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Bacillus anthracis causes anthrax through virulence factors encoded on two plasmids. However, non- B. anthracis organisms within the closely related, environmentally ubiquitous Bacillus cereus group (BCG) may cause an anthrax-like disease in humans through the partial adoption of anthrax-associated virulence genes, challenging the definition of anthrax disease. To elucidate these phenomena and their evolutionary past, we performed whole-genome sequencing on non- anthracis BCG isolates, including 93 archival (1967-2003) and 5 contemporary isolates (2019-2023). We produced annotated genomic assemblies and performed a pan-genome analysis to identify evidence of virulence gene homology and virulence gene acquisition by linear inheritance or horizontal gene transfer. At least one anthrax-associated virulence gene was annotated in ten isolates. Most homologous sequences in archival isolates showed evidence of pseudogenization and subsequent gene loss. The presence or absence of accessory genes, including anthrax-associated virulence genes, aligned with the phylogenetic structure of the BCG core genome. These findings support the hypothesis that anthrax-associated virulence genes were inherited from a common ancestor in the BCG and were retained or lost across different lineages, and contribute to a growing body of work informing public health strategies related to anthrax surveillance and identification.

Familial communication of results and cascade genetic testing (CGT) can extend the benefits of genetic screening beyond the patient to their at-risk relatives. While an increasing number of health systems are offering genetic screening as an elective clinical service, data are limited about how often results are shared and how often results lead to CGT. From 2018 to 2022, the Sanford Health system offered the Sanford Chip, an elective genomic test that included screening for medically actionable predispositions for disease recommended by the American College of Medical Genetics and Genomics for secondary findings disclosure, to its adult primary care patients. We analyzed patient-reported data about familial sharing of results and CGT among patients who received Sanford Chip results at least 1 year previously. Among the patients identified with medically actionable predispositions, 94.6% (53/56) reported disclosing their result to at least one family member, compared with 46.7% (423/906) of patients with uninformative findings (p < 0.001). Of the patients with actionable predispositions, 52.2% (12/23) with a monogenic disease risk and 12.1% (4/33) with a carrier status reported that their relatives underwent CGT. Results suggest that while the identification of monogenic risk during elective genomic testing motivates CGT in many at-risk relatives, there remain untested at-risk relatives who may benefit from future CGT. Findings identify an area that may benefit from increased genetic counseling and the development of tools and resources to encourage CGT for family members., (© 2024 National Society of Genetic Counselors.)

The number of ground-nesting ducks in the wetlands of Great Salt Lake, Utah has drastically decreased in the past few decades. A potential cause for this decline is the increase of predator species and their abundances, which has caused most nests to fail from depredation. Ground-nesting ducks may be able to reduce the risk of nest depredation by selecting nest sites where local physical structures or vegetation provides olfactory or visual concealment. To test this, we used logistic exposure models to look at the effect of nest-site characteristics on daily survival rates (DSRs) of nests during 2019, 2020, and 2021 in the wetlands of Great Salt Lake, Utah. We found 825 duck nests including 458 cinnamon teal ( Spatula cyanoptera ), 166 mallards ( Anas platyrhynchos ), and 201 gadwalls ( Mareca strepera ). DSRs were 0.9714 ± 0.0019 in 2019, 0.9282 ± 0.0049 in 2020, and 0.8274 ± 0.0185 in 2021. Survival rates varied among years but not among duck species. Striped skunks ( Mephitis mephitis ) and raccoons ( Procyon lotor ) were responsible for 85% of depredated nests. Nests located near other duck nests had higher DSRs than more dispersed nests. Neither visual nor olfactory characteristics correlated with increased DSRs based on AIC c analysis. Nests located inside a mixed nesting colony of American avocets ( Recurvirostra americana ), black-necked stilts ( Himantopus mexicanus ), and common terns ( Sterna hirundo ) had higher DSRs than duck nests outside the colony. Increased nesting densities of ducks and other colonial waterbirds had the greatest impact on nesting success. Increased nest density may be encouraged through early spring green-up., Competing Interests: Neither of the authors have any conflicts of interest in this study. Permission to reproduce materials from other sources (mention “None” if not applicable for your article): None., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

This review serves as an update to the previous Nocardia review by Brown-Elliott et al. published in 2006 (B. A. Brown-Elliott, J. M. Brown, P. S. Conville, and R. J. Wallace. Jr., Clin Microbiol Rev 19:259-282, 2006, https://doi.org/10.1128/CMR.19.2.259-282.2006). Included is a discussion on the taxonomic expansion of the genus, current identification methods, and the impact of new technology (including matrix-assisted laser desorption ionization-time of flight [MALDI-TOF] and whole genome sequencing) on diagnosis and treatment. Clinical manifestations, the epidemiology, and geographic distribution are briefly discussed. An additional section on actinomycotic mycetoma is added to address this often-neglected disease.

Rat bite fever and Haverhill fever are often difficult to diagnose in a clinical setting. This difficulty results in part from clinicians and laboratory professionals not being able to reliably recover the causative agent Streptobacillus moniliformis using culture-based methods. After utilizing an automated continuous-monitoring blood culture bottle system, we showed that the organism can be reliably cultured when a blood volume inoculum of 10 mL is used. Further, we showed that when the above recommendation is followed, sodium polyanethole sulfonate (up to a concentration of 0.05% w/v) in commercially purchased blood culture bottle formulations seems to be inactivated, allowing for the growth and detection of S. moniliformis. Herein, we offer data and methods used to overcome these clinical limitations. This is a comprehensive study of the historical collection of S. moniliformis isolates maintained by our facility and believed to be the largest of its kind to date., (Published by Oxford University Press on behalf of American Society for Clinical Pathology 2021.)

Given the number of veterans who have experienced military sexual trauma (MST) and the impact of these experiences on veteran health, Veterans Health Administration (VHA) providers frequently communicate with patients about these experiences, either as part of the VHA's universal MST screening program or more comprehensive clinical care. The purpose of this study was to understand veterans' perceptions of communication related to MST disclosures with VHA providers. We conducted qualitative interviews, including a numeric rating question, with 55 veterans whose medical records indicated recent MST-related interactions with VHA providers. The sample included men and women, with and without histories of MST. We analyzed interview transcripts using matrices and identified themes related to satisfaction with communication. Veterans from all groups reported generally high satisfaction with MST-related communication, although men, as a group, reported a much larger range of satisfaction ratings than women. Key provider-related indicators of satisfaction included providers' communication mechanics and nonspecific patient-centered skills and characteristics. One patient-related indicator of lower satisfaction-inherent discomfort discussing MST experiences-was particularly represented among men with MST histories. These data from veteran patients will be reassuring to providers whose concerns about patient reactions to these conversations may inhibit them from raising this important issue. Understanding variables that promote patient satisfaction with MST disclosure communication is critical for promoting sensitive patient-provider interactions about MST. This ultimately can have important downstream effects on veteran health, allowing veterans to forge satisfying relationships with providers and ultimately facilitate recovery from traumatic experiences. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose of Review: To review research on breast cancer mortality disparities, emphasizing research conducted in the Carolina Breast Cancer Study, with a focus on challenges and opportunities for integration of tumor biology and access characteristics across the cancer care continuum., Recent Findings: Black women experience higher mortality following breast cancer diagnosis, despite lower incidence compared to white women. Biological factors, such as stage at diagnosis and breast cancer subtypes, play a role in these disparities. Simultaneously, social, behavioral, environmental, and access to care factors are important. However, integrated studies of biology and access are challenging and it is uncommon to have both data types available in the same study population. The central emphasis of Phase 3 of the Carolina Breast Cancer Study, initiated in 2008, was to collect rich data on biology (including germline and tumor genomics and pathology) and health care access in a diverse study population, with the long term goal of defining intervention opportunities to reduce disparities across the cancer care continuum., Summary: Early and ongoing research from CBCS has identified important interactions between biology and access, leading to opportunities to build greater equity. However, sample size, population-specific relationships among variables, and complexities of treatment paths along the care continuum pose important research challenges. Interdisciplinary teams, including experts in novel data integration and causal inference, are needed to address gaps in our understanding of breast cancer disparities., Competing Interests: Conflict of Interest Marc A. Emerson, Katherine E. Reeder-Hayes, Heather J. Tipaldos, Mary E. Bell, Marina R. Sweeney, Lisa A. Carey, H. Shelton Earp, Andrew F. Olshan and Melissa A. Troester declare no conflicts of interest relevant to this manuscript.

The genus Chryseobacterium in the family Weeksellaceae is known to be polyphyletic. Amino acid identity (AAI) values were calculated from whole-genome sequences of species of the genus Chryseobacterium, and their distribution was found to be multi-modal. These naturally-occurring non-continuities were leveraged to standardise genus assignment of these species. We speculate that this multi-modal distribution is a consequence of loss of biodiversity during major extinction events, leading to the concept that a bacterial genus corresponds to a set of species that diversified since the Permian extinction. Transfer of nine species ( Chryseobacterium arachidiradicis , Chryseobacterium bovis, Chryseobacterium caeni, Chryseobacterium hispanicum, Chryseobacterium hominis, Chryseobacterium hungaricum , , Chryseobacterium pallidum and Chryseobacterium zeae ) to the genus Epilithonimonas and eleven ( Chryseobacterium anthropi , Chryseobacterium antarcticum , Chryseobacterium carnis , Chryseobacterium chaponense , Chryseobacterium haifense, Chryseobacterium jeonii , Chryseobacterium montanum , Chryseobacterium palustre , Chryseobacterium solincola , Chryseobacterium treverense and Chryseobacterium yonginense ) to the genus Kaistella is proposed. Two novel species are described: Kaistella daneshvariae sp. nov. and Epilithonimonas vandammei sp. nov. Evidence is presented to support the assignment of Planobacterium taklimakanense to a genus apart from Chryseobacterium, to which Planobacterium salipaludis comb nov. also belongs. The novel genus Halpernia is proposed, to contain the type species Halpernia frigidisoli comb. nov., along with Halpernia humi comb. nov., and Halpernia marina comb. nov.

Background: After controlling for baseline disease factors, researchers have found that black women have worse breast cancer survival, and this suggests that treatment differences may contribute to poorer outcomes. Delays in initiating and completing treatment are one proposed mechanism., Methods: Phase 3 of the Carolina Breast Cancer Study involved a large, population-based cohort of women with incident breast cancer. For this analysis, we included black women (n = 1328) and white women (n = 1331) with stage I to III disease whose treatment included surgery with or without adjuvant therapies. A novel treatment pathway grouping was used to benchmark the treatment duration (surgery only, surgery plus chemotherapy, surgery plus radiation, or all 3). Models controlled for the treatment pathway, age, and tumor characteristics and for demographic factors related to health care access. Exploratory analyses of the association between delays and cancer recurrence were performed., Results: In fully adjusted analyses, blacks had 1.73 times higher odds of treatment initiation more than 60 days after their diagnosis in comparison with whites (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.04-2.90). Black race was also associated with a longer treatment duration. Blacks were also more likely to be in the highest quartile of treatment duration (OR, 1.69; 95% CI, 1.41-2.02), even after adjustments for demographic and tumor characteristics (OR, 1.31; 95% CI, 1.04-1.64). A nonsignificant trend toward a higher recurrence risk was observed for patients with delayed initiation (hazard ratio, 1.44; 95% CI, 0.89-2.33) or the longest duration (hazard ratio, 1.17; 95% CI, 0.87-1.59)., Conclusions: Black women more often had delayed treatment initiation and a longer duration than whites receiving similar treatment. Interventions that target access barriers may be needed to improve timely delivery of care., (© 2019 American Cancer Society.)

Background: Differential use of endocrine therapy (ET) by race may contribute to breast cancer outcome disparities, but racial differences in ET behaviors are poorly understood., Methods: Women aged 20-74 years with a first primary, stage I-III, hormone receptor-positive (HR+) breast cancer were included. At 2 years postdiagnosis, we assessed nonadherence, defined as not taking ET every day or missing more than two pills in the past 14 days, discontinuation, and a composite measure of underuse, defined as either missing pills or discontinuing completely. Using logistic regression, we evaluated the relationship between race and nonadherence, discontinuation, and overall underuse in unadjusted, clinically adjusted, and socioeconomically adjusted models., Results: A total of 1280 women were included; 43.2% self-identified as black. Compared to white women, black women more often reported nonadherence (13.7% vs 5.2%) but not discontinuation (10.0% vs 10.7%). Black women also more often reported the following: hot flashes, night sweats, breast sensitivity, and joint pain; believing that their recurrence risk would not change if they stopped ET; forgetting to take ET; and cost-related barriers. In multivariable analysis, black race remained statistically significantly associated with nonadherence after adjusting for clinical characteristics (adjusted odds ratio = 2.72, 95% confidence interval = 1.75 to 4.24) and after adding socioeconomic to clinical characteristics (adjusted odds ratio = 2.44, 95% confidence interval = 1.50 to 3.97) but was not independently associated with discontinuation after adjustment. Low recurrence risk perception and lack of a shared decision making were strongly predictive of ET underuse across races., Conclusions: Our results highlight important racial differences in ET-adherence behaviors, perceptions of benefits/harms, and shared decision making that may be targeted with culturally tailored interventions., (© The Author(s) 2018. Published by Oxford University Press.)

Nosocomial infections of Elizabethkingia species can have fatal outcomes if not identified and treated properly. The current diagnostic tools available require culture and isolation, which can extend the reporting time and delay treatment. Using comparative genomics, we developed an efficient multiplex real-time PCR for the simultaneous detection of all known species of Elizabethkingia , as well as differentiating the two most commonly reported species, Elizabethkingia anophelis and Elizabethkingia meningoseptica ., (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)

Corynebacterium bovis is an opportunistic bacterial pathogen shown to cause eye and prosthetic joint infections as well as abscesses in humans, mastitis in dairy cattle, and skin disease in laboratory mice and rats. Little is known about the genetic characteristics and genomic diversity of C. bovis because only a single draft genome is available for the species. The overall aim of this study was to sequence and compare the genome of C. bovis isolates obtained from different species, locations, and time points. Whole-genome sequencing was conducted on 20 C. bovis isolates (six human, four bovine, nine mouse and one rat) using the Illumina MiSeq platform and submitted to various comparative analysis tools. Sequencing generated high-quality contigs (over 2.53 Mbp) that were comparable to the only reported assembly using C. bovis DSM 20582T (97.8 ± 0.36% completeness). The number of protein-coding DNA sequences (2,174 ± 12.4) was similar among all isolates. A Corynebacterium genus neighbor-joining tree was created, which revealed Corynebacterium falsenii as the nearest neighbor to C. bovis (95.87% similarity), although the reciprocal comparison shows Corynebacterium jeikeium as closest neighbor to C. falsenii. Interestingly, the average nucleotide identity demonstrated that the C. bovis isolates clustered by host, with human and bovine isolates clustering together, and the mouse and rat isolates forming a separate group. The average number of genomic islands and putative virulence factors were significantly higher (p<0.001) in the mouse and rat isolates as compared to human/bovine isolates. Corynebacterium bovis' pan-genome contained a total of 3,067 genes of which 1,354 represented core genes. The known core genes of all isolates were primarily related to ''metabolism" and ''information storage/processing." However, most genes were classified as ''function unknown" or "unclassified". Surprisingly, no intact prophages were found in any isolate; however, almost all isolates had at least one complete CRISPR-Cas system., Competing Interests: The authors have declared that no competing interests exist.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported 1,2 . Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source 3 , and its subsequent localization 4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys 5 .

Sulfur-based cathodes are promising to enable high-energy-density lithium-sulfur batteries; however, elemental sulfur as active material faces several challenges, including undesirable volume change (∼80%) when completely reduced and high dependence on liquid electrolyte wherein an electrolyte/sulfur ratio >10 μL mg -1 is required for high material utilization. These limit the attainable energy densities of these batteries. Herein, we introduce a new class of phenyl polysulfides C 6 H 5 S x C 6 H 5 (4 ≤ x ≤ 6) as liquid cathode materials synthesized in a facile and scalable route to mitigate these setbacks. These polysulfides possess sufficiently high theoretical specific capacities, specific energies, and energy densities. Spectroscopic techniques verify their chemical composition and computation shows that the volume change when reduced is about 37%. Lithium half-cell testing shows that phenyl hexasulfide (C 6 H 5 S 6 C 6 H 5 ) can provide a specific capacity of 650 mAh g -1 and capacity retention of 80% through 500 cycles at 1 C rate along with superlative performance up to 10 C. Furthermore, 1302 Wh kg -1 and 1720 Wh L -1 are achievable at a low electrolyte/active material ratio, i.e., 3 μL mg -1 . This work adds new members to the cathode family for Li-S batteries, reduces the gap between the theoretical and practical energy densities of batteries, and provides a new direction for the development of alternative high-capacity cathode materials.

Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western microbiomes, but how dietary changes may have impacted their ecology is unclear. Here, we compared the in vitro and in vivo effects of 18:2 on Lactobacillus reuteri and L. johnsonii . Directed evolution in vitro in both species led to strong 18:2 resistance with mutations in genes for lipid biosynthesis, acid stress, and the cell membrane or wall. Small-intestinal Lactobacillus populations in mice were unaffected by chronic and acute 18:2 exposure, yet harbored both 18:2- sensitive and resistant strains. This work shows that extant small intestinal lactobacilli are protected from toxic dietary components via the gut environment as well as their own capacity to evolve resistance., Competing Interests: SD, JJ, EK, MB, QS, JW, PL, JB, RB, JW No competing interests declared, RL Guest Reviewing Editor for eLife microbiome special issue, (© 2018, Di Rienzi et al.)

We report here a nearly complete draft genome sequence for a Corynebacterium mastitidis isolate from a mouse. The total read coverage is 198×, and the genome size is 2,264,319 bp with a 69.04% GC content. This genome complements the only other genome available for C. mastitidis , which was obtained from a sheep., (Copyright © 2018 Cheleuitte-Nieves et al.)

Background: Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium., Methods: Using immunohistochemistry (IHC), we quantified the expression of ER, PR, HER2, the proliferation marker Ki67, and two basal-like biomarkers, epidermal growth factor receptor (EGFR) and cytokeratin (CK)5/6, in 1381 invasive breast tumors from African American women. RNA-based (prediction analysis of microarray 50 (PAM50)) subtype, available for 574 (42%) cases, was used to optimize classification. Subtype frequency was calculated, and associations between subtype and tumor characteristics were estimated using logistic regression., Results: Relative to ER, PR and HER2 from medical records, central IHC staining and the addition of Ki67 or combined tumor grade improved accuracy for classifying PAM50-based luminal subtypes. Few triple negative cases (< 2%) lacked EGFR and CK5/6 expression, thereby providing little improvement in accuracy for identifying basal-like tumors. Relative to luminal A subtype, all other subtypes had higher combined grade and were larger, and ER-/HER2+ tumors were more often lymph node positive and late stage tumors. The frequency of basal-like tumors was 31%, exceeded only slightly by luminal A tumors (37%)., Conclusions: Our findings indicate that automated IHC-based classification produces tumor subtype frequencies approximating those from PAM50-based classification and highlight high frequency of basal-like and low frequency of luminal A breast cancer in a large study of African American women.

Wohlfahrtiimonas species bacteria were isolated from the bloodstream of a patient with septicemia and wound myiasis. Environmental investigations identified a Wohlfahrtiimonas sp. among insects in the Americas and in a previously undescribed vector, the green bottle fly (Lucilia sericata). The isolates possibly represent a new species within the genus Wohlfahrtiimonas.

Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype., Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+)., Results: In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype., Conclusions: Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.

An atypically large outbreak of Elizabethkingia anophelis infections occurred in Wisconsin. Here we show that it was caused by a single strain with thirteen characteristic genomic regions. Strikingly, the outbreak isolates show an accelerated evolutionary rate and an atypical mutational spectrum. Six phylogenetic sub-clusters with distinctive temporal and geographic dynamics are revealed, and their last common ancestor existed approximately one year before the first recognized human infection. Unlike other E. anophelis, the outbreak strain had a disrupted DNA repair mutY gene caused by insertion of an integrative and conjugative element. This genomic change probably contributed to the high evolutionary rate of the outbreak strain and may have increased its adaptability, as many mutations in protein-coding genes occurred during the outbreak. This unique discovery of an outbreak caused by a naturally occurring mutator bacterial pathogen provides a dramatic example of the potential impact of pathogen evolutionary dynamics on infectious disease epidemiology.

Gram-stain-positive, partially acid-fast, non-spore-forming, anaerobic, catalase-positive, pleomorphic bacteria were isolated from human abscesses. Strains X1036T, X1698 and NML 120705, were recovered from a spinal abscess, a peritoneal abscess and a breast abscess respectively. A phylogenetic analysis of the 16S rRNA gene sequences showed that the strains shared 100 % similarity, and the nearest phylogenetic neighbour was Dietzia timorensis DSM 45568T (95%). Chemotaxonomic characteristics of the strains were consistent with those described for members of the suborder Corynebacterineae. Mycolic acids were detected using HPLC and one-dimensional TLC; whole-cell hydrolysates yielded meso-diaminopimelic acid with arabinose and galactose as the predominant sugars; the muramic acid acyl type was acetylated; the major menaquinone was MK-9 (96.3%); polar lipids detected were phosphatidylglycerol, phosphatidylinositol and an unknown glycophospholipid. Cellular fatty acids were hexadecanoic acid (C16 : 0), octadecenoic acid (C18 : 1ω9c) and decanoic acid (C10 : 0). Tuberculostearic acid was not detected. Based on the results of this polyphasic study, we conclude that these strains represent a novel genus and species within the suborder Corynebacterineae for which we propose the name Lawsonella clevelandensis gen. nov., sp. nov., with the type strain X1036T (=DSM 45743T=CCUG 66657T).

The complete circularized genome sequences of selected specimens from the largest known Elizabethkingia anophelis outbreak to date are described here. Genomic rearrangements observed among the outbreak strains are discussed., (Copyright © 2016 Nicholson et al.)

Purpose: Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype., Methods: Using population-based case-control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers. We used logistic regression models to estimate case-control odds ratios (OR) and 95 % confidence intervals (CI)., Results: Ever smoking (current and former) was associated with a weakly increased risk of Luminal breast cancer (OR 1.12, 95 % CI 0.92-1.36) and was not associated with risk of Basal-like breast cancer (OR 0.96, 95 % CI 0.69-1.32). Similarly, smoking duration of more than 20 years was associated with increased risk of Luminal (OR 1.51, 95 % CI 1.19-1.93), but not Basal-like breast cancer (OR 0.90, 95 % CI 0.57-1.43). When stratified by race, elevated odds ratios between smoking and Luminal breast cancer risk were found among black women across multiple exposure measures (ever smoking, duration, and dose); conversely, among white women odds ratios were attenuated or null., Conclusions: Results from our study demonstrate a positive association between smoking and Luminal breast cancer risk, particularly among black women and women with long smoking histories. Addressing breast cancer heterogeneity in studies of smoking and breast cancer risk may elucidate associations masked in prior studies.

Three human clinical strains (W9323(T), X0209(T) and X0394) isolated from a lung biopsy, blood and cerebral spinal fluid, respectively, were characterised using a polyphasic taxonomic approach. Comparative analysis of the 16S rRNA gene sequences showed the three strains belong to two novel branches within the genus Kroppenstedtia: 16S rRNA gene sequence analysis of W9323(T) showed close sequence similarity to Kroppenstedtia eburnea JFMB-ATE(T) (95.3 %), Kroppenstedtia guangzhouensis GD02(T) (94.7 %) and strain X0209(T) (94.6 %); sequence analysis of strain X0209(T) showed close sequence similarity to K. eburnea JFMB-ATE(T) (96.4 %) and K. guangzhouensis GD02(T) (96.0 %). Strains X0209(T) and X0394 were 99.9 % similar to each other by 16S rRNA gene sequence analysis. The DNA-DNA relatedness was 94.6 %, confirming that X0209(T) and X0394 belong to the same species. Chemotaxonomic data for strains W9323(T) and X0209(T) were consistent with those described for the members of the genus Kroppenstedtia: the peptidoglycan was found to contain LL-diaminopimelic acid; the major cellular fatty acids were identified as iso-C15 and anteiso-C15; and the major menaquinone was identified as MK-7. Differences in endospore morphology, carbon source utilisation profiles, and cell wall sugar patterns of strains W9323(T) and X0209(T), supported by phylogenetic analysis, enabled us to conclude that the strains each represent a new species within the genus Kroppenstedtia, for which the names Kroppenstedtia pulmonis sp. nov. (type strain W9323(T) = DSM 45752(T) = CCUG 68107(T)) and Kroppenstedtia sanguinis sp. nov. (type strain X0209(T) = DSM 45749(T) = CCUG 38657(T)) are proposed.

The eclipses of certain types of binary millisecond pulsars (i.e. 'black widows' and 'redbacks') are often studied using high-time-resolution, 'beamformed' radio observations. However, they may also be detected in images generated from interferometric data. As part of a larger imaging project to characterize the variable and transient sky at radio frequencies <200 MHz, we have blindly detected the redback system PSR J2215+5135 as a variable source of interest with the Low-Frequency Array (LOFAR). Using observations with cadences of two weeks - six months, we find preliminary evidence that the eclipse duration is frequency dependent (∝ν -0.4 ), such that the pulsar is eclipsed for longer at lower frequencies, in broad agreement with beamformed studies of other similar sources. Furthermore, the detection of the eclipses in imaging data suggests an eclipsing medium that absorbs the pulsed emission, rather than scattering it. Our study is also a demonstration of the prospects of finding pulsars in wide-field imaging surveys with the current generation of low-frequency radio telescopes.

We report on the results of a search for radio transients between 115 and 190 MHz with the LOw-Frequency ARray (LOFAR). Four fields have been monitored with cadences between 15 min and several months. A total of 151 images were obtained, giving a total survey area of 2275 deg 2 . We analysed our data using standard LOFAR tools and searched for radio transients using the LOFAR Transients Pipeline. No credible radio transient candidate has been detected; however, we are able to set upper limits on the surface density of radio transient sources at low radio frequencies. We also show that low-frequency radio surveys are more sensitive to steep-spectrum coherent transient sources than GHz radio surveys. We used two new statistical methods to determine the upper limits on the transient surface density. One is free of assumptions on the flux distribution of the sources, while the other assumes a power-law distribution in flux and sets more stringent constraints on the transient surface density. Both of these methods provide better constraints than the approach used in previous works. The best value for the upper limit we can set for the transient surface density, using the method assuming a power-law flux distribution, is 1.3 × 10 -3  deg -2 for transients brighter than 0.3 Jy with a time-scale of 15 min, at a frequency of 150 MHz. We also calculated for the first time upper limits for the transient surface density for transients of different time-scales. We find that the results can differ by orders of magnitude from previously reported, simplified estimates.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal comes from accelerators capable of producing cosmic rays of these energies. Cosmic rays initiate air showers--cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground. Current measurements have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays is a rapidly developing technique for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10(17)-10(17.5) electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.

Purpose: Alcohol is an established breast cancer risk factor, but there is little evidence on whether the association differs between African Americans and whites., Methods: Invasive breast cancers (n = 1,795; 1,014 white, 781 African American) and age- and race-matched controls (n = 1,558; 844 white, 714 African American) from the Carolina Breast Cancer Study (Phases I-II) were used to estimate odds ratios (ORs) and 95 % confidence interval (CI) for pre-diagnosis drinks per week and breast cancer risk., Results: African American controls reported lower alcohol intake than white controls across all age groups. Light drinking (0 to ≤2 per week) was more prevalent among African American controls. Moderate-to-heavy drinking was more prevalent in white controls. African Americans who reported drinking >7 drinks per week had an elevated risk compared to light drinkers [adjusted OR, 95% CI 1.62 (1.03-2.54)]. A weaker association was observed among whites [adjusted OR, 95% CI 1.20 (0.87-1.67)]. The association of >7 drinks per week with estrogen receptor-negative [adjusted OR, 95% CI 2.17 (1.25-3.75)] and triple-negative [adjusted OR, 95% CI 2.12 (1.12-4.04)] breast cancers was significant for African American, but not white women. We observed significantly elevated ORs for heavy intake at ages <25 and >50 years of age for African American women only. We found no evidence of statistical interaction between alcohol intake and oral contraceptive use or smoking., Conclusions: Drinking more than seven alcoholic beverages per week increased invasive breast cancer risk among white and African American women, with significant increases only among African American women. Genetic or environmental factors that differ by race may mediate the alcohol-breast cancer risk association.

Resurgent interest in synaptic circuitry and plasticity has emphasized the importance of 3D reconstruction from serial section electron microscopy (3DEM). Three volumes of hippocampal CA1 neuropil from adult rat were imaged at X-Y resolution of ~2 nm on serial sections of ~50-60 nm thickness. These are the first densely reconstructed hippocampal volumes. All axons, dendrites, glia, and synapses were reconstructed in a cube (~10 μm(3)) surrounding a large dendritic spine, a cylinder (~43 μm(3)) surrounding an oblique dendritic segment (3.4 μm long), and a parallelepiped (~178 μm(3)) surrounding an apical dendritic segment (4.9 μm long). The data provide standards for identifying ultrastructural objects in 3DEM, realistic reconstructions for modeling biophysical properties of synaptic transmission, and a test bed for enhancing reconstruction tools. Representative synapses are quantified from varying section planes, and microtubules, polyribosomes, smooth endoplasmic reticulum, and endosomes are identified and reconstructed in a subset of dendrites. The original images, traces, and Reconstruct software and files are freely available and visualized at the Open Connectome Project (Data Citation 1).

Nascent zones and active zones are adjacent synaptic regions that share a postsynaptic density, but nascent zones lack the presynaptic vesicles found at active zones. Here dendritic spine synapses were reconstructed through serial section electron microscopy (3DEM) and EM tomography to investigate nascent zone dynamics during long-term potentiation (LTP) in mature rat hippocampus. LTP was induced with theta-burst stimulation, and comparisons were made with control stimulation in the same hippocampal slices at 5 minutes, 30 minutes, and 2 hours post-induction and to perfusion-fixed hippocampus in vivo. Nascent zones were present at the edges of ∼35% of synapses in perfusion-fixed hippocampus and as many as ∼50% of synapses in some hippocampal slice conditions. By 5 minutes, small dense-core vesicles known to transport active zone proteins moved into more presynaptic boutons. By 30 minutes, nascent zone area decreased, without significant change in synapse area, suggesting that presynaptic vesicles were recruited to preexisting nascent zones. By 2 hours, both nascent and active zones were enlarged. Immunogold labeling revealed glutamate receptors in nascent zones; however, average distances from nascent zones to docked presynaptic vesicles ranged from 170 ± 5 nm in perfusion-fixed hippocampus to 251 ± 4 nm at enlarged synapses by 2 hours during LTP. Prior stochastic modeling suggests that decrease in glutamate concentration reduces the probability of glutamate receptor activation from 0.4 at the center of release to 0.1 just 200 nm away. Thus, conversion of nascent zones to functional active zones likely requires the recruitment of presynaptic vesicles during LTP., (© 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate if and to what extent the degree of subspecialization in abdominal imaging (AI) affects rates of discrepancies identified on review of body CT studies initially interpreted by board-certified radiologists not specialized in AI., Method and Materials: AI division radiologists at one academic medical center were classified as primary or secondary members of the division based on whether they perform more or less than 50% of their clinical duties in AI. Primary AI division radiologists were further subdivided based on whether or not they focus their clinical duties almost exclusively in AI. All AI radiologists performed subspecialty review of all after-hours body CT studies initially interpreted by any non-division radiologist. The discrepancies identified in the subspecialty review of consecutive after-hours body CT scans performed between 7/1/10 and 12/31/10 were analyzed and placed into one of three categories: (1) discrepancies that potentially affect patient care ("clinically relevant discrepancies", or CRD); (2) discrepancies that would not affect patient care ("incidental discrepancies", or ID); and (3) other types of comments. Rates of CRD and ID detection were compared between subgroups of Abdominal Imaging Division radiologists divided by the degree of subspecialization., Results: 1303 studies met the inclusion criteria. Of 742 cases reviewed by primary members of the AI division, 33 (4.4%) had CRD and 78 (10.5%) had ID. Of 561 cases reviewed by secondary members of the AI division, 11 (2.0%) had CRD and 36 (6.5%) had ID. The differences between the groups for both types of discrepancies were statistically significant (p = 0.01). When primary members of the AI division were further subdivided based on extent of clinical focus on abdominal imaging, rates of CRD and ID detection were higher for the subgroup with more clinical focus on abdominal imaging., Conclusion: The degree of AI subspecialization affects the rate of clinically relevant and ID identified in body CT interpretations initially rendered by board certified but non-abdominal imaging subspecialized radiologists.

Research has shown that experiences ofmilitary sexual assault and harassment can have a negative impact on veterans' health and functioning, even years or decades later, thus clearly identifying this as an important area of concern for social workers. In addition to understanding the scope and general impact of military sexual assault and harassment, social workers also must thoroughly understand how different cultural factors may intersect with veterans' experiences. To this end, this article reviews the current knowledge base on how veterans' life experiences related to gender can affect their experience of and recovery from military sexual assault and harassment, highlights common gender-specific issues, and discusses implications for practice.

Given the importance of reporting to sexual harassment prevention and intervention efforts, it is not surprising that an extensive scientific literature has developed on predictors of victims' decisions about making a formal report to authorities about their experiences. In contrast, little empirical work has focused on how reporting affects victims, particularly their psychosocial well-being. This study used a national sample of 1,562 former military Reservists who had experienced sexual harassment during their service to examine the relationship between reporting; experiences reporting; and psychosocial well-being, as indicated by post-harassment functioning, worst symptoms of posttraumatic stress disorder (PTSD) following the harassment, and current symptoms of depression. Making a formal report was not associated with well-being, but among those who did report, perceiving that the report had resulted in the harassment being addressed by authorities was associated with better post-harassment functioning and fewer symptoms of PTSD. Satisfaction with the reporting process showed the strongest association with well-being, demonstrating small but meaningful associations with depression and medium-to-large and medium associations with post-harassment functioning and PTSD, respectively. Although findings did not vary by gender, predictors accounted for more variance in well-being for men than women. In the whole sample, satisfaction with the reporting process mediated the relationship between victims' perceptions of system responsiveness to the report and post-harassment functioning and PTSD. Findings suggest that a victim's perceptions of and satisfaction with the reporting process may impact well-being more strongly than whether the victim made a report to authorities. Men may be even more strongly impacted by their experiences with the reporting process than women.

Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Intimate partner violence (IPV) victims often report feeling confused and uninformed about court proceedings, including even about the final disposition of the case against their partner. This is problematic because victims' decisions in responding to subsequent abuse may be significantly influenced by their beliefs about the outcomes of prior court experiences. Also, researchers often rely on victim report of court case outcomes; discrepancies between women's reports and official records may account for some of the conflicting findings in the empirical literature. In the current study, we compared the reports of case outcome given by 81 women recruited immediately after the final hearing of an IPV-related criminal case against their perpetrator with court records of case outcome. Findings revealed a fair level of agreement between women's reports and court files that was significantly different from the level of agreement expected by chance, but far from perfect. Level of agreement increased substantially when cases involving suspended sentences were removed. In reviewing these findings, we discuss the extent to which results can or cannot be interpreted as reflecting the accuracy of women's knowledge and review their implications for IPV researchers and court systems.

Objectives: We examine gender differences in population rates of various types of interpersonal violence in a U.S. national sample and investigate gender as a moderator of the associations between interpersonal violence and lifetime mental disorders and suicide attempts., Methods: Data were drawn from the National Comorbidity Survey-Replication study; 5,692 women and men completed interviews assessing lifetime exposure to nine types of interpersonal violence, Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) mental health diagnoses, and suicide attempts., Results: Approximately 46% of women and 42% of men reported one or more types of interpersonal violence. Women were more likely to experience kidnapping, physical assault by an intimate partner, rape, sexual assault, and stalking, whereas men were more likely to experience mugging or physical assault by someone other than parents or an intimate partner. Interpersonal violence was associated with risk for many mental disorders and attempted suicide. Although women were at higher risk for several forms of interpersonal violence, the impact of interpersonal violence on mental health outcomes did not vary by gender., Conclusions: It is clearly important to identify and provide mental health treatment to women after interpersonal violence exposure. Findings also underscore the need for prevention and intervention efforts for women and men, including routine screening for interpersonal violence by health care providers and appropriate treatment to address mental health conditions.

Purpose: Tobacco and alcohol use are well-known risk factors for squamous cell carcinoma of the head and neck (SCCHN), but there has been little examination of disparities in SCCHN and racial patterns of tobacco and alcohol use, especially for African-Americans. The Carolina Head and Neck Cancer Study, a population-based case-control study, was utilized to determine whether relationships between tobacco and alcohol use and SCCHN differed by race., Methods: Using a rapid case ascertainment system, cases were recruited from 46 contiguous counties in North Carolina from 2002 to 2006. Controls, selected from motor vehicle records, were frequency-matched to cases on age, sex, and race. This analysis was based on 989 white and 351 African-American cases and 1,114 white and 264 African-American controls. Analyses were performed using unconditional logistic regression, adjusting for age, sex, race, education, and fruit and vegetable consumption., Results: The association between SCCHN and ever tobacco use among African-Americans (odds ratio (OR), 9.68; 95 % confidence interval (CI), 4.70, 19.9) was much greater than that observed in whites (OR, 1.94; 95 % CI, 1.51, 2.50). Smaller differences were observed when examining ever alcohol use (African-Americans: OR, 3.71; CI, 1.65, 8.30, and Whites: OR, 1.31: CI 0.96, 1.78). African-Americans consistently had greater effect measure estimates when examining common levels of duration and intensity metrics of tobacco and alcohol use, both independently and jointly. No racial differences in the effects of environmental (passive) tobacco smoke were observed., Conclusions: These findings suggest racial differences in SCCHN are not solely explained by differences in consumption patterns, and tobacco and alcohol may have greater impact in African-Americans.

Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.

PCR detecting the protein D (hpd) and fuculose kinase (fucK) genes showed high sensitivity and specificity for identifying Haemophilus influenzae and differentiating it from H. haemolyticus. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for H. influenzae and H. haemolyticus.

Although most battered women seeking formal help have some contact with court, limited research exists on what they find helpful and harmful about these experiences. Using qualitative data from low-income, largely Black battered women, this study finds that issues related to court outcomes, such as case disposition and enforcement, are important to evaluations of helpfulness. More frequently mentioned, however, are court processes, including treatment by staff, process length, and public disclosure. Results highlight the importance of research and practice attending to issues beyond court outcomes, as well as the potential impact supportive treatment at court may have for victims' recovery.

Given the frequent occurrence and significant health impact of sexual harassment and sexual assault in the military, it is important that for health care providers working with Veterans to have at least some basic knowledge in this area. Targeting providers addressing mental health and psychosocial issues, but also applicable to clinicians working with survivors in a variety of capacities, this article provides an overview of clinical care with survivors of sexual trauma in the military, particularly those who are OEF/OIF Veterans. We cover basic background information, focusing primarily on the impact of sexual trauma in the military, how survivor's reactions are shaped by various aspects of the military context, and general principles to assist clinicians in working effectively with survivors, whatever their role.

Objective: Recent reports have linked oral health and periodontal disease indicators with increased risk of squamous cell carcinoma of head and neck (SCCHN). Thus far, evidence has been inconclusive; our objective was to study the association between oral health and SCCHN risk in the context of a large population-based study., Methods: A population-based case-control study of incident SCCHN, the Carolina Head and Neck Cancer Study was carried out in 2002-2006 in 46 counties in North Carolina. Controls (n = 1,361) were frequency matched with cases (n = 1,289) on age, race, and gender. Oral health was assessed using interview data on tooth loss and mobility, mouthwash use, and frequency of dental visits., Results: Subjects were 26-80 years old (median age = 61). The distribution of tooth loss among controls was 0-5 teeth = 60%; 5-14 = 15%; and 16-28 = 25%. After controlling for covariates, tooth loss did not yield any notable association with SCCHN (16-28 vs. 0-5 lost teeth: OR: 1.21, 95% CI: 0.94, 1.56). Self-reported history of tooth mobility was moderately associated with increased SCCHN risk (OR: 1.33, 95% CI: 1.07, 1.65); however, the association did not persist among never smokers. Routine dental visits were associated with 30% risk reduction (OR: 0.68, 95% CI: 0.53, 0.87)., Conclusions: These data provide support for a possible modest association of periodontal disease, as measured by self-reported tooth loss indicators, but not tooth loss per se, with SCCHN risk.

Assessment of seizure risk traditionally occurs late in the drug discovery process using low-throughput, resource intensive in vivo assays. Such approaches do not allow sufficient time to mitigate risk by influencing chemical design. Early identification using cheaper, higher throughput assays with lower animal and compound requirements would be preferable. Here we review the current techniques available to assess this issue and describe how they may be combined in a rational step-wise cascade allowing more effective assessment of seizure risk.

Bread wheat (Triticum aestivum L.) produces glutenin storage proteins in the endosperm. The HMW glutenins confer distinct viscoelastic properties to bread dough. The genetics of HMW glutenin proteins have been extensively studied, and information has accumulated about individual subunits, chromosomal locations and DNA sequences, but little is known about the regulators of the HMW glutenins. This investigation addressed the question of glutenin regulators. Expression of the glutenins was analyzed using QRT-PCR in ditelosomic (dt) Chinese Spring (CS) lines. Primers were designed for each of 4 CS glutenin genes and a control, non-storage protein endosperm-specific gene Agp-L (ADP-glucose pyrophosphorylase). Each line represents CS wheat, lacking one chromosome arm. The effect of a missing arm could feasibly cause an increase, decrease or no change in expression. For each HMW glutenin, results indicated there were, on average, 8 chromosome arms with an up-regulatory effect and only one instance of a down-regulatory effect. There were significant correlations between orthologous and paralogous HMW glutenins for effects of chromosome groups B and D. Some or all the glutenin alleles shared regulatory loci on chromosome arms 2BS, 7BS, 4DS, 5DS and 6DS, and Agp-L shared regulatory loci with glutenins on arms 7AS, 7BS, 2DS, 3DS, 4DS and 5DS. These results suggest a few chromosome arms contain putative regulatory genes affecting the expression of conserved cis elements of 4 HMW glutenin and Agp-L genes in CS. Regulation by common genes implies the regulators have diverged little from the common wheat ancestor, and furthermore, some regulation may be shared by endosperm-specific-genes. Significant common regulators have practical implications.

Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a chronic stressor, the steroids act in brain in a feed-forward fashion to recruit a stress-response network that biases ongoing autonomic, neuroendocrine, and behavioral outflow as well as responses to novel stressors. We review evidence for the role of glucocorticoids in activating the central stress-response network, and for mediation of this network by corticotropin-releasing factor (CRF). We briefly review the effects of CRF and its receptor antagonists on motor outflows in rodents, and examine the effects of glucocorticoids and CRF on monoaminergic neurons in brain. Corticosteroids stimulate behaviors that are mediated by dopaminergic mesolimbic "reward" pathways, and increase palatable feeding in rats. Moreover, in the absence of corticosteroids, the typical deficits in adrenalectomized rats are normalized by providing sucrose solutions to drink, suggesting that there is, in addition to the feed-forward action of glucocorticoids on brain, also a feedback action that is based on metabolic well being. Finally, we briefly discuss the problems with this network that normally serves to aid in responses to chronic stress, in our current overindulged, and underexercised society.

The hypothalamic-pituitary-adrenocortical axis plays an essential role in the maturation of fetal organs and, in sheep, birth. Lesioning the paraventricular nucleus (PVN) in fetal sheep prevents adrenocortical maturation and parturition without altering plasma immunoreactive ACTH concentrations. The purpose of this study was to determine the effect of PVN lesion on anterior pituitary processing of proopiomelanocortin (POMC) to ACTH, plasma concentrations of ACTH and ACTH precursors (POMC; 22-kDa proACTH), and expression of subtilisin-like prohormone convertase 3 (SPC3) in corticotropes in fetal sheep. PVN lesion did not affect anterior pituitary POMC and 22-kDa proACTH levels, whereas ACTH was significantly affected. The ACTH precursor (POMC plus 22-kDa proACTH) to ACTH ratio in the anterior pituitary was significantly increased after PVN lesion. Post-PVN lesion, fetal plasma ACTH(1-39), was below the limit of detection, whereas ACTH precursors (POMC plus 22-kDa proACTH) were not affected. In the inferior region of the anterior pituitary, 40-50% of corticotropes had detectable SPC3 hybridization signal, and PVN lesion did not change the extent of colocalization of POMC and SPC3, or SPC3 mRNA levels within corticotropes. Neither the percent of corticotropes in the superior region containing SPC3 hybridization (7-12%) or hybridization signal strength was altered in response to PVN lesion. In conclusion, the fetal PVN is necessary for sustaining adequate anterior pituitary processing of POMC to ACTH and ACTH release needed for maturing the adrenal cortex in the sheep fetus.

The effects of adrenal corticosteroids on subsequent adrenocorticotropin secretion are complex. Acutely (within hours), glucocorticoids (GCs) directly inhibit further activity in the hypothalamo-pituitary-adrenal axis, but the chronic actions (across days) of these steroids on brain are directly excitatory. Chronically high concentrations of GCs act in three ways that are functionally congruent. (i) GCs increase the expression of corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala, a critical node in the emotional brain. CRF enables recruitment of a chronic stress-response network. (ii) GCs increase the salience of pleasurable or compulsive activities (ingesting sucrose, fat, and drugs, or wheel-running). This motivates ingestion of "comfort food." (iii) GCs act systemically to increase abdominal fat depots. This allows an increased signal of abdominal energy stores to inhibit catecholamines in the brainstem and CRF expression in hypothalamic neurons regulating adrenocorticotropin. Chronic stress, together with high GC concentrations, usually decreases body weight gain in rats; by contrast, in stressed or depressed humans chronic stress induces either increased comfort food intake and body weight gain or decreased intake and body weight loss. Comfort food ingestion that produces abdominal obesity, decreases CRF mRNA in the hypothalamus of rats. Depressed people who overeat have decreased cerebrospinal CRF, catecholamine concentrations, and hypothalamo-pituitary-adrenal activity. We propose that people eat comfort food in an attempt to reduce the activity in the chronic stress-response network with its attendant anxiety. These mechanisms, determined in rats, may explain some of the epidemic of obesity occurring in our society.

To begin to understand the effects of chronic stress on food intake and energy stores, the effects of increased activity in the hypothalamo-pituitary-adrenal (HPA) axis and glucocorticoids (GCs) on the body and brain must first be understood. We propose two major systems that are both GC sensitive: a metabolic feedback that is inhibitory and a direct central GC drive. Under basal conditions, the metabolic feedback signal to brain is dominant, although infusion of GC into a lateral brain ventricle blocks the effects of the metabolic feedback. Chronic stress activates GC secretion and brain nuclear GC receptor occupancy, markedly changing the normal relationships between these two major corticosteroid-activated systems. The stressor-induced switch in the relative strengths of these signals determines subsequent brain regulation of stress responses (behavioral, neuroendocrine and autonomic outflows). The metabolic feedback effects of GCs are mimicked by voluntary sucrose ingestion in adrenalectomized rats, and experiments suggest that the metabolic feedback also inhibits the stressor-induced direct GC drive on brain. We speculate that the interaction between peripheral and central GC-sensitive signaling systems may be coupled through the inhibitory actions of endogenous opiatergic inputs on corticotropin-releasing factor (CRF) neurons.