender diverse youth can retransition without experiencing rejection, distress, and regret.

Adults' pedagogical messages engender children's preference for self-resembling others.

These studies investigate the influence of adults' explicit attention to commonalities of appearance on children's preference for individuals resembling themselves. Three findings emerged: (1) An adult's identification of two dolls' respective similarity to and difference from the child led 3-year-olds to prefer the similar doll (study 1, n = 32). (2) When the adult did not comment on similarity, children age 6 years but not younger preferred physically similar individuals (study 2, n = 68), suggesting that a spontaneous preference for physically similar others does not emerge before school age. (3) Four- but not 3-year-olds generalized an adult's pedagogical cues about similarity, leading them to prefer a self-resembling doll in a new context (study 3, n = 80). These findings collectively suggest that the preference for individuals resembling ourselves develops through a process of internalizing adults' attention to, and messages about, similarities of appearance.

Gender Development in Gender Diverse Children.

Within "mainstream" developmental science, gender researchers largely study the developmental trajectory of children considered to be "gender-typical", while research housed primarily in psychiatry and clinical psychology often documents the trajectories of gender diverse children. This article aims to bridge the studies of gender diversity and "mainstream" gender development. First, we review literature on the development of four commonly studied subgroups of gender diverse children - children referred to medical clinics because of their gender identity and expression, transgender children, female children with congenital adrenal hyperplasia, and tomboys - highlighting how these gender trajectories do or do not align with modal developmental patterns. We then describe social, cognitive, and biological determinants of gender in light of their implications for understanding diverse gender development. Finally, we note methodological suggestions for future research, with an eye toward better integrating research on gender diversity into "mainstream" gender development research.

A New 3-Stage Approach for Reoperative Hypospadias.

BACKGROUND: Most hypospadias patients undergo 1 surgical procedure and go on to live normal lives. However, there is a small subset of patients who have remaining functional complications after their repair. Patients presenting with diffuse scarring of the urethral plate and a shortage of penile skin for closure are referred to as "hypospadias cripples." We present our experience using tissue expanders in the treatment of reoperative hypospadias with skin deficiency. METHODS: We retrospectively reviewed hospital records from 2009 to 2019. Five hypospadias cripple patients were encountered. A multidisciplinary team involving plastic surgery and pediatric urology collaborated a 3-stage reconstructive plan:Stage 1-Scar excision and buccal mucosal graft harvestStage 2-Dorsal tissue expander placementStage 3-Tissue expander explantation, creation of neourethra, and skin closure. RESULTS: Successful skin closures were achieved in all patients. There were no cases of expander explanation. Average time between tissue expander placement and final reconstruction ranged from 3 to 4 months. Complications included 2 cases of penile cellulitis, 1 with an associated abscess, and 2 limited urethrocutaneous fistulas, which were addressed with an additional operative procedure. CONCLUSIONS: The 3-stage approach is advantageous in treating hypospadias cripple patients. This population can benefit greatly from tissue expander placement after buccal result with an acceptable complication rate. Using a multidisciplinary approach is beneficial in treating these complex patients.

Improving Antioxidant Capacity in Children With Autism: A Randomized, Double-Blind Controlled Study With Cysteine-Rich Whey Protein.

Previous studies indicate that children with autism spectrum disorder (ASD) have lower levels of glutathione. Nutritional interventions aim to increase glutathione levels suggest a positive effect on ASD behaviors, but findings are mixed or non-significant. A commercially available nutritional supplement comprising a cysteine-rich whey protein isolate (CRWP), a potent precursor of glutathione, was previously found to be safe and effective at raising glutathione in several conditions associated with low antioxidant capacity. Therefore, we investigated the effectiveness of a 90-day CRWP intervention in children with ASD and examined whether intracellular reduced and oxidized glutathione improvements correlated with behavioral changes. We enrolled 46 (of 81 screened) 3-5-year-old preschool children with confirmed ASD. Using a double-blind, randomized, placebo-controlled design, we evaluated the effectiveness of daily CRWP (powder form: 0.5 g/kg for children <20 kg or a 10-g dose for those >20 kg), compared with placebo (rice protein mimicking the protein load in the intervention group), on glutathione levels and ASD behaviors assessed using different behavioral scales such as Childhood Autism Rated Scale, Preschool Language Scale, Social Communication Questionnaire, Childhood Behavioral Checklist and the parent-rated Vineland Adaptive Behavior Scale, 2nd edition (VABS-II). Forty children (CRWP, 21; placebo, 19) completed the 90-day treatment period. Improvements observed in some behavioral scales were comparable. However, the VABS-II behavioral assessment, demonstrated significant changes only in children receiving CRWP compared to those observed in the placebo group in the composite score (effect size 0.98; 95% confidence intervals 1.42-4.02; p = 0.03). Further, several VABS-II domain scores such as adaptive behavior (p = 0.03), socialization (p = 0.03), maladaptive behavior (p = 0.04) and internalizing behavior (p = 0.02) also indicated significant changes. Children assigned to the CRWP group showed significant increases in glutathione levels (p = 0.04) compared to those in the placebo group. A subanalysis of the VABS-II scale results comparing responders (>1 SD change from baseline to follow up) and non-responders in the CRWP group identified older age and higher levels of total and reduced glutathione as factors associated with a response. CRWP nutritional intervention in children with ASD significantly improved both glutathione levels and some behaviors associated with ASD. Further studies are needed to confirm these results. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/study/NCT01366859, identifier: NCT01366859.

Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart.

Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue.

RUNX2/miR­31/SATB2 pathway in nickel­induced BEAS­2B cell transformation.

Nickel (Ni) compounds are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) and are known to be carcinogenic to the lungs. In our previous study, special AT­rich sequence­binding protein 2 (SATB2) was required for Ni­induced BEAS­2B cell transformation. In the present study, a pathway that regulates the expression of SATB2 protein was investigated in Ni­transformed BEAS­2B cells using western blotting and RT­qPCR for expression, and soft agar, migration and invasion assays for cell transformation. Runt­related transcription factor 2 (RUNX2), a master regulator of osteogenesis and an oncogene, was identified as an upstream regulator for SATB2. Ni induced RUNX2 expression and initiated BEAS­2B transformation and metastatic potential. Previously, miRNA­31 was identified as a negative regulator of SATB2 during arsenic­induced cell transformation, and in the present study it was identified as a downstream target of RUNX2 during carcinogenesis. miR­31 expression was reduced in Ni­transformed BEAS­2B cells, which was required to maintain cancer hallmarks. The expression level of miR­31 was suppressed by RUNX2 in BEAS­2B cells, and this increased the expression level of SATB2, initiating cell transformation. Ni caused the repression of miR­31 by placing repressive marks at its promoter, which in turn increased the expression level of SATB2, leading to cell transformation.

Are category labels primary? Children use similarities to reason about social groups.

While interpersonal similarities impact young children's peer judgments, little work has assessed whether they also guide group-based reasoning. A common assumption has been that category labels rather than 'mere' similarities are unique constituents of such reasoning; the present work challenges this. Children (ages 3-9) viewed groups defined by category labels or shared preferences, and their social inferences were assessed. By age 5, children used both types of information to licence predictions about preferences (Study 1, n = 129) and richer forms of coalitional structure (Study 2, n = 205). Low-level explanations could not account for this pattern (Study 3, n = 72). Finally, older but not younger children privileged labelled categories when they were pitted against similarity (Study 4, n = 51). These studies show that young children use shared preferences to reason about relationships and coalitional structure, suggesting that similarities are central to the emergence of group representations.

Characterization of Guided Entry of Tail-Anchored Proteins 3 Homologues in Mycobacterium tuberculosis.

We characterized an operon in Mycobacterium tuberculosis, Rv3679-Rv3680, in which each open reading frame is annotated to encode "anion transporter ATPase" homologues. Using structure prediction modeling, we found that Rv3679 and Rv3680 more closely resemble the guided entry of tail-anchored proteins 3 (Get3) chaperone in eukaryotes. Get3 delivers proteins into the membranes of the endoplasmic reticulum and is essential for the normal growth and physiology of some eukaryotes. We sought to characterize the structures of Rv3679 and Rv3680 and test if they have a role in M. tuberculosis pathogenesis. We solved crystal structures of the nucleotide-bound Rv3679-Rv3680 complex at 2.5 to 3.2 Å and show that while it has some similarities to Get3 and ArsA, there are notable differences, including that these proteins are unlikely to be involved in anion transport. Deletion of both genes did not reveal any conspicuous growth defects in vitro or in mice. Collectively, we identified a new class of proteins in bacteria with similarity to Get3 complexes, the functions of which remain to be determined.IMPORTANCE Numerous bacterial species encode proteins predicted to have similarity with Get3- and ArsA-type anion transporters. Our studies provide evidence that these proteins, which we named BagA and BagB, are unlikely to be involved in anion transport. In addition, BagA and BagB are conserved in all mycobacterial species, including the causative agent of leprosy, which has a highly decayed genome. This conservation suggests that BagAB constitutes a part of the core mycobacterial genome and is needed for some yet-to-be-determined part of the life cycle of these organisms.

Zinc intoxication induces ferroptosis in A549 human lung cells.

Zinc (Zn) is an essential trace metal required for all forms of life, but is toxic at high concentrations. While the toxic effects of high levels of Zn are well documented, the mechanism of cell death appears to vary based on the study and concentration of Zn. Zn has been proposed as an anti-cancer treatment against non-small cell lung cancer (NSCLC). The goal of this analysis was to determine the effects of Zn on metabolism and cell death in A549 cells. Here, high throughput multi-omics analysis identified the molecular effects of Zn intoxication on the proteome, metabolome, and transcriptome of A549 human NSCLC cells after 5 min to 24 h of Zn exposure. Multi-omics analysis combined with additional experimental evidence suggests Zn intoxication induces ferroptosis, an iron and lipid peroxidation-dependent programmed cell death, demonstrating the utility of multi-omics analysis to identify cellular response to intoxicants.

An Integrated, High-Throughput Strategy for Multiomic Systems Level Analysis.

Proteomics, metabolomics, and transcriptomics generate comprehensive data sets, and current biocomputational capabilities allow their efficient integration for systems biology analysis. Published multiomics studies cover methodological advances as well as applications to biological questions. However, few studies have focused on the development of a high-throughput, unified sample preparation approach to complement high-throughput omic analytics. This report details the automation, benchmarking, and application of a strategy for transcriptomic, proteomic, and metabolomic analyses from a common sample. The approach, sample preparation for multi-omics technologies (SPOT), provides equivalent performance to typical individual omic preparation methods but greatly enhances throughput and minimizes the resources required for multiomic experiments. SPOT was applied to a multiomics time course experiment for zinc-treated HL-60 cells. The data reveal Zn effects on NRF2 antioxidant and NFkappaB signaling. High-throughput approaches such as these are critical for the acquisition of temporally resolved, multicondition, large multiomic data sets such as those necessary to assess complex clinical and biological concerns. Ultimately, this type of approach will provide an expanded understanding of challenging scientific questions across many fields.

Cytokinin Signaling in Mycobacterium tuberculosis.

It was recently reported that the human-exclusive pathogen Mycobacterium tuberculosis secretes cytokinins, which had only been known as plant hormones. While cytokinins are well-established, adenine-based signaling molecules in plants, they have never been shown to participate in signal transduction in other kingdoms of life. M. tuberculosis is not known to interact with plants. Therefore, we tested the hypothesis that cytokinins trigger transcriptional changes within this bacterial species. Here, we show cytokinins induced the strong expression of the M. tuberculosis gene Rv0077c. We found that Rv0077c expression is repressed by a TetR-like transcriptional repressor, Rv0078. Strikingly, cytokinin-induced expression of Rv0077c resulted in a loss of acid-fast staining of M. tuberculosis While acid-fast staining is thought to be associated with changes in the bacterial cell envelope and virulence, Rv0077c-induced loss of acid-fastness did not affect antibiotic susceptibility or attenuate bacterial growth in mice, consistent with an unaltered mycolic acid profile of Rv0077c-expressing cells. Collectively, these findings show cytokinins signal transcriptional changes that can affect M. tuberculosis acid-fastness and that cytokinin signaling is no longer limited to the kingdom Plantae.IMPORTANCE Cytokinins have only previously been known as plant hormones. The discovery that they can be used as signaling molecules outside of plants broadens the repertoire of small molecules that can potentially affect gene expression in all domains of life.

Not Noble Savages after all: Limits to early altruism.

Many scholars draw on evidence from evolutionary biology, behavioral economics, and infant research to argue that humans are "noble savages", endowed with indiscriminate kindness. We believe this is mistaken. While there is evidence for an early-emerging moral sense - even infants recognize and favor instances of fairness and kindness amongst third parties - altruistic behaviors are selective from the start. Babies and young children favor those who have been kind to them in the past, and favor familiar individuals over strangers. They hold strong biases for ingroup over outgroup and for self over other, and indeed are more unequivocally selfish than older children and adults. Much of what is most impressive about adult morality arises not through inborn capacities, but a fraught developmental process that involves exposure to culture and the exercise of rationality.

Role of miR-31 and SATB2 in arsenic-induced malignant BEAS-2B cell transformation.

Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.

Exploring the association between initial serum alcohol concentration and polysubstance use: More than a simple "gateway drug" effect?

INTRODUCTION: Polysubstance abuse (PSA) is a significant problem affecting our society. In addition to negatively affecting the health and well-being of substance users, alcohol and/or drug abuse is also associated with heavy injury burden. The goal of this study was to determine if elevated serum alcohol (EtOH) levels on initial trauma evaluation correlate with the simultaneous presence of other substances of abuse (SOAs). We hypothesized that PSA would be more common among patients who present with EtOH levels in excess of the legal blood alcohol content (BAC) (≥0.10%). METHODS: An audit of trauma registry records from January 2009 to June 2015 was performed. Abstracted data included patient demographics, BAC measurements, all available formal determinations of urine/serum "drug screening," Glasgow Coma Scale (GCS) assessments, injury mechanism/severity, and 30-day mortality. Stratification of BAC was based on the 0.10% cutoff. Parametric and nonparametric statistical testing was performed, as appropriate, with significance set at α = 0.05. RESULTS: We analyzed 1550 patients (71% males, mean age: 38.7 years) who had both EtOH and SOA screening. Median GCS was 15 (interquartile range [IQR]: 14-15). Median ISS was 9 (IQR: 5-17). Overall 30-day mortality was 4.25%, with no difference between elevated (≥0.10) and normal (<0.10) EtOH groups. For the overall study sample, the median BAC was 0.10% (IQR: 0-0.13). There were 1265 (81.6%) patients with BAC <0.10% and 285 (18.4%) patients with BAC ≥0.10%. The two groups were similar in terms of mechanism of injury (both, ∼95% blunt). Patients with BAC ≥0.10% on initial trauma evaluation were significantly more likely to have the findings consistent with PSA (e.g., EtOH + additional substance) than patients with BAC <0.10% (377/1265 [29.8%] vs. 141/285 [49.5%], respectively, P < 0.001). Among polysubstance users, BAC ≥0.10% was significantly associated with cocaine, marijuana, and opioid use. CONCLUSIONS: This study confirms that a significant proportion of trauma patients with admission BAC ≥0.10% present with the evidence of additional substance use. Cocaine and opioids were most strongly associated with acute alcohol intoxication. Our findings support the need for further research in this important area of public health concern. In addition, specific efforts should focus on primary identification, remediation of withdrawal symptoms, prevention of drug-drug interactions, and early PSA intervention.

Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation.

Both nickel and cadmium compounds have been established as group I carcinogens for several decades. Despite over-whelming evidence of these compounds' carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal induced cellular transformation remain unclear. In this study, we found that there were slightly different effects on decreased SLBP mRNA and protein as well as increased polyA H3.1 in our nickel exposed cells. This suggested that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. We also saw that the depletion of SLBP protein was reversed by inhibiting the proteosome. Finally, we showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel's effects on SLBP may be mediated via epigenetic mechanisms. Taken together these results suggest a similar mechanism by which both arsenic and nickel may exert their carcinogenic effects.

Tungsten exposure causes a selective loss of histone demethylase protein.

In the course of our investigations into the toxicity of tungstate, we discovered that cellular exposure resulted in the loss of the histone demethylase protein. We specifically investigated the loss of two histone demethylase dioxygenases, JARID1A and JMJD1A. Both of these proteins were degraded in the presence of tungstate and this resulted in increased global levels of H3K4me3 and H3K9me2, the substrates of JARID1A and JMJD1A, respectively. Treatment with MG132 completely inhibited the loss of the demethylase proteins induced by tungstate treatment, suggesting that tungstate activated the proteasomal degradation of these proteins. The changes in global histone marks and loss of histone demethylase protein persisted for at least 48 h after removing sodium tungstate from the culture. The increase in global histone methylation remained when cells were cultured in methionine-free media, indicating that the increased histone methylation did not depend upon any de novo methylation process, but rather was due to the loss of the demethylase protein. Similar increases of H3K4me3 and H3K9me2 were observed in the livers of the mice that were acutely exposed to tungstate via their drinking water. Taken together, our results indicated that tungstate exposure specifically reduced histone demethylase JARID1A and JMJD1A via proteasomal degradation, leading to increased histone methylation.