The intrinsic substrate specificity of the human tyrosine kinome.

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1-3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4-7. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review.

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.

Psychosocial stressors of adolescents with E-cigarette, or vaping, product-use associated lung injury: A qualitative study.

BACKGROUND AND OBJECTIVES: Adolescent electronic cigarette (EC) use has reached epidemic rates and has been linked to numerous mental health and psychosocial stressors (PS). There is limited qualitative data on PS for adolescents with e-cigarette, or vaping, product-use associated lung injury (EVALI), a severe complication of EC use. METHODS: All patients hospitalized at Children's Medical Center in Dallas, Texas from 2018 to 2022 and met CDC case definitions for EVALI were included in the analysis. PS were extracted from the electronic health record and analyzed for recurring themes using the HEADSS assessment as a framework. Results were summarized using descriptive statistics, and representative quotations were selected to highlight each theme. RESULTS: Forty-three adolescents (mean age 16.3 years; 62.8 % male; 39.5 % Non-Hispanic White, 60.5 % Hispanic) were included in the analysis, and 40 (93 %) reported PS. The most common themes were family (51 %; "restraining order issued against 28-year-old brother"), polysubstance use (77 %; "experimenting with…ecstasy, LSD, CCC, misusing Adderall"), and mental health (63 %; "has been suicidal since he was 'a toddler'"). Less commonly, patients reported PS related to peers (28 %; "spending the entire day at the cemetery where his best friend was buried"), school (49 %; "attending his second alternative school"), and the legal system (19 %; "placed in juvenile detention, released, and will be on probation"). CONCLUSIONS: Adolescents with EVALI had PS that were chronic, severe, and involving multiple domains. These findings emphasize the importance of psychosocial screening in adolescents and coordinating interdisciplinary care with mental health and social services.

Timbral effects on consonance disentangle psychoacoustic mechanisms and suggest perceptual origins for musical scales.

The phenomenon of musical consonance is an essential feature in diverse musical styles. The traditional belief, supported by centuries of Western music theory and psychological studies, is that consonance derives from simple (harmonic) frequency ratios between tones and is insensitive to timbre. Here we show through five large-scale behavioral studies, comprising 235,440 human judgments from US and South Korean populations, that harmonic consonance preferences can be reshaped by timbral manipulations, even as far as to induce preferences for inharmonic intervals. We show how such effects may suggest perceptual origins for diverse scale systems ranging from the gamelan's slendro scale to the tuning of Western mean-tone and equal-tempered scales. Through computational modeling we show that these timbral manipulations dissociate competing psychoacoustic mechanisms underlying consonance, and we derive an updated computational model combining liking of harmonicity, disliking of fast beats (roughness), and liking of slow beats. Altogether, this work showcases how large-scale behavioral experiments can inform classical questions in auditory perception.

The Influences of Supportive Leadership and Family Social Support on Female Managers' Organizational Effectiveness: The Mediating Effect of Positive Spillover between Work and Family.

This study aims to examine the influence of supportive leadership and family social support for female managers on organizational effectiveness and test the mediating effect of positive spillover between work and family (PSWF). This study utilized data of 974 married female managers from the 6th Korean Female Manager Panel (KWMP) survey to analyze the relationship between the latent variables. Hypotheses of this study were tested using Structural Equation Model Analysis (SEM). This study found that supportive leadership and PSWF have a positive influence on female managers' organizational effectiveness. However, family support had no significant effect on the organizational effectiveness of female managers. The analysis showed that supportive leadership and family social support positively influenced female manager's PSWF. Also, PSWF mediated the relationship between family social support and organizational effectiveness as well as between supportive leadership and organizational effectiveness. This study provides a better understanding of PSWF as a mediator between family social support and organizational effectiveness. Contrary to previous studies that focused on the negative effects of work-family conflicts, this study highlighted the role of PSWF, justifying the need for governmental or organizational programs to increase PSWF.

Large-scale iterated singing experiments reveal oral transmission mechanisms underlying music evolution.

Speech and song have been transmitted orally for countless human generations, changing over time under the influence of biological, cognitive, and cultural pressures. Cross-cultural regularities and diversities in human song are thought to emerge from this transmission process, but testing how underlying mechanisms contribute to musical structures remains a key challenge. Here, we introduce an automatic online pipeline that streamlines large-scale cultural transmission experiments using a sophisticated and naturalistic modality: singing. We quantify the evolution of 3,424 melodies orally transmitted across 1,797 participants in the United States and India. This approach produces a high-resolution characterization of how oral transmission shapes melody, revealing the emergence of structures that are consistent with widespread musical features observed cross-culturally (small pitch sets, small pitch intervals, and arch-shaped melodic contours). We show how the emergence of these structures is constrained by individual biases in our participants-vocal constraints, working memory, and cultural exposure-which determine the size, shape, and complexity of evolving melodies. However, their ultimate effect on population-level structures depends on social dynamics taking place during cultural transmission. When participants recursively imitate their own productions (individual transmission), musical structures evolve slowly and heterogeneously, reflecting idiosyncratic musical biases. When participants instead imitate others' productions (social transmission), melodies rapidly shift toward homogeneous structures, reflecting shared structural biases that may underpin cross-cultural variation. These results provide the first quantitative characterization of the rich collection of biases that oral transmission imposes on music evolution, giving us a new understanding of how human song structures emerge via cultural transmission.

Aligning NIH's existing data use restrictions to the GA4GH DUO standard.

It is widely accepted that large-scale genomic data (e.g., whole-genome sequencing, whole-exome sequencing, and genome-wide association study data) be shared through a controlled-access mechanism. This protects the privacy of research participants and ensures downstream uses of data align with participants' informed consent regarding future sharing of their data. In 2019, GA4GH approved the Data Use Ontology (DUO) standard to define data use terms with machine-readable representations to represent how a dataset can be used. We endeavored to determine the parity of existing data use restrictions ("Data Use Limitations" [DULs]) for datasets registered in the National Institutes of Health database for Genotypes and Phenotypes (dbGaP) with the DUO standard. We found substantial (93%) parity between the dbGaP DULs (n = 3,575) and DUO. This study demonstrates the comprehensiveness of the DUO standard and encourages data stewards to standardize data use restrictions in machine-readable formats to facilitate data sharing.

Here comes the sun: music features of popular songs reflect prevailing weather conditions.

We examine associations between prevailing weather conditions and music features in all available songs that reached the United Kingdom weekly top charts throughout a 67-year period (1953-2019), comprising 23 859 unique entries. We found that music features reflecting high intensity and positive emotions were positively associated with daily temperatures and negatively associated with rainfall, whereas music features reflecting low intensity and negative emotions were not related to weather conditions. These results held true after controlling for the mediating effects of year (temporal patterns) and month (seasonal patterns). However, music-weather associations were more nuanced than previously assumed by linear models, becoming only meaningful in those months and seasons when changes in weather were the most notable. Importantly, the observed associations depended on the popularity of the music: while songs in the top 10 of the charts exhibited the strongest associations with weather, less popular songs showed no relationship. This suggests that a song's fit with prevailing weather may be a factor pushing a song into the top of the charts. Our work extends previous research on non-musical domains (e.g. finance, crime, mental health) by showing that large-scale population-level preferences for cultural phenomena (music) are also influenced by broad environmental factors that exist over long periods of time (weather) via mood-regulation mechanisms. We discuss these results in terms of the limited nature of correlational studies and cross-cultural generalizability.

Clinical manifestations of EVALI in adolescents before and during the COVID-19 pandemic.

INTRODUCTION: E-cigarette, or vaping, product use-associated lung injury (EVALI) results from inhaling the aerosol of e-cigarettes and has similar clinical features to coronavirus disease 2019 (COVID-19). EVALI case counts since the declaration of the COVID-19 pandemic is unknown. METHODS: A retrospective electronic health record chart review of adolescents hospitalized at one institution with EVALI was conducted. Clinical characteristics and hospital course of patients hospitalized during the pandemic were compared to those prepandemic. RESULTS: The clinical presentation of adolescents hospitalized prior-to (n = 19) and during the COVID-19 pandemic (n = 22) were similar with respect to constitutional, respiratory, and gastrointestinal symptoms. All patients hospitalized during the pandemic were tested for COVID-19 at least once. Only one patient had a positive SARS-CoV-2 RT-PCR test result. Thirty-one out of 39 patients treated with corticosteroids had clinical improvement within 24 h (79%). Patients hospitalized during the pandemic had a shorter median length of stay (5 vs. 7 days, p < 0.01), and were less often discharged with home oxygen (1 vs. 6 patients, p = 0.04). Pulmonary function tests improved pre- to postcorticosteroid treatment and postcorticosteroid to follow-up. CONCLUSIONS: Eliciting a history of vaping in adolescents presenting with constitutional, respiratory, and gastrointestinal symptoms is important to identify EVALI cases, which have continued throughout the COVID-19 pandemic. A shorter length of stay with less need for mechanical ventilation and home oxygen in adolescents hospitalized during the pandemic may reflect increased familiarity with EVALI characteristics. Corticosteroids led to clinical and pulmonary function improvement.

Neighborhood Characteristics and the Burden of E-Cigarette, or Vaping, Product Use-Associated Lung Injury: An Ecological Comparison Study.

Purpose: E-cigarette, or vaping, product use-associated lung injury (EVALI) is a severe consequence of vaping first described in 2019. Investigating associations between neighborhood-level characteristics and EVALI cases is an important step in identifying at-risk communities to implement future targeted prevention programs. Methods: We retrospectively identified 41 adolescents <19 years hospitalized for treatment for EVALI at Children's Medical Center Dallas from December 2018 to June 2021. Patient ZIP codes were extracted from the electronic medical record and were compared with Dallas area ZIP codes containing no EVALI cases. Socioeconomic status (SES) characteristics were obtained from the 2019 American Community Survey, and they were mapped for ZIP codes using ESRI ArcMap geospatial processing software. A parallel analysis was conducted utilizing data of adolescents hospitalized with appendicitis. Results: Ninety-five percent of our cohort used tetrahydrocannabinol-containing products, and 66% obtained their vaping products from informal sources. EVALI cases were less likely to reside in higher SES ZIP codes as measured by the proportion of the population with at least a high school education (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.99), access to broadband access (OR: 0.95, 95% CI: 0.91-0.99), and private health insurance (OR: 0.97, 95% CI: 0.95-0.99). Alternatively, they were more likely to reside in lower SES ZIP codes as measured by proportion of the population without any health insurance (OR: 1.07, 95% CI: 1.01-1.12). No neighborhood level low SES characteristics were associated with appendicitis hospitalizations. Conclusions: Although small in magnitude, EVALI cases were associated with lower SES ZIP codes but not with vape shop density.

A Millimeter-Scale Soft Robot for Tissue Biopsy Procedures.

While interest in soft robotics as surgical tools has grown due to their inherently safe interactions with the body, their feasibility is limited in the amount of force that can be transmitted during procedures. This is especially apparent in minimally invasive procedures where millimeter-scale devices are necessary for reaching the desired surgical site, such as in interventional bronchoscopy. To leverage the benefits of soft robotics in minimally invasive surgery, a soft robot with integrated tip steering, stabilization, and needle deployment capabilities is proposed for lung tissue biopsy procedures. Design, fabrication, and modeling of the force transmission of this soft robotic platform allows for integration into a system with a diameter of 3.5 mm. Characterizations of the soft robot are performed to analyze bending angle, force transmission, and expansion during needle deployment. In-vitro experiments of both the needle deployment mechanism and fully integrated soft robot validate the proposed workflow and capabilities in a simulated surgical setting.

The Timbre Perception Test (TPT): A new interactive musical assessment tool to measure timbre perception ability.

To date, tests that measure individual differences in the ability to perceive musical timbre are scarce in the published literature. The lack of such tool limits research on how timbre, a primary attribute of sound, is perceived and processed among individuals. The current paper describes the development of the Timbre Perception Test (TPT), in which participants use a slider to reproduce heard auditory stimuli that vary along three important dimensions of timbre: envelope, spectral flux, and spectral centroid. With a sample of 95 participants, the TPT was calibrated and validated against measures of related abilities and examined for its reliability. The results indicate that a short-version (8 minutes) of the TPT has good explanatory support from a factor analysis model, acceptable internal reliability (α = .69, ωt = .70), good test-retest reliability (r = .79) and substantial correlations with self-reported general musical sophistication (ρ = .63) and pitch discrimination (ρ = .56), as well as somewhat lower correlations with duration discrimination (ρ = .27), and musical instrument discrimination abilities (ρ = .33). Overall, the TPT represents a robust tool to measure an individual's timbre perception ability. Furthermore, the use of sliders to perform a reproductive task has shown to be an effective approach in threshold testing. The current version of the TPT is openly available for research purposes.

Signals through music and dance: Perceived social bonds and formidability on collective movement.

Previous studies have suggested that the prosocial effects which arise following synchrony during music and dance may serve as a mechanism for people to bond socially. However, other research has proposed that synchrony could be a mechanism for signalling coalition to demonstrate fitness, which is expressed by a group's ability to effectively cooperate. In the present studies, we compared these theories by showing participants realistic virtual avatars engaged in different forms of group dance and then examining their perceived social closeness and formidability of the dance groups. We conducted two studies to assess the perceptual influence of movement type (unison vs. coordinated) and movement quality (temporally aligned vs. temporally misaligned). We predicted that the difference in the ratings of closeness and formidability would only emerge when the groups align movements, and this was supported. We also hypothesised that unison movement would better signal formidability while coordinated movement would better signal a group's social closeness. However, unison movement yielded higher ratings than coordinated movement for both formidability and social closeness, suggesting that a group should move in complete synchrony to maximally indicate their fitness and social bonds.

The Impact of Body Weight Change on Bone Mineral Density of the Lumbar Spine in Perimenopausal Women: A Retrospective, One-year Follow-up Study.

BACKGROUND: Low body weight was one of the risk factors of osteoporosis. Little is known about the correlation between body weight change and bone mineral density (BMD) in Korean women. Therefore, this study was designed to reveal the impact of body weight change on BMD of the lumbar spine in perimenopausal women. METHODS: 105 healthy perimenopausal women aged between 44 and 50 years old were enrolled from August 2002 to March 2009. BMD was measured by dual energy X-ray absorptiometry. Partial correlation coefficients between body weight change and BMD change were calculated after the adjustments for several variables. BMD changes among groups based on BMI and the percentage change in body weight during 1-year follow-up period were compared. RESULTS: At both baseline and year 1, BMD of lumbar spine tended to be associated more with body weight. There was a significant association between body weight change and BMD change in lumbar spine during 1-year follow-up period. The weight gain group relatively showed an increase in BMD of lumbar spines than weight loss group. There was no BMD change in BMI less than 23 kg/m(2) group, but in case of BMI more than 23 kg/m(2) group, BMD in weight gain group increased more than the weight maintaining group. CONCLUSION: This study demonstrated that body weight change is associated with change in BMD of lumbar spine in perimenopausal women especially if they are overweight.