Miracle-dz/UniFAR-FTUs huggingface dataset:
Polysialic Acid Regulates Sympathetic Outflow by Facilitating Information Transfer within the Nucleus of the Solitary Tract

Expression of the large extracellular glycan, polysialic acid (polySia), is restricted in the adult, to brain regions exhibiting high levels of plasticity or remodeling, including the hippocampus, prefrontal cortex, and the nucleus of the solitary tract (NTS). The NTS, located in the dorsal brainstem, receives constant viscerosensory afferent traffic as well as input from central regions controlling sympathetic nerve activity, respiration, gastrointestinal functions, hormonal release, and behavior. Our aims were to determine the ultrastructural location of polySia in the NTS and the functional effects of enzymatic removal of polySia, both in vitro and in vivo. polySia immunoreactivity was found throughout the adult rat NTS. Electron microscopy demonstrated polySia at sites that influence neurotransmission: the extracellular space, fine astrocytic processes, and neuronal terminals. Removing polySia from the NTS had functional consequences. Whole-cell electrophysiological recordings revealed altered intrinsic membrane properties, enhancing voltage-gated K+ currents and increasing intracellular Ca2+. Viscerosensory afferent processing was also disrupted, dampening low-frequency excitatory input and potentiating high-frequency sustained currents at second-order neurons. Removal of polySia in the NTS of anesthetized rats increased sympathetic nerve activity, whereas functionally related enzymes that do not alter polySia expression had little effect. These data indicate that polySia is required for the normal transmission of information through the NTS and that changes in its expression alter sympathetic outflow. polySia is abundant in multiple but discrete brain regions, including sensory nuclei, in both the adult rat and human, where it may regulate neuronal function by mechanisms identified here. SIGNIFICANCE STATEMENT All cells are coated in glycans (sugars) existing predominantly as glycolipids, proteoglycans, or glycoproteins formed by the most complex form of posttranslational modification, glycosylation. How these glycans influence brain function is only now beginning to be elucidated. The adult nucleus of the solitary tract has abundant polysialic acid (polySia) and is a major site of integration, receiving viscerosensory information which controls critical homeostatic functions. Our data reveal that polySia is a determinant of neuronal behavior and excitatory transmission in the nucleus of the solitary tract, regulating sympathetic nerve activity. polySia is abundantly expressed at distinct brain sites in adult, including major sensory nuclei, suggesting that sensory transmission may also be influenced via mechanisms described here. These findings hint at the importance of elucidating how other glycans influence neural function.
MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers

Purpose: Expression of the PGE2 receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 receptor is not known. The present study was conducted to investigate the regulation of EP4 receptor by miRNAs. Experimental Design: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings. Results: We observed an inverse correlation between the levels of miR-101 and EP4 receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 receptor-3'-UTR. In contrast, a mutant EP4 receptor-3'-UTR construct was unaffected. Ectopic expression of miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, the pharmacologic inhibition of EP4 receptor signaling or silencing of EP4 receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 receptor is negatively regulated by miR-101. Conclusions: These data provide new insights in the modulation of EP-4 receptor expression at the post-transcriptional level by miR-101 and suggests therapeutic strategies against miR-101 targets may be warranted.
Perceptual Competition Promotes Suppression of Reward Salience in Behavioral Selection and Neural Representation

Visual attentional selection is influenced by the value of objects. Previous studies have demonstrated that reward-associated items lead to rapid distraction and associated behavioral costs, which are difficult to override with top-down control. However, it has not been determined whether a perceptually competitive environment could render the reward-driven distraction more susceptible to top-down suppression. Here, we trained both genders of human subjects to associate two orientations with high and low magnitudes of reward. After training, we collected fMRI data while the subjects performed a categorical visual search task. The item in the reward-associated orientation served as the distractor, and the relative physical salience between the target and distractor was carefully controlled to modulate the degree of perceptual competition. The behavioral results showed faster searches in the presence of high, relative to low, reward-associated distractors. However, this effect was evident only if the physical salience of the distractor was higher than that of the target, indicating a context-dependent suppression effect of reward salience that relied on high perceptual competition. By analyzing the fMRI data in primary visual cortex, we found that the behavioral pattern of results could be predicted by the suppressed channel responses tuned to the reward-associated orientation in the distractor location, accompanied by increased responses in the midbrain dopaminergic region. Our results suggest that the learned salience of a reward plays a flexible role in solving perceptual competition, enabling the neural system to adaptively modulate the perceptual representation for behavioral optimization. SIGNIFICANCE STATEMENT The predictiveness principle in learning theory suggests that the stimulus with high predictability of reward receives priority in attentional selection. This selection bias leads to difficulties in changing approach behaviors, and thus becomes an important factor related to psychiatric disorders with attentional deficits. Here, we demonstrated that such principle is adaptively implemented in attentional suppression in visual search. We showed that the learned salience induced the suppression of the reward-associated distractor if its competition with the target was strong and could not be readily solved. This behavioral pattern was accompanied by increased midbrain fMRI activity and weakened sensory representation of the reward-associated distractor in V1. Our findings provided direct evidence that our brain flexibly uses learned regularities in attentional control.
A Test of the Stereausis Hypothesis for Sound Localization in Mammals

The relative arrival times of sounds at both ears constitute an important cue for localization of low-frequency sounds in the horizontal plane. The binaural neurons of the medial superior olive (MSO) act as coincidence detectors that fire when inputs from both ears arrive near simultaneously. Each principal neuron in the MSO is tuned to its own best interaural time difference (ITD), indicating the presence of an internal delay, a difference in the travel times from either ear to the MSO. According to the stereausis hypothesis, differences in wave propagation along the cochlea could provide the delays necessary for coincidence detection if the ipsilateral and contralateral inputs originated from different cochlear positions, with different frequency tuning. We therefore investigated the relation between interaural mismatches in frequency tuning and ITD tuning during in vivo loose-patch (juxtacellular) recordings from principal neurons of the MSO of anesthetized female gerbils. Cochlear delays can be bypassed by directly stimulating the auditory nerve; in agreement with the stereausis hypothesis, tuning for timing differences during bilateral electrical stimulation of the round windows differed markedly from ITD tuning in the same cells. Moreover, some neurons showed a frequency tuning mismatch that was sufficiently large to have a potential impact on ITD tuning. However, we did not find a correlation between frequency tuning mismatches and best ITDs. Our data thus suggest that axonal delays dominate ITD tuning. SIGNIFICANCE STATEMENT Neurons in the medial superior olive (MSO) play a unique role in sound localization because of their ability to compare the relative arrival time of low-frequency sounds at both ears. They fire maximally when the difference in sound arrival time exactly compensates for the internal delay: the difference in travel time from either ear to the MSO neuron. We tested whether differences in cochlear delay systematically contribute to the total travel time by comparing for individual MSO neurons the best difference in arrival times, as predicted from the frequency tuning for either ear, and the actual best difference. No systematic relation was observed, emphasizing the dominant contribution of axonal delays to the internal delay.
Physiological and pathophysiological functions of different angiotensins in the brain

The renin–angiotensin system (RAS) is better known for its role in the control of blood pressure, but evidence obtained from animal experiments and clinical trials suggests that it is involved in complex brain functions. It is now well accepted that neuronal AT1 receptors mediate the stimulatory actions of angiotensin II regarding blood pressure and the intake of water and salt. In contrast, neuronal AT2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic AT1 receptors. Angiotensin‐(1‐7) [Ang‐(1‐7)] mediates its antihypertensive effects by stimulating synthesis and release of vasodilator prostaglandins and nitric oxide. New data concerning the receptor types binding angiotensin IV or Ang‐(1‐7) also support the existence of complex site‐specific interactions between multiple angiotensins and multiple receptors in the mediation of important central functions of the RAS. Different angiotensin receptors (AT1, AT2, AT4, Mas) are also present in memory‐relevant structures. The effects of different angiotensins on cognition initiated the search for their mechanisms of action. Studies looking for a possible link between the RAS and brain disorders (stress, anxiety, depression, alcohol abuse, epilepsy, Alzheimer's disease) either inherited or acquired have been reviewed. The therapeutic potential of different angiotensins, as well as the potential use of agents known to influence the RAS, will be considered.
Infra-Slow EEG Fluctuations Are Correlated with Resting-State Network Dynamics in fMRI

Ongoing neuronal activity in the CNS waxes and wanes continuously across widespread spatial and temporal scales. In the human brain, these spontaneous fluctuations are salient in blood oxygenation level-dependent (BOLD) signals and correlated within specific brain systems or “intrinsic-connectivity networks. ” In electrophysiological recordings, both the amplitude dynamics of fast (1–100 Hz) oscillations and the scalp potentials per se exhibit fluctuations in the same infra-slow (0.01–0.1 Hz) frequency range where the BOLD fluctuations are conspicuous. While several lines of evidence show that the BOLD fluctuations are correlated with fast-amplitude dynamics, it has remained unclear whether the infra-slow scalp potential fluctuations in full-band electroencephalography (fbEEG) are related to the resting-state BOLD signals. We used concurrent fbEEG and functional magnetic resonance imaging (fMRI) recordings to address the relationship of infra-slow fluctuations (ISFs) in scalp potentials and BOLD signals. We show here that independent components of fbEEG recordings are selectively correlated with subsets of cortical BOLD signals in specific task-positive and task-negative, fMRI-defined resting-state networks. This brain system-specific association indicates that infra-slow scalp potentials are directly associated with the endogenous fluctuations in neuronal activity levels. fbEEG thus yields a noninvasive, high-temporal resolution window into the dynamics of intrinsic connectivity networks. These results support the view that the slow potentials reflect changes in cortical excitability and shed light on neuronal substrates underlying both electrophysiological and behavioral ISFs.
Survey of the awareness level of nurses about last guidelines 2010 of cardiopulmonary resuscitation (CPR) in educational hospitals.

Aims: Cardiopulmonary resuscitation (CPR) is the most important skill of clinical staff and it is necessary for them to be aware of its last changes. This study had been done to determine the awareness level of nurses of the last 2010 CPR guidelines. Methods: This descriptive cross-sectional study was conducted with 321 samples, which had been chosen with sample randomly method in Kermanshah’s hospitals in 2011. The tools for collecting data were a researcher made questionnaire with face and content and reliability of (r=%74). Data was analyzed by STATA-11 software and ANOVA, Tukay,Tamhane and Bonferoni tests. Results: Level of awareness was classified to: %20.2 excellent, %65.4 good, %14 moderate and %3 weak. There was no significant statistical correlation between level of awareness and age, work experience and graduate degree, but level of awareness was higher in nurses that had experience of passing CPR training, doing or observing it (p<0.001). The most score of awareness was related to external cardiac massage. Conclusion: It is suggested that to teach CPR according to guidelines of 2010 in nurses postgraduate training and to have more emphasis on electroshock therapy and Automatic External Defibrillation (AED), Laryngeal Mask Airway (LMA) and combitube intubations, reasons of termination and undoing of CPR interaoseus injection and induced hypothermia. Please cite this paper as: Poormirza K. R. , Saboor B. , Naderipoor A. , Almasi A. , Goodarzi A. , Mirzaii M. ; Survey of the awareness level of nurses about last guidelines of cardiopulmonary resuscitation (CPR) in educational hospitals. Iran J Crit Care Nurs 2012;5(2):7786.
VEGF inhibitors for the treatment of neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical activator of angiogenesis in neovascular AMD is VEGF. Several therapies have been and are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, VEGF receptor decoy VEGF Trap, small interfering RNA-based therapies bevasiranib and AGN211745, sirolimus, and tyrosine kinase inhibitors including vatalanib, pazopanib, TG100801, TG101095, AG013958 and AL39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still investigational in nature offer the potential for further advances.
Interindividual variability in oral antidiabetic drug disposition and response: the role of drug transporter polymorphisms

Background: Numerous effective oral pharmacologic therapies are available to treat type 2 diabetes. However, a substantial number of patients do not achieve the expected glucose-lowering response, or may be predisposed to adverse effects, from these agents. The application of pharmacogenetics to the field of type 2 diabetes is one step towards the goal of improved pharmacotherapeutic management of this progressive disease. Methods: A PubMed literature search was conducted to identify clinical studies that have examined the extent to which drug-transporter gene polymorphisms influence interindividual variability in oral antidiabetic drug disposition and response in humans. Results/conclusion: Available data suggest that drug transporters play an important role in the disposition of some oral antidiabetic drugs in the body, particularly the meglitinides and metformin. Moreover, polymorphisms in genes encoding drug transport proteins may alter the pharmacodynamic profile of these agents. Drug transporters, drug-metabolizing enzymes, and drug targets each play a distinct and important role in the disposition and action of many oral antidiabetic agents. Thus, future studies may need to take a pharmacogenomic (i.e., multiple gene) approach in order to comprehensively understand the extent to which genetic variation contributes to interindividual differences in oral antidiabetic drug clinical pharmacology.
Comparative Strength and Dendritic Organization of Thalamocortical and Corticocortical Synapses onto Excitatory Layer 4 Neurons

Thalamus is a potent driver of cortical activity even though cortical synapses onto excitatory layer 4 neurons outnumber thalamic synapses 10 to 1. Previous in vitro studies have proposed that thalamocortical (TC) synapses are stronger than corticocortical (CC) synapses. Here, we investigated possible anatomical and physiological differences between these inputs in the rat in vivo. We developed a high-throughput light microscopy method, validated by electron microscopy, to completely map the locations of synapses across an entire dendritic tree. This demonstrated that TC synapses are slightly more proximal to the soma than CC synapses, but detailed compartmental modeling predicted that dendritic filtering does not appreciably favor one synaptic class over another. Measurements of synaptic strength in intact animals confirmed that both TC and CC synapses are weak and approximately equivalent. We conclude that thalamic effectiveness does not rely on enhanced TC strength, but rather on coincident activation of converging inputs.
Evolution and the Genetics of Populations. Volume 2. The theory of gene frequencies . By Sewall Wright. Pp. 511. (University of Chicago Press, London 1970.) Price £6·75.

frequency changes resulting from altered environment; but due to intermixture and difficulties in determining the initial frequencies in the parental populations this is a treacherous approach. The book is solidly bound and has clear, readable type. Few typographical errors were noticed. It will certainly remain a valuable work of reference for many years. As usual nowadays, it is too expensive for most of us but one can recommend human biologists to borrow it from the library.
Rat Orbitofrontal Cortex Separately Encodes Response and Outcome Information during Performance of Goal-Directed Behavior

Orbitofrontal cortex (OFC) neurons encode rewards and the cues that predict them, providing a neural substrate for outcome expectancy, an important component of goal-directed behavior in animals and humans. Here, we recorded and analyzed single units from rat lateral OFC during performance of a task in which the encoding of an expected rewarding outcome could be isolated from the response made in obtaining it. We found concurrent encoding of the expected outcome and the behavioral response in mostly separate populations of OFC units, in each phase of task performance: odor sampling, behavioral response, and waiting during the delay before reward delivery. Population analyses showed that outcome encoding broadly spanned across each behavioral phase, whereas response-selective firings were time-locked to the behavioral events, especially the completion of the behavioral response. A significant subset of outcome-selective units maintained selective firings from either odor sampling or response initiation until reward delivery. In contrast, response-selective units typically showed transient activation time locked to the behavioral events and were less likely to maintain selective firings across behavioral phases than outcome-selective units. These data demonstrate a broader role of OFC information processing in goal-directed behavior, beyond its widely recognized role in outcome expectancy.
Adenocarcinoma of the duodenum: Factors influencing survival

The records of 66 patients with histologically proven adenocarcinoma of the duodenum were reviewed retrospectively to determine factors influencing survival. The parameters studied were age, sex, weight loss, jaundice, anaemia, duodenal stenosis, type of surgical procedure, tumour size and location, depth of parietal invasion, presence and location of lymph node metastases, and pancreatic invasion. These factors were assessed in a group of 46 patients who underwent curative resection of the tumour; 20 patients who received palliative procedures were excluded from statistical analysis. Survival curves were established by the Kaplan‐Meier method and compared by the Mantel‐Haentszel test. The actuarial 3‐ and 5‐year survival rates of patients undergoing curative resection were 59 and 45 per cent respectively. None of the prognostic factors studied influenced survival. These results indicate that resection of adenocarcinoma of the duodenum should be performed whenever possible, even in the presence of lymph node metastasis and pancreatic spread.