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PubMed2003

The role of working memory in motor learning and performance.

Three experiments explore the role of working memory in motor skill acquisition and performance. Traditional theories postulate that skill acquisition proceeds through stages of knowing, which are initially declarative but later procedural. The reported experiments challenge that view and support an independent, parallel processing model, which predicts that procedural and declarative knowledge can be acquired separately and that the former does not depend on the availability of working memory, whereas, the latter does. The behaviour of these two processes was manipulated by providing or withholding visual (and auditory) appraisal of outcome feedback. Withholding feedback was predicted to inhibit the use of working memory to appraise success and, thus, prevent the formation of declarative knowledge without affecting the accumulation of procedural knowledge. While the first experiment failed to support these predictions, the second and third experiments demonstrated that procedural and declarative knowledge can be acquired independently. It is suggested that the availability of working memory is crucial to motor performance only when the learner has come to rely on its use.

Adult↗
PubMed2000

Neuronal nicotinic receptors in the human brain.

Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand gated ion channels which are widely distributed in the human brain. Multiple subtypes of these receptors exist, each with individual pharmacological and functional profiles. They mediate the effects of nicotine, a widely used drug of abuse, are involved in a number of physiological and behavioural processes and are additionally implicated in a number of pathological conditions such as Alzheimer's disease, Parkinson's disease and schizophrenia. The nAChRs have a pentameric structure composed of five membrane spanning subunits, of which nine different types have thus far been identified and cloned. The multiple subunits identified provide the basis for the heterogeneity of structure and function observed in the nAChR subtypes and are responsible for the individual characteristics of each. A substantial amount of information on human nAChR structure and function has come from studies on neuroblastoma cell lines which naturally express nAChRs and from recombinant nAChRs expressed in Xenopus oocytes. In vitro brain nAChR distribution can be mapped with a number of appropriate agonist and antagonist radioligands and subunit distribution may be mapped by in situ hybridization using subunit specific mRNA probes. Receptor distribution in the living human brain can be studied with noninvasive imaging techniques such as PET and SPECT, with a significant reduction in nAChRs in the brains of Alzheimer's patients having been identified with [11C] nicotine in PET studies. Despite the significant body of knowledge now accumulated about nAChRs, much remains to be elucidated. This review will attempt to describe the current knowledge on the nAChR subtypes in the human brain, their functional roles and neuropathological involvement.

Animals↗
PubMed2003

Nitric oxide synthase gene transfer as a tool to study biology of endothelial cells.

During the past decade, the development of gene transfer technology provided a powerful and facile tool that afforded the genetic modification of vascular endothelial function. This development has coincided with molecular cloning and extensive accumulation of knowledge concerning the role of nitric oxide synthase isoforms in vascular homeostasis. Experimental evidence continues to accumulate that in vivo adenovirus-mediated gene transfer into the vessel wall is a very useful technique in studies designed to characterize function of a given gene or protein. In this review, we will use nitric oxide synthase gene transfer as a paradigm to illustrate how gene transfer technology can be used to address key issues in the vascular biology of endothelium.

Animals↗
PubMed1991

Adenosine: a physiological brake on renin release.

Since the discovery over 20 years ago that adenosine inhibits renin release, our knowledge of the biochemistry, cell biology, and renal physiology of adenosine has expanded enormously. Despite this rapid accumulation of knowledge, an integrated view of the role of adenosine in renin release was lacking. It is my hope that the model of renin release presented in this review--although perhaps incorrect in some details--provides a consolidated, and therefore useful, perspective on the role of adenosine as a regulator of renin release.

Adenosine↗
PubMed2001

Pulp-dentin biology in restorative dentistry. Part 1: normal structure and physiology.

Considerable knowledge has accumulated over the years on the structure and function of the dental pulp and dentin. Some of this knowledge has important clinical implications. This review, which is the first of seven articles, will be limited to those parts of the normal structure and physiology of the pulp and dentin that have been shown to result in, or are likely lead to, tissue reactions associated with the clinical treatment of these tissues. Although certain normal structures will be highlighted in some detail, a basic knowledge of pulpal and dentinal development and structure is a prerequisite for an understanding of this text.

Biology↗
PubMed1996

Regulation of essential heavy metals (Cu, Cr, and Zn) by the freshwater prawn Macrobrachium malcolmsonii (Milne Edwards).

Despite the low concentrations of heavy metals in the surrounding medium, aquatic organisms take them up and accumulate them in their soft tissues to concentrations several fold higher than those of ambient levels (Bryan 1979; Rainbow et al. 1990). Knowledge of accumulation patterns of a particular trace metal is a prerequisite for understanding the significance of an observed metal concentration in a particular animal, especially from the aspect of biomonitoring. Many marine invertebrates accumulate heavy metals without any regulation and the accumulation necessarily being associated with mechanisms to store the metals in a detoxified form. Two detoxification mechanisms have been described, both of which may occur in one specimen. Heavy metals can either be bound up in insoluble metalliferous 'granules' (Mason and Nott 1981), or are bound to soluble metal-binding ligands, such as metallothioneins (Roesijadi 1992). Some marine decapod crustaceans have an innate ability to regulate the internal concentrations of essential but potentially toxic metals within a constant level, presumably to meet their metabolic demands (Rainbow 1985, 1992). However, at present, there is no such information relating to freshwater decapod crustaceans, especially shrimps which occupy a totally different environment. Macrobrachium malcolmsonii (Milne Edwards), a potential aquaculture species for freshwater is found in abundance in one of the major Indian rivers, the Cauvery. In the present study, an attempt was made to determine whether the freshwater prawn, M. malcolmsonii, is able to regulate the three essential elements, copper, chromium and zinc, over a wide range of dissolved concentrations. These three metals were chosen because the Cauvery River receives pollutants containing these metals (Vijayram et al. 1990).

Animals↗
PubMed2006

Internal migration and contraceptive knowledge and use in Guatemala.

CONTEXT: Levels of modern contraceptive knowledge and use among people living in rural areas of Guatemala differ substantially from those of people living in urban areas. Understanding the pace and extent of rural-to-urban migrants' adoption of urban contraceptive practices is important in determining if there is a strong need for migrant-focused reproductive health programs. METHODS: Bivariate and multivariate analyses of data on 971 married male and female respondents in the 1999 Guatemalan Migration and Reproductive Health Survey were used to examine how migration status and duration of residence in an urban area are associated with knowledge of modern contraceptive methods and current contraceptive use. RESULTS: Migrants' contraceptive knowledge was positively associated with the number of years they had lived in an urban area. Mayan migrants in Guatemala City did not accumulate contraceptive knowledge at the same rate as non-Mayan migrants, perhaps due to cultural and linguistic barriers to obtaining knowledge of and access to contraceptives. Rural-to-urban migrants eventually achieve a level of modern contraceptive use slightly below that of urban nonmigrants, with the level of contraceptive knowledge being an important factor associated with use of modern methods. CONCLUSIONS: Migrants possess limited knowledge of modern contraceptive methods and, therefore, may experience unmet need for contraception or may have a limited choice of modern contraceptive methods during their first years in an urban destination. Programs designed to raise contraceptive awareness and use should target recent migrants--particularly indigenous Mayans--in urban areas.

Adolescent↗
PubMed2005

Groundwater and human development: challenges and opportunities in livelihoods and environment.

At less than 1000 km3/year, the world's annual use of groundwater is 1.5% of renewable water resource but contributes a lion's share of water-induced human welfare. Global groundwater use however has increased manifold in the past 50 years; and the human race has never had to manage groundwater use on such a large scale. Sustaining the massive welfare gains groundwater development has created without ruining the resource is a key water challenge facing the world today. In exploring this challenge, we have focused a good deal on conditions of resource occurrence but less so on resource use. I offer a typology of five groundwater demand systems as Groundwater Socio-ecologies (GwSE), each embodying a unique pattern of interactions between socio-economic and ecological variables, and each facing a distinct groundwater governance challenge. During the past century, a growing corpus of experiential knowledge has accumulated in the industrialized world on managing groundwater in various uses and contexts. A daunting global groundwater issue today is to apply this knowledge intelligently to by far the more formidable challenge that has arisen in developing regions of Asia and Africa, where groundwater irrigation has evolved into a colossal anarchy supporting billions of livelihoods but threatening the resource itself.

Africa↗
PubMed2006

Gene networks controlling early cerebral cortex arealization.

Early thalamus-independent steps in the process of cortical arealization take place on the basis of information intrinsic to the cortical primordium, as proposed by Rakic in his classical protomap hypothesis [Rakic, P. (1988)Science, 241, 170-176]. These steps depend on a dense network of molecular interactions, involving genes encoding for diffusible ligands which are released around the borders of the cortical field, and transcription factor genes which are expressed in graded ways throughout this field. In recent years, several labs worldwide have put considerable effort into identifying members of this network and disentangling its topology. In this respect, a considerable amount of knowledge has accumulated and a first, provisional description of the network can be delineated. The aim of this review is to provide an organic synthesis of our current knowledge of molecular genetics of early cortical arealization, i.e. to summarise the mechanisms by which secreted ligands and graded transcription factor genes elaborate positional information and trigger the activation of distinctive area-specific morphogenetic programs.

Animals↗
PubMed2002

The regulation of phagosome maturation in Dictyostelium.

Macropinocytosis (fluid uptake) and phagocytosis (particle uptake) are processes that result in the formation of intracellular membrane enclosed vacuoles termed macropinosomes and phagosomes, respectively. Macropinosomes and phagosomes are modified by fission and fusion reactions with the endo-lysosomal pathway that eventually transform these vacuoles into a lysosomal environment. Many human bacterial pathogens, including species of Mycobacteria, Legionella, and Chlamydia, are thought to survive by disrupting the normal membrane trafficking events that usually result in the formation of phago-lysosomes and death of the microorganism. In addition, a number of important pathogens facilitate homotypic phagosome fusion in order to generate an intracellular environment conducive for survival. A greater understanding of the regulation of phagosomal maturation and fusion will be critical in designing new therapies to treat infections caused by intracellular pathogens. The genetically tractable phagocyte, D. discoideum, has proven extremely useful in dissecting the signaling pathways regulating macropinocytosis, phagocytosis, phagosomal maturation and phagosome-phagosome fusion. A body of knowledge has accumulated and demonstrates important roles for Rab GTPases, the cytoskeleton, phosphoinositide metabolism and pH regulation in regulating phagosome maturation. This review will summarize the current state of knowledge.

Animals↗
PubMed2005

Advances since the paper by Zander and Glass (1949) on the pursuit of healing methods for pulpal exposures: historical perspectives.

Clinical observations and experimental studies in humans and laboratory animals have demonstrated that healing and repair of pulpal exposures by caries, trauma, or iatrogenic causes are possible with a variety of wound treatment methods. Yet clinical trials have shown that predictable long-term pulp tissue preservation may be an elusive goal and has led to doubts about pulp capping and pulpotomy as valid clinical procedures. Nevertheless substantial knowledge has accumulated over the years on the mechanisms and the treatment factors that are important to promote/support continued vital pulp functions. This article highlights some key contributions to our current knowledge base, which have come to light during the more than 50 years since a pioneering experimental study by Zander and Glass was published in the Triple O journal.

Aluminum Compounds↗
PubMed2006

Uptake of C60 by human monocyte macrophages, its localization and implications for toxicity: studied by high resolution electron microscopy and electron tomography.

Despite great interest in the engineering applications of carbon-based nanoparticles, recent studies have raised concerns about their potential toxicity and safety. The release of C(60) into the environment has been suggested to be a potential risk with possible ecological implications. Here we evaluate energy-filtered transmission electron microscopy (EFTEM) and scanning transmission electron microscopy (STEM)-based electron tomography as techniques for imaging the three-dimensional (3-D) distribution of nanoparticles within cells. Our aim was to establish if human monocyte macrophages internalise nanoparticles and to assess whether nanoparticles are modified by cells following uptake. Using these techniques we were able to show a marked increased in the amount of information gained from 3-D imaging. 3-D electron tomography revealed several sub-cellular compartments containing C(60) within the cell: secondary lysosomes, along the outer and nuclear membrane and most notably inside the nucleus of the cell. Using EFTEM and STEM-based techniques we were able to visualize cell structures such as membranes, the mitochondria, ribosomes and the nucleus, without the need for traditional staining techniques. In particular we demonstrate the potential of electron tomography for whole cell studies to enable 3-D distributions of particles within cells. The concentrations of C(60) used in this study were not toxic and were chosen to study which sub-cellular compartments accumulated C(60). Knowledge of the sites of accumulation of nanoparticles will allow us to predict vulnerability if the nanoparticles can generate free radicals.

Cell Culture Techniques↗
PubMed2004

Living related liver donor transplantation: techniques and caution.

LDLT is often performed under less than ideal circumstances, such as limited graft mass, aberrant vascular and biliary anatomy, limited sources of venous grafts, and a recipient in a state of deterioration. The margin for error is small in both recipients and donors. Every step of the surgery needs to be planned and performed in a meticulous and synchronized manner. Small errors or absences of coordination can lead to unexpected complications. In addition, use of a segmental graft requires the knowledge of the safety margin of hepatic adaptation to nonphysiologic situations for the safety of both recipient and donor. Scientific and clinical evidences for precise individualization of the tactics are still not sufficient. Further accumulation of knowledge and experience is awaited for the safest performance of this evolving surgery.

Anastomosis, Surgical↗
PubMed1998

Organizational guidelines for dual disorders programs.

Dual disorders--combined severe mental disorders and substance use disorders--were barely recognized two decades ago. As a result of the high prevalence and serious consequences of these disorders, they have received considerable attention over the last two decades. Knowledge has accumulated about dual disorders and their treatment, and treatment providers may now consider numerous options for clinical interventions and program designs. In this article, we offer guidelines concerning these options. We review the current knowledge about dual disorders and the results of recent research on the assessment and treatment of these disorders. We present treatment principles, recommendations on the components and organization of dual disorders programs, and suggestions for dealing with clinical issues that remain controversial. We conclude with comments on the demands of the managed care environment and the heightened importance of continued research in this area.

Counseling↗
PubMed1996

Attention control: explorations of the work of an executive controller.

This contribution reviews three lines of studies set to investigate attention control and executive operations, in the general context of the interplay between bottom-up and top-down processes in the conduct of proficient behavior. One line of studies focused on the act of switching attention between tasks and the mental costs associated with it. A second group of experiments investigated attention strategies and resource management in coping with high load and concurrent task demands. A third line of studies examined the influence of enhanced knowledge and accumulated experience on coping with malfunctions and mishaps in system response. The experimental results of all studies lend strong support to the existence and influence of executive control processes. These types of processes operate on the established representations and knowledge bases of tasks, to make the best use of processing and response facilities. The experiments shed light on the nature of the processes and the variables that influence them. It is shown that proficient performance is far from being exclusively guided by automatic processing and response routines triggered directly by events in the environment. Instead it is a joint and non-trivial product of these two types of processes. Executive control is required not only in early stages of training, but also at high levels of mastery and proficiency. Automatism does not eliminate or reduce the importance of executive control and strategic behavior. A new and powerful class of processes comes into play at this level of expertise, with strong influence on modes of behavior and the overall efficiency of performance.

Adaptation, Psychological↗
PubMed1998

Tropical medicine: 100 years of progress.

Over the past century, tropical medicine has passed through several overlapping phases. Initially, the picture was of endemic and epidemic diseases that wreaked havoc on people living in warm climates and visitors to these areas. High morbidity and mortality associated with these diseases reflected the poor state of knowledge about their causes and epidemiology and the lack of effective technologies for their control. At this stage, tropical medicine was dominated by parasitic and infectious diseases that had affinity for warm climates and some specific nutritional disorders. The next phase involved the steady accumulation of knowledge about the aetiological agents and, in the case of parasitic and infectious diseases, identification of reservoirs and vectors. The development of new and improved technologies for the control of tropical diseases characterised the third phase. The new products included drugs, diagnostic tools, vector control measures and vaccines. In the fourth phase, the new technologies are being deployed in programmes aimed at achieving disease control and, where feasible, total elimination of the problem. In the course of these operations, many useful lessons have been learnt from both the successes and failures of major schemes. In particular, experience has shown the important role of research not only in providing new technologies but also in optimising their effectiveness when applied in control programmes. The role of social and behavioural factors in the epidemiology and control of tropical diseases has drawn attention to the value of a multidisciplinary approach in designing and implementing control programmes. There is a sense of cautious optimism that, if the lessons learnt over the past century are carefully applied, further gains can be made in controlling and eliminating the classical problems that characterised tropical medicine at the beginning of this century.

Disease Outbreaks↗
PubMed2001

Therapeutic perspectives of in vivo cell electropermeabilization.

Cell electropermeabilization (also termed cell electroporation) is nowadays a routine technique used in biochemical and pharmacological studies for the in vitro introduction of nonpermeant molecules into living cells. But electric pulses can be used as well in vivo for the delivery of drugs or DNA into cells of tissues. This review then gives an updated overview of the therapeutic perspectives of cell electropermeabilization in vivo, in particular of the antitumour electrochemotherapy (i.e., the combination of a cytotoxic nonpermeant drug with permeabilizing electric pulses delivered to the tumours) and of in vivo DNA electrotransfer for gene therapy. After a short summary of the present knowledge on cell electropermeabilization (particularly in vivo), the basis, the present achievements, and the challenges of electrochemotherapy are described and discussed, which includes an overview of still open questions and an update on recent clinical trials. DNA electrotransfer for gene therapy is an emerging field in which results are rapidly accumulating. Present knowledge on DNA electrotransfer mechanisms, as wel as the potentialities of DNA electrotransfer to become an efficient non-viral approach for gene therapy, are reviewed.

Animals↗
PubMed1992

Ethnic minority status and adolescent mental health services utilization.

Adolescents who are members of ethnic minority groups constitute a large and ever increasing proportion of the population. While the information base regarding mental health problems and mental health services utilization in adolescents in general is slowly increasing, relatively little knowledge has accumulated about the particular needs and practices of youth of color. The purpose of this article is to review the available literature about adolescent mental health needs and service utilization as well as literature regarding adult ethnicity and mental health service utilization. The conclusion of this review is that significant gaps exist in our knowledge base regarding ethnicity in adolescents and its implications for the utilization of mental health services. The limited data available suggest that significant numbers of adolescents of color have multiple needs for mental health care and that a complex set of barriers exists to prevent them from obtaining appropriate services. A variety of suggestions are offered to improve the opportunities for and the quality of mental health services for ethnic minority adolescents.

Adolescent↗