Miracle-dz/UniFAR-FTUs huggingface dataset:
Ca2+ influx modulation of temporal and spatial patterns of inositol trisphosphate‐mediated Ca2+ liberation in Xenopus oocytes.

Inositol 1,4,5‐trisphosphate (InsP3) functions as a second messenger by liberating intracellular Ca2+ and by promoting influx of extracellular Ca2+. We examined the effects of Ca2+ influx on the temporal and spatial patterns of intracellular Ca2+ liberation in Xenopus oocytes by fluorescence imaging of cytosolic free Ca2+ together with voltage clamp recording of Ca(2+)‐activated Cl‐ currents. Oocytes were injected with a poorly metabolized InsP3 analogue (3‐F‐InsP3; see Introduction) to induce sustained activation of InsP3 signalling, and Ca2+ influx was controlled by applying voltage steps to change the driving force for Ca2+ entry. Positive‐ and negative‐going potential steps (corresponding, respectively, to decreases and increases in Ca2+ influx) evoked damped oscillatory Cl‐ currents, accompanied by cyclical changes in cytosolic free Ca2+. The source of this Ca2+ was intracellular, since oscillations persisted when Ca2+ entry was suppressed by removing extracellular Ca2+ or by polarization close to the Ca2+ equilibrium potential. Fluorescence recordings from localized (ca 5 microns) spots on the oocyte showed repetitive Ca2+ spikes. Their frequency increased at more negative potentials, but they became smaller and superimposed on a sustained ‘pedestal’ of Ca2+. Spike periods ranged from about 50 s at +20 mV to 4s at potentials between ‐60 and ‐120 mV. Ca2+ spike frequency decreased after removing extracellular Ca2+, but the spike amplitude was not reduced and low frequency spikes continued for at least 30 min in the absence of extracellular Ca2+. Membrane current oscillations decayed in amplitude following voltage steps, while locally recorded Ca2+ spikes did not. This probably arose because Ca2+ release was initially synchronous across the cell, leading to large Ca(2+)‐activated Cl‐ currents, but the currents then diminished as different areas of the cell began to release Ca2+ asynchronously. Fluorescence imaging revealed that Ca2+ liberation in 3‐F‐InsP3‐loaded oocytes occurred as transient localized puffs and as propagating waves. Polarization to more negative potentials increased the frequency of puffs and the number of sites at which they were seen, and enhanced their ability to initiate waves. The frequency and velocity of Ca2+ waves increased at more negative potentials. When the potential was returned to more positive levels, repetitive Ca2+ spikes at first occurred synchronously across the recording area, but this synchronization was gradually lost and Ca2+ waves began at several foci. We conclude that influx of extracellular Ca2+ regulates the temporal and spatial patterns of Ca2+ liberation from InsP3‐sensitive intracellular stores, probably as a result of dual excitatory and inhibitory actions of cytosolic Ca2+ on the InsP3 receptor. (ABSTRACT TRUNCATED AT 400 WORDS)
Structure of the N-Terminal Gyrase B Fragment in Complex with ADP⋅Pi Reveals Rigid-Body Motion Induced by ATP Hydrolysis

Type II DNA topoisomerases are essential enzymes that catalyze topological rearrangement of double-stranded DNA using the free energy generated by ATP hydrolysis. Bacterial DNA gyrase is a prototype of this family and is composed of two subunits (GyrA, GyrB) that form a GyrA2GyrB2 heterotetramer. The N-terminal 43-kDa fragment of GyrB (GyrB43) from E. coli comprising the ATPase and the transducer domains has been studied extensively. The dimeric fragment is competent for ATP hydrolysis and its structure in complex with the substrate analog AMPPNP is known. Here, we have determined the remaining conformational states of the enzyme along the ATP hydrolysis reaction path by solving crystal structures of GyrB43 in complex with ADP⋅BeF3, ADP⋅Pi, and ADP. Upon hydrolysis, the enzyme undergoes an obligatory 12° domain rearrangement to accommodate the 1.5 Å increase in distance between the γ- and β-phosphate of the nucleotide within the sealed binding site at the domain interface. Conserved residues from the QTK loop of the transducer domain (also part of the domain interface) couple the small structural change within the binding site with the rigid body motion. The domain reorientation is reflected in a significant 7 Å increase in the separation of the two transducer domains of the dimer that would embrace one of the DNA segments in full-length gyrase. The observed conformational change is likely to be relevant for the allosteric coordination of ATP hydrolysis with DNA binding, cleavage/re-ligation and/or strand passage.
FOLK MEDICINAL KNOWLEDGE AND CONSERVATION STATUS OF SOME ECONOMICALLY VALUED MEDICINAL PLANTS OF DISTRICT SWAT, PAKISTAN

This paper is based on an ethnobotanical project, carried out in the remote Hindu Kush mountain region of District Swat, Pakistan. The prime objectives of the project were to explore the conservation status, folk medicinal knowledge and traditional pre and post harvesting techniques of some economically important medicinal plants of the area. It was observed that 49 medicinal plants belonging to 32 families were collected and traded in the herb markets of Swat. Most of these plants are used by local population for curing different ailments, while some are exported to other parts of Pakistan. The traditional plant collection techniques have resulted in huge losses of these valuable plant resources. The conservation assessment of these plants revealed that due to increased exploitation and un-sustainable harvesting, 49% of these economically valued medicinal plant species are threatened.
Transfer Effects to a Multimodal Dual-Task after Working Memory Training and Associated Neural Correlates in Older Adults – A Pilot Study

Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.
Enhancement of HCO(3)(-) permeability across the apical membrane of bovine corneal endothelium by multiple signaling pathways.

PURPOSE In this study, the involvement of signaling pathways in the regulation of HCO(3)(-) permeability across the apical membrane of the corneal endothelium was examined. METHODS Cultured bovine corneal endothelial cells (CBCECs) were grown to confluence on permeable membranes. Apical and basolateral sides were perfused with a HCO(3)(-)-rich Cl(-)-free Ringer's solution (28.5 mM; pH 7.5). Relative changes in apical HCO(3)(-) permeability were assayed by pulsing the apical perfusion bath with a low-HCO(3)(-) Cl(-)-free Ringer's solution (2.85 mM; pH 6.5), in the presence or absence of agonists or inhibitors, and comparing the rates of change in intracellular pH (pH(i)), as measured with a pH-sensitive dye. Ca(2+)-activated signaling was measured with the Ca(2+)-sensitive dye Fura-2. Qualitative changes in membrane potential (E(m)) were measured with a voltage-sensitive dye. RT-PCR using calcium-activated chloride channel (CLCA)-specific primers was used to examine the expression of CLCA in the corneal endothelium. RESULTS The adenoceptor agonist adenosine (20 M) enhanced HCO(3)(-) permeability by a factor of 2. Forskolin (40 microM) exerted a 6.3-fold increase of HCO(3)(-) permeability, which was inhibited by the Cl(-) channel blockers, glibenclamide (50 microM) and niflumic acid (100 microM). Adenosine triphosphate (ATP) and ATPgammaS, P(2) receptor agonists that increased intracellular Ca(2+) in corneal endothelium, enhanced HCO(3)(-) permeability by 87% and 79%, respectively. ATPgammaS induced depolarization of the E(m), consistent with anion channel activation, rather than activation of Ca(2+)-dependent K(+) channels, which could secondarily increase extrusion of anions by E(m) hyperpolarization. Cyclopiazonic acid (CPA), an endoplasmic reticulum (ER) Ca(2+)-pump inhibitor that increased [Ca(2+)](i), also enhanced HCO(3)(-) permeability by 95%. Both the calmodulin kinase II (CaMKII) inhibitor KN-62 and the PKC inhibitor bisindolylmaleimide I (BIMI), decreased HCO(3)(-) permeability induced by ATPgammaS. The PKC activator PMA also increased HCO(3)(-) permeability by a factor of 1.8. RT-PCR using CLCA-specific primers showed the expression of CLCA1 in both fresh and cultured BCECs. CONCLUSIONS Activation of adenoceptors and purinoceptors enhances HCO(3)(-) permeability across the apical membrane of the cultured corneal endothelium. Multiple signaling pathways (PKA, PKC, and Ca(2+)/CaMKII) contribute to the HCO(3)(-) transport in cultured corneal endothelium. Both cAMP and Ca(2+)-activated Cl(-) channels (possibly CLCA) may be involved in HCO(3)(-) transport.
FIELD WATER MANAGEMENT AND N-RATES TO SAVE WATER AND CONTROL IRON TOXICITY IN LOWLAND RICE

Poor level of development of lowlands in West Africa, epitomized with bad water management generates favorable conditions for occurrence of iron toxicity which is responsible for limiting yields of lowland rice. Field trial was conducted in 2009, 2010 and 2011 to evaluate the effect of water and nitrogen management on iron toxicity and yield of lowland rice in the Bida, Niger State, Nigeria. Treatments imposed were: (1) Continuous flooding with 5 cm water head from transplanting to hard dough stage. (2) Alternate 30 days flooding with 5 cm water head - 7 days drainage - 30 days flooding - 7 days drainage - 30 days flooding -7 days drainage and flood up to hard dough stage. (3) Alternate 60 days flood with 5 cm water head - 7 days drainage - 30 days flooding - 7 days drainage and flood up to hard dough stage. (4) Alternate 90 days flooding with 5 cm water head - 7 days drainage - flood up to hard dough stage. The N-rates applied were: 40 (control), 60, 80 and 100 kg N ha -1 . Treatments were replicated four times and data obtained were statistically analyzed using SAS statistical package. Results obtained showed that irrigation and N-rates had significant influence (P<0.05) on plant height, panicles number, straw and grain yield when compared with the control (farmers practice). There were no significant differences in grain yield between application of 80 kg N ha -1 and 100 kg N ha -1 . Yields generally increased with increasing levels of nitrogen up to 80 kg N ha -1 and declined with further increase in N-level. Nitrogen use efficiency decreased with increasing levels of nitrogen rates and was 25 kg kg -1 for application of 40 kg N ha -1 . There were also significant differences in plant tissue iron content. Iron concentration was higher in the control than treatments with higher levels of nitrogen. Continuous flooding with 5 cm water head from transplanting to hard dough and the application of 80 kg N ha -1 gave the highest yield in the 3 seasons. The average irrigation water applied for the 3 seasons was 1441 mm including rainfall and crop water use. Treatment 2 of water management saved 143 mm and average water use efficiency was 3.80 kg mm -1 . This treatment also had a marginal decline in grain yield but there was a tradeoff between yield and drainage. Appropriate water and nitrogen management can reduce the intensity of iron in rice to enhance sustainable yield increases of paddy rice in the lowland soils of Bida area.
Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches

In this study, we tested the hypothesis that a CB1 TMH3-4-5-6 aromatic microdomain, which includes F3.25(190), F3.36(201), W5.43(280), and W6.48(357), is centrally involved in CB1 receptor activation, with the F3.36(201)/W6.48(357) interaction key to the maintenance of the CB1-inactive state. We have shown previously that when F3.36(201), W5.43(280), and W6.48(357) are individually mutated to alanine, a significant reduction in ligand binding affinity is observed in the presence of WIN 55,212-2 and SR141716A but not CP55,940 and anandamide. In the work presented here, we report a detailed functional analysis of the F3.36(201)A, F3.25(190)A, W5.43(280)A, and W6.48(357)A mutant receptors in stable cell lines created in HEK cells for agonist-stimulated guanosine 5′-3-O-(thio)triphosphate (GTPγS) binding and GIRK1/4 channel current effects in Xenopus oocytes where the mutant proteins were expressed transiently. The F3.36(201)A mutation showed statistically significant increases in ligand-independent stimulation of GTPγS binding versus wild type CB1, although basal levels for the W6.48(357)A mutant were not statistically different from wild type CB1. F3.36(201)A demonstrated a limited activation profile in the presence of multiple agonists. In contrast, enhanced agonist activation was produced by W6.48(357)A. These results suggest that a F3.36(201)/W6.48(357)-specific contact is an important constraint for the CB1-inactive state that may need to break during activation. Modeling studies suggest that the F3.36(201)/W6.48(357) contact can exist in the inactive state of CB1 and be broken in the activated state via a χ1 rotamer switch (F3.36(201) trans, W6.48(357) g+) → (F3.36(201) g+, W6.48(357) trans). The F3.36(201)/W6.48(357) interaction therefore may represent a “toggle switch” for activation of CB1.
Endocrine disrupting, mutagenic, and teratogenic effects of upper Danube River sediments using effect‐directed analysis

Effect‐directed analysis (EDA) can be useful in identifying and evaluating potential toxic chemicals in matrixes. Previous investigations of extracts of sediments from the upper Danube River in Germany revealed acute nonspecific and mechanism‐specific toxicity as determined by several bioassays. In the present study, EDA was used to further characterize these sediments and identify groups of potentially toxic chemicals. Four extracts of sediments were subjected to a novel fractionation scheme coupled with identification of chemicals to characterize their ability to disrupt steroidogenesis or cause mutagenic and/or teratogenic effects. All four whole extracts of sediment caused significant alteration of steroidogenesis and were mutagenic as well as teratogenic. The whole extracts of sediments were separated into 18 fractions and these fractions were then subjected to the same bioassays as the whole extracts. Fractions 7 to 15 of all four extracts were consistently more potent in both the Ames fluctuation and H295R assays. Much of this toxicity could be attributed to polycyclic aromatic hydrocarbons, sterols, and in fraction 7‐naphthoic acids. Because the fraction containing polychlorinated biphenyls, polychlorodibenzodioxin/furan, dichlorodiphenyltrichloroethane, and several organophosphates did not cause any observable effects on hormone production or a mutagenic response, or were not detected in any of the samples, these compounds could be eliminated as causative agents for the observed effects. These results demonstrate the value of using EDA, which uses multiple bioassays and new fractionation techniques to assess toxicity. Furthermore, to our knowledge this is the first study using the recently developed H295R assay within EDA strategies. Environ. Toxicol. Chem. 2012; 31: 1053–1062. © 2012 SETAC
Optimal distributed Kalman filtering fusion for a linear dynamic system with cross-correlated noises

In this article, we study the distributed Kalman filtering fusion problem for a linear dynamic system with multiple sensors and cross-correlated noises. For the assumed linear dynamic system, based on the newly constructed measurements whose measurement noises are uncorrelated, we derive a distributed Kalman filtering fusion algorithm without feedback, and prove that it is an optimal distributed Kalman filtering fusion algorithm. Then, for the same linear dynamic system, also based on the newly constructed measurements, a distributed Kalman filtering fusion algorithm with feedback is proposed. A rigorous performance analysis is dedicated to the distributed fusion algorithm with feedback, which shows that the distributed fusion algorithm with feedback is also an optimal distributed Kalman filtering fusion algorithm; the P matrices are still the estimate error covariance matrices for local filters; the feedback does reduce the estimate error covariance of each local filter. Simulation results are provided to demonstrate the validity of the newly proposed fusion algorithms and the performance analysis.
Cohesive zone model to predict fracture in bituminous materials and asphaltic pavements: state-of-the-art review

Cohesive zone (CZ) modelling has been receiving increasing attention from the asphaltic materials and pavement mechanics community as a mechanistic approach to model crack initiation and propagation in materials and structures. The CZ model provides a powerful and efficient tool that can be easily implemented in existing computational methods for brittle, quasi-brittle and ductile failure as well as interfacial fracture, all of which are frequently observed in asphaltic materials. Accordingly, this paper introduces the CZ modelling approach in the form of a state-of-the-art review addressing the concept of CZ modelling, CZ constitutive relations, their implementation into computational methods and up-to-date applications of CZ modelling to bituminous mixtures and pavement structures. This paper also includes a brief discussion on the current challenges that researchers face and the future directions to the modelling of fracture in bituminous materials and pavements. CZ modelling is not a topic that can be possibly discussed in a single article; therefore, it should be clearly noted that this review primarily attempts to deliver some of the core aspects of CZ modelling in the area of bituminous composites.
Beyond Managing Uncertainty: Insights From Studying Equivocality in the Fuzzy Front End of Product and Process Innovation Projects

Previous research has shown uncertainty reduction to be critical in the fuzzy front end of the innovation process, but little attention has been given to the equally important concept of equivocality, although it is a defining characteristic of many front-end projects. To address this research gap, this paper report the results from a longitudinal, multiple case study of four large companies oriented to both product and process innovation. First, our results show that both uncertainty and equivocality is more effectively reduced in successful front-end projects than in unsuccessful ones. Second, the negative consequences of equivocality appear more critical to front-end performance than the consequences following uncertainty. Third, our results show that uncertainty and equivocality are reduced sequentially in successful projects and simultaneously in unsuccessful projects. Finally, uncertainty and equivocality takes longer time to reduce in process innovation projects than in product innovation projects, which is a consequence of the systemic nature of process innovation. Altogether, these findings provide strong implications for managing front-end projects more proficiently.
A Stochastic Approach to “Dynamic-Demand” Refrigerator Control

Dynamic demand management is a very promising research direction for improving power system resilience. This paper considers the problem of managing power consumption by means of “smart” thermostatic control of domestic refrigerators. In this approach, the operating temperature of these appliances and thus their energy consumption, is modified dynamically, within a safe range, in response to mains frequency fluctuations. Previous research has highlighted the potential of this idea for responding to sudden power plant outages. However, deterministic control schemes have proved inadequate as individual appliances tend to “synchronize” with each other, leading to unacceptable levels of overshoot in energy demand, when they “recover” their steady-state operating cycles. In this paper we design decentralized random controllers that are able to respond to sudden plant outages and which avoid the instability phenomena associated with other feedback strategies. Stochasticity is used to achieve desynchronization of individual refrigerators while keeping overall power consumption tightly regulated.
Variation in El Niño Circulation Patterns and Winter Storm Impacts in Southern California.

Variation in El Niño Circulation Patterns and Winter Storm Impacts in Southern California. El Niño episodes have historically been associated with an increased frequency of extratropical cyclones and cold front passages in Southern California, largely as the result of a southward shift in the Jet Stream. Thus, increases in precipitation, along with hazards, such as flooding and coastal erosion, normally increase during winters when El Niño circulation is strong. However, the strong El Niño episode of 2015-2016 did not confirm this expectation, further contributing to the growing body of evidence that El Niño episodes vary considerably. A common classification system, as outlined by Yu and Kim (2013), differentiates El Niño circulation modes based on the location of the initial appearance of warm water in the Equatorial Pacific. Quantitative and qualitative analyses are used to assess whether this classification of El Niño episodes is useful in the context of winter storm impacts in California. There is some evidence that Central Pacific (CP) episodes may be associated with higher levels of rainfall than Eastern Pacific (EP) episodes, owing to increased storm duration. Eastern Pacific episodes, most notably in 1982-1983, and 1997-1998, generated energetic waves and caused severe beach erosion, although nearly as much coastal impact was observed during the 2009-2010 CP El Niño episode. Overall the influence of circulation mode appeared to be weak, variation between El Niño years appears to be more strongly determined by the tracks and characteristics of individual winter storms than by overall mode of El Niño circulation. However, since winter storms are the only significant source of precipitation and are the primary cause of episodic coastal erosion in Southern California, further study of the differing effects of EP and CP El Niño episodes is crucial for planning for the future in the region.