Effects of Metabolic Risk Factors and Type 1 Diabetes on Brain Glucose and Brain Metabolites

The metabolic syndrome and type 1 diabetes are associated with brain alterations such as cognitive decline brain infarctions, atrophy, and white matter lesions. Despite the importance of these alterations, their pathomechanism is still poorly understood. This study was conducted to investigate brain glucose and metabolites in healthy individuals with an increased cardiovascular risk and in patients with type 1 diabetes in order to discover more information on the nature of the known brain alterations. We studied 43 20- to 45-year-old men. Study I compared two groups of non-diabetic men, one with an accumulation of cardiovascular risk factors and another without. Studies II to IV compared men with type 1 diabetes (duration of diabetes 6.7 ± 5.2 years, no microvascular complications) with non-diabetic men. Brain glucose, N-acetylaspartate (NAA), total creatine (tCr), choline, and myo-inositol (mI) were quantified with proton magnetic resonance spectroscopy in three cerebral regions: frontal cortex, frontal white matter, thalamus, and in cerebellar white matter. Data collection was performed for all participants during fasting glycemia and in a subgroup (Studies III and IV), also during a hyperglycemic clamp that increased plasma glucose concentration by 12 mmol/l. In non-diabetic men, the brain glucose concentration correlated linearly with plasma glucose concentration. The cardiovascular risk group (Study I) had a 13% higher plasma glucose concentration than the control group, but no difference in thalamic glucose content. The risk group thus had lower thalamic glucose content than expected. They also had 17% increased tCr (marker of oxidative metabolism). In the control group, tCr correlated with thalamic glucose content, but in the risk group, tCr correlated instead with fasting plasma glucose and 2-h plasma glucose concentration in the oral glucose tolerance test. Risk factors of the metabolic syndrome, most importantly insulin resistance, may thus influence brain metabolism. During fasting glycemia (Study II), regional variation in the cerebral glucose levels appeared in the non-diabetic subjects but not in those with diabetes. In diabetic patients, excess glucose had accumulated predominantly in the white matter where the metabolite alterations were also the most pronounced. Compared to the controls values, the white matter NAA (marker of neuronal metabolism) was 6% lower and mI (glia cell marker) 20% higher. Hyperglycemia is therefore a potent risk factor for diabetic brain disease and the metabolic brain alterations may appear even before any peripheral microvascular complications are detectable. During acute hyperglycemia (Study III), the increase in cerebral glucose content in the patients with type 1 diabetes was, dependent on brain region, between 1.1 and 2.0 mmol/l. An every-day hyperglycemic episode in a diabetic patient may therefore as much as double brain glucose concentration. While chronic hyperglycemia had led to accumulation of glucose in the white matter, acute hyperglycemia burdened predominantly the gray matter. Acute hyperglycemia also revealed that chronic fluctuation in blood glucose may be associated with alterations in glucose uptake or in metabolism in the thalamus. The cerebellar white matter appeared very differently from the cerebral (Study IV). In the non-diabetic men it contained twice as much glucose as the cerebrum. Diabetes had altered neither its glucose content nor the brain metabolites. The cerebellum seems therefore more resistant to the effects of hyperglycemia than is the cerebrum.

Mesh Processing for Computerized Facial Anthropometry

Understanding of the shape and size of different features of the human body from scanned data is necessary for automated design and evaluation of product ergonomics. In this paper, a computational framework is presented for automatic detection and recognition of important facial feature regions, from scanned head and shoulder polyhedral models. A noise tolerant methodology is proposed using discrete curvature computations, band-pass filtering, and morphological operations for isolation of the primary feature regions of the face, namely, the eyes, nose, and mouth. Spatial disposition of the critical points of these isolated feature regions is analyzed for the recognition of these critical points as the standard landmarks associated with the primary facial features. A number of clinically identified landmarks lie on the facial midline. An efficient algorithm for detection and processing of the midline, using a point sampling technique, is also presented. The results obtained using data of more than 20 subjects are verified through visualization and physical measurements. A color based and triangle skewness based schemes for isolation of geometrically nonprominent features and ear region are also presented. [DOI: 10.1115/1.3330420]

A new method for modulating the activity of parvalbumin-positive neurons and cerebellar Purkinje cells in vivo

Neurons can be divided into various classes according to their location, morphology, neurochemical identity and electrical properties. They form complex interconnected networks with precise roles for each cell type. GABAergic neurons expressing the calcium-binding protein parvalbumin (Pv) are mainly interneurons, which serve a coordinating function. Pv-cells modulate the activity of principal cells with high temporal precision. Abnormalities of Pv-interneuron activity in cortical areas have been linked to neuropsychiatric illnesses such as schizophrenia. Cerebellar Purkinje cells are known to be central to motor learning. They are the sole output from the layered cerebellar cortex to deep cerebellar nuclei. There are still many open questions about the precise role of Pv-neurons and Purkinje cells, many of which could be answered if one could achieve rapid, reversible cell-type specific modulation of the activity of these neurons and observe the subsequent changes at the whole-animal level. The aim of these studies was to develop a novel method for the modulation of Pv-neurons and Purkinje cells in vivo and to use this method to investigate the significance of inhibition in these neuronal types with a variety of behavioral experiments in addition to tissue autoradiography, electrophysiology and immunohistochemistry. The GABA(A) receptor γ2 subunit was ablated from Pv-neurons and Purkinje cells in four separate mouse lines. Pv-Δγ2 mice had wide-ranging behavioral alterations and increased GABA-insensitive binding indicative of an altered GABA(A) receptor composition, particularly in midbrain areas. PC-Δγ2 mice experienced little or no motor impairment despite the lack of inhibition in Purkinje cells. In Pv-Δγ2-partial rescue mice, a reversal of motor and cognitive deficits was observed in addition to restoration of the wild-type γ2F77 subunit to the reticular nucleus of thalamus and the cerebellar molecular layer. In PC-Δγ2-swap mice, zolpidem sensitivity was restored to Purkinje cells and the administration of systemic zolpidem evoked a transient motor impairment. On the basis of these results, it is concluded that this new method of cell-type specific modulation is a feasible way to modulate the activity of selected neuronal types. The importance of Purkinje cells to motor control supports previous studies, and the crucial involvement of Pv-neurons in a range of behavioral modalities is confirmed.

Benchmarking recognition results on camera captured word image data sets

We have benchmarked the maximum obtainable recognition accuracy on five publicly available standard word image data sets using semi-automated segmentation and a commercial OCR. These images have been cropped from camera captured scene images, born digital images (BDI) and street view images. Using the Matlab based tool developed by us, we have annotated at the pixel level more than 3600 word images from the five data sets. The word images binarized by the tool, as well as by our own midline analysis and propagation of segmentation (MAPS) algorithm are recognized using the trial version of Nuance Omnipage OCR and these two results are compared with the best reported in the literature. The benchmark word recognition rates obtained on ICDAR 2003, Sign evaluation, Street view, Born-digital and ICDAR 2011 data sets are 83.9%, 89.3%, 79.6%, 88.5% and 86.7%, respectively. The results obtained from MAPS binarized word images without the use of any lexicon are 64.5% and 71.7% for ICDAR 2003 and 2011 respectively, and these values are higher than the best reported values in the literature of 61.1% and 41.2%, respectively. MAPS results of 82.8% for BDI 2011 dataset matches the performance of the state of the art method based on power law transform.

Tonic current through GABAA receptors and hyperpolarization-activated cyclic nucleotide-gated channels modulate resonance properties of rat subicular pyramidal neurons

The subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. Using pharmacological agents, we show the involvement of alpha 5 beta gamma GABA(A) receptors in the picrotoxin-sensitive tonic current in subicular pyramidal neurons. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. We demonstrate that tonic GABAergic inhibition can actively modulate subthreshold properties, including resonance due to HCN channels, which can potentially alter the response dynamics of subicular pyramidal neurons in an oscillating neuronal network.

Description of Early Larvae of Four Northern California Species of Rockfishes (Scorpaenidae: Sebastes) from Rearing Studies

About 72 species of Sebastes (Family Scorpaenidae) are found along the eastern Pacific coast of North America, some of which are heavily exploited by both commercial and sport fisheries. Because of the large number of species, the identification of early life stages has progressed slowly. The objectives of this study were 1) to rear the larvae of four species of rockfish (Sebastes mystinus, S. carnatus, S. atrovirens, and S. rastrelliger); and 2) to describe the larvae using morphometric measurements, pigmentation patterns, and head spination. Pigmentation was the most useful feature for identification purposes. Two general patterns were found: 1) a short row of ventral midline melanophores on the tail, and none or very little postero-dorsal pigmentation (S. mystinus); and 2) complete ventral midline pigmentation on the tail, and anterior and postero-dorsal melanophores (S. carnatus, S. atrovirens, and S. rastrelliger). With the exception of very early stages of S. carnatus and S. atrovirens, these species can be readily identified. Morphometric proportions and head spination did not show major differences among species. Because of the great similarities found among species in this genus, descriptions from field studies are uncertain to some extent. Laboratory rearings, although difficult, can at least provide early larvae from known species which allow precise identification as well as an estimation ofvariability of characters (e.g., pigmentation) within and between broods.(PDF file contains 22 pages.)

A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

A model of the olfactory bulb and beyond

The olfactory bulb of mammals aids in the discrimination of odors. A mathematical model based on the bulbar anatomy and electrophysiology is described. Simulations of the highly non-linear model produce a 35-60 Hz modulated activity, which is coherent across the bulb. The decision states (for the odor information) in this system can be thought of as stable cycles, rather than as point stable states typical of simpler neuro-computing models. Analysis shows that a group of coupled non-linear oscillators are responsible for the oscillatory activities. The output oscillation pattern of the bulb is determined by the odor input. The model provides a framework in which to understand the transformation between odor input and bulbar output to the olfactory cortex. This model can also be extended to other brain areas such as the hippocampus, thalamus, and neocortex, which show oscillatory neural activities. There is significant correspondence between the model behavior and observed electrophysiology.

It has also been suggested that the olfactory bulb, the first processing center after the sensory cells in the olfactory pathway, plays a role in olfactory adaptation, odor sensitivity enhancement by motivation, and other olfactory psychophysical phenomena. The input from the higher olfactory centers to the inhibitory cells in the bulb are shown to be able to modulate the response, and thus the sensitivity, of the bulb to odor input. It follows that the bulb can decrease its sensitivity to a pre-existing and detected odor (adaptation) while remaining sensitive to new odors, or can increase its sensitivity to discover interesting new odors. Other olfactory psychophysical phenomena such as cross-adaptation are also discussed.

Avaliação tridimensional da sínfise mandibular em crânios secos e sua associação com diferentes classificações de tipos faciais

O objetivo deste trabalho foi desenvolver um estudo morfológico quantitativo e qualitativo da região da sínfise mandibular (SM), através da construção de modelos tridimensionais (3D) e avaliar o seu grau de associação com diferentes classificações de padrões faciais. Foram avaliados 61 crânios secos humanos de adultos jovens com oclusão normal, com idade entre 18 e 45 anos e dentadura completa. Tomografias computadorizadas de feixe cônico (TCFC) de todos os crânios foram obtidas de forma padronizada. O padrão facial foi determinado por método antropométrico e cefalométrico. Utilizando o critério antropométrico, tomando como referência o índice facial (IF), o padrão facial foi classificado em: euriprósopo (≤84,9), mesoprósopo (85,0 - 89,9) e leptoprósopo (≥90,0). Pelo critério cefalométrico, o plano mandibular (FMA) determinou o padrão facial em curto (≤21,0), médio (21,1 - 29,0) e longo (≥29,1); e o índice de altura facial (IAF) classificou a face em hipodivergente (≥0,750), normal (0,749 - 0,650) e hiperdivergente (≤0,649). A construção de modelos 3D, representativos da região da SM, foi realizada com o auxílio do software ITK-SNAP. Os dentes presentes nesta região, incisivos, caninos e pré-molares inferiores, foram separados do modelo por técnica de segmentação semi-automática, seguida de refinamento manual. Em seguida, foram obtidos modelos 3D somente com o tecido ósseo, possibilitando a mensuraçãodo volume ósseo em mm3 (VOL) e da densidade radiográfica, pela média de intensidade dos voxels (Mvox). No programa Geomagic Studio 10 foi feita uma superposição anatômica dos modelos 3D em bestfit para estabelecer um plano de corte padronizado na linha média. Para cada sínfise foi medida a altura (Alt), a largura (Larg) e calculado o índice de proporção entre altura e largura (PAL). A avaliação da presença de defeitos alveolares foi feita diretamente na mandíbula,obtendo-se a média de todas as alturas ósseas alveolares (AltOss) e a média da dimensão das deiscências presentes (Medef). O índice de correlação intra-classe (ICC) com valores entre 0,923 a 0,994,indicou alta reprodutibilidade e confiabilidade das variáveis medidas. As diferenças entre os grupos, determinados pelas classificações do padrão facial (IF, FMA e IAF), foram avaliadas através da análise de variância (oneway ANOVA) seguida do teste post-hoc de Tukey. O grau de associação entre o padrão facial e as variáveis Vol, Mvox, PAL, Alt, Larg, AltOss e Medef foi avaliado pelo coeficiente de correlação de Pearson com um teste t para r. Os resultados indicaram ausência de diferença ou associação entre o volume, densidade radiográfica e presença de defeitos alveolares da SM e o padrão facial quando determinado pelo IF, FMA e IAF. Verificou-se tendência de SM mais longas nos indivíduos com face alongada, porém a largura não mostrou associação com o padrão facial. Estes resultados sugerem que as classificações utilizadas para determinar o padrão facial não representam satisfatoriamente o caráter 3D da face humana e não estão associadas com a morfologia da SM.

Larval development and identification of the genus Triglops (Scorpaeniformes: Cottidae)

Prior to Pietsch’s (1993) revision of the genus Triglops, identification of their larvae was difficult; six species co-occur in the eastern North Pacific Ocean and Bering Sea and three co-occur in the western North Atlantic Ocean. We examined larvae from collections of the Alaska Fisheries Science Center and Atlantic Reference Centre and used updated meristic data, pigment patterns, and morphological characters to identify larvae of Triglops forficatus, T. macellus, T. murrayi, T. nybelini, T. pingeli, and T. scepticus; larvae of T. metopias, T. dorothy, T. jordani, and T. xenostethus have yet to be identified and are thus not included in this paper. Larval Triglops are characterized by a high myomere count (42–54), heavy dorsolateral pigmentation on the gut, and a pointed snout. Among species co-occurring in the eastern North Pacific Ocean, T. forficatus, T. macellus, and T. pingeli larvae are distinguished from each other by meristic counts and presence or absence of a series of postanal ventral melanophores. Triglops scepticus is differentiated from other eastern North Pacific Ocean larvae by having 0–3 postanal ventral melanophores, a large eye, and a large body depth. Among species co-occurring in the western North Atlantic Ocean, T. murrayi and T. pingeli larvae are distinguished from each other by meristic counts (vertebrae, dorsal-fin rays, and anal-fin rays once formed), number of postanal ventral melanophores, and first appearance and size of head spines. Triglops nybelini is distinguished from T. murrayi and T. pingeli by a large eye, pigment on the lateral line and dorsal midline in flexion larvae, and a greater number of dorsal-fin rays and pectoral-fin rays once formed.

Description and growth of larval and pelagic juvenile pygmy rockfish (Sebastes wilsoni) (family Sebastidae)

A developmental series of larval and pelagic juvenile pygmy rockfish (Sebastes wilsoni) from central California is illustrated and described. Sebastes wilsoni is a non- commercially, but ecologically, important rockfish, and the ability to differentiate its young stages will aid researchers in population abundance studies. Pigment patterns, meristic characters, morphometric measurements, and head spination were recorded from specimens that ranged from 8.1 to 34.4 mm in standard length. Larvae were identified initially by meristic characters and the absence of ventral and lateral midline pigment. Pelagic juveniles developed a prominent pigment pattern of three body bars that did not extend to the ventral surface. Species identification was confirmed subsequently by using mitochondrial sequence data of four representative specimens of various sizes. As determined from the examination of otoliths, the growth rate of larval and pelagic juvenile pygmy rockfish was 0.28 mm/day, which is relatively slow in comparison to the growth rate of other species of Sebastes. These data will aid researchers in determining species abundance.

Shape vs. volume: Invariant shape descriptors for 3D region of interest characterization in MRI

We propose a new approach for quantifying regions of interest (ROIs) in medical image data. Rotationally invariant shape descriptors (ISDs) were applied to 3D brain regions extracted from MRI scans of 5 Parkinson's patients and 10 control subjects. We concentrated on the thalamus and the caudate nucleus since prior studies have suggested they are affected in Parkinson's disease (PD). In the caudate, both the ISD and volumetric analyses found significant differences between control and PD subjects. The ISD analysis however revealed additional differences between the left and right caudate nuclei in both control and PD subjects. In the thalamus, the volumetric analysis showed significant differences between PD and control subjects, while ISD analysis found significant differences between the left and right thalami in control subjects but not in PD patients, implying disease-induced shape changes. These results suggest that employing ISDs for ROI characterization both complements and extends traditional volumetric analyses. © 2006 IEEE.

An in computo investigation of the Landau-Kleffner syndrome

We describe a computational model of the thalamus and the cortex able to reproduce some essential epileptiform features commonly observed in the Landau-Kleffner syndrome. Investigation with this realistic model leads us to the formulation of a cellular mechanism that could be responsible for the epileptic discharges occuring with this severe syndrome. Understanding this mechanism is of prime importance for developing new therapeutical strategies. © 2007 IEEE.

Zebrafish eaf1 and eaf2/u19 Mediate Effective Convergence and Extension Movements through the Maintenance of wnt11 and wnt5 Expression

Studies have attributed several functions to the Eaf family, including tumor suppression and eye development. Given the potential association between cancer and development, we set forth to explore Eaf1 and Eaf2/U19 activity in vertebrate embryogenesis, using zebrafish. In situ hybridization revealed similar eaf1 and eaf2/u19 expression patterns. Morpholino-mediated knockdown of either eaf1 or eaf2/u19 expression produced similar morphological changes that could be reversed by ectopic expression of target or reciprocal-target mRNA. However, combination of Eaf1 and Eaf2/U19 (Eafs)-morpholinos increased the severity of defects, suggesting that Eaf1 and Eaf2/U19 only share some functional redundancy. The Eafs knockdown phenotype resembled that of embryos with defects in convergence and extension movements. Indeed, knockdown caused expression pattern changes for convergence and extension movement markers, whereas cell tracing experiments using kaeda mRNA showed a correlation between Eafs knockdown and cell migration defects. Cardiac and pancreatic differentiation markers revealed that Eafs knockdown also disrupted midline convergence of heart and pancreatic organ precursors. Noncanonical Wnt signaling plays a key role in both convergence and extension movements and midline convergence of organ precursors. We found that Eaf1 and Eaf2/U19 maintained expression levels of wnt11 and wnt5. Moreover, wnt11 or wnt5 mRNA partially rescued the convergence and extension movement defects occurring in eafs morphants. Wnt11 and Wnt5 converge on rhoA, so not surprisingly, rhoA mRNA more effectively rescued defects than either wnt11 or wnt5 mRNA alone. However, the ectopic expression of wnt11 and wnt5 did not affect eaf1 and eaf2/u19 expression. These data indicate that eaf1 and eaf2/u19 act upstream of noncanonical Wnt signaling to mediate convergence and extension movements.

Revision of the genus Niwaella in China (Pisces, Cobitidae), with description of two new species

Loaches of the genus Niwaella, family Cobitidae, are distributed only in East Asia. At present only in Japan and South Korea have fishes of the genus Niwaella been found. Herein we revise the genus Niwaella in China. Son and He ( 2001) transferred the species Cobitis laterimaculata to the genus Niwaella, but their specimens were not N. laterimaculata, but a new species, N. longibarba sp. n., collected from Cao'ejiang River, Huangzezhen, Chengxian County, Zhejiang Province. The new species is distinguished from N. laterimaculata by its colour pattern of a row of slightly large, and long, scattered dark brown vertical bars on the dorsolateral surface, two or three striations on the caudal fin, and long barbels and undeveloped mental lobes. In this paper we also describe another new species, N. xinjiangensis sp. n., collected from Xinjiang River, Guangfeng County, Jiangxi Province, May 1990, with diagnostic colour pattern of 17 - 20 large and long, dark brown vertical bars on the dorsolateral surface, a dark stripe or rounded black spots along the lateral midline and some blotches below the lateral midline; it is a large-sized species, with shorter barbels, and longer caudal peduncle. Thus five species of the genus Niwaella are known, three are endemic to eastern China and two are endemic to either Japan or South Korea.