Evaluating psychological distress associated with life events under the traumatic experience threshold in patients with major depressive and bipolar disorder.

Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience psychological distress associated with daily events that do not meet the threshold for traumatic experiences, referred to as event-related psychological distress (ERPD). Recently, we developed an assessment tool for ERPD, the ERPD-24. This tool considers four factors of ERPD: feelings of revenge, rumination, self-denial, and mental paralysis. We conducted a cross-sectional study between March 2021 and October 2022 to identify the differences and clinical features of ERPD among patients with MDD and BD and healthy subjects who did not experience traumatic events. Specifically, we assessed ERPD using the ERPD-24 and anxiety-related symptoms with the State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, and anxious-depressive attack. Regarding the ERPD-24 scores among the groups, as the data did not rigorously follow the test of normality, the Kruskal-Wallis test was used to compare the differences among the groups, followed by the Dunn-Bonferroni adjusted post-hoc test. Non-remitted MDD patients and BD patients, regardless of remission/non-remission, presented more severe ERPD than healthy subjects. This study also demonstrated the relationships between all anxiety-related symptoms, including social phobia and anxious-depressive attack and ERPD, in both BD and MDD patients and in healthy subjects. In conclusion, patients with non-remitted MDD and with BD regardless of remission/non-remission experience severe ERPD related to anxiety-related symptoms.

Live two-way video versus face-to-face treatment for depression, anxiety, and obsessive-compulsive disorder: A 24-week randomized controlled trial.

AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

Micelle Formation of Dodecanoic Acid with Alkali Metal Counterions.

Alkali series with different atomic numbers affect the physicochemical properties of aqueous solutions. The micellar properties of aqueous solutions of dodecanoate as surfactants were measured by changing the counterions (C12-Na, C12-K, C12-Rb, and C12-Cs). A plot of Krafft temperature vs. alkali metal atomic number showed a downward convex curve, with its minimum temperature (20°C) in the C12-K system. By contrast, a plot of the critical micelle concentration (CMC) vs. alkali metal atomic number exhibited an upward convex curve with the maximum CMC (25.6 mmol L-1) at C12-K. Furthermore, the minimum surface tension (γ min ) of the solution at the CMC increased with increasing atomic number (C12-Na ≈ C12-K < C12-Rb < C12-Cs). The size of the dodecanoate micelles decreased with increasing atomic number. The ionization degree of the micelles also increased with increasing atomic number of the alkali metal. Small-angle X-ray scattering (SAXS) measurements revealed that alkali dodecanoate micelles formed spherical to ellipsoidal structures. In addition, micelles from the shell region showed large electrostatic repulsion, judging from the shape of the spectrum in the higher Q -1 region. From the measurement results of the solubilization of naphthalene into the micelles, the size of the micelles corresponded to the maximum solubilization quantity of naphthalene.

Chronic neuronal excitation leads to dual metaplasticity in the signaling for structural long-term potentiation.

Synaptic plasticity is long-lasting changes in synaptic currents and structure. When neurons are exposed to signals that induce aberrant neuronal excitation, they increase the threshold for the induction of long-term potentiation (LTP), known as metaplasticity. However, the metaplastic regulation of structural LTP (sLTP) remains unclear. We investigate glutamate uncaging/photoactivatable (pa)CaMKII-dependent sLTP induction in hippocampal CA1 neurons after chronic neuronal excitation by GABAA receptor antagonists. We find that the neuronal excitation decreases the glutamate uncaging-evoked Ca2+ influx mediated by GluN2B-containing NMDA receptors and suppresses sLTP induction. In addition, single-spine optogenetic stimulation using paCaMKII indicates the suppression of CaMKII signaling. While the inhibition of Ca2+ influx is protein synthesis independent, the paCaMKII-induced sLTP suppression depends on it. Our findings demonstrate that chronic neuronal excitation suppresses sLTP in two independent ways (i.e., dual inhibition of Ca2+ influx and CaMKII signaling). This dual inhibition mechanism may contribute to robust neuronal protection in excitable environments.

Japanese Project for Telepsychiatry Evaluation during COVID-19: Treatment Comparison Trial (J-PROTECT): Rationale, design, and methodology.

INTRODUCTION: The COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date. METHODS: The targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a "telepsychiatry group" (at least 50% of treatments to be conducted using telemedicine, with at least one face-to-face treatment [FTF] within six months) or an "FTF group" (all treatments to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group. DISCUSSION: This study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry. TRIAL REGISTRATION: jRCT1030210037, Japan Registry of Clinical Trials (jRCT).

Identifying factors associated with criminal responsibility by analyzing court trial verdicts.

The criminal responsibility of offenders with mental disorders is a key issue in forensic psychiatry. Japan's implementation of the Medical Treatment and Supervision Act and Lay Judge Act in the early 2000s raised public awareness of this issue. To determine how criminal court judges in Japan assess the criminal responsibility of offenders, we examined 453 district court verdicts that mention psychiatric evidence. We extracted elements from each verdict that may be associated with courts' decision-making regarding criminal responsibility and analyzed the relationship between each element and the adjudication of criminal responsibility. We investigated the changes in each element's prevalence over time. A logistic regression analysis revealed that the following were independently associated with the court decisions that offenders' criminal responsibility was intact: understandable motivation for committing the offense, homogeneity of the offense from the defendant's usual behavioral pattern, a coherent process used to commit the offense, alertness while offending, and absence of psychotic symptoms. We observed that recent verdicts are more focused on the offender's perception of illegality and the coherence of the offending process while disregarding the defendant's consciousness and memory while offending. Thus, the courts focus on some specific elements for evaluating the criminal responsibility of each offender.

Identification of psychological features and development of an assessment tool for event-related psychological distress after experiencing non-traumatic stressful events.

Stressful events in daily life that are non-traumatic (e.g., family-, school-, work-, interpersonal-, and health-related problems) frequently cause various mood disturbances. For some people, being exposed to non-traumatic but stressful events could trigger the onset and relapse of mood disorders. Furthermore, non-traumatic stressful events also cause event-related psychological distress (ERPD), similar to that of post-traumatic stress disorder (PTSD; i.e., intense intrusive imagery or memory recall, avoidance, and hyperarousal) in the general population and individuals with mood disorders. However, previous ERPD studies only showed that people with ERPD display PTSD-like symptoms after non-traumatic experiences; they failed to get to the crux of the matter by only utilizing trauma- or PTSD-related assessment tools. We thus aimed to identify the psychological phenomena and features of ERPD after individuals experienced non-traumatic stressful events, and to develop and validate an appropriate ERPD assessment tool. First, we conducted a qualitative study to obtain the psychological features through interviews with 22 individuals (mean age = 41.50 years old, SD = 12.24) with major depressive disorder or bipolar disorder. Second, in the quantitative component, we implemented a web-based survey with 747 participants of the general population (mean age = 41.96 years old, SD = 12.64) by using ERPD-related questionnaires created based on the qualitative study; then, we examined the reliability and validity of the ERPD assessment tool. Results yielded that the psychological features of ERPD comprised four factors: feelings of revenge, rumination, self-denial, and mental paralysis. These were utilized in the developed 24-item measure of ERPD-a novel self-report assessment tool. For various professionals involved in mental healthcare, this tool can be used to clarify and assess psychological phenomena in people with ERPD.

Photoactivatable CaMKII induces synaptic plasticity in single synapses.

Optogenetic approaches for studying neuronal functions have proven their utility in the neurosciences. However, optogenetic tools capable of inducing synaptic plasticity at the level of single synapses have been lacking. Here, we engineered a photoactivatable (pa)CaMKII by fusing a light-sensitive domain, LOV2, to CaMKIIα. Blue light or two-photon excitation reversibly activated paCaMKII. Activation in single spines was sufficient to induce structural long-term potentiation (sLTP) in vitro and in vivo. paCaMKII activation was also sufficient for the recruitment of AMPA receptors and functional LTP in single spines. By combining paCaMKII with protein activity imaging by 2-photon FLIM-FRET, we demonstrate that paCaMKII activation in clustered spines induces robust sLTP via a mechanism that involves the actin-regulatory small GTPase, Cdc42. This optogenetic tool for dissecting the function of CaMKII activation (i.e., the sufficiency of CaMKII rather than necessity) and for manipulating synaptic plasticity will find many applications in neuroscience and other fields.

The Effect of Grandmothers' Presence on the Provision of Multidisciplinary Perinatal Support for Pregnant and Postpartum Women with Psychosocial Problems.

BACKGROUND: Pregnant and postpartum women with psychosocial problems are prone to face limited or absent perinatal functional support from biological grandmothers due to familial dysfunction. The study aimed to investigate whether the involvement and presence of biological maternal grandmothers providing practical support for their pre/postnatal daughters (ie, pregnant women) during the perinatal period may influence the number of support services provided by multidisciplinary agencies, including child consultation centers and municipal offices. PARTICIPANTS AND METHODS: This is a retrospective cohort study based on the medical records of all pregnant women with psychosocial problems that visited, gave birth, and received intervention from the hospital-based child protection unit at the Chiba University Hospital between February 2018 to March 2019. The primary outcome was to identify whether there was a difference in the number of multidisciplinary agencies providing perinatal support between pregnant women with and without the presence of functional support from biological maternal grandmothers during the perinatal period. RESULTS: We identified 114 pregnant and postpartum women with psychosocial problems. Seventy-six of these participants (66.7%) had functional support from their biological maternal grandmothers during the perinatal period, and 38 participants (33.3%) did not. The number of agencies involved with participants who lacked functional support was significantly higher than participants with functional support (t(55.14) = 2.98, p < 0.01). This finding was consistent among pregnant and postpartum primipara participants (n = 70) (t(68) = 3.87, p < 0.001), but not multipara (n = 44). CONCLUSION: The findings indicate that the presence and functional support of biological maternal grandmothers influence the support that is needed from multidisciplinary perinatal support systems by pregnant and postpartum women with psychosocial problems. Primipara mothers without support from their own mothers may need greater multidisciplinary support.

Outcomes of administrative involuntary hospitalization: A national retrospective cohort study in Japan.

BACKGROUND: Treatment for offenders with mental disorders is a key concern in public mental health. Provision of adequate psychiatric treatment is important for the offender and their community. An approach used in Japan to address this issue is administrative involuntary hospitalization. Under this scheme, a person at risk for harming themselves or others because of a mental disorder can be involuntarily hospitalized in a designated psychiatric hospital. However, this scheme does not include tracking of these patients after discharge. Although some data for administrative involuntary hospitalizations are available, it remains unclear what happens to these patients after discharge. AIM: To evaluate follow-up of patients under administrative involuntary hospitalization after discharge and obtain data for later comparisons with outcomes. METHODS: We used a retrospective design and conducted a national survey of administrative involuntary hospitalizations. Questionnaires were distributed to 939 facilities across Japan. The questionnaire collected data for selected involuntary hospitalization cases in the hospital on June 30, 2010 (census date), and the prognoses of each patient on a specified date in 2011 and 2012. We also asked about the treatment provided to each patient. We stratified patients by prognosis (good or poor), and used logistic regression analysis to examine the relationship between treatment and prognosis. RESULTS: We received completed questionnaires from 292 facilities (response rate 31.1%); 105 facilities had no relevant patients. Our analysis included data for 394 patients with valid data. Official statistics indicated 1503 patients were under administrative involuntary hospitalization as at June 30, 2012, meaning the capture rate was 27.2%. Approximately a fourth (104/394) at 1 year, and a third (137/294) at 2 years after the census had unknown prognosis. Treatment content included multi-disciplinary team meetings (78.2% of patients), counseling by public workers (59.9%), and discussion with external specialists (32.5%). Overall, 116 patients were categorized as having a good prognosis at 1 year, and 168 had a poor prognosis. At the 2-year point, 102 patients had a good prognosis and 150 had a poor prognosis. "Discussion with external specialists" was positively associated with a good prognosis at both 1 year (P = 0.016) and 2 years (P = 0.036). CONCLUSION: We found that facilities in Japan currently have limited ability to track the prognoses of patients who were hospitalized involuntarily. Discussion with external specialists is associated with a good prognosis.

ShadowR: a novel chromoprotein with reduced non-specific binding and improved expression in living cells.

Here we developed an orange light-absorbing chromoprotein named ShadowR as a novel acceptor for performing fluorescence lifetime imaging microscopy-based Förster resonance energy transfer (FLIM-FRET) measurement in living cells. ShadowR was generated by replacing hydrophobic amino acids located at the surface of the chromoprotein Ultramarine with hydrophilic amino acids in order to reduce non-specific interactions with cytosolic proteins. Similar to Ultramarine, ShadowR shows high absorption capacity and no fluorescence. However, it exhibits reduced non-specific binding to cytosolic proteins and is highly expressed in HeLa cells. Using tandem constructs and a LOVTRAP system, we showed that ShadowR can be used as a FRET acceptor in combination with donor mRuby2 or mScarlet in HeLa cells. Thus, ShadowR is a useful, novel FLIM-FRET acceptor.

The recognition and expectations of ex-inpatients of mental health services: A web-based questionnaire survey in Japan.

Concern about mental health issues and the treatment of mentally disordered offenders attracts considerable public attention. This study aimed to gather the experiences and opinions of people who have experienced admission to a psychiatric ward in order to grasp their reaction to, and understanding of, the legislation behind the involuntary admission of psychiatric patients. A web-based questionnaire survey was conducted with a total of 379 participants, using a cross-sectional, exploratory design. The data were analyzed using a chi-squared test, Fisher's exact test, and a logistic regression analysis. According to the results, many patients were satisfied with their treatment during psychiatric admission; however, only few participants said that they had been given an adequate explanation for their involuntary treatment. Most participants expected qualified assistance after discharge, although the prospect of a regular visit from an official was not entirely supported by the participants. Patient satisfaction was relevant to the discussion of their needs after discharge and in developing a crisis plan during admission. These findings suggest that psychiatric patients accept inpatient treatment as long as they receive an adequate explanation. More qualified care such as relapse prevention would be expected to lead to better satisfaction. For them to welcome regular visits from an official, patients may need more information and discussion.

MYC-type transcription factors, MYC67 and MYC70, interact with ICE1 and negatively regulate cold tolerance in Arabidopsis.

The expression of hundreds of genes is induced by low temperatures via a cold signaling pathway. ICE1, a MYC-type transcription factor, plays an important role in the induction of CBF3/DREB1A to control cold-responsive genes and cold tolerance. To elucidate other molecular factors, a yeast 2-hybrid screening was performed. Two MYC-type transcription factors, MYC67 and MYC70, were identified as ICE1-interacting proteins. The myc mutants were more tolerant to freezing temperatures than wild type. CBF3/DREB1A and other cold-responsive genes were up-regulated in the myc mutants. Overexpression of the MYC genes increased the cold sensitivity and down-regulated the expression of cold-responsive genes. The MYC proteins interacted with the cis-elements in the CBF3/DREB1A promoter, probably to interfere interaction between ICE1 and the cis-elements. Taken together, these results demonstrate that MYC67 and MYC70, ICE1 interactors, negatively regulate cold-responsive genes and cold tolerance.

Diminished nuclear RNA decay upon Salmonella infection upregulates antibacterial noncoding RNAs.

Cytoplasmic mRNA degradation controls gene expression to help eliminate pathogens during infection. However, it has remained unclear whether such regulation also extends to nuclear RNA decay. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection.

Psychological Distress Symptoms Associated With Life Events in Patients With Bipolar Disorder: A Cross-Sectional Study.

Stressful life events, although less serious than traumatic experiences, affect the clinical course of patients with bipolar disorder. We previously found that bipolarity in patients with major depression is related to the severity of psychological distress symptoms associated with onset-related events. Here, we investigated whether, and to what extent, bipolar patients perceive stressful events as psychological distress symptoms, specifically, intrusion, avoidance, and hyperarousal. Further, we investigated the relationship between the clinical features and the severity of psychological distress symptoms associated with stressful life events, according to mood states. We recruited 79 bipolar patients (depression group, n = 32; mania, n = 22; euthymia, n = 25) in this cross-sectional study. We adopted the Impact of Event Scale-Revised (IES-R) to assess the severity of psychological distress symptoms associated with past stressful events. We also evaluated the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The mean (standard deviation) IES-R scores of bipolar patients with a depressive episode (38.06 [16.56], p = 0.0005) and of those with a manic/hypomanic episode (44.56 [24.14], p = 0.004) were significantly higher than of those with euthymia (19.81 [12.86]). The HDRS, but not the YMRS, scores showed significant correlations with the IES-R scores, regardless of mood episodes (depression group, r = 0.42; mania, r = 0.64; euthymia, r = 0.70). This study demonstrates that bipolar patients with a manic/hypomanic or depressive episode perceive stressful life events as more severe psychological distress symptoms than do euthymic patients. Moreover, in patients with bipolar disorder, the severity of depressive symptoms, but not of manic symptoms, is positively correlated with that of the psychological distress symptoms, regardless of their mood episodes or euthymic state. Therefore, depressive symptoms may be closely related to the psychological distress symptoms associated with stressful past events in patients with bipolar disorder.

Differences between British and Japanese perspectives on forensic mental health systems: A preliminary study.

AIM: To clarify the differences in views on forensic mental health (FMH) systems between the United Kingdom and Japan. METHODS: We conducted a series of semi-structured interviews with six leading forensic psychiatrists. Based on a discussion by the research team, we created an interview form. After we finished conducting all the interviews, we qualitatively analyzed their content. RESULTS: In the United Kingdom the core domain of FMH was risk assessment and management; however, in Japan, the core domain of FMH was psychiatric testimony. In the United Kingdom, forensic psychiatrists were responsible for ensuring public safety, and psychopathy was identified as a disease but deemed as not suitable for medical treatment. On the other hand, in Japan, psychopathy was not considered a mental illness. CONCLUSION: In conclusion, there are considerable differences between the United Kingdom and Japan with regard to the concepts of FMH. Some ideas taken from both cultures for better FMH practice were suggested.

Effect of educational intervention on attitudes toward the concept of criminal responsibility.

AIM: To evaluate the effect of educational intervention on individuals' knowledge of and attitudes toward forensic mental health. METHODS: We conducted a questionnaire regarding attitudes toward various ideas about forensic mental health. The respondents attended a 1-h seminar regarding forensic mental health after answering the questionnaire. On completion of the seminar, the respondents answered another questionnaire containing many of the same questions as contained in the pre-seminar questionnaire. RESULTS: A total of 86 individuals attended the seminar, and 78 responded to the questionnaire. Only 13 (18.8%) participants were supportive of the concept of criminal responsibility initially, and there was a statistically significant increase in those who became more supportive after the seminar, with 22 (33%) being supportive after the seminar (Wilcoxon signed-rank test, P < 0.001). Logistic regression analysis revealed that participants who were skeptical about forensic mental systems and those with fewer opportunities to see media reports regarding psychiatry were likely to become supportive of criminal responsibility after the intervention. CONCLUSION: These results suggest that public attitudes toward criminal responsibility and mental health can be influenced via educational interventions.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.

Genomic landscape of liposarcoma.

Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% of all adult sarcomas. Due to absence of clinically effective treatment options in inoperable situations and resistance to chemotherapeutics, a critical need exists to identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing and targeted exome sequencing to uncover the genomic information for development of specific anti-cancer targets. SNP array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) and important novel genes (UAP1, MIR557, LAMA4, CPM, IGF2, ERBB3, IGF1R). Carboxypeptidase M (CPM), recurrently amplified gene in well-differentiated/de-differentiated LPS was noted as a putative oncogene involved in the EGFR pathway. Notable deletions were found at chromosome 1p (RUNX3, ARID1A), chromosome 11q (ATM, CHEK1) and chromosome 13q14.2 (MIR15A, MIR16-1). Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%). Further, in vitro and in vivo functional studies provided evidence for the tumor suppressor role for Neurofibromin 1 (NF1) gene in different subtypes of LPS. Pathway analysis of recurrent mutations demonstrated signaling through MAPK, JAK-STAT, Wnt, ErbB, axon guidance, apoptosis, DNA damage repair and cell cycle pathways were involved in liposarcomagenesis. Interestingly, we also found mutational and copy number heterogeneity within a primary LPS tumor signifying the importance of multi-region sequencing for cancer-genome guided therapy. In summary, these findings provide insight into the genomic complexity of LPS and highlight potential druggable pathways for targeted therapeutic approach.

Iron deficiency regulated OsOPT7 is essential for iron homeostasis in rice.

The molecular mechanism of iron (Fe) uptake and transport in plants are well-characterized; however, many components of Fe homeostasis remain unclear. We cloned iron-deficiency-regulated oligopeptide transporter 7 (OsOPT7) from rice. OsOPT7 localized to the plasma membrane and did not transport Fe(III)-DMA or Fe(II)-NA and GSH in Xenopus laevis oocytes. Furthermore OsOPT7 did not complement the growth of yeast fet3fet4 mutant. OsOPT7 was specifically upregulated in response to Fe-deficiency. Promoter GUS analysis revealed that OsOPT7 expresses in root tips, root vascular tissue and shoots as well as during seed development. Microarray analysis of OsOPT7 knockout 1 (opt7-1) revealed the upregulation of Fe-deficiency-responsive genes in plants grown under Fe-sufficient conditions, despite the high Fe and ferritin concentrations in shoot tissue indicating that Fe may not be available for physiological functions. Plants overexpressing OsOPT7 do not exhibit any phenotype and do not accumulate more Fe compared to wild type plants. These results indicate that OsOPT7 may be involved in Fe transport in rice.