Antigravitropic PIN polarization maintains non-vertical growth in lateral roots.

Lateral roots are typically maintained at non-vertical angles with respect to gravity. These gravitropic setpoint angles are intriguing because their maintenance requires that roots are able to effect growth response both with and against the gravity vector, a phenomenon previously attributed to gravitropism acting against an antigravitropic offset mechanism. Here we show how the components mediating gravitropism in the vertical primary root-PINs and phosphatases acting upon them-are reconfigured in their regulation such that lateral root growth at a range of angles can be maintained. We show that the ability of Arabidopsis lateral roots to bend both downward and upward requires the generation of auxin asymmetries and is driven by angle-dependent variation in downward gravitropic auxin flux acting against angle-independent upward, antigravitropic flux. Further, we demonstrate a symmetry in auxin distribution in lateral roots at gravitropic setpoint angle that can be traced back to a net, balanced polarization of PIN3 and PIN7 auxin transporters in the columella. These auxin fluxes are shifted by altering PIN protein phosphoregulation in the columella, either by introducing PIN3 phosphovariant versions or via manipulation of levels of the phosphatase subunit PP2A/RCN1. Finally, we show that auxin, in addition to driving lateral root directional growth, acts within the lateral root columella to induce more vertical growth by increasing RCN1 levels, causing a downward shift in PIN3 localization, thereby diminishing the magnitude of the upward, antigravitropic auxin flux.

Extracellular ATP targets Arabidopsis RIBONUCLEASE 1 to suppress mycotoxin stress-induced cell death.

Extracellular ATP is a purinergic signal with important functions in regulating plant growth and stress-adaptive responses, including programmed cell death. While signalling events proximate to receptor activation at the plasma membrane have been characterised, downstream protein targets and the mechanism of cell death activation/regulation are unknown. We designed a proteomic screen to identify ATP-responsive proteins in Arabidopsis cell cultures exposed to mycotoxin stress via fumonisin B1 (FB1) application. Arabidopsis RIBONUCLEASE 1 (RNS1) was identified by the screen, and transgenic plants overexpressing native RNS1 showed greater susceptibility to FB1, while a gene knockout rns1 mutant and antisense RNS1 transgenic plants were resistant to FB1-induced cell death. Native RNS1 complemented rns1 mutants and restored the cell death response to FB1, while a catalytically inactive version of the ribonuclease could not. The FB1 resistance of salicylic acid (SA)-depleted nahG-expressing plants was abolished by transformation with native RNS1, but not the catalytically dead version. The mechanism of FB1-induced cell death is activation of RNS1-dependent RNA cleavage, which is blocked by ATP via RNS1 suppression, or enhanced by SA through induction of RNS1 expression. Our study reveals RNS1 as a previously unknown convergence point of ATP and SA signalling in the regulation of stress-induced cell death.

Addressing the mental health needs of learners and nonlearners in an academic medical center during COVID-19.

The coronavirus disease (COVID-19) has impacted life for people throughout the world, especially for those in health care who experience unique stressors. To support the psychological needs of staff, faculty, and learners at a biomedical sciences university, faculty at Baylor College of Medicine created a mental health and wellness support program consisting of multiple behavioral health care pathways, including phone support, a self-guided mental health app, a coping skills group, and individual therapy services. The authors present this program as a model for academic institutions to support the well-being of faculty, staff, and learners.

Isolation of Arabidopsis extracellular ATP binding proteins by affinity proteomics and identification of PHOSPHOLIPASE C-LIKE 1 as an extracellular protein essential for fumonisin B1 toxicity.

ATP is secreted to the extracellular matrix, where it activates plasma membrane receptors for controlling plant growth and stress-adaptive processes. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), was the first plant ATP receptor to be identified but key downstream proteins remain sought after. Here, we identified 120 proteins secreted by Arabidopsis cell cultures and screened them for putative stress-responsive proteins using ATP-affinity purification. We report three Arabidopsis proteins isolated by ATP-affinity: PEROXIDASE 52, SUBTILASE-LIKE SERINE PROTEASE 1.7 and PHOSPHOLIPASE C-LIKE 1. In wild-type Arabidopsis, the expression of genes encoding all three proteins responded to fumonisin B1, a cell death-activating mycotoxin. The expression of PEROXIDASE 52 and PHOSPHOLIPASE C-LIKE 1 was altered in fumonisin B1-resistant salicylic acid induction-deficient (sid2) mutants. Exposure to fumonisin B1 suppressed PHOSPHOLIPASE C-LIKE 1 expression in sid2 mutants, suggesting that the inactivation of this gene might provide mycotoxin tolerance. Accordingly, gene knockout mutants of PHOSPHOLIPASE C-LIKE 1 were resistant to fumonisin B1-induced death. The activation of PHOSPHOLIPASE C-LIKE 1 gene expression by exogenous ATP was not blocked in dorn1 loss-of-function mutants, indicating that DORN1 is not required. Furthermore, exogenous ATP rescued both the wild type and the dorn1 mutants from fumonisin-B1 toxicity, suggesting that different ATP receptor(s) are operational in this process. Our results point to the existence of additional plant ATP receptor(s) and provide crucial downstream targets for use in designing screens to identify these receptors. Finally, PHOSPHOLIPASE C-LIKE 1 serves as a convergence point for fumonisin B1 and extracellular ATP signalling, and functions in the Arabidopsis stress response to fumonisin B1.

Stress-adaptive gene discovery by exploiting collective decision-making of decentralized plant response systems.

Despite having a network of cytoplasmic interconnections (plasmodesmata) facilitating rapid exchange of metabolites and signal molecules, plant cells use the extracellular matrix as an alternative route for cell-cell communication. The need for extracellular signalling in plasmodesmata-networked tissues is baffling. A hypothesis is proposed that this phenomenon defines the plant extracellular matrix as a 'democratic space' for collective decision-making in a decentralized system, similar to quorum-sensing in bacteria. Extracellular communication enables signal integration and coordination across several cell layers through ligand-activated plasma membrane receptors. Recent results from drought stress-adaptive responses and light-mediated signalling in cell death activation show operational utility of this decision-making process. Opportunities are discussed for new innovations in drought gene discovery using platforms targeting the extracellular matrix.

Primary blood-hosts of mosquitoes are influenced by social and ecological conditions in a complex urban landscape.

BACKGROUND: Temperate urban landscapes support persistent and growing populations of Culex and Aedes mosquito vectors. Large urban mosquito populations can represent a significant risk for transmission of emergent arboviral infection. However, even large mosquito populations are only a risk to the animals they bite. The purpose of this study is to identify and assess spatial patterns of host-use in a temperate urban landscape with heterogeneous socio-economic and ecological conditions. RESULTS: Mosquito blood meals were collected from neighborhoods categorized along a socio-economic gradient in Baltimore, MD, USA. Blood meal hosts were identified for two Aedes (Ae. albopictus and Ae. japonicus) and three Culex (Cx. pipiens, Cx. restuans and Cx. salinarius) species. The brown rat (Rattus norvegicus) was the most frequently detected host in both Aedes species and Cx. salinarius. Human biting was evident in Aedes and Culex species and the proportion of human blood meals from Ae. albopictus varied significantly with neighborhood socio-economic status. Aedes albopictus was most likely to feed on human blood hosts (at 50%) in residential blocks categorized as having income above the city median, although there were still more total human bites detected from lower income blocks where Ae. albopictus was more abundant. Birds were the most frequently detected Culex blood hosts but were absent from all Aedes sampled. CONCLUSIONS: This study highlights fine-scale variation in host-use by medically important mosquito vectors and specifically investigates blood meal composition at spatial scales relevant to urban mosquito dispersal and human exposure. Further, the work emphasizes the importance of neighborhood economics and infrastructure management in shaping both the relative abundance of vectors and local blood feeding strategies. The invasive brown rat was an important blood source across vector species and neighborhoods in Baltimore. We show that social and economic conditions can be important predictors of transmission potential in urban landscapes and identify important questions about the role of rodents in supporting urban mosquito populations.

Acoustic and kinetic behaviour of definity in mice exposed to high frequency ultrasound.

Microbubble contrast agents have shown clinical potential for characterising blood flow using 1 to 10 MHz ultrasound; however, scaling their use for similar applications in the mouse with high frequency ultrasound (20 to 60 MHz) has not been addressed. The goal was to determine the utility of microbubbles for mouse imaging with 30 MHz ultrasound by investigating their attenuation and backscatter characteristics as a function of concentration in vitro and dose response in vivo. The agent was exposed to a 30 MHz, 20% bandwidth pulse with a peak negative pressure of 244 kPa. In vitro results showed that the attenuation and backscatter increased linearly for concentrations between 2.8 x 10(6) and 28 x 10(6) bubbles per mL of deionized water. In vivo experiments where performed in the jugular vein of CD-1 mice and time intensity curves were acquired for doses between 10 and 100 microL kg(-1). These doses corresponded to the range of concentrations used in vitro. In vivo results showed that the peak enhancement of the agent increased linearly for doses between 10 and 60 microL kg(-1), the duration of enhancement varied between 200 to 300 s and the integrated enhancement (area under the curve) increased linearly up to 100 microL kg(-1). A maximum enhancement of 13 dB over the blood pool was observed for a dose of 100 microL kg(-1). The intra- and inter-mouse variabilities were 10% to 40% and indicate that further optimisations are required. These results suggest that quantitative contrast flow studies in the mouse using high frequency ultrasound are possible for doses between 10 and 60 microL kg(-1).

Correlates of persistent postconcussional disorder: DSM-IV criteria versus ICD-10.

Controversy surrounding the causation of symptom complaints after mild traumatic brain injury (MTBI) is reflected by the existence of alternative diagnostic criteria for postconcussional syndrome (PCS) in the International Classification of Diseases (ICD) and postconcussional disorder (PCD) in the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Previous studies of persisting symptoms have employed various symptom checklists rather than uniform criteria-based diagnoses. This is the first prospective study of persisting symptom complaints using the formal diagnostic criteria for PCD and PCS and comparing these criteria sets in terms of prevalence, relationship to potential compensation, and emotional/functional status. In this prospective study, an unselected series of adults with uncomplicated MTBI (N = 139) was assessed at 6 months postinjury with a brief neuropsychological battery and measures of psychiatric symptoms/disorders, social support/community integration, health-related quality of life, and global outcome. In parallel analyses, participants with PCD/PCS were compared to those without the disorder. Potential compensation was an equally significant factor in both criteria sets. Persistent PCS criteria were met 3.1 times more frequently than persistent PCD criteria. Significant racial differences in fulfilling PCD/PCS criteria were found. No differences in emotional/functional status patterns or global outcome were found between the criteria sets except for minor dissimilarities in the social/community integration domain. The results demonstrate that despite large differences in the frequency of patients meeting the two diagnostic criteria sets, a clear basis for preferring either the PCD or PCS criteria remains to be determined.

Confirmatory factor structure of the Center for Epidemiologic Studies-Depression scale (CES-D) in mild-to-moderate traumatic brain injury.

PRIMARY OBJECTIVE: The Center for Epidemiologic Studies Depression scale (CES-D) is a frequently-used self-report measure of depressive symptom severity. Brief depression screening measures can be important in the identification and prediction of depression following traumatic brain injury. The objective of this study was to investigate the validity of the CES-D in measuring depressive symptoms in patients with mild-to-moderate TBI as it has been rarely used in neurologically compromised populations. RESEARCH DESIGN: Inception cohort. METHODS AND PROCEDURES: The CES-D was administered to 340 participants with mild-to-moderate TBI at 3-months post-injury. MAIN OUTCOMES AND RESULTS: Confirmatory factor analysis of the CES-D indicated that the data are a reasonable fit similar to that of Radloff 's original 4-factor model. CONCLUSIONS: These findings suggest that the CES-D may be appropriate for use in patients with mild-to-moderate TBI.

Diagnostic criteria for postconcussional syndrome after mild to moderate traumatic brain injury.

This study evaluated the prevalence and specificity of diagnostic criteria for postconcussional syndrome (PCS) in 178 adults with mild to moderate traumatic brain injury (TBI) and 104 with extracranial trauma. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and International Classification of Diseases (ICD-10) criteria for PCS were evaluated 3 months after injury. The results showed that prevalence of PCS was higher using ICD-10 (64%) than DSM-IV criteria (11%). Specificity to TBI was limited because PCS criteria were often fulfilled by patients with extracranial trauma. The authors conclude that further refinement of the DSM-IV and ICD-10 criteria for PCS is needed before these criteria are routinely employed.

Postconcussional disorder: Are the DSM-IV criteria an improvement over the ICD-10?

Little is known about the characteristics and outcomes of patients diagnosed with postconcussional disorder (PCD) under the provisionally proposed criteria in the DSM-IV and how they differ from patients diagnosed with postconcussional syndrome (PCS) under the International Classification of Diseases, 10th edition clinical (ICD-10) criteria. This study investigated differences in outcome based on a diagnosis of PCD (DSM-IV) versus PCS (ICD-10 clinical criteria) as to which criteria set might be preferred for clinical practice. A consecutive series of adult patients with mild (N = 319) to moderate (N = 21) traumatic brain injury was assessed at 3 months postinjury with a brief neuropsychological battery and measures of specific outcome domains. In two separate series of analyses, patients with PCD were compared with those without PCD, and those with PCS were compared with those without PCS. Although the two criteria sets resulted in markedly different incidence rates, there was no substantial pattern of differences between the DSM-IV and ICD-10 in the outcome domains of psychiatric symptoms and disorders, social and community integration, health-related quality of life, or global outcome as measured by the Glasgow Outcome Scale-Extended. In spite of significant differences between the two diagnostic criteria sets and different incidence rates for PCD/PCS, outcome in all measured domains was very similar at 3 months postinjury. There is no compelling evidence, based on these outcome domains, to suggest which of the two diagnostic criteria sets should be clinically preferred.

Predicting depression following mild traumatic brain injury.

CONTEXT: Minimizing negative consequences of major depression following traumatic brain injury is an important public health objective. Identifying high-risk patients and referring them for treatment could reduce morbidity and loss of productivity. OBJECTIVE: To develop a model for early screening of patients at risk for major depressive episode at 3 months after traumatic brain injury. DESIGN: Prediction model using receiver operating characteristic curve. SETTING: Level I trauma center in a major metropolitan area. PARTICIPANTS: Prospective cohort of 129 adults with mild traumatic brain injury. MAIN OUTCOME MEASURES: Center for Epidemiologic Studies Depression Scale score and current major depressive episode module of the Structured Clinical Interview for the DSM-IV. RESULTS: A prediction model including higher 1-week Center for Epidemiologic Studies Depression Scale score, older age, and computed tomographic scans of intracranial lesions yielded 93% sensitivity and 62% specificity. CONCLUSION: This study supports the feasibility of identifying patients with mild traumatic brain injury who are at high risk for developing major depressive episode by 3 months' postinjury, which could facilitate selective referral for potential treatment and reduction of negative outcomes.

Limited agreement between criteria-based diagnoses of postconcussional syndrome.

The objectives of this study were to compare diagnoses of postconcussional syndrome between the International Classification of Diseases, 10th revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). The patient sample was comprised of 178 adults with mild-moderate traumatic brain injury (TBI). The study design was inception cohort, and the main outcome measure was a structured interview 3 months after injury. The results were that, despite concordance of DSM-IV and ICD-10 symptom criteria (kappa=0.73), agreement between overall DSM-IV and ICD-10 diagnoses was slight (kappa=0.13) because fewer patients met the DSM-IV cognitive deficit and clinical significance criteria. Agreement between DSM-IV postconcussional disorder and ICD-10 postconcussional syndrome appears limited by different prevalences and thresholds.