Memory reconsolidation for natural language processing

We propose a model of memory reconsolidation that can output new sentences with additional meaning after refining information from input sentences and integrating them with related prior experience. Our model uses available technology to first disambiguate the meanings of words and extracts information from the sentences into a structure that is an extension to semantic networks. Within our long-term memory we introduce an action relationships database reminiscent of the way symbols are associated in brain, and propose an adaptive mechanism for linking these actions with the different scenarios. The model then fills in the implicit context of the input and predicts relevant activities that could occur in the context based on a statistical action relationship database. The new data both of the more complete scenario and of the statistical relationships of the activities are reconsolidated into memory. Experiments show that our model improves upon the existing reasoning tool suggested by MIT Media lab, known as ConceptNet.     

Memory,consciousness and neuroimaging.

Neuroimaging techniques that allow the assessment of memory performance in healthy human volunteers while simultaneously obtaining measurements of brain activity in vivo may offer new information on the neural correlates of particular forms of memory retrieval and their association with consciousness and intention. We consider evidence from studies with positron emission tomography and functional magnetic resonance imaging indicating that priming, a form of implicit retrieval, is associated with decreased activity in various cortical regions. We also consider evidence concerning the question of whether two components of explicit retrieval--intentional or effortful search and successful conscious recollection--are preferentially associated with increased activity in prefrontal and medial temporal regions, respectively. Last, we consider recent efforts to probe the relation between the phenomenological character of remembering and neural activity. In this instance we broaden our scope to include studies employing event-related potentials and consider evidence concerning the neural correlates of qualitatively different forms of memory, including memory that is specifically associated with a sense of self, and the recollection of particular temporal or perceptual features that might contribute to a rich and vivid experience of the past.     

Memory, learning and neuromediators.

We consider a model of a neural network where the individual cells interact only by releasing and absorbing the molecules of a neuromediator. We show that such a system can realize the function of associative memory. A learning mechanism based on the chemotaxis is proposed and numerically investigated.     

Understanding ageing.

A broad biological approach makes it possible to understand why ageing exists and also why different mammalian species have very different maximum longevities. The adult organism is maintained in a functional state by at least ten major mechanisms, which together comprise a substantial proportion of all biological processes. These maintenance mechanisms eventually fail, because the evolved physiological and anatomical design of higher animals is incompatible with continual survival. The lifespan of each mammalian species depends on the efficiency of maintenance of their cells, tissues and organisms, and there is much evidence that such maintenance is more effective in long-lived species, such as man, than in short-lived small mammals. It is also evident that there is an inverse relationship between reproductive potential and longevity, which would be expected if total metabolic resources are shared between investment in reproduction, and investment in the preservation of the adult body. It is proposed that the eventual failure of maintenance leads to the pathological changes seen in age-associated disease. Although we now have a biological understanding of the ageing process, much future research will be needed to uncover the cellular and molecular changes which give rise to age-associated diseases. The major aim of such research is to devise procedures to delay or prevent the onset of these diseases.     

Smoking,health and ageing

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lecture of V. Nicita-Mauro on Smoking, health and ageing is summarized. Smoking represents an important ageing accelerator, both directly by triggering an inflammatory responses, and indirectly by favoring the occurrence of several diseases where smoking is a recognized risk factor. Hence, non-smokers can delay the appearance of diseases and of ageing process, so attaining longevity.     

Immunity,ageing and cancer

Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient.     

Osteoporosis,inflammation and ageing

Osteoporosis is a condition characterized by low bone mass and increased bone fragility, putting patients at risk of fractures, which are major causes of morbidity substantially in older people. Osteoporosis is currently attributed to various endocrine, metabolic and mechanical factors. However, emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on bone turnover, inducing osteoporosis. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodelling characteristic of ageing, as well as of other pathological conditions commonly associated with osteoporosis, may be determinant pathogenetic factors. The present article will review the current perspectives on the interaction between bone and immune system in the elderly, providing an interpretation of osteoporosis in the light of inflamm-ageing.     

Pathophysiology of ageing.

Ageing is characterized by a gradual decline in organ functional reserves which reduces the ability to maintain homeostasis under conditions of stress. Introduction of cell culture and molecular biology techniques has provided new experimental tools for the analysis of ageing at the molecular level. During ageing progressive degeneration of cells and loss of regenerative capacity are enhanced and with time the alterations caused by them ultimately lead to death. In this paper the current knowledge of the mechanisms of ageing is summarized.     

Hippocampus, ageing, and taste memories

Previous studies have shown that ageing may induce deficits in hippocampal-dependent learning and memory tasks, the spatial task being most extensively applied in rats. It is proposed that taste learning and memory tasks may assist in understanding the ageing of memory systems, giving access to a more complete picture. Taste learning tasks allow us to explore a variety of learning phenomena in safe and aversive memories using similar behavioral procedures. In demanding the same sensory, response, and motivational requirements, this approach provides reliable comparisons between the performance of hippocampal lesioned and aged rats in different types of memory. Present knowledge on the effect of both ageing and hippocampal damage in complex taste learning phenomena is reviewed. Besides inducing deficits in hippocampal-dependent phenomena, such as blocking of conditioned taste aversion, while at the same time leaving intact nonhippocampal-dependent effects, such as latent inhibition, ageing is also associated with an increased neophobia by previous aversive taste memories and enhanced taste aversion conditioning which cannot be explained by age-related changes in taste or visceral distress sensitivity. In all, the results indicate a peculiar organization of the memory systems during aging that cannot be explained by a general cognitive decline or exclusively by the decay of the hippocampal function.     

Reproductive ageing and the menopause.

This brief review describes early work initiated by Anne McLaren and John Biggers, in which they repeated on mice a very early experiment carried out by John Hunter on pigs, to test the effect of unilateral ovariectomy on subsequent breeding performance. This and subsequent experiments led to the conclusion that reproductive ageing in the female mouse was largely due to ageing changes in the uterus. As a result of these changes fewer implanted blastocysts are carried to term in the older females, with the result that the size of litters produced gradually drops and ceases altogether well before the expected time of death, thus leading to a period of reproductive inactivity at the end of life. Other organs undergo ageing changes but it appears to be those in the uterus which limit reproductive performance in the female. The somatic organs concerned in bringing the male gametes into the environment are still able to function effectively almost until the time of death so that males have a very short period of reproductive inactivity at the end of their lives. Due to the prenatal onset of meiosis in the germ cells, female mammals and some, but not all, other vertebrates are born with a finite crop of oocytes in the ovary, which cannot be increased after birth. Nevertheless, with the exception of women, female mammals appear to be able to produce ova well into old age, and have them fertilized. When examined after death the ovaries still contain oocytes so this is not a limiting factor in reproduction in old females. In women the situation is completely different. They also have an extended period of reproductive quiescence in middle and old age, the menopause, but, unlike other female mammals, this is not due to failure of the uterus but is caused by the ovary becoming depleted of oocytes in middle age. The reason women run out of oocytes before the end of life, whereas the other mammals which have been studied do not, is associated with the greatly extended lifespan of humans compared to other mammals of equivalent size. There is a linear relationship between longevity and body weight in mammals, small mammals have much shorter lives than large ones. This is probably associated with the increased production of free radical oxygen necessary to maintain body temperature in smaller animals. Heat is lost through the body surface which becomes relatively less as the animal increases in weight, so the smaller animal has to metabolise and thus produces more free radical oxygen to maintain body temperature. For reasons unknown this seems not to apply to humans. The menopause has thus evolved as a consequence of two adaptations: the prenatal onset of meiosis, common to all mammals and many other vertebrates and the greatly increased longevity of all humans, both male and female. In view of this dual origin it is unlikely to have evolved in response to an adaptive need to have grandmothers to help rear the young, as has been suggested!     

DNA methylation and cellular ageing.

Methylated cytosine (m5C) in DNA appears to be an important modulator of the expression of some genes. There are several lines of evidence that gradual loss of m5C is relevant to in vitro cellular ageing: m5C loss occurs during cell culture; m5C loss is detectable at an early stage of culture; m5C loss appears to be related to cell division not just duration in culture; the rate of m5C loss appears to be related to in vitro lifespan of the cell strain in question; and the total loss of m5C during an in vitro lifespan is significant by comparison with induced-changes in m5C levels which effect cell growth, or cause cell-death in culture. Progressive loss of m5C in dividing cells may thus produce the multi-step cell division "clock" which underlies the Hayflick phenomenon.     

Memory.

The key interrelated issues in the neurobiology of memory are to identify the neural circuitries essential for memory formation, localize sites of memory storage and analyze mechanisms of memory formation, storage and retrieval. Several circuits have now been identified in vertebrates and researchers are investigating their properties, in particular the role of glutamate receptors and long-term potentiation, in memory formation. Invertebrate preparations continue to be of value and recent studies suggest that changes in gene expression and protein synthesis may be important in long-term sensitization.     

Evolution, language and analogy in functional genomics.

Almost a century ago, Wittgenstein pointed out that theory in science is intricately connected to language. This connection is not a frequent topic in the genomics literature. But a case can be made that functional genomics is today hindered by the paradoxes that Wittgenstein identified. If this is true, until these paradoxes are recognized and addressed, functional genomics will continue to be limited in its ability to extrapolate information from genomic sequences.