Heterologous expression and purification of glutamate decarboxylase-1 from the model plant Arabidopsis thaliana: characterization of the enzyme's in vitro truncation by thiol endopeptidase activity.

Plant glutamate decarboxylase (GAD) is a Ca2+-calmodulin (CaM) activated enzyme that produces γ-aminobutyrate (GABA) as the first committed step of the GABA shunt. Our prior research established that in vivo phosphorylation of AtGAD1 (AT5G17330) occurs at multiple N-terminal serine residues following Pi resupply to Pi-starved cell cultures of the model plant Arabidopsis thaliana. The aim of the current investigation was to purify recombinant AtGAD1 (rAtGAD1) following its expression in Escherichia coli to facilitate studies of the impact of phosphorylation on its kinetic properties. However, in vitro proteolytic truncation of an approximate 5 kDa polypeptide from the C-terminus of 59 kDa rAtGAD1 subunits occurred during purification. Immunoblotting demonstrated that most protease inhibitors or cocktails that we tested were ineffective in suppressing this partial rAtGAD1 proteolysis. Although the thiol modifiers N-ethylmaleimide or 2,2-dipyridyl disulfide negated rAtGAD1 proteolysis, they also abolished its GAD activity. This indicates that an essential -SH group is needed for catalysis, and that rAtGAD1 is susceptible to partial degradation either by an E. coli cysteine endopeptidase, or possibly via autoproteolytic activity. The inclusion of exogenous Ca2+/CaM facilitated the purification of non-proteolyzed rAtGAD1 to a specific activity of 27 (µmol GABA produced/mg) at optimal pH 5.8, while exhibiting an approximate 3-fold activation by Ca2+/CaM at pH 7.3. By contrast, the purified partially proteolyzed rAtGAD1 was >40% less active at both pH values, and only activated 2-fold by Ca2+/CaM at pH 7.3. These results emphasize the need to diagnose and prevent partial proteolysis before conducting kinetic studies of purified regulatory enzymes.

Examining the impact of brief couples-based posttraumatic stress disorder treatments on anger and psychological aggression in veterans and their partners.

Anger can adversely impact functioning in veterans. Psychological aggression, which is related to but distinct from anger, is particularly detrimental to veterans' mental health. Research examining anger and psychological aggression following individual therapy for posttraumatic stress disorder (PTSD) has demonstrated small effect sizes. Treatments that directly target conflict management and interpersonal functioning, both regarding content and delivery to veterans and their loved ones (e.g., couples-based PTSD treatments), may be more effective in alleviating anger symptoms. This study examined whether larger reductions in anger and psychological aggression would be observed in a couples-based intervention compared to an active comparator at posttreatment and follow-up. Data were derived from a randomized trial comparing brief cognitive-behavioral conjoint therapy for PTSD (bCBCT) and PTSD family education (PFE). Participants were 137 veterans and their intimate partners (bCBCT: n = 92, PFE: n = 45). We observed within-condition significant reductions in angry temperament, d = -0.47, p < .001, and angry reaction, d = -0.26, p = .004, among veterans in bCBCT but not PFE, |d|s = 0.13-0.17, ps = .166-.268. Veterans and partners in both conditions reported reductions in psychological aggression, |d|s = 1.09-1.46, ps < .001. There were no significant differences between the treatment conditions on any outcome, ps = .103-.443, and there were no significant changes in anger between posttreatment and follow-up, |d|s = 0.07-0.24, ps = .052-.582. Couples-based interventions for PTSD, including bCBCT and PFE, can be effective in improving aspects of anger among veterans and their intimate partners.

Cell cycle stress in normal human cells: A route to "first cells" (with/without fitness gain) and cancer-like cell-shape changes.

We have presented an in vitro trackable model system, atavistic induced from conservation in our genome, which strongly is applicable to tumorigenesis start and evolution. The inducing factor was death signals to proliferating normal human cells (primary cell strains), which respon-ded by a special type of tetraploidization, chromosomes with 4-chromatids (diplochromosomes, earlier described in cancer cells). The response included cell cycle stress, which prolonged S-period with result of mitotic slippage process, forming the special 4n cells by re-replication of diploid cells, which showed cell division capability to unexpected, genome reduced diploid cells which remarkably, showed fitness gain. This unique response through cell cycle stress and mitotic slippage process was further discovered to be linked to a rather special characteristic of the, 4n nucleus. The nucleus turned, self-inflicted, 90° perpendicular to the cell's cytoskeleton axis, importantly, before the special 4n-division system produced genome reduce diploid cells, we call "first cells", because of fitness gain. These 2n cells also showed the nuclear dependent 90° turn, which in both cases was associated with cells gaining cell shape changes, herein illustrated from normal fibroblastic cells changing to roundness cells, indistinguishable from todays' diagnostic cancer cell morphology. This 3-D ball-like cell shape, in metastasis, sque-ezing in and out between (?) endothelial cells in the lining of blood veins during disbursement, would be advantageous.

Characterization of low-density granulocytes in COVID-19.

Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.

Glutamate decarboxylase-1 is essential for efficient acclimation of Arabidopsis thaliana to nutritional phosphorus deprivation.

Glutamate decarboxylase (GAD) is a Ca2+ -calmodulin-activated, cytosolic enzyme that produces γ-aminobutyrate (GABA) as the committed step of the GABA shunt. This pathway bypasses the 2-oxoglutarate to succinate reactions of the tricarboxylic acid (TCA) cycle. GABA also accumulates during many plant stresses. We tested the hypothesis that AtGAD1 (At5G17330) facilitates Arabidopsis acclimation to Pi deprivation. Quantitative RT-PCR and immunoblotting revealed that AtGAD1 transcript and protein expression is primarily root-specific, but inducible at lower levels in shoots of Pi-deprived (-Pi) plants. Pi deprivation reduced levels of the 2-oxoglutarate dehydrogenase (2-OGDH) cofactor thiamine diphosphate (ThDP) in shoots and roots by > 50%. Growth of -Pi atgad1 T-DNA mutants was significantly attenuated relative to wild-type plants. This was accompanied by: (i) an > 60% increase in shoot and root GABA levels of -Pi wild-type, but not atgad1 plants, and (ii) markedly elevated anthocyanin and reduced free and total Pi levels in leaves of -Pi atgad1 plants. Treatment with 10 mM GABA reversed the deleterious development of -Pi atgad1 plants. Our results indicate that AtGAD1 mediates GABA shunt upregulation during Pi deprivation. This bypass is hypothesized to circumvent ThDP-limited 2-OGDH activity to facilitate TCA cycle flux and respiration by -Pi Arabidopsis.

In-office, in-home, and telehealth cognitive processing therapy for posttraumatic stress disorder in veterans: a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies for combat-related posttraumatic stress disorder (PTSD) in military veterans are efficacious, but there are many barriers to receiving treatment. The objective of this study was to determine if cognitive processing therapy (CPT) for PTSD among active duty military personnel and veterans would result in increased acceptability, fewer dropouts, and better outcomes when delivered In-Home or by Telehealth as compared to In-Office treatment. METHODS: The trial used an equipoise-stratified randomization design in which participants (N = 120) could decline none or any 1 arm of the study and were then randomized equally to 1 of the remaining arms. Therapists delivered CPT in 12 sessions lasting 60-min each. Self-reported PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5) served as the primary outcome. RESULTS: Over half of the participants (57%) declined 1 treatment arm. Telehealth was the most acceptable and least often refused delivery format (17%), followed by In-Office (29%), and In-Home (54%); these differences were significant (p = 0.0008). Significant reductions in PTSD symptoms occurred with all treatment formats (p < .0001). Improvement on the PCL-5 was about twice as large in the In-Home (d = 2.1) and Telehealth (d = 2.0) formats than In-Office (d = 1.3); those differences were statistically large and significant (d = 0.8, 0.7 and p = 0.009, 0.014, respectively). There were no significant differences between In-Home and Telehealth outcomes (p = 0.77, d = -.08). Dropout from treatment was numerically lowest when therapy was delivered In-Home (25%) compared to Telehealth (34%) and In-Office (43%), but these differences were not statistically significant. CONCLUSIONS: CPT delivered by telehealth is an efficient and effective treatment modality for PTSD, especially considering in-person restrictions resulting from COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02290847 (Registered 13/08/2014; First Posted Date 14/11/2014).

Taking account of others' goals in social information use: Developmental changes in 3- to 7-year-old children.

The ability to take mental states such as goals into account when interpreting others' behavior has been proposed to be what sets human use of social information apart from that of other animals. If so, children's social information use would be expected to change as their understanding of others' mental states develops. We explored age-related changes in 3- to 7-year-old children's ability to strategically use social information by taking into account another's goal when it was, or was not, aligned with their own. Children observed as a puppet demonstrator selected a capsule, peeked inside, and chose to accept or reject it, following which children made their own selection. Children were able to account for others' conflicting motivations from around 4 years of age and reliably inferred the outcome of others' behavior from 6 years. However, using social information based on such inferences appeared to be challenging regardless of whether the demonstrator's goal was, or was not. aligned to that of the participant. We found that social information use improved with age; however, this improvement was restricted to cases in which the appropriate response was to avoid copying the demonstrator's selection. In contrast to previous research, appropriate copying responses remained at chance. Possible explanations for this unexpected pattern of results are discussed. The cognitive challenge associated with the ability to account for others' goals could offer humans a significant advantage over that of other animals in their ability to use social information.

Correlates of Incarceration History Among Military Veterans.

Veterans with histories of incarceration are at greater risk for poor physical and mental health outcomes, yet prior research in this population has focused on specific subsets of veterans or a narrow range of predictors. We utilized the Bronfenbrenner Socioecological Model as the framework to evaluate correlates of incarceration history in a large sample of Iraq and Afghanistan-era veterans at four levels: demographic, historical, clinical, and contextual. Participants were 2,904 veterans (76.9% male; 49.5% White and 46.5% Black; mean age 38.08, SD = 10.33), 700 of whom reported a history of incarceration. Four logistic regression models predicting history of incarceration were tested, adding demographic, historical, clinical, and contextual variables hierarchically. In the final model, younger age (OR=0.99, 95% CI=0.98-1.00), male gender (OR of being female =0.28, 95% CI=0.21-0.38), belonging to a historically marginalized group (OR of being White =0.69, 95% CI=0.56-0.84), family history of incarceration (OR=1.47, 95% CI=1.10-1.94), adult interpersonal trauma (OR=1.39, 95% CI=1.28-1.51), problematic alcohol use (OR=1.03, 95% CI=1.02-1.05), drug abuse (OR=1.15, 95% CI=1.11-1.19), and unemployment (OR for being employed=0.76, 95% CI=0.62-0.92) were significantly associated with a history of incarceration. Implications of these findings for developing interventions and supporting systems to effectively target this high-risk population of veterans are discussed.

Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction.

Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.

The complex role of prostaglandin E2-EP receptor signaling in wound healing.

Prostaglandins are critical lipid mediators involved in the wound healing response, with prostaglandin E2 (PGE2) being the most complex and exhibiting the most diverse physiological outputs. PGE2 signals via four G protein-coupled receptors, termed EP-receptors 1-4 that induce distinct signaling pathways upon activation and lead to an array of different outputs. Recent studies examining the role of PGE2 and EP receptor signaling in wound healing following various forms of tissue damage are discussed in this review.

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study.

OBJECTIVE: We aimed to examine the impact of resumption of home antiseizure drugs alone (ASD-) compared with adjunct administration of scheduled intravenous (IV) lorazepam 2 mg every 6 h (ASD+) following ictal single-photon emission computed tomography (SPECT) injection on the localization value of SPECT studies and treatment-emergent adverse events (TEAEs). METHODS: We conducted a prospective study at Mayo Clinic inpatient epilepsy monitoring unit (EMU) between January 2018 and May 2020 in Jacksonville, Florida. The ASD- and ASD+ groups were compared for concordance of SPECT studies with the epilepsy surgical conference (ESC) consensus or intracranial electroencephalography (icEEG) findings as reference. Treatment-emergent adverse events, obtained from surveys at 24 h and one week postictal SPECT injection, were also compared between both groups. RESULTS: Twenty-two consecutive patients with temporal (eight patients, 36%) and extratemporal (14 patients, 64%) epilepsy were included: 12 ASD+ and 10 ASD-. The two groups were well matched with regard to clinical and ictal SPECT injection characteristics including the occurrence of seizure between ictal and interictal SPECT injections. The localization value of SPECT studies was similar in the two groups. Patients in the ASD+ group reported higher rates of dizziness and excessive sedation at 24 h (p-value = 0.008). Fourteen patients (64%) underwent icEEG monitoring. For the entire cohort, the localization concordance of SPECT analysis by statistical parametric mapping (SPM) was superior to raw ictal SPECT (p-value = 0.003) and subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM; p-value = 0.021). Eventually, seven patients (31.8%) underwent resective brain surgery of whom four (57.1%) became seizure-free (median follow-up = 22 months). CONCLUSIONS: Our findings suggest that resuming home ASDs without the addition of scheduled IV lorazepam following inpatient ictal SPECT injection is equally efficacious for seizure onset zone (SOZ) localization on SPECT studies, especially SPM. This approach is also associated with fewer transient TEAEs and lower financial cost with no difference in preventing seizure between ictal and interictal SPECT injections.

The Impact of Hostility on Quality of Life, Functioning, and Suicidal Ideation Among Male Veterans with Posttraumatic Stress Disorder.

Veterans with posttraumatic stress disorder (PTSD) often experience high levels of hostility. Although studies have found that PTSD is associated with poorer quality of life (QoL), increased functional impairment, lower levels of social support, and increased suicidal ideation, it is unclear if hostility impacts these domains in veterans with PTSD above and beyond the impact from PTSD and depressive symptoms. The present study aimed to examine whether hostility is related to several indices of poorer QoL and functioning after controlling for demographic characteristics, PTSD symptoms, and depressive symptoms. Participants (N = 641) were male U.S. veterans seeking PTSD treatment through a specialty clinic in the Veterans Affairs Healthcare System. Veterans completed the Davidson Trauma Scale for DSM-IV (DTS), Personality Assessment Inventory (PAI), Quality of Life Inventory, and the Sheehan Disability Scale. Hierarchical regressions were conducted to examine the impact of PAI measures of hostility on QoL, functioning, social support, and suicidal ideation beyond DTS, depression, race, and age. After covarying for DTS total score, depression symptoms, age, and race, higher levels of hostility were significantly associated with higher degrees of functional impairment and lower degrees of social support, ΔR2 = .01 and ΔR2 = .02, respectively. Higher levels of hostility were significantly related to diminished functioning and lower social support beyond PTSD and depressive symptoms in veterans seeking treatment for PTSD. These findings highlight the importance of assessing and treating hostility in veterans with PTSD.

Bootstrapping and Pinning down the Root Meristem; the Auxin-PLT-ARR Network Unites Robustness and Sensitivity in Meristem Growth Control.

After germination, the meristem of the embryonic plant root becomes activated, expands in size and subsequently stabilizes to support post-embryonic root growth. The plant hormones auxin and cytokinin, together with master transcription factors of the PLETHORA (PLT) family have been shown to form a regulatory network that governs the patterning of this root meristem. Still, which functional constraints contributed to shaping the dynamics and architecture of this network, has largely remained unanswered. Using a combination of modeling approaches we reveal how the interplay between auxin and PLTs enables meristem activation in response to above-threshold stimulation, while its embedding in a PIN-mediated auxin reflux loop ensures localized PLT transcription and thereby, a finite meristem size. We furthermore demonstrate how this constrained PLT transcriptional domain enables independent control of meristem size and division rates, further supporting a division of labor between auxin and PLT. We subsequently reveal how the weaker auxin antagonism of the earlier active Arabidopsis response regulator 12 (ARR12) may arise from the absence of a DELLA protein interaction domain. Our model indicates that this reduced strength is essential to prevent collapse in the early stages of meristem expansion while at later stages the enhanced strength of Arabidopsis response regulator 1 (ARR1) is required for sufficient meristem size control. Summarizing, our work indicates that functional constraints significantly contribute to shaping the auxin-cytokinin-PLT regulatory network.

Halotropism requires phospholipase Dζ1-mediated modulation of cellular polarity of auxin transport carriers.

Endocytosis and relocalization of auxin carriers represent important mechanisms for adaptive plant growth and developmental responses. Both root gravitropism and halotropism have been shown to be dependent on relocalization of auxin transporters. Following their homology to mammalian phospholipase Ds (PLDs), plant PLDζ-type enzymes are likely candidates to regulate auxin carrier endocytosis. We investigated root tropic responses for an Arabidopsis pldζ1-KO mutant and its effect on the dynamics of two auxin transporters during salt stress, that is, PIN2 and AUX1. We found altered root growth and halotropic and gravitropic responses in the absence of PLDζ1 and report a role for PLDζ1 in the polar localization of PIN2. Additionally, irrespective of the genetic background, salt stress induced changes in AUX1 polarity. Utilizing our previous computational model, we found that these novel salt-induced AUX1 changes contribute to halotropic auxin asymmetry. We also report the formation of "osmotic stress-induced membrane structures." These large membrane structures are formed at the plasma membrane shortly after NaCl or sorbitol treatment and have a prolonged presence in a pldζ1 mutant. Taken together, these results show a crucial role for PLDζ1 in both ionic and osmotic stress-induced auxin carrier dynamics during salt stress.

Periodic Lateral Root Priming: What Makes It Tick?

Conditioning small groups of root pericycle cells for future lateral root formation has a major impact on overall plant root architecture. This priming of lateral roots occurs rhythmically, involving temporal oscillations in auxin response in the root tip. During growth, this process generates a spatial pattern of prebranch sites, an early stage in lateral root formation characterized by a stably maintained high auxin response. To date, the molecular mechanism behind this rhythmicity has remained elusive. Some data implicate a cell-autonomous oscillation in gene expression, while others strongly support the importance of tissue-level modulations in auxin fluxes. Here, we summarize the experimental data on periodic lateral root priming. We present a theoretical framework that distinguishes between a priming signal and its subsequent memorization and show how major roles for auxin fluxes and gene expression naturally emerge from this framework. We then discuss three mechanisms that could potentially induce oscillations of auxin response: cell-autonomous oscillations, Turing-type patterning, and tissue-level oscillations in auxin fluxes, along with specific properties of lateral root priming that may be used to discern which type of mechanism is most likely to drive lateral root patterning. We conclude with suggestions for future experiments and modeling studies.

Using Interpretation Bias Modification to Reduce Anger in Veterans with Posttraumatic Stress Disorder: A Pilot Study.

Difficulty controlling anger is the most commonly reported reintegration concern among veterans with posttraumatic stress disorder (PTSD). One of the mechanisms associated with problematic anger is a tendency to interpret ambiguous interpersonal situations as hostile, known as the hostile interpretation bias (HIB). A computer-based interpretation bias modification (IBM) intervention has been shown to successfully reduce HIB and anger but has not been tested in veterans with PTSD. The current study was a pilot trial of this IBM intervention modified to address problematic anger among veterans with PTSD. Veterans with PTSD and a high level of anger (N = 7) completed eight sessions of IBM treatment over the course of 4 weeks. Participants completed self-report questionnaires at pre- and posttreatment assessment visits, as well as a treatment acceptability interview at posttreatment. Veterans experienced large reductions in hostile interpretation bias and anger from pre- to posttreatment, ds = 1.03-1.96, although these estimates may be unstable due to the small sample size. The feasibility for recruitment, retention, and treatment completion were high. Questionnaire and interview data demonstrated that most participants were satisfied with the treatment and found it helpful and easy to use. Overall, IBM for anger was feasible and acceptable to veterans with PTSD and was associated with reductions in hostile interpretations and self-reported anger outcomes. Further research examining this approach is warranted.

The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis.

As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.

Changes in anger and aggression after treatment for PTSD in active duty military.

OBJECTIVE: To examine whether treating posttraumatic stress disorder (PTSD) reduces anger and aggression and if changes in PTSD symptoms are associated with changes in anger and aggression. METHOD: Active duty service members (n = 374) seeking PTSD treatment in two randomized clinical trials completed a pretreatment assessment, 12 treatment sessions, and a posttreatment assessment. Outcomes included the Revised Conflict Tactics Scale and state anger subscale of the State-Trait Anger Expression Inventory. RESULTS: Treatment groups were analyzed together. There were small to moderate pretreatment to posttreatment reductions in anger (standardized mean difference [SMD] = -0.25), psychological aggression (SMD = -0.43), and physical aggression (SMD = -0.25). The majority of participants continued to endorse anger and aggression at posttreatment. Changes in PTSD symptoms were mildly to moderately associated with changes in anger and aggression. CONCLUSIONS: PTSD treatments reduced anger and aggression with effects similar to anger and aggression treatments; innovative psychotherapies are needed.

Development of the Response to Fearful Situations Scale.

BACKGROUND: Most measures of anxious avoidance are limited to disorder-specific mechanisms and ignore the measurement of courage/approach responding in confronting fearful situations. AIMS: The purpose of the present study was to construct and validate a self-report assessment of the tendency towards avoidant or approach responding in fearful situations, the Response to Fearful Situations Scale (RFSS). METHOD AND RESULTS: In Study 1 (n = 241), exploratory factor analysis resulted in two factors, avoidance and approach. Study 2 (n = 423) replicated the two-factor structure and established test-re-test reliability. In Study 3 (n = 44), the RFSS demonstrated predictive validity on a behavioural avoidance task. In Studies 4 (n = 253) and 5 (n = 256), the RFSS was associated with clinical symptoms above existing measures of avoidance. DISCUSSION: These results validate the use of the RFSS as a transdiagnostic measure of avoidance and approach.

Modeling halotropism: a key role for root tip architecture and reflux loop remodeling in redistributing auxin.

A key characteristic of plant development is its plasticity in response to various and dynamically changing environmental conditions. Tropisms contribute to this flexibility by allowing plant organs to grow from or towards environmental cues. Halotropism is a recently described tropism in which plant roots bend away from salt. During halotropism, as in most other tropisms, directional growth is generated through an asymmetric auxin distribution that generates differences in growth rate and hence induces bending. Here, we develop a detailed model of auxin transport in the Arabidopsis root tip and combine this with experiments to investigate the processes generating auxin asymmetry during halotropism. Our model points to the key role of root tip architecture in allowing the decrease in PIN2 at the salt-exposed side of the root to result in a re-routing of auxin to the opposite side. In addition, our model demonstrates how feedback of auxin on the auxin transporter AUX1 amplifies this auxin asymmetry, while a salt-induced transient increase in PIN1 levels increases the speed at which this occurs. Using AUX1-GFP imaging and pin1 mutants, we experimentally confirmed these model predictions, thus expanding our knowledge of the cellular basis of halotropism.