bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid levels after exposure to predator odor and chronic psychosocial stress with dexamethasone application in rats
Authors: Starcevic Ana , Petricevic Sasa , Radojicic Zoran , Djulejic Vuk , Ilankovic Andrej , Starcevic Branislav , Filipovic Branislav 
Published: May 2016

AbstractThis study was conducted to explore the effects of specific psychosocial paradigm on predator animal posttraumatic stress model and to test the hypothesis that psychosocially stressed rats would exibit abnormal levels of cortisol and a larger suppression of cortisol levels after the application of dexamethasone. Animals were divided in two groups: experimental and control groups. The experimental group was exposed to two types of stressors: acute immobilization stress, and combined predator stress and daily social stress with application of dexamethasone. Blood sampling was performed at three different times. We found statistically significant results after analyzing the differences between cortisol levels in different times of blood sampling in the group of animals exposed to stress with dexamethasone application. Statistical significance was found when we compared the experimental group with the control group in terms of elevated cortisol levels during blood sampling after stress paradigm exposition. Many significant disruptions in the functioning of the hypothalamic–pituitary–adrenal axis were observed, such as decrease in basal cortisol levels and enhanced dexamethasone‐induced inhibition of cortisol levels. These findings are important because their impact can translate to human individuals with posttraumatic stress disorder, which is the most important role of every animal model in research.
Stakeholder Judgments of Value
Authors: Lankoski Leena , Smith N. Craig , Van Wassenhove Luk 
Published: May 2016

ABSTRACT:Although central to stakeholder theory, stakeholder value is surprisingly neglected in the literature. We draw upon prospect theory to show how stakeholder judgments of value depend crucially on the reference state, how there are several alternative reference states that may be operative when stakeholders judge value, how the choice of reference state for stakeholders’ value judgments can occur intuitively or deliberately, and how the level of the operant reference state may change with time and may also be incorrectly perceived by stakeholders or managers. Our theorizing results in a fundamentally different way of perceiving the value of corporate actions to stakeholders and shifts understanding of the avenues available for companies and others to influence stakeholder judgments of value. This novel perspective has implications both for theory and management practice, and not least for normative business ethics, if business is about stakeholder value creation.
Supportive medical care in life-threatening illness: A pilot study
Authors: Young William C. , Nadarajah Sheeba R. , Berger Ann M. 
Published: May 2016

AbstractObjective:The goal of this pilot study was to identify the processes by which healing occurs in patients who experience a life-threatening illness.Method:Healing was examined by using two qualitative studies that employed a semistructured interview process (interviews lasted between 30 and 115 minutes). There were 10 cardiac event survivors and 9 cancer survivors. These participants came from a community hospital setting (cardiac), nonmedical holistic services organization (cancer), and a research hospital (cancer). Before participants could take part in the study, they were administered preliminary screening measurements, the first of which was an instrument similar to the Distress Thermometer. Participants then self-reported their positive life-transforming changes. If one to three changes were reported six months after onset of the illness, participants were deemed to have passed the screening. Finally, participants were tested for speaking volume and clarity.Results:An overall theme that was prevalent throughout the interviews was medical support. Participants found that their positive, life-transforming changes were typically connected with supportive caregivers who helped to create a culture of care. They also indicated that an absence of this medical supportive care hindered development of such life-transforming changes.Significance of Results:Our results indicate that a medical care team will be more effective if a positive culture of care is created. This can be implemented if the team provides comfort, which involves being more engaged in the treatment of patients as well as being more attentive to their psychosocial needs.
Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells
Authors: Liu Xiao-Ping , Koehler Karl R. , Mikosz Andrew M. , Hashino Eri , Holt Jeffrey R. 
Published: May 2016

AbstractInner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs. We find that organoid hair cells acquire mechanosensitivity equivalent to functionally mature hair cells in postnatal mice. The organoid hair cells also progress through a similar dynamic developmental pattern of ion channel expression, reminiscent of two subtypes of native vestibular hair cells. We conclude that our 3D culture system can generate large numbers of fully functional sensory cells which could be used to investigate mechanisms of inner ear development and disease as well as regenerative mechanisms for inner ear repair.
Protons at the speed of sound: Predicting specific biological signaling from physics
Authors: Fichtl Bernhard , Shrivastava Shamit , Schneider Matthias F. 
Published: May 2016

AbstractLocal changes in pH are known to significantly alter the state and activity of proteins and enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. membranes) would therefore constitute an important pillar towards a physical mechanism of biological signaling. Here we investigate the pH-induced physical perturbation of a lipid interface and the physicochemical nature of the subsequent acoustic propagation. Pulses are stimulated by local acidification and propagate – in analogy to sound – at velocities controlled by the interface’s compressibility. With transient local pH changes of 0.6 directly observed at the interface and velocities up to 1.4 m/s this represents hitherto the fastest protonic communication observed. Furthermore simultaneously propagating mechanical and electrical changes in the lipid interface are detected, exposing the thermodynamic nature of these pulses. Finally, these pulses are excitable only beyond a threshold for protonation, determined by the pKa of the lipid head groups. This protonation-transition plus the existence of an enzymatic pH-optimum offer a physical basis for intra- and intercellular signaling via sound waves at interfaces, where not molecular structure and mechano-enyzmatic couplings, but interface thermodynamics and thermodynamic transitions are the origin of the observations.
Motile properties of the bi-directional kinesin-5 Cin8 are affected by phosphorylation in its motor domain
Authors: Shapira Ofer , Gheber Larisa 
Published: May 2016

AbstractThe Saccharomyces cerevisiae kinesin-5 Cin8 performs essential mitotic functions in spindle assembly and anaphase B spindle elongation. Recent work has shown that Cin8 is a bi-directional motor which moves towards the minus-end of microtubules (MTs) under high ionic strength (IS) conditions and changes directionality in low IS conditions and when bound between anti-parallel microtubules. Previous work from our laboratory has also indicated that Cin8 is differentially phosphorylated during late anaphase at cyclin-dependent kinase 1 (Cdk1)-specific sites located in its motor domain. In vivo, such phosphorylation causes Cin8 detachment from spindles and reduces the spindle elongation rate, while maintaining proper spindle morphology. To study the effect of phosphorylation on Cin8 motor function, we examined in vitro motile properties of wild type Cin8, as well as its phosphorylation using phospho-deficient and phospho-mimic variants, in a single molecule fluorescence motility assay. Analysis was performed on whole cell extracts and on purified Cin8 samples. We found that addition of negative charges in the phospho-mimic mutant weakened the MT-motor interaction, increased motor velocity and promoted minus-end-directed motility. These results indicate that phosphorylation in the catalytic domain of Cin8 regulates its motor function.
Marked long-term decline in ambient CO mixing ratio in SE England, 1997–2014: evidence of policy success in improving air quality
Authors: Lowry D. , Lanoisellé M. E. , Fisher R. E. , Martin M. , Fowler C. M. R. , France J. L. , Hernández-Paniagua I. Y. , Novelli P. C. , Sriskantharajah S. , O’Brien P. , Rata N. D. , Holmes C. W. , Fleming Z. L. , Clemitshaw K. C. , Zazzeri G. , Pommier M. , McLinden C. A. , Nisbet E. G. 
Published: May 2016

AbstractAtmospheric CO at Egham in SE England has shown a marked and progressive decline since 1997, following adoption of strict controls on emissions. The Egham site is uniquely positioned to allow both assessment and comparison of ‘clean Atlantic background’ air and CO-enriched air downwind from the London conurbation. The decline is strongest (approximately 50 ppb per year) in the 1997–2003 period but continues post 2003. A ‘local CO increment’ can be identified as the residual after subtraction of contemporary background Atlantic CO mixing ratios from measured values at Egham. This increment, which is primarily from regional sources (during anticyclonic or northerly winds) or from the European continent (with easterly air mass origins), has significant seasonality, but overall has declined steadily since 1997. On many days of the year CO measured at Egham is now not far above Atlantic background levels measured at Mace Head (Ireland). The results are consistent with MOPITT satellite observations and ‘bottom-up’ inventory results. Comparison with urban and regional background CO mixing ratios in Hong Kong demonstrates the importance of regional, as opposed to local reduction of CO emission. The Egham record implies that controls on emissions subsequent to legislation have been extremely successful in the UK.
Loss of Nrf2 abrogates the protective effect of Keap1 downregulation in a preclinical model of cutaneous squamous cell carcinoma
Authors: Knatko Elena V. , Higgins Maureen , Fahey Jed W. , Dinkova-Kostova Albena T. 
Published: May 2016

AbstractCutaneous squamous cell carcinomas (cSCC) are the most common and highly mutated human malignancies, challenging identification of driver mutations and targeted therapies. Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates a cytoprotective inducible program, which counteracts the damaging effects of solar UV radiation, the main etiological factor in cSCC development. Downregulation of Kelch-like ECH-associated protein 1 (Keap1), a Cullin-3/Rbx1 ubiquitin ligase substrate adaptor protein, which mediates the ubiquitination and proteasomal degradation of Nrf2, has a strong protective effect in a preclinical model of cSCC. However, in addition to Nrf2, Keap1 affects ubiquitination of other proteins in the carcinogenesis process, including proteins involved in inflammation and DNA damage repair. Here, we generated Keap1flox/flox SKH-1 hairless mice in which Nrf2 is disrupted (Keap1flox/flox/Nrf2−/−) and subjected them chronically to solar-simulated UV radiation. We found that the incidence, multiplicity and burden of cSCC that form in Keap1flox/flox/Nrf2−/− mice are much greater than in their Keap1flox/flox/Nrf2+/+ counterparts, establishing Nrf2 activation as the protection mediator. Our findings further imply that inhibition of Nrf2 globally, a strategy proposed for cancer treatment, is unlikely to be beneficial.
Levels of albuminuria and risk of developing macroalbuminuria in type 2 diabetes: historical cohort study
Authors: Chida Shoma , Fujita Yoshikuni , Ogawa Akifumi , Hayashi Akinori , Ichikawa Raishi , Kamata Yuji , Takeuchi Akihiro , Takano Koji , Shichiri Masayoshi 
Published: May 2016

AbstractAlthough increased urinary albumin excretion may increase the risk of adverse renal outcomes in patients with diabetes, it remains unclear whether microalbuminuria is associated with a higher incidence of macroalbuminuria in the absence of non-diabetic kidney events that frequently develop during the long-term course of type 2 diabetes. This historical cohort study included patients with type 2 diabetes, spot urine albumin:creatinine ratio (ACR) <300 mg/gCr and normal serum creatinine concentrations treated between August 1988 and April 2015. Patients with any evidence suggesting non-diabetic kidney diseases at baseline were excluded. Over a median follow-up of 50 months, 70 of the 1760 included patients developed macroalbuminuria. Twenty-one of these patients were diagnosed with non-diabetic renal events. The five-year cumulative incidence of macroalbuminuria in patients with ACRs of 0–7.5 mg/gCr, 7.5–30 mg/gCr, 30–150 mg/gCr, and 150–300 mg/gCr were 0%, 0.53%, 3.5%, and 36.0%, respectively, with significant differences between each pair of ACR categories. In type 2 diabetes, higher urinary ACR, even within a level of normoalbuminuria, was associated with a greater incidence of macroalbuminuria when non-diabetic renal events were excluded. These results conflict with findings suggesting that microalbuminuria is a poor indicator for the progression of diabetic nephropathy.
Horizontal Gene Transfer of Pectinases from Bacteria Preceded the Diversification of Stick and Leaf Insects
Authors: Shelomi Matan , Danchin Etienne G. J. , Heckel David , Wipfler Benjamin , Bradler Sven , Zhou Xin , Pauchet Yannick 
Published: May 2016

AbstractGenes acquired by horizontal transfer are increasingly being found in animal genomes. Understanding their origin and evolution requires knowledge about the phylogenetic relationships from both source and recipient organisms. We used RNASeq data and respective assembled transcript libraries to trace the evolutionary history of polygalacturonase (pectinase) genes in stick insects (Phasmatodea). By mapping the distribution of pectinase genes on a Polyneoptera phylogeny, we identified the transfer of pectinase genes from known phasmatodean gut microbes into the genome of an early euphasmatodean ancestor that took place between 60 and 100 million years ago. This transfer preceded the rapid diversification of the suborder, enabling symbiont-free pectinase production that would increase the insects’ digestive efficiency and reduce dependence on microbes. Bacteria-to-insect gene transfer was thought to be uncommon, however the increasing availability of large-scale genomic data may change this prevailing notion.
Fermi-Surface Topological Phase Transition and Horizontal Order-Parameter Nodes in CaFe2As2 Under Pressure
Authors: Gonnelli R. S. , Daghero D. , Tortello M. , Ummarino G. A. , Bukowski Z. , Karpinski J. , Reuvekamp P. G. , Kremer R. K. , Profeta G. , Suzuki K. , Kuroki K. 
Published: May 2016

AbstractIron-based compounds (IBS) display a surprising variety of superconducting properties that seems to arise from the strong sensitivity of these systems to tiny details of the lattice structure. In this respect, systems that become superconducting under pressure, like CaFe2As2, are of particular interest. Here we report on the first directional point-contact Andreev-reflection spectroscopy (PCARS) measurements on CaFe2As2 crystals under quasi-hydrostatic pressure, and on the interpretation of the results using a 3D model for Andreev reflection combined with ab-initio calculations of the Fermi surface (within the density functional theory) and of the order parameter symmetry (within a random-phase-approximation approach in a ten-orbital model). The almost perfect agreement between PCARS results at different pressures and theoretical predictions highlights the intimate connection between the changes in the lattice structure, a topological transition in the holelike Fermi surface sheet, and the emergence on the same sheet of an order parameter with a horizontal node line.
Abrogation of collagen-induced arthritis by a peptidyl arginine deiminase inhibitor is associated with modulation of T cell-mediated immune responses
Authors: Kawalkowska Joanna , Quirke Anne-Marie , Ghari Fatemeh , Davis Simon , Subramanian Venkataraman , Thompson Paul R. , Williams Richard O. , Fischer Roman , La Thangue Nicholas B. , Venables Patrick J. 
Published: May 2016

AbstractProteins containing citrulline, a post-translational modification of arginine, are generated by peptidyl arginine deiminases (PAD). Citrullinated proteins have pro-inflammatory effects in both innate and adaptive immune responses. Here, we examine the therapeutic effects in collagen-induced arthritis of the second generation PAD inhibitor, BB-Cl-amidine. Treatment after disease onset resulted in the reversal of clinical and histological changes of arthritis, associated with a marked reduction in citrullinated proteins in lymph nodes. There was little overall change in antibodies to collagen or antibodies to citrullinated peptides, but a shift from pro-inflammatory Th1 and Th17-type responses to pro-resolution Th2-type responses was demonstrated by serum cytokines and antibody subtypes. In lymph node cells from the arthritic mice treated with BB-Cl-amidine, there was a decrease in total cell numbers but an increase in the proportion of Th2 cells. BB-Cl-amidine had a pro-apoptotic effect on all Th subsets in vitro with Th17 cells appearing to be the most sensitive. We suggest that these immunoregulatory effects of PAD inhibition in CIA are complex, but primarily mediated by transcriptional regulation. We suggest that targeting PADs is a promising strategy for the treatment of chronic inflammatory disease.
Quantitative Proteomics Analysis of Tissue Interstitial Fluid for Identification of Novel Serum Candidate Diagnostic Marker for Hepatocellular Carcinoma
Authors: Sun Wei , Xing Baocai , Guo Lihai , Liu Zhilei , Mu Jinsong , Sun Longqin , Wei Handong , Zhao Xiaohang , Qian Xiaohong , Jiang Ying , He Fuchu 
Published: May 2016

AbstractHepatocellular carcinoma (HCC) is the fifth most common malignant cancer in the world. The sensitivity of alpha-fetoprotein (AFP) is still inadequate for HCC diagnosis. Tissue interstitial fluid (TIF), as the liquid microenvironment of cancer cells, was used for biomarker discovery in this study. Paired tumor and nontumor TIF samples from 6 HBV-HCC patients were analyzed by a proteomic technique named iTRAQ (isobaric tag for relative and absolute quantitation). Totally, 241 up-regulated proteins (ratio ≥ 1.3, p < 0.05) and 288 down-regulated proteins (ratio ≤ −1.3, p < 0.05) in tumor TIF were identified. Interestingly, proteins in S100 family were found remarkably up-regulated in tumor TIF. One dramatically up-regulated protein S100A9 (ratio = 19) was further validated by ELISA in sera from liver cirrhosis (LC, HCC high risk population) and HCC patients (n = 47 for each group). The level of this protein was significantly elevated in HCC sera compared with LC (p < 0.0001). The area under the curve of this protein to distinguish HCC from LC was 0.83, with sensitivity of 91% (higher than AFP) and specificity of 66%. This result demonstrated the potential of S100A9 as a candidate HCC diagnostic biomarker. And TIF was a kind of promising material to identify candidate tumor biomarkers that could be detected in serum.
Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia
Authors: Zhao Yanxin , Chen Xizhuo , Zhong Suyu , Cui Zaixu , Gong Gaolang , Dong Qi , Nan Yun 
Published: May 2016

AbstractCongenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia.
Piezoelectric Templates – New Views on Biomineralization and Biomimetics
Authors: Stitz Nina , Eiben Sabine , Atanasova Petia , Domingo Neus , Leineweber Andreas , Burghard Zaklina , Bill Joachim 
Published: May 2016

AbstractBiomineralization in general is based on electrostatic interactions and molecular recognition of organic and inorganic phases. These principles of biomineralization have also been utilized and transferred to bio-inspired synthesis of functional materials during the past decades. Proteins involved in both, biomineralization and bio-inspired processes, are often piezoelectric due to their dipolar character hinting to the impact of a template’s piezoelectricity on mineralization processes. However, the piezoelectric contribution on the mineralization process and especially the interaction of organic and inorganic phases is hardly considered so far. We herein report the successful use of the intrinsic piezoelectric properties of tobacco mosaic virus (TMV) to synthesize piezoelectric ZnO. Such films show a two-fold increase of the piezoelectric coefficient up to 7.2 pm V−1 compared to films synthesized on non-piezoelectric templates. By utilizing the intrinsic piezoelectricity of a biotemplate, we thus established a novel synthesis pathway towards functional materials, which sheds light on the whole field of biomimetics. The obtained results are of even broader and general interest since they are providing a new, more comprehensive insight into the mechanisms involved into biomineralization in living nature.