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PubMedDate not supplied

Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning.

Many behavioral and electrophysiological studies in animals and humans have suggested that sleep and circadian rhythms influence memory consolidation. In rodents, hippocampus-dependent memory may be particularly sensitive to sleep deprivation after training, as spatial memory in the Morris water maze is impaired by rapid eye movement sleep deprivation following training. Spatial learning in the Morris water maze, however, requires multiple training trials and performance, as measured by time to reach the hidden platform is influenced by not only spatial learning but also procedural learning. To determine if sleep is important for the consolidation of a single-trial, hippocampus-dependent task, we sleep deprived animals for 0-5 and 5-10 h after training for contextual and cued fear conditioning. We found that sleep deprivation from 0-5 h after training for this task impaired memory consolidation for contextual fear conditioning whereas sleep deprivation from 5-10 h after training had no effect. Sleep deprivation at either time point had no effect on cued fear conditioning, a hippocampus-independent task. Previous studies have determined that memory consolidation for fear conditioning is impaired when protein kinase A and protein synthesis inhibitors are administered at the same time as when sleep deprivation is effective, suggesting that sleep deprivation may act by modifying these molecular mechanisms of memory storage.

Analysis of Variance↗

PubMed1993

Novel immunosuppressive and antiinflammatory drugs. A 1993 perspective.

Research on immunosuppressive and antiinflammatory drugs is progressing rapidly. Several new drugs are in development, and learning how to combine them optimally, for treatment of different diseases and prolonging graft survival, will be a major task for the next few years. Decreasing the incidence of complications following transplantation will reduce patient anxiety and cost, and the shortage of donor organs is an additional reason for wishing to prolong graft acceptance. Many clinical findings with the new drug combinations should be published by the end of the century. We can begin the next millennium with improved immunosuppressive and antiinflammatory drugs discussed at the Orlando conference.

Animals↗

PubMed1999

Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay.

The role of the opioid-like receptor 1 (ORL1) and its endogenous ligand, nociceptin/orphanin FQ (N/OFQ), in nociception, anxiety, and learning remains to be defined. To allow the rapid identification of agonists and antagonists, a reporter gene assay has been established in which the ORL1 receptor is functionally linked to the cyclic AMP-dependent expression of luciferase. N/OFQ and N/OFQ(1-13)NH(2) inhibited the forskolin-induced luciferase gene expression with IC(50) values of 0.81 +/- 0.5 and 0.87 +/- 0.16 nM, respectively. Buprenorphine was identified as a full agonist at the ORL1 receptor with an IC(50) value of 8.4 +/- 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ((1-13))NH(2) clearly behaved as an agonist in this assay with an IC(50) value of 85 +/- 47 nM. Thus, there is still a need for antagonistic tool compounds that might help to elucidate the neurophysiological role of N/OFQ.

Animals↗

PubMed1994

Modulation of cortical motor output maps during development of implicit and explicit knowledge.

The excitability of the human motor cortex during the development of implicit and declarative knowledge of a motor task was examined. During a serial reaction time test, subjects developed implicit knowledge of the test sequence, which was reflected by diminishing response times. Motor cortical mapping with transcranial magnetic stimulation revealed that the cortical output maps to the muscles involved in the task became progressively larger until explicit knowledge was achieved, after which they returned to their baseline topography. These results illustrate the rapid functional plasticity of cortical outputs associated with learning and with the transfer of knowledge from an implicit to explicit state.

Brain Mapping↗

PubMed1991

Use of a tissue adhesive to repair fetal bodies after dissection.

The repair of fetal bodies after dissection is extremely difficult because of the delicacy of the skin. A tissue adhesive, Histoacryl blue, was used to repair bodies that had been dissected either before or after immersion in formalin. The repairs were achieved rapidly and neatly. The technique was easy to learn and, providing the method of repair described was followed, there was no breakdown subsequently. The body cavities and reflected skin surfaces were lightly dried with absorbent paper towels and the body loosely packed with cotton wool. "Holding lines" of glue were made and a mid-line strip of glue was applied to the sternum, abdomen, and skull vault, allowing the skin edges to align neatly. Care must be taken to avoid using excess glue as this produces an exothermic reaction. It is recommended that if a fetus has to be repaired after dissection Histoacryl blue will give a good result.

Autopsy↗

PubMed2001

Extracellular calcium sensing and extracellular calcium signaling.

The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

Alternative Splicing↗

PubMed1997

The challenge of change.

To succeed in modern life, you must learn to be comfortable with the inevitability of rapid change. The author presents five keys to the successful management of change.

Anger↗

PubMed1976

Attention in the pigeon: a reevaluation.

During training sessions, pigeons were successively exposed to compounds consisting of a white triangle on a red background and a white circle on a green background. Key pecking intermittently produced grain reinforcers in the presence of one form-color compound. Once key pecking was confined to the compound associated with reinforcement, the elements-red, green, triangle, and circle-were presented during a test in which no reinforcement was available. Each bird pecked nearly exclusively in the presence of the color previously associated with reinforcement, a result that might be interpreted as indicating that the subjects had attended to color, but not form during training. Pecking was next reinforced when either the triangle or the circle was present. Pecking in the presence of the form previously associated with reinforcement was acquired more rapidly. This result suggests that the birds had learned about the forms during training, and that conclusions about attention based on the lack of differential pecking in the nonreinforcement test may not be appropriate.

Journal Article↗

PubMed2002

Gene control of synaptic plasticity and memory formation: implications for diseases and therapeutic strategies.

There has been nearly a century of interest in the idea that information is stored in the brain as changes in the efficacy of synaptic connections between neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular and molecular bases of learning and memory. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. Here we briefly review these mechanisms and illustrate with a few examples of animal models of neurological disorders how new knowledge about these mechanisms can provide valuable insights into identifying the mechanisms that go awry when memory is deficient, and how, in turn, characterisation of the dysfunctional mechanisms offers prospects to design and evaluate molecular and biobehavioural strategies for therapeutic prevention and rescue.

Aging↗

PubMed2026

Large language models in bioinformatics: a comprehensive survey.

The emergence of foundation models with trillion-level parameters has redefined the landscape of artificial intelligence. Various fields are developing their own large-scale models, which can solve many problems within the field and improve work efficiency. Biological large-scale models are a cross-disciplinary research field that combines mathematics, computer science, and biology, aiming to simulate and understand the structure, function, and dynamic changes of biological systems through the establishment of complex computational models. This field covers multiple levels such as biological pathways, population dynamics, protein folding, etc., providing us with tools for deep exploration of the mysteries of life and applications in medicine, ecology, and other fields. This article reviews the background and research status of biological large-scale models, and discusses future directions. Large language models (LLMs) and other large-scale foundation models have rapidly advanced in recent years, enabling powerful representation learning and generation across text, sequences, and multimodal data. In bioinformatics and biomedicine, these models are increasingly used to analyze genomic sequences, infer protein properties and structures, support drug discovery, and integrate heterogeneous biomedical evidence. This survey reviews the basic principles of LLMs and summarizes representative applications in (i) gene and genome sequence analysis, (ii) protein structure and function prediction, and (iii) drug design, including virtual screening and personalized medicine. We also discuss emerging multi-model modeling approaches, as well as key challenges such as data quality and privacy, interpretability, generalization to new organisms and tasks, and responsible deployment in health-related settings. Finally, we outline future directions for developing reliable, scalable, and explainable bioinformatics foundation models.

bioinformatics↗

PubMed2004

Cool, calm, and collected: medical center successfully regroups after financial crisis.

Declining Medicare payment. Increasing competition from niche players. Rising labor costs. Waning commitment of employed physicians. Taken alone, each of these circumstances can pose a significant challenge for a healthcare organization. Together, however, they can add up to a severe financial crisis. Via Christi Regional Medical Center in Wichita, Kan., learned that surviving such a crisis depends on rapid implementation of a well-conceived action plan, taking into account the multiple perspectives of leadership, physicians, staff, and patients.

Efficiency↗

PubMed1997

A new trocar approach insertion site for laparoscopic surgery: the xiphoidal approach.

Laparoscopic cholecystectomy (LC) has become the standard treatment for removing a diseased gallbladder. Endoscopic surgical techniques are used to perform appendectomies, bowel resections, and gastrectomies. This minimally invasive surgery is favored because it decreases the patients' postoperative pain and length of hospitalization. However the incidence of complications with this technique is not negligible. As a new technique is evolving, the potential for complications is high. This increase in complication rate is undoubtedly due to inexperience during the initial phase of the surgeon's learning curve. Demand for the procedure has required rapid training and credentialing of many surgeons with limited experience in endoscopy and the use of instruments that allow only limited viewing of abdominal structures.

Journal Article↗

PubMed2003

Working together: supporting projects through action learning.

Recent years have seen tremendous growth in knowledge management projects within the NHS. Project staff must acquire rapidly a wide range of task-related skills. Conventional training courses may be inappropriately timed or unavailable to project staff. Action learning provides a group-based means of meeting skills deficits associated with project management and delivery. This paper describes an action learning set for project staff on five knowledge management projects within Trent Region. A brief evaluation aimed to identify most and least useful and most and least enjoyable features of the action learning set. Comments on the facilitation and the content of the action learning sessions are analysed. Action learning is feasible in meeting the training needs of project staff. It may also provide a means of meeting the shared learning needs of communities of practice within a virtual environment. Knowledge management does not merely involve management and delivery within innovative projects but also requires exploiting shared learning across projects.

Cooperative Behavior↗

PubMed1995

Semantic and phonological coding in poor and normal readers.

Three studies were conducted evaluating semantic and phonological coding deficits as alternative explanations of reading disability. In the first study, poor and normal readers in second and sixth grade were compared on various tests evaluating semantic development as well as on tests evaluating rapid naming and pseudoword decoding as independent measures of phonological coding ability. In a second study, the same subjects were given verbal memory and visual-verbal learning tasks using high and low meaning words as verbal stimuli and Chinese ideographs as visual stimuli. On the semantic tasks, poor readers performed below the level of the normal readers only at the sixth grade level, but, on the rapid naming and pseudoword learning tasks, they performed below the normal readers at the second as well as at the sixth grade level. On both the verbal memory and visual-verbal learning tasks, performance in poor readers approximated that of normal readers when the word stimuli were high in meaning but not when they were low in meaning. These patterns were essentially replicated in a third study that used some of the same semantic and phonological measures used in the first experiment, and verbal memory and visual-verbal learning tasks that employed word lists and visual stimuli (novel alphabetic characters) that more closely approximated those used in learning to read. It was concluded that semantic coding deficits are an unlikely cause of reading difficulties in most poor readers at the beginning stages of reading skills acquisition, but accrue as a consequence of prolonged reading difficulties in older readers. It was also concluded that phonological coding deficits are a probable cause of reading difficulties in most poor readers.

Child↗

PubMed2005

Comparison of 25 and 27 gauge needle in spinal anesthesia learning curve for anesthesia residency training.

BACKGROUND AND RATIONALE: Size of spinal needle may be a factor which influences the success rate of spinal anesthesia. OBJECTIVES: To compare learning curves of using 25G and 27G quincke spinal needle for spinal anesthesia. SETTING: Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital. DESIGN: Prospective randomized control trial. MATERIAL AND METHOD: Ten new first year anesthesia residents were randomized to 2 groups: Group I (n = 5) used 25G Quincke spinal needle, Group II (n = 5) used 27G Quincke spinal needle to perform 200 consecutive cases of spinal anesthesia. Number of success and failure was recorded by each individual resident anonymously. The learning curves of plotted by cumulative sum of success rate revealed an initial rapid improvement of success during the first 20 cases in both groups. The overall success rate of group I was 84% (95CI, 66.5-100) and group II was 87% (95%CI, 61.5-100); p = 0.89. The widest difference between the 2 learning curves at 20 attempts intervals was at the twentieth attempts with a success rate of 76.0% VS 65.0% in group I and group II respectively; p = 0.54. CONCLUSION: The learning curves of spinal anesthesia using 25G and 27G Quincke spinal needle showed rapid improvement of success rate at the first 20 spinal block and high overall success rate with no significant difference between the groups.

Adult↗

PubMedDate not supplied

Active Learning Centre: design and evaluation of an educational World Wide Web site.

OBJECTIVE: A new medium--World Wide Web (WWW)--has grown rapidly over the last few years. It provides opportunities for development of new educational tools and facilitates learning through interactivity, self-paced study and easy access. The aim of this project was to devise all educational WWW site (Active Learning Centre) that would take advantage of the capabilities of the new medium and assess its utilization by users. METHODS: Active Learning Centre provides customizable computer-generated feedback tests, searchable databases (currently Microbiology, Pharmacology, Vaccines, and Spanish-language Cardiovascular Medications), remote WWW-based database authoring, and multilingual support. Its modular architecture allows easy expansion into new areas of knowledge. To evaluate the Active Learning Centre we conducted a study evaluating utilization of the site and user feedback. RESULTS: The site is being used by thousands of patrons from around the world, the majority of whom are health professionals/health profession students from English-speaking countries. Customizable interactive tests are the most popular feature of the site. Most users give the site high ratings and would like it to expand further. CONCLUSION: The paradigm of combining interactive feedback tests with searchable % reference databases has been successful. Further expansion of the site to incorporate other areas of knowledge is planned.

Computer-Assisted Instruction↗

PubMed2004

Are multi-layer backpropagation networks catastrophically amnesic?

Connectionist models with a backpropagation learning rule are known to have a serious problem. Such models exhibit catastrophic interference (or forgetting) with sequential training. Having learned a set of patterns, if the model is trained on another set of patterns, its performance on the first set can dramatically deteriorate very rapidly. The present study reconsiders this issue with four simulations. The model learned arithmetic facts sequentially, but the interference was only modest with random (hence approximately orthogonal) inputs. Essentially the same result was obtained when the inputs are made less orthogonal by adding irrelevant elements. Reducing the number of hidden units did not have major effects. This study suggests that the interference problem has been somewhat overstated.

Algorithms↗

PubMed2003

The acquisition, retention and reversal of spatial learning in the morris water maze task following withdrawal from an escalating dosage schedule of amphetamine in wistar rats.

Two experiments were carried out to evaluate the effects of amphetamine withdrawal in rats on spatial learning in the water maze. A schedule of repeated d-amphetamine administration lasting for 6 days, with three injections per day (1-5 mg/kg, i.p.), was employed. Experiment 1 demonstrated that amphetamine withdrawal did not impair the acquisition of the water maze task (third to fourth withdrawal days), but amphetamine-withdrawn rats made more target-zone visits and reached the former location of the platform quicker than controls during the probe test (fifth withdrawal day). In experiment 2, retention of the location of the escape platform was assessed in animals having been pre-trained on the water maze task before treatment. On the third withdrawal day, retention of the former platform location was assessed in a probe test. Retention was only clearly seen in the measure of target zone visits, and performance did not differ between groups. Next, the animals were trained to escape to a new location in the water maze on withdrawal days 4-5. A reversal effect could be discerned across the first four trials, as evident by the animals' tendency to search in the former target quadrant. This interfered with the new learning, but amphetamine-withdrawn animals appeared to overcome it more rapidly than saline-treated controls. This finding is consistent with the view that amphetamine withdrawal can enhance behavioural switching, which could be expressed as a reduction of proactive interference during learning; and, it is in line with our previous finding that latent inhibition is also attenuated during amphetamine withdrawal.

Amphetamine↗