Laragustafson2024
Docking with Toll-like receptor (TLR-2) molecule confirmed the effective interaction of the vaccine with the receptor. The vaccine efficiency in generating an effective immune response in the host was evaluated by immune simulation. Finally, in silico cloning confirmed that the constructed vaccine can be efficiently expressed in E. coli. However, the designed vaccine needs experimental validation to determine the effectiveness and immunogenicity profile, which will ensure an active immunity against S. epidermidis.Resurgence refers to a behavioral process in which a recent response is extinguished (or reinforcement conditions worsen) and a previously extinguished response recurs. In previous research, resurgence has been reliably produced when the resurgence procedure is repeated. Changes in the degree of increase of the resurging response across iterations of the procedure have been inconsistent, however, with some studies showing increases and some showing no changes or decreases in resurgence magnitude. The present study examined the nature of resurgence across repeated iterations of the conventional resurgence procedure by exposing four pigeons to the resurgence procedure six times in succession. In the first condition of the resurgence procedure, pecks on one key (e.g., the left) were reinforced under a variable-interval (VI) 30-s schedule. In the second condition pecks on that key were extinguished, and pecks on another key (e.g., the right) were reinforced under the same schedule. In the final condition there were no programmed consequences for either response. Resurgence was observed in 21 of 24 opportunities (87.5%). Iteration-over-iteration increases in resurgence were observed in 15 of 20 opportunities (75.0%), and this increase was found to be statistically significant. These findings demonstrate that, under certain conditions, resurgence generally increases in magnitude with repeated exposure to the procedures that generate it.Impulsive choice may play an important role in serious health-related decisions, like addiction tendencies. Thus, there is merit in exploring interventions that reduce impulsive choice. Delay-exposure training involves extended experience with delayed reinforcement. Following training, delay-exposed rats make fewer impulsive choices than control rats. The reducing effects of delay exposure training on impulsive choice have been replicated in male rats seven times. For the first time, this study evaluated the effects of delay exposure training in female rats. Thirty-six rats were randomly assigned to either delay-exposure or immediacy-exposure training. Then, rats underwent two impulsive choice assessments in which they chose between one immediate pellet or three delayed pellets. In the first assessment, delays increased within-sessions, across trial blocks from 0, 8, 16, to 32 s. In the second assessment, delays to the larger reward increased between-sessions, from 8, 16, 32, to 4 s. Unlike findings with male rats, delay-exposure training produced a reduction in impulsive choice only in the initial five sessions in female rats. Possible reasons for the lack of lasting effect in female rats are discussed and future research directions are identified.Social learning is widespread across species; however, we still know little about the impact of individual differences in behaviour on social transmission. We aimed to investigate factors influencing social learning in free-living Rhabdomys pumilio, a group-living, arid-adapted mouse. We studied 52 mice in a lid opening task in a field laboratory. We created observer-demonstrator dyads with demonstrators either opening lids or not. We measured success of observers to open lids, their attention and latency to open and time spent interacting with the device. We also considered influences of observer age, sex, group size and personality traits. Demonstrator success did not influence observer success, although attention towards the demonstrator did impact the observers' time spent with the device. Males were more successful than females and more active/explorative observers interacted with the device faster and for a longer time compared to less active/explorative counterparts. We found no influence of age and group size on mouse success. Striped mice appeared to use cues from other individuals to learn how to solve the task and it was influenced by sex and personality. Striped mice in this studied population may use local enhancement to acquire information socially.The krüppel-like factor (KLF) family is a group of zinc finger transcription factors and contributes to different cellular processes such as differentiation, proliferation, migration, and apoptosis. While different studies show the roles of this family in skeletal development-specifically in chondrocyte and osteocyte development and bone homeostasis-there are few reviews summarizing their importance. To fill this gap, this review discusses current knowledge on different functions of the KLF family during skeletal development, including their roles in stem cell maintenance and differentiation, cell apoptosis, and cell cycle. To understand the importance of the KLF family, we also review genotype-phenotype correlations in different animal models. We also discuss how KLF proteins function through different signaling pathways and display their paramount importance in skeletal development. To highlight their roles in cartilage- or bone-related cells, we also use single-cell RNA sequencing publicly available data on mouse hindlimb. We also challenge our knowledge of how the KLF family is epigenetically regulated-e.g., using DNA methylation, histone modifications, and noncoding RNAs-during chondrocyte and osteocyte development.Exposure to trichloroethylene (TCE), an industrial solvent, is associated with several adverse pregnancy outcomes in humans and decreased fetal weight in rats. However, effects of TCE on energy metabolites in amniotic fluid, which have associations with pregnancy outcomes, has not been published previously. In the current exploratory study, timed-pregnant Wistar rats were exposed to 480 mg TCE/kg/day via vanilla wafer or to vehicle (wafer) alone from gestational day (GD) 6-16. Amniotic fluid collected on GD 16 was analyzed for metabolites important in energy metabolism using short chain fatty acid and tricarboxylic acid plus platforms (N = 4 samples/sex/treatment). TCE decreased concentrations of the following metabolites in amniotic fluid for both fetal sexes 6-phosphogluconate, guanosine diphosphate, adenosine diphosphate, adenosine triphosphate, and flavin adenine dinucleotide. TCE decreased fructose 1,6-bisphosphate and guanosine triphosphate concentrations in amniotic fluid of male but not female fetuses. Moreover, TCE decreased uridine diphosphate-D-glucuronate concentrations, and increased arginine and phosphocreatine concentrations, in amniotic fluid of female fetuses only. No metabolites were increased in amniotic fluid of male fetuses. Pathway analysis suggested that TCE altered folate biosynthesis and pentose phosphate pathway in both sexes. Using metabolite ratios to investigate changes within specific pathways, some ratio alterations, including those in arginine metabolism and phenylalanine metabolism, were detected in females only. Ratio analysis also suggested enzymes, including gluconokinase, as potential TCE targets. Together, results from this exploratory study suggest that TCE differentially modified energy metabolites in amniotic fluid based on sex. These findings may inform future studies of TCE reproductive toxicity.This study aimed at determining the effect of prenatal ethanol exposure (PEE) on the expression and activity of cytochrome P450 (CYP) isozymes at different life stages of male rat offspring. Pregnant Wistar rats were administered with ethanol (4 g/kg/d) intragastrically from gestational day (GD) 9-20. Male offspring's gene and activity of CYP isozymes were analyzed on GD 20 (only expression), postnatal day (PD) 84 and 196. Using aniline as probe, we compared the enzyme kinetics of hepatic CYP2E1 between two groups. Expression of CYP isozymes was examined in rat primary hepatocytes and human hepatic cell lines treated with ethanol or/and glucocorticoid. Gene level of Cyp1a2, 2b1, 2d1, 2e1, 3a1 and aryl hydrocarbon receptor were increased in PEE group on GD 20 and PD 84 and Cyp2e1 still exhibited an increasing trend on PD 196 compared with the control. PEE inhibited CYP2D1 and 2E1 activities in male offspring on PD 84. CYP activities in two groups became the same level on PD 196. PEE induced an opposite change in gene and protein level of hepatic CYP2E1 before and after birth. In consistent with lower protein level, aniline metabolism in PEE was weaker in liver microsome. Both single and combined use of ethanol or/and glucocorticoid increased CYPs expression in vitro. In conclusion, PEE programmed a higher gene and lower protein level of CYPs in male offspring, which dwindled with age. Impairment of protein levels and enzyme activities of CYPs may affect individual metabolism of endogenous and exogenous substances in early adulthood.
To understand whether perioperative SARS-CoV-2 infection increases risk of pulmonary complications in children.
A retrospective cohort study of children who underwent surgery with perioperative SARS-CoV-2 infection at a children's hospital from March 1, 2020, to June 30, 2021. Uninfected, age-matched control patients who underwent the same procedure as infected patients over the past ten years were included in the study in a 31 ratio to infected patients. see more Primary outcomes were 7- and 30-day mortality. Secondary outcomes were development of pulmonary complications, readmission, length of hospital or ICU stay, and oxygen administration in post-anesthesia care unit (PACU).
Our study included 73 patients who underwent surgery with perioperative diagnosis of SARS-CoV-2, and 218 control patient undergoing similar procedures. One total mortality event was observed within 7 days in an uninfected control patient, and none occurred in infected patients. Perioperative SARS-CoV-2 infection was associated with increased risk for pulmonary complications in univariate analysis. Infection was not associated with any of our other secondary outcomes. Symptomatic SARS-CoV-2 infection and timing of diagnosis was not associated with development of pulmonary complications among infected patients.
Children with perioperative SARS-CoV-2 infection may be at increased risk for development of pulmonary complications. Larger studies should be performed to confirm our results.
Children with perioperative SARS-CoV-2 infection may be at increased risk for development of pulmonary complications. Larger studies should be performed to confirm our results.For human immunodeficiency virus 1 (HIV-1) to infect non-dividing cells, pre-integration complex (PIC) must be transported into the nucleus within the replication cycle. We previously reported that the karyopherin β1 (KPNB1)-nucleoporin Pom121 pathway, related to the downstream process of PIC nuclear import, mediates efficient HIV-1 PIC nuclear import. Further, our earlier RNA transcriptome sequencing revealed that karyopherin α2 (KPNA2) was among the differentially expressed importin family members during monocyte to macrophage differentiation. Although PIC transport into the nucleus in HIV-1 has been widely studied, much remains to be understood about it. In this study, we confirmed our previous RNA sequencing results and found that HIV-1 replication was significantly lower in 293T cells with siRNA-mediated KPNA2 knockdown and higher in KPNA2-upregulated cells. Quantitative PCR indicated that viral replication was impaired during cDNA nuclear import. The N-terminal of the capsid protein p24 interacted with KPNA2, and KPNB1 participated in KPNA2-mediated PIC nuclear import.