Intracellular Ca2+ oscillation frequency and amplitude modulation mediate epithelial apical and basolateral membranes crosstalk.

Since the early seminal studies on epithelial solute transport, it has been understood that there must be crosstalk among different members of the transport machinery to coordinate their activity and, thus, generate localized electrochemical gradients that force solute flow in the required direction that would otherwise be thermodynamically unfavorable. However, mechanisms underlying intracellular crosstalk remain unclear. We present evidence that crosstalk between apical and basolateral membrane transporters is mediated by intracellular Ca2+ signaling in insect renal epithelia. Ion flux across the basolateral membrane is encoded in the intracellular Ca2+ oscillation frequency and amplitude modulation and that information is used by the apical membrane to adjust ion flux accordingly. Moreover, imposing experimentally generated intracellular Ca2+ oscillation modulation causes cells to predictably adjust their ion transport properties. Our results suggest that intracellular Ca2+ oscillation frequency and amplitude modulation encode information on transmembrane ion flux that is required for crosstalk.

cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine.

A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na+ channel (ENaC), yielding increased Na+ reabsorption and airway dehydration. We use a non-invasive self-referencing Na+-selective microelectrode technique to measure Na+ transport across individual folds of distal airway surface epithelium preparations from CFTR-/- (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na+ transport that are unaffected by the ENaC blocker amiloride. However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na+, while CFTR-/- tissues absorb small, but potentially important, amounts of Na+. In cAMP-stimulated conditions, amiloride inhibits Na+ absorption in CFTR-/- tissues but does not affect secretion in WT tissues. Our results are consistent with the hypothesis that ENaC-mediated Na+ absorption may contribute to dehydration of CF distal airways.

Nebulized hypertonic saline triggers nervous system-mediated active liquid secretion in cystic fibrosis swine trachea.

Inhaled hypertonic saline (HTS) treatment is used to improve lung health in patients with cystic fibrosis (CF). The current consensus is that the treatment generates an osmotic gradient that draws water into the airways and increases airway surface liquid (ASL) volume. However, there is evidence that HTS may also stimulate active secretion of ASL by airway epithelia through the activation of sensory neurons. We tested the contribution of the nervous system and airway epithelia on HTS-stimulated ASL height increase in CF and wild-type swine airway. We used synchrotron-based imaging to investigate whether airway neurons and epithelia are involved in HTS treatment-triggered ASL secretion in CFTR-/- and wild-type swine. We showed that blocking parasympathetic and sensory neurons in airway resulted in ~50% reduction of the effect of HTS treatment on ASL volume in vivo. Incubating tracheal preparations with inhibitors of epithelial ion transport across airway decreased secretory responses to HTS treatment. CFTR-/- swine ex-vivo tracheal preparations showed substantially decreased secretory response to HTS treatment after blockage of neuronal activity. Our results indicated that HTS-triggered ASL secretion is partially mediated by the stimulation of airway neurons and the subsequent activation of active epithelia secretion; osmosis accounts for only ~50% of the effect.

Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia.

Phase and precession evolution in the Burgers equation.

We present a phenomenological study of the phase dynamics of the one-dimensional stochastically forced Burgers equation, and of the same equation under a Fourier mode reduction on a fractal set. We study the connection between coherent structures in real space and the evolution of triads in Fourier space. Concerning the one-dimensional case, we find that triad phases show alignments and synchronisations that favour energy fluxes towards small scales --a direct cascade. In addition, strongly dissipative real-space structures are associated with entangled correlations amongst the phase precession frequencies and the amplitude evolution of Fourier triads. As a result, triad precession frequencies show a non-Gaussian distribution with multiple peaks and fat tails, and there is a significant correlation between triad precession frequencies and amplitude growth. Links with dynamical systems approach are briefly discussed, such as the role of unstable critical points in state space. On the other hand, by reducing the fractal dimension D of the underlying Fourier set, we observe: i) a tendency toward a more Gaussian statistics, ii) a loss of alignment of triad phases leading to a depletion of the energy flux, and iii) the simultaneous reduction of the correlation between the growth of Fourier mode amplitudes and the precession frequencies of triad phases.

How social interactions affect emotional memory accuracy: Evidence from collaborative retrieval and social contagion paradigms.

In daily life, emotional events are often discussed with others. The influence of these social interactions on the veracity of emotional memories has rarely been investigated. The authors (Choi, Kensinger, & Rajaram Memory and Cognition, 41, 403-415, 2013) previously demonstrated that when the categorical relatedness of information is controlled, emotional items are more accurately remembered than neutral items. The present study examined whether emotion would continue to improve the accuracy of memory when individuals discussed the emotional and neutral events with others. Two different paradigms involving social influences were used to investigate this question and compare evidence. In both paradigms, participants studied stimuli that were grouped into conceptual categories of positive (e.g., celebration), negative (e.g., funeral), or neutral (e.g., astronomy) valence. After a 48-hour delay, recognition memory was tested for studied items and categorically related lures. In the first paradigm, recognition accuracy was compared when memory was tested individually or in a collaborative triad. In the second paradigm, recognition accuracy was compared when a prior retrieval session had occurred individually or with a confederate who supplied categorically related lures. In both of these paradigms, emotional stimuli were remembered more accurately than were neutral stimuli, and this pattern was preserved when social interaction occurred. In fact, in the first paradigm, there was a trend for collaboration to increase the beneficial effect of emotion on memory accuracy, and in the second paradigm, emotional lures were significantly less susceptible to the "social contagion" effect. Together, these results demonstrate that emotional memories can be more accurate than nonemotional ones even when events are discussed with others (Experiment 1) and even when that discussion introduces misinformation (Experiment 2).

Older adults can suppress unwanted memories when given an appropriate strategy.

Memory suppression refers to the ability to exclude distracting memories from conscious awareness, and this ability can be assessed with the think/no-think paradigm. Recent research with older adults has provided evidence suggesting both intact and deficient memory suppression. The present studies seek to understand the conditions contributing to older adults' ability to suppress memories voluntarily. We report 2 experiments indicating that the specificity of the think/no-think task instructions contributes to older adults' suppression success: When older adults receive open-ended instructions that require them to develop a retrieval suppression strategy on their own, they show diminished memory suppression compared with younger adults. Conversely, when older adults receive focused instructions directing them to a strategy thought to better isolate inhibitory control, they show suppression-induced forgetting similar to that exhibited by younger adults. Younger adults demonstrate memory suppression regardless of the specificity of the instructions given, suggesting that the ability to select a successful suppression strategy spontaneously may be compromised in older adults. If so, this deficit may be associated with diminished control over unwanted memories in naturalistic settings if impeded strategy development reduces the successful deployment of inhibitory control.

Serotonin triggers cAMP and PKA-mediated intracellular calcium waves in Malpighian tubules of Rhodnius prolixus.

Rhodnius prolixus is a hematophagous insect vector of Chagas disease capable of ingesting up to 10 times its unfed body weight in blood in a single meal. The excess water and ions ingested with the meal are expelled through a rapid postprandial diuresis driven by the Malpighian tubules. Diuresis is triggered by at least two diuretic hormones, a CRF-related peptide and serotonin, which were traditionally believed to trigger cAMP as an intracellular second messenger. Recently, calcium has been suggested to act as a second messenger in serotonin-stimulated Malpighian tubules. Thus, we tested the role of calcium in serotonin-stimulated Malpighian tubules from R. prolixus. Our results show that serotonin triggers cAMP-mediated intracellular Ca(2+) waves that were blocked by incubation in Ca(2+)-free saline containing the cell membrane-permeant Ca(2+) chelator BAPTA-AM, or the PKA blocker H-89. Treatment with 8-Br-cAMP triggered Ca(2+) waves that were blocked by H-89 and BAPTA-AM. Analysis of the secreted fluid in BAPTA-AM-treated tubules showed a 75% reduction in fluid secretion rate with increased K(+) concentration, reduced Na(+) concentration. Taken together, the results indicate that serotonin triggers cAMP and PKA-mediated Ca(2+) waves that are required for maximal ion transport rate.

The use of cone-beam computed tomography to determine cochlear implant electrode position in human temporal bones.

OBJECTIVE: To assess the utility of cone-beam computed tomography (CBCT) imaging in the estimation of cochlear implant (CI) electrode position in implanted temporal bones. STUDY DESIGN: Eight fresh frozen temporal bones were mounted and oriented as for standard surgery and were implanted with Cochlear Slim-Straight (SS) or Contour Advance electrode arrays by 2 CI surgeons. The bones were then imaged using an Accuitomo F170 CBCT scanner (isometric 250 µm voxel size) and were then processed for histologic sectioning (500 µm sections). MAIN OUTCOME MEASURES: The CBCT images and the histologic micrographs (providing the "gold standard") were examined independently by several observers who assessed the scalar position (tympani or vestibuli) of each electrode in each temporal bone specimen. RESULTS: Examination of the histologic micrographs confirmed that all electrodes were positioned within the scala tympani in all 8 bones. Similar judgments were made by the observers rating the CBCT images, except that one of the 2 observers estimated some of the apical electrodes to be located in the scala vestibuli in two of the bones implanted with the SS electrode. CONCLUSION: Cone-beam CT imaging is able to provide a good indication of the scalar position of implanted electrodes, although estimation may be slightly less reliable for apical electrodes and for straight electrode designs. Additional advantages of using CBCT for this purpose are shorter acquisition time and reduction of radiation dose as compared with conventional CT.

The route to an integrative associative memory is influenced by emotion.

Though the hippocampus typically has been implicated in processes related to associative binding, special types of associations--such as those created by integrative mental imagery--may be supported by processes implemented in other medial temporal-lobe or sensory processing regions. Here, we investigated what neural mechanisms underlie the formation and subsequent retrieval of integrated mental images, and whether those mechanisms differ based on the emotionality of the integration (i.e., whether it contains an emotional item or not). Participants viewed pairs of words while undergoing a functional MRI scan. They were instructed to imagine the two items separately from one another ("non-integrative" study) or as a single, integrated mental image ("integrative" study). They provided ratings of how successful they were at generating vivid images that fit the instructions. They were then given a surprise associative recognition test, also while undergoing an fMRI scan. The cuneus showed parametric correspondence to increasing imagery success selectively during encoding and retrieval of emotional integrations, while the parahippocampal gyri and prefrontal cortices showed parametric correspondence during the encoding and retrieval of non-emotional integrations. Connectivity analysis revealed that selectively during negative integration, left amygdala activity was negatively correlated with frontal and hippocampal activity. These data indicate that individuals utilize two different neural routes for forming and retrieving integrations depending on their emotional content, and they suggest a potentially disruptive role for the amygdala on frontal and medial-temporal regions during negative integration.

Age-related changes in associative memory for emotional and nonemotional integrative representations.

Events often include novel combinations of items. Sometimes, through the process of integration, we experience and remember these items as parts of a whole rather than as separate entities. Recent research with younger adults has demonstrated that successfully integrating 2 nonemotional items at encoding, instead of imagining them separately, produces a disproportionately larger associative memory benefit than integrating an emotional and a nonemotional item. In the first study to examine whether age and emotion interact to influence integration, we used 2 measures of integrative success-the ability to successfully retrieve integrations, measured through associative cued recall, and the ability to successfully generate integrated representations at encoding, measured through self report. The cued-recall results (Experiments 1 and 2) revealed that the emotional content of the word pairs interacts to influence the effect of integration on older adults' associative memory, but in the opposite direction of younger adults: Older adults showed no associative retrieval benefit of integration over nonintegration for nonemotional pairs, but they showed a significant integrative benefit for emotional pairs. We also demonstrated (Experiment 2) that encoding time interacts with emotion and integration in different ways for older and younger adults: Putting younger adults under time pressure reduced their success in generating integrated representations at encoding for nonemotional pairs, whereas for older adults it disrupted their ability to generate integrated representations for emotional pairs. We discuss possible age-related differences in the processes used to create emotional and nonemotional integrations.

Oversimplification in the study of emotional memory.

This Short Review critically evaluates three hypotheses about the effects of emotion on memory: First, emotion usually enhances memory. Second, when emotion does not enhance memory, this can be understood by the magnitude of physiological arousal elicited, with arousal benefiting memory to a point but then having a detrimental influence. Third, when emotion facilitates the processing of information, this also facilitates the retention of that same information. For each of these hypotheses, we summarize the evidence consistent with it, present counter-evidence suggesting boundary conditions for the effect, and discuss the implications for future research.

A review of the neural and behavioral consequences for unitizing emotional and neutral information.

A special type of association, called a "unitization," is formed when pieces of information are encoded as a single representation in memory (e.g., "shirt" and "blue" are encoded as a "blue shirt"; Graf and Schacter, 1989) and typically are later reactivated in memory as a single unit, allowing access to the features of multiple related stimuli at once (Bader et al., 2010; Diana et al., 2011). This review examines the neural processes supporting memory for unitizations and how the emotional content of the material may influence unitization. Although associative binding is typically reliant on hippocampal processes and supported by recollection, the first part of this review will present evidence to suggest that when two items are unitized into a single representation, memory for those bound items may be accomplished on the basis of familiarity and without reliance on the hippocampus. The second part of this review discusses how emotion may affect the processes that give rise to unitizations. Emotional information typically receives a mnemonic benefit over neutral information, but the literature is mixed on whether the presence of emotional information impedes or enhances the associative binding of neutral information (reviewed by Mather, 2007). It has been suggested that the way the emotional and neutral details are related together may be critical to whether the neutral details are enhanced or impeded (Mather, 2007; Mather and Sutherland, 2011). We focus on whether emotional arousal aids or inhibits the creation of a unitized representation, presenting preliminary data, and future directions to test empirically the effects of forming and retrieving emotional and neutral unitizations.

The use of cone beam imaging to determine cochlear implant electrode position in human temporal bones.

This paper describes the outcomes of cochlear implantation in eight cadaveric temporal bones using cone-beam CT imaging and histological examination with respect to scalar position of the electrode array.

The effects of emotion and encoding strategy on associative memory.

Research has demonstrated that when discrete pieces of information are integrated together at encoding--imagining two items together as a single entity, for example--there is a mnemonic benefit for their relationship. A separate body of literature has indicated that the presence of emotional information can have an impact on the binding of associated neutral details, in some cases facilitating associative binding (MacKay et al. Memory and cognition 32:474-488, 2004; Mather, perspectives on psychological science 2:33-52, 2007), and in other cases impeding the processing of associated details (Easterbrook, Psychological Review 66:183-201, 1959; Kensinger, Emotion review 1:99-113, 2009). In the present experiments, we investigated how memory for neutral words is affected by the emotionality of the information with which they are presented (whether with an emotional word or a second neutral word) and the encoding context (integrated or nonintegrated strategy). Participants viewed word pairs and were instructed to visualize the items as an integrated unit or to visualize them separately from one another. The results of Experiment 1 showed a disproportionate mnemonic benefit for neutral items that were integrated with other neutral items over those integrated with emotional items. The results of Experiments 2A and 2B showed that this effect interacted with encoding time: When given 2 s to encode, participants showed no effect of integration on memory for neutral-neutral pairs, but showed a significant mnemonic benefit for integrating emotional-neutral pairs. When given 4 or 6 s, the integrative benefit increased significantly for neutral-neutral pairs but decreased for emotional-neutral pairs. These results suggest that creating an integrated mental image of two neutral items requires a more time-consuming process than integrating an emotional and a neutral item, but that extra effort may result in a downstream mnemonic benefit.

Effects of emotion and age on performance during a think/no-think memory task.

Recent studies have demonstrated that young adults can voluntarily suppress information from memory when directed to. After learning novel word pairings to criterion, participants are shown individual words and instructed either to "think" about the associated word, or to put it out of mind entirely ("no-think"). When given a surprise cued recall test, participants typically show impaired recall for no-think words relative to think or "control" (un-manipulated) words. The present study investigated whether this controlled suppression effect persists in an aged population, and examined how the emotionality of the to-be-suppressed word affects suppression ability. Data from four experiments using the think/no-think task demonstrate that older and younger adults can suppress information when directed to (Experiment 1), and the age groups do not differ significantly in this ability. Experiments 2 through 4 demonstrate that both age groups can suppress words that are emotional (positive or negative valence) or neutral. The suppression effect also persists even if participants are tested using independent probe words that are semantically related to the target words but were not the studied cue words (Experiments 3 and 4). These data suggest that the cognitive functioning necessary to suppress information from memory is present in older adulthood, and that both emotional and neutral information can be successfully suppressed from memory.

New cochlear implant coding strategy for tonal language speakers.

Accurate pitch perception on the basis of fundamental frequency patterns is essential for the processing of lexical tones in tonal languages such as Cantonese. Speech intelligibility in Cantonese-speaking CI recipients was compared using current signal processing strategies, which typically result in poor pitch perception, and a new strategy, known as the multi-channel envelope modulation (MEM) strategy, was designed to enhance temporal periodicity cues to the fundamental frequency. Performance of nine postlingually hearing-impaired adult cochlear implant users was measured twice using each strategy, initially after a four week trial, and again after two weeks of use with each strategy. Speech intelligibility in speech-spectrum shaped noise was measured using the Cantonese hearing in noise test. A fixed noise level of 65 dB A was used and the signal-to-noise ratios were fixed at either +10, +15, or +20 dB, depending on the baseline performance of individual subjects using the clinical processor. Self-reported benefit in 18 listening situations and overall preference for strategies were obtained at the end of these trial periods. Results showed poorer speech intelligibility with CIS while results obtained using ACE and MEM were comparable. Unfamiliar place coding might have contributed to poorer performance using CIS. Self-reported benefit across strategies did not differ in most listening situations. Participants preferred ACE for listening overall in daily situations, and a few preferred MEM in noise. Whilst the results did not demonstrate any advantages for speech recognition in noise when using MEM compared to ACE, no degradation in performance was observed. This implies that the form of processing employed by MEM retains similar segmental information to that provided by ACE and that potentially, future variations/optimizations of MEM may lead to some improvement in tone perception.

The influence of breed and mh-genotype on carcass conformation, meat physico-chemical characteristics, and the fatty acid profile of muscle from yearling bulls.

The influence of breed and mh-genotype on carcass conformation, meat physico-chemical characteristics and the fatty acid profile of muscle were studied. Samples from 16 yearling bulls from "Asturiana de los Valles" (AV, n=12) and "Asturiana de la Montaña" (AM, n=4) were collected. AV animals were classified into three groups according to the presence of the gene causing double-muscling (AV double-muscled (mh/mh), n=4; AV heterozygous (mh/+), n=4; AV normal (+/+), n=4). Double-muscled animals displayed better carcass traits, lower total fat (comprised of subcutaneous (SC), intermuscular (IT) and intramuscular (IM) deposits), higher lean, moisture and drip loss, and lighter meat than AV normal animals. Heterozygous animals showed intermediate characteristics. AM animals, being a more rustic and smaller breed, showed lower conformation, higher total fat (SC, IT and IM), lower moisture and darker meat. According to the intramuscular fatty acid profile, mh/mh animals showed a lower proportion of SFA and MUFA, and a higher proportion of PUFA with an equal proportion of CLA in total fatty acid content. The P/S ratio increased with increasing number of mh alleles (or double-muscling character), while no differences between animal groups were found for the n-6/n-3 ratio.