The
comprise a group of highly adapted bacterial pathogens sharing a unique intracellular lifestyle. Three
species are pathogenic to humans:
, and
.
is the leading bacterial cause of ...sexually-transmitted infections and infectious blindness worldwide.
is a major cause of community-acquired atypical pneumonia.
primarily affects psittacine birds and can be transmitted to humans causing psittacosis, a potentially fatal form of pneumonia. As opposed to other bacterial pathogens, the spread of clinically relevant antimicrobial resistance genes does not seem to be a major problem for the treatment of
infections. However, when exposed to stressing conditions, like those arising from exposure to antimicrobial stimuli, these bacteria undergo a temporary interruption in their replication cycle and enter a viable but non-cultivable state known as persistence. When the stressing conditions are removed,
resumes replication and generation of infectious particles. This review gives an overview of the different survival strategies used by
to evade the deleterious effects of penicillin and IFNγ, with a focus on the different models used to study
persistence, their contribution to elucidating the molecular basis of this complex phenomenon and their potential implications for studies in animal models of infection.
Persistence was recently identified to have three dimensions: persistence despite difficulties (PDD), persistence despite fear (PDF), and inappropriate persistence (IP). To promote the study of ...multidimensional persistence, we integrate the approach/avoidance framework with PDD, PDF, and IP. We assess the relations of these three dimensions with both known and novel outcomes, and we also test whether approach and avoidance motivations mediate these effects. From a time-separated study, our results show that PDD and PDF produce beneficial work and well-being outcomes, whereas IP produces detrimental work and well-being outcomes. Approach motivations also mediated the relations of PDD with outcomes, whereas avoidance motivations mediated the relations of PDF and IP with outcomes. These results support that the approach/avoidance framework is a viable perspective to understand the outcomes of persistence. We recommended that future researchers should assess the broader proposals of the approach/avoidance framework regarding persistence, and we also suggest that future researchers can now link persistence with other outcomes previously associated with approach and avoidance motivations.
The efficacy of chimeric antigen receptor (CAR) T cell therapy is limited in solid tumors by several factors including the immunosuppressive tumor microenvironment that gives rise to poorly ...persisting and metabolically dysfunctional T cells and a lack of long-term persistence. To overcome this, we sought to identify transcription factors that could enhance CAR T cell metabolic fitness and enhance their durability and therapeutic activity. Through this work we identified FOXO1 as a master regulator of CAR T cell “stemness” and demonstrated that FOXO1 overexpression significantly enhanced CAR T cell efficacy against solid tumors (Chan et al. 2024, Nature, in press).
IL-15 has previously been demonstrated to impart a pro-memory T cell phenotype and to favorably modify CAR T cell metabolism. We therefore sought to identify transcription factors that governed the phenotype induced by IL-15. To this end we interrogated transcriptional and epigenetic analyses of IL-15 conditioned CAR T cells and identified FOXO1 as a putative master regulator of CAR T cell stemness. We subsequently overexpressed FOXO1 both in murine anti-Her2 CAR T cells and human anti-Lewis Y CAR T cells and assessed their function in syngeneic and xenograft models respectively. Furthermore the mechanism by which FOXO1 enhanced CAR T cell stemness was interrogated through RNA-Seq, ATAC-Seq and scRNA-seq analyses.
Overexpression of Foxo1 enhanced the therapeutic efficacy of murine CAR T cells in the setting of syngeneic immunocompetent models and was dependent on the sustained production of proinflammatory cytokines. FOXO1 overexpression in human CAR T cells enforced broad transcriptional and epigenetic changes that led to a more “stem-like” phenotype and similarly improved therapeutic efficacy. Enhanced efficacy was associated with improved mitochondrial fitness and 20 fold increased persistence in vivo. FOXO1 overexpression also led to a more stem like phenotype and increased persistence of patient derived CAR T cells.
These findings were corroborated by an independent study by the Weber/ Mackall groups that demonstrated that FOXO1 overexpression also enhanced therapeutic activity against B-ALL (also accepted at Nature).
Therefore, FOXO1 overexpression is a promising strategy to enhance the persistence and effectiveness of CAR T cells in the context of both solid cancers and hematological malignancies.
Background
Item response times in computerized assessments are frequently used to identify rapid guessing behaviour as a manifestation of response disengagement. However, non‐rapid responses (i.e., ...with longer response times) are not necessarily engaged, which means that response‐time‐based procedures could overlook disengaged responses. Therefore, the identification of disengaged responses could be improved by considering additional indicators of disengagement. We investigated the extent to which decreases in individuals' item solution probabilities over the course of a test reflect disengaged response behaviour.
Objectives
To disentangle different types of possibly disengaged responses and better understand non‐effortful test‐taking behaviour, we augmented responses‐time‐based procedures for identifying rapid guessing with strategies for detecting disengaged responses on the basis of performance declines in non‐rapid responses.
Methods
We combined item response theory (IRT) models for rapid guessing and test‐taking persistence to examine the capability of response times and item positions to capture response disengagement. We used a computerized assessment in which science items were randomly distributed across positions for each student. This allowed us to estimate individual differences in test‐taking persistence (i.e., the duration for which the initial level of performance is maintained) while accounting for rapid responses.
Results and Conclusions
Response times did not fully explain disengagement; item responses reflected test‐taking persistence even when rapid responses were accounted for. This interpretation was supported by a strong correlation of test‐taking persistence with decreases in self‐reported test‐taking effort. Furthermore, our results suggest that IRT models for test‐taking persistence can effectively account for the undesirable impact of low test‐taking effort even when response times are unavailable.
Practitioner Notes
Assessments of proficiencies that attempt to quantify what individuals know and can do lead to biased results when individuals provide disengaged responses.
Item response times are frequently used to identify rapid guessing behaviour as a manifestation of response disengagement, but response‐time‐based procedures could overlook disengaged responses.
To disentangle different types of possibly disengaged responses and better understand non‐effortful test‐taking behaviour, we augmented responses‐time‐based procedures for identifying rapid guessing with strategies for detecting disengaged responses on the basis of performance declines in non‐rapid responses.
In a sample of fifth and sixth graders, we found that response times did not fully explain disengagement, as many students showed performance declines in non‐rapid item responses.
Our results suggest that item response theory models for test‐taking persistence can effectively account for the undesirable impact of low test‐taking effort even when response times are unavailable.
Lactobacillus is a commonly used probiotic, and many researchers have focused on its stress response to improve its functionality and survival. However, studies on persister cells, dormant cells that ...aid bacteria in surviving general stress, have focused on pathogenic bacteria that cause infection, not Lactobacillus. Thus, understanding Lactobacillus persister cells will provide essential clues for understanding how Lactobacillus survives and maintains its function under various environmental conditions. We treated Lactobacillus strains with various antibiotics to determine the conditions required for persister formation using kill curves and transmission electron microscopy. In addition, we observed the resuscitation patterns of persister cells using single-cell analysis. Our results show that Lactobacillus creates a small population of persister cells (0.0001-1% of the bacterial population) in response to beta-lactam antibiotics such as ampicillin and amoxicillin. Moreover, only around 0.5- 1% of persister cells are heterogeneously resuscitated by adding fresh media; the characteristics are typical of persister cells. This study provides a method for forming and verifying the persistence of Lactobacillus and demonstrates that antibiotic-induced Lactobacillus persister cells show characteristics of dormancy, sensitivity of antibiotics, same as exponential cells, multi-drug tolerance, and resuscitation, which are characteristics of general persister cells. This study suggests that the mechanisms of formation and resuscitation may vary depending on the characteristics, such as the membrane structure of the bacterial species.
This longitudinal study investigated development in expectancy for success (perceived competence), 3 types of task value (utility, interest, attainment), and 3 types of perceived cost (opportunity, ...effort, psychological) for engineering students during their first 2 years of college. Latent growth curve models indicated declines in expectancy and values, with attainment value declining more slowly than expectancy, interest value, and utility value. Costs increased over time, with effort cost increasing more rapidly than psychological cost. Demographic differences were observed in initial levels of motivation, but not in rates of change over time. Students with slower declines in expectancy and value and slower increases in effort cost achieved higher grades and were more likely to remain in an engineering major. The attainment value model explained the largest amount of variance in engineering major retention, while the expectancy model explained the largest amount of variance in GPA. Taking a supportive gateway course in the first semester rather than later was associated with slower declines in utility value and attainment value, and slower increases in effort cost. Results suggest expectancy, values, and costs display unique patterns of development and uniquely relate to predictors and outcomes, extending our theoretical understanding of motivation in early college. Implications for practice include the promise of programmatic efforts to support students' motivation in engineering through supportive gateway courses early in college.
Educational Impact and Implications Statement
Motivation processes provide a promising avenue for addressing attrition and representation issues in STEM fields. Yet, little is known about the development of specific forms of motivation and their correlates during the first 2 years of college, a key time for shaping motivational beliefs and future choices. Among college engineering students, positive motivational beliefs (expectancy for success, interest value, attainment value, and utility value) regarding engineering declined over time while negative motivational beliefs (perceived opportunity cost, effort cost, and psychological cost) increased over time. Differential rates of change for each motivation construct suggest that developmental processes differ across motivational constructs. Women did not report different trajectories than men; however, underrepresented minority students and first-generation college students reported more adaptive patterns of motivation when beginning college. Developmental trajectories of motivation constructs were significantly related to retention and grades, with expectancy most strongly predicting grades and identity-related attainment value most strongly predicting major retention. Lastly, students enrolled in a supportive gateway course in their first semester (vs. later) exhibited slower declines in attainment and utility value, and slower increases in effort cost. Results highlight the importance of supporting college students' motivation in STEM fields and of the key role of supportive gateway courses. Furthermore, differences in developmental trajectories and their relations to predictors highlight the need to understand students' specific motivational needs. Results also suggest implications for the timing and design of motivational interventions to support college student success in STEM.
In order to study the influence of entrepreneurial passion on entrepreneurs’ psychology and behavior, based on the theory of self-efficacy, a model of relationship between entrepreneurial passion and ...entrepreneurs’ psychology and behavior was constructed, relevant hypotheses were proposed, and the promotion mechanism of entrepreneurial passion on entrepreneurial behavior and enterprise performance was analyzed. A survey of 300 entrepreneurs from Hangzhou, Wenzhou, Jiaxing, Shaoxing, and Huzhou was conducted to verify the reliability of the questionnaire through statistical description and analysis. Then exploratory factor analysis and confirmatory factor analysis (CFA) were conducted to test the correlation between variables. Finally, the structural equation was simulated to verify the correctness of the proposed hypothesis and model. The results show that the designed questionnaire has good reliability the correction item total correlation coefficients (CITC) of all scales are greater than 0.3, values of Cronbach’s α are higher than 0.6, the validity (all inventory accumulation explanation degree are higher than 50%) and the fitting (χ
2
/df values of all scales are less than 3, comparative fitness index (CFI), goodness of fitness index (GFI), and incremental fitness index (IFI) are greater than 0.9, root-mean-square error of approximation (RMSEA) value is less than 0.08). The direct effect of harmonious passion on entrepreneurial persistence and enterprise performance is not significant, while the direct effect of compulsive passion on entrepreneurial persistence and enterprise performance is significant. Harmonious passion (
P
< 0.001) and compulsive passion (
P
< 0.01) are significantly correlated with entrepreneurial self-efficacy, and self-efficacy plays a mediating role between entrepreneurial passion and entrepreneur psychology and behavior (
P
< 0.05), and the hypothesis proposed is basically valid. Therefore, entrepreneurial passion can positively guide the entrepreneurial persistence of entrepreneurs, and at the same time promote the performance of enterprises by stimulating the positive emotions of entrepreneurs. In addition, entrepreneurs can enhance their entrepreneurial role identity, maintain a positive attitude, stimulate creativity, and innovation, to enhance their sense of energy efficiency. The government can also promote successful business cases to build an inclusive and innovative social environment and stimulate the entrepreneurial passion of entrepreneurs. This study reveals the relationship between entrepreneurial passion, self-efficacy, and entrepreneur psychology and behavior, and extends the application of entrepreneurial passion in the field of entrepreneurship.
The so-called leaking STEM pipeline (dropout in STEM education) has been the subject of many studies. The large interest of scholars in plausible causes of this leakage has resulted in a number of ...meta-reviews describing factors at system, school and student level related to interest and persistence in STEM education. The STEM pipeline discussion has also resulted in a large number of programmes aimed at enhancing STEM interest and persistence in STEM education. Although these programmes have been widely evaluated, there seems to be no consensus about which interventions are successful in raising interest in STEM or persistence in STEM education. This study reports the results of a systematic review of empirical studies in which the effectiveness of STEM-related interventions are assessed. Initially, 538 studies were found. The quality analyses showed that only a few of these evaluation studies are designed in such a way that it is likely that the found effects are caused by the intervention. Although some potentially effective interventions were found, this review shows that there is still a need for research into the effectiveness of those programmes, especially with regard to programmes preventing talented and initially motivated STEM students to drop out of STEM education.
To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19).
We measured anti-RBD (receptor ...binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay.
Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7–87.8), 3 (103.2 U/mL, 95%CI: 87.9–121.2; p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4–147.0; p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9–24.0), 3 (15.2 AU/mL, 95%CI: 13.2–17.6; p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7–11.4; p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics.
Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.
A wide range of occupations require science, technology, engineering, and mathematics (STEM) skills, yet almost half of students who intend to pursue a postsecondary STEM education abandon these ...plans before graduating from college. This attrition is especially pronounced among underrepresented groups (i.e., racial/ethnic minorities and first-generation college students). We conducted a 2-year follow-up of a utility-value intervention that had been implemented in an introductory biology course. This intervention was previously shown to improve performance in the course, on average and especially among underrepresented students, reducing the achievement gap. The goal of the present study was to examine whether the intervention also impacted persistence in the biomedical track throughout college. The intervention had a more positive impact on long-term persistence for students who were more confident that they could succeed at the beginning of the course, and this effect was partially driven by the extent to which students reflected on the personal relevance of biological topics in their essays. This mechanism was distinct from the process that had been found to underlie intervention effects on performance-engagement with course material-suggesting that utility-value interventions may affect different academic outcomes by initiating distinct psychological processes. Although we did not find that the intervention was differentially effective for underrepresented students in terms of persistence, we found that positive effects on performance were associated with increased persistence for these students. Results suggest that utility-value interventions in an introductory course can be an effective strategy to promote persistence in the biomedical sciences throughout college.
Educational Impact and Implications Statement
We conducted a 2-year follow-up study of a utility-value intervention (UVI) in which students wrote about the personal value of course topics in an introductory biology course for biomedical majors, and examined persistence in terms of subsequent course-taking and whether students were biomedical majors. The original study found that the UVI improved course grades for all students, on average, as well as for underrepresented students, by promoting engagement with intervention writing assignments. In the current follow-up, we found that the UVI indirectly increased persistence through the original effects on course grades, for all students on average and for underrepresented students in particular: better course grades were associated with higher levels of persistence. In addition, we found that among students who received the UVI, those who were more confident that they could succeed in the course were more likely to persist in a biomedical education 2 years later, an effect explained by increased focus on personal relevance in students' biology writing assignments. This study has important implications for college science educators who seek to retain their students and promote diversity in the biomedical sciences.
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