Clostridium perfringens Produces an Adhesive Pilus Required for the Pathogenesis of Necrotic Enteritis in Poultry.

Clostridium perfringens type G strains cause necrotic enteritis (NE) in poultry, an economically important disease that is a major target of in-feed antibiotics. NE is a multifactorial disease, involving not only the critically important NetB toxin but also additional virulence and virulence-associated factors. We previously identified a C. perfringens chromosomal locus (VR-10B) associated with disease-causing strains that is predicted to encode a sortase-dependent pilus. In the current study, we sought to provide direct evidence for the production of a pilus by C. perfringens and establish its role in NE pathogenesis. Pilus structures in virulent C. perfringens strain CP1 were visualized by transmission electron microscopy (TEM) of immunogold-labeled cells. Filamentous structures were observed extending from the cell surface in wild-type CP1 but not from isogenic pilin-null mutant strains. In addition, immunoblotting of cell surface proteins demonstrated that CP1, but not the null mutant strains, produced a high molecular weight ladder-like pattern characteristic of a pilus polymer. Binding to collagen types I, II, and IV was significantly reduced (Tukey's test, P < 0.01) in all three pilin mutants compared to CP1 and could be specifically blocked by CnaA and FimA antisera, indicating that these pilins participate in adherence. Furthermore, fimA and fimB null mutants were both severely attenuated in their ability to cause disease in an in vivo chicken NE challenge model. Together, these results provide the first direct evidence for the production of a sortase-dependent pilus by C. perfringens and confirm its critical role in NE pathogenesis and collagen binding.IMPORTANCE In necrotic enteritis (NE), an intestinal disease of chickens, Clostridium perfringens cells adhere tightly to damaged intestinal tissue, but the factors involved are not known. We previously discovered a cluster of C. perfringens genes predicted to encode a pilus, a hair-like bacterial surface structure commonly involved in adherence. In the current study, we have directly imaged this pilus using transmission electron microscopy (TEM). We also show that inactivation of the pilus genes stops pilus production, significantly reducing the bacterium's ability to bind collagen and cause disease. Importantly, this is the first direct evidence for the production of a sortase-dependent pilus by C. perfringens, revealing a promising new target for developing therapeutics to combat this economically important disease.

The problem with assumptions: Revisiting "The dark figure of sexual recidivism".

What is the actual rate of sexual recidivism given the well-known fact that many crimes go unreported? This is a difficult and important problem, and in "The dark figure of sexual recidivism," Nicholas Scurich and Richard S. John (2019) attempt to make progress on it by "estimat[ing] actual recidivism rates . . . given observed rates of reoffending" (p. 171). In this article, we show that the math in their probabilistic model is flawed, but more importantly, we demonstrate that their conclusions follow ineluctably from their empirical assumptions and the unrepresentative empirical research they cite to benchmark their calculations. Scurich and John contend that their analysis undermines what they call the "orthodoxy in academic circles" (p. 173) of low sexual recidivism rates among individuals convicted of sexual offenses, but we underscore that their article does not analyze data in the traditional sense; instead, it just interprets past scholarly work through the use of strong assumptions in a way that, for practitioners, is likely to be opaque and misleading (and, for us, strays into speculation, argument, or advocacy and away from objective research). Our simple calculations show that their findings are highly sensitive to their assumptions, and we conclude that courts and others should recognize Scurich and John's work for what it is-a set of complex hypotheticals that are no more reliable than what judges and lawyers accomplish on their own by simply recognizing the basic problem that not all sexual offenses are reported.

Relationships between food neophobia and food intake and preferences: Findings from a sample of New Zealand adults.

Food neophobia (FN) has been shown to be a strong influence on food preferences using primarily small data sets. This has limited the explanatory power of FN and the extent to which it can be related to other factors that influence food choice. To address these limitations, we collected Food Neophobia Scale data from 1167 adults from New Zealand over a 45-month period. Participants also completed a 112-item food preference questionnaire and a self-report 24 h, a 145 item food intake recall survey, and the Food Choice Questionnaire (FCQ). As a way of providing a structure to the food intake and preference data, in each case the food items were condensed into patterns described in terms of the foods/beverages with highest factor loadings. We then determined the impact of season and participant age, gender, education and income on these factors, as well as the interaction of these variables with FN scores, divided into tertiles. FN was a strong influence on both intake frequency and preferences in the majority of the intake/preference factor patterns. When significant associations with FN were established, both frequency of intake and preference was lower among high FN individuals. Notably, the effect of FN on food preferences was evident on many commonplace foods making up the diet, suggesting that high FN individuals like food overall less than do those with lower degrees of FN. Seasonal effects in food intake were demonstrated, but with smaller impact for higher levels of FN. While associations between FN varied according to all demographic variables, these relationships varied as a function of the intake/preference patterns. Overall, the results suggest that FN is an important barrier to dietary change and addressing diet-related health problems.

A prospective cohort study of endometriosis and subsequent risk of infertility.

STUDY QUESTION: Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates. WIDER IMPLICATIONS OF THE FINDINGS: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.

Toxicokinetics and toxicity of atorvastatin in dogs.

HMG-CoA reductase inhibitors (e.g., statins) are an important clinical option to lower cholesterol and treat co-morbidities. Atorvastatin is the most prescribed statin and has obtained generic status. We recently had a clinical development program evaluating a combination of atorvastatin with a GPR119 agonist as a treatment for dyslipidemia, where toxicological evaluations in dogs were completed. There were several challenges related to selecting doses for atorvastatin, including understanding the dose-exposure relationship from different drug forms used by the innovator in their general toxicology studies, bioanalytical assays that did not separate and quantify parent from metabolites, and high variability in the systemic exposures following oral dosing. The studies in this report characterized the toxicokinetics and toxicity of atorvastatin in the dog for up to 13-weeks. Overall, there were no notable differences in the toxicokinetics of atorvastatin or the two active hydroxylated metabolites between the sexes at Week 13. However, systemic exposures were markedly lower at Week 13 compared to that observed at Week 4, suggesting induction of metabolism or reduced absorption from the gastrointestinal tract following oral dosing. Changes in laboratory chemistries included increased liver enzyme levels and lower cholesterol levels. Histopathologic evaluation revealed multifocal minimal to slight hemorrhages in the submucosa of the gallbladder; all findings were reversible. The information from these studies along with the existing clinical experience with atorvastatin can be used to design robust toxicology studies in dogs and reduce animal use.

Nonculture molecular techniques for diagnosis of bacterial disease in animals: a diagnostic laboratory perspective.

The past decade has seen remarkable technical advances in infectious disease diagnosis, and the pace of innovation is likely to continue. Many of these techniques are well suited to pathogen identification directly from pathologic or clinical samples, which is the focus of this review. Polymerase chain reaction (PCR) and gene sequencing are now routinely performed on frozen or fixed tissues for diagnosis of bacterial infections of animals. These assays are most useful for pathogens that are difficult to culture or identify phenotypically, when propagation poses a biosafety hazard, or when suitable fresh tissue is not available. Multiplex PCR assays, DNA microarrays, in situ hybridization, massive parallel DNA sequencing, microbiome profiling, molecular typing of pathogens, identification of antimicrobial resistance genes, and mass spectrometry are additional emerging technologies for the diagnosis of bacterial infections from pathologic and clinical samples in animals. These technical advances come, however, with 2 caveats. First, in the age of molecular diagnosis, quality control has become more important than ever to identify and control for the presence of inhibitors, cross-contamination, inadequate templates from diagnostic specimens, and other causes of erroneous microbial identifications. Second, the attraction of these technologic advances can obscure the reality that medical diagnoses cannot be made on the basis of molecular testing alone but instead through integrated consideration of clinical, pathologic, and laboratory findings. Proper validation of the method is required. It is critical that veterinary diagnosticians understand not only the value but also the limitations of these technical advances for routine diagnosis of infectious disease.

Sweet liking predicts liking and familiarity of some alcoholic beverages, but not alcohol intake: A population study using a split-sample approach.

Sweetness has been proposed to be an important quality in the decision to consume alcohol, and strong preferences for sweet tastes have been associated with alcohol abuse. However, alcohol is characterized by a number of other sensory properties, including astringency and bitterness that may drive preference and consumption. Spinelli et al. (2021) classified individuals into three sweet-sensory liking clusters (High Sweet-Liking, Moderate Sweet-Liking, and Inverted-U) that differed in their sweetness optima and sensory-liking patterns (relationship between liking and sweetness, bitterness and astringency perception in a food model). The current paper replicates the sweet sensory-liking clusters in a new set of participants (n = 1976), and extends the predicted value of these clusters examining their relationship to wine and other types of alcoholic beverages by gender using a split-sample approach on a total of over 3000 adults. The sweet sensory-liking clusters had a predictive relationship for the familiarity and liking of some alcoholic beverages characterized by stronger tastes, but not weekly alcohol intake levels. Thus, although sweet sensory-liking clusters may be associated with the type of beverages and frequency with which a person will drink and enjoy a type of alcoholic beverage, they are poor predictors of the quantity of alcohol that a person ingests over the course of a week.

Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats.

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles. Herein, we investigate the permissiveness of Angolan free-tailed bats (AFBs), known to harbour Bombali virus, to other filoviruses: Ebola, Marburg, Taï Forest and Reston viruses. We demonstrate that only the bats inoculated with EBOV show high and disseminated viral replication and infectious virus shedding, without clinical disease, while the other filoviruses fail to establish productive infections. Notably, we evidence placental-specific tissue tropism and a unique ability of EBOV to traverse the placenta, infect and persist in foetal tissues of AFBs, which results in distinct genetic signatures of adaptive evolution. These findings not only demonstrate plausible routes of horizontal and vertical transmission in these bats, which are expectant of reservoir hosts, but may also reveal an ancillary transmission mechanism, potentially required for the maintenance of EBOV in small reservoir populations.

Identification of accessory genome regions in poultry Clostridium perfringens isolates carrying the netB plasmid.

Necrotic enteritis (NE) is an economically important disease of poultry caused by certain Clostridium perfringens type A strains. NE pathogenesis involves the NetB toxin, which is encoded on a large conjugative plasmid within a 42-kb pathogenicity locus. Recent multilocus sequence type (MLST) studies have identified two predominant NE-associated clonal groups, suggesting that host genes are also involved in NE pathogenesis. We used microarray comparative genomic hybridization (CGH) to assess the gene content of 54 poultry isolates from birds that were healthy or that suffered from NE. A total of 400 genes were variably present among the poultry isolates and nine nonpoultry strains, many of which had putative functions related to nutrient uptake and metabolism and cell wall and capsule biosynthesis. The variable genes were organized into 142 genomic regions, 49 of which contained genes significantly associated with netB-positive isolates. These regions included three previously identified NE-associated loci as well as several apparent fitness-related loci, such as a carbohydrate ABC transporter, a ferric-iron siderophore uptake system, and an adhesion locus. Additional loci were related to plasmid maintenance. Cluster analysis of the CGH data grouped all of the netB-positive poultry isolates into two major groups, separated according to two prevalent clonal groups based on MLST analysis. This study identifies chromosomal loci associated with netB-positive poultry strains, suggesting that the chromosomal background can confer a selective advantage to NE-causing strains, possibly through mechanisms involving iron acquisition, carbohydrate metabolism, and plasmid maintenance.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Telomere length and ischaemic stroke in women: a nested case-control study.

BACKGROUND AND PURPOSE: Telomere shortening has been implicated in cardiovascular disease (CVD). However, prospective data on the association between relative telomere length (RTL) and ischaemic stroke are scarce and inconclusive. METHODS: We used a nested case-control design among women participating in the prospective Nurses' Health Study. Participants provided blood samples in 1990 and were followed till 2006. Women with confirmed incident ischaemic stroke were matched to controls by age, smoking, postmenopausal status and postmenopausal hormone use. Quantitative polymerase chain reaction was used to determine RTL in genomic DNA extracted from peripheral blood leukocytes. Conditional logistic regression was used to determine the risk of ischaemic stroke associated with RTL, using RTL quartiles and as dichotomous according to the median. RESULTS: Data on RTL were available from 504 case-control pairs. Results did not suggest an association between RTL and ischaemic stroke. The odds ratio (OR) for ischaemic stroke was 0.82 [95% confidence interval (CI) 0.52-1.32] comparing lowest with the highest RTL quartile and 0.90 (95% CI 0.65-1.24) comparing RTL below the median with RTL above the median. Associations were unchanged after additional adjustment for cardiovascular risk factors. Further analyses suggested an association between RTL and fatal ischaemic stroke (54 case-control pairs; lowest versus highest quartile OR = 1.99, 95%CI 0.26-14.9); however, results were statistically insignificant. CONCLUSION: In this large nested case-control study among women RTL was not associated with ischaemic stroke. In light of the varying study results in the literature on the association between telomere length and stroke, additional research is warranted.

Critical research needs for managing coral reef marine protected areas: perspectives of academics and managers.

Marine protected areas (MPAs) are a primary policy instrument for managing and protecting coral reefs. Successful MPAs ultimately depend on knowledge-based decision making, where scientific research is integrated into management actions. Fourteen coral reef MPA managers and sixteen academics from eleven research, state and federal government institutions each outlined at least five pertinent research needs for improving the management of MPAs situated in Australian coral reefs. From this list of 173 key questions, we asked members of each group to rank questions in order of urgency, redundancy and importance, which allowed us to explore the extent of perceptional mismatch and overlap among the two groups. Our results suggest the mismatch among MPA managers and academics is small, with no significant difference among the groups in terms of their respective research interests, or the type of questions they pose. However, managers prioritised spatial management and monitoring as research themes, whilst academics identified climate change, resilience, spatial management, fishing and connectivity as the most important topics. Ranking of the posed questions by the two groups was also similar, although managers were less confident about the achievability of the posed research questions and whether questions represented a knowledge gap. We conclude that improved collaboration and knowledge transfer among management and academic groups can be used to achieve similar objectives and enhance the knowledge-based management of MPAs.

Responsiveness to warning sensations and anxiety-related psychological traits modulate individual differences in preference for vegetable foods with varied sensory properties.

The innate aversion to warning sensations is an important barrier to the acceptance of vegetable food often characterized by bitter and sour tastes, and astringency. Large individual variations exist in preference for this food category. The present study aimed at exploring differences in demographics, anthropometrics, taste responsiveness, personality traits and attitudes in consumers differing in their preference for vegetable food with varied levels of warning sensations. A panel of Italian consumers (n = 718; 53.6% women, age 18-74 years) self-reported familiarity with, preference for and choice of vegetables with high and low levels of warning sensations. Two clusters were identified: High Warning-Vegetable Consumers (HWVC, n = 464) and Low-Warning Vegetable Consumers (LWVC, n = 254). HWVC showed higher familiarity with and preference for vegetables as a whole and higher choice of vegetables characterized by warning sensations than LWVC. HWVC were more represented by older and normal weight individuals as compared to LWVC. Differences among clusters in liking for and perception of a phenol-enriched plant-based food model specifically developed to induce different levels of bitterness, sourness and astringency were found. HWVC rated bitterness, sourness, and astringency lower and liking higher than LWVC. Scores in anxiety-related psychological traits were lower while attitudes to healthy and high-quality food choice were higher in HWVC than in LWVC. The results of the present study depicted a coherent interplay among several person-related dimensions in modulating preference for vegetable foods. Higher responsiveness to warning sensations, higher level of anxiety-related traits, lower importance assigned to food healthy/quality aspects and younger age all acted as barriers to exposure and acceptance of vegetable food and call for a multidimensional approach to promote the consumption of this food category.

Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study.

STUDY QUESTION: Is the association between paternal age at birth and offspring leukocyte telomere length (LTL) an artifact of early life socioeconomic status (SES)? SUMMARY ANSWER: Indicators of early life SES did not alter the relationship between paternal age at birth and offspring LTL among a population of white female nurses. WHAT IS KNOWN ALREADY: Telomere length is considered a highly heritable trait. Recent studies report a positive correlation between paternal age at birth and offspring LTL. Maternal age at birth has also been positively associated with offspring LTL, but may stem from the strong correlation with paternal age at birth. STUDY DESIGN, SIZE AND DURATION: The Nurses' Health Study (NHS) is an ongoing prospective cohort study of 121 700 female registered nurses who were enrolled in 1976. Great effort goes into maintaining a high degree of follow-up among our cohort participants (>95% of potential person-years). In 1989-1990, a subset of 32 826 women provided blood samples from which we selected participants for several nested case-control studies of telomere length and incident chronic disease. We used existing LTL data on a total of 4250 disease-free women who also reported maternal and paternal age at birth for this study. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Nested case-control studies of stroke, myocardial infarction, cancers of the breast, endometrium, skin, pancreas and colon, as well as colon adenoma, were conducted within the blood sub-cohort. Each study used the following study design: for each case of a disease diagnosed after blood collection, a risk-set sampling scheme was used to select from one to three controls from the remaining participants in the blood sub-cohort who were free of that disease when the case was diagnosed. Controls were matched to cases by age at blood collection (± 1 year), date of blood collection (± 3 months), menopausal status, recent postmenopausal hormone use at blood collection (within 3 months, except for the myocardial infarction case-control study), as well as other factors carefully chosen for each individual study. The current analysis was limited to healthy controls. We also included existing LTL data from a small random sample of women participating in a cognitive sub-study. LTL was measured using the quantitative PCR-based method. Exposure and covariate information are extracted from biennial questionnaires completed by the participants. MAIN RESULTS AND THE ROLE OF CHANCE: We found a strong association between paternal age at birth and participant LTL (P = 1.6 × 10(-5)) that remained robust after controlling for indicators of early life SES. Maternal age at birth showed a weak inverse association with participant LTL after adjusting for age at blood collection and paternal age at birth (P = 0.01). We also noted a stronger association between paternal age at birth and participant LTL among premenopausal than among postmenopausal women (P(interaction) = 0.045). However, this observation may be due to chance as premenopausal women represented only 12.6% (N = 535) of the study population and LTL was not correlated with age at menopause, total or estrogen-only hormone therapy (HT) use suggesting that changes in in vivo estrogen exposure do not influence telomere length regulation. LIMITATIONS AND REASONS FOR CAUTION: The women in our study are not representative of the general US female population, with an underrepresentation of non-white and low social class groups. Although the interaction was not significant, we noted that the paternal age at birth association with offspring LTL appeared weaker among women whose parents did not own their home at the time of the participant's birth. As telomere dynamics may differ among individuals who are most socioeconomically deprived, SES indicators may have more of an influence on the relationship between paternal age at birth and offspring LTL in such populations. WIDER IMPLICATIONS OF THE FINDINGS: As of yet, our and prior studies have not identified childhood or adult characteristics that confound the paternal age at birth association with offspring LTL, supporting the hypothesis that offspring may inherit the longer telomeres found in sperm of older men. The biological implications of the paternal age effect are unknown. A recent theory proposed that the inheritance of longer telomere from older men may be an adaptive signal of reproductive lifespan, while another theory links telomere length attrition to female reproductive senescence. However, we are unaware of any data to substantiate a relationship between paternal age at birth and daughter's fertility. Generalizability of our study results to other white female populations is supported by prior reports of paternal age at birth and offspring telomere length. Furthermore, a confounding relationship between paternal or maternal age at birth and SES was not observed in a study of SES and telomere length. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institutes of Health (grants numbers: CA87969, CA49449, CA065725, CA132190, CA139586, HL088521, CA140790, CA133914, CA132175, ES01664 to M.D.); and by the American Health Association Foundation. We have no competing interests to declare.

Configural memory of a blending aromatic mixture reflected in activation of the left orbital part of the inferior frontal gyrus.

Blending aromatic mixtures components naturally fuse to form a unique odor - a configuration- qualitatively different from each component's odor. Repeated exposure to the components either in the mixture or separately, favors respectively, configural and elemental processings. The neural bases of such processes are still unknown. We examined the brain correlates of the experienced-induced configural processing of a well-known model of binary blending odor mixture, the aromatic pineapple blending (AB, ethyl maltol + ethyl isobutyrate). Before fMRI recording, half of the participants were repeatedly exposed to the mixture (AB, group Gmix), with the other half exposed to its separate components (A and B; Gcomp). During the fMRI recording, all participants were stimulated with the mixture (AB) and the components (A and B). Finally, participants rated the number of odors perceived for each stimulus. Gmix perceived the AB mixture as less complex than did Gcomp. While Gcomp perceived the mixture as more complex than its components, Gmix did not. These results show the presence of experience-induced configural or elemental processing of the AB mixture in each group. Contrasting the brain activity of Gcomp and Gmix, when stimulated with AB, revealed higher activation in the left orbital part of the inferior frontal gyrus. This result sheds light on this area's function, commonly found activated in olfactory studies, and closely connected with the lateral orbitofrontal cortex. We discuss the role of this area as a mediator of configural percepts between temporal and orbitofrontal areas involved in configural memory processes.

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir - Mastomys natalensis.

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.

The mouse mammary tumor virus envelope gene product is required for superantigen presentation to T cells.

Transgenic mice expressing either the mouse mammary tumor virus (MMTV) superantigen gene (sag) alone or in combination with the viral envelope genes (env) (LEL), or all of the viral genes (gag, pol, env, and sag) (HYB PRO), deleted V beta 14+ T cells from their immune repertoire. However, only LEL or HYB PRO transgenic antigen-presenting cells were capable of stimulating a proliferative response from nontransgenic primary T cells or interleukin 2 production from a V beta 15-bearing T cell hybridoma. These T cell responses could be inhibited by a monospecific antibody directed against the MMTV gp52 cell surface glycoprotein. These results indicate that the MMTV gp52 gene product participates in the presentation of superantigen to T cells, resulting in their stimulation, a requisite step in the MMTV infection pathway. Thus, gp52 could play a role in the transfer of virus between different subsets of lymphocytes.

Semi-automated segmentation to assess the lateral meniscus in normal and osteoarthritic knees.

OBJECTIVE: The goal of this study was to develop an algorithm to semi-automatically segment the meniscus in a series of magnetic resonance (MR) images to use for normal knees and those with moderate osteoarthritis (OA). METHOD: The segmentation method was developed then evaluated on 10 baseline MR images obtained from subjects with no evidence, symptoms, or risk factors of knee (OA), and 14 from subjects with established knee OA enrolled in the Osteoarthritis Initiative (OAI). After manually choosing a seed point within the meniscus, a threshold level was calculated through a Gaussian fit model. Under anatomical, intensity, and range constraints, a threshold operation was completed followed by conditional dilation and post-processing. The post-processing operation reevaluates the pixels included and excluded in the area surrounding the meniscus to improve accuracy. The developed method was evaluated for both normal and degenerative menisci by comparing the segmentation algorithm results with manual segmentations from five human readers. RESULTS: The semi-automated segmentation method produces results similar to those of trained observers, with an average similarity index over 0.80 for normal participants and 0.75, 0.67, and 0.64 for participants with established knee OA with Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) scores of 0, one, and two respectively. CONCLUSION: The semi-automatic segmentation method produced accurate and consistent segmentations of the meniscus when compared to manual segmentations in the assessment of normal menisci in mild to moderate OA. Future studies will examine the change in volume, thickness, and intensity characteristics at different stages of OA.

Mass mortality of harbor seals: pneumonia associated with influenza A virus.

More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7). The virus has avian characteristics, replicates principally in mammals, and causes mild respiratory disease in experimentally infected seals. Concurrent infection with a previously undescribed mycoplasma or adverse environmental conditions may have triggered the epizootic. The similarities between this epizootic and other seal mortalities in the past suggest that these events may be linked by common biological and environmental factors.