bluuebunny/crossref_metadata_2025 huggingface dataset:
Philosophy in Eastern Han Dynasty China (25–220 CE)
Authors: McLeod Alexus
Published: June 2015

The philosophy of the Han Dynasty, especially that of the Eastern Han (25–220 CE), is an unjustly neglected area of scholarship on early Chinese thought. In this article, I introduce the thought of a number of important Eastern Han philosophers, with particular attention to Wang Chong, Wang Fu, Xu Gan, and Wang Su. I also explain the major features of Eastern Han thought as distinct from that of the Warring States and Western Han periods, and consider their origins in reaction to Western Han ideas and their further development in the Wei‐Jin period.
Confucianism and American Pragmatism
Authors: Foust Mathew A.
Published: June 2015

One area of the East–West comparative philosophy that has received a good deal of attention in recent years is the relationship between Confucianism and American Pragmatism. Scholars engaging these traditions have argued that they are mutually elucidating and mutually reinforcing. Often, upon locating resonance(s) between a Confucian philosopher and an American Pragmatist philosopher, scholars combine the conceptual resources of the two, developing a Confucian–Pragmatist hybrid concept or theory. Some critics have been skeptical of the alleged compatibility between Confucian and American Pragmatism, holding that proper understanding of Confucian and American Pragmatist traditions reveals an unbridgeable incommensurability between the two. This article describes the state of the comparative scholarship on Confucianism and American Pragmatism, identifying thematic trends and areas of debate. In addition, some lines of scholarship that might augment this area of comparative philosophy are suggested.
Screening of BCOR‐CCNB3 sarcoma using immunohistochemistry for CCNB3: A clinicopathological report of three pediatric cases
Authors: Shibayama Takahiro , Okamoto Takeshi , Nakashima Yasuaki , Kato Takaaki , Sakurai Takaki , Minamiguchi Sachiko , Kataoka Tatsuki R. , Shibuya Shinsuke , Yoshizawa Akihiko , Toguchida Junya , Haga Hironori
Published: June 2015

BCOR‐CCNB3 sarcoma is a recently recognized tumor morphologically and clinically simulating Ewing sarcoma. We herein retrospectively collected clinicopathologic data on BCOR‐CCNB3 sarcoma in the Kyoto University Hospital over the last 10 years. Three (20%) bone sarcomas were revealed to be diffusely positive for CCNB3 immunohistochemistry among 15 pediatric cases of undifferentiated sarcoma morphologically similar to Ewing sarcoma, while the other cases showed completely negative staining. The three patients with immunohistochemically CCNB3‐positive tumors were all male, aged between 11 and 17, and confirmed to have the BCOR‐CCNB3 fusion transcript by RT‐PCR. Radiologically, all cases had well‐demarcated solid masses with bone destruction. Although the tumors were basically small round cell tumors, less monomorphic histological patterns such as short spindle cells, a myxoid matrix, and hemangiopericytoma‐like pattern were also observed in both biopsy and resected specimens. Two patients achieved a complete response after chemotherapy for Ewing sarcoma and osteosarcoma, respectively. These results demonstrated that the application of CCNB3 immunostaining was useful for differentiating BCOR‐CCNB3 from a group of ‘Ewing‐like sarcomas’ and may contribute to the evaluation of treatment strategies for bone sarcomas.
Development of a tomato plant resistant to Clavibacter michiganensis using the endolysin gene of bacteriophage CMP1 as a transgene
Authors: Wittmann J. , Brancato C. , Berendzen K. W. , Dreiseikelmann B.
Published: June 2015

The bacteriophage CMP1 endolysin gene (lys), encoding, a peptidase that was shown to effectively reduce Clavibacter michiganensis by specifically hydrolysing its murein, was transferred into tomato plants by Agrobacterium‐mediated transformation. The presence of the gene was verified by PCR and the gene product was confirmed in immunoblots and stably expressed over three generations. Transgenic tomato plants did not show disease symptoms after infection with C. michiganensis subsp. michiganensis, despite the fact that small amounts of bacteria could still be identified in xylem sap and leaf extracts, although in significantly reduced amounts.
What does cognitive control feel like? Effective and ineffective cognitive control is associated with divergent phenomenology
Authors: Saunders Blair , Milyavskaya Marina , Inzlicht Michael
Published: June 2015

Cognitive control is accompanied by observable negative affect. But how is this negative affect experienced subjectively, and are these feelings related to variation in cognitive control? To address these questions, 42 participants performed a punished inhibitory control task while periodically reporting their subjective experience. We found that within‐subject variation in subjective experience predicted control implementation, but not neural monitoring (i.e., the error‐related negativity, ERN). Specifically, anxiety and frustration predicted increased and decreased response caution, respectively, while hopelessness accompanied reduced inhibitory control, and subjective effort coincided with the increased ability to inhibit prepotent responses. Clarifying the nature of these phenomenological results, the effects of frustration, effort, and hopelessness—but not anxiety—were statistically independent from the punishment manipulation. Conversely, while the ERN was increased by punishment, the lack of association between this component and phenomenology suggests that early monitoring signals might precede the development of control‐related subjective experience. Our results indicate that the types of feelings experienced during cognitively demanding tasks are related to different aspects of controlled performance, critically suggesting that the relationship between emotion and cognitive control extends beyond the dimension of valence.
Managing process development: key issues and dimensions in the front end
Authors: Frishammar Johan , Lichtenthaler Ulrich , Richtnér Anders
Published: June 2015

Beyond the traditional focus on product innovation, prior research and practical examples from a variety of industrial settings underscore the importance of the early phases of process development and process innovation. Despite the potential for large cost savings and efficiency gains, however, little is known about what firms actually do in the early design and concept creation phases of process development, and what guides their subsequent formal process development efforts. By means of a longitudinal multiple case study of four large companies, we bridge this gap by conceptualizing a ‘process definition’. This process definition includes a process concept and is the ‘process equivalent’ of a product definition. Our analysis shows that firms create such process definitions through iterative trial‐and‐error processes, in which experiments, environmental scanning, and administrative planning constitute key methods for uncertainty reduction. Mainstream theory on product definitions fails to account for the key dimensions of a process definition. On the contrary, dimensions such as the understanding of production needs, assessment of product consequences, a thorough implementation plan and early anticipation of intended outcomes, constitute key dimensions of a successful process definition. These findings are particularly relevant to process development managers, plant managers, and others interested in process development and management of production processes.
Exploration and exploitation in product and process innovation in the chemical industry
Authors: Bauer Manuel , Leker Jens
Published: June 2015

Achieving a well‐balanced innovation portfolio is an often advocated goal for R&D managers, but guidelines how to achieve this are scarce in the innovation and management literature. In this study, we investigate the effects that balancing R&D budget allocation between exploratory and exploitative innovation activities has on new product performance. Furthermore, we distinguish between product and process exploratory and exploitative innovation activities offering a new and highly relevant contingency perspective on the requirement to balance exploratory and exploitative innovation activities within a portfolio. In doing so, we integrate these two important dimensions of innovative activity in a framework that can help senior managers to decide how to allocate scarce R&D resources within an innovation portfolio to maximize returns. Based on a unique data set of objective, internal financial accounting data from strategic business units in the chemical industry, we found not only that new product performance is enhanced through the simultaneous pursuit of exploratory and exploitative innovation activities (i.e., they are complementary) which holds true for product and process innovation alike. But we are also able to show that in process innovation, exploration requires more funding to achieve maximal performance when compared to product innovation. An imbalance of exploration and exploitation has less severe consequences than in product innovation efforts. Our study design that is based on firm‐internal R&D budget data allows R&D managers to directly compare their budget allocation practice with our findings that are derived from a wide range of business units in one of the main process industries. Furthermore, our results have important implications for the practice of R&D budget allocation, since they highlight how product and process innovation efforts differ with respect to their impact of the exploration–exploitation balance on new product performance relationship.
TheŚrāddha: The Development of Ancestor Worship in Classical Hinduism
Authors: Sayers Matthew R.
Published: June 2015

The association of Hinduism with reincarnation is well‐known, but this connection obscures a long tradition of ancestor worship. The ritual texts of the Vedic and later Hindu traditions describe in detail the procedure for several forms of ancestral rite. This paper outlines the development of the theological discourse on ancestor worship from its earliest expression to the formation of Classical Hinduism early in the Common Era and highlights the underlying theological, social, and practical concerns that shaped that discourse. The development that culminated in the theological construction of an enduring model of ancestor veneration, theśrāddha, revolves around two central tensions, between the solemn and domestic ritual traditions and between the ritual and renunciation traditions. The resolution of the first tension produces theśrāddha. The reactions to the second tension in the ritual literature shape theśrāddha, bringing it to its classical form, and generate the complex soteriology of later Hinduism.
Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice
Authors: Hua Wen , Liu Hui , Xia Li‐Xia , Tian Bao‐Ping , Huang Hua‐Qiong , Chen Zhi‐Yang , Ju Zhen‐Yu , Li Wen , Chen Zhi‐Hua , Shen Hua‐Hao
Published: June 2015

Background and objective

The mammalian target of rapamycin (mTOR) signalling pathway regulates immune responses, and promotes cell growth and differentiation. Inhibition of mTOR with rapamycin modulates allergic asthma, while the underlying molecular mechanisms remain elusive. Here, we demonstrate that rapamycin, effectively inhibits eosinophil differentiation, contributing to its overall protective role in allergic airway inflammation.

Methods

Rapamycin was administered in a mouse model of ovalbumin‐induced allergic airway inflammation, and the eosinophil differentiation was analysed in vivo and in vitro.

Results

Rapamycin significantly attenuated allergic airway inflammation and markedly decreased the amount of eosinophils in local airways, peripheral blood and bone marrow, independently of levels of interleukin‐5 (IL‐5). In vitro colony forming unit assay and liquid culture demonstrated that rapamycin directly inhibited IL‐5‐induced eosinophil differentiation. In addition, rapamycin reduced the production of IL‐6 and IL‐13 by eosinophils. Rapamycin was also capable of reducing the eosinophil levels in IL‐5 transgenic NJ.1638 mice, again regardless of the constitutive high levels of IL‐5. Interestingly, rapamycin inhibition of eosinophil differentiation in turn resulted in an accumulation of eosinophil lineage‐committed progenitors in bone marrow.

Conclusions

Altogether these results clearly demonstrate a direct inhibitory role of rapamycin in eosinophil differentiation and function, and reemphasize the importance of rapamycin and possibly, mTOR, in allergic airway disease.
Increases in peripheral SIRT1: A new biological characteristic of asthma
Authors: Wang Yajun , Li Dongming , Ma Guoda , Li Wen , Wu Jun , Lai Tianwen , Huang Dan , Zhao Xuanna , Lv Quanchao , Chen Min , Wu Bin
Published: June 2015

Background and objective

Silent information regulator 1 (SIRT1) is a class III histone deacetylase that exerts both anti‐inflammatory and anti‐aging effects. However, no data are available regarding SIRT1 expression in patients with asthma. Here, we studied SIRT1 levels in the serum of patients with asthma and analysed the distribution of SIRT1 in both the serum and the lungs in an asthmatic mouse model to determine its clinical significance.

Methods

Serum SIRT1 levels, total immunoglobulin E (IgE) levels and peripheral blood eosinophil percentages as well as pulmonary function were quantified in 97 patients with asthma and 118 healthy volunteers. BALB/c mice were sensitized and challenged using ovalbumin (OVA) to produce the asthmatic model, and SIRT1 levels in both the serum and the lung tissues were subsequently measured.

Results

The serum SIRT1 levels were significantly elevated in the patients with asthma compared with the controls. Serum SIRT1 levels positively correlated with total IgE levels and negatively correlated with pulmonary function. In the OVA‐sensitized and challenged mice, an increased serum SIRT1 level was confirmed, whereas decreased SIRT1 expression was observed in the lung tissues.

Conclusions

These data indicate that lung SIRT1 expression decreased while serum SIRT1 increased in the setting of asthma. Serum SIRT1 levels correlate positively with both IgE levels and negatively with pulmonary function, suggesting that increased peripheral SIRT1 levels represent a new biological characteristic of asthma. Increased serum SIRT1 may be an auxiliary index for the diagnosis of asthma and elevating lung SIRT1 levels may be a new strategy for asthma therapy.
Palaeoceanographic controls on spatial redox distribution over the Yangtze Platform during the Ediacaran–Cambrian transition
Authors: Och Lawrence M. , Cremonese Lorenzo , Shields‐Zhou Graham A. , Poulton Simon W. , Struck Ulrich , Ling Hongfei , Li Da , Chen Xi , Manning Christina , Thirlwall Matthew , Strauss Harald , Zhu Maoyan
Published: June 2015

The Ediacaran–Cambrian interval was an eventful transitional period, when dynamic interactions between the biosphere and its physical environment allowed the Earth System to cross into a new state, characterized by the presence of metazoans, more equable climates and more expansive oxygenation of the oceans. Due to the retreat of widespread sulphidic conditions, redox‐sensitive trace‐metals could accumulate to a greater extent in ‘black shales’ deposited in localized anoxic/euxinic environments, such as highly productive ocean margins. This study investigates the concentrations of the redox‐sensitive trace‐metals molybdenum and vanadium in organic‐rich sedimentary rocks from seven sections of the Yangtze Platform, slope and basin. Iron speciation analyses were carried out in order to distinguish oxic, anoxic‐ferruginous and anoxic‐sulphidic settings, while sulphur and nitrogen isotope ratios were measured to gain insight into sulphate and nitrate availability, respectively, in the context of changing redox conditions. The data herein demonstrate an overall increase in redox‐sensitive trace‐metal contents in black shales across the Ediacaran–Cambrian transition, but with marked temporal and spatial variability. Euxinia is evident in South China before 551 Ma in the Ediacaran, and again in the early Cambrian. However, some time‐equivalent sections are not enriched in redox‐sensitive trace‐metals, and also exhibit contrasting S‐isotope and N‐isotope systematics. A more complex configuration of the Yangtze Platform, for example with vast intra‐shelf basins, together with changing (generally rising) eustatic sea‐level may account for this variability. In this regard, it is proposed that a mid‐depth sulphidic wedge, caused by nutrient upwelling over the south‐east platform margins, migrated over time (but generally landward), leading to spatially variable redox conditions determined by sea‐level, currents and bathymetric constraints. The changing extents of anoxia and euxinia appear to have limited the distribution of emerging Ediacaran and Cambrian ecosystems.
Alexithymia and Early Maladaptive Schemas in chronic pain patients
Authors: Saariaho Anita S. , Saariaho Tom H. , Mattila Aino K. , Karukivi Max , Joukamaa Matti I.
Published: June 2015

Psychological factors have an impact on subjective pain experience. The aim of this study was to explore the occurrence of alexithymia and Early Maladaptive Schemas in a sample of 271 first visit chronic pain patients of six pain clinics. The patients completed the study questionnaire consisting of the Toronto Alexithymia Scale‐20, the Finnish version of the Young Schema Questionnaire short form‐extended, the Beck Depression Inventory‐II, and pain variables. Alexithymic patients scored higher on Early Maladaptive Schemas and had more pain intensity, pain disability and depression than nonalexithymic patients. Both alexithymia and depression correlated significantly with most Early Maladaptive Schemas. The co‐occurrence of alexithymia, Early Maladaptive Schemas and depression seems to worsen the pain experience. Screening of alexithymia, depression and Early Maladaptive Schemas may help to plan psychological treatment interventions for chronic pain patients.
Trait Extraversion and Dopamine Function
Authors: Wacker Jan , Smillie Luke D.
Published: June 2015

An influential theory within personality neuroscience suggests that trait extraversion is underpinned by individual differences in dopamine function. In a review of the relevant literature, we evaluate this theory in light of the evidence from molecular genetics, neuroimaging, and psychopharmacology. Evidence linking individual differences in extraversion with dopamine‐relevant genes, structural volume of dopamine‐rich brain regions (e.g., in striatal and ventral prefrontal areas), dopamine receptor availability, and frontal alpha asymmetry is mixed at best. Evidence concerning both scalp recorded (electroencephalogram) and hemodynamic (functional magnetic resonance imaging) neural responses to rewards appears somewhat more promising. Perhaps the best evidence concerns extraversion‐dependent responses – both neural and behavioural – to dopaminergic drugs. Future research in this area must go beyond the demonstration of theoretically consistent associations and attempt to provide more specific causal evidence for the dopamine hypothesis of extraversion. A further challenge is to expand this hypothesis to incorporate other neurobiological processes that are likely to underlie this trait.
The Evolution and Social Dynamics of Compassion
Authors: Gilbert Paul
Published: June 2015

The inner processes that make compassion possible arose from the evolutionary advantage of caring for others, especially offspring, kin and in‐group allies. This paper explores issues in defining compassion and its link to similar concepts such as altruism. It also explores compassion as a social motive and social mentality that choreographs social interactions and how the successful enactment of compassion is dependent on certain competencies such as sympathy, empathy, perspective taking, and distress tolerance (among others), as well as social contexts. As a motivational system, compassion has to compete with other socially choreographed motives, such as tribalism and individualistic competitiveness – much darker sides of the human psyche that have been harmful in human history. One of the challenges for compassion is to explore not only how it can promote personal well‐being but also how it can counteract the destructive sides of our other motives and social mentalities.
Young adult gender differences in forearm skin‐to‐fat tissue dielectric constant values measured at 300 MHz
Authors: Mayrovitz H. N. , Grammenos A. , Corbitt K. , Bartos S.
Published: June 2015

Background/Purpose

Skin‐to‐fat tissue dielectric constant (TDC) values depend on measurement depth and gender. Our goal was to assess male–female differences in TDC values associated with differing skin depths.

Methods

Bilateral forearm TDC measurements were made on young adult male and females with mean ages from 24.7 to 27.3 years. There were four measurement groups distinguished by the TDC measurement depth and include the following numbers of subjects for each gender; 30, 150, 60, and 50 for probe‐measurement depths of 0.5, 1.5, 2.5, and 5.0 mm. Data were subsequently compared with values calculated with a simple two‐layer model.

Results

For females and males, there was a significant difference in TDC values among depths (P < 0.001) with TDC values decreasing with increasing depth. Gender comparisons showed that TDC values of males were significantly (P < 0.001) greater than values for females at each depth. Male–female percentage differences ranged from 14.8% to 22.0%. Model calculations suggest that gender differences might be explained by skin thickness differences.

Conclusion

Findings indicate that decisions with regard to skin water content among or between groups based on TDC measurements need to account for gender and are best made when corresponding skin thickness measurements are available. However, changes in TDC values assessed in individual patients and comparisons between corresponding skin areas in affected and non‐affected sites are not limited. Thus, assessments of acute treatment effects and assessments of inter‐arm or inter‐leg TDC differences or ratios within genders are a useful and suitable method to characterize edema and lymphedema features.
Age‐related differences in tissue dielectric constant values of female forearm skin measured noninvasively at 300 MHz
Authors: Mayrovitz H. N. , Singh A. , Akolkar S.
Published: June 2015

Background/Purpose

We hypothesized that reported age‐related shifts in skin water from less‐to‐more mobile states would result in increased skin tissue dielectric constant (TDC) values as TDC values depend strongly on water content and state. One aim was to test this hypothesis. Further, as skin‐to‐fat TDC values are used as a tool for edema and lymphedema assessment, a second aim was to establish reference values suitable for young and older women.

Methods

TDC was measured bilaterally on volar forearm skin in young (20–40 years) and older (≥60 years) women. There were four groups with 50, 50, 100, and 50 subjects per age group measured to depths of 0.5, 1.5, 2.5, and 5.0 mm, respectively.

Results

For each age group, TDC values decreased with increasing depth (P < 0.001). TDC values at 0.5 and 1.5 mm were greater for older women (P < 0.001). At 2.5 mm, there was no age‐group difference (P = 0.108). At 5.0 mm the direction of the difference reversed with older TDC values less than the younger (P < 0.001).

Conclusion

Results are consistent with age‐related shifts in water state from less‐to‐more mobile and explain depth‐dependence differences between age groups. Data also give age‐related TDC reference values for assessing local edematous or lymphedematous states.
KIR3DL1*0250103: a novel three‐domain KIR allele isolated in West African samples
Authors: Yindom L. ‐M. , de Silva T. I. , Rowland‐Jones S. L.
Published: June 2015

The full length sequence of KIR3DL1*0250103 differs from that of KIR3DL1*0150101 with nine single‐nucleotide polymorphisms
Expression of TaCYP78A3, a gene encoding cytochrome P450 CYP78A3 protein in wheat (Triticum aestivum L.), affects seed size
Authors: Ma Meng , Wang Qian , Li Zhanjie , Cheng Huihui , Li Zhaojie , Liu Xiangli , Song Weining , Appels Rudi , Zhao Huixian
Published: June 2015

Several studies have described quantitative trait loci (QTL) for seed size in wheat, but the relevant genes and molecular mechanisms remain largely unknown. Here we report the functional characterization of the wheat TaCYP78A3 gene and its effect on seed size. TaCYP78A3 encoded wheat cytochrome P450 CYP78A3, and was specifically expressed in wheat reproductive organs. TaCYP78A3 activity was positively correlated with the final seed size. Its silencing caused a reduction of cell number in the seed coat, resulting in an 11% decrease in wheat seed size, whereas TaCYP78A3 over‐expression induced production of more cells in the seed coat, leading to an 11–48% increase in Arabidopsis seed size. In addition, the cell number in the final seed coat was determined by the TaCYP78A3 expression level, which affected the extent of integument cell proliferation in the developing ovule and seed. Unfortunately, TaCYP78A3 over‐expression in Arabidopsis caused a reduced seed set due to an ovule developmental defect. Moreover, TaCYP78A3 over‐expression affected embryo development by promoting embryo integument cell proliferation during seed development, which also ultimately affected the final seed size in Arabidopsis. In summary, our results indicated that TaCYP78A3 plays critical roles in influencing seed size by affecting the extent of integument cell proliferation. The present study provides direct evidence that TaCYP78A3 affects seed size in wheat, and contributes to an understanding of the cellular basis of the gene influencing seed development.
An unusual xylan in Arabidopsis primary cell walls is synthesised by GUX3, IRX9L, IRX10L and IRX14
Authors: Mortimer Jenny C. , Faria‐Blanc Nuno , Yu Xiaolan , Tryfona Theodora , Sorieul Mathias , Ng Yao Z. , Zhang Zhinong , Stott Katherine , Anders Nadine , Dupree Paul
Published: June 2015

Xylan is a crucial component of many plant primary and secondary cell walls. However, the structure and function of xylan in the dicotyledon primary cell wall is not well understood. Here, we characterized a xylan that is specific to tissues enriched in Arabidopsis primary cell walls. Unlike previously described xylans, this xylan carries a pentose linked 1–2 to the α‐1,2‐d‐glucuronic acid (GlcA) side chains on the β‐1,4‐Xyl backbone. The frequent and precisely regular spacing of GlcA substitutions every six xylosyl residues along the backbone is also unlike that previously observed in secondary cell wall xylan. Molecular genetics, in vitro assays, and expression data suggest that IRX9L, IRX10L and IRX14 are required for xylan backbone synthesis in primary cell wall synthesising tissues. IRX9 and IRX10 are not involved in the primary cell wall xylan synthesis but are functionally exchangeable with IRX9L and IRX10L. GUX3 is the only glucuronyltransferase required for the addition of the GlcA decorations on the xylan. The differences in xylan structure in primary versus secondary cell walls might reflect the different roles in cross‐linking and interaction with other cell wall components.
Interaction of MYC2 and GBF1 results in functional antagonism in blue light‐mediated Arabidopsis seedling development
Authors: Maurya Jay P. , Sethi Vishmita , Gangappa Sreeramaiah N. , Gupta Nisha , Chattopadhyay Sudip
Published: June 2015

Regulations of Arabidopsis seedling growth by two proteins, which belong to different classes of transcription factors, are poorly understood. MYC2 and GBF1 belong to bHLH and bZIP classes of transcription factors, respectively, and function in cryptochrome‐mediated blue light signaling. Here, we have investigated the molecular and functional interrelation of MYC2 and GBF1 in blue light‐mediated photomorphogenesis. Our study reveals that MYC2 and GBF1 colocalize and physically interact in the nucleus. This interaction requires the N‐terminal domain of each protein. The atmyc2 gbf1 double mutant analyses and transgenic studies have revealed that MYC2 and GBF1 act antagonistically and inhibit the activity of each other to regulate hypocotyl growth and several other biological processes. This study further reveals that MYC2 and GBF1 bind to HYH promoter and inhibit each other through non‐DNA binding bHLH–bZIP heterodimers. These results, taken together, provide insights into the mechanistic view on the concerted regulatory role of MYC2 and GBF1 in Arabidopsis seedling development.
Secondary siRNAs from Medicago NB‐LRRs modulated via miRNA–target interactions and their abundances
Authors: Fei Qili , Li Pingchuan , Teng Chong , Meyers Blake C.
Published: June 2015

Small RNAs are a class of non‐coding RNAs that are of great importance in gene expression regulatory networks. Different families of small RNAs are generated via distinct biogenesis pathways. One such family specific to plants is that of phased, secondary siRNAs (phasiRNAs); these require RDR6, DCL4, and (typically) a microRNA (miRNA) trigger for their biogenesis. Protein‐encoding genes are an important source of phasi‐RNAs. The model legume Medicago truncatula generates phasiRNAs from many PHAS loci, and we aimed to investigate their biogenesis and mechanism by which miRNAs trigger these molecules. We modulated miRNA abundances in transgenic tissues showing that the abundance of phasiRNAs correlates with the levels of both miRNA triggers and the target, precursor transcripts. We identified sets of phasiRNAs or PHAS loci that predominantly and substantially increase in response to miRNA overexpression. In the process of validating targets from miRNA overexpression tissues, we found that in the miRNA‐mRNA target pairing, the 3′ terminal nucleotide (the 22nd position), but not the 10th position, is important for phasiRNA production. Mutating the single 3′ terminal nucleotide dramatically diminishes phasiRNA production. Ectopic expression of Medicago NB‐LRR‐targeting miRNAs in Arabidopsis showed that only a few NB‐LRRs are capable of phasiRNA production; our data indicate that this might be due to target inaccessibility determined by sequences flanking target sites. Our results suggest that target accessibility is an important component in miRNA–target interactions that could be utilized in target prediction, and the evolution of mRNA sequences flanking miRNA–target sites may be impacted.
Cryopreservation alters the membrane and cytoskeletal protein profile of platelet microparticles
Authors: Raynel Sarah , Padula Matthew P. , Marks Denese C. , Johnson Lacey
Published: June 2015

BACKGROUND

Cryopreservation of platelets (PLTs) in dimethyl sulfoxide (DMSO) and storage at −80°C extends the PLT shelf life to at least 2 years, allowing greater accessibility in military and rural environments. While cryopreserved PLTs have been extensively characterized, the microparticles formed as a result of cryopreservation are yet to be fully described.

STUDY DESIGN AND METHODS

Apheresis PLTs were cryopreserved at −80°C with 5% DMSO and sampled before freezing and after thawing. Microparticle number, size, surface receptor phenotype, and function were assessed by microscopy, flow cytometry, dynamic light scattering, and thrombin‐generating capacity. Proteomic changes were examined using two‐dimensional gel electrophoresis and Western blotting.

RESULTS

PLT cryopreservation resulted in a 15‐fold increase in the number of microparticles compared to fresh PLTs. The surface receptor phenotype of these microparticles differed to microparticles from fresh PLTs, with more microparticles expressing glycoprotein (GP)IV, GPIIb, and the GPIb‐V‐IX complex. Cryopreservation drastically altered the abundance of many cytoskeletal proteins in the PLT microparticles, including actin, filamin, gelsolin, and tropomyosin. Despite these changes, PLT microparticles were functional and contributed to phosphatidylserine‐ and tissue factor– induced thrombin generation.

CONCLUSION

This study demonstrates that PLT microparticles formed by cryopreservation are phenotypically distinct from those present before freezing. These differences may be associated with the procoagulant properties of cryopreserved PLTs.
Bilateral removal of the mandibular and medial retropharyngeal lymph nodes through a single ventral midline incision for staging of head and neck cancers in dogs: a description of surgical technique
Authors: Green K. , Boston S. E.
Published: June 2015

Currently, there is no standard protocol for removal of regional lymph nodes for the staging of head and neck cancers in dogs. Palpation and fine needle aspiration of mandibular lymph nodes are most commonly performed for staging of head and neck cancers. Although cytology is commonly performed for staging of head and neck, cancers histopathology is required for definitive lymph node staging. When regional lymph node biopsy is performed, mandibular lymph nodes are most commonly sampled due to their accessibility. The medial retropharyngeal lymph nodes may be the most relevant draining lymph node of the head and neck, but they are not routinely sampled due to their anatomic location medial to the salivary glands. The technique described here will allow for a standardized surgical approach for the efficient removal of both mandibular and medial retropharyngeal lymph nodes for staging of head and neck tumours via a single ventral midline approach.
The activity and inhibition of poly(ADP‐ribose) polymerase‐1 in equine peripheral blood mononuclear cells in vitro
Authors: Douglas Hope F. , Southwood Louise L. , Meyer‐Ficca Mirella L. , Hart Samantha K. , Meyer Ralph G.
Published: June 2015

Objectives

To evaluate the poly (ADP‐ribose) polymerase‐1 (PARP1) enzyme and its inhibition in horses and explore its potential as a novel therapeutic target for equine intestinal ischemia‐reperfusion injury by (1) identifying poly (ADP‐ribose) (PAR) as an indication of PARP1 activation in equine cells using available immunoblot analytical techniques, (2) inducing PARP1 activation in an in vitro oxidative DNA damage model, (3) and demonstrating the inhibition of PARP1 in equine cells using commercially available PARP1 inhibitors.

Design

Experimental study.

Animals

Blood samples were collected from systemically healthy ponies (n= 3) and horses (n= 3).

Interventions

(1) Equine peripheral blood mononuclear cells were exposed to 3 different concentrations of hydrogen peroxide (H2O2) and were lysed at specific time points. PARP1 activity was then assessed by using immunoblot analyses to determine PAR levels. (2) Equine peripheral blood mononuclear cells were preincubated with defined concentrations of PARP1 inhibitors prior to H2O2‐mediated PARP1 stimulation. PAR levels reflecting PARP1 activity were determined using immunoblot analyses.

Measurements and Main Results

Commercially available anti‐PAR antibodies were used successfully to identify equine PAR. There was a significant increase in PAR accumulation following treatment with H2O2. All of the tested PARP inhibitors significantly reduced PAR accumulation to or below basal levels following treatment with H2O2.

Conclusions

This proof of principle study demonstrated that PAR, an indicator of PARP1 activity, can be identified in the equine species using immunoblot techniques, that equine PARP1 can be activated by H2O2‐induced DNA damage, and that this activation can be inhibited by PARP1 enzyme inhibitors. The data suggest that the PARP1 pathway plays a role in the equine cellular response to oxidative DNA damage and supports its potential as a novel therapeutic target. Further research documenting an increase in PAR levels in vivo and the efficacy of PARP1 inhibitors in an equine intestinal ischemia‐reperfusion model is needed.
Protozoal infections of the cornea and conjunctiva in dogs associated with chronic ocular surface disease and topical immunosuppression
Authors: Beckwith‐Cohen Billie , Gasper David J. , Bentley Ellison , Gittelman Howard , Ellis Angela E. , Snowden Karen F. , Shock Barbara C. , Yabsley Michael J. , Dubielzig Richard R.
Published: June 2015

Objective

To describe five cases of protozoal keratitis or conjunctivitis in dogs with chronic preexisting ocular surface disease treated with long‐term immunosuppression.

Animals studied

Five dogs that developed corneal or conjunctival mass lesions.

Procedures

The database of the Comparative Ocular Pathology Laboratory of Wisconsin was searched for canine cases diagnosed with corneal or conjunctival protozoal infection. Five cases were identified, and tissues were examined using routine and special histochemical stains: immunohistochemical labels forNeospora caninum,Toxoplasma gondii, andLeishmaniaspp., and tissue sample PCR forLeishmaniaspp., Trypanosoma cruzi,tissue coccidia (i.e.,T. gondii/Sarcocystis/Neospora),piroplasms, trichomonads, andAcanthamoeba. Electron microscopy was performed for two cases, and serology forN. caninumandT. gondiiwas available for three cases.

Results

Preexisting ocular diseases included keratoconjunctivitis sicca and pigmentary keratitis (n = 4) and pyogranulomatous meibomian adenitis (n = 1). All dogs were treated with tacrolimus or cyclosporine for at least 1.2 years. Dogs were presented with fleshy corneal or conjunctival masses that were clinically suspected to be neoplastic (n = 4) or immune mediated (n = 1). Histologic examination revealed granulomatous inflammation with intralesional protozoal organisms. Amoeba (n = 2),T. gondii(n = 2), orLeishmania mexicana(n = 1) were identified using molecular techniques. Serological tests were negative.

Conclusions

Protozoal keratitis and conjunctivitis without systemic involvement appears rare and may be associated with chronic preexisting ocular surface disease treated with long‐term immunosuppression. Based upon clinical appearance, lesions could be confused with neoplasia. This is the first report of amoebic keratoconjunctivitis in dogs and ofL. mexicanain dogs in the United States.
Postexercise orthostatic intolerance: influence of exercise intensity
Authors: Mündel Toby , Perry Blake G. , Ainslie Philip N. , Thomas Kate N. , Sikken Elisabeth L. G. , Cotter James D. , Lucas Samuel J. E.
Published: June 2015

New Findings

What is the central question of this study?

Following exercise, hypotension is often reported and syncope is more likely. It is unresolved whether the postexercise hypotension associated with different exercise intensities contributes to the rate at which syncope develops.

What is the main finding and its importance?

The physiological events that induce presyncope are the same both before and after exercise; however, more intense exercise accelerated the development of hypocapnia, hypotension and, ultimately, syncope. These data indicate that higher intensity exercise induces a postexercise hypotension that reduces cardiovascular reserve, an earlier development of hypocapnia and, ultimately, cerebral hypoperfusion.

After exercise, a reduction in mean arterial pressure is often experienced and is referred to as postexercise hypotension. Whilst syncope is more likely following exercise, it is unknown whether orthostatic tolerance is impacted by any exercise intensity‐mediated effect on postexercise hypotension. We examined the effect of exercise intensity on time to presyncope, induced via combined head‐up tilt and lower body negative pressure following 1 h of cycling at 30 and 70% of heart rate range. Healthy participants (n = 8; mean ± SD, 28 ± 5 years old) completed orthostatic testing to presyncope before and after exercise. Beat‐to‐beat middle cerebral artery blood flow velocity (MCAv), mean arterial pressure and cerebral oxygenation (measured by near‐infrared spectroscopy) were recorded continuously throughout orthostatic testing. During exercise, heart rates were 95 ± 6 and 147 ± 5 beats min−1 for 30 and 70% heart rate range, respectively, with average power outputs of 103 ± 22 and 221 ± 45 W, respectively. Time to presyncope occurred 32% sooner after the 70% heart rate range trial (952 ± 484 versus 1418 ± 435 s; P = 0.004). Both before and after exercise, presyncope occurred at the same reduction in MCAv (grouped mean, −30 ± 11 cm s−1), mean arterial pressure (−18 ± 13 mmHg), total oxygenation index (−6 ± 2%) and partial pressure of end‐tidal CO2 (−16 ± 8 mmHg; all P > 0.1). At presyncope following exercise, the MCAv response was related more to the change in partial pressure of end‐tidal CO2 from the baseline preceding orthostatic testing (r2 = 0.50, P = 0.01) than to the hypotension (r2 = 0.12, P = 0.17). Presyncope both before and after exercise occurred as a result of the same physiological perturbations, albeit greatly accelerated following more intense exercise.
Glucocorticoids as regulatory signals during intrauterine development
Authors: Fowden Abigail L. , Forhead Alison J.
Published: June 2015

New Findings

What is the topic of this review?

This review discusses the role of the glucocorticoids as regulatory signals during intrauterine development. It examines the functional significance of these hormones as maturational, environmental and programming signals in determining offspring phenotype.

What advances does it highlight?

It focuses on the extensive nature of the regulatory actions of these hormones. It highlights the emerging data that these actions are mediated, in part, by the placenta, other endocrine systems and epigenetic modifications of the genome.

Glucocorticoids are important regulatory signals during intrauterine development. They act as maturational, environmental and programming signals that modify the developing phenotype to optimize offspring viability and fitness. They affect development of a wide range of fetal tissues by inducing changes in cellular expression of structural, transport and signalling proteins, which have widespread functional consequences at the whole organ and systems levels. Glucocorticoids, therefore, activate many of the physiological systems that have little function in utero but are vital at birth to replace the respiratory, nutritive and excretory functions previously carried out by the placenta. However, by switching tissues from accretion to differentiation, early glucocorticoid overexposure in response to adverse conditions can programme fetal development with longer term physiological consequences for the adult offspring, which can extend to the next generation. The developmental effects of the glucocorticoids can be direct on fetal tissues with glucocorticoid receptors or mediated by changes in placental function or other endocrine systems. At the molecular level, glucocorticoids can act directly on gene transcription via their receptors or indirectly by epigenetic modifications of the genome. In this review, we examine the role and functional significance of glucocorticoids as regulatory signals during intrauterine development and discuss the mechanisms by which they act in utero to alter the developing epigenome and ensuing phenotype.
An Equilibrium Constitutive Model of Anisotropic Cartilage Damage to Elucidate Mechanisms of Damage Initiation and Progression
Authors: Stender Michael E. , Regueiro Richard A. , Klisch Stephen M. , Ferguson Virginia L.
Published: June 2015

Traumatic injuries and gradual wear-and-tear of articular cartilage (AC) that can lead to osteoarthritis (OA) have been hypothesized to result from tissue damage to AC. In this study, a previous equilibrium constitutive model of AC was extended to a constitutive damage articular cartilage (CDAC) model. In particular, anisotropic collagen (COL) fibril damage and isotropic glycosaminoglycan (GAG) damage were considered in a 3D formulation. In the CDAC model, time-dependent effects, such as viscoelasticity and poroelasticity, were neglected, and thus all results represent the equilibrium response after all time-dependent effects have dissipated. The resulting CDAC model was implemented in two different finite-element models. The first simulated uniaxial tensile loading to failure, while the second simulated spherical indentation with a rigid indenter displaced into a bilayer AC sample. Uniaxial tension to failure simulations were performed for three COL fibril Lagrangian failure strain (i.e., the maximum elastic COL fibril strain) values of 15%, 30%, and 45%, while spherical indentation simulations were performed with a COL fibril Lagrangian failure strain of 15%. GAG damage parameters were held constant for all simulations. Our results indicated that the equilibrium postyield tensile response of AC and the macroscopic tissue failure strain are highly dependent on COL fibril Lagrangian failure strain. The uniaxial tensile response consisted of an initial nonlinear ramp region due to the recruitment of intact fibrils followed by a rapid decrease in tissue stress at initial COL fibril failure, as a result of COL fibril damage which continued until ultimate tissue failure. In the spherical indentation simulation, damage to both the COL fibril and GAG constituents was located only in the superficial zone (SZ) and near the articular surface with tissue thickening following unloading. Spherical indentation simulation results are in agreement with published experimental observations. Our results indicate that the proposed CDAC model is capable of simulating both initial small magnitude damage as well as complete failure of AC tissue. The results of this study may help to elucidate the mechanisms of AC tissue damage, which initiate and propagate OA.
Alternating Frequency–Time Finite Element Method: High-Fidelity Modeling of Nonlinear Wave Propagation in One-Dimensional Waveguides
Authors: Liu Yu , Dick Andrew J.
Published: June 2015

In this paper, a spectral finite element method (SFEM) based on the alternating frequency–time (AFT) framework is extended to study impact wave propagation in a rod structure with a general material nonlinearity. The novelty of combining AFT and SFEM successfully solves the computational issue of existing nonlinear versions of SFEM and creates a high-fidelity method to study impact response behavior. The validity and efficiency of the method are studied through comparison with the prediction of a qualitative analytical study and a time-domain finite element method (FEM). A new analytical approach is also proposed to derive an analytical formula for the wavenumber. By using the wavenumber equation and with the help of time–frequency analysis techniques, the physical meaning of the nonlinear behavior is studied. Through this combined effort with both analytical and numerical components, distortion of the wave shape and dispersive behavior have been identified in the nonlinear response. The advantages of AFT-FEM are (1) high-fidelity results can be obtained with fewer elements for high-frequency impact shock response conditions; (2) dispersion or dissipation is not erroneously introduced into the response as can occur with time-domain FEM; (3) the high-fidelity properties of SFEM enable it to provide a better interpretation of nonlinear behavior in the response; and (4) the AFT framework makes it more computationally efficient when compared to existing nonlinear versions of SFEM which often involve convolution operations.