Search

Distinguishing syncope from epileptic seizures in patients with sudden loss of consciousness is important. Various blood tests have been used to indicate epileptic seizures in patients with impaired consciousness. This retrospective study aimed to predict the diagnosis of epilepsy in patients with transient loss of consciousness using the initial blood test results. A seizure classification model was constructed using logistic regression, and predictors were selected from a cohort of 260 patients using domain knowledge and statistical methods. The study defined the diagnosis of seizures and syncope based on the consistency of the diagnosis made by an emergency medicine specialist at the first visit to the emergency room and the diagnosis made by an epileptologist or cardiologist at the first outpatient visit using the International Classification of Diseases 10th revision (ICD-10) code. Univariate analysis showed higher levels of white blood cells, red blood cells, hemoglobin, hematocrit, delta neutrophil index, creatinine kinase, and ammonia levels in the seizure group. The ammonia level had the highest correlation with the diagnosis of epileptic seizures in the prediction model. Therefore, it is recommended to be included in the first examination at the emergency room.

Sleep deprivation is known to have adverse effects on various cognitive abilities. In particular, a lack of sleep has been reported to disrupt memory consolidation and cognitive control functions. Here, focusing on long-term memory and cognitive control processes, we review the consistency and reliability of the results of previous studies of sleep deprivation effects on behavioral performance with variations in the types of stimuli and tasks. Moreover, we examine neural response changes related to these behavioral changes induced by sleep deprivation based on human fMRI studies to determine the brain regions in which neural responses increase or decrease as a consequence of sleep deprivation. Additionally, we discuss about the possibility that light as an environmentally influential factor affects our sleep cycles and related cognitive processes.

Background: Post-cardiac arrest syndrome (PCAS) is one of the critical conditions which can result in a more serious brain injury. Early and accurate prognostication is crucial for deciding the patient’s therapeutic plan and setting the treatment goal. This study aimed to establish the prognostication values of quantitative electroencephalography (QEEG) in PCAS patients.Methods: We recruited 183 PCAS patients treated with therapeutic hypothermia. Electroencephalography (EEG) data within 72 hours after cardiac arrest (CA) and clinical data were collected. QEEG analysis including power spectral density (PSD) and connectivity analysis of default mode network (DMN) with imaginary coherence were performed.Results: There were significantly different patterns of PSD between neurologic good and poor outcome groups; absolute and relative power of the alpha 2 and beta 1 frequency (10-15 Hz) bands were increased in all brain regions of good outcome group. However, the relative power of the delta band and higher frequency bands over fast alpha (beta 3 and gamma bands over 20 Hz) were poor outcome markers. We found out that connectivity of DMN were significantly decreased in the poor outcome group compared with the good outcome group.Conclusions: These findings suggest that QEEG analysis could quantify and automate the interpretation of EEG. Furthermore, they can improve the prognostic values for neurologic outcomes relatively accurately and objectively in PCAS patients treated with hypothermia compared with traditional visual grading.

Purpose: The present study sought to identify prognostic factors for breast cancer survival and recurrence using a machine learning approach and electronic medical record data.Methods: We used a machine learning technique called feature selection to identify factors influencing breast cancer prognosis, and factors affecting survival and recurrence in a Cox regression model. Results: History of relapse, type of surgery, diagnostic route, SEER stage, and hormone therapy all affected breast cancer survival. Recurrence of breast cancer was affected by age, history of diabetes, breast reconstruction, pain, breast lumps, nipple discharge, and the presence of other symptoms. According to the survival analysis based on feature selection, patients with diabetes had a significantly higher risk of early recurrence of breast cancer (hazard ratio, 4.8; 95% confidence interval, 2.04–11.2, p < 0.05). Conclusions: The present study identified several factors associated with breast cancer prognosis. While survival was affected by the diagnostic route, recurrence was primarily influenced by breast cancer symptoms and other underlying health conditions. A more accurate and standardized model considering time-to-event data could be developed in the future to evaluate prognostic factors and predict prognoses, and for clinical validation

The recognition of emotional facial expressions is critical for our social interactions. While some prior studies have shown that a high anxiety level is associated with more sensitive recognition of emotion, there are also reports supporting that anxiety did not affect or reduce the sensitivity to the recognition of facial emotions. To reconcile these results, here we investigated whether the effect of individual anxiety on the recognition of facial emotions is dependent on the emotion category and the race of the target faces. We found that, first, there was a significant positive correlation between the individual anxiety level and the recognition sensitivity for angry faces but not for sad or happy faces. Second, while the correlation was significant for both low- and high-intensity angry faces during the recognition of the observer's own-race faces, there was significant correlation only for low-intensity angry faces during the recognition of other-race faces. Collectively, our results suggest that the influence of anxiety on the recognition of facial emotions is flexible depending on the characteristics of the target face stimuli including emotion category and race., Graphical Abstract

The ventral striatum (VS) is considered a key region that flexibly updates recent changes in reward values for habit learning. However, this update process may not serve to maintain learned habitual behaviors, which are insensitive to value changes. Here, using fMRI in humans and single-unit electrophysiology in macaque monkeys we report another role of the primate VS: that the value memory subserving habitual seeking is stably maintained in the VS. Days after object-value associative learning, human and monkey VS continue to show increased responses to previously rewarded objects, even when no immediate reward outcomes are expected. The similarity of neural response patterns to each rewarded object increases after learning among participants who display habitual seeking. Our data show that long-term memory of high-valued objects is retained as a single representation in the VS and may be utilized to evaluate visual stimuli automatically to guide habitual behavior., Ventral striatum is known to be involved in the value update for habit learning. Here, the authors report neural and behavioural correlates for the long-term maintenance of value memory for previously rewarded objects in the ventral striatum of humans and monkeys.

Emotion is thought to cause focal enhancement or distortion of certain components of memory, indicating a complex property of emotional modulation on memory rather than simple enhancement. However, the neural basis for detailed modulation of emotional memory contents has remained unclear. Here has been shown that the information processing of the prefrontal cortex differentially affects sensory representations during experience of emotional information compared with neutral information, using functional magnetic resonance imaging (fMRI). It was found that during perception of emotional pictures, information representation in primary visual cortex (V1) significantly corresponded with the representations in dorsolateral prefrontal cortex (dlPFC). This correspondence was not observed for neutral pictures. Furthermore, participants with greater correspondence between visual and prefrontal representations showed better memory for high‐level semantic components but not for low‐level visual components of emotional stimuli. These results suggest that sensory representation during experience of emotional stimuli, compared with neutral stimuli, is more directly influenced by internally generated higher‐order information from the prefrontal cortex., We show that the visual representation during perception of emotional stimuli reflects more higher‐order information from the prefrontal cortex than that during perception of neutral stimuli. Furthermore, participants with greater correspondence between visual and prefrontal representations showed better memory for high‐level semantic components but not for low‐level visual components of emotional stimuli. Our results suggest that sensory representation during experience of emotional stimuli compared to neutral stimuli, is more directly influenced by internally generated higher‐order information from the prefrontal cortex.

Memory reconsolidation holds great hope for memory modification approaches and clinical treatments of mental disorders associated with maladaptive memories. However, it remains controversial as to whether reconsolidation is a general property of all types of memory. Especially, discrepancies have been reported in research focusing on whether declarative memory undergoes reconsolidation, and whether old memories can be reorganized after retrieval. Here, we discuss how these inconsistent results can be reconciled and what information we need to uncover for the general use of reconsolidation.

Gene therapy is a promising method for the treatment of vascular disease; however, successful strategies depend on the development of safe and effective delivery technologies with specific targeting to a diseased point of vasculature. Reactive oxygen species (ROS) are overproduced by vascular smooth muscle cells (VSMCs) at critical stages of atherosclerosis progression. Therefore, ROS were exploited as a stimulus for vascular targeted gene delivery in this study. A combination of bio-conjugation methods and controlled reverse addition-fragmentation chain-trasfer (RAFT) polymerization was utilized to synthesize a new ROS-cleavable, pH-responsive mPEG113-b-CP5K-b-PDMAEMA42-b-P(DMAEMA22-co-BMA40-co-PAA24) (PPDDBP) polymer as a nanocarrier for plasmid DNA (pDNA) delivery. The ros degradability of PPDDBP polymers was confirmed by SIN-1-mediated cleavage of CP5K peptide linkers through a shift in GPC chromatogram with an appearance of mPEG shoulder peak and an increase in zeta potential (ζ). The polyplex nanocarrier also demonstrated effective PDNA loading, serum stability, and hemocompatibility, indicating its excellent performance under physiological conditions. The polyplexes demonstrated ideal pH responsiveness for endosomal escape and effective ROS responsiveness for improved targeting in an in vitro model of pathogenic VSMCs in terms of both uptake and expression of reporter gene. These data suggest this novel nanocarrier polyplex system is a promising gene delivery tool for preventing or treating areas of high ROS, such as atherosclerotic lesions.

Memory retrieval is thought to depend on interactions between hippocampus and cortex, but the nature of representation in these regions and their relationship remains unclear. Here, we performed an ultra-high field fMRI (7T) experiment, comprising perception, learning and retrieval sessions. We observed a fundamental difference between representations in hippocampus and high-level visual cortex during perception and retrieval. First, while object-selective posterior fusiform cortex showed consistent responses that allowed us to decode object identity across both perception and retrieval one day after learning, object decoding in hippocampus was much stronger during retrieval than perception. Second, in visual cortex but not hippocampus, there was consistency in response patterns between perception and retrieval, suggesting that substantial neural populations are shared for both perception and retrieval. Finally, the decoding in hippocampus during retrieval was not observed when retrieval was tested on the same day as learning suggesting that the retrieval process itself is not sufficient to elicit decodable object representations. Collectively, these findings suggest that while cortical representations are stable between perception and retrieval, hippocampal representations are much stronger during retrieval, implying some form of reorganization of the representations between perception and retrieval.

Thermo-responsive shape memory polymers (SMPs) can be programmed to fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly(e-caprolactone)-co-y%(α-allyl carboxylate e-caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit highly elastic, switch-like shape recovery near 37 °C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. Statement of Significance With the ongoing thrust to make surgeries minimally-invasive, it is prudent to develop new biomaterials that are highly compatible and effective in this workflow. Thermo-responsive shape memory polymers (SMPs) have great potential for minimally-invasive applications because SMP medical devices (e.g. stents, grafts) can fit into small-bore minimally-invasive surgical devices and recover their functional shape when deployed in the body. To realize their potential, it is imperative to devise combinatorial approaches that enable optimization of mechanical, SM, and cellular responses for a particular application. In this study, a new class of thermo-responsive SMPs is created in a robust, facile manner with readily tunable material properties. Materials exhibit excellent, switch-like shape recovery near body temperature and promising biocompatibility for minimally-invasive vascular applications.

Top-down signals can influence our visual perception by providing guidance on information processing. Especially, top-down control between two basic frameworks, “Individuation” and “grouping”, is critical for information processing during face perception. Individuation of faces supports identity recognition while grouping subserves higher category level face perception such as race or gender. However, it still remains elusive how top-down dependent control between individuation and grouping affects cortical representations during face perception. Here we performed an fMRI experiment to investigate whether representations across early and high-level visual areas can be altered by top-down control between individuation and grouping process during face perception. Focusing on neural response patterns across the early visual cortex (EVC) and the face-selective area (the fusiform face area (FFA)), we found that the discriminability of individual faces from the response patterns was strong in the FFA but weak in the EVC during the individuation task whereas the EVC but not the FFA showed significant face discrimination during the grouping tasks. Thus, these findings suggest that the representation of face information across the early and high-level visual cortex is flexible depending on the top-down control of the perceptual framework between individuation and grouping.

Generalization of learned fear has been considered to be critical for our survival. Patients with anxiety problems show overgeneralization of learned fear, as reflected by defensive physiological responses to harmless stimuli. Together with these physiological responses, conscious feeling of fear is a seminal part of emotional process that is directly related to the suffering of anxiety patients. However, the effect of anxiety on the generalization of conscious feeling remains unclear. We thus focused on the question whether the generalization of conscious feeling of fear depends on individual anxiety level in nonpatient participants. To address this question, we developed a fear generalization paradigm using natural scene images. We found that subjective feeling of fear was generalized to similar stimuli with the conditioned stimuli (CS), and that this generalization of conscious fear was positively correlated with the level of individual anxiety. Anxiety and depression frequently co-occur, but the individual depression level was not correlated with the fear generalization. These suggest that individual anxiety level mainly affects the generalization of conscious fear., Graphical Abstract

Peripheral artery disease (PAD) is characterized by vessel occlusion and ischemia in the limbs. Treatment for PAD with surgical interventions has been showing limited success. Moreover, recent clinical trials with treatment of angiogenic growth factors proved ineffective as increased angiogenesis triggered severe inflammation in a proportionally coupled fashion. Hence, the overarching goal of this research was to address this issue by developing a biomaterial system that enables controlled, dual delivery of pro-angiogenic C16 and anti-inflammatory Ac-SDKP peptides in a minimally-invasive way. To achieve the goal, a peptide-loaded injectable microgel system was developed and tested in a mouse model of PAD. When delivered through multiple, low volume injections, the combination of C16 and Ac-SDKP peptides promoted angiogenesis, muscle regeneration, and perfusion recovery, while minimizing detrimental inflammation. Additionally, this peptide combination regulated inflammatory TNF-α pathways independently of MMP-9 mediated pathways of angiogenesis in vitro, suggesting a potential mechanism by which angiogenic and inflammatory responses can be uncoupled in the context of PAD. This study demonstrates a translatable potential of the dual peptide-loaded injectable microgel system for PAD treatment.

Broad band and wide area satellite communication has advantage that can be always communicate with anyone regardless of time and space. In the other hands, its communication quality is easy to be affected by interference signals. Due to the fact that interference signal can be transmitted from everywhere, it's hard to find the illegal source of signal and it has huge influence. In this paper, with this influence of interference signal, we introduce the interference rejection method, implementation and test result in the digital satellite communication processing the signal using variety of digital method. It will be useful information to improve the interference rejection function and also be helpful on the field of satellite communication. ※ 본 연구는 방위사업청 및 국방과학연구소의 디지털중계기 핵심기술사업의 연구결과로 수행되었음 ° First Author and Corresponding Author : 삼성탈레스(주) C4I연구소, changyoung.lee@samsung.com, 정회원 * 삼성탈레스(주) C4I연구소, jehyun.jun@samsung.com, suehyun.lee@samsung.com ** 국방과학연구소, hkseo@add.re.kr, khsleo@add.re.kr, jhwill@add.re.kr 논문번호:KICS2013-08-338, 접수일자:2013년 8월 19일, 심사일자 : 2013년 10월 22일, 최종논문접수일자 : 2013년 12월 18일 I. 서 론 위성 통신은 광대역성과 광역성의 특징을 가지고 있다. 통신 위성 중계기는 수십MHz 이상의 대역폭을 사용하여 영상 신호와 고속 디지털 회선 신호를 쉽게 전송할 수 있으며 위성의 빔 커버리지 범위에 있는 지 역이면 어디에서나 전파 송수신이 가능하다. 이러한 광대역성과 광역성을 가지고 있는 위성통신의 특성은 시간과 공간에 관계없이 누구와도 통신할 수 있다는 장점이 있는 반면, 어디서나 통신방해가 가능해 간섭 논문 / 디지털 위성중계기를 이용한 간섭제거기능 설계 및 구현 37 신호에 항상 영향을 받을 수 있는 특징을 가지고 있 다. 특히 위성통신의 광대역 주파수 대역에 불법 광대 역주파수 간섭이 들어오게 될 경우 어느 특정 수신자 가 아닌 전지역을 상대로 송수신이 가능하기에 불법 광대역 주파수원을 찾기가 매우 어렵다. 또한 위성링 크는 개별 가입자 통신개념보다는 Trunk Line1)개념 으로 운용되므로(주파수자원도 지역별로 운영되는 지 상주파수와 다르게 광역주파수 자원을 사용), 간섭신 호가 전체망에 미치는 영향성은 지상망에서 간섭신호 가 국지적으로 미치는 영향과는 비교할 수 없을 정도 로 크고 심각하다. Fig. 1. Trunk, Satellite link of Trunk Concept 게다가 불법 광대역주파수를 높은 파워로 송출할 경우, 위성의 중계기가 포화되거나 전체 중계기 차원 에서 전력손실(운영자원 손실)이 발생하게 되는 특징 을 가지고 있다. 이런 영향성에 따라 위성통신에서는 간섭제거를 위하여 통신위성(중계기)에서의 대응을 주로 수행한다. 통신 중계기는 신호처리 방식에 따라 아날로그(transparent 또는 bent-pipe) 통신 중계기과 디지털 통신 중계기로 구분될 수 있다. 즉, 아날로그 통신 중계기는 위성에서 수신되는 상향링크 신호를 단순히 아날로그적으로 증폭/주파수변환 시켜 지상으 로 재송신하는 기능을 수행하며, 디지털 통신 중계기 는 상향링크 아날로그 신호를 디지털 신호로 변환하 여 여러 가지 형태로 디지털 신호처리 후 지상으로 송 신하는 기능을 수행한다. 디지털 통신위성은 또한 신 호처리 방식에 따라 재생형(regenerative)과 수동형 (digital transparent)으로 나뉠수 있다. 디지털 통신 중계기는 상향링크 잡음의 최소화, 중 계기의 비선형특성 최소화, 하향링크시 전력분배 손실 1) 간선(幹線, Trunk Line) 교환대와 교환대 간에 연결되어 교 환대에 가입된 가입자를 상호 연결(통화)시키는 통신 회선 제거, 효율적 위성자원관리, 간섭신호의 제거등 많은 장점이 있다. 재생형 디지털 통신 중계기는 추가로 상 향링크 시 발생되는 심볼간/인접채널간 간섭을 하향링 크에서 완전 분리시킬 수 있는 장점이 있으나 상향링 크 신호를 복조하여야 하므로 위성 발사 이전에 지상 단말과의 변/복조방식을 확정시켜야 하는 부담이 있 다. 이에 반해 수동형 디지털 통신 중계기는 변/복조 방식에 무관하게 스위칭 및 부채널간 증폭만 수행하 므로 이런 부담은 없다. [2] 본 논문에서는 위성통신에서의 간섭신호에 의한 영 향을 최소화하기 위해, 수동형 위성 디지털중계기를 이용한 간섭제거 방식 소개 및 실제 구현한 시험 결과 를 소개한다.

Background and Purpose An interarm blood pressure difference (IABD) is independently related to the occurrence of cardiovascular disease and mortality. Cerebral small-vessel diseases (SVDs) are important risk factors for stroke, cognitive dysfunction, and mortality. We aimed to determine whether IABD is related to cerebral SVDs. Methods This study included 1,205 consecutive noncardioembolic ischemic stroke patients as confirmed by brain MRI and simultaneously measured the bilateral brachial blood pressures. We investigated cerebral SVDs based on high-grade white-matter hyperintensities (HWHs), presence of cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) on brain MRI. Results In multivariate logistic regression, an interarm systolic blood pressure difference (IASBD) ≥10 mm Hg was independently related to the existence of HWHs [odds ratio (OR)=1.94, 95% CI=1.32–2.84, p=0.011] and had a tendency to be associated with the presence of HPVSs (OR=1.45, 95% CI=0.49–2.23, p=0.089) and ALIs (OR=1.42, 95% CI=0.96–2.11, p=0.052), but not with the presence of CMBs (OR=1.09, 95% CI=0.73–1.61, p=0.634). In multivariate linear regression adjusted for age, sex, and variables with p

EQM Model Digital transponder applying the Korean's own designing and manufacturing technology has gone through a series of trials and errors during the development. In particular, lack of thermal designs expedience for the vacuum causes variety of errors in designing, assembling transponder and setting up the test at the first thermal vacuum test (TVAC). Since the first TVAC test could not accomplished its aims successfully, so the second TVAC should be performed as make up test with revised Digital transponder. In this paper, the defects that identified in the first TVAC are analyzed and applied solutions and its results at the second TVAC are presented. Using the lessons from the first and second TVAC, we will be able to make more reliable digital transponders in the next phase of project. In addition it also be useful as a reference when we design another satellite payloads.

Recently, significant progress has been made in developing “stimuli-sensitive” biomaterials as a new therapeutic approach to interact with dynamic physiological conditions. Reactive oxygen species (ROS) production has been implicated in important pathophysiological events, such as atherosclerosis, aging, and cancer. ROS are often overproduced locally in diseased cells and tissues, and they individually and synchronously contribute to many of the abnormalities associated with local pathogenesis. Therefore, the advantages of developing ROS-responsive materials extend beyond site-specific targeting of therapeutic delivery, and potentially include navigating, sensing, and repairing the cellular damages via programmed changes in material properties. Here we review the mechanism and development of biomaterials with ROS-induced solubility switch or degradation, as well as their performance and potential for future biomedical applications.

Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF. ApCPEB4 which we have named after its mammalian CPEB4-like homolog lacks a prion-like domain, is responsive to 5-hydroxytryptamine, and is translated (but not transcribed) in an emetine-sensitive, rapamycin-insensitive, and PKA-dependent manner. The ApCPEB4 binds to different target RNAs than does ApCPEB. Knock-down of ApCPEB4 blocked the induction of LTF, whereas overexpression of ApCPEB4 reduces the threshold of the formation of LTF. Thus, our findings suggest that the two different forms of CPEBs play distinct roles in LTF; ApCPEB is required for maintenance of LTF, whereas the ApCPEB4, which lacks a prion-like domain, is required for the initiation of LTF. Electronic supplementary material The online version of this article (doi:10.1186/s13041-016-0271-x) contains supplementary material, which is available to authorized users.

Figure S1. A representative Western blot (left) and quantification (right) of ApCPEB4 in Aplysia pleural ganglia extracts prepared from animals exposed to 5-HT in vivo for 2Â h. Total extracts were prepared at indicated times and 20Â Îźg of proteins were blotted with anti-ApCPEB4 antibodies (left, top panel). The same extracts were also stained with Coomassie blue as loading controls (left, bottom panel). (PDF 49 kb)

The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia , and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval.

During mental imagery, visual representations can be evoked in the absence of “bottom-up” sensory input. Prior studies have reported similar neural substrates for imagery and perception, but studies of brain-damaged patients have revealed a double dissociation with some patients showing preserved imagery in spite of impaired perception and others vice versa. Here, we used fMRI and multi-voxel pattern analysis to investigate the specificity, distribution, and similarity of information for individual seen and imagined objects to try and resolve this apparent contradiction. In an event-related design, participants either viewed or imagined individual named object images on which they had been trained prior to the scan. We found that the identity of both seen and imagined objects could be decoded from the pattern of activity throughout the ventral visual processing stream. Further, there was enough correspondence between imagery and perception to allow discrimination of individual imagined objects based on the response during perception. However, the distribution of object information across visual areas was strikingly different during imagery and perception. While there was an obvious posterior–anterior gradient along the ventral visual stream for seen objects, there was an opposite gradient for imagined objects. Moreover, the structure of representations (i.e. the pattern of similarity between responses to all objects) was more similar during imagery than perception in all regions along the visual stream. These results suggest that while imagery and perception have similar neural substrates, they involve different network dynamics, resolving the tension between previous imaging and neuropsychological studies.

Serotonin (5-HT) plays a critical role in modulating synaptic plasticity in the marine mollusc Aplysia and in the mammalian nervous system. In Aplysia sensory neurons, 5-HT can activate several signal cascades, including PKA and PKC, presumably via distinct types of G protein-coupled receptors. However, the molecular identities of these receptors have not yet been identified. We here report the cloning and functional characterization of a 5-HT receptor that is positively coupled to adenylyl cyclase in Aplysia neurons. The cloned receptor, 5-HT apAC1 , stimulates the production of cAMP in HEK293T cells and in Xenopus oocytes. Moreover, the knockdown of 5-HT apAC1 expression by RNA interference blocked 5-HT-induced cAMP production in Aplysia sensory neurons and blocked synaptic facilitation in nondepressed or partially depressed sensory-to-motor neuron synapses. These data implicate 5-HT apAC1 as a major modulator of learning related synaptic facilitation in the direct sensory to motor neuron pathway of the gill withdrawal reflex.

SummaryRepeated pulses of serotonin (5-HT) induce long-term facilitation (LTF) of the synapses between sensory and motor neurons of the gill-withdrawal reflex in Aplysia. To explore how apCAM downregulation at the plasma membrane and CREB-mediated transcription in the nucleus, both of which are required for the formation of LTF, might relate to each other, we cloned an apCAM-associated protein (CAMAP) by yeast two-hybrid screening. We found that 5-HT signaling at the synapse activates PKA which in turn phosphorylates CAMAP to induce the dissociation of CAMAP from apCAM and the subsequent translocation of CAMAP into the nucleus of sensory neurons. In the nucleus, CAMAP acts as a transcriptional coactivator for CREB1 and is essential for the activation of ApC/EBP required for the initiation of LTF. Combined, our data suggest that CAMAP is a retrograde signaling component that translocates from activated synapses to the nucleus during synapse-specific LTF.

Thermo-responsive shape memory polymers (SMPs) can be programmed to fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly(e-caprolactone)-co-y%(α-allyl carboxylate e-caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit highly elastic, switch-like shape recovery near 37 °C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. Statement of Significance With the ongoing thrust to make surgeries minimally-invasive, it is prudent to develop new biomaterials that are highly compatible and effective in this workflow. Thermo-responsive shape memory polymers (SMPs) have great potential for minimally-invasive applications because SMP medical devices (e.g. stents, grafts) can fit into small-bore minimally-invasive surgical devices and recover their functional shape when deployed in the body. To realize their potential, it is imperative to devise combinatorial approaches that enable optimization of mechanical, SM, and cellular responses for a particular application. In this study, a new class of thermo-responsive SMPs is created in a robust, facile manner with readily tunable material properties. Materials exhibit excellent, switch-like shape recovery near body temperature and promising biocompatibility for minimally-invasive vascular applications.

Significant progress has been made in nanomedicine, primarily in the form of nanoparticles, for theranostic applications to various diseases. A variety of materials, both organic and inorganic, have been used to develop nanoparticles with promise to achieve improved efficacy in medical applications as well as reduced systemic side effects compared to current standard of care medical practices. In particular, this article highlights the recent development and application of nanoparticles for diagnosing and treating nephropathologies.

In regions of the circulation where vessels are straight and unbranched, blood flow is laminar and unidirectional. In contrast, at sites of curvature, branch points, and regions distal to stenoses, blood flow becomes disturbed. Atherosclerosis preferentially develops in these regions of disturbed blood flow. Current therapies for atherosclerosis are systemic and may not sufficiently target these atheroprone regions. In this study, we sought to leverage the alterations on the luminal surface of endothelial cells caused by this atheroprone flow for nanocarrier targeting. In vivo phage display was used to discover unique peptides that selectively bind to atheroprone regions in the mouse partial carotid artery ligation model. The peptide GSPREYTSYMPH (PREY) was found to bind 4.5-fold more avidly to the region of disturbed flow and was used to form targeted liposomes. When administered intravenously, PREY-targeted liposomes preferentially accumulated in endothelial cells in the partially occluded carotid artery and other areas of disturbed flow. Proteomic analysis and immunoblotting indicated that fibronectin and Filamin-A were preferentially bound by PREY nanocarriers in vessels with disturbed flow. In additional experiments, PREY nanocarriers were used therapeutically to deliver the nitric oxide synthase cofactor tetrahydrobiopterin (BH4), which we have previously shown to be deficient in regions of disturbed flow. This intervention increased vascular BH4 and reduced vascular superoxide in the partially ligated artery in wild-type mice and reduced plaque burden in the partially ligated left carotid artery of fat fed atheroprone mice (ApoE(-/-)). Targeting atheroprone sites of the circulation with functionalized nanocarriers provides a promising approach for prevention of early atherosclerotic lesion formation.

Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF–ApC/EBP heterodimer transactivates enhancer response element–containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF–ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.

SummaryIn Aplysia, long-term synaptic plasticity is induced by serotonin (5-HT) or neural activity and requires gene expression. Here, we demonstrate that ApLLP, a novel nucleolus protein, is critically involved in both long-term facilitation (LTF) and behavioral sensitization. Membrane depolarization induced ApLLP expression, which activated ApC/EBP expression through a direct binding to CRE. LTF was produced by a single pulse of 5-HT 30 min after the membrane depolarization. This LTF was blocked when either ApLLP or ApC/EBP were blocked by specific antibodies. In contrast, ApLLP overexpression induced LTF in response to a single 5-HT treatment. Simultaneously, a siphon noxious stimulus (SNS) to intact Aplysia induced ApLLP and ApC/EBP expression, and single tail shock 30 min after SNS transformed short-term sensitization to long-term sensitization of siphon withdrawal reflex. These results suggest that ApLLP is an activity-dependent transcriptional activator that switches short-term facilitation to long-term facilitation.