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Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

The lexicon of emotion words is fundamental to interpersonal communication. To examine how emotion word acquisition interacts with societal context, the present study investigated emotion word development in three groups of child Korean users aged 4-13 years: those who use Korean primarily outside the home as a majority language (MajKCs) or inside the home as a minority language (MinKCs), and those who use Korean both inside and outside the home (KCs). These groups, along with a group of L1 Korean adults, rated the emotional valence of 61 Korean emotion words varying in frequency, valence, and age of acquisition. Results showed KCs, MajKCs, and MinKCs all converging toward adult-like valence ratings by ages 11-13 years; unlike KCs and MajKCs, however, MinKCs did not show age-graded development and continued to diverge from adults in emotion word knowledge by these later ages. These findings support the view that societal context plays a major role in emotion word development, offering one reason for the intergenerational communication difficulties reported by immigrant families.

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.

BackgroundMuscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles.MethodsEight muscles from 10 independent human cadaver hips were used in this study (n = 80 muscles). Architectural measurements were made on pectineus, piriformis, gemelli, obturators, quadratus femoris, and gluteus minimus. Muscle mass, fiber length, sarcomere length, and pennation angle were used to calculate the normalized muscle fiber length, which defines excursion, and physiological cross-sectional area (PCSA), which defines force-producing capacity.ResultsGluteus minimus had the largest PCSA (8.29 cm2) followed by obturator externus (4.54 cm2), whereas superior gemellus had the smallest PCSA (0.68 cm2). Fiber lengths clustered into long (pectineus - 10.38 cm and gluteus minimus - 10.30 cm), moderate (obturator internus - 8.77 cm and externus - 8.04 cm), or short (inferior gemellus - 5.64 and superior gemellus - 4.85). There were no significant differences among muscles in pennation angle which were all nearly zero. When the gemelli and obturators were considered as a single functional unit, their collective PCSA (10.00 cm2) exceeded that of gluteus minimus as a substantial force-producing group.ConclusionsThe key findings are that these muscles have relatively small individual PCSAs, short fiber lengths, and low pennation angles. The large collective PCSA and short fiber lengths of the gemelli and obturators suggest that they primarily play a stabilizing role rather than a joint rotating role.

Study designRetrospective Review.ObjectivesCompare clinical outcomes and radiographic correction of adult degenerative scoliosis (ADS) patients treated with lateral lumbar interbody fusion (LLIF), combined either with percutaneous (no laminectomy) versus open laminectomy/pedicle screw instrumentation.MethodsTwenty-two ADS patients undergoing combined LLIF and posterior instrumentation were divided into two groups: thirteen patients underwent LLIF with open laminectomy and posterior pedicle instrumentation (Group-1, six revision); nine patients underwent LLIF with percutaneous pedicle instrumentation (no decompression) (Group-2). Radiographs, CT/MRI, peri-operative complications, VAS, SF-12, and ODI were measured.ResultsAverage follow up was 22 months. In Group-1 and Group-2, respectively: Mean coronal Cobb angle corrected 12.6° and 5.8°; Mean regional lumbar lordosis improved 11.1° and 3.8°; Pelvic incidence minus lumbar lordosis mismatch corrected to within +/-9° in 46% and 0% of patients; Mean VAS improved from 5.4 to 2.8 and 6.3 to 1; Mean ODI improved 19% and 22%. Improvements were found in SF-12 PCS and MCS scores.ConclusionsBoth open and percutaneous posterior techniques following LLIF significantly improved clinical outcomes. Open procedures resulted in significantly better radiographic improvements but also higher complication rates. LLIF with percutaneous posterior fixation, without decompression, should be considered part of the algorithm in select ADS patients with remaining compensatory mechanisms and understanding that greater degrees of correction may require an open, more extensive approach.

We conceptualize the reach of the state by examining how the physical presence of the state helps the state project its power by signaling state interests and strength. We present a new measurement strategy to capture the territorial reach of the state using points-of-interest data provided by location-based service companies. Our measure exhibits several advantages: (1) it draws on firm-produced or crowd-sourced (rather than government-produced) data, (2) it includes highly precise, geo-referenced location information, which can be aggregated to any geographical or administrative level, (3) it traces temporal changes, and (4) it covers different types of state agencies. We illustrate its features using original databases that we compiled on state agencies in China and other countries. We demonstrate how researchers can use our measure by examining the locations and effects of coercive organizations and provide our data, code, and a tutorial to help researchers explore new avenues of inquiry. [ABSTRACT FROM AUTHOR]

The contribution of early education to children's well-being and school success is widely recognized. Effective teachers are the most critical factor in the quality of a child's education. The key to sustaining teacher effectiveness and supporting continuous growth is high-quality professional development. Despite its critical importance, professional development for early childhood teachers is inconsistent and fragmented. The field of early education lacks a common conceptual framework to organize and integrate teacher development experiences. In this paper, the "whole teacher" development approach is proposed as an organizing framework. The approach is distinguished by its simultaneous focus on teacher attitudes, skills and knowledge, and practices. Also distinctive is its application of an integrated developmental framework that promotes teacher proficiency in a wide range of specific domains. To test the approach, a study of teachers' technology proficiency was carried out. The study analyzed relationships among teacher attitudes, skills, and practices, using data collected from teachers in the process of developing computer proficiency. Among teachers who participated in a technology program based on the "whole teacher" development approach, significant degrees of association among attitudes, skills, and practices were found. Further, program participants reported significantly higher levels of technology skill and classroom practice than nonparticipants. Distinctive features of the approach are compared to other professional development practices in early childhood education. Implications for conceptualizing and designing effective professional development programs for early childhood teachers are discussed.

In liberal democracies, journalists can engage the government by unearthing its scandals. Authoritarian regimes, where negative news about the government is heavily guarded, lack this process. Yet, rulers in China do propagate political scandals about themselves. Why? I theorize that they do so to engage citizens with propaganda and strategically control their risk with Information and Communications Technologies (ICT). I test my theory by analyzing a novel dataset of news stories and reader comments posted by Chinese citizens over the course of China's anticorruption campaign between 2012 and 2015. My findings show that users' comments about stories of corrupt national officials were unexpectedly lower than those about lower-ranking officials. Such irregularity suggests that either algorithms or censorship suppressed comments on national-level corruption, which indicates the ruler's uneasiness toward propagating scandals that may implicate themselves. I also find that China's rulers reduce their risks by outsourcing reports of their scandals to media outlets less closely linked to the state. My findings show that advancements in ICT and increasing competition among new media firms can help authoritarian rulers finetune their propaganda by promoting self-damaging political messages. [ABSTRACT FROM AUTHOR]

Mutations in the gene encoding the transcription factor regulatory factor X-box binding 6 (RFX6) are associated with human diabetes. Within pancreatic islets, RFX6 expression is most abundant in islet α-cells, and α-cell RFX6 expression is altered in diabetes. However, the roles of RFX6 in regulating gene expression, glucagon output, and other crucial human adult α-cell functions are not yet understood. We developed a method for selective genetic targeting of human α-cells and assessed RFX6 -dependent α-cell function. RFX6 suppression with RNA interference led to impaired α-cell exocytosis and dysregulated glucagon secretion in vitro and in vivo. By contrast, these phenotypes were not observed with RFX6 suppression across all islet cells. Transcriptomics in α-cells revealed RFX6 -dependent expression of genes governing nutrient sensing, hormone processing, and secretion, with some of these exclusively expressed in human α-cells. Mapping of RFX6 DNA-binding sites in primary human islet cells identified a subset of direct RFX6 target genes. Together, these data unveil RFX6-dependent genetic targets and mechanisms crucial for regulating adult human α-cell function. Article Highlights: RFX6 is expressed in all islet endocrine cell types and is dysregulated in multiple forms of diabetes, but its function has not yet been delineated in α-cells. We used specific targeting of shRNA-mediated suppression of RFX6 in primary human α-cells to unveil glucagon secretion phenotypes. RFX6 is required in adult human α-cells to maintain gene regulation and hallmark functions, including regulated glucagon secretion. RNA-sequencing and cleavage under targets and release using nuclease studies reveal distinct RFX6 genetic targets in adult human α- and β-cells. [ABSTRACT FROM AUTHOR]

This study investigated how bilinguals' perception of their first language (L1) differs according to age of reduced contact with L1 after immersion in a second language (L2). Twenty-one L1 Korean-L2 English bilinguals in the United States, ranging in age of reduced contact from 3 to 15 years, and 17 control participants in Korea were tested perceptually on three L1 contrasts differing in similarity to L2 contrasts. Compared to control participants, bilinguals were less accurate on L1-specific contrasts, and their accuracy was significantly correlated with age of reduced contact, an effect most pronounced for the contrast most dissimilar to L2. These findings suggest that the earlier bilinguals are extensively exposed to L2, the less likely they are to perceive L1 sounds accurately. However, this relationship is modulated by crosslinguistic similarity, and a turning point in L2 acquisition and L1 attrition of phonology appears to occur at around age 12.

Tone languages such as Mandarin use voice pitch to signal lexical contrasts, presenting a challenge for second/foreign language (L2) learners whose native languages do not use pitch in this manner. The present study examined components of an aptitude for mastering L2 lexical tone. Native English speakers with no previous tone language experience completed a Mandarin word learning task, as well as tests of pitch ability, musicality, L2 aptitude, and general cognitive ability. Pitch ability measures improved predictions of learning performance beyond musicality, L2 aptitude, and general cognitive ability and also predicted transfer of learning to new talkers. In sum, although certain nontonal measures help predict successful tone learning, the central components of tonal aptitude are pitch-specific perceptual measures. [This report was funded by the United States Government.]

Oxidation of Hg0 with any oxidant or converting it to a particle-bound form can facilitate its removal. Two sulfur-chlorine compounds, sulfur dichloride (SCl2) and sulfur monochloride (S2Cl2), were investigated as oxidants for Hg0 by gas phase reaction and by surface-involved reactions in the presence of flyash or activated carbon. The gas phase reaction rate constants between Hg0 and the sulfur/chlorine compounds were determined, and the effects of temperature and the main components in flue gases were studied. The gas phase reaction between Hg0 and SCl2 is shown to be more rapid than the gas phase reaction with chlorine, and the second order rate constant was 9.1(+-0.5) x 10-18 mL-molecules-1cdots-1 at 373oK. Nitric oxide (NO) inhibited the gas phase reaction of Hg0 with sulfur-chlorine compounds. The presence of flyash or powdered activated carbon in flue gas can substantially accelerate the reaction. The predicted Hg0 removal is about 90percent with 5 ppm SCl2 or S2Cl2 and 40 g/m3 of flyash in flue gas. The combination of activated carbon and sulfur-chlorine compounds is an effective alternative. We estimate that co-injection of 3-5 ppm of SCl2 (or S2Cl2) with 2-3 Lb/MMacf of untreated Darco-KB is comparable in efficiency to the injection of 2-3 Lb/MMacf Darco-Hg-LH. Extrapolation of kinetic results also indicates that 90percent of Hg0 can be removed if 3 Lb/MMacf of Darco-KB pretreated with 3percent of SCl2 or S2Cl2 is used. Unlike gas phase reactions, NO exhibited little effect on Hg0 reactions with SCl2 or S2Cl2 on flyash or activated carbon. Mercuric sulfide was identified as one of the principal products of the Hg0/SCl2 or Hg0/S2Cl2 reactions. Additionally, about 8percent of SCl2 or S2Cl2 in aqueous solutions is converted to sulfide ions, which would precipitate mercuric ion from FGD solution.