Actively changing the narrative: An exploration of culturally grounded parenting and social skills.

Recognizing culturally salient aspects of socialization practices and understanding how these practices support culturally valued aspects of development is an integral component in conducting anti-racist research and validating the lived experiences of minoritized families. With this aim, we explored how Active Direction, an observational rating of an African American approach to parenting measured during mother-child interactions at age 2.5 (n = 172), supported social skills and emotion regulation for children living in a Southwestern metropolitan area of the United States concurrently, in kindergarten (n = 109), and in 1st grade (n = 108). Descriptive findings indicated few significant associations between Active Direction and socials skills or emotion regulation. Exploratory analyses, which included traditional parenting behavior measures of Sensitivity and Intrusiveness, also indicated limited significant relations between any measure of parenting and child skills. However, moderation analyses indicated that high levels of Active Direction attenuated the effects of sensitivity on aspects of child social skills. The lack of significant findings across the current study highlight how extant measures-of child social skills and parentings behaviors-are not performing as expected within these African American families.

Reconocer aspectos culturalmente salientes de las prácticas de socialización y comprender cómo estas prácticas apoyan aspectos del desarrollo culturalmente valorados, es un componente integral para llevar a cabo la investigación antiracista y darle validez a las experiencias vividas de familias vistas como minorías. Con este propósito, exploramos cómo Activa Direccción, una evaluación de observación de un acercamiento afroamericano a la crianza medido durante las interacciones madre­niño a la edad de 2.5 (n = 172), apoyaba las habilidades sociales y la regulación de la emoción para niños que vivían en un área metropolitana de los Estados Unidos, de manera concurrente, en el kinder (n = 109) y en el primer grado (n = 108). Los resultados descriptivos señalaron pocas asociaciones significativas entre Activa Direccción y las habilidades sociales o la regulación de la emoción. Los análisis exploratorios, los cuales incluyen medidas de Sensibilidad y de Entremetimiento en cuanto al comportamiento de crianza tradicional, también señalaron limitadas relaciones significativas entre cualquier medida de crianza y las habilidades sociales. Sin embargo, los análisis de moderación señalaron que altos niveles de Activa Dirección atenúan los efectos de la Sensibilidad sobre los aspectos de las habilidades sociales del niño. La falta de resultados significativos, a lo largo del presente estudio, subraya hasta qué punto las medidas ­de habilidades sociales del niño y de comportamientos de crianza­ no están actuando de la manera esperada dentro de estas familias afroamericanas.

Complement 3a induces the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms during the development and progression of Alzheimer's disease.

As a central molecule in complement system (CS), complement (C) 3 is upregulated in the patients and animal models of Alzheimer's disease (AD). C3 will metabolize to iC3b and C3a. iC3b is responsible for clearing ß-amyloid protein (Aß). In this scenario, C3 exerts neuroprotective effects against the disease via iC3b. However, C3a will inhibit microglia to clear the Aß, leading to the deposition of Aß and impair the functions of synapses. To their effects on AD, activation of C3a and C3a receptor (C3aR) will impair the mitochondria, leading to the release of reactive oxygen species (ROS), which activates the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomes. The overloading of NLRP3 inflammasomes activate microglia, leading to the formation of inflammatory environment. The inflammatory environment will facilitate the deposition of Aß and abnormal synapse pruning, which results in the progression of AD. Therefore, the current review will decipher the mechanisms of C3a inducing the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms, which facilitates the understanding the AD.

Complement C3a/C3aR and C5a/C5aR deposits accelerate the progression of advanced IgA nephropathy to end-stage renal disease.

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732-0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079-9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.

Complement C3 deficient mice show more severe imiquimod-induced psoriasiform dermatitis than wild-type mice regardless of the commensal microbiota.

The complement active product, C3a, and the receptor C3aR comprise an axis that exerts various biological functions, such as protection against infection. C3a is highly expressed in the inflamed skin and blood from patients with psoriasiform dermatitis. However, the role of the C3a/C3aR axis in psoriasiform dermatitis remains unclear because conflicting results using C3-/- mice have been published. In this study, to elucidate the contribution of commensal microbiota in C3-/- and wild-type (WT) mice were subjected to imiquimod-induced psoriasiform dermatitis under different housing conditions. C3-/- mice showed increased epidermal thickness and keratinocyte proliferation markers in the inflamed ear compared to WT mice upon treatment with IMQ. These inflamed phenotypes were observed in both cohoused and separately housed conditions, and antibiotic treatment did not abolish the aggravation of IMQ-induced psoriasiform dermatitis in C3-/- mice. These results suggested that the difference of commensal microbiota is not important for the C3-involved psoriasiform dermatitis. Keratinocyte hyperproliferation is a major feature of the inflamed skin in patients with psoriasiform dermatitis. In vitro experiments showed that C3a and C3aR agonists inhibited keratinocyte proliferation, which was abolished by introduction of a C3aR antagonist. Collectively, these results suggest that the C3a/C3aR axis plays a critical role in psoriasiform dermatitis development by inhibiting keratinocyte proliferation, regardless of the regulation of the commensal microbiota.

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation.

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.

Audience segmentation approach to conservation messaging for transforming the exotic pet trade.

Advancing transformative change for sustainability requires population-wide behavior change. Yet, many behavioral interventions tackling environmental problems only examine average effects on the aggregate, overlooking the heterogeneous effects in a population. We developed and preregistered a novel audience segmentation approach to test the diverse impact of conservation messaging on reducing demand for exotic pets (private action - i.e., desire to own exotic pets or visit wildlife entertainment places) and fostering citizen engagement for system-wide change (civic action - e.g., signing a petition or participating in a protest against the exotic pet trade). Through an online survey with US participants (n = 2953), we identified 4 population segments (early adopters, early majority, late majority, and laggards), representing varying levels of commitment to wildlife conservation and then randomly assigned each segment to one of 3 messaging conditions. Messages highlighting negative consequences of the exotic pet trade and the power of collective action for system change effectively promoted private action among all segments except early adopters (ηp 2 = 0.005). Among civic actions, only the collective action message motivated early adopters and the early majority to sign petitions (φC = 0.193 and φC = 0.097, respectively). Furthermore, the 4 segments showed distinct reasoning for action and inaction on wildlife conservation, with certain relational values, such as care, serving as both motivations and barriers to action. These findings highlight the need for targeted behavioral interventions across diverse populations.

Estrategia de segmentación del público en los mensajes de conservación para transformar el mercado de mascotas exóticas Resumen El progreso en el cambio transformativo para la sustentabilidad requiere de cambios conductuales a nivel poblacional. Sin embargo, muchas intervenciones conductuales que abordan los problemas ambientales sólo analizan los efectos promedio sobre el agregado, lo que ignora los efectos heterogéneos sobre la población. Desarrollamos y preinscribimos una estrategia novedosa de segmentación del público para evaluar los diversos impactos de los mensajes de conservación sobre la reducción de la demanda de mascotas exóticas (acción privada [es decir, el deseo de poseer mascotas exóticas o visitar sitios de entretenimiento con fauna] y promover la participación ciudadana para un cambio sistémico [por ejemplo, firmar una petición o participar en una protesta contra el mercado de mascotas exóticas]). Realizamos una encuesta en línea con participantes estadunidenses (n = 2953) para identificar cuatro segmentos de la población (adoptadores tempranos, mayoría temprana, mayoría tardía y rezagados), los cuales representan diferentes niveles de compromiso con la conservación de fauna, y después le asignamos aleatoriamente a cada segmento una de las siguientes condiciones de mensaje: las consecuencias negativas del mercado de mascotas exóticas, el poder de la acción colectiva para el cambio sistémico e información neutral como control. Los mensajes que resaltaban las consecuencias negativas del mercado de mascotas exóticas y el poder de la acción colectiva promovieron de forma eficiente la acción privada en todos los segmentos excepto los adoptadores tempranos (ηp 2 = 0.005). Entre las acciones cívicas, sólo el mensaje de acción colectiva motivó a los adoptadores tempranos y a la mayoría temprana a firmar peticiones (φC = 0.193 y φC = 0.097, respectivamente). Además, los cuatro segmentos mostraron un razonamiento distinto para la acción e inacción para la conservación de fauna, con ciertos valores de relación, como el cuidado, fungiendo como motivación o barreras para la acción. Estos resultados enfatizan la necesidad de tener intervenciones conductuales focalizadas entre las diferentes poblaciones.

Evaluation of Food Homogenates on Cell Survival In Vitro.

A critical review on the approaches to assess the infectivity of the Hepatitis E virus (HEV) in food recommended that a cell culture-based method should be developed. Due to the observations that viral loads in food may be low, it is important to maximise the potential for detection of HEV in a food source in order to fully assess infectivity. To do so, would require minimal processing of any target material. In order to proceed with the development of an infectivity culture method that is simple, robust and reproducible, there are a number of points to address; one being to assess if food homogenates are cytotoxic to HEV susceptible target cells. Food matrices previously shown to have detectable HEV nucleic acid were selected for analysis and assessed for their effect on the percentage survival of three cell lines commonly used for infectivity assays. Target cells used were A549, PLC/PRF/5 and HepG2 cells. The results showed that, as expected, various food homogenates have differing effects on cells in vitro. In this study, the most robust cell line over a time period was the A549 cell line in comparison to HepG2, with PLC/PRF/5 cells being the most sensitive. Overall, this data would suggest that FH can be left in contact with A549 cells for a period of up to 72 h to maximise the potential for testing infection. Using food homogenates directly would negate any concerns over losing virus as a result of any additional processing steps.

The influence of social identity on attitudes toward wildlife.

Wildlife conservation depends on supportive social as well as biophysical conditions. Social identities such as hunter and nonhunter are often associated with different attitudes toward wildlife. However, it is unknown whether dynamics within and among these identity groups explain how attitudes form and why they differ. To investigate how social identities help shape wildlife-related attitudes and the implications for wildlife policy and conservation, we built a structural equation model with survey data from Montana (USA) residents (n = 1758) that tested how social identities affect the relationship between experiences with grizzly bears (Ursus arctos horribilis) and attitudes toward the species. Model results (r2 = 0.51) demonstrated that the hunter identity magnified the negative effect of vicarious property damage on attitudes toward grizzly bears (ß = -0.381, 95% confidence interval [CI]: -0.584 to -0.178, p < 0.001), which in turn strongly influenced acceptance (ß = -0.571, 95% CI: -0.611 to -0.531, p < 0.001). Our findings suggested that hunters' attitudes toward grizzly bears likely become more negative primarily because of in-group social interactions about negative experiences, and similar group dynamics may lead nonhunters to disregard the negative experiences that out-group members have with grizzly bears. Given the profound influence of social identity on human cognitions and behaviors in myriad contexts, the patterns we observed are likely important in a variety of wildlife conservation situations. To foster positive conservation outcomes and minimize polarization, management strategies should account for these identity-driven perceptions while prioritizing conflict prevention and promoting positive wildlife narratives within and among identity groups. This study illustrates the utility of social identity theory for explaining and influencing human-wildlife interactions.

La influencia de la identidad social sobre la actitud hacia la fauna Resumen La conservación de la fauna depende de condiciones de apoyo tanto sociales como biofísicas. La identidad social, como ser cazador o no, con frecuencia está asociada a las diferentes actitudes hacia la fauna. Sin embargo, no sabemos si las dinámicas dentro y entre estos grupos de identidad explican cómo las actitudes se forman y porqué son diferentes. Construimos un modelo de ecuación estructural con información de encuestas realizadas a 1,758 residentes de Montana (Estados Unidos) para conocer cómo la identidad social ayuda a formar la actitud relacionada con la fauna y las implicaciones que tiene para la conservación y políticas de fauna. El modelo analizó cómo la identidad social afecta la relación entre las experiencias con osos pardos (Ursus arctos horribilis) y la actitud hacia la especie. Los resultados del modelo (r2 = 0.51) demostraron que la identidad de cazador aumentaba el efecto negativo del daño indirecto a la propiedad sobre la actitud hacia los osos (ß=­0.381, 95% CI ­0.584 a ­0.178, p<0.001), lo cual en cambio tenía una gran influencia sobre la aceptación (ß=­0.571, 95% CI ­0.611 a ­0.531, p<0.001). Nuestros descubrimientos sugieren que la actitud de los cazadores hacia los osos probablemente se vuelve más negativa principalmente debido a las interacciones sociales del endogrupo en torno a las experiencias negativas; las dinámicas similares pueden llevar a los no cazadores a menospreciar las experiencias negativas que los miembros del exogrupo han tenido con los osos. Dada la influencia profunda que tiene la identidad social sobre la cognición humana y el comportamiento en una miríada de contextos, los patrones que observamos probablemente sean importantes en una variedad de situaciones de conservación de fauna. Para promover los resultados positivos de conservación y minimizar la polarización, las estrategias de manejo deberían considerar estas percepciones influenciadas por la identidad mientras se prioriza la prevención de conflictos y se promueven narrativas positivas de fauna dentro y entre los grupos de identidad. Este estudio demuestra la utilidad que tiene la teoría de identidad social para explicar e influenciar las interacciones humano­fauna.

Influence of ozonation and UV/H2O2 on the genotoxicity of secondary wastewater effluents.

The implementation of novel wastewater treatment technologies, including Advanced Oxidation Processes (AOPs) such as ozonation and ultraviolet radiation (UV) combined with hydrogen peroxide (H2O2), can be a promising strategy for enhancing the quality of these effluents. However, during effluent oxidation AOPs may produce toxic compounds that can compromise the water reuse and the receiving water body. Given this possibility, the aim of this study was to evaluate the genotoxic potential of secondary effluents from two different Wastewater Treatment Plants (WWTP) that were subjected to ozonation or UV/H2O2 for periods of 20 (T1) and 40 (T2) minutes. The genotoxic potential was carried out with the Comet assay (for clastogenic damage) and the Micronucleus assay (for clastogenic and aneugenic damage) in HepG2/C3A cell culture (metabolizing cell line). The results of the comet assay revealed a significant increase in tail intensity in the Municipal WWTP (dry period) effluents treated with UV/H2O2 (T1 and T2). MN occurrence was noted across all treatments in both Pilot and Municipal WWTP (dry period) effluents, whereas nuclear buds (NBs) were noted for all Pilot WWTP treatments and UV/H2O2 treatments of Municipal WWTP (dry period). Moreover, the UV/H2O2 (T1) treatment of Municipal WWTP (dry period) exhibited a noteworthy incidence of multiple alterations per cell (MN + NBs). These findings imply that UV/H2O2 treatment demonstrates higher genotoxic potential compared to ozonation. Furthermore, seasonal variations can have an impact on the genotoxicity of the samples. Results of the study emphasize the importance of conducting genotoxicological tests using human cell cultures, such as HepG2/C3A, to assess the final effluent quality from WWTP before its discharge or reuse. This precaution is essential to safeguard the integrity of the receiving water body and, by extension, the biotic components it contains.

Complement activation and cellular inflammation in Fabry disease patients despite enzyme replacement therapy.

Defective α-galactosidase A (AGAL/GLA) due to missense or nonsense mutations in the GLA gene results in accumulation of the glycosphingolipids globotriaosylceramide (Gb3) and its deacylated derivate globotriaosylsphingosine (lyso-Gb3) in cells and body fluids. The aberrant glycosphingolipid metabolism leads to a progressive lysosomal storage disorder, i. e. Fabry disease (FD), characterized by chronic inflammation leading to multiorgan damage. Enzyme replacement therapy (ERT) with agalsidase-alfa or -beta is one of the main treatment options facilitating cellular Gb3 clearance. Proteome studies have shown changes in complement proteins during ERT. However, the direct activation of the complement system during FD has not been explored. Here, we demonstrate strong activation of the complement system in 17 classical male FD patients with either missense or nonsense mutations before and after ERT as evidenced by high C3a and C5a serum levels. In contrast to the strong reduction of lyso-Gb3 under ERT, C3a and C5a markedly increased in FD patients with nonsense mutations, most of whom developed anti-drug antibodies (ADA), whereas FD patients with missense mutations, which were ADA-negative, showed heterogenous C3a and C5a serum levels under treatment. In addition to the complement activation, we found increased IL-6, IL-10 and TGF-ß1 serum levels in FD patients. This increase was most prominent in patients with missense mutations under ERT, most of whom developed mild nephropathy with decreased estimated glomerular filtration rate. Together, our findings demonstrate strong complement activation in FD independent of ERT therapy, especially in males with nonsense mutations and the development of ADAs. In addition, our data suggest kidney cell-associated production of cytokines, which have a strong potential to drive renal damage. Thus, chronic inflammation as a driver of organ damage in FD seems to proceed despite ERT and may prove useful as a target to cope with progressive organ damage.

Streptococcus suis subtilisin-like serine proteases SspA-1 and SspA-2 interplay with complement C3a and C5a to facilitate bacterial immune evasion and infection.

Streptococcus suis (S. suis), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome, meningitis, septicaemia, and abrupt fatality. The multifaceted roles of complement components C5a and C3a extend to orchestrating inflammatory cells recruitment, oxidative burst induction, and cytokines release. Despite the pivotal role of subtilisin-like serine proteases in S. suis pathogenicity, their involvement in immune evasion remains underexplored. In the present study, we identify two cell wall-anchored subtilisin-like serine proteases in S. suis, SspA-1 and SspA-2, as binding partners for C3a and C5a. Through Co-Immunoprecipitation, Enzyme-Linked Immunosorbent and Far-Western Blotting Assays, we validate their interactions with the aforementioned components. However, SspA-1 and SspA-2 have no cleavage activity against complement C3a and C5a performed by Cleavage assay. Chemotaxis assays reveal that recombinant SspA-1 and SspA-2 effectively attenuate monocyte chemotaxis towards C3a and C5a. Notably, the ΔsspA-1, ΔsspA-1, and ΔsspA-1/2 mutant strains exhibit compromised survival in blood, and resistance of opsonophagocytosis, alongside impaired survival in blood and in vivo colonization compared to the parental strain SC-19. Critical insights from the murine and Galleria mellonella larva infection models further underscore the significance of sspA-1 in altering mortality rates. Collectively, our findings indicate that SspA-1 and SspA-2 are novel binding proteins for C3a and C5a, thereby shedding light on their pivotal roles in S. suis immune evasion and the pathogenesis.

Decoding anaphylatoxins: unveiling the molecular mechanisms of complement receptor activation and signaling.

Recent advances in cryo-electron microscopy (Cryo-EM) have revolutionized our understanding of the complement C5a/C3a receptors that are crucial in inflammation. A recent report by Yadav et al. has elucidated the activation, ligand binding, selectivity, and signaling bias of these receptors, thereby enhancing structure-guided drug discovery. This paves the way for more effective anti-inflammatory therapies that target these receptors with unprecedented precision.

Coculture model of a liver sinusoidal endothelial cell barrier and HepG2/C3a spheroids-on-chip in an advanced fluidic platform.

The liver is one of the main organs involved in the metabolism of xenobiotics and a key organ in toxicity studies. Prior to accessing the hepatocytes, xenobiotics pass through the hepatic sinusoid formed by liver sinusoidal endothelial cells (LSECs). The LSECs barrier regulates the kinetics and concentrations of the xenobiotics before their metabolic processing by the hepatocytes. To mimic this physiological situation, we developed an in vitro model reproducing an LSECs barrier in coculture with a hepatocyte biochip, using a fluidic platform. This technology made dynamic coculture and tissue crosstalk possible. SK-HEP-1 and HepG2/C3a cells were used as LSECs and as hepatocyte models, respectively. We confirmed the LSECs phenotype by measuring PECAM-1 and stabilin-2 expression levels and the barrier's permeability/transport properties with various molecules. The tightness of the SK-HEP-1 barrier was enhanced in the dynamic coculture. The morphology, albumin secretion, and gene expression levels of markers of HepG2/C3a were not modified by coculture with the LSECs barrier. Using acetaminophen, a well-known hepatotoxic drug, to study tissue crosstalk, there was a reduction in the expression levels of the LSECs markers stabilin-2 and PECAM-1, and a modification of those of CLEC4M and KDR. No HepG2/C3a toxicity was observed. The metabolisation of acetaminophen by HepG2/C3a monocultures and cocultures was confirmed. Although primary cells are required to propose a fully relevant model, the present approach highlights the potential of our system for investigating xenobiotic metabolism and toxicity.

Do toys get in the way? The duration of shared emotional experiences is longer when mothers engage their infants without toys.

During mother-infant interaction, shared emotional experiences, defined as reciprocal and synchronous emotional sharing between mother and infant, are an indicator of early relational health. Yet, it is unclear how mothers' efforts to engage with their infants relate to dyadic-level shared emotional experiences. Utilizing a sample of 80 randomly selected videos of the NICHD Study of Early Child Care and Youth Development, we examined how mothers' bids for interaction with their 6-month-old infants related to the duration of shared emotional experiences. An event sampling, sequential coding system was used to identify a maternal bid for interaction (i.e., with toy, without toy) and the subsequent presence or absence of a shared emotional experience, including duration of the shared emotional experience. Results indicated that shared emotional experiences were longer following mothers' efforts to engage their infants in play without toys. Findings suggest that methods matter; researchers and practitioners interested in studying and promoting shared emotional experiences between mothers and infants may wish to focus on dyadic interactions without toys.

Durante la interacción madre-infante, las experiencias emocionalmente compartidas, definidas como el recíproco y síncrono compartir emocional entre madre e infante, son un indicador de la temprana saludable relación. Aún así, no está claro cómo los esfuerzos de las madres para compartir con sus infantes se relacionan con las experiencias emocionales compartidas al nivel de la díada. Utilizando un grupo muestra de 80 videos del Estudio NICHD del Temprano Cuidado Infantil y Desarrollo de la Juventud, seleccionados al azar, examinamos cómo las posturas de las madres para interactuar con sus infantes de 6 meses de edad se relacionaban con la duración de las experiencias emocionales compartidas. Se usó un sistema de codificación secuencial de muestreo de eventos para identificar una postura materna para la interacción (v.g., con juguete, sin juguete) y la subsecuente presencia o ausencia de una experiencia emocional compartida, incluyendo la duración de la experiencia emocional compartida. Los resultados indicaron que las experiencias emocionales compartidas eran más largas cuando los esfuerzos de las madres para interactuar con sus infantes en el juego no incluían juguetes. Los resultados sugieren que los métodos importan; los investigadores y profesionales de la práctica interesados en estudiar y promover las experiencias emocionales compartidas entre madres e infantes pudieran querer enfocarse en las interacciones diádicas sin juguetes.

Study of the DNA damage and cell death in human peripheral blood mononuclear and HepG2/C3A cells exposed to the synthetic 3-(3-hydroxyphenyl)-7-hydroxycoumarin.

Hydroxycoumarins are an important source of biologically active compounds. Previous studies have shown that the number and position of the hydroxyl substituents in the scaffold play an important role for the observed biological activity. In the present study, 3-(3-hydroxyphenyl)-7-hydroxycoumarin was synthesized, and potential cytogenotoxic effects determined in human HepG2/C3A cells displaying phase 1 and phase 2 enzymes (metabolizing cell ability) and compared to human peripheral blood mononuclear cells (PBMC) without xenobiotics metabolizing capacity. Cell viability was determined with concentrations between 0.01 and 10 µg/ml of 3-(3-hydroxyphenyl)-7-hydroxycoumarin using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and trypan blue tests. Genotoxicity was determined utilizing the comet assay, and the clastogenic/aneugenic potential employing the micronucleus (MN) test. The results of the in vitro cytotoxicity assays showed a significant decrease in cell viability of PBMC following exposure to 10 µg/ml concentration of the studied compound after 48 and 72 hr. Comet assay observations noted significant DNA damage in PBMC after 4 hr treatment. No marked cytogenotoxic effects were found in HepG2/C3A cells. No chromosomal mutations were observed in both cell lines. It is important to note that 3-(3-hydroxyphenyl)-7-hydroxycoumarin may exert beneficial pharmacological actions at the low micromolar range and with half-life less than 24 hr. Therefore, the results obtained encourage the continuation of studies on this new molecule for medicinal purposes, but its potential toxicity at higher concentrations and longer exposure times needs to be investigated in further studies.

Experimentally testing animal responses to prescribed fire size and severity.

Deserts are often highly biodiverse and provide important habitats for many threatened species. Fire is a dominant disturbance in deserts, and prescribed burning is increasingly being used by conservation managers and Indigenous peoples to mitigate the damaging effects of climate change, invasive plants, and land-use change. The size, severity, and patchiness of fires can affect how animals respond to fire. However, there are almost no studies examining such burn characteristics in desert environments, which precludes the use of such information in conservation planning. Using a before-after control-impact approach with 20 sampling sites, we studied the outcomes of 10 prescribed burns of varying size (5-267 ha), severity, and patchiness to identify which variables best predicted changes in small mammal and reptile species richness and abundance. Three of the 13 species showed a clear response to fire. Captures increased for 2 species (1 mammal, 1 reptile) and decreased for 1 species (a reptile) as the proportional area burned around traps increased. Two other mammal species showed weaker positive responses to fire. Total burn size and burn patchiness were not influential predictors for any species. Changes in capture rates occurred only at sites with the largest and most severe burns. No fire-related changes in capture rates were observed where fires were small and very patchy. Our results suggest that there may be thresholds of fire size or fire severity that trigger responses to fire, which has consequences for management programs underpinned by the patch mosaic burning paradigm. The prescribed burns we studied, which are typical in scale and intensity across many desert regions, facilitated the presence of some taxa and are unlikely to have widespread or persistent negative impacts on small mammal or reptile communities in this ecosystem provided that long unburned habitat harboring threatened species is protected.

Prueba experimental de la respuesta animal al tamaño y gravedad de los incendios controlados Resumen Los desiertos suelen contar con mucha biodiversidad y proporcionar hábitats importantes para una variedad de especies amenazadas. El fuego es una perturbación que domina en los desiertos, y los incendios controlados cada vez se usan más por los gestores de la conservación y los pueblos indígenas para mitigar los efectos dañinos del cambio climático, las plantas invasoras y el cambio de uso de suelo. El tamaño, gravedad y fragmentación de los incendios pueden afectar cómo los animales responden al fuego. Sin embargo, casi no existen estudios que analicen dichas características de la quema en los ambientes desérticos, lo que excluye a dicha información de la planeación de la conservación. Usamos una estrategia de antes­después del control­impacto en 20 sitios de muestreo para estudiar los resultados de diez incendios controlados de diferentes tamaños (5­267 ha), gravedad y fragmentación para identificar cuáles variables pronostican mejor los cambios en la riqueza de especies y abundancia de mamíferos pequeños y reptiles. Tres de las 13 especies mostraron una respuesta clara al incendio. Las capturas incrementaron en dos especies (una de mamífero y una de reptil) y disminuyeron en una especie (un reptil) conforme incrementó el área proporcional incendiada alrededor de las trampas. Otras dos especies de mamíferos mostraron respuestas positivas más débiles ante el fuego. El tamaño total y la fragmentación del incendio no fueron influyentes sobre los pronosticadores de cualquier especie. Los cambios en las tasas de captura ocurrieron solamente en los sitios con los incendios más graves y grandes. No observamos cambios relacionados al incendio en las tasas de captura en donde los incendios fueron pequeños y muy fragmentados. Nuestros resultados sugieren que podría haber umbrales del tamaño o gravedad del incendio que provocan las respuestas al fuego, lo que tiene consecuencias para los programas de manejo sustentados en el paradigma del mosaico de fragmentos del incendio. Los incendios controlados que estudiamos, que son típicos en escala e intensidad en muchas regiones desérticas, facilitaron la presencia de algunos taxones y no tuvieron probabilidad de tener un impacto negativo extenso o persistente sobre las comunidades de mamíferos pequeños y reptiles en este ecosistema, siempre y cuando se proteja el hábitat que lleva mucho tiempo sin incendios y en donde viven las especies amenazadas.

P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain. 3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine (P7C3-A20) can be neuroprotective in various diseases, including ischemic stroke and neurodegenerative diseases. However, whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear. Therefore, in the present study, we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms. We established a traumatic brain injury rat model using a modified weight drop method. P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury. Severe neurological deficits were found in rats after traumatic brain injury, with deterioration in balance, walking function, and learning memory. Furthermore, hematoxylin and eosin staining showed significant neuronal cell damage, while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis. The presence of autolysosomes was observed using transmission electron microscope. P7C3-A20 treatment reversed these pathological features. Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-II (LC3-II) autophagy protein, apoptosis-related proteins (namely, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 [BNIP3], and Bcl-2 associated x protein [Bax]), and elevated ubiquitin-binding protein p62 (p62) autophagy protein expression. Thus, P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Follicular fluid C3a-peptide promotes oocyte maturation through F-actin aggregation.

BACKGROUND: Immature cumulus-oocyte complexes are retrieved to obtain mature oocytes by in vitro maturation (IVM), a laboratory tool in reproductive medicine to obtain mature oocytes. Unfortunately, the efficiency of IVM is not satisfactory. To circumvent this problem, we therefore intended to commence with the composition of ovarian follicular fluid (FF), an important microenvironment influencing oocyte growth. It is well known that FF has a critical role in oocyte development and maturation. However, the components in human FF remain largely unknown, particularly with regard to small molecular peptides. RESULTS: In current study, the follicular fluid derived from human mature and immature follicles were harvested. The peptide profiles of FF were further investigated by using combined ultrafiltration and LC-MS/MS. The differential peptides were preliminary determined by performing differentially expressed analysis. Human and mouse oocyte culture were used to verify the influence of differential peptides on oocyte development. Constructing plasmids, cell transfecting, Co-IP, PLA etc. were used to reveal the detail molecular mechanism. The results from differentially expressed peptide as well as cultured human and mouse oocytes analyses showed that highly conserved C3a-peptide, a cleavage product of complement C3a, definitely affected oocytes development. Intriguingly, C3a-peptide possessed a novel function that promoted F-actin aggregation and spindle migration, raised the percentage of oocytes at the MII stage, without increasing the chromosome aneuploidy ratio, especially in poor-quality oocytes. These effects of C3a-peptide were attenuated by C3aR morpholino inhibition, suggesting that C3a-peptide affected oocytes development by collaborating with its classical receptor, C3aR. Specially, we found that C3aR co-localized to the spindle with ß-tubulin to recruit F-actin toward the spindle and subcortical region of the oocytes through specific binding to MYO10, a key regulator for actin organization, spindle morphogenesis and positioning in oocytes. CONCLUSIONS: Our results provide a new perspective for improving IVM culture systems by applying FF components and also provide molecular insights into the physiological function of C3a-peptide, its interaction with C3aR, and their roles in enabling meiotic division of oocytes.

C3aR Antagonist Alleviates C3a Induced Tubular Profibrotic Phenotype Transition via Restoring PPARα/CPT-1α Mediated Mitochondrial Fatty Acid Oxidation in Renin-Dependent Hypertension.

BACKGROUND: Renin-dependent hypertension with tubulointerstitial injury remains a problem with high prevalence in the clinic. However, whether and how renin participates in tubulointerstitial injury remains incompletely understood. New evidence suggests that renin cleaves C3 into C3a and C3b. In the present study, we aimed to explore the role of renin-mediated C3a/C3a receptor (C3aR) signaling in renin-dependent hypertension-induced kidney injury and illustrate the detailed mechanisms. METHODS: C3a concentration changes in serum from healthy volunteers incubated with recombinant renin were detected by ELISA. C3aR expression in human tubular epithelial cells was evaluated in renal biopsy sections from malignant arteriolonephrosclerosis and benign arteriolonephrosclerosis patients. C3aR changes in human kidney 2 (HK2) cells were detected after the cells were treated with human serum, renin and aliskiren. The C3a analogue and C3aR antagonist SB290157 were used to stimulate HK2 cells to explore the downstream signaling of C3a/C3aR activation. For in vivo studies, two-kidney, one-clipped (2K1C) hypertensive rat model was established to simulate renin-dependent hypertension conditions. C3a and C3aR expression was detected in the clipped kidneys. SB290157 was injected intraperitoneally to block C3a/C3aR signaling in 2K1C rats. RESULTS: The results showed that renin cleaved C3 into C3a and activated C3a/C3aR signaling in tubular epithelial cells (TECs) from both humans and rats. In vitro results demonstrated that C3a/C3aR activation impaired peroxisome proliferator-activated receptor alpha (PPARα)/carnitine palmitoyltransterase-1alpha (CPT-1α)-mediated mitochondrial fatty acid oxidation (Mito FAO) in HK2 cells and induced HK2 cell transition to a profibrotic phenotype, which was inhibited by treatment with the C3aR antagonist SB290157. In vivo results showed that renin mRNA levels, C3a concentrations, C3aR levels and tubulointerstitial fibrosis increased concurrently in the clipped kidney cortex of 2K1C rats. Treatment with the C3aR antagonist SB290157 significantly mitigated the effect of renin induction of C3aR expression and alleviated renin-dependent hypertension-induced tubulointerstitial fibrosis by improving PPARα/CPT-1α-mediated Mito FAO in TECs, as well as inhibiting tubular profibrotic phenotype transition. CONCLUSIONS: Our results prove that renin activates C3a/C3aR signaling to promote renal tubulointerstitial fibrosis by impairing PPARα/CPT-1α-mediated tubular Mito FAO. SB290157 confers a potential therapeutic approach for renin-dependent hypertension-induced kidney injury.

Effects of protection and temperature variation on temporal stability in a marine reserve network.

Understanding the drivers of ecosystem stability has been a key focus of modern ecology as the impacts of the Anthropocene become more prevalent and extreme. Marine protected areas (MPAs) are tools used globally to promote biodiversity and mediate anthropogenic impacts. However, assessing the stability of natural ecosystems and responses to management actions is inherently challenging due to the complex dynamics of communities with many interdependent taxa. Using a 12-year time series of subtidal community structure in an MPA network in the Channel Islands (United States), we estimated species interaction strength (competition and predation), prey species synchrony, and temporal stability in trophic networks, as well as temporal variation in sea surface temperature to explore the causal drivers of temporal stability at community and metacommunity scales. At the community scale, only trophic networks in MPAs at Santa Rosa Island showed greater temporal stability than reference sites, likely driven by reduced prey synchrony. Across islands, competition was sometimes greater and predation always greater in MPAs compared with reference sites. Increases in interaction strength resulted in lower temporal stability of trophic networks. Although MPAs reduced prey synchrony at the metacommunity scale, reductions were insufficient to stabilize trophic networks. In contrast, temporal variation in sea surface temperature had strong positive direct effects on stability at the regional scale and indirect effects at the local scale through reductions in species interaction strength. Although MPAs can be effective management strategies for protecting certain species or locations, our findings for this MPA network suggest that temperature variation has a stronger influence on metacommunity temporal stability by mediating species interactions and promoting a mosaic of spatiotemporal variation in community structure of trophic networks. By capturing the full spectrum of environmental variation in network planning, MPAs will have the greatest capacity to promote ecosystem stability in response to climate change.

Efectos de la protección y variación de la temperatura sobre la estabilidad temporal en una red de reservas marinas Resumen El conocimiento sobre las causas de la estabilidad ambiental ha sido un enfoque importante de la ecología moderna conforme el impacto del Antropoceno se vuelve más prevaleciente y extremo. Las áreas marinas protegidas (AMP) son herramientas que se usan en todo el mundo para promover la biodiversidad y mediar el impacto antropogénico. Sin embargo, analizar la estabilidad de los ecosistemas naturales y la respuesta a las acciones de manejo es complicado debido a las dinámicas complejas entre las comunidades y varios taxones interdependientes. Usamos una serie temporal de 12 años de estructura comunitaria submareal en una red de AMP en las Islas del Canal (Estados Unidos) para estimar la fuerza de interacción de las especies (competencia y depredación), la sincronía de las especies depredadas y la estabilidad temporal en las redes tróficas, así como la variación temporal de la temperatura superficial del mar para explorar los factores causales de la estabilidad temporal a escala comunitaria y meta-comunitaria. A nivel de comunidad, sólo las redes tróficas en las AMP de la Isla Santa Rosa mostraron una estabilidad temporal mayor que en los sitios de referencia, probablemente debido a la reducción en la sincronía de presas. Entre las islas, la competencia a veces fue mayor y la depredación siempre fue mayor en las AMP comparadas con los sitios de referencia. Los incrementos en la fuerza de interacción causaron una menor estabilidad temporal en las redes tróficas. Aunque las AMP redujeron la sincronía de presas a nivel meta-comunitario, las reducciones no fueron suficientes para estabilizar las redes tróficas. Por el contrario, la variación temporal de la temperatura en la superficie marina tuvo grandes efectos positivos directos sobre la estabilidad a nivel regional y efectos indirectos a escala local por medio de reducciones en la fuerza de interacción entre las especies. Aunque las AMP pueden ser una estrategia efectiva de manejo para proteger ciertas especies o localidades, nuestros hallazgos en esta red de AMP sugieren que la variación térmica tiene una influencia más fuerte sobre la estabilidad temporal metacomunitaria cuando regula las interacciones entre especies y promueve un mosaico de variación espaciotemporal en la estructura comunitaria de las redes tróficas. Cuando se captura el espectro completo de variación ambiental en la planeación de redes, las AMP logran tener la capacidad máxima para promover la estabilidad del ecosistema como respuesta al cambio climático.