Identification of plant transcriptional activation domains.

Gene expression in Arabidopsis is regulated by more than 1,900 transcription factors (TFs), which have been identified genome-wide by the presence of well-conserved DNA-binding domains. Activator TFs contain activation domains (ADs) that recruit coactivator complexes; however, for nearly all Arabidopsis TFs, we lack knowledge about the presence, location and transcriptional strength of their ADs1. To address this gap, here we use a yeast library approach to experimentally identify Arabidopsis ADs on a proteome-wide scale, and find that more than half of the Arabidopsis TFs contain an AD. We annotate 1,553 ADs, the vast majority of which are, to our knowledge, previously unknown. Using the dataset generated, we develop a neural network to accurately predict ADs and to identify sequence features that are necessary to recruit coactivator complexes. We uncover six distinct combinations of sequence features that result in activation activity, providing a framework to interrogate the subfunctionalization of ADs. Furthermore, we identify ADs in the ancient AUXIN RESPONSE FACTOR family of TFs, revealing that AD positioning is conserved in distinct clades. Our findings provide a deep resource for understanding transcriptional activation, a framework for examining function in intrinsically disordered regions and a predictive model of ADs.

Protein Charge Neutralization Is the Proximate Driver Dynamically Tuning Reflectin Assembly.

Reflectin is a cationic, block copolymeric protein that mediates the dynamic fine-tuning of color and brightness of light reflected from nanostructured Bragg reflectors in iridocyte skin cells of squids. In vivo, the neuronally activated phosphorylation of reflectin triggers its assembly, driving osmotic dehydration of the membrane-bounded Bragg lamellae containing the protein to simultaneously shrink the lamellar thickness and spacing while increasing their refractive index contrast, thus tuning the wavelength and increasing the brightness of reflectance. In vitro, we show that the reduction in repulsive net charge of the purified, recombinant reflectin-either (for the first time) by generalized anionic screening with salt or by pH titration-drives a finely tuned, precisely calibrated increase in the size of the resulting multimeric assemblies. The calculated effects of phosphorylation in vivo are consistent with these effects observed in vitro. The precise proportionality between the assembly size and charge neutralization is enabled by the demonstrated rapid dynamic arrest of multimer growth by a continual, equilibrium tuning of the balance between the protein's Coulombic repulsion and short-range interactive forces. The resulting stability of reflectin assemblies with time ensures a reciprocally precise control of the particle number concentration, encoding a precise calibration between the extent of neuronal signaling, osmotic pressure, and the resulting optical changes. The charge regulation of reflectin assembly precisely fine-tunes a colligative property-based nanostructured biological machine. A physical mechanism is proposed.

Y-Site Compatibility of Intravenous Levetiracetam With Commonly Used Critical Care Medications.

Purpose: Levetiracetam is an antiepileptic medication commonly used in critical care areas for seizure treatment or prophylaxis. Compatibility data of levetiracetam with other critical care medications are limited, which can make administration challenging. This study aims to assess the physical Y-site compatibility of intravenous levetiracetam with some other commonly used critical care medications. Methods: Y-site administration was simulated by independently mixing levetiracetam with each of 11 selected medications in a 4-dram, colorless, screw-cap, glass vial, at a 1:1 ratio. Clinically used concentrations of each medication were compounded in 0.9% sodium chloride following United States Pharmacopeia chapter 797 standards. Physical compatibility was observed and assessed at 0, 15, and 30 minutes after mixing. Medication mixtures were considered physically incompatible if there was visual evidence of color change, gas evolution, haze, or particulate formation, pH change >10%, or if they had an absorbance value >0.010 A. Results: No evidence of physical incompatibility was observed during simulated Y-site testing with cisatracurium 1 mg/mL, dexmedetomidine 4 µg/mL, fosphenytoin 15 mg PE/mL, norepinephrine 16 mg/mL, norepinephrine 32 mg/mL, norepinephrine 64 mg/mL, piperacillin-tazobactam 33.75 mg/mL, propofol 10 mg/mL, vancomycin 5 mg/mL, or vasopressin 1 unit/mL when tested in 0.9% sodium chloride. Levetiracetam was incompatible with piperacillin-tazobactam 45 mg/mL. Conclusion: Levetiracetam 5 mg/mL in 0.9% sodium chloride was found to be physically compatible for 30 minutes with 10 of the 11 medications tested during simulated Y-site administration.

Assessment of caregiver expectations of physician communication in a pediatric setting.

BACKGROUND: In pediatrics, communication often occurs through an intermediary such as a caregiver. The goal of this study is to assess caregiver communication expectations and determine if meeting expectations influences caregiver satisfaction or instruction retention. METHODS: A survey study was performed at the Children's Hospital of Philadelphia. Before the visit, caregivers completed a survey on communication expectations, Caregiver Expected Kalamazoo Essential Elements Communication Checklist (Caregiver Expected KEECC). After the visit, caregivers were surveyed on their perception of physician communication (Caregiver Perceived KEECC) and satisfaction. Caregivers were contacted 1 week after the clinic visit to assess instruction retention. Meeting of caregiver expectation was calculated by the difference between Caregiver Expected and Caregiver Perceived KEECC scores. RESULTS: 112 caregivers participated in the study. There was no significant difference in Caregiver Expected KEECC versus Caregiver Perceived KEECC score (4.39 vs 4.56). Caregiver communication expectations were exceeded in 51.5% of the visits. Communication expectations were exceeded more among caregivers with at a college education (p <  0.01) and more among White caregivers (p <  0.01). The average caregiver satisfaction score with the clinic visit was 4.67. Higher satisfaction scores were observed in caregivers who had their communication expectations met or exceeded (p <  0.01). Caregivers with communication expectations exceeded had higher percentage recall of physician instructions (p <  0.01). CONCLUSIONS: Caregiver communication expectations may be influenced by demographic factors. Communication expectation affects visit outcomes including caregiver satisfaction and instruction retention. Therefore, physicians need to be cognizant of caregiver communication expectations, which can impact quality of the healthcare experience.

Noise-invariant neurons in the avian auditory cortex: hearing the song in noise.

Given the extraordinary ability of humans and animals to recognize communication signals over a background of noise, describing noise invariant neural responses is critical not only to pinpoint the brain regions that are mediating our robust perceptions but also to understand the neural computations that are performing these tasks and the underlying circuitry. Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant signal in a range of listening conditions have yet to be discovered. Here we found neurons in a secondary area of the avian auditory cortex that exhibit noise-invariant responses in the sense that they responded with similar spike patterns to song stimuli presented in silence and over a background of naturalistic noise. By characterizing the neurons' tuning in terms of their responses to modulations in the temporal and spectral envelope of the sound, we then show that noise invariance is partly achieved by selectively responding to long sounds with sharp spectral structure. Finally, to demonstrate that such computations could explain noise invariance, we designed a biologically inspired noise-filtering algorithm that can be used to separate song or speech from noise. This novel noise-filtering method performs as well as other state-of-the-art de-noising algorithms and could be used in clinical or consumer oriented applications. Our biologically inspired model also shows how high-level noise-invariant responses could be created from neural responses typically found in primary auditory cortex.

The Effects of Burnout, Team Support, and Perceived Leader Effectiveness on Career Intentions Among JAG Corps Personnel.

INTRODUCTION: Destructive interpersonal relationships at work may result in negative feelings among employees that hinder personal and organizational productivity, which may also result in high levels of job disengagement and subsequent career turnover intentions. Leaders play a key role in creating work environments conducive to optimizing employee performance, organizational culture, and workplace well-being. Social support, which may include support from one's supervisor, colleagues, and loved ones, has been shown to reduce strains and perceived stressors at work. In the Army, the Judge Advocate General's Corps (JAGC) personnel have a unique position as lawyers and legal staff and have been shown to have high rates of burnout. To promote soldier health, well-being, and career longevity, it is important to understand the impact interpersonal relationships have on career intentions. The current study assesses the relationship between perceived leadership effectiveness and career intentions as moderated by burnout measured by job disengagement and team care activities in JAGC personnel. MATERIALS AND METHODS: The Walter Reed Army Institute of Research conducted a survey to understand factors affecting the well-being of the JAGC's soldier and civilian personnel as requested by the JAGC. JAGC personnel were administered several questionnaires covering a range of work and mental health topics. Job disengagement, career intentions, team care activities, and general leadership were assessed. A total of 831 JAGC personnel completed the survey, the majority (92%) of which were soldiers. Among soldiers, first lieutenants and captains (∼49%) were the majority. The sample largely consisted of men (∼63%), White individuals (∼76%), married individuals, (70%), and individuals with graduate degrees (∼81%). RESULTS: One in four participants (∼29%) experienced high levels of disengagement, with their work. Over two-thirds of participants agreed that their immediate supervisor is an effective leader. When asked about career intentions, the majority of JAGC participants (54%) indicated that they would probably or definitely stay in the JAGC until retirement. Ordinal logistic regressions were conducted to assess the relationship between perceived leader effectiveness and career intentions, assessing the main effects of job disengagement and team care activities, and the interactions between those variables. No interaction effects were found to be significant, but main effects for perceived leader effectiveness were significant. CONCLUSIONS: JAGC personnel reported higher levels of job disengagement for those with career intentions that were undecided or definitely leaving the JAGC after their current obligation. Those who were engaged in more team care activities had lower levels of disengagement. While the majority of the JAGC participants indicated career intentions to stay in the JAGC until retirement, increasing perceived effectiveness of leaders could help increase attrition and career intentions to stay in the JAGC beyond one's current obligation.

Attributions to discrimination in multiracial contexts: Isolating the effect of target group membership.

Historically, psychological models of how people make judgments of discrimination have relied on a binary conceptualization of intergroup relations, making it unclear how people make judgments of discrimination in diverse, multigroup contexts. We propose that groups can vary in the extent to which they fit the prototype for targets of discrimination and that this variation influences judgments of discrimination in ambiguous circumstances. The present research examined attributions to discrimination when job applicants are rejected for a white-collar position. People consistently made more attributions to discrimination (ATDs) when managers rejected Black American as compared to Asian American job applicants, and when managers rejected Asian American as compared to White American job applicants. People also made more ATDs for rejected Black American as compared to Latino American applicants, but ATDs were similar for Latino and Asian American applicants. Overall, similar patterns were observed in majority White American samples and a Black/African American sample; only an Asian American sample did not make more ATDs for rejected Black than Asian American applicants. Six experiments (N = 2,321) found strong support for the relative fit hypothesis and suggest that, in a white-collar employment context, White Americans are a distant fit to the prototype for targets of discrimination, Asian and Latino Americans are an intermediate fit, and Black Americans are a close fit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Unsupervised formation of vocalization-sensitive neurons: a cortical model based on short-term and homeostatic plasticity.

The discrimination of complex auditory stimuli relies on the spatiotemporal structure of spike patterns arriving in the cortex. While recordings from auditory areas reveal that many neurons are highly selective to specific spatiotemporal stimuli, the mechanisms underlying this selectivity are unknown. Using computer simulations, we show that selectivity can emerge in neurons in an entirely unsupervised manner. The model is based on recurrently connected spiking neurons and synapses that exhibit short-term synaptic plasticity. During a developmental stage, spoken digits were presented to the network; the only type of long-term plasticity present was a form of homeostatic synaptic plasticity. From an initially unresponsive state, training generated a high percentage of neurons that responded selectively to individual digits. Furthermore, units within the network exhibited a cardinal feature of vocalization-sensitive neurons in vivo: differential responses between forward and reverse stimulus presentations. Direction selectivity deteriorated significantly, however, if short-term synaptic plasticity was removed. These results establish that a simple form of homeostatic plasticity is capable of guiding recurrent networks into regimes in which complex stimuli can be discriminated. In addition, one computational function of short-term synaptic plasticity may be to provide an inherent temporal asymmetry, thus contributing to the characteristic forward-reverse selectivity.

Review of interruptions in a pediatric subspecialty outpatient clinic.

INTRODUCTION: The objective of this study was to describe interruptions in the pediatric ambulatory setting and to assess their impact on perceived physician communication, patient satisfaction and recall of provided physician instructions. METHODS: An observational study was performed at the Children's Hospital of Philadelphia, Pediatric Gastroenterology clinic. Participation consisted of video recording the clinic visit and the caregiver completed post-visit surveys on communication and satisfaction. Video recordings were coded for interruptions, which were divided into 3 main categories: Visit Associated, Pediatric Associated, and Unanticipated. An interruption rate was calculated and correlated with the following outcome variables to assess the impact of interruptions: caregiver satisfaction, caregiver perception on the quality of physician communication, and caregiver instruction recall. RESULTS: There were 675 interruptions noted in the 81 clinic visits, with an average of 7.96 (σ = 7.68) interruptions per visit. Six visits had no interruptions. The Patient was the most frequent interrupter. Significantly higher interruption rates occurred in clinic visits with younger patients (<7 years old) with most of the interruptions being Pediatric Associated interruptions. There was minimal correlation between the clinic visit interruption rate and caregiver satisfaction with the communication, caregiver perception of quality of communication, or caregiver instruction recall rate. CONCLUSION: The effect of interruptions on the pediatric visit remains unclear. Interruptions may be part of the communication process to ensure alignment of the patient's agenda. Additional studies are needed to help determine the impact of interruptions and guide medical education on patient communication.

A Randomized Trial of Voice-Generated Inpatient Progress Notes: Effects on Professional Fee Billing.

BACKGROUND: Prior evaluations of automated speech recognition (ASR) to create hospital progress notes have not analyzed its effect on professional revenue billing codes. As ASR becomes a more common method of entering clinical notes, clinicians, hospital administrators, and payers should understand whether this technology alters charges associated with inpatient physician services. OBJECTIVES: This study aimed to measure the difference in professional fee charges between using voice and keyboard to create inpatient progress notes. METHODS: In a randomized trial of a novel voice with ASR system, called voice-generated enhanced electronic note system (VGEENS), to generate physician notes, we compared 1,613 notes created using intervention (VGEENS) or control (keyboard with template) created by 31 physicians. We measured three outcomes, as follows: (1) professional fee billing levels assigned by blinded coders, (2) number of elements within each note domain, and (3) frequency of organ system evaluations documented in review of systems (ROS) and physical exam. RESULTS: Participants using VGEENS generated a greater portion of high-level (99233) notes than control users (31.8 vs. 24.3%, p < 0.01). After adjustment for clustering by author, the finding persisted; intervention notes were 1.43 times more likely (95% confidence interval [CI]: 1.14-1.79) to receive a high-level code. Notes created using voice contained an average of 1.34 more history of present illness components (95% CI: 0.14-2.54) and 1.62 more review of systems components (95% CI: 0.48-2.76). The number of physical exam components was unchanged. CONCLUSION: Using this voice with ASR system as tested slightly increases documentation of patient symptom details without reliance on copy and paste and may raise physician charges. Increased provider reimbursement may encourage hospital and provider group to offer use of voice and ASR to create hospital progress notes as an alternative to usual methods.

Decoding the Semantic Content of Natural Movies from Human Brain Activity.

One crucial test for any quantitative model of the brain is to show that the model can be used to accurately decode information from evoked brain activity. Several recent neuroimaging studies have decoded the structure or semantic content of static visual images from human brain activity. Here we present a decoding algorithm that makes it possible to decode detailed information about the object and action categories present in natural movies from human brain activity signals measured by functional MRI. Decoding is accomplished using a hierarchical logistic regression (HLR) model that is based on labels that were manually assigned from the WordNet semantic taxonomy. This model makes it possible to simultaneously decode information about both specific and general categories, while respecting the relationships between them. Our results show that we can decode the presence of many object and action categories from averaged blood-oxygen level-dependent (BOLD) responses with a high degree of accuracy (area under the ROC curve > 0.9). Furthermore, we used this framework to test whether semantic relationships defined in the WordNet taxonomy are represented the same way in the human brain. This analysis showed that hierarchical relationships between general categories and atypical examples, such as organism and plant, did not seem to be reflected in representations measured by BOLD fMRI.