Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

Swine Housing Impacts on Environment and Behavior: A comparison between hoop structures and total environmental control

The effect of housing on animal environment and behavior have been studied in a comparative trial with three deep-bedded hoop structures and one totally, environmentally- controlled slatted-floor building. In order to assess animal welfare, behavior indicative of both poor and rich welfare were quantified. Behavior indicative of poor welfare were considered to be the performance of aberrant behavior, stereotypical behavior and excessive fighting. Behaviors indicative of rich behavior were the performance of normal maintenance behaviors and play behavior. Hoop structures experienced lower winter air temperatures than did the confinement building (mean, 4.8 0 vs. 18.1 0 C), but effective temperatures for the animals were enhanced in the hoop structure by heat generated by the decomposing bedded pack (ranging from approximately –1.1 0 C to 47 0 C). The confinement building maintained a higher ammonia level than did the hoop structures. Pigs raised in the confinement system which did use bedding were found to be resting more often (P \u3c .03); however, they were also found to perform more aberrant and stereotypical behavior in addition to more frequent fighting (P \u3c .03). Pigs raised in the hoop structure were found to perform more play behavior than confinement raised pigs (P \u3c .03). Based on the greater incidence of aberrant, stereotyped, and agonistic behavior of confinement pigs and the greater incidence of play behavior by hoop raised pigs; the welfare of hoop raised pigs is considered to be richer than that of confinement raised pigs. The major contributing factor to explain this is likely the provision of bedding, which allows the pigs an opportunity to perform species typical behavior

Pharmacological Blockade of TRPM8 Ion Channels Alters Cold and Cold Pain Responses in Mice

TRPM8 (Transient Receptor Potential Melastatin-8) is a cold- and menthol-gated ion channel necessary for the detection of cold temperatures in the mammalian peripheral nervous system. Functioning TRPM8 channels are required for behavioral responses to innocuous cool, noxious cold, injury-evoked cold hypersensitivity, cooling-mediated analgesia, and thermoregulation. Because of these various roles, the ability to pharmacologically manipulate TRPM8 function to alter the excitability of cold-sensing neurons may have broad impact clinically. Here we examined a novel compound, PBMC (1-phenylethyl-4-(benzyloxy)-3-methoxybenzyl(2-aminoethyl)carbamate) which robustly and selectively inhibited TRPM8 channels in vitro with sub-nanomolar affinity, as determined by calcium microfluorimetry and electrophysiology. The actions of PBMC were selective for TRPM8, with no functional effects observed for the sensory ion channels TRPV1 and TRPA1. PBMC altered TRPM8 gating by shifting the voltage-dependence of menthol-evoked currents towards positive membrane potentials. When administered systemically to mice, PBMC treatment produced a dose-dependent hypothermia in wildtype animals while TRPM8-knockout mice remained unaffected. This hypothermic response was reduced at lower doses, whereas responses to evaporative cooling were still significantly attenuated. Lastly, systemic PBMC also diminished cold hypersensitivity in inflammatory and nerve-injury pain models, but was ineffective against oxaliplatin-induced neuropathic cold hypersensitivity, despite our findings that TRPM8 is required for the cold-related symptoms of this pathology. Thus PBMC is an attractive compound that serves as a template for the formulation of highly specific and potent TRPM8 antagonists that will have utility both in vitro and in vivo

Estimativa do crescimento de povoamentos de Eucalyptus baseada na teoria dos modelos não lineares em multinível de efeito misto.

This study was based on the application of the nonlinear multilevel mixed-effects theory in modeling the height growth of Eucalyptus plantation. The database was from individual tree measurements, taken from different sites and over time. This type of database is considered as longitudinal, irregularly spaced, unbalanced, with autocorrelation and  heteroscedasticity. The tree-parameter logistic model was used to estimate the height growth with fixed and random effects in two levels: sample units (level 1) and trees inside sample units (level 2). By including both levels, the standard error of estimate was reduced significantly. Also, the estimates were improved by modeling the variance heterogeneity and the autocorrelation, using the ARMA(2,1) structure.O presente estudo foi baseado na utilização da teoria dos modelos não-lineares de efeito misto em multiníveis para a modelagem do crescimento em altura de povoamentos clonais de Eucalyptus. A base de dados utilizada representa medições de árvores individuais, tomadas em diferentes locais e no tempo, sendo a mesma classificada de longidudinal, irregularmente espaçada, não-balanceada, com autocorrelação e com a presença de heterogeneidade de variância. O modelo logístico de três parâmetros foi utilizado para a estimativa do crescimento em altura. Os parâmetros do modelo foram estimados como de efeitos fixos e aleatórios em dois níveis: unidade amostral (nível 1) e árvore individual dentro das unidades amostrais (nível 2). A inclusão de tais níveis reduziu sensivelmente o erro padrão da estimativa para o modelo. As estimativas também foram melhoradas com a modelagem da heterogeneidade da variância, utilizando estruturas diagonais, e da autocorrelação, com a estrutura ARMA(2,1)

GROWTH ESTIMATE OF Eucalyptus STANDS BASED ON NONLINEAR MULTILEVEL MIXEDEFFECTS MODEL THEORY

O presente estudo foi baseado na utiliza\ue7\ue3o da teoria dos modelos n\ue3o-lineares de efeito misto em multin\uedveis para a modelagem do crescimento em altura de povoamentos clonais de Eucalyptus. A base de dados utilizada representa medi\ue7\uf5es de \ue1rvores individuais, tomadas em diferentes locais e no tempo, sendo a mesma classificada de longidudinal, irregularmente espa\ue7ada, n\ue3o-balanceada, com autocorrela\ue7\ue3o e com a presen\ue7a de heterogeneidade de vari\ue2ncia. O modelo log\uedstico de tr\ueas par\ue2metros foi utilizado para a estimativa do crescimento em altura. Os par\ue2metros do modelo foram estimados como de efeitos fixos e aleat\uf3rios em dois n\uedveis: unidade amostral (n\uedvel 1) e \ue1rvore individual dentro das unidades amostrais (n\uedvel 2). A inclus\ue3o de tais n\uedveis reduziu sensivelmente o erro padr\ue3o da estimativa para o modelo. As estimativas tamb\ue9m foram melhoradas com a modelagem da heterogeneidade da vari\ue2ncia, utilizando estruturas diagonais, e da autocorrela\ue7\ue3o, com a estrutura ARMA(2,1).This study was based on the application of the nonlinear multilevel mixed-effects theory in modeling the height growth of Eucalyptus plantation. The database was from individual tree measurements, taken from different sites and over time. This type of database is considered as longitudinal, irregularly spaced, unbalanced, with autocorrelation and heteroscedasticity. The tree-parameter logistic model was used to estimate the height growth with fixed and random effects in two levels: sample units (level 1) and trees inside sample units (level 2). By including both levels, the standard error of estimate was reduced significantly. Also, the estimates were improved by modeling the variance heterogeneity and the autocorrelation, using the ARMA(2,1) structure

Individual Characteristics Associated with PBDE Levels in U.S. Human Milk Samples

BackgroundReported polybrominated diphenyl ether (PBDE) concentrations in human samples in the United States have been higher than in Europe and Asia. Little is known about factors that contribute to individual variability in body burden.ObjectiveIn this large study we measured PBDE concentrations in human milk from the United States during 2004–2006. We assessed characteristics associated with concentrations in milk and change in milk concentration between 3 and 12 months postpartum.MethodsWe analyzed 303 milk samples obtained 3 months postpartum for PBDEs. A second sample was analyzed for 83 women still lactating 12 months postpartum. PBDE concentrations in milk and variability by individual characteristics such as age, parity, and prepregnancy body mass index (BMI) were evaluated using generalized linear models.ResultsPBDE congeners BDEs 28, 47, 99, 100, and 153 were detected in > 70% of samples. BDE-47 concentrations were the highest, ranging from below the limit of detection to 1,430 ng/g lipid, with a median of 28 ng/g lipid. Concentrations of most individual PBDE congeners and the sum of BDEs 28, 47, 99, 100, and 153 (∑PBDE) were lower among mothers > 34 years of age compared with those 25–29 years of age and higher among mothers with high compared with normal BMI, after adjustment for other covariates. Parity was not associated with PBDE concentration. The change in ∑PBDE concentration in milk between 3 and 12 months postpartum was highly variable (median increase, 14%; interquartile range, −26% to 50%).ConclusionsPBDEs were detected in nearly all human milk samples, varying by maternal weight and age and over the course of breast-feeding

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Ursinus College Alumni Journal, March 1967

The paradox of urbia • The joyful acceptance of technopolis • Toward a new kind of freedom • Bill Daniels leads a creative life of action in urbia • Who is educated to plan the urban environment? • From the President • Concerning Freeland Seminary: An alumna writes a history of Collegeville • Discovery in Europe, student style • Personal calls will climax \u2767 Centennial Fund • Candidates for office • Springtime is alumni time • Student magazine focuses on political affairs • A theory of non-interference • From the Perkiomen to the Potomac • In the land of the four 70s • Sporting scene: Wrestling; Indoor track; Cross country; Basketball; Women\u27s hockey; Other women\u27s sports; Scheduling correction • Campus clippings: Financial support; Student lounge a success; Selma sheriff speaks; The amazing Evening School; Questionnaires returned; Book on urbia still available; Honor graduate; Sign to show the way • Class notebook • Physicians Alumni Club of Ursinus College organizes • Weddings • Births • In memoriamhttps://digitalcommons.ursinus.edu/alumnijournal/1088/thumbnail.jp