A bed nucleus of stria terminalis microcircuit regulating inflammation-associated modulation of feeding

Loss of appetite or anorexia associated with inflammation impairs quality of life and increases morbidity in many diseases. However, the exact neural mechanism that mediates inflammation-associated anorexia is still poorly understood. Here we identified a population of neurons, marked by the expression of protein kinase C-delta, in the oval region of the bed nucleus of the stria terminalis (BNST), which are activated by various inflammatory signals. Silencing of these neurons attenuates the anorexia caused by these inflammatory signals. Our results demonstrate that these neurons mediate bidirectional control of general feeding behaviors. These neurons inhibit the lateral hypothalamus-projecting neurons in the ventrolateral part of BNST to regulate feeding, receive inputs from the canonical feeding regions of arcuate nucleus and parabrachial nucleus. Our data therefore define a BNST microcircuit that might coordinate canonical feeding centers to regulate food intake, which could offer therapeutic targets for feeding-related diseases such as anorexia and obesity.NARSAD Young Investigator Award from the Brain & Behavior Research Foundation; Bio5 Institute at the University of ArizonaOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Efficacy of Mammographic Evaluation of Breast Cancer in Women Less Than 40 Years of Age: Experience from a Single Medical Center in Taiwan

Background/PurposeMammography is the standard imaging modality for breast cancer diagnosis. However, the value of mammographic diagnosis in breast cancer patients aged less than 40 years old has not been well assessed. The goal of our study was to determine the diagnostic efficacy of mammography for the detection of breast cancer in women under 40 years of age in a single medical center in Taiwan.MethodsOf 1766 women diagnosed with breast cancer in one medical center between 1999 and 2005, 227 (12.9%) who were younger than 40 years of age were enrolled, and 105 of these 227 patients had pre-biopsy mammograms available for analysis. The sensitivities for mammography at first (prospective) and second (retrospective) readings and for corresponding ultrasound were calculated. The distribution of different breast composition between the mammographic true-positive (TP) and false-negative (FN) lesions at the first and second readings was analyzed.ResultsOf the 105 patients, 104 presented with a palpable mass and the other one was asymptomatic. There were 109 pathologically proven breast cancers from the 105 patients; 92 of 109 cancerous lesions were detected at the first mammographic reading (sensitivity 84.4%), and the most common mammographic sign was microcalcifications (40.2%). The second reading detected seven additional cancers (99 of 109 lesions; sensitivity 90.8%). There was no significant difference between mammographic TP and FN lesions for the different breast composition on first and second readings. Ninety patients also had ultrasound available for correlation with 94 cancers diagnosed from them. The diagnostic sensitivity of ultrasound was 94.7% (89 of 94 lesions).ConclusionMammography has an acceptable sensitivity for the detection of breast cancer in women aged less than 40 years, regardless of different breast composition. Breast ultrasound can offer a higher sensitivity for such a population

Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study

<p>Abstract</p> <p>Background</p> <p>The study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system.</p> <p>Methods</p> <p>The study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youden's Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youden's Index.</p> <p>Results</p> <p>For the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%.</p> <p>Conclusions</p> <p>We established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose.</p> <p>Trial Registration</p> <p>NCT00166998.</p

Activation of Myocardial Phosphoinositide-3-Kinase p110α Ameliorates Cardiac Dysfunction and Improves Survival in Polymicrobial Sepsis

Phosphoinositide-3-kinase (PI3K)/Akt dependent signaling has been shown to improve outcome in sepsis/septic shock. There is also ample evidence that PI3K/Akt dependent signaling plays a crucial role in maintaining normal cardiac function. We hypothesized that PI3K/Akt signaling may ameliorate septic shock by attenuating sepsis-induced cardiac dysfunction. Cardiac function and survival were evaluated in transgenic mice with cardiac myocyte specific expression of constitutively active PI3K isoform, p110α (caPI3K Tg). caPI3K Tg and wild type (WT) mice were subjected to cecal ligation/puncture (CLP) induced sepsis. Wild type CLP mice showed dramatic cardiac dysfunction at 6 hrs. Septic cardiomyopathy was significantly attenuated in caPI3K CLP mice. The time to 100% mortality was 46 hrs in WT CLP mice. In contrast, 80% of the caPI3K mice survived at 46 hrs after CLP (p30 days (

Primer set 2.0 for highly parallel qPCR array targeting antibiotic resistance genes and mobile genetic elements

The high-throughput antibiotic resistance gene (ARG) qPCR array, initially published in 2012, is increasingly used to quantify resistance and mobile determinants in environmental matrices. Continued utility of the array; however, necessitates improvements such as removing or redesigning questionable primer sets, updating targeted genes and coverage of available sequences. Towards this goal, a new primer design tool (EcoFunPrimer) was used to aid in identification of conserved regions of diverse genes. The total number of assays used for diverse genes was reduced from 91 old primer sets to 52 new primer sets, with only a 10% loss in sequence coverage. While the old and new array both contain 384 primer sets, a reduction in old primer sets permitted 147 additional ARGs and mobile genetic elements to be targeted. Results of validating the updated array with a mock community of strains resulted in over 98% of tested instances incurring true positive/negative calls. Common queries related to sensitivity, quantification and conventional data analysis (e.g. Ct cutoff value, and estimated genomic copies without standard curves) were also explored. A combined list of new and previously used primer sets is provided with a recommended set based on redesign of primer sets and results of validation

Babesia duncani multi-omics identifies virulence factors and drug targets

Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.We thank R. Gao for her contribution to the initial eforts to sequence the B. duncani genome. C.B.M.’s research was supported by grants from the National Institutes of Health (AI097218, GM110506, AI123321 and R43AI136118), the Steven and Alexandra Cohen Foundation (Lyme 62 2020), and the Global Lyme Alliance. S.L.’s research was supported by grants by the US National Science Foundation (IIS 1814359) and the National Institutes of Health (1R01AI169543-01). K.G.L.R.’s research was supported by the National Institutes of Allergy and Infectious Diseases (R01 AI136511, R01 AI142743-01 and R21 AI142506-01), the University of California, Riverside (NIFA-Hatch-225935) and the Health Institute Carlos III (PI20CIII/00037).S

Temporal scale‐dependence of plant–pollinator networks

The study of mutualistic interaction networks has led to valuable insights into ecological and evolutionary processes. However, our understanding of network structure may depend upon the temporal scale at which we sample and analyze network data. To date, we lack a comprehensive assessment of the temporal scale-dependence of network structure across a wide range of temporal scales and geographic locations. If network structure is temporally scale-dependent, networks constructed over different temporal scales may provide very different perspectives on the structure and composition of species interactions. Furthermore, it remains unclear how various factors – including species richness, species turnover, link rewiring and sampling effort – act in concert to shape network structure across different temporal scales. To address these issues, we used a large database of temporally-resolved plant–pollinator networks to investigate how temporal aggregation from the scale of one day to multiple years influences network structure. In addition, we used structural equation modeling to explore the direct and indirect effects of temporal scale, species richness, species turnover, link rewiring and sampling effort on network structural properties. We find that plant–pollinator network structure is strongly temporally-scale dependent. This general pattern arises because the temporal scale determines the degree to which temporal dynamics (i.e. phenological turnover of species and links) are included in the network, in addition to how much sampling effort is put into constructing the network. Ultimately, the temporal scale-dependence of our plant–pollinator networks appears to be mostly driven by species richness, which increases with sampling effort, and species turnover, which increases with temporal extent. In other words, after accounting for variation in species richness, network structure is increasingly shaped by its underlying temporal dynamics. Our results suggest that considering multiple temporal scales may be necessary to fully appreciate the causes and consequences of interaction network structure.Fil: Schwarz, Benjamin. Albert Ludwigs University of Freiburg; AlemaniaFil: Vazquez, Diego P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Cara Donna, Paul J.. Chicago Botanic Garden; Estados UnidosFil: Knight, Tiffany M.. German Centre for Integrative Biodiversity Research; AlemaniaFil: Benadi, Gita. Albert Ludwigs University of Freiburg; AlemaniaFil: Dormann, Carsten F.. Albert Ludwigs University of Freiburg; AlemaniaFil: Gauzens, Benoit. German Centre for Integrative Biodiversity Research; AlemaniaFil: Motivans, Elena. German Centre for Integrative Biodiversity Research; AlemaniaFil: Resasco, Julian. University of Colorado; Estados UnidosFil: Blüthgen, Nico. Universitat Technische Darmstadt; AlemaniaFil: Burkle, Laura A.. Montana State University; AlemaniaFil: Fang, Qiang. Henan University of Science and Technology; ChinaFil: Kaiser Bunbury, Christopher N.. University of Exeter; Reino UnidoFil: Alarcón, Ruben. California State University; Estados UnidosFil: Bain, Justin A.. Chicago Botanic Garden; Estados UnidosFil: Chacoff, Natacha Paola. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; ArgentinaFil: Huang, Shuang Quan. Central China Normal University; ChinaFil: LeBuhn, Gretchen. San Francisco State University; Estados UnidosFil: MacLeod, Molly. Rutgers University; Estados UnidosFil: Petanidou, Theodora. Univversity of the Aegean; Estados UnidosFil: Rasmussen, Claus. University Aarhus; DinamarcaFil: Simanonok, Michael P.. Montana State University; Estados UnidosFil: Thompson, Amibeth H.. German Centre for Integrative Biodiversity Research; AlemaniaFil: Fründ, Jochen. Albert Ludwigs University of Freiburg; Alemani

mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron

Do people with risky behaviours participate in biomedical cohort studies?

BACKGROUND: Analysis was undertaken on data from randomly selected participants of a bio-medical cohort study to assess representativeness. The research hypotheses was that there was no difference in participation and non-participations in terms of health-related indicators (smoking, alcohol use, body mass index, physical activity, blood pressure and cholesterol readings and overall health status) and selected socio-demographics (age, sex, area of residence, education level, marital status and work status). METHODS: Randomly selected adults were recruited into a bio-medical representative cohort study based in the north western suburbs of the capital of South Australia – Adealide. Comparison data was obtained from cross-sectional surveys of randomly selected adults in the same age range and in the same region. The cohort participants were 4060 randomly selected adults (18+ years). RESULTS: There were no major differences between study participants and the comparison population in terms of current smoking status, body mass index, physical activity, overall health status and proportions with current high blood pressure and cholesterol readings. Significantly more people who reported a medium to very high alcohol risk participated in the study. There were some demographic differences with study participants more likely to be in the middle level of household income and education level. CONCLUSION: People with risky behaviours participated in this health study in the same proportions as people without these risk factors

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

BACKGROUND: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. METHODS: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. RESULTS: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4 CONCLUSION: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals