A quantitative approach to cytoarchitectonics

Summary The boundaries of neo-and allocortical areas of Galago demidovii are analyzed with an automatic quantitative procedure using an image analyzer. The results are summarized in a cortical map and compared with a cortical map of Tupaia. Galago shows a highly differentiated temporal lobe and no homogeneous peristriate area comparable to the classical concept of Brodmann's Area 19. Primary motor, somatosensory, auditory, and visual areas are delineated and shown to be surrounded by distinct secondary areas.Supported by Deutsche Forschungsgemeinschaft grants Zi 192/1 and 192/3     

Distribution of lithostathine in the mouse lemur brain with aging and Alzheimer's-like pathology

We analyzed the cellular distribution of the pancreatic inflammatory protein lithostathine and its receptor EXTL3 in the brain of the lemurian primate Microcebus murinus which develops amyloid deposits along with aging. In adult animals (2-4.5 years old), lithostathine and EXTL3 immunoreactivities were largely distributed in the whole brain, and more intensively in almost all cortical layers and hippocampal formation. Lithostathine was observed in the perikarya and neurites of cortical neurons but also in glial cells in the border of the ventricle and the corpus callosum. In healthy aged animals (8-13 years old), highest densities of lithostathine-containing cells were observed, mainly in occipital and parietal cortex. In aged animals with Aβ deposits, the increase in lithostathine immunoreactivity was lower as compared with aged animals. Noteworthy, lithostathine-immunopositive cells did almost never colocalize with Aβ plaques. In conclusion, lithostathine immunoreactivity in adult Microcebus murinus appeared ubiquitous and particularly in visual, sensorial, and cognitive brain areas. Immunoreactivity increased with aging and appeared markedly affected in neuropathological conditions. Its possible neuroprotection or neurodegeneration role in Alzheimer pathology deserves therefore to be investigated.     

The Forearm Musculature of the Gray Mouse Lemur (Microcebus murinus): An Ontogenetic Study

Although studies have sought to characterize variation in forearm muscular anatomy across the primate order, none have attempted to quantify ontogenetic changes in forearm myology within a single taxon. Herein, we present muscle architecture data for the forearm musculature (flexors and extensors of the wrist and digits) of Microcebus murinus, a small Lemuroid that has been the focus of several developmental studies. A quadratic curvilinear model described ontogenetic changes in muscle mass and fascicle length; however, fascicle lengths reached peak levels at an earlier age and showed a stronger decline during senescence. Conversely, physiological cross-sectional area followed a more linear trend, increasing steadily throughout life. As previous studies into the functional role of the primate forelimb emphasize the importance of long muscle fascicles within arboreal taxa in order to maximize mobility and flexibility, the early attainment of peak fascicle lengths may consequently reflect the importance of agility within this mobile and highly arboreal species. Similarly, observed myological trends in forearm strength are supported by previous in vivo data on grip strength within M. murinus in which senescent individuals showed no decline in forearm force relative to prime age individuals. This trend is interpreted to reflect compensation for the previously reported decline in hind limb grip strength in the hind limb with age, such that older individuals are able to maintain arboreal stability. Interestingly, the ontogenetic trajectory of each architectural variable mirrored previous observations of the masticatory musculature in M. murinus, suggesting that ontogenetic trends are relatively conserved between anatomical regions. Anat Rec, 303:1354–1363, 2020. © 2019 American Association for Anatomy     

”Rodent-like” and ”primate-like” types of astroglial architecture in the adult cerebral cortex of mammals: a comparative study

Previous observations disclosed that astroglia with interlaminar processes were present in the cerebral cortex of adult New and Old World monkeys, but not in the rat, and scarcely in the prosimian Microcebus murinus. The present report is a more systematic and comprehensive comparative analysis of the occurrence of such processes in the cerebral cortex of several mammalian species. Brain samples were obtained from adult individuals from the following orders: Carnivora (canine), Rodentia (rat and mouse), Marsupialia (Macropus eugenii), Artiodactyl (bovine and ovine), Scandentia (Tupaia glis), Chiroptera (Cynopteris horsfieldii and C. brachyotis), and Primate: Prosimian (Eulemur fulvus), non-human primate species (Cebus apella, Saimiri boliviensis, Callithrix, Macaca mulatta, Papio hamadryas, Macaca fascicularis, Cercopithecus campbelli and C. ascanius) and from a human autopsy. Tissues were processed for immunocytochemistry using several antibodies directed against glial fibrillary acidic protein (GFAP), with or without additional procedures aimed at the retrieval of antigens and enhancement of their immunocytochemical expression. The cerebral cortex of non-primate species had an almost exclusive layout of stellate astrocytes, with only the occasional presence of long GFAP-IR processes in the dog that barely crossed the extent of lamina I, which in this species had comparatively increased thickness. Species of Insectivora and Chiroptera showed presence of astrocytes with long processes limited to the ventral basal cortex. Interlaminar GFAP-IR processes were absent in Eulemur fulvus, at variance with their limited presence and large within- and inter-individual variability as reported previously in Microcebus murinus. In New World monkeys such processes were absent in Callithrix samples, at variance with Cebus apella and Saimirí boliviensis. Overall, the expression of GFAP-IR interlaminar processes followed a progressive pattern: bulk of non-primate species (lack of interlaminar processes) –Chiroptera and Insectivora (processes restricted to allocortex) <strepsirhini <haplorhini (platirrhini<catarrhini). This trend is suggestive of the emergence of new evolutionary traits in the organization of the cerebral cortex, namely, the emergence of GFAP-IR long, interlaminar processes in the primate brain. Interlaminar processes may participate in a spatially restricted astroglial role, as compared to the one provided by the astroglial syncytium. It is proposed that the widely accepted concept of an exclusively astroglial syncytium is probably linked with a specific laboratory animal species (”rodent-type” or, rather, ”general mammalian-type” model) that misrepresents the astroglial architecture present in the cerebral cortex of most anthropoid adult primates (”primate-type” model), including man. Accepted: 28 June 1999     

The grey mouse lemur: a non-human primate model for ageing studies

The use of non-human primate models is required to understand the ageing process and evaluate new therapies against age-associated pathologies. The present article summarizes all the contributions of the grey mouse lemur Microcebus murinus, a small nocturnal prosimian primate, to the understanding of the mechanisms of ageing. Results from studies of both healthy and pathological ageing research on the grey mouse lemur demonstrated that this animal is a unique model to study age-dependent changes in endocrine systems, biological rhythms, thermoregulation, sensorial, cerebral and cognitive functions.     

Distribution of Olfactory and Nonolfactory Surface Area in the Nasal Fossa of Microcebus murinus: Implications for Microcomputed Tomography and Airflow Studies

The nasal fossa of most mammals exemplifies extreme skeletal complexity. Thin scrolls of bone (turbinals) that both elaborate surface area (SA) and subdivide nasal space are used as morphological proxies for olfactory and respiratory physiology. The present study offers additional details on the nasal fossa of the adult mouse lemur (Microcebus murinus), previously described by Smith and Rossie (Smith and Rossie [ 2008 ]; Anatomical Record 291:895–915). Additional, intervening histological sections of the specimen were used to map and quantify the distribution of olfactory and nonolfactory mucosa on the smaller turbinal of the frontal recess (FR; frontoturbinal) and those that occur between ethmoturbinals (ETs; interturbinals). A second adult Microcebus specimen, available as a dried skull, was scanned using microcomputed tomography (microCT) and reconstructed to infer the position of these turbinals within the nasal airway. Overall, turbinal bones comprise more than half of internal nasal SA. All ETs combined comprise about 30% of total nasal fossa SA, and contribute nearly half of all olfactory SA. Of these, the nasoturbinal (NT) is most completely covered with olfactory mucosa, whereas ET I is least covered with olfactory mucosa. The FR contributes significantly to total olfactory SA (ca. 20%). This recess and the single frontoturbinal within it lie in a more lateral pathway of airflow compared with interturbinals, which lie in more central zone just anterior to the olfactory recess of Microcebus. Variations in the turbinals and recesses that complicate central and paranasal in primates should be investigated further in light of zone‐specific distributions of olfactory receptors (ORs) that differ between these regions in rodents. Anat Rec, 2011 © 2011 Wiley‐Liss, Inc.     

The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

The masticatory apparatus has been the focus of many studies in comparative anatomy—especially analyses of skulls and teeth, but also of the mandibular adductor muscles which are responsible for the production of bite force and the movements of the mandible during food processing and transport. The fiber architecture of these muscles has been correlated to specific diets (e.g., prey size in felids) and modes of foraging (e.g., tree gouging in marmosets). Despite the well-elucidated functional implications of this architecture, little is known about its ontogeny. To characterize age-related myological changes, we studied the masticatory muscles in a large (n = 33) intraspecific sample of a small, Malagasy primate, Microcebus murinus including neonatal through geriatric individuals. We removed each of the mandibular adductors and recorded its mass as well as other linear measurements. We then chemically dissected each muscle to study its architecture—fascicle length and physiological cross-sectional area (PCSA) which relate to stretch (gape) and force capabilities, respectively. We observed PCSA and muscle mass to increase rapidly and plateau in adulthood through senescence. Fascicle lengths remained relatively constant once maximal length was reached, which occurred early in life, suggesting that subsequent changes in PCSA are driven by changes in muscle mass. Quadratic curvilinear models of each of the architectural variables of all adductors combined as well as individual muscles regressed against age were all significant. Anat Rec, 303:1364–1373, 2020. © 2019 American Association for Anatomy     

Demonstration of hypothalamo-cerebellar and cerebello-hypothalamic fibres in a prosimian primate (Galago crassicaudatus)

Summary Hypothalamo-cerebellar and cerebello-hypothalamic fibres in the greater bushbaby (Galago crassicaudatus) have been demonstrated by means of retrograde and anterograde transport of the wheat germ agglutinin-horseradish peroxidase complex. The hypothalamo-cerebellar projection is bilateral and has its main origin in the lateral hypothalamic area. The posterior and dorsal hypothalamic areas and the lateral mammillary, tuberomammillary and periventricular nuclei also project to cerebellum. Cerebello-hypothalamic fibres are crossed and terminate in the dorsal, posterior and lateral hypothalamic areas. The hypothalamo-cerebellar and cerebello-hypothalamic projections appear to be in part reciprocal.The results are discussed with reference to our findings in other species, and some comments are made concerning the possible circuits involved in cerebellar regulation of non-somatic responses.     

Neuronal connections of orbital cortex in rats: topography of cortical and thalamic afferents

The cortical and thalamic afferent connections of rat orbital cortex were investigated using fluorescent retrograde axonal tracers. Each of the four orbital areas has a distinct pattern of connections. Corticocortical connections involving the ventral and ventrolateral orbital areas are more extensive than those of the medial and lateral orbital areas. The medial orbital area has cortical connections with the cingulate, medial agranular (Fr2) and posterior parietal (PPC) cortices. The ventral orbital area has connections with the cingulate area, area Fr2, secondary somatic sensory area Par2, PPC, and visual areas Oc2M and Oc2L. The ventrolateral orbital area (VLO) receives cortical input from insular cortex, area Fr2, somatic sensory areas Par1 and Par2, PPC and Oc2L. The lateral orbital area has cortical connections limited to the agranular and granular insular areas, and Par2. Thalamic afferents to the four orbital fields are also topographically organized, and are focused in the submedial and mediodorsal nuclei. The ventrolateral orbital area receives input from the entirety of the submedial nucleus, whereas the other orbital areas receive input from its periphery only. Each orbital area is connected with a particular segment of the mediodorsal nucleus. The medial orbital area receives its principal thalamic afferents from the parataenial nucleus, the dorsocentral portion of the mediodorsal nucleus, and the ventromedial portion of the submedial nucleus. The ventral orbital area receives input from the lateral segment of the mediodorsal nucleus, the rostromedial portion of the submedial nucleus and the central lateral nucleus. Thalamic afferents to the ventrolateral orbital area arise from the entirety of the submedial nucleus and from the lateral segment of the mediodorsal nucleus. The lateral orbital area receives thalamic afferents from the central segment of the mediodorsal nucleus, the ventral portion of the submedial nucleus and the ventromedial nucleus. The paraventricular, ventromedial, rhomboid and reuniens nuclei also provide additional input to the four orbital areas. The connections of the ventrolateral orbital area are interpreted in the context of its role in directed attention and allocentric spatial localization. The present findings provide anatomical support for the view that areas Fr2, PPC and VLO comprise a cortical network mediating such functions.     

The ovoimplantation of Microcebus murinus miller (primates,lemuroidea, strepsirhini)

The process of nidation of Microcebus murinus may be subdivided into several stages (preadhesion, apposition, attachment and invasion), as is indicated for protracted phases of preimplantation. Not until the apposition stage does the inner cell mass orient itself orthomesometrially, while concurrently a nidation plaque develops in the abembryonal trophoblast that overlies and resorbs the coalescent glands. During the subsequent adhesion stage, the paraembryonal, bilaminar omphalochorion becomes attached to the uterine epithelium, with focal resorption of the latter. In addition, chorionic vesicles begin to develop. In the meantime, the embryonic disc has lost its trophoblastic cover as a preliminary to the formation of the pleuramnion. The formation of a nidation plaque, together with the subsequent central implantation of Microcebus, suggests a close relationship to Loris tardigradus, characterizing the mode of implantation of Strepsirhini. The nidation plaque and its invasive capacity, giving rise to a syndesmochorial placental nucleus, provide a placentological link to Galago demidovii.     

Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1‐q44 duplication including the AKT3 gene

Somatic and germline duplications or activating mutations of AKT3 have been reported in patients with hemimegalencephaly and megalencephaly. We performed array comparative genomic hybridization on brain tissue and blood in 16 consecutive patients with symptomatic epilepsy due to focal or multilobar malformations of cortical development who underwent surgical treatment of epilepsy. One patient with infantile spasms and a dysplastic left frontal lobe harboured a somatic trisomy of the 1q21.1‐q44 chromosomal region, encompassing the AKT3 gene, in the dysplastic brain tissue but not in blood and saliva. Histopathology revealed severe cortical dyslamination, a thin cortex in the premotor area with microgyri and microsulci, immature neurons with disoriented dendrites and areas of cortical heterotopia in the sub‐cortical white matter. These cytoarchitectural changes are close to those defining type Ib focal cortical dysplasia. Immunohistochemistry in brain specimens showed hyperactivation of the PI3K/AKT/mTOR pathway. These findings indicate that AKT3 upregulation may cause focal malformations of cortical development. There appears to be an etiologic continuum between hemimegalencephaly and focal cortical dysplastic lesions. The extent of brain malformations due to AKT3 upregulation may be related to the embryonic stage when the post‐zygotic gene alteration occurs.     

Association between Q192R paraoxonase 1 polymorphism and serumadipocyte-fatty acid binding protein (FABP4) levels in Mexican women

Aim: This study aimed to evaluate the genetic effects of PON1 Q192R polymorphism on serum FABP4 levels in Mexican women.

Methods: PON1 Q192R polymorphism was genotyped using a TaqMan allelic discrimination assay and serum FABP4 concentration was measured using an enzyme-linked immunosorbent assay.

Results: The distribution of genotype frequencies in the assessed women (PON1 Q192R polymorphism) was QQ?=?20%, QR?=?48% and RR?=?32%. Significantly higher serum FABP4 levels were found in women with genotype QR/RR (20.6?±?2.20?ng/mL), when compared with the levels found in the QQ group (12.8?±?1.70?ng/mL) (p?=?.004). After, the odds ratio (OR) was calculated by binomial logistic regression analysis and a significantly higher OR was found in the QR/RR group when compared with the QQ group (OR?=?3.45; 95% CI?=?1.80–16.50; p?Conclusion: The results support an association between 192R-allele of the PON1 polymorphism (Q192R) and increased serum FABP4 levels (suggested as an early biomarker of CVDs risk) in assessed Mexican women.     

Hantaviruses in small mammals and humans in the coastal region of Zhejiang Province,China

To gain more insights into the epidemiology of hantaviruses in the coastal region of Zhejiang Province, China, the morbidity and mortality of hemorrhagic fever with renal syndrome (HFRS) were analyzed in two coastal areas: Cixi (hilly terrain) and Wenzhou (mountainous terrain). More HFRS cases have been reported in Cixi than in Wenzhou. Annual incidence rate of HFRS in Cixi had been on the level of approximately 1.5/100,000 from 1968 (when the first HFRS case was reported) to 2007, with the highest incidence rate of 8.54/100,000 in 1999. The annual incidence rate in Wenzhou has been relatively low, less than 0.5/100,000 since the first HFRS case was reported in 1981. A total of 461 rodents and 199 shrews were captured in these two areas. Hantavirus antibodies were detected in 16 of 241 (6.64%) Rattus norvegicus and 13 of 122 (10.66%) R. flavipectus. Interestingly, hantavirus antigens were identified in 6 of 196 (3.06%) Suncus murinus. Genetic analysis showed that partial M and S segment sequences recovered from rats in the two regions belong to Seoul virus (SEOV) and can be assigned into two genetic lineages. SEOV variants that belong to these two lineages of viruses are distributed widely in China and have been found outside China. As most trapped rodents were rats and SEOV was the only hantavirus detected, these results suggested that SEOV plays an important role in human hantavirus infections. They also reinforce the need for vigilance in preventing HFRS caused by hantaviruses in the coastal region. J. Med. Virol. 82:987–995, 2010. © 2010 Wiley‐Liss, Inc.     

A quantitative approach to cytoarchitectonics

Summary A map of the areal pattern of the hyperstriatum ventrale in the domestic pigeon (Columba livia f.d.) is proposed. This map is based mainly on the distribution of the grey level index which has been characterized using an automatic image analyzer. Twelve areas are described. They are classified into two groups (Hvm 1–6, Hvl 1–6) which are defined by a different range of grey level indices. Three of these areas show topographic relationships to primary projection areas in the neighbouring neostriatum (Nucleus basalis, Ectostriatum, Feld L), and connections are in part well known. Therefore, these areas are assumed to be associative in function. The function of the other areas remains an open question.Supported by Deutsche Forschungsgemeinschaft (SFB 114, Zi 192/4-4)Dedicated to Dr. H. Stephan, Frankfurt/Main, on the occasion of his 60th birthday     

Nasal Fossa of Mouse and Dwarf Lemurs (Primates,Cheirogaleidae)

Dimensions of the external midface in mammals are sometimes related to olfactory abilities (e.g., “olfactory snouts” of strepsirrhine primates). This association hinges on the largely unexplored relationship between the protruding midface and internal topography of the nasal fossae. Herein, serially sectioned heads of embryonic to adult cheirogaleid primates (mouse and dwarf lemurs) and a comparative sample were studied. To assess the anteroposterior distribution of olfactory epithelium (OE) within the nasal fossa, the surface area of OE and non‐OE was measured in two mouse lemurs (one adult, one infant). Prenatally, ethmoturbinal projections appear in an anteroposterior sequence. Fetal mouse lemurs, tenrecs, voles, and flying lemurs have four ethmoturbinals that project toward the nasal septum. Major distinctions among these mammals include the number of turbinals in recesses and the extent of the olfactory recess. Surface area measurements in the adult mouse lemur reveal that 31% of the entire nasal fossa is lined with OE. The majority is sequestered in a posterior recess (70% OE). Anterior to this space, only 28% of the nasal fossa is lined with OE. Ethmoturbinal I is lined with relatively less OE (35%) compared with more posterior ethmoturbinals (46–57%). Age comparisons support the idea that OE increases less than non‐OE between ages. Regionally, results suggest that most growth in surface area occurs in turbinals. But in all ethmoturbinals, surface area of non‐OE differs between ages more than that of OE. This study shows that the anterior part of the nasal fossa is mostly nonolfactory in Microcebus murinus. Anat Rec, 291:895–915, 2008. © 2008 Wiley‐Liss, Inc.     

β-Glucans in food modify colonic microflora by inducing antimicrobial protein,calprotectin, in a Dectin-1-induced-IL-17F-dependent manner

Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a^−/− mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c⁺/CD11b⁺ myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a^−/− and Il17f^−/− mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with β-glucan-free food. These observations suggest that food-derived β-glucans control the specific commensal microbiota via the Dectin-1–IL-17F–calprotectin axis to maintain the intestinal homeostasis.     

Fluoro-Gold tracing of zinc-containing afferent connections in the mouse visual cortices

Summary To identify zinc-containing projections to the visual areas, we injected Fluoro-Gold into the occipital cortex of the mouse. Five days later, the mice underwent an intravital selenium-labeling procedure to demonstrate the somata of neurons that give rise to zinc-containing boutons. Numerous double-labeled cells were seen in the ipsi- and contralateral primary (layers II/III and VI), and secondary visual cortices (layers II/III and VI). A few double-labeled cells were apparent in other cortical areas concerned with visual processing: the orbital cortex (layers II and III), the posterior portion of the medial agranular frontal cortex (layer V/VI border), and the temporal cortex (layer VI). The cingulate, retrosplenial, perirhinal, and lateral entorhinal cortices had lamina projecting to the visual cortex and separate lamina harboring zinc-containing cells. A spatial segregation of fluorescent and zinc-containing neurons was also seen in the claustrum. This integration or segregation of projecting and zinc-containing neurons may reflect the function of the cortical areas. N-methyl-d-aspartate receptor function is antagonized by physiological concentrations of zinc in vitro. It is proposed that zinc-positive projections from areas that perform basic visual functions are less likely to be modified by N-methyl-d-aspartate receptor-mediated processes than the zinc-negative connections from associational areas.     

Lumbar Vertebral Body Bone Microstructural Scaling in Small to Medium‐Sized Strepsirhines

Bone mass, architecture, and tissue mineral density contribute to bone strength. As body mass (BM) increases any one or combination of these properties could change to maintain structural integrity. To better understand the structural origins of vertebral fragility and gain insight into the mechanisms that govern bone adaptation, we conducted an integrative analysis of bone mass and microarchitecture in the last lumbar vertebral body from nine strepsirhine species, ranging in size from 42 g (Microcebus rufus) to 2,440 g (Eulemur macaco). Bone mass and architecture were assessed via µCT for the whole body and spherical volumes of interest (VOI). Allometric equations were estimated and compared with predictions for geometric scaling, assuming axial compression as the dominant loading regime. Bone mass, microarchitectural, and vertebral body geometric variables predominantly scaled isometrically. Among structural variables, the degree of anisotropy (Tb.DA) was the only parameter independent of BM and other trabecular architectural variables. Tb.DA was related to positional behavior. Orthograde primates had higher average Tb.DA (1.60) and more craniocaudally oriented trabeculae while lorisines had the lowest Tb.DA (1.25), as well as variably oriented trabeculae. Finally, lorisines had the highest ratio of trabecular bone volume to cortical shell volume (～3x) and while there appears to be flexibility in this ratio, the total bone volume (trabecular + cortical) scales isometrically (BM^1.23, r² = 0.93) and appears tightly constrained. The common pattern of isometry in our measurements leaves open the question of how vertebral bodies in strepsirhine species compensate for increased BM. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.     

Paraoxonase 1 status in the Thai population

Human serum paraoxonase 1 (PON1), a high-density lipoprotein (HDL)-associated enzyme, has been shown to reduce the oxidation of low-density lipoprotein (LDL) and HDL by degrading lipid peroxides. This property of PON1 accounts for its ability to protect against atherosclerosis. In this study, we identified four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of the human PON1 gene in 202 healthy Thai individuals and investigated the influence of these polymorphisms on serum PON1 activity towards three substrates, namely, paraoxon, phenylacetate and diazoxon. The PON1 L55M, Q192R and G-909C polymorphisms significantly affected the variation in serum PON1 activity towards paraoxon. Serum PON1 activity towards paraoxon was significantly different among the genotype groups, as follows: 55LL > 55LM/55MM, 192RR > 192QR > 192QQ and –909CC > –909CG > –909GG. The PON1 Q192R and G-909C polymorphisms also influenced the variation in serum PON1 activity towards diazoxon but in the opposite direction to the activity towards paraoxon. Only the PON1 L55M polymorphism was associated with significant variation in serum PON1 activity towards phenylacetate while the PON1 T-108C polymorphism had no significant effect on serum PON1 activity towards any substrate. We also found linkage disequilibrium among the polymorphic sites, including Q192R versus L55M, Q192R versus T-108C and Q192R versus G-909C. Serum PON1 activity towards both paraoxon and phenylacetate, but not diazoxon, was positively correlated with HDL cholesterol (HDL-C) and apo AI concentrations. None of the PON1 polymorphisms significantly affected serum lipid, lipoprotein or apolipoprotein concentrations. Our findings suggest that the physiological relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity, and the impact of PON1 polymorphisms on this activity is substrate-dependent.     

Manganese‐enhanced MRI visualizes V1 in the non‐human primate visual cortex

MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl₂ · 4H₂O in the tail vein. We found a statistically significant decrease in T₁ in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T₁ shortening in V1 (ΔT₁ = 640 ms) relative to V2 (ΔT₁ = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T₁‐weighted MRI. Furthermore, the dorso‐medial (DM) and middle‐temporal (MT) areas of the visual pathway could be identified by their T₁‐weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese‐enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non‐destructive localization of cortical regions to guide in the implementation of functional techniques. Published in 2009 by John Wiley & Sons, Ltd.