Miracle-dz/UniFAR-FTUs huggingface dataset:
An Arabidopsis GPI-Anchor Plasmodesmal Neck Protein with Callose Binding Activity and Potential to Regulate Cell-to-Cell Trafficking[W]

Plasmodesmata (Pds) traverse the cell wall to establish a symplastic continuum through most of the plant. Rapid and reversible deposition of callose in the cell wall surrounding the Pd apertures is proposed to provide a regulatory process through physical constriction of the symplastic channel. We identified members within a larger family of X8 domain–containing proteins that targeted to Pds. This subgroup of proteins contains signal sequences for a glycosylphosphatidylinositol linkage to the extracellular face of the plasma membrane. We focused our attention on three closely related members of this family, two of which specifically bind to 1,3-β-glucans (callose) in vitro. We named this family of proteins Pd callose binding proteins (PDCBs). Yellow fluorescent protein-PDCB1 was found to localize to the neck region of Pds with potential to provide a structural anchor between the plasma membrane component of Pds and the cell wall. PDCB1, PDCB2, and PDCB3 had overlapping and widespread patterns of expression, but neither single nor combined insertional mutants for PDCB2 and PDCB3 showed any visible phenotype. However, increased expression of PDCB1 led to an increase in callose accumulation and a reduction of green fluorescent protein (GFP) movement in a GFP diffusion assay, identifying a potential association between PDCB-mediated callose deposition and plant cell-to-cell communication.
Neuronal Ca2+-Activated K+ Channels Limit Brain Infarction and Promote Survival

Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca2+ ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels in acute focal cerebral ischemia, we performed middle cerebral artery occlusion (MCAO) in mice lacking BK channels (homozygous mice lacking the BK channel alpha subunit, BK−/−). MCAO was performed in BK−/− and WT mice for 90 minutes followed by a 7-hour-reperfusion period. Coronal 1 mm thick sections were stained with 2,3,5-triphenyltetrazolium chloride to reveal the infarction area. We found that transient focal cerebral ischemia by MCAO produced larger infarct volume, more severe neurological deficits, and higher post-ischemic mortality in BK−/− mice compared to WT littermates. However, the regional cerebral blood flow was not significantly different between genotypes as measured by Laser Doppler (LD) flowmetry pre-ischemically, intra-ischemically, and post-ischemically, suggesting that the different impact of MCAO in BK−/− vs. WT was not due to vascular BK channels. Furthermore, when NMDA was injected intracerebrally in non-ischemic mice, NMDA-induced neurotoxicity was found to be larger in BK−/− mice compared to WT. Whole-cell patch clamp recordings from CA1 pyramidal cells in organotypic hippocampal slice cultures revealed that BK channels contribute to rapid action potential repolarization, as previously found in acute slices. When these cultures were exposed to ischemia-like conditions this induced significantly more neuronal death in BK−/− than in WT cultures. These results indicate that neuronal BK channels are important for protection against ischemic brain damage.
The Posterior Parietal Cortex Subserves Precise Motor Timing in Professional Drummers

The synchronization task is a well-established paradigm for the investigation of motor timing with respect to an external pacing signal. It requires subjects to synchronize their finger taps in synchrony with a regular metronome. A specific significance of the posterior parietal cortex (PPC) for superior synchronization in professional drummers has been suggested. In non-musicians, modulation of the excitability of the left PPC by means of transcranial direct current stimulation (tDCS) modulates synchronization performance of the right hand. In order to determine the significance of the left PPC for superior synchronization in drummers, we here investigate the effects of cathodal and anodal tDCS in 20 professional drummers on auditory-motor synchronization of the right hand. A continuation and a reaction time task served as control conditions. Moreover, the interaction between baseline performance and tDCS polarity was estimated in precise as compared to less precise synchronizers according to median split. Previously published data from 16 non-musicians were re-analyzed accordingly in order to highlight possible differences of tDCS effects in drummers and non-musicians. TDCS was applied for 10 min with an intensity of 0.25 mA over the left PPC. Behavioral measures were determined prior to and immediately after tDCS. In drummers the overall analysis of synchronization performance revealed significantly larger tap-to-tone asynchronies following anodal tDCS with the tap preceding the tone replicating findings in non-musicians. No significant effects were found on control tasks. The analysis for participants with large as compared to small baseline asynchronies revealed that only in drummers with small asynchronies tDCS interfered with synchronization performance. The re-analysis of the data from non-musicians indicated the reversed pattern. The data support the hypothesis that the PPC is involved in auditory-motor synchronization and extend previous findings by showing that its functional significance varies with musical expertise.
Incorporation of oat β-glucan in pasta and the effect on product quality

Consumers’ growing interest in healthy food products has opened up a new market for the food industry. In an attempt to exploit this market there is a constant search for health promoting ingredients which can be incorporated into functional food products. The cereal fibre mixed-linkage (1→3), (1→4)-β-D-glucan has provoked a special interest due to well documented health benefits and approved health claims. This project aimed at developing pasta with high content of oat β-glucan and to evaluate how incorporation of β-glucan affects cooking quality, colour and sensory properties of semolina pasta. A secondary objective was to review the literature regarding prebiotic potential of cereal β-glucans. Pasta was produced by substituting durum semolina with different levels of β-glucan rich wholegrain oat flour or oat bran concentrate. For each β-glucan source, three tagli-atelle samples containing 1%, 2%, or 3% β-glucan were produced. A sample containing both oat flour and oat bran concentrate was also developed. Cooking quality was evaluated by measuring optimal cooking time, cooking loss and water absorption. Stickiness, firmness, elasticity, grain flavour and colour were also evaluated. Generally, addition of β-glucan was found to increase cooking loss, decrease elasticity and to reduce the brightness and yellowness of pasta. The effect was dependent both on the source of β-glucan, and on the level of incorporation. Overall, oat flour had a negative impact on pasta quality, while pasta with oat bran concentrate showed quality characteristics similar to the control. This study suggests that the use of oat fractions to replace semolina may be possible in order to obtain pasta with high content of β-glucan and potential health benefits. The results also suggest that it is possible to produce acceptable pasta which fulfils the criteria for health claims regarding β-glucan and maintained and/or reduced cholesterol levels. Regarding prebiotic effect of β-glucan enriched products the evidence is still insufficient and more in vivo studies are required to determine if β-glucan selectively promotes growth and activity of probiotic bacteria.
MicroRNA Regulation of Molecular Networks Mapped by Global MicroRNA, mRNA, and Protein Expression in Activated T Lymphocytes

MicroRNAs (miRNAs) regulate specific immune mechanisms, but their genome-wide regulation of T lymphocyte activation is largely unknown. We performed a multidimensional functional genomics analysis to integrate genome-wide differential mRNA, miRNA, and protein expression as a function of human T lymphocyte activation and time. We surveyed expression of 420 human miRNAs in parallel with genome-wide mRNA expression. We identified a unique signature of 71 differentially expressed miRNAs, 57 of which were previously not known as regulators of immune activation. The majority of miRNAs are upregulated, mRNA expression of these target genes is downregulated, and this is a function of binding multiple miRNAs (combinatorial targeting). Our data reveal that consideration of this complex signature, rather than single miRNAs, is necessary to construct a full picture of miRNA-mediated regulation. Molecular network mapping of miRNA targets revealed the regulation of activation-induced immune signaling. In contrast, pathways populated by genes that are not miRNA targets are enriched for metabolism and biosynthesis. Finally, we specifically validated miR-155 (known) and miR-221 (novel in T lymphocytes) using locked nucleic acid inhibitors. Inhibition of these two highly upregulated miRNAs in CD4+ T cells was shown to increase proliferation by removing suppression of four target genes linked to proliferation and survival. Thus, multiple lines of evidence link top functional networks directly to T lymphocyte immunity, underlining the value of mapping global gene, protein, and miRNA expression.
Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

Objectives To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Materials and methods Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Results Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P<0.0001, P=0.015, and P<0.01, respectively). Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups (P=0.017 and P=0.001; P<0.01 and P<0.0001). Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I/R group (P<0.0001). Conclusion Alprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury.
Neural-Induced Human Mesenchymal Stem Cells Promote Cochlear Cell Regeneration in Deaf Guinea Pigs

Objectives In mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae. Methods HMSCs were isolated from the bone marrow which was obtained from the mastoid process during mastoidectomy for ear surgery. Following neural induction with basic fibroblast growth factor and forskolin, we studied the several neural marker and performed electrophysiological analysis. NI-hMSCs were transplanted into the neomycin treated deafened guinea pig cochlea. Engraftment of NI-hMSCs was evaluated immunohistologically at 8 weeks after transplantation. Results Following neural differentiation, hMSCs expressed high levels of neural markers, ionic channel markers, which are important in neural function, and tetrodotoxin-sensitive voltage-dependent sodium currents. After transplantation into the scala tympani of damaged cochlea, NI-hMSCs-injected animals exhibited a significant increase in the number of SGNs compared to Hanks balanced salt solution-injected animals. Transplanted NI-hMSCs were found within the perilymphatic space, the organ of Corti, along the cochlear nerve fibers, and in the spiral ganglion. Furthermore, the grafted NI-hMSCs migrated into the spiral ganglion where they expressed the neuron-specific marker, NeuN. Conclusion The results show the potential of NI-hMSCs to give rise to replace the lost cochlear cells in hearing loss mammals.
The role of the positive emotional attractor in vision and shared vision: toward effective leadership, relationships, and engagement

Personal and shared vision have a long history in management and organizational practices yet only recently have we begun to build a systematic body of empirical knowledge about the role of personal and shared vision in organizations. As the introductory paper for this special topic in Frontiers in Psychology, we present a theoretical argument as to the existence and critical role of two states in which a person, dyad, team, or organization may find themselves when engaging in the creation of a personal or shared vision: the positive emotional attractor (PEA) and the negative emotional attractor (NEA). These two primary states are strange attractors, each characterized by three dimensions: (1) positive versus negative emotional arousal; (2) endocrine arousal of the parasympathetic nervous system versus sympathetic nervous system; and (3) neurological activation of the default mode network versus the task positive network. We argue that arousing the PEA is critical when creating or affirming a personal vision (i.e., sense of one’s purpose and ideal self). We begin our paper by reviewing the underpinnings of our PEA–NEA theory, briefly review each of the papers in this special issue, and conclude by discussing the practical implications of the theory.
External and internal constraints on eukaryotic chemotaxis

Chemotaxis, the chemically guided movement of cells, plays an important role in several biological processes including cancer, wound healing, and embryogenesis. Chemotacting cells are able to sense shallow chemical gradients where the concentration of chemoattractant differs by only a few percent from one side of the cell to the other, over a wide range of local concentrations. Exactly what limits the chemotactic ability of these cells is presently unclear. Here we determine the chemotactic response of Dictyostelium cells to exponential gradients of varying steepness and local concentration of the chemoattractant cAMP. We find that the cells are sensitive to the steepness of the gradient as well as to the local concentration. Using information theory techniques, we derive a formula for the mutual information between the input gradient and the spatial distribution of bound receptors and also compute the mutual information between the input gradient and the motility direction in the experiments. A comparison between these quantities reveals that for shallow gradients, in which the concentration difference between the back and the front of a 10-μm-diameter cell is <5%, and for small local concentrations (<10 nM) the intracellular information loss is insignificant. Thus, external fluctuations due to the finite number of receptors dominate and limit the chemotactic response. For steeper gradients and higher local concentrations, the intracellular information processing is suboptimal and results in a smaller mutual information between the input gradient and the motility direction than would have been predicted from the ligand–receptor binding process.
Sutureless coronary anastomosis with an anastomotic device and tissue adhesive in off-pump porcine coronary bypass grafting.

OBJECTIVE In the search for a facilitated coronary artery anastomosis, we assessed the feasibility of a hybrid anastomosis technique that used a prototype anastomotic device with an extraluminal frame (crinoline-like) and octyl-cyanoacrylate adhesive. METHODS During off-pump coronary artery bypass grafting in pigs (n = 8), a left internal thoracic artery-right coronary artery anastomosis was constructed and evaluated during the operation and at 5 postoperative weeks. The anastomosis was examined by flow measurement, angiography, intraluminal cast geometric analysis, and histologic analysis. RESULTS Anastomosis construction required 6.2 +/- 1.3 minutes (mean +/- SD). At 5 weeks all anastomoses were fully patent, with minor anastomotic diameter narrowing (median 16%, 15th-85th percentile 16%-26%). After 30-second graft occlusion, median peak hyperemic flow response was 5.0 (15th-85th percentile 4.4-6.5). As a result of complete, streamlining filling of anastomotic wall recesses by neointima formation, more intimal hyperplasia was found in the crinoline-adhesive anastomoses than in sutured control anastomoses. No excessive, lumen-narrowing neointima formation was observed, however. CONCLUSIONS The hybrid coronary anastomosis technique was feasible without any need for dedicated application tools. If technical improvements can be realized, the hybrid technique may provide an alternative to manual suturing.
Best bang for your buck: GPU nodes for GROMACS biomolecular simulations

The molecular dynamics simulation package GROMACS runs efficiently on a wide variety of hardware from commodity workstations to high performance computing clusters. Hardware features are well‐exploited with a combination of single instruction multiple data, multithreading, and message passing interface (MPI)‐based single program multiple data/multiple program multiple data parallelism while graphics processing units (GPUs) can be used as accelerators to compute interactions off‐loaded from the CPU. Here, we evaluate which hardware produces trajectories with GROMACS 4.6 or 5.0 in the most economical way. We have assembled and benchmarked compute nodes with various CPU/GPU combinations to identify optimal compositions in terms of raw trajectory production rate, performance‐to‐price ratio, energy efficiency, and several other criteria. Although hardware prices are naturally subject to trends and fluctuations, general tendencies are clearly visible. Adding any type of GPU significantly boosts a node's simulation performance. For inexpensive consumer‐class GPUs this improvement equally reflects in the performance‐to‐price ratio. Although memory issues in consumer‐class GPUs could pass unnoticed as these cards do not support error checking and correction memory, unreliable GPUs can be sorted out with memory checking tools. Apart from the obvious determinants for cost‐efficiency like hardware expenses and raw performance, the energy consumption of a node is a major cost factor. Over the typical hardware lifetime until replacement of a few years, the costs for electrical power and cooling can become larger than the costs of the hardware itself. Taking that into account, nodes with a well‐balanced ratio of CPU and consumer‐class GPU resources produce the maximum amount of GROMACS trajectory over their lifetime. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
Computational Pathology to Discriminate Benign from Malignant Intraductal Proliferations of the Breast

The categorization of intraductal proliferative lesions of the breast based on routine light microscopic examination of histopathologic sections is in many cases challenging, even for experienced pathologists. The development of computational tools to aid pathologists in the characterization of these lesions would have great diagnostic and clinical value. As a first step to address this issue, we evaluated the ability of computational image analysis to accurately classify DCIS and UDH and to stratify nuclear grade within DCIS. Using 116 breast biopsies diagnosed as DCIS or UDH from the Massachusetts General Hospital (MGH), we developed a computational method to extract 392 features corresponding to the mean and standard deviation in nuclear size and shape, intensity, and texture across 8 color channels. We used L1-regularized logistic regression to build classification models to discriminate DCIS from UDH. The top-performing model contained 22 active features and achieved an AUC of 0.95 in cross-validation on the MGH data-set. We applied this model to an external validation set of 51 breast biopsies diagnosed as DCIS or UDH from the Beth Israel Deaconess Medical Center, and the model achieved an AUC of 0.86. The top-performing model contained active features from all color-spaces and from the three classes of features (morphology, intensity, and texture), suggesting the value of each for prediction. We built models to stratify grade within DCIS and obtained strong performance for stratifying low nuclear grade vs. high nuclear grade DCIS (AUC = 0.98 in cross-validation) with only moderate performance for discriminating low nuclear grade vs. intermediate nuclear grade and intermediate nuclear grade vs. high nuclear grade DCIS (AUC = 0.83 and 0.69, respectively). These data show that computational pathology models can robustly discriminate benign from malignant intraductal proliferative lesions of the breast and may aid pathologists in the diagnosis and classification of these lesions.
Presence of pituitary adenylate cyclase activating polypeptide-38 in human plasma and milk.

OBJECTIVE Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic and multifunctional neuropeptide widely distributed throughout the body. It is involved in the regulation of various physiological and pathophysiological processes, such as reproduction, thermoregulation, motor activity, brain development, neuronal survival, inflammation and pain. Since little is known about its distribution in humans, our aim was to examine PACAP-38 in human plasma. Furthermore, based on the presence of vasoactive intestinal peptide, structurally the closest to PACAP, in milk and PACAP and its receptors in the mammary gland, our aim was to study PACAP-38 in human milk. DESIGN AND METHODS The presence of PACAP-38 was determined by mass spectrometry in plasma samples from healthy male and female volunteers (age: 20-40), as well as in plasma and milk samples from lactating women (age: 20-35). PACAP concentration was measured with a specific and sensitive RIA. RESULTS Our results revealed that PACAP-38 is present in human plasma, its concentration is relatively stable in healthy volunteers and it is not significantly altered by gender, age, food intake or hormonal cycle in females. However, PACAP-38 plasma levels significantly increased in lactating women having 1-6 month-old babies. Moreover, this study is the first which provides evidence for the presence of PACAP-38 in the human milk with levels 5-20-fold greater in the milk whey than in the respective plasma samples. CONCLUSIONS We found PACAP-38 in human plasma and its increase during the first 6 months of the lactation period. A prominent, nearly 10-fold higher concentration of this peptide was detected in human milk. Based on the literature, several important actions of milk-derived PACAP-38 can be suggested such as mammary gland proliferation, nutrient transfer as well as regulation of growth/differentiation of certain tissues of the neonates. The novelty of the present descriptive data provides a basis for further investigations on the mechanism of PACAP-38 secretion in human milk and its functional significance.