Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Core features of callous-unemotional traits: a cross-cultural comparison of youth in four countries.

With considerable debate concerning the impact of culture on the expression of callous-unemotional (CU) traits, it is unclear whether the core features of CU traits generalize to youth across cultures. This study aimed to examine whether cultural differences are reflected in the core features of CU traits and the associations among these features. Network analysis was employed to identify the core features and to examine the network structure of CU traits operationalized by the Inventory of Callous Unemotional traits (ICU) in four community youth samples from different nations (Australia, N = 190; the UK, N = 437; the USA, N = 330; China, N = 503). The item "Apologizes to people" was identified as a cross-cultural core feature in the ICU network with a greater centrality of this item compared to others in all four samples. In addition, some items were identified as culture-specific core features in the network, differing in their centrality across samples. The network structures of the youth self-report ICU items were moderately similar across samples, while the structures of parent-report items showed substantial differences. These findings have important implications for cross-cultural research on CU traits as well as practical implications for screening and treatment. The core features of ICU appear to be generalizable in youth across cultures, although cultural-specific manifestations should be noted.

TaCHP encoding C1-domain protein stably enhances wheat yield in saline-alkaline fields.

Overexpression of the zinc finger gene TaCHP stably enhanced wheat yield in saline-alkaline conditions in a multi-year, three-site field trial, and the genetic variations in its promoter contribute to saline-alkaline tolerance of wheat accessions. TaCHP and its tolerant haplotype have great potential for molecular breeding of stress-tolerant wheat.

Resting heart rate moderates the relationship between parental emotion socialization and callous-unemotional traits in children.

Although empirical findings have indicated that both familial and neurobiological risk factors contribute to the development of callous-unemotional (CU) traits in children, relatively few studies have investigated how these two factors interact to influence these traits. The current study focused on the combined effects of parental emotion socialization and child's resting heart rate on CU traits. Parents of Chinese children (N = 166) completed the Coping with Children's Negative Scale when children were 9.39 years old (SD = 0.92), while children's resting heart rate data were collected when they were 10.21 years old (SD = 0.72). When they were 11.15 years old (SD = 0.67), parents completed the Inventory of Callous-Unemotional Traits Short-Form. Results showed that parental supportive emotion socialization was negatively associated with CU traits and Callous behaviors in particular. In addition, resting heart rate moderated the relationship between parental emotion socialization and child's CU traits. Findings provide further evidence that an interdisciplinary approach that combines both psychosocial and biological factors is essential to further our understanding of CU traits in youth.

Hand Posture and Force Estimation Using Surface Electromyography and an Artificial Neural Network.

OBJECTIVE: The purpose of this study was to develop an approach to predict hand posture (pinch versus grip) and grasp force using forearm surface electromyography (sEMG) and artificial neural networks (ANNs) during tasks that varied repetition rate and duty cycle. BACKGROUND: Prior studies have used electromyography with machine learning models to predict grip force but relatively few studies have assessed whether both hand posture and force can be predicted, particularly at varying levels of duty cycle and repetition rate. METHOD: Fourteen individuals participated in this experiment. sEMG data for five forearm muscles and force output data were collected. Calibration data (25, 50, 75, 100% of maximum voluntary contraction (MVC)) were used to train ANN models to predict hand posture (pinch versus grip) and force magnitude while performing tasks that varied load, repetition rate, and duty cycle. RESULTS: Across all participants, overall hand posture prediction accuracy was 79% (0.79 ± .08), whereas overall hand force prediction accuracy was 73% (0.73 ± .09). Accuracy ranged between 0.65 and 0.93 based on varying repetition rate and duty cycle. CONCLUSION: Hand posture and force prediction were possible using sEMG and ANNs, though there were important differences in the accuracy of predictions based on task characteristics including duty cycle and repetition rate. APPLICATION: The results of this study could be applied to the development of a dosimeter used for distal upper extremity biomechanical exposure measurement, risk assessment, job (re)design, and return to work programs.

TaSRO1 plays a dual role in suppressing TaSIP1 to fine tune mitochondrial retrograde signalling and enhance salinity stress tolerance.

Initially discovered in yeast, mitochondrial retrograde signalling has long been recognised as an essential in the perception of stress by eukaryotes. However, how to maintain the optimal amplitude and duration of its activation under natural stress conditions remains elusive in plants. Here, we show that TaSRO1, a major contributor to the agronomic performance of bread wheat plants exposed to salinity stress, interacted with a transmembrane domain-containing NAC transcription factor TaSIP1, which could translocate from the endoplasmic reticulum (ER) into the nucleus and activate some mitochondrial dysfunction stimulon (MDS) genes. Overexpression of TaSIP1 and TaSIP1-∆C (a form lacking the transmembrane domain) in wheat both compromised the plants' tolerance of salinity stress, highlighting the importance of precise regulation of this signal cascade during salinity stress. The interaction of TaSRO1/TaSIP1, in the cytoplasm, arrested more TaSIP1 on the membrane of ER, and in the nucleus, attenuated the trans-activation activity of TaSIP1, therefore reducing the TaSIP1-mediated activation of MDS genes. Moreover, the overexpression of TaSRO1 rescued the inferior phenotype induced by TaSIP1 overexpression. Our study provides an orchestrating mechanism executed by the TaSRO1-TaSIP1 module that balances the growth and stress response via fine tuning the level of mitochondria retrograde signalling.

The Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA): Factor Structure and Measurement Invariance in a Chinese Student Samples.

The present study aimed to examine the factor structure and measurement invariance of the Emotion Regulation Questionnaire for children and adolescents (ERQ-CA) in Chinese youth (N = 484, Mage = 10.43, SDage = .88). Three versions (i.e., ERQ-CA-10, ERQ-CA-9, and ERQ-CA-8) of the ERQ-CA were tested and compared using confirmatory factor analysis, measurement invariance, and correlation analysis. Results showed that the eight-item version of the ERQ-CA (ERQ-CA-8) fit the data best in all conditions. However, measurement invariance across gender and after a one-year retest interval was achieved using all three versions of the measurement. The three ERQ-CA versions exhibited similar patterns of correlates with external measures (i.e., perceived parental marital conflict, r = -.17 to -.20, ps < .001, emotion expression, and callous-unemotional traits, r = -.26 to -.29, p < .001). Furthermore, the ERQ-CA-10 (i.e., the original ERQ-CA) showed better reliability than the other two versions. In conclusion, although further validity studies are needed, our findings suggest that the original ERQ-CA as well as the ERQ-CA-8 both have good psychometric properties and can be used to measure emotion regulation strategies in Chinese youth.

The Shift in Synonymous Codon Usage Reveals Similar Genomic Variation during Domestication of Asian and African Rice.

The domestication of wild rice occurred together with genomic variation, including the synonymous nucleotide substitutions that result in synonymous codon usage bias (SCUB). SCUB mirrors the evolutionary specialization of plants, but its characteristics during domestication were not yet addressed. Here, we found cytosine- and guanidine-ending (NNC and NNG) synonymous codons (SCs) were more pronounced than adenosine- and thymine-ending SCs (NNA and NNT) in both wild and cultivated species of Asian and African rice. The ratios of NNC/G to NNA/T codons gradually decreased following the rise in the number of introns, and the preference for NNA/T codons became more obvious in genes with more introns in cultivated rice when compared with those in wild rice. SCUB frequencies were heterogeneous across the exons, with a higher preference for NNA/T in internal exons than in terminal exons. The preference for NNA/T in internal but not terminal exons was more predominant in cultivated rice than in wild rice, with the difference between wild and cultivated rice becoming more remarkable with the rise in exon numbers. The difference in the ratios of codon combinations representing DNA methylation-mediated conversion from cytosine to thymine between wild and cultivated rice coincided with their difference in SCUB frequencies, suggesting that SCUB reveals the possible association between genetic and epigenetic variation during the domestication of rice. Similar patterns of SCUB shift in Asian and African rice indicate that genomic variation occurs in the same non-random manner. SCUB representing non-neutral synonymous mutations can provide insight into the mechanism of genomic variation in domestication and can be used for the genetic dissection of agricultural traits in rice and other crops.

Effects of variations in the tragus expansion angle on physical comfort for in-ear wearables.

Tragus expansion angle (TEA) is an angular variable that quantifies the outward degree of expansion of the tragus cartilage induced by in-ear wearables (designed with hard materials) fitted into the external ear. It is a physical factor that directly influence user's comfort experience during interaction with in-ear wearables. This study was aimed at quantifying the effects of variations in TEA on physical comfort. TEA was measured and normalised employing a measuring device and Tragus Expansion Index (TEI) proposed in this study. Physical (dis)comfort was assessed using a rating scale designed based on the 5-point Likert and Borg-CR10 scales. Comparatively, the comfort range of variations in TEA was similar for both genders. Males could endure a higher level of variations in TEA compared to females. A quantitative relationship between variations in TEA and (dis)comfort ratings was established using TEI values and GaussAmp function, which can be employed for ergonomic design purposes. Practitioner summary: This study provides an empirical and available source for quantifying the effects of variations in the tragus expansion angle on physical comfort, including quantitative tools and (dis)comfort rating models, which could be used as a reference for improving the fit, comfort and functional capacity of in-ear wearable devices.

Psychometric Properties of the Youth Psychopathic Traits Inventory Triarchic Scales and Its Short Version in Chinese Male Juvenile Offenders.

The triarchic conceptualization of psychopathy encompasses three distinct dispositional components: boldness, meanness, and disinhibition. The current study aimed to validate triarchic construct scales composed of items from the Youth Psychopathic Traits Inventory (YPI) in a sample of Chinese male juvenile offenders (N = 613, mean age = 17.14 years, SD = 1.09 years). Although the CFA and ESEM models failed to support the three-factor structure for YPI-based triarchic scores, the convergent and criteria validity of the YPI-Tri and YPI-Tri-S were supported as they demonstrated the expected relation with other psychopathic traits or component measures and aggressive behavior measures. The internal consistency of the YPI-Tri and YPI-Tri-S scores ranged from marginal to good. The findings provide preliminary evidence for the YPI-based triarchic scores and support for the utility of the YPI-Tri and YPI-Tri-S in assessing psychopathy in Chinese male juvenile offenders.

Assessing the Measurement Invariance of the Inventory of Callous-Unemotional Traits in School Students in China and the United Kingdom.

The current study investigated the measurement invariance of the Inventory of Callous-Unemotional Traits in school-attending youth in the UK (N = 437) and China (N = 364). The original 24-item ICU and five shortened versions proposed in previous studies were tested and compared using confirmatory factor analysis in the UK sample. Results indicated that the original ICU was a poor fit in the UK sample. A shortened, 11-item version (ICU-11) featuring two factors (Callousness and Uncaring) provided the best fit and was invariant across gender in both the UK and Chinese samples. Comparisons of the ICU-11 in UK and Chinese school children revealed a similar item-factor combination and factor loadings, but different item thresholds. Findings indicate that the ICU-11 may be a preferable alternative to the original version, but that average ICU-11 scores may have a different meaning in the UK and China.

Core features of callous-unemotional traits: Network analysis of the inventory of callous-unemotional traits in offender and community samples.

OBJECTIVE: Callous-unemotional (CU) traits have been added as a specifier labeled with "Limited Prosocial Emotion" used to diagnose conduct disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. However, little is known about the core features of CU traits. Thus, this study aimed to identify the most central component of CU traits from a network perspective. METHOD: Network analysis was applied to investigate the network structure of CU traits operationalized by the Inventory of Callous-Unemotional Traits in a sample of juvenile offenders (Mage = 17.14, N = 609) and community youths (Mage = 10.82, N = 487). RESULTS: Our findings showed that items assessing callousness are the most central in the network across both samples. Also, the unemotional items were found to be located at a peripheral position, with fewer links apparent to callousness and uncaring items. CONCLUSIONS: Callousness might be the key feature of CU traits in youths. Our findings further advance the general understanding about the core features of CU traits in clinical practice.

Analysis of the external acoustic meatus for ergonomic design: part II - anthropometric variations of the external acoustic meatus by sex, age and side in Chinese population.

For devices worn inside the ear, detailed anthropometric data of the external acoustic meatus (EAM) is needed, yet lacking due to the complex and costly methodology associated with attaining such measurements. The purpose of this study was to provide the anthropometric characteristics of the EAM including variations by age group, sex, and side (right/left). 1400 external ears (700 Chinese subjects) were casted and scanned. A total of 23 EAM dimensions of length, width, angle, circumference and area were measured, most of which changed by age group, sex and side. 19 measurements were larger in males and 17 measurements were larger in left-side ears. Except the entrance length and circumference, measurements were not statistically significant between left- and right-side ears. This study provides key anthropometric measurements of the EAM in a Chinese population which can be used for ergonomic design purposes. Practitioner summary: This study provides an available source for anthropometric variations of the external acoustic meatus by age, gender and side in the Chinese population, which can be used as a reference to improve the fit, comfort and function of in-ear wearable devices.

Analysis of the external acoustic meatus for ergonomic design: part I - measurement of the external acoustic meatus using casting, scanning and rapid estimation approaches.

Numerous ear-related wearables require precise measurements of the external acoustic meatus (EAM) to optimise function and comfort. The purpose of this study is to describe a novel methodology for measuring the EAM. A total of 23 measurement variables (18 novel) of the EAM from the entrance to the second bend were collected on 700 Chinese subjects (age: 15-83) using casting and 3D scanning over seven age spans: 10, 20, 30, 40, 50, 60 s and 70+. The ear horizontal plane was identified as a new reference plane for measurements and the medial concha was selected as the reference point for positioning the entrance. A detailed approach to characterising the EAM was developed as was an approach for the rapid estimation of circumference and area using regression equations making it ideal for use in early design conceptualizations. Practitioner summary: This study provides a scalable measurement methodology for determining anthropometric measurements of the external acoustic meatus. The measurement methodology and its application to the design and fitting of ear-related wearables are important to optimising their function and comfort.

The non-random patterns of genetic variation induced by asymmetric somatic hybridization in wheat.

BACKGROUND: Asymmetric somatic hybridization is an efficient crop breeding approach by introducing several exogenous chromatin fragments, which leads to genomic shock and therefore induces genome-wide genetic variation. However, the fundamental question concerning the genetic variation such as whether it occurs randomly and suffers from selection pressure remains unknown. RESULTS: Here, we explored this issue by comparing expressed sequence tags of a common wheat cultivar and its asymmetric somatic hybrid line. Both nucleotide substitutions and indels (insertions and deletions) had lower frequencies in coding sequences than in un-translated regions. The frequencies of nucleotide substitutions and indels were both comparable between chromosomes with and without introgressed fragments. Nucleotide substitutions distributed unevenly and were preferential to indel-flanking sequences, and the frequency of nucleotide substitutions at 5'-flanking sequences of indels was obviously higher in chromosomes with introgressed fragments than in those without exogenous fragment. Nucleotide substitutions and indels both had various frequencies among seven groups of allelic chromosomes, and the frequencies of nucleotide substitutions were strongly negatively correlative to those of indels. Among three sets of genomes, the frequencies of nucleotide substitutions and indels were both heterogeneous, and the frequencies of nucleotide substitutions exhibited drastically positive correlation to those of indels. CONCLUSIONS: Our work demonstrates that the genetic variation induced by asymmetric somatic hybridization is attributed to both whole genomic shock and local chromosomal shock, which is a predetermined and non-random genetic event being closely associated with selection pressure. Asymmetric somatic hybrids provide a worthwhile model to further investigate the nature of genomic shock induced genetic variation.

Autonomic conditioning to monetary and social stimuli and aggression in children.

Poor conditioning to punishment, such as loud tones or electric shock, has been proposed as an important factor involved in the etiology of aggressive and psychopathic behavior. However, it is not known whether the association holds when monetary or social stimulus is used as the unconditioned stimulus, and if aggressive individuals also have impaired conditioning to rewards. In this study, skin conductance responses in a conditioning task involving both monetary/social reward and punishment as unconditioned stimuli were assessed in 340 male and female 8- to 9-year-old children from the community. Children reported their reactive and proactive aggression using the Reactive and Proactive Aggression Questionnaire (RPQ; Raine et al., 2006). Results showed that monetary/social reward and punishment were effective in eliciting physiological classical conditioning in children, and that reduced reward conditioning was associated with high levels of proactive aggression in particular. Findings highlight the importance of distinguishing between reactive and proactive aggression when examining antisocial behavior in children, and suggest that reward-oriented treatment programs may not be effective for children with more proactive, instrumental aggressive behavior.

The wheat TaGBF1 gene is involved in the blue-light response and salt tolerance.

Light and abiotic stress both strongly modulate plant growth and development. However, the effect of light-responsive factors on growth and abiotic stress responses in wheat (Triticum aestivum) is unknown. G-box binding factors (GBFs) are blue light-specific components, but their function in abiotic stress responses has not been studied. Here we identified a wheat GBF1 gene that mediated both the blue light- and abiotic stress-responsive signaling pathways. TaGBF1 was inducible by blue light, salt and exposure to abscisic acid (ABA). TaGBF1 interacted with a G-box light-responsive element in vitro and promoted a blue-light response in wheat and Aradidopsis thaliana. Both TaGBF1 over-expression in wheat and its heterologous expression in A. thaliana heighten sensitivity to salinity and ABA, but its knockdown in wheat conferred resistance to high salinity and ABA. The expression of AtABI5, a key component of the ABA signaling pathway in A. thaliana, and its homolog Wabi5 in wheat was increased by transgenic expression of TaGBF1. The hypersensitivity to salt and ABA caused by TaGBF1 was not observed in the abi5 mutant background, showing that ABI5 is the mediator in TaGBF1-induced abiotic stress responses. However, the hypersensitivity to salt conferred by TaGBF1 is not dependent on light. This suggests that TaGBF1 is a common component of blue light- and abiotic stress-responsive signaling pathways.

A wheat superoxide dismutase gene TaSOD2 enhances salt resistance through modulating redox homeostasis by promoting NADPH oxidase activity.

Superoxide dismutase (SOD) is believed to enhance abiotic stress resistance by converting superoxide radical (O2 (-)) to H2O2 to lower ROS level and maintain redox homeostasis. ROS level is controlled via biphasic machinery of ROS production and scavenging. However, whether the role of SOD in abiotic stress resistance is achieved through influencing the biophasic machinery is not well documented. Here, we identified a wheat copper-zinc (Cu/Zn) SOD gene, TaSOD2, who was responsive to NaCl and H2O2. TaSOD2 overexpression in wheat and Arabidopsis elevated SOD activities, and enhanced the resistance to salt and oxidative stress. TaSOD2 overexpression reduced H2O2 level but accelerated O2 (-) accumulation. Further, it improved the activities of H2O2 metabolic enzymes, elevated the activity of O2 (-) producer NADPH oxidase (NOX), and promoted the transcription of NOX encoding genes. The inhibition of NOX activity and the mutation of NOX encoding genes both abolished the salt resistance of TaSOD2 overexpression lines. These data indicate that Cu/Zn SOD enhances salt resistance, which is accomplished through modulating redox homeostasis via promoting NOX activity.

A putative pyruvate transporter TaBASS2 positively regulates salinity tolerance in wheat via modulation of ABI4 expression.

BACKGROUND: High salinity adversely affects crop production. Pyruvic acid is the precursor of abscisic acid (ABA) and other chemicals that are synthesized in chloroplast, some of which are involved in the response to salt. The transportation of pyruvic acid into chloroplast is mediated by pyruvate transporters. However, whether pyruvate transporters are involved in salt response has not been studied so far. Here, we answered this issue by assessing the function of a wheat pyruvate transporter in salt response. RESULTS: A pyruvate transporter TaBASS2 was isolated from salt-tolerant wheat cultivar Shanrong 3. The expression of TaBASS2 was induced by NaCl stress as well as H2O2 and ABA treatments. Constitutive expression of TaBASS2 in Arabidopsis bass2-1 mutant complemented the mevastatin-sensitive phenotype that reflects the deficiency of transporting pyruvic acid into chloroplast. Overexpression of TaBASS2 enhanced salinity tolerance and reactive oxygen species scavenging in wheat. Arabidopsis constitutively expressing TaBASS2 also exhibited enhanced tolerance to salinity and oxidative stress. In Arabidopsis, TaBASS2 repressed the expression of ABA INSENSITIVE 4 (ABI4), a node linking ABA signaling and plastid retrograde signaling pathways. However, the enhanced salinity tolerance of TaBASS2 overexpression Arabidopsis was abolished when ABI4 expression was restored to the level of wild-type through overexpressing ABI4. CONCLUSIONS: Our work demonstrates that TaBASS2 enhances salinity tolerance of plants via modulating ABI4 expression. This indicates that pyruvate transporters indeed participate in the interaction of plants with environmental stimuli.

A wheat histone variant gene TaH2A.7 enhances drought tolerance and promotes stomatal closure in Arabidopsis.

KEY MESSAGE: We found a histone variant enhances drought tolerance partially via promoting stomatal closure other than osmotic stress resistance, indicating the crucial and complicated contribution of epigenetic regulation to abiotic stress response. Histone variants epigenetically regulate gene transcription through remodeling chromatin. They have been implicated in modulating plant abiotic stress response, however, the role(s) is not well documented. Here, we identified an abiotic stress responsive H2A variant gene TaH2A.7 from wheat. TaH2A.7 shared high identity with H2A homologs and localized to the nucleus. TaH2A.7 overexpression in Arabidopsis significantly enhanced drought tolerance, but had no effect on the response to saline, osmotic and oxidative stresses. TaH2A.7 lowered water loss rate, and promoted ABA-induced stomatal closure. In TaH2A.7 overexpression plants, the mRNA levels of numerous genes involved in the ABA pathway and stomatal movement signaling pathway were elevated, H2O2 level in guard cells was increased, as well. Together, TaH2A.7 can enhance drought tolerance via, at least in part, promoting stomatal closure, and appears to be a promising target for molecular breeding.