bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast
Authors: Cisneros-Barroso Eugenia , Yance-Chávez Tula , Kito Ayako , Sugiura Reiko , Gómez-Hierro Alba , Giménez-Zaragoza David , Aligue Rosa 
Published: August 2014

Abstract
Calcium signals trigger the translocation of the Prz1 transcription factor from the cytoplasm to the nucleus. The process is regulated by the calcium-activated phosphatase calcineurin, which activates Prz1 thereby maintaining active transcription during calcium signalling. When calcium signalling ceases, Prz1 is inactivated by phosphorylation and exported to the cytoplasm. In budding yeast and mammalian cells, different kinases have been reported to counter calcineurin activity and regulate nuclear export. Here, we show that the Ca2+/calmodulin-dependent kinase Cmk1 is first phosphorylated and activated by the newly identified kinase CaMKK2 homologue, Ckk2, in response to Ca2+. Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca2+. Furthermore, Cdc25 phosphatase is also phosphorylated by Cmk1, inducing cell cycle arrest in response to an increase in Ca2+. Moreover, cmk1 deletion shows a high tolerance to chronic exposure to Ca2+, due to the lack of cell cycle inhibition and elevated Prz1 activity. This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription. These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.
The yeast prefoldin-like URI-orthologue Bud27 associates with the RSC nucleosome remodeler and modulates transcription
Authors: Mirón-García María Carmen , Garrido-Godino Ana Isabel , Martínez-Fernández Verónica , Fernández-Pevida Antonio , Cuevas-Bermúdez Abel , Martín-Expósito Manuel , Chávez Sebastián , de la Cruz Jesús , Navarro Francisco 
Published: August 2014

Abstract
Bud27, the yeast orthologue of human URI/RMP, is a member of the prefoldin-like family of ATP-independent molecular chaperones. It has recently been shown to mediate the assembly of the three RNA polymerases in an Rpb5-dependent manner. In this work, we present evidence of Bud27 modulating RNA pol II transcription elongation. We show that Bud27 associates with RNA pol II phosphorylated forms (CTD-Ser5P and CTD-Ser2P), and that its absence affects RNA pol II occupancy of transcribed genes. We also reveal that Bud27 associates in vivo with the Sth1 component of the chromatin remodeling complex RSC and mediates its association with RNA pol II. Our data suggest that Bud27, in addition of contributing to Rpb5 folding within the RNA polymerases, also participates in the correct assembly of other chromatin-associated protein complexes, such as RSC, thereby modulating their activity.
Chimeric bifunctional oligonucleotides as a novel tool to invade telomerase assembly
Authors: Azhibek Dulat , Zvereva Maria , Zatsepin Timofei , Rubtsova Maria , Dontsova Olga 
Published: August 2014

Abstract
Telomerase is a key participant in the telomere length maintaining system in eukaryotic cells. Telomerase RNA and protein reverse transcriptase subunits are essential for the appearance of active telomerase in vitro. Telomerase is active in many cancer types and is a potential target for anticancer drug development. Here we report a new approach for impairing telomerase function at the stage of human telomerase assembly. The approach is based on the application of chimeric bifunctional oligonucleotides that contain two oligonucleotide parts complementary to the functional domains of telomerase RNA connected with non-nucleotide linkers in different orientations (5′-3′, 5′-5′ or 3′-3′). Such chimeras inhibited telomerase in vitro in the nM range, but were effective in vivo in sub-nM concentrations, predominantly due to their effect on telomerase assembly and dimerization.
RNA recognition and self-association of CPEB4 is mediated by its tandem RRM domains
Authors: Schelhorn Constanze , Gordon James M.B. , Ruiz Lidia , Alguacil Javier , Pedroso Enrique , Macias Maria J. 
Published: August 2014

Abstract
Cytoplasmic polyadenylation is regulated by the interaction of the cytoplasmic polyadenylation element binding proteins (CPEB) with cytoplasmic polyadenylation element (CPE) containing mRNAs. The CPEB family comprises four paralogs, CPEB1–4, each composed of a variable N-terminal region, two RNA recognition motif (RRM) and a C-terminal ZZ-domain. We have characterized the RRM domains of CPEB4 and their binding properties using a combination of biochemical, biophysical and NMR techniques. Isothermal titration calorimetry, NMR and electrophoretic mobility shift assay experiments demonstrate that both the RRM domains are required for an optimal CPE interaction and the presence of either one or two adenosines in the two most commonly used consensus CPE motifs has little effect on the affinity of the interaction. Both the single RRM1 and the tandem RRM1–RRM2 have the ability to dimerize, although representing a minor population. Self-association does not affect the proteins’ ability to interact with RNA as demonstrated by ion mobility–mass spectrometry. Chemical shift effects measured by NMR of the apo forms of the RRM1–RRM2 samples indicate that the two domains are orientated toward each other. NMR titration experiments show that residues on the β-sheet surface on RRM1 and at the C-terminus of RRM2 are affected upon RNA binding. We propose a model of the CPEB4 RRM1–RRM2–CPE complex that illustrates the experimental data.
Structural Modifications of Gluten Proteins in Strong and Weak Wheat Dough During Mixing
Authors: Jazaeri Sahar , Bock Jayne E. , Bagagli Marcela P. , Iametti Stefania , Bonomi Francesco , Seetharaman Koushik 
Published: August 2014

ABSTRACTThe network‐forming attributes of gluten have been investigated for decades, but no study has comprehensively addressed the differences in gluten network evolution between strong and weak wheat types (hard and soft wheat). This study monitored changes in SDS protein extractability, SDS‐accessible thiols, protein surface hydrophobicity, molecular weight distribution, and secondary structural features of proteins during mixing to bring out the molecular determinants of protein network formation in hard and soft wheat dough. Soft wheat flour and dough exhibited greater protein extractability and more accessible thiols than hard wheat flour and dough. The addition of the thiol‐blocking agent N‐ethylmaleimide (NEM) resulted in similar results for protein extractability and accessible thiols in hard and soft wheat samples. Soft wheat dough had greater protein surface hydrophobicity than hard wheat and exhibited a larger decrease in surface hydrophobicity in the presence of NEM. Formation of high‐molecular‐weight (HMW) protein in soft wheat dough was primarily because of formation of disulfides among low‐molecular‐weight (LMW) proteins, as indicated by the absence of changes in protein distribution when NEM was present, whereas in hard wheat dough the LMW fraction formed disulfide interaction with the HMW fraction. Fourier transform infrared spectroscopy indicated formation of β‐sheets in dough from either wheat type at peak mixing torque. Formation of β‐sheets in soft wheat dough appears to be driven by hydrophobic interactions, whereas disulfide linkages stabilize secondary structure elements in hard wheat dough.
Arabidopsis SNAREs SYP61 and SYP121 Coordinate the Trafficking of Plasma Membrane Aquaporin PIP2;7 to Modulate the Cell Membrane Water Permeability
Authors: Hachez Charles , Laloux Timothée , Reinhardt Hagen , Cavez Damien , Degand Hervé , Grefen Christopher , De Rycke Riet , Inzé Dirk , Blatt Michael R. , Russinova Eugenia , Chaumont François 
Published: August 2014

Abstract
Plant plasma membrane intrinsic proteins (PIPs) are aquaporins that facilitate the passive movement of water and small neutral solutes through biological membranes. Here, we report that post-Golgi trafficking of PIP2;7 in Arabidopsis thaliana involves specific interactions with two syntaxin proteins, namely, the Qc-SNARE SYP61 and the Qa-SNARE SYP121, that the proper delivery of PIP2;7 to the plasma membrane depends on the activity of the two SNAREs, and that the SNAREs colocalize and physically interact. These findings are indicative of an important role for SYP61 and SYP121, possibly forming a SNARE complex. Our data support a model in which direct interactions between specific SNARE proteins and PIP aquaporins modulate their post-Golgi trafficking and thus contribute to the fine-tuning of the water permeability of the plasma membrane.
In vitro study of the effect of small interfering ribonucleic acid on the expression of FOXN1 and B cell‐attracting chemokine 1 in thymoma cell lines
Authors: Zhang Hui , Zhang Peng , Liu Yimei , Lv Peng , Wang Yuanguo , Chen Yuan 
Published: August 2014

AbstractBackgroundTo determine the relationship between FOXN1 (a transcription factor) and B cell‐attracting chemokine 1 (BCA1, a chemotactic factor), and their influence on thymoma cell proliferation.MethodsWe initially used immunohistochemical methods to compare the expression levels of FOXN1 and BCA1 in thymoma and non‐thymomatous tissue samples. Reverse transcription polymerase chain reaction (RT‐PCR) and Western blotting were used to compare the expression of FOXN1 and BCA1 in thymoma cells (Thy0517) and normal thymic epithelial cells (CRL7660). We used ribonucleic acid interference (RNAi) to downregulate FOXN1 and BCA1 expression in Thy0517 cells to determine the relationship of the two factors with cell regulation. We also performed methyl thiazolyl tetrazolium (MTT) [3‐(4,5)‐dimethylthiahiazo(‐z‐y1)‐3,5‐di‐phenytetrazoliumromide] assays to detect the changes in Thy0517 cells after RNAi of FOXN1 and BCA1.ResultsFOXN1 and BCA1 expression levels were higher in thymoma tissues and Thy0517 cells compared to non‐thymomatous tissue and CRL7660 cells (P < 0.05). RT‐PCR and Western blot following RNAi showed that FOXN1 controlled BCA1 expression. MTT assay showed that FOXN1 and BCA1 downregulation rapidly inhibited Thy0517 cell proliferation.ConclusionsFOXN1 and BCA1 expression was higher in thymoma tissue samples and cell lines than in non‐thymomatous tissue and normal thymic epithelial cells. FOXN1 acts upstream of BCA1 and both FOXN1 and BCA1 promote thymoma cell proliferation.
Inflated reward value in early opiate withdrawal
Authors: Wassum Kate M. , Greenfield Venuz Y. , Linker Kay E. , Maidment Nigel T. , Ostlund Sean B. 
Published: August 2014

AbstractThrough incentive learning, the emotional experience of a reward in a relevant need state (e.g. hunger for food) sets the incentive value that guides the performance of actions that earn that reward when the need state is encountered again. Opiate withdrawal has been proposed as a need state in which, through experience, opiate value can be increased, resulting in escalated opiate self‐administration. Endogenous opioid transmission plays anatomically dissociable roles in the positive emotional experience of reward consumption and incentive learning. We, therefore, sought to determine if chronic opiate exposure and withdrawal produces a disruption in the fundamental incentive learning process such that reward seeking, even for non‐opiate rewards, can become maladaptive, inconsistent with the emotional experience of reward consumption and irrespective of need. Rats trained to earn sucrose or water on a reward‐seeking chain were treated with morphine (10–30 mg/kg, s.c.) daily for 11 days prior to testing in withdrawal. Opiate‐withdrawn rats showed elevated reward‐seeking actions, but only after they experienced the reward in withdrawal, an effect that was strongest in early (1–3 days), as opposed to late (14–16 days), withdrawal. This was sufficient to overcome a negative reward value change induced by sucrose experience in satiety and, in certain circumstances, was inconsistent with the emotional experience of reward consumption. Lastly, we found that early opiate withdrawal‐induced inflation of reward value was blocked by inactivation of basolateral amygdala mu opioid receptors. These data suggest that in early opiate withdrawal, the incentive learning process is disrupted, resulting in maladaptive reward seeking.
The ISNT rule in glaucoma: revisiting with spectral domain optical coherence tomography
Authors: Rao Harsha L. , Yadav Ravi K. , Addepalli Uday K. , Begum Viquar U. , Senthil Sirisha , Choudhari Nikhil S. , Garudadri Chandra S. 
Published: August 2014

AbstractPurposeTo evaluate the ability of the neuroretinal rim (NRR) rules determined using spectral domain optical coherence tomography (SDOCT) in diagnosing glaucoma and to study the effect of optic disc size and disease severity on the diagnostic ability of these rules.MethodsIn a cross‐sectional study, 125 eyes of 96 glaucoma patients and 96 eyes of 72 control subjects underwent optic nerve head (ONH) imaging with SDOCT. Inferior (I), superior (S), nasal (N) and temporal (T) NRR areas were automatically determined by the sdoct software. Diagnostic abilities of ISNT (I > S > N > T), IT (I > T) and ST (S > T) rules in glaucoma were evaluated using sensitivity, specificity and likelihood ratios (LR). Effect of optic disc size and disease severity [based on mean deviation (MD) on visual fields] on the diagnostic ability of the NRR rules was evaluated using regression models.ResultsSensitivities of ISNT, IT and ST rules were 80.8%, 60.0% and 29.6%, respectively, and the specificities were 32.3%, 84.4% and 93.8%, respectively. Positive LRs of ISNT, IT and ST rules were 1.19, 3.84 and 4.74, respectively, and negative LRs were 0.60, 0.47 and 0.75, respectively. Sensitivities of ISNT (coefficient: −1.06, p = 0.02) and IT (−0.71, 0.05) rules decreased with increasing disc size. Positive LR of IT rule increased significantly (−0.01, 0.04) with decreasing MD, and negative LR of IT rule decreased (got better) significantly (0.26, 0.05) with decreasing disc size.ConclusionsNeuroretinal rim rules, as determined by SDOCT, do not allow robust differentiation of glaucomatous from non‐glaucomatous discs.
Oxidative status in the macula densa modulates tubuloglomerular feedback responsiveness in Angiotensin II‐induced hypertension
Authors: Song J. , Lu Y. , Lai E. Y. , Wei J. , Wang L. , Chandrashekar K. , Wang S. , Shen C. , Juncos L. A. , Liu R. 
Published: August 2014

AbstractAimTubuloglomerular feedback (TGF) is an important mechanism in control of signal nephron glomerular filtration rate. The oxidative stress in the macula densa, primarily determined by the interactions between nitric oxide (NO) and superoxide (), is essential in maintaining the TGF responsiveness. However, few studies examining the interactions between and amount of NO and generated by the macula densa during normal and hypertensive states.MethodsIn this study, we used isolated perfused juxtaglomerular apparatus to directly measure the amount and also studied the interactions between NO and in macula densa in both physiological and slow pressor Angiotensin II (Ang II)‐induced hypertensive mice.ResultsWe found that slow pressor Ang II at a dose of 600 ng kg−1 min−1 for two weeks increased mean arterial pressure by 26.1 ± 5.7 mmHg. TGF response increased from 3.4 ± 0.2 μm in control to 5.2 ± 0.2 μm in hypertensive mice. We first measured generation by the macula densa and found it was undetectable in control mice. However, generation by the macula densa increased to 21.4 ± 2.5 unit min−1 in Ang II‐induced hypertensive mice. We then measured NO generation and found that NO generation by the macula densa was 138.5 ± 9.3 unit min−1 in control mice. The NO was undetectable in the macula densa in hypertensive mice infused with Ang II.ConclusionsUnder physiological conditions, TGF response is mainly controlled by the NO generated in the macula densa; in Ang II induced hypertension, the TGF response is mainly controlled by the generated by the macula densa.
E‐learning in multicultural environments: An analysis of online flight attendant training
Authors: de Brito Neto Jose Felix , Smith MaryJo , Pedersen David 
Published: August 2014

AbstractThroughout the first decade of this century, financial challenges in the airline industry compelled airlines to maximize competitive advantage through a focus on human resource management. Consequently, e‐learning gained increasing attention as it imparted knowledge on an asynchronous and global basis with substantially reduced costs. However, while focusing on learning technologies, airlines failed to acknowledge learners' needs and cultural backgrounds by creating culturally neutral e‐learning environments, resulting in ineffective training and negligible performance improvement. This research aimed to study the perceptions of a multicultural group of flight attendants about e‐learning courses developed by their employing airline. A questionnaire verified the opinion of these flight attendants on course relevance and learner motivation; cultural sensitivity; course organization; and course interactivity. The results showed that the employing airline developed e‐learning courses that were highly technological and interactive, but had little regard for learners' cultural and language backgrounds. Consequently, ineffective e‐learning prevailed.
Impact of pretransplant serum ferritin level on risk of invasive mold infection after allogeneic hematopoietic stem cell transplantation
Authors: Dadwal Sanjeet S. , Tegtmeier Bernard , Liu Xueli , Frankel Paul , Ito James , Forman Stephen J. , Pullarkat Vinod 
Published: August 2014

AbstractInvasive mold infections (IMI) are life‐threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT) and are mostly caused by Aspergillus species and Mucorales. We examined whether elevated serum ferritin prior to HSCT was associated with increased risk of IMI after allogeneic HSCT. Elevated serum ferritin was defined as values ≥1000 ng/mL. Pretransplant ferritin levels were available for 477 transplants. Nine developed IMI at day 30 and 21 had IMI at day 100 for a cumulative incidence of 1.9% and 4.4%, respectively. Among the high ferritin group, eight of 220 transplant cases (3.6%) developed an IMI within 30 d after HSCT compared with one of 257 (0.4%) in the low ferritin group (P = 0.01). Fourteen of 220 (6.4%) and seven of 257 transplant cases (2.7%) in the high and low ferritin groups, respectively, had developed an IMI by day 100 after HSCT (P = 0.07). Nine of 53 (17%) patients with grades III and IV acute GVHD and iron overload experienced IMI, when compared to three of 37 (8.1%) with high‐grade aGVHD, but no iron overload. Among patients without aGVHD, those with elevated ferritin had a 2.7% incidence of IMI compared with 0.9% for patients without elevated ferritin. There was a marginally significant difference in cumulative incidence function between high and low ferritin groups for IMI (P = 0.06). However, elevated serum ferritin (≥1000 ng/mL) was not a significant risk factor for IMI in a multivariate competing risk regression model after adjusting for aGVHD.
Sensory characteristics and storage quality indicators of surimi franks nutritionally enhanced with omega‐3 rich flaxseed oil and salmon oil
Authors: Sell Christin , Beamer Sarah , Jaczynski Jacek , Matak Kristen E. 
Published: August 2014

SummarySurimi franks were fortified with flaxseed or salmon oil at 2 g/100 g sample, franks without added oil served as a control. Thiobarbituric acid reactive substances values were highest (P < 0.001) in salmon oil franks; however, these values did not change over the 21‐day storage period regardless of frank type (P > 0.05). Frank pH decreased over time (P = 0.011) for all frank types. There were differences in textural properties between frank types (P < 0.05), with the flaxseed franks being softer and less gummy, cohesive and chewy than the control franks. Participants (n = 79; age 18–35) evaluated visual appeal, colour, aroma, texture, flavour and acceptability on a hedonic scale; there were no differences (P > 0.05) between franks. Fifty‐four panellists reported consuming sausage on a weekly to monthly basis, and most (50/79) indicated interest in purchasing this type product. The surimi franks were accepted by young adult consumers, which may indicate market potential of these types of products.
A social cognitive explanation of situational and individual effects on moral sensitivity
Authors: Sparks John R. 
Published: August 2014

AbstractModels of moral decision making describe the process as beginning with the recognition of moral content in the decision environment. This recognition ability, or moral sensitivity, represents a key input to moral decision making. Adopting a social cognitive perspective, this paper studies the degree to which moral sensitivity is explained in terms of moral schema activation. In a single experiment, two situational factors (moral content priming and issue moral intensity) and two individual characteristics (moral identity and need for cognition) are tested for their effects on moral sensitivity. Results support the social cognitive explanation of moral sensitivity. The moral schema's propensity for activation, development, and accessibility significantly influence the ability to recognize moral issues in the decision environment.
The Impact of Ambiguity on Managerial Investment and Cash Holdings
Authors: Neamtiu Monica , Shroff Nemit , White Hal D. , Williams Christopher D. 
Published: August 2014

AbstractStandard finance theory suggests that managers invest in projects that, in expectation, produce returns that justify the use of capital. An underlying assumption is that managers have the information necessary to understand the distributional properties of the pay‐offs underlying the decision. This paper examines firm investment behavior when managers are likely to find it more challenging to develop expectations of pay‐offs, namely during periods of increased macroeconomic ambiguity. In particular, we examine how macroeconomic ambiguity – proxied by the variance premium (Drechsler, ) and the dispersion in forecasts of corporate profits from the Survey of Professional Forecasters (Anderson et al., ) – impacts managerial capital investment and cash holdings. Consistent with ambiguity theory, we find that macroeconomic ambiguity is negatively associated with capital investment and positively associated with cash holdings. These results are robust to alternative explanations related to risk, investor sentiment and economic conditions. Moreover, consistent with recent theoretical real options literature, we find that ambiguity reduces the value of investment opportunities, while risk increases the value of such opportunities. Overall, these findings provide initial empirical evidence on the economic distinction between ambiguity and risk with respect to managerial investment and cash holdings.