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[Spreading of porcine kidney epithelial cells under normal conditions and under the effect of inhibitors of energy metabolism. II. Behavior of cellular organelles].

In the present work the behavior of mitochondria and lysosomes during cell spreading has been investigated in normal conditions and under ATP-synthesis inhibitors: sodium aside and N,N-dicyclohexylcarbodiimide (DCCD). In the control culture, microtubules run along the stable edge and perpendicular to the leading edge in most of spreading cells. As a whole, microtubules form a dense network in these cells. However, the radial cells contain bundles of microtubules, radiating from the perinuclear area or form circular arrays around the nucleus. The microtubule network is more dense under inhibitory treatment, than in control conditions. In the control culture the spherical cells display numerous small mitochondria (staining with Rhodamine 123). In the process of cell spreading some elongated mitochondria appear, most of them being localized in the perinuclear area. The mitochondria of cells with radial microtubule organization are directed towards the cell periphery, while in cells with circular bundles of microtubules the mitochondria are localized chaotically. Under DCCD treatment the mitochondria retain the staining for 2-3 h. In the spreading cells, round mitochondria may be distributed all over the cytoplasm. In the presence of sodium aside the mitochondria are not stained. However, by means of phase contrast microscopy some disoriented thread-shaped structures are observed, obviously corresponding to mitochondria. In the control conditions, lysosomes (stained with Acridine orange) in spreading cells are dispersed chaotically, all over the cytoplasm, or are localized in the perinuclear area. In the presence of sodium aside lysosomes are observed only in the perinuclear area. Under DCCD treatment lysosomes do not accumulate the dye. Thus, the cytoskeleton modification and changes in the properties of membrane organelles, induced by ATP-synthesis inhibitors, do not prevent attachment, spreading or cell polarization.

Adenosine Triphosphate↗

Design and training of a neural network for predicting the solvent accessibility of proteins.

A feed-forward neural network has been developed to predict the solvent accessibility/accessible surface area (ASA) of proteins using improved design and training methods. Several network issues ranging from the coding of ASA states to the problem of local minima of learning curve, have been addressed. Successful new approaches to overcome these problems are presented. Set of trained network weights for each ASA threshold is provided. It has been established that the prediction accuracy results with neural network are better than other reported results of ASA prediction, despite a high test to training data ratio.

Amino Acids↗

The Yoruba farm market as a communication channel in guinea worm disease surveillance.

Disease eradication programmes are by definition time bound and require strategies that facilitate timely intervention. Surveillance, which undergirds eradication, also requires timely strategies. Finding such strategies is especially challenging when the target disease is endemic in remote areas, e.g. guinea worm disease, the focus of this study. A strategy of market based surveillance was pilot tested in Ifeloju Local Government Area (LGA) of Oyo State, Nigeria. The project goal was to design a surveillance system that both fit into the natural communication network of rural people, and also enlisted their active involvement. Ethnographic research methods were employed to learn about market location, structure, catchment area and attendance pattern. Four larger farm markets (serving 164 hamlets with 17,000 population) were chosen. Each hamlet was visited and a volunteer 'reporter' was recruited. Reporters were trained on case recognition and detection, first aid and prevention, with a sensitivity to distinguishing indigenous and clinical perceptions of guinea worm. The market cycle was based on the traditional four-day week. Field workers visited every second market 16 times between October 1990 and February 1991. The reporter was expected to identify correctly the first case of the season and thus label the village as endemic for the season. Reporters gave oral reports, and positive indications were followed up within 48 hr by field workers, who verified the case and administered first aid. All hamlets were visited once a month to verify negative reports. Reporter attendance was monitored. Those who had a formal role in the market, e.g. sales agents, had better attendance than ordinary farmers who came only to sell their own produce. Knowledge of market structure and attender roles offers a guide for adapting this surveillance approach to other cultural systems and health issues.

Adolescent↗

Broca's area and inflectional morphology: evidence from broca's aphasia and computer modeling.

In a series of articles Ullman (2001, 2004; Ullman et al., 1997) has proposed that regular inflection is critically subserved by Broca's area. This suggestion is motivated by the finding that English speaking Broca's aphasics show selective deficits with regular inflection. Here we argue that this proposal does not hold cross-linguistically but is based on a confound between inflectional suffix and regularity that is specific to the English language. We present data from two experimental studies of participle inflection with 13 German and 12 Dutch Broca's aphasics. None of these aphasic speakers are selectively impaired for regular inflection but instead most of them show selective deficits with irregular inflection. These data suggest that a selective regular deficit is not a characteristic of Broca's aphasia across languages, and that Broca's area is not critically involved in regular inflection. To investigate the nature and localization of the processes underlying inflection we present a connectionist neural network model that accounts for the deficits of the German aphasic speakers. The model implements the view that the inflection of all verb types is based on a single mechanism with multiple representations that emerge from experience-dependent brain development. We show that global damage to this model results in a selective deficit for irregular inflection that is comparable to that of the German aphasic speakers. This finding suggests that a selective impairment of irregular participles as observed by German and Dutch aphasic speakers does not presuppose two distinctly localized mechanisms or processes that can be selectively affected by brain damage.

Adult↗

Responses of the rat medullary neurons to central penicillin microinjection.

BACKGROUND: The microinjection of penicillin in the medulla oblongata caused different alterations in the global respiratory output. The purpose of this paper was to study the involvement of impulse activity and the functional relationship of bulbar neurons in mechanisms underlying experimentally induced respiratory arrhythmias. METHODS: Extracellular activity of neurons and diaphragmatic electromyogram activity were recorded and analyzed. RESULTS: Penicillin microinjection increased the mean discharge rate of bulbar neurons and caused the prolongation of discharge of inspiratory neurons. Cross-correlation analysis revealed new excitatory connections between neurons and a high level of positive synchronization of neuronal activity. CONCLUSION: The local blockage of synaptic inhibition by penicillin within respiratory areas leads to drastic changes in the functioning of neuronal elements of the single respiratory network.

Action Potentials↗

The Twin Cities biomedical consortium.

Twenty-eight health science libraries in the St. Paul-Minneapolis area formed the Twin Cities Biomedical Consortium with the intention of developing a strong network of biomedical libraries in the Twin Cities area. Toward this end, programs were designed to strengthen lines of communication and increase cooperation among local health science libraries; improve access to biomedical information at the local level; and enable the Consortium, as a group, to meet an increasing proportion of its members' needs for biomedical information. Presently, the TCBC comprises libraries in twenty-two hospitals, two county medical societies, one school of nursing, one junior college, and two private corporations.

Information Services↗

Nontuberculous mycobacterial infections after cosmetic surgery--Santo Domingo, Dominican Republic, 2003-2004.

Rapidly growing mycobacteria have been associated with postoperative infections in patients undergoing cosmetic surgery procedures. In April 2004, CDC received reports of infections caused by rapidly growing mycobacteria in patients who had undergone cosmetic surgery procedures in Santo Domingo, Dominican Republic (DR). CDC, along with state and local health departments, is investigating additional cases identified by passive surveillance (i.e., solicitation of reports from clinicians by using electronic networks) and, in some areas, active surveillance (i.e., review of laboratory reports).

Adult↗

Estrogen- and tamoxifen-induced rearrangement of cytoskeletal and adhesion structures in breast cancer MCF-7 cells.

The cytoskeleton, the shape, and the adhesion complexes of MCF-7 breast carcinoma cells have been studied by fluorescence, phase contrast, and interference reflection microscopy. Cells have been grown in media containing different concentrations of estrogen and with or without the addition of the antiestrogen tamoxifen. The pattern of actin microfilaments and keratin intermediate filaments (tonofilaments) and the distribution of adhesion areas change as a function of the estrogen concentration. When cells are cultured in estrogen-deprived medium, they appear roundish and flattened and adhere firmly to the substratum, with multiple vinculin-positive adhesion plaques at their ventral surface. Upon stimulation with estrogen, these cells display pseudopodial cytoplasmic protrusions and ruffling membranes; in interference reflection microscopy the adhesion areas are mostly localized in these projections. A rearrangement of microfilaments and of tonofilaments in the cell projections and the formation of a dense network of keratin fibers takes place. Tamoxifen affects cellular shape and cytoskeletal arrangement in a way similar to that induced by estrogen. An effect of estrogen-receptor stimulation on the adhesion structures and on the rearrangement of intermediate and actin filaments (and accordingly of the shape and internal structure of breast cancer cells) can be suggested. Such an effect might be direct or mediated through unknown mechanisms; it seems, however, to be independent of the well known estrogenic effect on cell proliferation.

Actins↗

Blockade of neuronal activity during hippocampal development produces a chronic focal epilepsy in the rat.

During brain development, neuronal activity can transform neurons characterized by widely ranging axonal projections to ones with more restricted patterns of synaptic connectivity. Previous studies have shown that an exuberant outgrowth of local recurrent excitatory axons occurs in hippocampal area CA3 during postnatal weeks 2 and 3. Axons are remodeled with maturation, and nearly half of the branches are eliminated. Postnatal weeks 2 and 3 also coincide with a "critical" period of development, when CA3 networks have a marked propensity to generate electrographic seizures. In an attempt to prevent axonal remodeling, local circuit activity was blocked unilaterally in dorsal hippocampus by continuous infusion of tetrodotoxin (TTX). Field potential recordings from behaving animals were dramatically altered when TTX infusion was initiated at the beginning of the critical period, week 2, but not later in life. Spontaneous, synchronized spikes and electrographic seizures with behavioral accompaniments were observed after 4 weeks of TTX infusion and persisted into adulthood. When recordings were made during TTX infusion, synchronized spiking was recorded in ventral hippocampus as early as 2 weeks after infusate introduction. At this same time, extracellular field recordings from in vitro slices demonstrated spontaneous network-driven "mini-bursts" arising from ventral hippocampal slices. These were abolished by glutamate receptor antagonists. Whole-cell recordings from CA3 neurons revealed bursts of excitatory synaptic potentials coincident with the network bursts recorded extracellularly. Thus, local assemblies of mutually excitatory CA3 pyramidal cells are hyperexcitable in these rats. Whether alterations in developmental axonal remodeling mediate these effects awaits further studies.

Animals↗

Architecture of optimal transport networks.

We analyze the structure of networks minimizing the global resistance to flow (or dissipative energy) with respect to two different constraints: fixed total channel volume and fixed total channel surface area. First, we show that channels must be straight and have uniform cross-sectional areas in such optimal networks. We then establish a relation between the cross-sectional areas of adjoining channels at each junction. Indeed, this relation is a generalization of Murray's law, originally established in the context of local optimization. We establish a relation too between angles and cross-sectional areas of adjoining channels at each junction, which can be represented as a vectorial force balance equation, where the force weight depends on the channel cross-sectional area. A scaling law between the minimal resistance value and the total volume or surface area value is also derived from the analysis. Furthermore, we show that no more than three or four channels meet at each junction of optimal bidimensional networks, depending on the flow profile (e.g., Poiseuille-like or pluglike) and the considered constraint (fixed volume or surface area). In particular, we show that sources are directly connected to wells, without intermediate junctions, for minimal resistance networks preserving the total channel volume in case of plug flow regime. Finally, all these results are compared with the structure of natural networks.

Journal Article↗

[Exposure to VHF and UHF electromagnetic fields among workers employed in radio and TV broadcast centers. I. Assessment of exposure].

Nowadays, radio and television have become one of the areas of the human technical activity that develops most rapidly. Also ultra-short waves of VHF (30-300 MHz) and UHF (0.3-3 GHz) bands have proved to be the most important carriers of radio and TV-programs. In Poland, a network of radio and TV broadcast centers (RTCN) with high (over 200 m) masts was set up in the 1960s and 1970s. These centers concentrate the majority of stations broadcasting national and local programs (for areas within the RTCN range). At present, the RTCN established several decades ago are equally important. The assessment of the exposure to electromagnetic fields among workers of multi-program broadcast stations is complicated and feasible only to a certain degree of approximation because of changing conditions of exposure in individual stations during their long history, resulting from the changing numbers and types of transmitters installed. In this work, the method of retrospective estimation of exposure dose is described, and the results of the assessment carried out at three kinds of typical RTCN are discussed. The results of the analysis indicate that the workers of RTCN are exposed primarily to electromagnetic fields of VHF and UHF bands, but this exposure may be considered as admissible, hence it should not exert an adverse effect on the workers' health.

Electromagnetic Fields↗

Early onset of post-movement beta electroencephalogram synchronization in the supplementary motor area during self-paced finger movement in man.

A voluntary finger movement is accompanied by an event-related desynchronization followed by a short burst of beta oscillations or event-related synchronization. These beta bursts are dominant over the contralateral hand representation area, but also appear over the midcentral area overlaying the supplementary motor area (SMA) and the foot representation area. We show that the induced midcentral beta oscillations following movement-offset display not only slightly higher frequency components, but have also a significantly earlier onset. These beta oscillations arise likely from the SMA. Assuming that the short-lasting beta synchronizations at frequencies below 35 Hz after termination of a movement reflect a state of localized cortical inhibition, we propose that the induced midcentral oscillations reflect the inhibition of networks within the SMA. This assumed resetting or inhibitory process within the SMA precedes that of the networks within the primary motor hand area.

Beta Rhythm↗

Aging is associated with contrasting changes in local and distant cortical connectivity in the human motor system.

Pathophysiological changes in neurological and neuropsychiatric diseases are increasingly described in terms of abnormal network connectivity. However, the anatomical integrity and efficacy of connections among multiple brain regions change with aging, even in healthy adults. We combined low-frequency transcranial magnetic stimulation and positron emission tomography to study the age-related changes in regional activation and effective connectivity, associated with voluntary action by healthy adults between 22 and 68 years old. Contrasting effects of aging on the motor network were seen using analyses of regional activation, effective connectivity mediating task-related neuronal activation and effective connectivity in response to transcranial magnetic stimulation. Low-frequency rTMS reduced cerebral blood flow during both movement and resting conditions, at the site of stimulation and neighboring frontal cortex. Aging was associated with increased movement-related activation in premotor cortex, bilaterally. Increasing age also increased the susceptibility of the cortex to the inhibitory effects of rTMS, at the site of stimulation and its contralateral homologue. Moreover, older subjects showed enhanced local effective connectivity, centered on the left premotor cortex, but reduced effective connectivity between distant motor-related cortical areas. We discuss these results in relation to the HAROLD model of aging and propose that there are differential effects of aging on local and distributed neuronal subpopulations in the motor network. This differential effect of aging has important implications for the study of neurodegenerative and cerebrovascular diseases that primarily affect older people, as well as our understanding of the normal aging process.

Adult↗

A more biologically plausible learning rule than backpropagation applied to a network model of cortical area 7a.

Area 7a of the posterior parietal cortex of the primate brain is concerned with representing head-centered space by combining information about the retinal location of a visual stimulus and the position of the eyes in the orbits. An artificial neural network was previously trained to perform this coordinate transformation task using the backpropagation learning procedure, and units in its middle layer (the hidden units) developed properties very similar to those of area 7a neurons presumed to code for spatial location (Andersen and Zipser, 1988; Zipser and Andersen, 1988). We developed two neural networks with architecture similar to Zipser and Andersen's model and trained them to perform the same task using a more biologically plausible learning procedure than backpropagation. This procedure is a modification of the Associative Reward-Penalty (AR-P) algorithm (Barto and Anandan, 1985), which adjusts connection strengths using a global reinforcement signal and local synaptic information. Our networks learn to perform the task successfully to any degree of accuracy and almost as quickly as with backpropagation, and the hidden units develop response properties very similar to those of area 7a neurons. In particular, the probability of firing of the hidden units in our networks varies with eye position in a roughly planar fashion, and their visual receptive fields are large and have complex surfaces. The synaptic strengths computed by the AR-P algorithm are equivalent to and interchangeable with those computed by backpropagation. Our networks also perform the correct transformation on pairs of eye and retinal positions never encountered before. All of these findings are unaffected by the interposition of an extra layer of units between the hidden and output layers. These results show that the response properties of the hidden units of a layered network trained to perform coordinate transformations, and their similarity with those of area 7a neurons, are not a specific result of backpropagation training. The fact that they can be obtained by a more biologically plausible learning rule corroborates the validity of this neural network's computational algorithm as a plausible model of how area 7a may perform coordinate transformations.

Algorithms↗

[Telemedicine stroke department network. Introduction of a telemedicine pilot project for integrated stroke management in South Bavaria and analysis of its efficiency].

More than 100 stroke units have been established in Germany. In rural areas, however, acute stroke care needs to be improved. In order to advance clinical stroke therapy, two specialized stroke centers founded a telemedicine network (TEMPiS) among 12 community hospitals in eastern Bavaria. Each network hospital established specialized stroke wards where qualified teams manage acute stroke patients. Twenty-four hours daily, physicians in local hospitals are able to contact the stroke centers via videoconferencing including transmission of digital DICOM data. To study the efficacy of this network, a controlled trial will be performed. Five TEMPiS-network hospitals will be matched with five other hospitals equal in size, catchment area, and diagnostic techniques. For about 1 year, all consecutive stroke cases in the matched study hospitals will be prospectively recorded in a database. Neurological deficits will be quantified on the National Institute of Health Stroke Scale within 24 h after stroke onset. Mortality and institutional care as a combined primary endpoint will be assessed after 3 and 12 months. Furthermore, functional outcome according to the modified Rankin scale, Barthel score, and quality of life will be assessed using a standard telephone interview. Data acquisition started in July 2003, and final results are expected in 2005.

Centralized Hospital Services↗

[Connectionist modeling of higher-level cognitive processes].

Connectionist modeling is one approach to understanding human intelligence using simulated networks of neuron-like processing units. In this article, we report on recent progress in connectionist models that simulate empirical data of higher-level cognitive processes, these being memory, learning, language, thinking, cognitive development, and social cognition. We also review and summarize the advantages and disadvantages of these connectionist models. The computational framework of connectionist modeling has the potential to integrate specialized psychological findings of different areas using the same architectures and local functions of units and connections, inspired from neuroscience. In particular, the problems of dealing with structured information in distributed form, and doing tasks that require variable binding in connectionist networks are discussed from several different perspectives. As one possible solution to treat systematic mental representations properly, the symbolic connectionist model, which is a hybrid approach using symbolic representations and connectionist architectures, is explained. We argue that connectionist computer simulation offers significant benefits for today's psychological researches, and that connectionist modeling is likely to have an important influence on future studies.

Cognition↗

APA/HRSA National Faculty Development Scholars Program: community-based teaching track.

OBJECTIVES: Goals and objectives of the APA/HRSA National Faculty Development Scholars Program are described in a companion article in this supplement. Program objectives of the Community-Based Teaching Track were to 1) identify individuals with faculty development skills to serve as regional leaders, conducting local and regional workshops; 2) create a national network of leaders, thereby promoting sustainability; and 3) increase educational contributions of office-based preceptors. Participant objectives were to 1) meet expectations of the program; 2) possess knowledge, skills, and attitudes needed to recruit and retain community-based preceptors; 3) possess knowledge and skills needed to conduct faculty development workshops for practitioners; and 4) form local and national collegial networks. METHODS: Academicians and practitioners were selected to form 2 cohorts, starting in 1999 (N = 20) and 2000 (N = 22), respectively. Workshops were developed on the basis of projected needs and iterative needs assessments of the participants. Each participant was required to conduct workshops between meetings, first locally and then regionally or nationally. OUTCOMES: Forty-two participants conducted 307 workshops attended by 3815 individuals. Participants reported specific knowledge and skills gained from the program and increases in multiple areas of competence. Networks were formed, leading to collaborative regional and national presentations and formation of an APA Faculty Development Special Interest Group. Participants reported increased recruitment of training sites and preceptors, with enhanced relationships. CONCLUSION: Program and participant objectives of the Community-Based Teaching Track were met, including implementation of multiple new workshops, development of skills, and creation of a support network to enhance the sustainability of that success.

Ambulatory Care↗

Neuropeptide Y: brain localization and central effects on plasma insulin levels in chicks.

A rich network of NPY-like immunoreactive fibers was found in the paraventricular nucleus and the ventromedial region of the hypothalamus juxtapositioned to the third ventricle, including the median eminence. Brain regions, areas or nuclei found densely innervated by NPY-like immunoreactive fibers included the olfactory bulb region, septal area, organum vasculosum of the lamina terminalis, preoptic periventricular nucleus, hypothalamic periventricular nucleus, medial suprachiasmatic nucleus, subseptal (subfornical) organ, ventromedial hypothalamic nucleus, infundibular nucleus and nucleus tractus solitarius. NPY-like containing perikarya were localized within the hippocampus, bed nucleus of the stria terminalis and surrounding the nucleus rotundus and nucleus of the basal optic root. Since the immunocytochemical study showed that NPY was localized in brain structures known to alter food intake and the compound is a member of the pancreatic polypeptide family, a second study was designed to determine if the neuropeptide altered plasma concentrations of insulin, glucagon and glucose following intracerebroventricular administration. It was found that NPY significantly increased plasma concentration of insulin. It is proposed that two reasons why NPY is such a potent orexigenic agent is that the paraventricular nucleus and structures surrounding the third ventricle throughout the ventromedial hypothalamic region show high levels of NPY-like immunoreactivity. Secondly, NPY effects an increase in plasma insulin in the periphery.

Animals↗