Writing about a stressful experience can impair visual working memory.

Acute stress has been well-established to impair working memory. However, less is known about how writing about an unresolved stressor may influence working memory or working memory processes. We addressed these issues in the present study (N = 282) by randomly assigning participants to write about an unresolved stressful experience (stressful writing condition or the events of the previous day). We then both measured performance on a change detection task and used computational modeling to estimate the processes underlying performance: attention, capacity, and guessing bias. We found that, relative to the control condition, writing about a stressful experience impaired change detection task performance and significantly impaired task attention. These results show that the effects of writing about an unresolved stressor may mimic the effects of acute stress on working memory, rather than conforming to expectations from mood-as-information theory.

Sarbecovirus disease susceptibility is conserved across viral and host models.

Coronaviruses have caused three severe epidemics since the start of the 21st century: SARS, MERS and COVID-19. The severity of the ongoing COVID-19 pandemic and increasing likelihood of future coronavirus outbreaks motivates greater understanding of factors leading to severe coronavirus disease. We screened ten strains from the Collaborative Cross mouse genetic reference panel and identified strains CC006/TauUnc (CC006) and CC044/Unc (CC044) as coronavirus-susceptible and resistant, respectively, as indicated by variable weight loss and lung congestion scores four days post-infection. We generated a genetic mapping population of 755 CC006xCC044 F2 mice and exposed the mice to one of three genetically distinct mouse-adapted coronaviruses: clade 1a SARS-CoV MA15 (n=391), clade 1b SARS-CoV-2 MA10 (n=274), and clade 2 HKU3-CoV MA (n=90). Quantitative trait loci (QTL) mapping in SARS-CoV MA15- and SARS-CoV-2 MA10-infected F2 mice identified genetic loci associated with disease severity. Specifically, we identified seven loci associated with variation in outcome following infection with either virus, including one, HrS43, that is present in both groups. Three of these QTL, including HrS43, were also associated with HKU3-CoV MA outcome. HrS43 overlaps with a QTL previously reported by our lab that is associated with SARS-CoV MA15 outcome in CC011xCC074 F2 mice and is also syntenic with a human chromosomal region associated with severe COVID-19 outcomes in humans GWAS. The results reported here provide: (a) additional support for the involvement of this locus in SARS-CoV MA15 infection, (b) the first conclusive evidence that this locus is associated with susceptibility across the Sarbecovirus subgenus, and (c) demonstration of the relevance of mouse models in the study of coronavirus disease susceptibility in humans.

Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.

National Beef Quality Audit-2022 Phase 1: face-to-face and digital interviews.

The National Beef Quality Audit (NBQA) has been conducted regularly since 1991 to assess and benchmark quality in the U.S. beef industry, with the most recent iteration conducted in 2022. The goal of NBQA Phase I is to evaluate what needs to be managed to improve beef quality and demand. Interviews (n = 130) of industry personnel were conducted with the aid of routing software. In total, packers (n = 24), retailers (n = 20), further processors (n = 26), foodservice (n = 18), and allied government agencies and trade organizations (n = 42) were interviewed. Interviews were routed in software based on interviewee involvement in either the fed steer and heifer market cow and bull sectors, or both. Interviews were structured to elicit random responses in the order of determining "must-have" criteria (quality factors that are required to make a purchase), best/worst ranking (of quality factors based on importance), how interviewees defined quality terms, a strength, weakness, opportunities, threats (SWOT) analysis, general beef industry questions, and sustainability goals (the latter four being open-ended). Quality factors were 1) visual characteristics, 2) cattle genetics, 3) food safety, 4) eating satisfaction, 5) animal well-being, 6) weight and size, and 7) lean, fat, and bone. Best/worst analysis revealed that "food safety" was the most (P < 0.05) important factor in beef purchasing decisions for all market sectors and frequently was described as "everything" and "a way of business." Culture surrounding food safety changed compared to previous NBQAs with interviewees no longer considering food safety as a purchasing criterion, but rather as a market expectation. The SWOT analysis indicated that "eating quality of U.S. beef" was the greatest strength, and cited that educating both consumers and producers on beef production would benefit the industry. Irrespective of whether companies' products were fed or market cow/bull beef, respondents said that they believed "environmental concerns" were among the major threats to the industry. Perceived image of the beef industry in the market sectors has improved since NBQA-2016 for both fed cattle and market cow/bull beef.

A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice.

BACKGROUND: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice. OBJECTIVE: This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice. METHODS: A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains. RESULTS: Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge-6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. CONCLUSIONS: Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.

A mismatch between early and recent life stress predicts better response inhibition, but not cognitive inhibition.

A growing body of work has found that a mismatch between early and recent life stress, more than a cumulative influence of stress, contributes to detrimental stress-related health outcomes. To date, however, no work has examined how such a mismatch might relate to stress-related cognitive outcomes. We addressed this gap in the current study by assessing participants' (N = 154, Mage = 18.7, 104 female) early and recent life stress using the same inventory, and subsequently assessing their inhibitory control in a hybrid stop-signal/flanker task. Surprisingly, we found that a greater degree of stressor mismatch was associated with better response inhibition (i.e. smaller stop-signal reaction time) across a number of analytic approaches. Cognitive inhibition (i.e. the flanker interference effect) was not associated with stressor mismatch. These results thus show that a greater degree of mismatch between early and recent life stress is related to response inhibition in the same way as acute stress affects response inhibition, suggesting that response inhibition may be an important cognitive process for navigating both acute stress and general environmental conditions that do not match the conditions in which expected stress occurrence was established.

Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans.

Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.

Acute stress influences the emotional foundations of executive control: Distinct effects on control-related affective and cognitive processes.

Acute stress is known to influence performance on various task outcomes indicative of executive functioning (i.e., the top-down, goal-directed control of cognition and behavior). The most common interpretation of these effects is that stress influences control processes themselves. Another possibility, though, is that stress does not impair control per se, but instead alters the affective dynamics underlying the recruitment of control (e.g., reducing the extent to which making an error is aversive), resulting in less recruitment of control and thus poor performance. To date, however, no work has examined whether stress effects on executive function outcomes are driven by affective dynamics related to the recruitment of control. In the current study, we found that acute stress influenced-and cortisol responses related to-both executive control-related performance outcomes (e.g., post-error slowing) and control-related affective dynamics (e.g., negative affect following recruitment of control) in a modified Stroop task, but that these effects appeared to be independent of each other: The effects of stress on, and associations of cortisol with, control-related cognitive outcomes were not statistically mediated by task- or control-related affective dynamics. These results thus suggest that although stress influences affective dynamics underlying executive function, the effects of stress on executive function outcomes appear to be at least partially dependent on nonaffective processes, such as control processes themselves.

Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice.

BACKGROUND AIMS: Human genetic variation is thought to guide the outcome of HCV infection, but model systems within which to dissect these host genetic mechanisms are limited. Norway rat hepacivirus, closely related to HCV, causes chronic liver infection in rats but causes acute self-limiting hepatitis in typical strains of laboratory mice, which resolves in 2 weeks. The Collaborative Cross (CC) is a robust mouse genetics resource comprised of a panel of recombinant inbred strains, which model the complexity of the human genome and provide a system within which to understand diseases driven by complex allelic variation. APPROACH RESULTS: We infected a panel of CC strains with Norway rat hepacivirus and identified several that failed to clear the virus after 4 weeks. Strains displayed an array of virologic phenotypes ranging from delayed clearance (CC046) to chronicity (CC071, CC080) with viremia for at least 10 months. Body weight loss, hepatocyte infection frequency, viral evolution, T-cell recruitment to the liver, liver inflammation, and the capacity to develop liver fibrosis varied among infected CC strains. CONCLUSIONS: These models recapitulate many aspects of HCV infection in humans and demonstrate that host genetic variation affects a multitude of viruses and host phenotypes. These models can be used to better understand the molecular mechanisms that drive hepacivirus clearance and chronicity, the virus and host interactions that promote chronic disease manifestations like liver fibrosis, therapeutic and vaccine performance, and how these factors are affected by host genetic variation.

Writing about a stressful experience improves semantic clustering of memory in men, not women.

Writing about negative experiences can produce multiple benefits, including improvements in mental and emotional health. However, writing about negative experiences potentially be detrimental, as reliving and reexperiencing a negative memory can be painful. Although the emotional effects of writing about negative experiences are well established, the cognitive effects are less heavily explored, and no work to date has examined how writing about a stressful experience might influence episodic memory. We addressed this issue in the present study (N = 520) by having participants encode a list of 16 words that were organised around four semantic clusters, randomly assigning participants to write about an unresolved stressful experience (n = 263) or the events of the previous day (n = 257), and assessing their memory in a free recall task. Writing about a stressful experience did not influence overall memory performance; however, the stressful writing manipulation increased semantic clustering of information within memory for men, whereas the stressful writing manipulation did not influence semantic clustering of information within memory in women. Additionally, writing with more positive sentiment improved semantic clustering and reduced serial recall. These results provide evidence for unique sex differences in writing about stressful experiences and the role of sentiment in the effects of expressive writing.

Is Irreligion a Risk Factor for Suicidality? Findings from the Nashville Stress and Health Study.

Suicide is a public health problem and one of the leading causes of death in the United States. Research exploring the linkages between religion and spirituality has received intermittent attention. Data was derived from the Nashville Stress and Health Study (2011-2014), a cross-sectional probability survey of black and white adults from Davidson County, Tennessee (n = 1252). Results indicate that those with no perceived belief in divine control had a higher likelihood of suicidality. This study provides a fresh perspective on the links between religious factors and suicidality by (a) considering multiple religious and spiritual domains and (b) focusing on the association between irreligion and suicidality.

A mutation in Themis contributes to peanut-induced oral anaphylaxis in CC027 mice.

Background: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, unlike C3H/HeJ (C3H) mice. Objective: To determine the genetic basis of orally-induced anaphylaxis to peanut in CC027 mice. Methods: A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 and five additional CC strains. Results: Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis, and 4% having severe anaphylaxis. A total of eight genetic loci were associated with variation in response to peanut challenge, six associated with anaphylaxis (temperature decrease) and two associated with peanut-specific IgE levels. There were two major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis (thymocyte-expressed molecule involved in selection) gene. Consistent with Themis' described functions, we found that CC027 have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. Conclusion: Our results demonstrate a key role for Themis in the orally-reactive CC027 mouse model of peanut allergy.

(A lack of) effects of acute social stress on attentional bias to threat.

Attentional biases toward or away from emotionally evocative stimuli have been well documented and are known to be clinically relevant, making it important to understand how various factors contribute to them. Some work has suggested that acute stress modulates attentional biases, but this work has produced inconsistent results. For example, many studies have found that stress enhances attentional bias, others that stress decreases attentional bias, and others still that there is no effect of stress at all. Methodological differences may explain these inconsistencies. For example, discrepancies exist between studies in participant sex (e.g., mixed sample vs. all men) and in the type of attentional bias paradigm. We addressed these gaps by examining the effects of an acute social stressor (vs. control) on attentional bias assessed via facial dot probe, focusing on potential sex differences in these effects (N = 141). We found that, overall, participants were significantly biased towards threat, but biases did not differ by stress condition or sex. These findings help to clarify the existing discrepancy in the literature, as we found that stress exerts little if any effect on attentional bias assessed via a facial dot probe.

APJ+ cells in the SHF contribute to the cells of aorta and pulmonary trunk through APJ signaling.

Outflow tract (OFT) develops from cardiac progenitor cells in the second heart field (SHF) domain. APJ, a G-Protein Coupled Receptor, is expressed by cardiac progenitors in the SHF. By lineage tracing APJ+SHF cells, we show that these cardiac progenitors contribute to the cells of OFT, which eventually give rise to aorta and pulmonary trunk/artery upon its morphogenesis. Furthermore, we show that early APJ â€‹+ â€‹cells give rise to both aorta and pulmonary cells but late APJ â€‹+ â€‹cells predominantly give rise to pulmonary cells. APJ is expressed by the outflow tract progenitors in the SHF but its role is unclear. We performed knockout studies to determine the role of APJ in SHF cell proliferation and survival. Our data suggested that APJ knockout in the SHF reduced the proliferation of SHF progenitors, while there was no significant impact on survival. In addition, we show that ectopic overexpression of WNT in these cells disrupted aorta and pulmonary morphogenesis from OFT. Overall, our study has identified APJ â€‹+ â€‹progenitor population within the SHF that give rise to aorta and pulmonary trunk/artery cells. Furthermore, we show that APJ signaling stimulates proliferation of these cells in the SHF.

Forward genetic screen of homeostatic antibody levels in the Collaborative Cross identifies MBD1 as a novel regulator of B cell homeostasis.

Variation in immune homeostasis, the state in which the immune system is maintained in the absence of stimulation, is highly variable across populations. This variation is attributed to both genetic and environmental factors. However, the identity and function of specific regulators have been difficult to identify in humans. We evaluated homeostatic antibody levels in the serum of the Collaborative Cross (CC) mouse genetic reference population. We found heritable variation in all antibody isotypes and subtypes measured. We identified 4 quantitative trait loci (QTL) associated with 3 IgG subtypes: IgG1, IgG2b, and IgG2c. While 3 of these QTL map to genome regions of known immunological significance (major histocompatibility and immunoglobulin heavy chain locus), Qih1 (associated with variation in IgG1) mapped to a novel locus on Chromosome 18. We further associated this locus with B cell proportions in the spleen and identify Methyl-CpG binding domain protein 1 under this locus as a novel regulator of homeostatic IgG1 levels in the serum and marginal zone B cells (MZB) in the spleen, consistent with a role in MZB differentiation to antibody secreting cells.

A comparison of Mini-FLOTAC and McMaster techniques, overdispersion and prevalence of parasites in naturally infected North American bison (Bison bison) in the USA.

Several quantitative diagnostic techniques are available to estimate gastrointestinal parasite counts in the feces of ruminants. Comparing egg and oocyst magnitudes in naturally infected samples has been a recommended approach to rank fecal techniques. In this study, we compared the Mini-FLOTAC (sensitivity of 5 eggs per gram (EPG)/oocysts per gram (OPG)) and different averaged replicates of the modified McMaster techniques (sensitivity of 33.33 EPG/OPG) in 387 fecal samples from 10 herds of naturally infected North American bison in the Central Great Plains region of the USA. Both techniques were performed with fecal slurries homogenized in a fill-FLOTAC device. In the study population, prevalence of strongyle eggs, Eimeria spp. oocysts, Moniezia spp. eggs and Trichuris spp. eggs was 81.4%, 73.9%, 7.5%, and 3.1%, respectively. Counts of strongyle eggs and Eimeria spp. oocysts obtained from 1 to 3 averaged technical replicates of the modified McMaster technique were compared to a single replicate of the Mini-FLOTAC. Correlation between the two techniques increased with an increase in the number of averaged technical replicates of the modified McMaster technique used to calculate EGP/OPG. The correlation for Moniezia spp. EPG when averaged triplicates of the modified McMaster technique were compared to a single replicate of the Mini-FLOTAC count was high; however, the correlation for Trichuris spp. eggs was low. Additionally, we used averaged counts from both techniques to show the overdispersion of parasites in bison herds.

A preliminary exploration of the impact of experiential learning on animal science undergraduates' perceptions of humane stunning and slaughter.

It is essential to educate students about humane slaughter as it is a critical component of livestock production, particularly for animal science students who represent future stakeholders in agriculture. There is limited research about the effects of experiential learning on student comfort in participating in education regarding sensitive, yet important topics in the animal sciences. A survey was developed to investigate how a teaching module using an experiential learning activity to teach undergraduates about the slaughter process affected student perceptions of stunning and slaughter. Students enrolled in an animal science course, in which live animals and carcasses are evaluated, were surveyed before and after a teaching module. The module included a lecture about proper stunning and a laboratory activity in which the students had the opportunity to shoot a captive bolt stunner on both model and carcass heads. Respondents completed a pre-survey, attended the laboratory activity, and completed a post-survey; 29 survey responses were recorded. Most respondents were women (23, 79.3%) between the ages of 18 and 21 years (25, 86.2%) and in their first year of college (11, 37.9%). The majority of respondents (22, 75.9%) reported using the captive bolt stunner to stun the model heads during the laboratory activity. After participating in the module, all students strongly agreed that "stunning" is a critical component of livestock slaughter (29, 100%) and most agreed that "stunning is a humane process that ensures animal welfare during the slaughter process" (25, 86.2%). The majority of respondents strongly agreed that the "humane stunning simulation was beneficial to their learning about livestock slaughter" (21, 72.4%) and "improved their understanding of slaughter" (16, 55.2%). Almost all of the survey respondents either agreed or strongly agreed that "the model heads and captive bolt demonstration made them more comfortable with the slaughter process" (14, 48.3%; 14, 48.3%, respectively). This research suggests that experiential learning opportunities are potentially effective teaching strategies for educating undergraduates about the slaughter process. Future research should focus on practical ways to integrate new teaching methods into existing animal science curricula, as this will be critical for educating students on important topics in livestock production and increasing student comfort with sensitive material.

Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.

Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter therapeutic efficacy and addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors and whole brain concentration of oxycodone metabolites. BALB/cJ females showed robust state-dependent oxycodone reward learning as measured via conditioned place preference when compared with the closely related BALB/cByJ substrain. Accordingly, BALB/cJ females also showed a robust increase in brain concentration of the inactive metabolite noroxycodone and the active metabolite oxymorphone compared with BALB/cByJ mice. Oxymorphone is a highly potent, full agonist at the mu opioid receptor that could enhance drug-induced interoception and state-dependent oxycodone reward learning. Quantitative trait locus (QTL) mapping in a BALB/c F2 reduced complexity cross revealed one major QTL on chromosome 15 underlying brain oxymorphone concentration that explained 32% of the female variance. BALB/cJ and BALB/cByJ differ by fewer than 10,000 variants, which can greatly facilitate candidate gene/variant identification. Hippocampal and striatal cis-expression QTL (eQTL) and exon-level eQTL analysis identified Zhx2, a candidate gene coding for a transcriptional repressor with a private BALB/cJ retroviral insertion that reduces Zhx2 expression and sex-dependent dysregulation of cytochrome P450 enzymes. Whole brain proteomics corroborated the Zhx2 eQTL and identified upregulated CYP2D11 that could increase brain oxymorphone in BALB/cJ females. To summarize, Zhx2 is a highly promising candidate gene underlying brain oxycodone metabolite levels. Future studies will validate Zhx2 and its site of action using reciprocal gene editing and tissue-specific viral manipulations in BALB/c substrains. SIGNIFICANCE STATEMENT: Our findings show that genetic variation can result in sex-specific alterations in whole brain concentration of a bioactive opioid metabolite after oxycodone administration, reinforcing the need for sex as a biological factor in pharmacogenomic studies. The cooccurrence of female-specific increased oxymorphone and state-dependent reward learning suggests that this minor yet potent and efficacious metabolite of oxycodone could increase opioid interoception and drug-cue associative learning of opioid reward, which has implications for cue-induced relapse of drug-seeking behavior and for precision pharmacogenetics.

Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice.

The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen's ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to create a resource for associating bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis of Mtb transposon mutant fitness (TnSeq) across the CC panel revealed that many virulence pathways are only required in specific host microenvironments, identifying a large fraction of the pathogen's genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits can be associated with genetic variants distributed across the mouse genome, making the CC a unique population for identifying specific host-pathogen genetic interactions that influence pathogenesis.

Stress and memory encoding: What are the roles of the stress-encoding delay and stress relevance?

The effects of acute stress on memory encoding are complex. Recent work has suggested that both the delay between stress and encoding and the relevance of the information learned to the stressor may modulate the effects of stress on memory encoding, but the relative contribution of each of these two factors is unclear. Therefore, in the present study, we manipulated (1) acute stress, (2) the delay between stress and encoding, and (3) the relevance of the information learned to the stressor. The results indicated that stress during encoding led to better memory for study materials that were related to the stressor relative to memory for study materials that were unrelated to the stressor. This effect was numerically reduced for materials that were encoded 40 min after stressor onset (23 min after the stressor had ended) compared with items encoded at the time of the stressor, but this difference was not significant. These results suggest that the relevance of the information learned to the stressor may play a particularly important role in the effects of stress on memory encoding, which has important implications for theories of stress and memory.