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Worldwide prevalence of cervical cancer decreased significantly with the use of human papilloma virus (HPV)‐targeted prophylactic vaccines. However, these multivalent antiviral vaccines are inert against established tumors, which leave patients with surgical ablative options possibly resulting in long‐term reproductive complications and morbidity. In an attempt to bypass this unmet medical need, we designed a new E7 protein‐based vaccine formulation using Accum™, a technology platform designed to promote endosome‐to‐cytosol escape as a means to enhance protein accumulation in target cells. Prophylactic vaccination of immunocompetent mice using the Accum‐E7 vaccine (aE7) leads to complete protection from cervical cancer despite multiple challenges conducted with ascending C3.43 cellular doses (0.5‐, 1.0‐, and 2.0 × 106 cells). Moreover, the humoral response induced by aE7 was higher in magnitude compared with naked E7 protein vaccination and displayed potent inhibitory effects on C3.43 proliferation in vitro. When administered therapeutically to animals with pre‐established C3.43 or Tal3 tumors, the vaccine‐induced response synergized with multiple immune checkpoint blockers (anti‐PD‐1, anti‐CTLA4, and anti‐CD47) to effectively control tumor growth. Mechanistically, the observed therapeutic effect requires cross‐presenting dendritic cells as well as CD8 T cells predominantly, with a non‐negligible role played by both CD4+ and CD19+ lymphocytes. good laboratory practice (GLP) studies revealed that aE7 is immunogenic and well tolerated by immunocompetent mice with no observed adverse effects despite the use of a fourfold exceeding dose. In a nutshell, aE7 represents an ideal vaccine candidate for further clinical development as it uses a single engineered protein capable of exhibiting both prophylactic and therapeutic activity. [ABSTRACT FROM AUTHOR]

The Accum™ technology was initially designed to enhance the bioaccumulation of a given molecule in target cells. It does so by triggering endosomal membrane damages allowing endocytosed products to enter the cytosol, escaping the harsh environmental cues of the endosomal lumen. In an attempt to minimize manufacturing hurdles associated with Accum™ conjugation, we tested whether free Accum™ admixed with antigens could lead to outcomes similar to those obtained with conjugated products. Surprisingly, unconjugated Accum™ was found to promote cell death in vitro, an observation further confirmed on various murine tumor cell lines (EL4, CT‐26, B16, and 4 T1). At the molecular level, unconjugated Accum™ triggers the production of reactive oxygen species and elicits immunogenic cell death while retaining its innate ability to cause endosomal damages. When administered as a monotherapy to animals with pre‐established EL4 T‐cell lymphoma, Accum™ controlled tumor growth in a dose‐dependent manner, and its therapeutic effect relies on CD4 and CD8 T cells. Although unconjugated Accum™ synergizes with various immune checkpoint inhibitors (anti‐CTLA4, anti‐PD‐1, or anti‐CD47) at controlling tumor growth, its therapeutic potency could not be further enhanced when combined with all three tested immune checkpoint inhibitors at once due to its dependency on a specific dosing regimen. In sum, we report in this study an unprecedented new function for unconjugated Accum™ as a novel anticancer molecule. These results could pave the path for a new line of investigation aimed at exploring the pro‐killing properties of additional Accum™ variants as a mean to develop second‐generation anticancer therapeutics. [ABSTRACT FROM AUTHOR]

While investigating aerobic anoxygenic phototrophs (AAP) from Lake Winnipeg's bacterial community, over 500 isolates were obtained. Relatives of 20 different species were examined simultaneously, identifying conditions for optimal growth or pigment production to determine features that may unify this group of phototrophs. All were distributed among assorted α‐Proteobacterial families including Erythrobacteraceae, Sphingomonadaceae, Sphingosinicellaceae, Acetobacteraceae, Methylobacteriaceae, and Rhodobacteraceae. Major phenotypic characteristics matched phylogenetic association, including pigmentation, morphology, metal transformations, tolerances, lipid configurations, and enzyme activities, which distinctly separated each taxonomic family. While varying pH and temperature had a limited independent impact on pigment production, bacteriochlorophyll synthesis was distinctly promoted under low nutrient conditions, whereas copiotrophy repressed its production but enhanced carotenoid yield. New AAP diversity was also reported by revealing strains related to non‐phototrophic Rubellimicrobium and Sphingorhabdus, as well as spread throughout Roseomonas, Sphingomonas, and Methylobacterium/Methylorubrum, which previously only had a few known photosynthetic members. This study exemplified the overwhelming diversity of AAP in a single aquatic environment, confirming cultivation continues to be of importance in microbial ecology to discover functionality in both new and previously reported cohorts of bacteria as specific laboratory conditions were required to promote aerobic bacteriochlorophyll production. [ABSTRACT FROM AUTHOR]

G‐protein‐coupled receptors (GPCRs) constitute the largest family of membrane receptors, and are involved in the transmission of a variety of extracellular stimuli such as hormones, neurotransmitters, light and odorants into intracellular responses. They regulate every aspect of physiology and, for this reason, about one third of all marketed drugs target these receptors. Classically, upon binding to their agonist, GPCRs are thought to activate G‐proteins from the plasma membrane and to stop signalling by subsequent desensitisation and endocytosis. However, accumulating evidence indicates that, upon internalisation, some GPCRs can continue to activate G‐proteins in endosomes. Importantly, this signalling from endomembranes mediates alternative cellular responses other than signalling at the plasma membrane. Endosomal G‐protein signalling and its physiological relevance have been abundantly documented for Gαs‐ and Gαi‐coupled receptors. Recently, some Gαq‐coupled receptors have been reported to activate Gαq on endosomes and mediate important cellular processes. However, several questions relative to the series of cellular events required to translate endosomal Gαq activation into cellular responses remain unanswered and constitute a new conundrum. How are these responses in endosomes mediated in the quasi absence of the substrate for the canonical Gαq‐activated effector? Is there another effector? Is there another substrate? If so, how does this alternative endosomal effector or substrate produce a downstream signal? This review aims to unravel and discuss these important questions, and proposes possible routes of investigation. [ABSTRACT FROM AUTHOR]

Psychological safety, defined as perceptions that an individual within a team is supported and feels safe to take interpersonal risks, voice opinions, and share ideas, is vital for organizational effectiveness. However, there is no consensus on how workplace psychological safety should be measured. We developed the Psychological Safety Inventory (PSI) in response to organizational needs to accurately assess psychological safety. A 70‐item version of the PSI was administered to 497 employees from Canada, the United States, and the United Kingdom. Based on factor analytic findings, we reduced the preliminary PSI to a 30‐item, five‐factor scale. The PSI showed high reliability and correlated as anticipated with convergent measures. Overall, the PSI is a valid and reliable measure of workplace psychological safety. Practitioner points: Feeling psychologically safe, whether at an individual or organizational level, is vital for organizational effectiveness.However, there is no consensus on how psychological safety should be measured in an occupational setting.Given this lack of consensus and limited reliability and validity information for available measures, there is a need for the development of a comprehensive psychological safety scale.We developed a comprehensive self‐report measure of psychological safety for use in workplace contexts titled the Psychological Safety Inventory (PSI).Based on exploratory and confirmatory factor analyses, we reduced the preliminary PSI to a 30‐item, five‐factor scale.The PSI subscales and total scale showed high reliability and correlated as anticipated with other measures of psychological safety, leadership, team climate, organizational perceptions, and organizational support.Our research can be used to inform organizational practices, such that leaders can assess their teams' levels of psychological safety to evaluate areas of need within the workplace context. [ABSTRACT FROM AUTHOR]

Pain experienced by Black individuals is systematically underestimated, and recent studies have shown that part of this bias is rooted in perceptual factors. We used Reverse Correlation to estimate visual representations of the pain expression in Black and White faces, in participants originating from both Western and African countries. Groups of raters were then asked to evaluate the presence of pain and other emotions in these representations. A second group of White raters then evaluated those same representations placed over a neutral background face (50% White; 50% Black). Image‐based analyses show significant effects of culture and face ethnicity, but no interaction between the two factors. Western representations were more likely to be judged as expressing pain than African representations. For both cultural groups, raters also perceived more pain in White face representations than in Black face representations. However, when changing the background stimulus to the neutral background face, this effect of face ethnic profile disappeared. Overall, these results suggest that individuals have different expectations of how pain is expressed by Black and White individuals, and that cultural factors may explain a part of this phenomenon [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is the most common intraocular tumor in adults. Recurrent mutations in BRCA1‐associated protein 1 (BAP1) and splicing factor 3B subunit 1 (SF3B1) display a mutually exclusive pattern in UM, but the underlying mechanism is unknown. We show that combined BAP1 deficiency and SF3B1 hotspot mutation lead to senescence and growth arrest in human UM cells. Although p53 protein expression is induced, deletion of TP53 (encoding p53) only modestly rescues the observed senescent phenotype. UM cells with BAP1 loss or SF3B1 mutation are more sensitive to chemotherapeutic drugs compared with their isogenic parental cells. Transcriptome analysis shows that DNA‐repair genes are downregulated upon co‐occurrence of BAP1 deletion and SF3B1 mutation, thus leading to impaired DNA damage response and the induction of senescence. The co‐occurrence of these two mutations reduces invasion of UM cells in zebrafish xenograft models and suppresses growth of melanoma xenografts in nude mice. Our findings provide a mechanistic explanation for the mutual exclusivity of BAP1 and SF3B1 mutations in human UM. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the association among admissions variables, dental school performance, and licensing exam performance for six cohorts of graduates of one dental school. Data from all dental school graduates of Schulich School of Medicine & Dentistry, Western University, Canada, from 2009 to 2014 who had matching National Dental Examining Board of Canada (NDEB) data (N=298) were analyzed. In the results, significant differences between cohorts were found on both the NDEB objective structured clinical examination (OSCE) and written scores. Approximately 18% of the variation in OSCE scores was attributable to cohort differences and 82% to student differences. Approximately 10% of the variation in written scores was attributable to cohort differences and 90% to student differences. Several multilevel models were conducted. The final predictive model for NDEB OSCE scores consisted of age, Canadian Dental Aptitude Test (DAT) reading comprehension scores, year 2 average, and year 4 average. For predicting NDEB written exam scores, the final model consisted of DAT chemistry and year 1, 2, and 4 averages. The findings of this study showed that academic performance on admissions variables and in training predicted performance on dental licensing exams, whereas variables that captured noncognitive or interpersonal skills, such as interview scores, were not predictive. This difference may be due to construct mismatch, such that the outcome variables had no theoretical association with the predictors. Additional outcome measures (including noncognitive) are needed that have greater ecological validity in predicting potential for competence in practice. [ABSTRACT FROM AUTHOR]

Whereas the bulk chemical industry has historically sought economic advantage through economies of scale, a paradigm shift has researchers developing systems on smaller scales. Nano‐cages and nano‐actuators increase selectivity and robustness at the molecular scale. In parallel, micro‐contactors with sub‐millimetre lateral dimensions are decreasing boundary layers that restrict heat and mass transfer and thus meet the objectives of process intensification with great increases in productivity with a smaller footprint. These contactors continue to serve chemical engineers and chemists to synthesize fine chemicals and characterize catalysts; however, they have now been adopted for sensors in biological and biochemical systems. A bibliometric analysis of articles indexed in the Web of Science in 2016 and 2017 identified five major clusters of research: catalysis and bulk chemicals; nanoparticles; organic synthesis and flow chemistry; systems and micro‐fluidics applied to biochemistry; and micro‐channel reactors and mass transfer. In the early 1990s, less than 100 articles a year mentioned micro‐reactors, while over 943 articles mentioned it in 2017. Here, we introduce micro‐reactors and their role in the continuous synthesis of fine chemicals across the various scales to commercialization. [ABSTRACT FROM AUTHOR]

The current study reports on a cross‐cultural validation of the recently developed Resiliency Scale for Young Adults (RSYA) with two samples consisting of 617 Canadian university students and 651 Chinese university students. Confirmatory factor analysis, tests of cultural invariance, and correlations with relevant individual difference variables were conducted as tests of validity. In the Chinese sample, confirmatory factor analysis supported the factor structure of the RSYA and internal consistency reliabilities for the three factors and 10 facets were good‐to‐excellent. Cultural and gender invariance were supported. Correlations with depression, anxiety, stress, flourishing, and life satisfaction were also in the expected direction in the Chinese sample. These findings provide additional support for the RSYA as a reliable and valid measure of personal resiliency for Chinese young adults. Findings support the three‐factor model of personal resiliency in both Canadian and Chinese young adults, as well as cultural and gender invariance. The robustness of this model has implications for assessing and developing resiliency cross‐culturally. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine whether different student profiles would emerge in terms of high and low GPA performance in each year of dental school and to investigate the utility of preadmissions variables in predicting performance and performance stability throughout each year of dental school. Data from 11 graduating cohorts (2004-14) at the Schulich School of Medicine & Dentistry, University of Western Ontario, Canada, were collected and analyzed using bivariate correlations, latent profile analysis, and hierarchical generalized linear models (HGLMs). The data analyzed were for 616 students in total (332 males and 284 females). Four models were developed to predict adequate and poor performance throughout each of four dental school years. An additional model was developed to predict student performance stability across time. Two separate student profiles reflecting high and low GPA performance across each year of dental school were identified, and scores on cognitive preadmissions variables differentially predicted the probability of grouping into high and low performance profiles. Students with higher pre-dental GPAs and DAT chemistry were most likely to remain stable in a high-performance group across each year of dental school. Overall, the findings suggest that selection committees should consider pre-dental GPA and DAT chemistry scores as important tools for predicting dental school performance and stability across time. This research is important in determining how to better predict success and failure in various areas of preclinical dentistry courses and to provide low-performing students with adequate academic assistance. [ABSTRACT FROM AUTHOR]

YAP is the major downstream effector of the Hippo pathway, which controls cell growth, tissue homeostasis, and organ size. Aberrant YAP activation, resulting from dysregulation of the Hippo pathway, is frequently observed in human cancers. YAP is a transcription co-activator, and the key mechanism of YAP regulation is its nuclear and cytoplasmic translocation. The Hippo pathway component, LATS, inhibits YAP by phosphorylating YAP at Ser127, leading to 14-3-3 binding and cytoplasmic retention of YAP. Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14-3-3, resulting in YAP nuclear accumulation and induction of downstream target gene expression. This osmotic stress-induced YAP activation enhances cellular stress adaptation. Our findings reveal a critical role for NLK-mediated Ser128 phosphorylation in YAP regulation and a crosstalk between osmotic stress and the Hippo pathway. [ABSTRACT FROM AUTHOR]

Model assessment is one of the most important aspects of statistical analysis. In geographical analysis, models represent spatial processes, where variability in mapped output results from uncertainty in parameter estimates. Slight spatial misalignments can cause inflated error scores when comparing maps of observed and predicted variables using traditional error metrics at the level of individual spatial units. We conceptualize spatial model assessment as a continuous value map comparison problem and employ methods from image analysis to score model outputs. The structural similarity index, a measure that attempts to replicate the human visual system using a local region approach, is used as an exploratory map comparison statistic. The measure is implemented within a Bayesian spatial modeling framework as a discrepancy measure in a posterior predictive check of model fit. Results are reported for simulation studies representing a variety of spatial processes in a spatial and space-time context. A case study of rainfall mapping in Sri Lanka demonstrates the proposed methodology applied to assessment of Bayesian kriging interpolations. Both simulation studies as well as the case study demonstrate that the approach reveals hidden spatial structure not uncovered by traditional methods. The spatially sensitive assessment methodology provides a diagnostic tool to support spatial modeling and analysis. La evaluación de modelos es uno de los aspectos más importantes de análisis estadístico. En el análisis geográfico, los modelos representan procesos espaciales en los que la variabilidad en los outputs es el resultado de la incertidumbre en los parámetros estimados. Leves desajustes espaciales pueden inflar los valores de error en la comparación entre los mapas de las observaciones y los mapas de las predicciones de las variables si es que se usan medidas tradicionales de medición de error al nivel de unidades espaciales individuales. Los autores conceptualizan la evaluación de modelos espaciales como un problema de comparación mapas de valor continuo y emplea métodos de análisis de imágenes para cuantificar los resultados del modelo. Se utiliza el índice de similitud estructural (SSIM), una medida que intenta replicar el sistema visual humano utilizando un enfoque de región local, como técnica de exploratoria comparación estadística de mapas. El índice es implementado dentro de un marco de modelización espacial bayesiano como medida de discrepancia en la comprobación posterior de predicción del desempeño del modelo. Los resultados se presentan para varios casos de simulación que representan una serie de procesos espaciales en un contexto espacio-temporal y espacial. Un estudio de caso de mapeo de lluvias en Sri Lanka sirve como demostración de la metodología propuesta y su aplicación a la evaluación de las interpolaciones tipo krigeage ( kriging) bayesianas. Tanto los estudios de simulación, así como el estudio de caso demuestran que el enfoque propuesto revela la estructura espacial oculta no evidenciada por métodos tradicionales. La metodología de evaluación espacialmente sensible que se presenta en este artículo proporciona una herramienta de diagnóstico para apoyar la elaboración de modelos y análisis espacial. 模型评估是统计分析中最为重要的内容之一。在地理分析中用模型表达空间过程，参数估计的不确定性会导致地图输出结果的可变性。当采用传统误差指标度量，在个体空间单位水平上进行观测和预测变量的地图比较时，微小的空间错位就可能导致误差的倍增。为此，本文通过将空间模型评估指标概念化为一个连续值图比较问题，并利用图像分析方法来评定模型输出。一种尝试以局域方法仿制人类视觉系统的度量指标--结构相似指数(SSIM)，被用作为探索性地图的比较统计量。在贝叶斯空间模型框架下实现其量算，并将其作为一个偏差度量应用于模型拟合的后预测校验。仿真研究的结果显示出空间及时空环境下多类空间过程。以斯里兰卡降雨过程图为案例，展示了上述方法对贝叶斯克里格插值的准确性评估。仿真研究与实证结果均证明本文提出的方法可揭示以往传统方法掩盖的空间结构特征，空间敏感性评价为本研究的空间建模和分析提供了一个诊断工具。 [ABSTRACT FROM AUTHOR]

R3531 --> 759.1 --> Blood flow restriction and ischemic preconditioning are occlusion techniques used in clinical and athletic populations as rehabilitation techniques and ergogenic aids. Both require determination of limb occlusion pressure (LOP) to know how much pressure to put in a limb‐worn cuff. Measurement of LOP takes sophisticated equipment and designing a low‐cost way of predicting LOP may allow for these occlusion techniques to be more readily used in field‐based settings. PURPOSE: To determine demographic and other variables that can be used to predict LOP. METHODS: Participants (n=23, 57% female) aged 18 to 53 years reported to the laboratory for a single session. Participant age, height, weight, body mass index (BMI), body fat percentage, thigh circumference of both legs, systolic, diastolic blood pressure of both arms and mean arterial pressure (MAP), resting heart rate, and single‐leg wall sit times for both legs were assessed. Additionally, participants lay in a supine position and were fitted with an automated system (Delfi) on the proximal thigh, one leg at a time, for determining LOP. LOP was confirmed for each leg using a Doppler ultrasound (GE logique) on the popliteal artery. Then, correlation and stepwise regression analyses were used to determine which variables were significant predictors of LOP. RESULTS: Right arm MAP (r=0.648) and BMI (r=0.539) had the highest correlations with LOP. Stepwise regression yielded two potential predictive equations to predict LOP. Equation 1: LOP = 2.117*MAP ‐ 6.678 (r2=0.42; standard error of estimate (SEE)=17.6 mmHg); Equation 2: LOP = 1.892*MAP + 2.441*BMI ‐ 52.059 (r2=0.62; SEE=14.6 mmHg). CONCLUSION: Arm blood pressure was most closely associated with leg LOP, and MAP along with BMI might serve as useful measures for predicting LOP in field settings. Cross‐validation is needed to confirm these preliminary findings, and further analysis should explore other variables that may allow for more accurate prediction of LOP in field settings. [ABSTRACT FROM AUTHOR]

R5034 --> 888.13 --> Background: Inspiratory muscle strength training (IMST) has been shown to bring about improvements in respiratory muscle strength and reductions in blood pressure after 6 weeks of daily high intensity training. However, there has been little investigation into the effects of IMST on limb blood flow, and it is unclear how hemodynamics are altered within a single bout of training. Purpose: To investigate the acute effects of one session of either low or high intensity IMST on blood flow in the upper and lower limbs. Methods: Participants (n=7, 57% female) aged 20 to 47 years completed two randomized laboratory visits wherein resting blood flow was measured via duplex Doppler ultrasound at the left brachial and popliteal arteries. Following baseline measures, participants' maximal inspiratory pressure (PImax) was measured using a PowerBreathe K3 device. Participants performed one session (30 breaths) of IMST at either 15% or 75% of their PImax, and blood flow was measured again at each artery for five breaths during the final ten breaths of the training. At their second visit, subjects performed whichever training level had yet to be completed and blood flow was assessed as described above. Results: Mean blood flow at the brachial artery appeared reduced during both 15% (p=0.070) and 75% training (p=0.078), which may be attributed to a significant increase in retrograde blood flow in both cases (p=0.014 and p=0.037, respectively). This increase in retrograde blood flow tended to be greater during the 75% training (p=0.066). Popliteal artery blood flow showed similar trends to brachial artery blood flow. Conclusions: While IMST appears to reduce brachial artery mean blood flow during a single training session, this may be due to alterations in retrograde blood flow, which tended to increase in an intensity‐dependent manner. Further investigation into the chronic hemodynamic effects of IMST is warranted. [ABSTRACT FROM AUTHOR]

Unerlässlich für die Transkription: Ein biologischer Ansatz unter Anwendung von chemischer Synthese und geöffneten Nucleinsäuren unterstreicht die unerwartet große Bedeutung eines intakten Zuckerrückgrats für die Transkription durch RNA ‐ Polymerase II (Pol II), was sowohl Effizienz als auch Genauigkeit betrifft. [ABSTRACT FROM AUTHOR]

It is well documented that neurofibrillary tangles composed of aggregated tau protein propagate in a predictable pattern in Alzheimer's disease ( AD). The mechanisms underlying the propagation of tau pathology are still poorly understood. Recent studies have provided solid data demonstrating that in several neurodegenerative diseases including AD, the spreading of misfolded protein aggregates in the brain would result from prion-like cell-to-cell transmission. Consistent with this new concept, recent studies have reported that human tau can be released in the extracellular space by an active process of secretion, and can be endocytosed both in vitro and in vivo. Most importantly, it was reported that the spreading of tau pathology was observed along synaptically connected circuits in a transgenic mouse model where human tau overexpression was restricted in the entorhinal cortex. This indicates that secretion of tau by presynaptic neurons and its uptake by postsynaptic neurons could be the sequential events leading to the propagation of tau pathology in the brain. [ABSTRACT FROM AUTHOR]

Hybrids of koi (an ornamental variant of the common carpCyprinus carpio) and goldfishCarassius auratus auratuswere produced by artificial spawning. All 3-year-old F1hybrid males examined were sterile, whereas some F1hybrid females were fertile and produced eggs after hormonal injection. Backcross progeny were obtained by using intact koi sperm to inseminate eggs from F1hybrid females; gynogenetic progeny were obtained by inseminating eggs from F1hybrid females with koi sperm that was genetically inactivated by ultraviolet irradiation. Flow cytometric analysis of DNA content indicated that the backcross progeny were triploid, while the gynogenetic progeny, pure koi, pure goldfish, and F1hybrids were all diploid. The triploidy of backcross progeny obtained without application of any treatment to the eggs demonstrates that the koi × goldfish hybrid females produce diploid eggs. Received November 11, 2011; accepted February 18, 2012 [ABSTRACT FROM PUBLISHER]

The effect of ploidy on scale-cover pattern in linear ornamental (koi) common carp Cyprinus carpio was investigated. To obtain diploid and triploid linear fish, eggs taken from a leather C. carpio female (genotype ssNn) and sperm taken from a scaled C. carpio male (genotype SSnn) were used for the production of control (no shock) and heat-shocked progeny. In heat-shocked progeny, the 2 min heat shock (40° C) was applied 6 min after insemination. Diploid linear fish (genotype SsNn) demonstrated a scale-cover pattern typical for this category with one even row of scales along lateral line and few scales located near operculum and at bases of fins. The majority (97%) of triploid linear fish (genotype SssNnn) exhibited non-typical scale patterns which were characterized by the appearance of additional scales on the body. The extent of additional scales in triploid linear fish was variable; some fish had large scales, which covered almost the entire body. Apparently, the observed difference in scale-cover pattern between triploid and diploid linear fish was caused by different phenotypic expression of gene N/n. Due to incomplete dominance of allele N, triploids Nnn demonstrate less profound reduction of scale cover compared with diploids Nn. [ABSTRACT FROM AUTHOR]

Intraorganizational employee navigation (IEN) is conceptualized as a means of better understanding how the organizational actor proactively works across their firm's internal environment in the execution of their jobs. Navigation is argued to be a precursor to the employee's overall performance through a class of mediating variables labeled 'socially derived outcomes,' which are variables inside the organization that are bestowed upon the employee as a result of them first engaging in proactive behavior (e.g., IEN). Two studies are reported. Study I sees IEN psychometrically validated versus a range of existing proactive behaviors and individual traits (discriminant, nomological, and criterion-related validity) with a heterogeneous sample of 704 employees. Study II then tests a model relating IEN to performance through six mediating 'socially derived outcomes' by leveraging data from 2 Fortune 500 firms. The results of Study II show that IEN significantly impacts multiple measures of the employee's overall performance through mediating effects brought about by key socially derived outcomes, such as the employee's 'manager alignment.' The contributions, broader implications, and limitations of the research are then put into context. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 114, 1353–1367. In tauopathies including Alzheimer’s disease, the axonal microtubule-associated protein tau becomes hyperphosphorylated at pathological epitopes and accumulates in the somato-dendritic compartment. However, it remains unclear whether tau becomes phosphorylated at these epitopes in the somato-dendritic compartment and/or in the axon. In primary hippocampal neurons where human tau was over-expressed both in the somato-dendritic compartment and the axon, the pathological epitopes recognized by the antibodies AT8 (S199/S202/T205), AT100 (T212/S214/T217), and AT180 (T231/S235) were found in the somato-dendritic compartment but not in the axon where tau was either not phosphorylated (T205 and T217) or not simultaneously phosphorylated (T231 and S235) at sites included in the above epitopes. When transfected neurons were treated with the phosphatase inhibitor, okadaic acid, AT8, AT100 and AT180 epitopes were observed in the axon, indicating that tau was dephosphorylated at selective sites of pathological epitopes in this compartment. Expression of tau mutants where one phosphorylation site included in the above epitopes was mutated in alanine showed that the formation of one of these epitopes was not required for the formation of the two others in primary hippocampal neurons. All together our results indicate that in the somato-dendritic compartment, the kinase and phosphatase activity does not prevent the formation of pathological epitopes whereas in the axon, the amount of tau phosphorylated at the pathological epitopes is regulated by phosphatase activity, most likely that of phosphoserine/phosphothreonine phosphatase 2A, the major tau phosphatase. This indicates that if the pathological epitopes are initially formed in the axon in Alzheimer’s disease brain, the activation of phosphatases could be an efficient way to abolish their generation. [ABSTRACT FROM AUTHOR]

We have developed a unique microfluidic platform capable of capturing circulating endothelial progenitor cells (EPCs) by understanding surface chemistries and adhesion profiles. The surface of a variable-shear-stress microfluidic device was conjugated with 6 different antibodies [anti-CD34, -CD31, -vascular endothelial growth factor receptor-2 (VEGFR-2), -CD146, -CD45, and -von Willebrand factor (vWF)] designed to match the surface antigens on ovine peripheral blood-derived EPCs. Microfluidic analysis showed a shear-stress-dependent decrease in EPC adhesion on attached surface antigens. EPCs exhibited increased adhesion to antibodies against CD34, VEGFR-2, CD31, and CD146 compared to CD45, consistent with their endothelial cell-specific surface profile, when exposed to a minimum shear stress of 1.47 dyn/cm². Bone-marrow-derived mesenchymal stem cells and artery-derived endothelial and smooth muscle cells were used to demonstrate the specificity of the EPC microfluidic device. Coated hematopoietic specific-surface (CD45) and granular vWF antibodies, as well as uncoated bare glass and substrate (1% BSA), were utilized as controls. Microfluidic devices have been developed as an EPC capture platform using immobilized antibodies targeted as EPC surface antigens. This EPC chip may provide a new and effective tool for addressing challenges in cardiovascular disease and tissue engineering. [ABSTRACT FROM AUTHOR]

Plouffe DA, Hanington PC, Walsh JG, Wilson EC, Belosevic M. Comparison of select innate immune mechanisms of fish and mammals.Xenotransplantation 2005.© Blackwell Munksgaard, 2005The study of innate immunity has become increasingly popular since the discovery of homologs of many of the innate immune system components and pathways in lower organisms including invertebrates. As fish occupy a key position in the evolution of the innate and adaptive immune responses, there has been a great deal of interest regarding similarities and differences between their defense mechanisms and those of higher vertebrates. This review focuses on describing select mechanisms of the innate immune responses of fish and the implications for evolution of immunity in higher vertebrates. [ABSTRACT FROM AUTHOR]

To compare event rates for osteoporotic fractures, cardiovascular events, and breast cancer in postmenopausal women with osteoporosis. A prospective, observational study of the placebo group in the double-blind, randomized Multiple Outcomes of Raloxifene Evaluation trial. One hundred eighty clinical research centers in 25 countries. Postmenopausal women (n=2,565, mean age=67) with osteoporosis were given calcium (500 mg/d) and vitamin D (400–600 IU/d) supplements. The occurrence of at least one new fracture, cardiovascular event, or breast cancer diagnosis at 3 years was identified and adjudicated. The occurrence of any fracture was the most common event in these women. In women without prevalent vertebral fractures (n=1,627), the event rates per 1,000 patient-years were 45.4 for any fracture, 15.2 for vertebral fracture, 4.7 for clinical vertebral fracture, 0.9 for hip fracture, 8.3 for any cardiovascular event, and 5.2 for all breast cancer. In women with prevalent vertebral fractures (n=938), the event rates per 1,000 patient-years were 117.4 for any new fracture, 77.1 for new vertebral fracture, 25.7 for clinical vertebral fracture, 5.8 for hip fracture, 15.1 for any cardiovascular event, and 2.6 for all breast cancer. The effect of prevalent fracture status on event rates was not dependent on whether women were older or younger than 65, but women aged 65 and older had a 3.6 times greater occurrence of cardiovascular events than younger women, irrespective of prevalent fracture status. These data on the relative incidence of clinically significant skeletal and extra-skeletal outcomes may be useful in choosing an agent for health maintenance for postmenopausal women with osteoporosis. [ABSTRACT FROM AUTHOR]

This study examined whether in vitro-cultured Trypanosoma danilewskyi were susceptible to lysis in the presence or absence of anti-parasite antibodies and complement. Cultured trypanosomes were resistant to lysis by either immune or non-immune goldfish serum. However, trypanosomes treated with the proteolytic enzyme trypsin, which destroys surface proteins of the parasites, became susceptible to lysis when exposed to either immune or nonimmune goldfish serum. The lysis by goldfish serum was dependent on the presence of heat-labile factors and occurred at 4 and 20 °C. The lysis was also dependent on the presence of Mg2+ ions but not Ca2+ ions. Furthermore, treatment of the parasites with different sialidases did not enhance their susceptibility to lysis by goldfish serum. Trypsinized parasites regained resistance to lysis after at least 6-h cultivation in the absence of trypsin and the restoration of full resistance was observed after 24-h cultivation. The resistance to lysis was abrogated when the protein synthesis inhibitor, puromycin, was added to the cultures. These results suggest that trypsinized trypanosomes were susceptible to lysis by goldfish complement (alternative pathway) and that protective surface proteins of the parasite were required for the resistance of normal trypanosomes to lysis. [ABSTRACT FROM AUTHOR]

There is increased acceptance of fortifying habitual foods with plant sterols and their saturated derivatives, stanols, at levels that are considered safe. These sterols and stanols are recognized as potentially effective dietary components for lowering plasma total and LDL cholesterol. Our previous studies have shown that daily consumption of plant sterols promotes strokes and shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats. These studies question the safety of plant sterol additives. The present study was performed to determine whether a large intake of plant stanols would cause nutritional effects similar to those seen with plant sterols in SHRSP rats. Young SHRSP rats (aged 26–29 d) were fed semipurified diets containing commercial margarines fortified with either plant stanols (1.1 g/100 g diet) or plant sterols (1.4 g/100 g diet). A reference group of SHRSP rats was fed a soybean oil diet (0.02 g plant sterols/100 g diet and no plant stanols). Compared to soybean oil, both plant stanol and plant sterol margarines significantly ( P<0.05) reduced the life span of SHRSP rats. At the initial stages of feeding, there was no difference in the survival rates between the two margarine groups, but after approximately 50 d of feeding, the plant stanol group had a slightly, but significantly ( P<0.05), lower survival rate. Blood and tissue (plasma, red blood cells, liver, and kidney) concentrations of plant sterols in the plant sterol margarine group were three to four times higher than the corresponding tissue concentrations of plant stanols in the plant stanol group. The deformability of red blood cells and the platelet count of SHRSP rats fed, the plant sterol margarine were significantly ( P<0.05) lower than those of the plant stanol margarine and soybean oil groups at the end of the study. These parameters did not differ between the soybean oil and plant stanol margarine groups. These results suggest that, at the levels tested in the present study, plant stanols provoke hemorrhagic stroke in SHRSP rats to a slightly greater extent than plant sterols. The results also suggest that the mechanism by which plant stanols shorten the life span of SHRSP rat might differ from that of plant sterols. [ABSTRACT FROM AUTHOR]

Traditional technology adoption research has assumed a single adopting group. However, there are many settings in which multiple groups must jointly adopt an innovation in order for it to succeed. This is particularly true for new information technology innovations that mediate the relationship between two groups. For example, online exchanges (e.g., Freemarkets, GoFish) must attract both suppliers and buyers in order to be successful. The same is true for providers of hardware/software solutions for electronic data interchange and supply chain management. This article describes the phenomenon of multigroup adoption with a particular focus on applications within the financial services and retailing industries. Empirically, the article reports findings from a study that illustrates the importance of evaluating and managing multigroup technology adoption in the specific context of an in-market trial of a new smart card-based electronic payment system. Two distinct groups critical to the smart card's success are studied: consumers (who must decide to use the new card) and retailers (who must agree to adopt and use new technology needed to process smart card transactions). The study identifies which characteristics of the smart card innovation are most closely linked to intention to adopt for each group, and examines how these key characteristics differ by group. Perceptual data were collected via a mail survey from consumers and merchants living in the city where a one-year market trial of the new card was taking place. Four separate sampling frames were established for both consumers and merchants who were participating in the trial as well as both consumers and merchants who were not participating in the trial. Random samples were then drawn from these frames. More than 350 consumers and over 250 merchants completed and returned the survey. Responses were analyzed separately for each of the four groups sampled. The most important characteristic leading to adoption identified by all four groups was relative advantage -- the smart card had to demonstrate a clear competitive advantage over what they currently used. Compatibility (i.e., the degree to which the smart card fit with their current preferences) was also noted as important to all but the nonparticipating merchant group. Beyond this, the key drivers of adoption differed considerably by group. Participating consumers and participating merchants appeared to possess different perspectives when assessing their decision to adopt the smart card technology. Consumers seemed to value the notion that the adoption decision is under their control, whereas merchants seemed to place more value on the antecedents that had the potential to add to their bottom line. This suggests that it is necessary to institute different marketing tactics to attract the early adopting groups. In addition, significant differences in the importance of antecedents between participating and nonparticipating consumers and participating and nonparticipating merchants suggest that, over time, it may also be necessary to develop and use different marketing tactics for later adopters. [ABSTRACT FROM AUTHOR]

In recent studies, the life span of stroke-prone spontaneously hypertensive (SHRSP) rats was altered by a variety of dietary fats. It was relatively shorter in rats fed canola oil as the sole source of fat. The present study was performed to find out whether the fatty acid profile and the high content of sulfur compounds in canola oil could modulate the life span of SHRSP rats. SHRSP rats (47 d old, n=23/group) were matched by body weight and systolic blood pressure and fed semipurified diets containing 10% canola oil, high-palmitic canola oil, low-sulfur canola oil, soybean oil, high-oleic safflower oil, a fat blend that mimicked the fatty acid composition of canola oil, or a fat blend high in saturated fatty acids. A 1% sodium chloride solution was used as drinking water to induce hypertension. After consuming the diets for 37 d, five rats from each dietary group were killed for collection of blood and tissue samples for biochemical analysis. The 18 remaining animals from each group were used for determining their life span. The mean survival time of SHRSP rats fed canola oil (87.4±4.0 d) was not significantly different ( P>0.05) from those fed low-sulfur canola oil (89.7±8.5 d), suggesting that content of sulfur in canola oil has no effect on the life span of SHRSP rats. The SHRSP rats fed the noncanola oil-based diets lived longer (mean survival time difference was 6–13 d, P<0.05) than those fed canola and low-sulfur canola oils. No marked differences in the survival times were observed among the noncanola oil-based groups. The fatty acid composition of the dietary oils and of red blood cells and liver of SHRSP rats killed after 37 d of treatment showed no relationship with the survival times. These results suggest that the fatty acid profile of vegetable oils plays no important role on the life span of SHRSP rat. However, phytosterols in the dietary oils and in liver and brain were inversely correlated with the mean survival times, indicating that the differential effects of vegetable oils might be ascribed, at least partly, to their different phytosterol contents. [ABSTRACT FROM AUTHOR]

Young and elderly women were compared on electrodermal measures of the orienting response (OR) to picture stimuli presented during the study phase of a free recall task. Responses were also recorded during a subsequent simple habituation paradigm which was designed to investigate stimulus priming effects. Young subjects recalled more pictures than the elderly and both groups remembered more pictures with common word names than pictures with uncommon verbal labels. Young and older subjects displayed larger skin conductance responses to recalled pictures, especially to recalled uncommon pictures. Older women, however, displayed consistently smaller SCRs than the young. Stimulus priming was observed on the first trial of habituation training where notrecalled pictures evoked smaller SCRs than pictures not shown in the study phase. There were no age differences in habituation across trials. In general, the results indicated that the electrodermal OR is functionally related to recall performance and that the age decrement in recall may be attributed to reduced cognitive effort in the elderly. [ABSTRACT FROM AUTHOR]

The 49-kDa, nuclear inclusion a-like, viral protein genome-linked proteinase (VPg-Pro) of turnip mosaic potyvirus (TuMV) was expressed in Escherichia coli. The protein was produced in a soluble form at high levels and was active, as demonstrated by intermolecular cleavage of the polymerase capsid protein (PoI-CP) substrate. The VPg-Pro was purified by metal-chelation and ion-exchange chromatographies. Two forms of VPg-Pro, which differed in molecular masses, were obtained during isolation; their identities were confirmed by immunoblot analysis and N-terminal amino acid sequencing. Data indicated that cleavage took place at a site near the C-terminus of VPg-Pro and was the result of the proteolytic activity of the viral protein. The purified proteinase retained enzymic activity on its natural substrate (Pol-CP) and was also capable of hydrolysing the synthetic peptide acyl-Ala-Ala-Val-Tyr, HisGln-Ala-Ala-NH2, derived from the consensus cleavage site for the TuMV polyprotein. Analysis by mass spectrometry of the two fragments resulting from this reaction indicated that cleavage took place between the Gln and Ala residues, as expected. A fluorogenic derivative of this peptide was hydrolysed by VPgPro affording a convenient quantitative assay for intermolecular proteolytic activity, and was used to determine the pH-activity profile. [ABSTRACT FROM AUTHOR]

Ein acyclisches synthetisches RNA ‐ Analogon half, die wichtige Rolle des Nucleotid ‐ Zuckerrings für die Genauigkeit der Transkription aufzudecken. In der Zuschrift auf S. 12567 ff. zeigen D. Wang et al., dass der Beitrag des intakten Nucleotid ‐ Zuckerrückgrats zur enzymatischen Effizienz und Genauigkeit der Transkription von RNA ‐ Polymerase II signifikant größer ist als der irgendeiner anderen funktionellen Gruppe des Nucleotids, einschließlich der Nucleobase und der Ribose ‐ 2′ ‐ OH ‐ Gruppe. [ABSTRACT FROM AUTHOR]

An acyclic synthetic RNA analogue was used to reveal the important role of the nucleotide sugar ring in transcriptional fidelity. In their Communication on page 12341 ff., D. Wang et al. demonstrate that the contribution of the intact nucleotide sugar backbone to the enzymatic efficiency and transcriptional fidelity of RNA polymerase II is significantly stronger than that of the other functional groups of the nucleotide, including the nucleobase and ribose 2′‐OH group. [ABSTRACT FROM AUTHOR]