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PubMed2000

Improved quantitative structure property relationships for the prediction of dielectric constants for a set of diverse compounds by subsetting of the data set

In a recent publication we explored the development of quantitative structure property relationships for the calculation of dielectric constants, which resulted in a general model for a wide range of compounds. Our current work explores the division of the set of compounds into eight more homogeneous subsets for which local models are developed. The full data set consists of 454 compounds with dielectric constants ranging from 1 to 40. A pool of up to 16 molecular descriptors is calculated for each of the eight data sets. The descriptors include dipole moment, polarizability, counts of elemental types or functional groups, charged partial surface area, and molecular connectivity. All possible 4-16 descriptor models are calculated for each of the eight data sets, and the best models are selected and compared to the results obtained from the best general model for all 454 compounds. Neural networks using the Broyden-Fletcher-Goldfarb-Shanno training algorithm are employed to build the models. The resulting combined mean test set error for the eight local models of 1.31 is significantly better than the mean test set error of 1.85 for the general model.

Journal Article↗
PubMed2006

Brain areas involved in medial temporal lobe seizures: a principal component analysis of ictal SPECT data.

The study describes brain areas involved in medial temporal lobe (mTL) seizures of 12 patients. All patients showed so-called oro-alimentary behavior within the first 20 s of clinical seizure manifestation characteristic of mTL seizures. Single photon emission computed tomography (SPECT) images of regional cerebral blood flow (rCBF) were acquired from the patients in ictal and interictal phases and from normal volunteers. Image analysis employed categorical comparisons with statistical parametric mapping and principal component analysis (PCA) to assess functional connectivity. PCA supplemented the findings of the categorical analysis by decomposing the covariance matrix containing images of patients and healthy subjects into distinct component images of independent variance, including areas not identified by the categorical analysis. Two principal components (PCs) discriminated the subject groups: patients with right or left mTL seizures and normal volunteers, indicating distinct neuronal networks implicated by the seizure. Both PCs were correlated with seizure duration, one positively and the other negatively, confirming their physiological significance. The independence of the two PCs yielded a clear clustering of subject groups. The local pattern within the temporal lobe describes critical relay nodes which are the counterpart of oro-alimentary behavior: (1) right mesial temporal zone and ipsilateral anterior insula in right mTL seizures, and (2) temporal poles on both sides that are densely interconnected by the anterior commissure. Regions remote from the temporal lobe may be related to seizure propagation and include positively and negatively loaded areas. These patterns, the covarying areas of the temporal pole and occipito-basal visual association cortices, for example, are related to known anatomic paths.

Adolescent↗
PubMed2001

Immunohistochemical localization of the vasopressin V1b receptor in the rat brain and pituitary gland: anatomical support for its involvement in the central effects of vasopressin.

Biological effects of vasopressin (VP) are mediated by four different receptors, two of which (the V1a and the oxytocin receptors) have been well characterized in the rodent brain, suggesting that these are the main receptors responsible for the central effects of VP. However, transcripts of the V1b VP receptor (V1bR) have been detected throughout the rat brain by RT-PCR and in situ hybridization, indicating that the V1bR adds to the population of central VP receptors. Because there are no specific ligands for the V1bR, the receptor protein itself has been difficult to visualize. In the present study, the distribution of the V1bR protein was investigated in the rat forebrain, midbrain, hindbrain, and cerebellum by immunohistochemistry using an antiserum raised against a synthetic fragment of the carboxylterminal of the rat V1bR protein. Immunohistochemistry revealed the presence of the V1bR in pituitary corticotrophs as expected. In naive, untreated rats, fiber networks containing V1bR-immunoreactivity were mainly concentrated in the hypothalamus, amygdala, cerebellum, and particularly in those areas with a leaky blood brain barrier or close to the circumventricular organs (medial habenula, subfornical organ, organum vasculosum laminae terminalis, median eminence, and nuclei lining to the third and fourth ventricles). A strikingly dense network was present in the external zone of the median eminence. Colchicine treatment was required to reveal the localization of V1bR-immunoreactive cell bodies. V1bR-containing cell bodies and associated protrusions were mainly located in the hippocampus, caudate putamen, cortex, thalamus, olfactory bulb, and cerebellum. These results demonstrate the widespread distribution of the V1bR protein in the rat brain over multiple, functionally distinct neuronal systems. These data suggest that the V1bR mediates different physiological functions of VP in the brain.

Animals↗
PubMed2006

Prediction of protein secondary structure content using amino acid composition and evolutionary information.

Knowing protein structure and inferring its function from the structure are one of the main issues of computational structural biology, and often the first step is studying protein secondary structure. There have been many attempts to predict protein secondary structure contents. Previous attempts assumed that the content of protein secondary structure can be predicted successfully using the information on the amino acid composition of a protein. Recent methods achieved remarkable prediction accuracy by using the expanded composition information. The overall average error of the most successful method is 3.4%. Here, we demonstrate that even if we only use the simple amino acid composition information alone, it is possible to improve the prediction accuracy significantly if the evolutionary information is included. The idea is motivated by the observation that evolutionarily related proteins share the similar structure. After calculating the homolog-averaged amino acid composition of a protein, which can be easily obtained from the multiple sequence alignment by running PSI-BLAST, those 20 numbers are learned by a multiple linear regression, an artificial neural network and a support vector regression. The overall average error of method by a support vector regression is 3.3%. It is remarkable that we obtain the comparable accuracy without utilizing the expanded composition information such as pair-coupled amino acid composition. This work again demonstrates that the amino acid composition is a fundamental characteristic of a protein. It is anticipated that our novel idea can be applied to many areas of protein bioinformatics where the amino acid composition information is utilized, such as subcellular localization prediction, enzyme subclass prediction, domain boundary prediction, signal sequence prediction, and prediction of unfolded segment in a protein sequence, to name a few.

Amino Acid Sequence↗
PubMed2002

Propagation of neuronal activity along the neocortical-perirhinal-entorhinal pathway in the guinea pig.

The study of synaptic interactions within the parahippocampal region is crucial to understand the integrative functions performed by this region during memory information processing. Despite the extensive anatomical studies, the intrinsic physiology of the parahippocampal area has been poorly investigated. We describe here the organization pattern of the synaptic network formed by the temporal neocortex, areas 36 and 35 of the perirhinal cortex (PRC) and the entorhinal cortex (EC), in the in vitro isolated guinea-pig brain. Current source density analysis of laminar field potential profiles was performed with multichannel silicon probes positioned in different parahippocampal subfields. Stimulation of the temporal neocortex induced monosynaptic and polysynaptic potentials in areas 35 and 36, respectively. Area 36 stimulation evoked monosynaptic responses within areas 36 and 35. Stimuli in area 35 induced responses that propagated longitudinally along area 35 itself. No local field responses were observed in the EC after stimulation of both neocortex and areas 35/36. Despite the absence of a local extracellular response, intracellular recordings demonstrated that subpopulations of superficial layer neurons in medial and lateral EC showed polysynaptic EPSPs after stimulation of area 35 and area 36. The results demonstrate that the propagation of neuronal activity across the rhinal sulcus in the direction from the PRC to the EC is finely and diffusely distributed. In agreement with previous reports, these findings suggest that the PRC-EC pathway is highly regulated by inhibitory network interactions.

Animals↗
PubMed2001

Reducing sediment inputs to Scottish streams: a review of the efficacy of soil conservation practices in upland forestry.

The historical process by which a soil conservation strategy has evolved within the UK forestry industry is briefly reviewed. Particular attention is given to the development of practical and effective guidelines to prevent both soil damage and sediment entering water courses. It is concluded that the 'Forest and Water Guidelines', together with other forest industry manuals, largely provide adequate protection for aquatic habitats from pre-afforestation cultivation and from harvesting activities. The problem of soil erosion owing to ploughing of open furrows has largely been obviated by improved drainage network design coupled with the use of vegetated buffer strips and sediment catchpits. Alternative site preparation techniques, such as 'moling' or 'dolloping' of afforestation sites, are now preferred. However, the effects on slope hydrology and the improved soil conservation associated with these methods require quantifying. Additional understanding of effective buffer strip function, for example, on a variety of slope angles, soil types and vegetation associations would be beneficial. The design of forest roads and the associated network of drains, culverts and sediment catchpits is addressed in forestry guidelines. Future potential in this area may involve the use of Geographical Information Systems in the effective design of road networks which minimise adverse effects on slope hydrology. Similarly computer simulation of flow routing might aid in the design of road drain networks. At the more local scale there remains scope for further research aimed at minimising soil disturbance by machinery. Consideration should also be given to the long-term sustainability of the soil structure through second and subsequent crop rotations.

Conservation of Natural Resources↗
PubMed1975

Mucocutaneous leishmaniasis in guinea-pigs inoculated intravenously with Leishmania enriettii. Preliminary report.

Seven guinea-pigs were inoculated intravenously with a rich suspension of Leishmania enriettii. During the sixth to the seventh week from inoculation, all of them developed lesions within the anterior nasal mucosa and in the vulva or scrotum. In one animal nodules occurred in the forepaws during the tenth week. The histology of the latter showed an epithelioid granuloma with multinucleate giant cells, while in all the others macrophages and monocytes highly parasitized with leishmania bodies, formed the main elements in the granulomatous infiltrate. Lesions seem to develop in the cool, non-hairy areas of the integument and those areas of the nasal mucosa which are constantly bombarded by the inhaled cool air stream. The anterior nasal mucosa, with its leaking venular network, its cool timperature, relative stasis and hypoxia probably provides the optimum micro-environment for the localization, survival and multiplication of the leishmanial protozoon.

Animals↗
PubMed2002

Variations in rural AIDS epidemiology and service delivery models in the United States.

This article reviews AIDS surveillance data and the rural health literature to summarize what is known about the rural AIDS epidemic, characteristics of rural environments that affect HIV service delivery, and approaches that rural areas are using to address the health and support service needs of HIV-positive residents. During 1999, nonmetropolitan (non-MSA) adult/adolescent AIDS rates were highest in the South (11 per 100,000) and Northeast (9 per 100,000). The South had the highest non-MSA proportion of adult/adolescent AIDS cases (12%), followed by the North Central region (9%), the West (4%), and the Northeast (3%). Variations in rural HIV/AIDS epidemiologic patterns and the demographic, socio-economic, and cultural characteristics of rural environments are likely to require different levels of resource investment and different methods of organizing and delivering HIV services. Currently, many HIV-positive rural residents are traveling to metropolitan areas for medical care because of concerns about confidentiality or a lack of confidence in the HIV management capabilities of local physicians. Rural communities are attempting to address these problems by developing the HIV care capacity of existing clinics, building local networks of physicians with HIV management experience, and cultivating "shared care" arrangements with urban-based specialists.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Male sexual behaviour during wife's pregnancy and postpartum abstinence period in Oyo State, Nigeria.

The traditional proscription against sex for women during pregnancy, and particularly in the postpartum period, in south-west Nigeria leaves many men without sexual access to their wives for extended periods of time. This practice raises the question whether men abstain or seek other sexual partners. A community-based study was conducted using 3,204 married men from randomly selected local government areas of the state. These men had wives who had delivered a baby in the 36 months prior to the study. Information was obtained on their sexual practices before and during pregnancy and the postpartum period. Male sexual networking was not absent outside the pregnancy and the postpartum periods. However, during pregnancy, a higher percentage of men (43.7%) had other partners compared with the period outside pregnancy and postpartum (42.1%). The difference was not significant (p>0.05). Similarly, in the postpartum abstinence period, more men (48%) had other sexual partners when compared with the period outside pregnancy and postpartum (42.1%; p<0.001). Sexual networking with non-regular and multiple partners was also more commonly observed in the postpartum period than in pregnancy (11.9% vs 10.4%; p<0.05). Significantly more rural than urban men had multiple sexual partners when their wife was pregnant (p=0.01) or in postpartum abstinence (p<0.05). Condom use with regular partners was largely absent, and consistent condom use with extramarital partners was very low among urban and rural men (6.3% vs 1.7%). The vast majority of men were having unprotected vaginal sex. Logistic regression analysis showed that polygamous men, those under 30 years in the urban area, and men with low or no education were more likely to have sex with other women when their wife was pregnant. During a wife's postpartum abstinence period, men in higher status occupations, younger urban men (<49 years), those with more children, the polygamous, and men with a first wife under 40 years in urban area were more likely to have other partners. In light of the heterosexual mode of HIV transmission in Nigeria, there is a dire need to design and implement an intervention programme targeted at married men, which takes into consideration cultural practices. This will hopefully help check the course of the disease in a country thought to be on the verge of an HIV epidemic.

Age Distribution↗
PubMed2002

[Epidemiology of smoking in Europe].

Tobacco is the most important preventable cause of mortality in European countries, accounting for over half a million deaths per year. A review is presented on the epidemiology of tobacco smoking in Europe, using a comprehensive approach on the health effects of smoking, the prevalence of tobacco consumption, and its evolution in the past decade. Tobacco industry efforts to promote and maintain smoking through production and pricing are also reviewed. Thirty out of every 100 European adults smoke everyday and one of every ten adults smokers will die from tobacco smoking; a higher ratio of 1:15 is found in Eastern Europe. The prevalence of smokers is decreasing among young adults in some European countries, while it is increasing among young women in Southern and Eastern Europe. Smoking cessation and prevention interventions should be implemented, such as banning smoking in public areas, banning direct and indirect advertising of tobacco products, crop reduction, and rising cigarette prices. These interventions should be designed, coordinated, and developed by and among the different sectors involved in tobacco control initiatives, together with social network at the local, regional, and national levels, with the support of national and international organizations.

Adolescent↗
PubMed1991

Leakage and neuronal uptake of serum protein in aged and Alzheimer brains. A postmortem phenomenon with antemortem etiology.

Abnormal extravasation of serum proteins has frequently been reported in Alzheimer's disease (AD) and less often in nondemented, aged individuals. In order to establish whether these are ante or postmortem phenomena, we have now compared the immunocytochemical localization of immunoglobulin in young, aged, and AD brains. In all the young brains, but only in some of the aged and AD brains, immunoglobulin was confined to a fine network of microvessels. In contrast, the majority of AD, as well as apparently normal, aged brains revealed both focal and diffuse extravascular localization in the form of neuronal labeling as well as a general, diffuse background. Since microvessels in these areas were no longer revealed, it was felt that the extravascular leakage occurred postmortem at a time when replacement of intravascular immunoglobulin had ceased. Furthermore, there was a correlation between the extent of leakage and time interval between death and autopsy. Postmortem leakage of serum protein was reproduced in a more controlled system using young and aged rats; serum protein leakage evolved from focal to diffuse patterns in aged brains as the postmortem period increased, whereas the leakage was restricted to the outer half of the cortices in young brains even after a prolonged postmortem period. Postmortem trauma to the rat brain also caused lesion-related leakage as well as neuronal labeling. It was concluded that extravascular leakage and neuronal uptake in aged and AD brains is a postmortem phenomenon, due to delay in autopsy or mishandling of brains, but dependent in severity upon antemortem circumstances.

Aged↗
PubMed1996

Yellow fever: an emerging threat for Kenya and other east African countries.

Yellow fever (YF) is a well known disease that had plagued the tropics relentlessly until an effective vaccine was developed. Although the yellow fever vaccine is relatively affordable and one dose protects for over ten years, its use has predominantly been for known endemic areas of the world and international travellers. Eastern and southern African states, have hitherto been free of epidemic yellow fever, hence routine YF vaccination is not a policy in these countries. The sudden emergence of YF in the Rift Valley in Kenya in 1992-1993, introduces new dimensions into the challenges of YF to eastern and southern African states. Isolation of a virus deemed to be native of the area is discussed in this article in the context of YF policy issues confronting the region. A case has been argued for the establishment of a network of active surveillance systems in the region backed by adequate laboratory YF expertise locally, regionally, and internationally.

Africa, Eastern↗
PubMed2004

Initiation of electrographic seizures by neuronal networks in entorhinal and perirhinal cortices in vitro.

The hippocampus is often considered to play a major role in the pathophysiology of mesial temporal lobe epilepsy. However, emerging clinical and experimental evidence suggests that parahippocampal areas may contribute to a greater extent to limbic seizure initiation, and perhaps epileptogenesis. To date, little is known about the participation of entorhinal and perirhinal networks to epileptiform synchronization. Here, we addressed this issue by using simultaneous field potential recordings in horizontal rat brain slices containing interconnected limbic structures that included the hippocampus proper. Epileptiform discharges were disclosed by bath applying the convulsant drug 4-aminopyridine (50 microM) or by superfusing Mg(2+)-free medium. In the presence of 4-aminopyridine, slow interictal- (duration=2.34+/-0.29 s; interval of occurrence=25.75+/-2.11 s, n=16) and ictal-like (duration=31.25+/-3.34 s; interval of occurrence=196.96+/-21.56 s, n=17) discharges were recorded in entorhinal and perirhinal cortices after abating the propagation of CA3-driven interictal activity to these areas following extended hippocampal knife cuts. Simultaneous recordings obtained from the medial and lateral entorhinal cortex, and from the perirhinal cortex revealed that interictal and ictal discharges could initiate from any of these areas and propagate to the neighboring structure with delays of 8-66 ms. However, slow interictal- and ictal-like events more often originated in the medial entorhinal cortex and perirhinal cortex, respectively. Cutting the connections between entorhinal and perirhinal cortices (n=10), or functional inactivation of cortical areas by local application of a glutamatergic receptor antagonist (n=11) made independent epileptiform activity occur in all areas. These procedures also shortened ictal discharge duration in the entorhinal cortices, but not in the perirhinal area. Similar results could be obtained by applying Mg(2+)-free medium (n=7). These findings indicate that parahippocampal networks provide independent epileptiform synchronization sufficient to sustain limbic seizures as well as that the perirhinal cortex plays a preferential role in in vitro ictogenesis.

4-Aminopyridine↗
PubMed1994

Telencephalin: a neuronal area code molecule?

Cell adhesion molecules (CAMs) with expression restricted to specific developmental and structural units of the brain and/or selective neuronal types would play critical roles in the formation of functional neuronal networks. In this article, we summarize recent progress in knowledge on a brain segment-specific CAM, telencephalin (TLN). TLN has the following characteristic properties. (1) TLN is a neuronal glycoprotein whose expression is restricted within telencephalon, the most rostal segment of the brain. (2) TLN is localized to the soma-dendritic membrane of subsets of telencephalic neurons, but not to the axonal membrane. (3) Abrupt appearance of TLN around birth parallels the timing of dendritic development and synapse formation in the telencephalon. (4) TLN belongs to the immunoglobulin superfamily and its structure is most closely related to intercellular adhesion molecules (ICAMs)-1 and -3. These findings suggest that TLN is the first example of dendrite-associated cell adhesion molecules (DenCAMs) and that TLN may be involved in the brain segmental organization, cell-cell interactions during dendritic development, and maintenance of functional neuronal networks. We discuss the possibility that TLN is an area code-like address signal that is displayed selectively by telencephalic neurons and is decoded by specific subsets of growing axons to make proper synaptic connections.

Animals↗
PubMed1994

Effects of fetal calf serum and disruption of cadherin function on the formation of bile canaliculi between hepatocytes.

The polarization of hepatocytes to form a connected network of bile canaliculi (BC) is necessary for the function of the liver. Hepatocyte polarization may be controlled by soluble factors and/or physical interactions between cells. Monolayer cultures of embryonic chicken hepatocytes in DMEM supplemented with ornithine, dexamethasone, and insulin express BC-specific antigens for at least 7 days. However, BC-specific antigen expression is lost within 3 days of culture initiation in DMEM containing 10% fetal calf serum. The dedifferentiating effects of fetal calf serum (FCS) can be reversed. Furthermore, cultures in medium containing ornithine, dexamethasone, insulin, and 10% FCS appear identical to cultures grown in 10% FCS alone. Thus FCS contains a soluble inhibitor of hepatocyte polarization. Aggregate cultures grown in suspension maintain hepatocyte polarization for 10-12 days. This may be due to the increased cell-cell contact between hepatocytes in aggregate culture or to more normal contact with the extracellular matrix. We have evaluated the role of cadherin-mediated interactions on hepatocyte polarization. Anti-E-cadherin Fab' fragments disrupted the formation of long networks of BC in monolayer cultures but did not stop polarized expression of BC-specific antigens. The BC antigens in anti-E-cadherin-treated cells were concentrated in small areas between cells and were present at lower levels uniformly on the cell surface. These results indicate that E-cadherin is required for the formation of extended BC networks, but that other factors are responsible for maintaining the synthesis and localization of BC-specific antigens.

Animals↗
PubMed1984

Cessation of capillary blood flow induced by localized application of carbon dioxide.

A small test area of the pulmonary capillary bed of frog's lung was exposed to carbon dioxide. The capillary bed was observed by means of a dark field episcopal microscope and recorded on video tapes via a TV-camera. Swollen capillaries forming a hexagonal network surrounded concave alveolar cells. The flow velocity of red blood cells through capillaries was reduced to 17.5% of the flow velocity during the control condition by the application of the moistened gas mixture containing 30% CO2. The blood flow in capillaries ceased when wet 100% CO2 was applied to the test area. Red blood cells were packed in capillaries. They disaggregated by the introduction of air in five seconds and were quickly flowing in an elongated leaflet shape in 30 seconds after the introduction of air.

Animals↗
PubMed1992

Local optimization of neuron arbors.

How parsimoniously is brain wiring laid out, that is, how well does a neuron minimize costs of connections among its synapses? Neural optimization of dendritic and axonic arbors can be evaluated using a generalization of the Steiner tree concept from combinatorial network optimization theory. Local branch-junction geometry of neuronal connecting structures fits a volume minimization model well. In addition, volume of the arborizations at this neighborhood level is significantly more strongly minimized than their length, signal propagation speed, or surface area. The mechanism of this local volume optimization resembles those involved in formation of nonliving tree structures such as river junctions and electric-discharge patterns, and appears to govern initial nerve growth-cone behavior through vector-mechanical energy minimization.

Animals↗
PubMed1983

Predictors of help-seeking in an urban setting: the search for child care.

The aim of this exploratory study was to identify variables which predict how parents search for child care. Structured interviews were conducted with 50 parents of young children who had searched for full-time nonrelative child care. The respondents represented a 1% sample of Detroit parents. Search behaviors were found to be related to perceived neighborhood age, personal social network ties, and income and family structure. Personal social network ties related to contrasting sets of search behaviors, described as cosmopolitan versus parochial help-seeking patterns. However, perceived neighborhood age modified the relationship between social network ties and search behaviors in that the contrast between cosmopolitan and parochial help-seeking patterns was found only in neighborhoods where most residents had lived more than 10 years (established areas). The findings point to the need for multivariate investigations of the relationship between neighborhood context and patterns of help-seeking, especially in regards to the role of personal social networks. Implications of the findings for the design of a local child care information and referral service are discussed.

Adolescent↗