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Author Correction: Faces of different socio-cultural identities impact emotional meaning learning for L2 words

Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish

The often-distinctive pigment patterns of vertebrates are varied in form and function and depend on several types of pigment cells derived from embryonic neural crest or latent stem cells of neural crest origin. These cells and the patterns they produce have been useful for uncovering features of differentiation and morphogenesis that underlie adult phenotypes, and they offer opportunities to discover how patterns and the cell types themselves have diversified. In zebrafish, a body pattern of stripes arises by self-organizing interactions among three types of pigment cells. Yet these fish also exhibit white ornamentation on their fins that depends on the transdifferentiation of black melanophores to white cells, “melanoleucophores.” To identify mechanisms underlying this conversion we used ultrastructural, transcriptomic, mutational, and other approaches. We show that melanophore–melanoleucophore transition depends on regional BMP signals transduced through noncanonical receptors (Rgmb-Neo1a-Lrig2) as well as BMP-dependent signaling by Agouti genes, asip1 and asip2b . These signals lead to expression of transcription factor genes including foxd3 and runx3 that are necessary to induce loss of melanin, curtail new melanin production, and deploy a pathway for accumulating guanine crystals that, together, confer a white phenotype. These analyses uncover an important role for positional information in specifying ornamentation in zebrafish and show how tissue environmental cues and an altered gene regulatory program have allowed terminal addition of a distinct phenotype to a preexisting cell type.

Impacts of a prolonged marine heatwave and chronic local human disturbance on juvenile coral assemblages

Coral reefs are threatened by climate change and chronic local human disturbances. Although some laboratory studies have investigated the effects of combined stressors, such as nutrient enrichment and heat stress, on growth and survival of early life stage corals, in situ studies remain limited. To assess the influence of multiple stressors on juvenile corals, we quantified densities of corals ≤ 5 cm at 18 forereef sites with different exposure levels to underlying chronic local human disturbance before, during, and after the 2015-2016 El Niño. This marine heatwave caused prolonged heat stress and devastating losses of coral cover on the shallow forereef’s of Kiritimati, in the central equatorial Pacific Ocean. Here, we enumerated a total of 7732 juvenile corals from 13 different families. Over 80% of corals were from four families: 70% from Agariciidae, Merulinidae, or Poritidae, which all have stress-tolerant life history strategies, and 11% from Acroporidae which has a competitive life-history strategy. Both local disturbance and heat stress were significantly negatively related to juvenile coral densities. Prior to the heatwave, juvenile densities were on average 72% lower at the most disturbed sites (7.2 ±  1.9 m -2 ) compared to the least disturbed ones (15.3 ±  3.8 m -2 ). Overall, juvenile corals had a lower bleaching prevalence and lower mortality during the heatwave when compared to their adult counterparts. Still, the heatwave resulted in the loss of half (49%) of all juvenile corals, with those corals with competitive or weedy life history strategies undergoing greater declines than stress-tolerant ones. Although juvenile coral densities increased slightly in the year following the heatwave, the effect was statistically non-significant. Our results highlight the influence of chronic local anthropogenic and marine heatwaves on juvenile coral densities.

Identification of a novel unfolded protein response related signature for predicting the prognosis of acute myeloid leukemia

Antagonizing <i>cis-</i> regulatory elements of a conserved flowering gene mediate developmental robustness

Developmental transitions require precise temporal and spatial control of gene expression. In plants, such regulation is critical for flower formation, which involves the progressive maturation of stem cell populations within shoot meristems to floral meristems, followed by rapid sequential differentiation into floral organs. Across plant taxa, these transitions are orchestrated by the F-box transcriptional cofactor gene UNUSUAL FLORAL ORGANS ( UFO ). The conserved and pleiotropic functions of UFO offer a useful framework for investigating how evolutionary processes have shaped the intricate cis- regulation of key developmental genes. By pinpointing a conserved promoter sequence in an accessible chromatin region of the tomato ortholog of UFO , we engineered in vivo a series of cis- regulatory alleles that caused both loss- and gain-of-function floral defects. These mutant phenotypes were linked to disruptions in predicted transcription factor binding sites for known transcriptional activators and repressors. Allelic combinations revealed dosage-dependent interactions between opposing alleles, influencing the penetrance and expressivity of gain-of-function phenotypes. These phenotypic differences support that robustness in tomato flower development requires precise temporal control of UFO expression dosage. Bridging our analysis to Arabidopsis , we found that although homologous sequences to the tomato regulatory region are dispersed within the UFO promoter, they maintain similar control over floral development. However, phenotypes from disrupting these sequences differ due to the differing expression patterns of UFO . Our study underscores the complex cis- regulatory control of dynamic developmental genes and demonstrates that critical short stretches of regulatory sequences that recruit both activating and repressing machinery are conserved to maintain developmental robustness.

Epidemiology of reported serious adverse drug reactions due to anti-infectives using nationwide database of Thailand

Serious Adverse Drug Reactions (ADRs) can cause a longer stay, which can result in fatal outcomes. Understanding the prognostic factors for the serious ADRs play a vital role in developing appropriate serious ADR prevention strategies. This study aimed to analyze nationwide database in Thailand to identify predisposing factors associated with the serious ADRs, explore drug exposure, distribution of serious ADRs, types of ADRs, and classify the determinants of serious ADR due to anti-infective in Thailand. The national database of anti-infective-induced ADRs from January 2012 to December 2021 in Thailand’s 77 provinces, Thai Vigibase at the Health Product Vigilance Center (HPVC), was considered. After pre-processing, frequencies and percentages were used to investigate the distribution of ADR seriousness. To determine the significance of the independent variables on the seriousness of anti-infective-induced ADRs, logistic regression and the Classification and Regression Tree (CART) model were performed. A p-value &lt; 0.05 was considered statistically significant. A total of 82,333 ADR cases, of which 20,692 were serious ADRs (25.13%). Serious ADRs is statistically associated with region, gender, ethnicity, age, type of patient, history of drug allergy, chronic disease and dose frequency (p-value &lt; 0.001). The most commonly reported serious ADRs were in the South region of Thailand (OR = 1.92, 95% CI = 1.88–1.97), followed by the North region (OR = 1.68, 95% CI = 1.64–1.71) of Thailand. Gender and history of drug allergy were also statistically associated with the seriousness of ADRs (p-value = 0.001). Reported ADRs revealed that patients were males (OR =  1.11, 95% CI = 1.11–1.13) and those with a prior history of drug allergy (OR = 1.22, 95% CI = 1.20–1.24) were more likely to experience serious ADRs. The risk of having an ADR reported as serious was significantly higher in patients aged 60 and over (OR = 1.42, 95% CI = 1.39–1.46) and patients aged 40–59 years (OR = 1.34, 95% CI = 1.31–1.37) compared to patients aged 0–19 years. IPD patients most commonly associated with serious ADRs. The results of this study will enable healthcare professionals to use caution when prescribing to those groups. Furthermore, developing a reporting system to reduce serious ADR evidence, such as software with electronic prescribing databases or applications that enable efficient detection of ADRs in high-risk groups, was critical in order to closely monitor and improve patient safety.

Enhancing E-commerce recommendations with sentiment analysis using MLA-EDTCNet and collaborative filtering

Reply to Jones et al.: Opportunities and considerations for valuing seagrass ecosystem services

Moderating and mediating mechanisms of the association between endogenous testosterone and aggression in youth: A study protocol

Background The role of testosterone, particularly in combination with cortisol, in aggression remains debated. According to the general aggression model, hormones interact with other variables, such individuals’ knowledge structures, to predict aggression. This model may help explain inconsistent findings of previous research. Furthermore, the model posits that the influence of hormones on aggressive behavior is mediated by the individual’s internal state. Accordingly, the objectives of this study are to assess whether (1) testosterone and cortisol, alone and in interaction with aggression-related knowledge structures, predict aggression in a standardized laboratory paradigm and whether (2) this association is mediated by hostile attribution, anger, and arousal. By identifying key moderators and mediators, this study seeks to make a very novel contribution to the understanding of the role of testosterone in aggressive behavior. These objectives will also be assessed separately for males and females. Methods The Point Subtraction Aggression Paradigm will be used to assess aggression. The sample will include 110 youths aged 17–19 (50% male). Participants will provide saliva samples before and after completing the paradigm, along with measures of three aggression-related knowledge structures (justification of violence, hostility, and narcissism) collected before the paradigm. Measures of two mediators (hostile attribution, anger) will be obtained after completing the paradigm. Arousal levels (heart rate and skin conductance) will be recorded before, after, and while completing the paradigm. The hypotheses will be tested using path analysis models, examining both the testosterone/cortisol ratio and the interaction between testosterone and cortisol as well as both baseline hormone levels and changes in hormone levels. Discussion Although it may be limited by the use of saliva for measuring hormones, this study will enhance the current understanding of the role of testosterone and cortisol in aggressive behavior among youths by investigating novel hypotheses related to psychological moderating and mediating factors.

MiR-340-5p regulates PD-L1 and predicts pembrolizumab response in extranodal NK/T-cell lymphoma

A bacterial effector manipulates host lysosomal protease activity–dependent plasticity in cell death modalities to facilitate infection

Crosstalk between cell death programs confers appropriate host anti-infection immune responses, but how pathogens co-opt host molecular switches of cell death pathways to reprogram cell death modalities for facilitating infection remains largely unexplored. Here, we identify mammalian cell entry 3C (Mce3C) as a pathogenic cell death regulator secreted by Mycobacterium tuberculosis (Mtb), which causes tuberculosis featured with lung inflammation and necrosis. Mce3C binds host cathepsin B (CTSB), a noncaspase protease acting as a lysosome-derived molecular determinant of cell death modalities, to inhibit its protease activity toward BH3-interacting domain death agonist (BID) and receptor-interacting protein kinase 1 (RIPK1), thereby preventing the production of proapoptotic truncated BID (tBID) while maintaining the abundance of pronecroptotic RIPK1. Disrupting the Mce3C–CTSB interaction promotes host apoptosis while suppressing necroptosis with attenuated Mtb survival and mitigated lung immunopathology in mice. Thus, pathogens manipulate host lysosomal protease activity–dependent plasticity in cell death modalities to promote infection and pathogenicity.

Effect of resistant compartment on pathogen strategy in partially migratory populations

Migration, the recurring movement of animals between habitats, can exert pressures on the pathogens they host. Properties of host populations can determine pathogen strategy (e.g. virulence) to increase pathogen fitness. To study the effect of adding a resistant compartment on virulence evolution, we developed an SIRS model and examined the winning pathogen strategy across different rates of recovery and of immunity loss. We find that when hosts spend a relatively long time in the resistant compartment, a more virulent pathogen evolves. These results have implications in conservation of migratory animal populations afflicted by disease.

Metre-scale vertical zonation of corals and sponges on a deep-marine cliff reflects trophic resource partitioning

Microevolution and phylogenomic study of Respiratory Syncytial Virus type A

Communal respiratory syncytial virus (RSV) causes mild to severe illnesses, predominantly in older adults, or people with certain chronic medical conditions, and in children. Symptoms may include rhinorrhea, cough, fever, and dyspnea. In most cases, the infection is mild and resolves on its own, but in some cases, it can lead to more serious illness such as bronchiolitis or pneumonia. The RSV genome codes for ten proteins, NS1, NS2, N, P, M, SH, G, F, M2 and L. We aimed to identify the RSV geographical transmission pattern based on parsimony and investigate hotspot regions across the complete RSV genomes. We employed Viral Evolutionary Network Analysis System on full-length available RSV genomes and with HyPhy for elucidating type of selection pressure. These results indicated that RSV strains circulating in South and North America are not mixed to the European samples, however, genomes reported from Australia are the direct decedents of European samples. Samples reported from the United Kingdom exhibited significant diversity, spanning almost every cluster. This report provides a complete mutational analysis of all the individual RSV genes, and particularly the 31 hotspot substituting regions circulating across the globe in RSV type A samples. Further, protein G and L displayed higher level of codons experienced positive selection. This analysis of RSV type A highlights mutational frequencies across the whole genome, offering valuable insights for epidemiological control and drug development.

Retraction Note: Relationship between melatonin receptor 1B and insulin receptor substrate 1 polymorphisms with gestational diabetes mellitus: a systematic review and meta-analysis

A new therapy to alleviate the inflammatory injury of piglet intestine caused by short-distance transportation——music

The purpose of this study was to explore whether music can reduce stress in animals by regulating the activity of the hypothalamus pituitary adrenal cortex (HPA) axis and reducing the concentration of cortisol. The control group was not played with any music or mechanical noise, the music group played music before and during transport, and the noise group played noise before and during transport as a positive control. The results showed that after two-hours of transportation, the concentrations of adrenocorticotropic hormone and cortisol in the music group were lower than that in the control and the noise groups, while the cortisol level in the noise group was higher than that in the music and the control groups. Plasma concentrations of D-lactic acid and diamine oxidase in the music group were lower than those in the control group and the noise group, and the noise group was higher than the control group. In addition, the concentrations of jejunal inflammatory factors interleukin-6 and interleukin-8 in the music group were lower than those in the control group and the noise group, but there was no difference of interleukin-12 in the three groups. However, there was no significant difference in Illinois-6, Illinois-12 and INF-γ between the noise group and the control group. The contents of reactive oxygen species, malondialdehyde and glutathione peroxidase in the music group had no changes compared with those in the control group, while the contents of reactive oxygen species and malondialdehyde in the noise group were higher than the control and the music groups, and the content of glutathione peroxidase was decreased. Compared with the music group, differently expressed genes analysis also showed that the mRNA expression level of inflammatory genes in the jejunum of the music group’ piglets decreased. In addition, compared with the music group, some Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to inflammation were highly expressed in the control group. In conclusion, our results showed that musical stimulation can reduce the inflammatory response of piglets caused by transportation by reducing the activity of HPA axis. Noise increased the activity of HPA axis, which aggravated the intestinal damage of piglets and caused intestinal oxidative damage

The economic burden of Myasthenia gravis from the patient´s perspective and reflected in German claims data

Abstract Myasthenia gravis (MG) is a neuromuscular disorder resulting in exertion-dependent muscle fatigability. Affecting all age groups MG is a chronic disease with unpredictable fluctuations and a range of symptom expression which can require costly immunosuppressive therapy and intensive care critically influencing economic burden. Here we aim to elucidate both the personal and societal economic burden of MG. Data were used from two sources: (1) a cross sectional study of MG patients registered in the German Myasthenia Society (DMG) collected by a survey in 2019 (n = 1660), and (2) from a dataset provided by a German health insurance company covering the period from 01/01/2014 to 31/12/2019 (n = 750) and categorized to similar subgroups for comparison. Individual and societal economic burden was highest in patients with intensified medical treatment. Absence days from work per patient year in the first year after index in claims data were 67.1 days (95% CI 66.1–68.2) (referring to n = 260 non-retired patients). Of 686 patients with early onset (&lt; 50 years) MG 260 (41.2%) reported loss of income due to MG in DMG data. Average inpatient costs from claims data in patients with intensified treatment (38,669€; 95% CI 38,627–38,712€) were particularly high compared with standard treatment (2980€; 95% CI 2975–2986€) and to no MG-related treatment (887€; 95% CI 877–886€). MG represents a major economic burden for the individual and the health care system. The costs are positively associated with the severity of disease. The economic burden is particularly high for working patients. UCB Pharma provided financial support for the subanalysis, but was not involved in the design of the study. Trial registration: clinicaltrials.gov, NCT03979521, submitted: June 7, 2019, first patient enrolled: May 1, 2019, https://clinicaltrials.gov/ct2/show/NCT03979521.

The role of livelihood diversification in agricultural modernization among tribal farmers in Bangladesh: A binary logistic model approach

This study aimed to evaluate the influence of livelihood diversification on tribal farmers’ decision to adopt modern agricultural practices, while also examining the profitability of various agricultural practices and identifying key challenges and policy recommendations for enhancing the sustainability of tribal farming livelihoods in Bangladesh. Data were collected through a structured questionnaire during the month of February 2021 from 115 tribal farmers, followed by a simple random sampling technique. In the study area, only 9.57% of farmers were involved in crop cultivation. The study calculated that human labor cost was the highest in rice production (about 37%). The benefit-cost ratio (BCR) of rice production, livestock rearing, and homestead gardening was estimated at 1.46, 1.41, and 1.09, respectively. Among all agricultural components practiced by the tribal farmers, rice production was more efficient than others. The binary logistic regression findings showed that livelihood diversification, age of the farmers, access to information, household income, and farming experience had a significant influence on the adoption decision of modern agricultural practices. Therefore, promoting livelihood diversification among tribal farmers is crucial for enhancing their resilience and income sustainability. This could include providing training, access to markets, and financial support for activities such as poultry and livestock rearing and non-farm enterprises like homestead gardening.

Establishment of an alternative splicing prognostic risk model and identification of FN1 as a potential biomarker in glioblastoma multiforme

Hypothalamic opsin 3 suppresses MC4R signaling and potentiates Kir7.1 to promote food consumption

Mammalian opsin 3 (OPN3) is a member of the opsin family of G-protein-coupled receptors with ambiguous light sensitivity. OPN3 was first identified in the brain (and named encephalopsin) and subsequently found to be expressed in other tissues. In adipocytes, OPN3 is necessary for light responses that modulate lipolysis and glucose uptake, while OPN3 in human skin melanocytes regulates pigmentation in a light-independent manner. Despite its initial discovery in the brain, OPN3 functional mechanisms in the brain remain elusive. Here, we investigated the molecular mechanism of OPN3 function in the paraventricular nucleus (PVN) of the hypothalamus. We show that Opn3 is coexpressed with the melanocortin 4 receptor ( Mc4r ) in a population of PVN neurons, where it negatively regulates MC4R-mediated cAMP signaling in a specific and Gα i/o -dependent manner. Under baseline conditions, OPN3 via Gα i/o potentiates the activity of the inward rectifying Kir7.1 channel, previously shown to be closed in response to agonist-mediated activation of MC4R in a Gα s -independent manner. In mice, we found that Opn3 in Mc4r -expressing neurons regulates food consumption. Our results reveal the first mechanistic insight into OPN3 function in the hypothalamus, uncovering a unique mechanism by which OPN3 functions to potentiate Kir7.1 activity and negatively regulate MC4R-mediated cAMP signaling, thereby promoting food intake.