Divergence patterns in Fucus seaweeds (Phaeophyceae) in the northern Baltic Sea and in the Tjongspollen area

To be able to interpret patterns of biodiversity it is important to understand the processes by which new species evolve and how closely related species remain reproductively isolated and ecologically differentiated. Divergence and differentiation can vary during speciation and it can be seen in different stages. Groups of closely related taxa constitute important case studies to understand species and new biodiversity formation. However, it is important to assess the divergence among them at different organismal levels and from an integrative perspective. For this purpose, this study used the brown seaweeds genus Fucus as a model to study speciation, as they constitute a good opportunity to study divergence at different stages. We investigated the divergence patterns in Fucus species from two marginal areas (northern Baltic Sea and the Tjongspollen area), based on phenetic, phylogenetic and biological taxonomical criteria that are respectively characterised by algal morphology, allele frequencies of five microsatellite loci and levels of secondary polyphenolic compounds called phlorotannins. The results from this study showed divergence at morphological and genetic levels to certain extent but complete lack of divergence at biochemical level (i.e. constitutive phlorotannin production) in the Baltic Sea or Norway. Morphological divergence was clearly evident in Tjongspollen (Norway) among putative taxa as they were identified in the field and this divergence corresponds with their neutral genetic divergence. In the Baltic, there are some distinguishable patterns in the morphology of the swedish and finnish individuals according to locality to certain extent but not among putative taxa within localities. Likewise, these morphological patterns have genetic correspondence among localities but not within each locality. At the biochemical level, measured by the phlorotannin contents there were neither evidence of divergence in Norway or the Baltic Sea nor any discernable aggregation pattern among or within localities. Our study have contributed with further understanding of the Baltic Sea Fucus system and its intriguingly rapid and recent divergence as well as of the Tjongspollen area systems where formally undescribed individuals have been observed for the first time; in fact they appear largely differentiated and they may well warrant a new species status. In current times, climate change threatens, peripheral ecosystems, biodiversity, and increased knowledge of processes generating and maintaining biodiversity in those ecosystems seem particularly important and needed.

Gray matter volume differences specific to formal thought disorder in schizophrenia

Formal thought disorder (FTD) is one of the main symptoms of schizophrenia. To date there are no whole brain volumetric studies investigating gray matter (GM) differences specifically associated with FTD. Here, we studied 20 right-handed schizophrenia patients that differed in the severity of formal thought disorder and 20 matched healthy controls, using voxel-based morphometry (VBM). The severity of FTD was measured with the Scale for the Assessment of Thought, Language, and Communication. The severity was negatively correlated with the GM volume of the left superior temporal sulcus, the left temporal pole, the right middle orbital gyrus and the right cuneus/lingual gyrus. Structural abnormalities specific for FTD were found to be unrelated to GM differences associated with schizophrenia in general. The specific GM abnormalities within the left temporal lobe may help to explain language disturbances included in FTD.

Structural plasticity in the language system related to increased second language proficiency

While functional changes linked to second language learning have been subject to extensive investigation, the issue of learning-dependent structural plasticity in the fields of bilingualism and language comprehension has so far received less notice. In the present study we used voxel-based morphometry to monitor structural changes occurring within five months of second language learning. Native English-speaking exchange students learning German in Switzerland were examined once at the beginning of their stay and once about five months later, when their German language skills had significantly increased. We show that structural changes in the left inferior frontal gyrus are correlated with the increase in second language proficiency as measured by a paper-and-pencil language test. Contrary to the increase in proficiency and grey matter, the absolute values of grey matter density and second language proficiency did not correlate (neither on first nor on second measurement). This indicates that the individual amount of learning is reflected in brain structure changes, regardless of absolute proficiency.

Different molecular and structural adaptations with eccentric and conventional strength training in elderly men and women

Reprogramming of gene expression contributes to structural and functional adaptation of muscle tissue in response to altered use. The aim of this study was to investigate mechanisms for observed improvements in leg extension strength, gain in relative thigh muscle mass and loss of body and thigh fat content in response to eccentric and conventional strength training in elderly men (n = 14) and women (n = 14; average age of the men and women: 80.1 ± 3.7 years) by means of structural and molecular analyses. Biopsies were collected from m. vastus lateralis in the resting state before and after 12 weeks of training with two weekly resistance exercise sessions (RET) or eccentric ergometer sessions (EET). Gene expression was analyzed using custom-designed low-density PCR arrays. Muscle ultrastructure was evaluated using EM morphometry. Gain in thigh muscle mass was paralleled by an increase in muscle fiber cross-sectional area (hypertrophy) with RET but not with EET, where muscle growth is likely occurring by the addition of sarcomeres in series or by hyperplasia. The expression of transcripts encoding factors involved in muscle growth, repair and remodeling (e.g., IGF-1, HGF, MYOG, MYH3) was increased to a larger extent after EET than RET. MicroRNA 1 expression was decreased independent of the training modality, and was paralleled by an increased expression of IGF-1 representing a potential target. IGF-1 is a potent promoter of muscle growth, and its regulation by microRNA 1 may have contributed to the gain of muscle mass observed in our subjects. EET depressed genes encoding mitochondrial and metabolic transcripts. The changes of several metabolic and mitochondrial transcripts correlated significantly with changes in mitochondrial volume density. Intramyocellular lipid content was decreased after EET concomitantly with total body fat. Changes in intramyocellular lipid content correlated with changes in body fat content with both RET and EET. In the elderly, RET and EET lead to distinct molecular and structural adaptations which might contribute to the observed small quantitative differences in functional tests and body composition parameters. EET seems to be particularly convenient for the elderly with regard to improvements in body composition and strength but at the expense of reducing muscular oxidative capacity.

Computerized tomographic morphometric analysis of the cervical spine

Detailed knowledge of cervical canal and transverse foramens' morphometry is critical for understanding the pathology of certain diseases and for proper preoperative planning. Lateral x-rays do not provide the necessary accuracy. A retrospective morphometric study of the cervical canal was performed at the authors' institution to measure mean dimensions of sagittal canal diameter (SCD), right and left transverse foramens' sagittal (SFD) and transverse (TFD) diameters and minimum distance between spinal canal and transverse foramens (dSC-TF) for each level of the cervical spine from C1-C7, using computerized tomographic scans, in 100 patients from the archives of the Emergency Room.

Insular volume abnormalities associated with different transition probabilities to psychosis

Background Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). Method We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. Results The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. Conclusions GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities.

Sonographic Assessment of the Umbilical Cord

The umbilical cord is not an inert structure, suspended between the fetus and placenta, but it plays an active role and it is involved in several processes afflicting the feto-placental unit. Its study has to be regarding not only its morphology and morphometry, and the impendance of blood flow by Doppler waveform analysis, but it includes also an analysis of the coiling type and the amount of the Wharton Jelly. The umbilical cord has been considered like an important and huge source of informations, useful to assess the well-being of the fetus and the outcome of pregnancy. The standardization of ultrasound techniques is the first step to speak the same language and make the study of this structure a fundamental part of well-being fetus assessment. This article is carefully focused on morphologic, morphometric and functional ultrasound examination of umbilical cord and suggests that any anomaly detected should provide an indication for an intense fetal follow-up, useful for early helpful therapy, preventing serious complication for the pregnancy.

Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis

BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) signalling is central in the activation of hepatic stellate cells (HSCs), the key source of extracellular matrix (ECM) in fibrotic liver. We tested the therapeutic potential of the mTOR inhibitor rapamycin in advanced cirrhosis. METHODS: Cirrhosis was induced by bile duct-ligation (BDL) or thioacetamide injections (TAA). Rats received oral rapamycin (0.5 mg/kg/day) for either 14 or 28 days. Untreated BDL and TAA-rats served as controls. Liver function was quantified by aminopyrine breath test. ECM and ECM-producing cells were quantified by morphometry. MMP-2 activity was measured by zymography. mRNA expression of procollagen-alpha1, transforming growth factor-beta1 (TGF-beta1) and beta2 was quantified by RT-PCR. RESULTS: Fourteen days of rapamycin improved liver function. Accumulation of ECM was decreased together with numbers of activated HSCs and MMP-2 activity in both animal models. TGF-beta1 mRNA was downregulated in TAA, TGF-beta2 mRNA was downregulated in BDL. 28 days of rapamycin treatment entailed a survival advantage of long-term treated BDL-rats. CONCLUSIONS: Low-dose rapamycin treatment is effectively antifibrotic and attenuates disease progression in advanced fibrosis. Our results warrant the clinical evaluation of rapamycin as an antifibrotic drug.

Oral imatinib treatment reduces early fibrogenesis but does not prevent progression in the long term

BACKGROUND/AIMS: Transactivated hepatic stellate cells (HSCs) represent the key source of extra cellular matrix (ECM) in fibrotic liver. Imatinib, a potent inhibitor of the PDGF receptor tyrosine kinase, reduces HSC proliferation and fibrogenesis when treatment is initiated before fibrosis has developed. We tested the antifibrotic potential of imatinib in ongoing liver injury and in established fibrosis. METHODS: BDL-rats were gavage fed with 20 mg/kg/d imatinib either early (days 0-21) or late (days 22-35) after BDL. Untreated BDL-rats served as controls. ECM and activated HSCs were quantified by morphometry. Tissue activity of MMP-2 was determined by gelatin zymography. mRNA expression of TIMP-1 and procollagen alpha1(I) were measured by RT-PCR. Liver tissue concentration of imatinib was measured by tandem mass spectrometry. RESULTS: Early imatinib reduced ECM formation by 30% (P=0.0455) but left numbers of activated HSCs and procollagen I expression unchanged. MMP-2 activity and TIMP-1 expression were reduced by 50%. Late imatinib treatment did not alter histological or molecular markers of fibrogenesis despite high imatinib tissue levels. CONCLUSIONS: The antifibrotic effectiveness of imatinib is limited to the early phase of fibrogenesis. In ongoing liver injury other mediators most likely compensate for the inhibited PDGF effect.

Magnetic resonance imaging, ultrasonography and histology of the suspensory ligament origin: a comparative study of normal anatomy of warmblood horses

REASONS FOR PERFORMING STUDY: The diagnosis of lameness caused by proximal metacarpal and metatarsal pain can be challenging. Magnetic resonance imaging (MRI) offers the possibility for further diagnosis but there have been no studies on the normal MRI appearance of the origin of the suspensory ligament (OSL) in conjunction with ultrasonography and histology. OBJECTIVES: To describe the MRI appearance of the OSL in fore- and hindlimbs of sound horses and compare it to the ultrasonographic and histological appearance. The findings can be used as reference values to recognise pathology in the OSL. METHODS: The OSL in the fore- and hindlimbs of 6 sound horses was examined by ultrasonography prior to death, and MRI and histology post mortem. Qualitative evaluation and morphometry of the OSL were performed and results of all modalities compared. RESULTS: Muscular tissue, artefacts, variable SL size and shape complicated ultrasonographic interpretation. In MRI and histology the forelimb OSL consisted of 2 portions, the lateral being significantly thicker than medial. The hindlimb SL had a single large area of origin. In fore- and hindlimbs, the amount of muscular tissue was significantly larger laterally than medially. Overall SL measurements using MRI were significantly higher than using histology and ultrasonography and histological higher than ultrasonographic measurements. Morphologically, there was a good correlation between MRI and histology. CONCLUSIONS: MRI provides more detailed information than ultrasonography regarding muscle fibre detection and OSL dimension and correlates morphologically well with histology. Therefore, ultrasonographic results should be regarded with caution. POTENTIAL RELEVANCE: MRI may be a diagnostic aid when other modalities fail to identify clearly the cause of proximal metacarpal and metatarsal pain; and may improve selection of adequate therapy and prognosis for injuries in this region.

Improved neo-endothelialization of small diameter ePTFEgrafts with titanium coating

BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.

On the postnatal development of the striate cortex (V1) in the tree shrew (Tupaia belangeri)

Histological serial sections, three-dimensional reconstructions and morphometry served to study the postnatal development of V1 in tree shrews. The main objectives were to evaluate the expansion of V1, the implications of its growth on the occipital cortex and, vice versa, the effects of the expanding neocortex on the topography of V1. The future V1 was identified on postnatal day 1 by its granular layer IV, covering the superior surface of the occipital cortices including the poles. A subdivision of layer IV, distinctive for the binocular part, was evident in the central region. V1 expanded continuously with age into all directions succeeded by the maturation of layering. The monocular part was recognized from day 15 onward, after the binocular part had reached its medial border. In reference to the retinotopic map of V1, regions emerged in a coherent temporo-spatial sequence delineating the retinal topography in a central to peripheral gradient beginning with the visual streak representation. The growth of V1 was greatest until tree shrews open their eyes, culminated during adolescence, and completed after a subsequent decrease in the young adult. Simultaneous expansion of the neocortex induced a shifting of V1. Translation and elongation of V1 entailed that the occipital cortex covered the superior colliculi along with a downward rotation of the poles. The enlargement of the occipital part of the hemispheres was in addition associated with the formation of a small occipital horn in the lateral ventricles, indicating an incipient 'true' occipital lobe harbouring mainly cortices involved in visual functions.

FUNCTIONAL PRINCIPAL COMPONENTS MODEL FOR HIGH-DIMENSIONAL BRAIN IMAGING

We establish a fundamental equivalence between singular value decomposition (SVD) and functional principal components analysis (FPCA) models. The constructive relationship allows to deploy the numerical efficiency of SVD to fully estimate the components of FPCA, even for extremely high-dimensional functional objects, such as brain images. As an example, a functional mixed effect model is fitted to high-resolution morphometric (RAVENS) images. The main directions of morphometric variation in brain volumes are identified and discussed.

ON THE MERITS OF VOXEL-BASED MORPHOMETRIC PATH-ANALYSIS FOR INVESTIGATING VOLUMETRIC MEDIATION OF A TOXICANT'S INFLUENCE ON COGNITIVE FUNCTION

We previously showed that lifetime cumulative lead dose, measured as lead concentration in the tibia bone by X-ray fluorescence, was associated with persistent and progressive declines in cognitive function and with decreases in MRI-based brain volumes in former lead workers. Moreover, larger region-specific brain volumes were associated with better cognitive function. These findings motivated us to explore a novel application of path analysis to evaluate effect mediation. Voxel-wise path analysis, at face value, represents the natural evolution of voxel-based morphometry methods to answer questions of mediation. Application of these methods to the former lead worker data demonstrated potential limitations in this approach where there was a tendency for results to be strongly biased towards the null hypothesis (lack of mediation). Moreover, a complimentary analysis using anatomically-derived regions of interest volumes yielded opposing results, suggesting evidence of mediation. Specifically, in the ROI-based approach, there was evidence that the association of tibia lead with function in three cognitive domains was mediated through the volumes of total brain, frontal gray matter, and/or possibly cingulate. A simulation study was conducted to investigate whether the voxel-wise results arose from an absence of localized mediation, or more subtle defects in the methodology. The simulation results showed the same null bias evidenced as seen in the lead workers data. Both the lead worker data results and the simulation study suggest that a null-bias in voxel-wise path analysis limits its inferential utility for producing confirmatory results.

Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy

Pericyte loss is an early pathologic feature of diabetic retinopathy, consistently present in retinae of diabetic humans and animals. Because pericyte recruitment and endothelial cell survival are controlled, in part, by the angiopoietin/Tie2 ligand/receptor system, we studied the expression of angiopoietin-2 and -1 in relation to the evolution of pericyte loss in diabetic rat retinae, using quantitative retinal morphometry, and in retinae from mice with heterozygous angiopoietin deficiency (Ang-2 LacZ knock-in mice). Finally, recombinant angiopoietin-2 was injected into eyes of nondiabetic rats, and pericyte numbers were quantitated in retinal capillaries. Angiopoietin-1 protein was present in the normal maturing retina and was upregulated 2.5-fold in diabetic retinae over 3 months of diabetes. In contrast, angiopoietin-2 protein was consistently upregulated more than 30-fold in the retinae of diabetic rats, preceding the onset of pericyte loss. Heterozygous angiopoietin-2 deficiency completely prevented diabetes-induced pericyte loss and reduced the number of acellular capillary segments. Injection of angiopoietin-2 into the eyes of normal rats induced a dose-dependent pericyte loss. These data show that upregulation of angiopoietin-2 plays a critical role in the loss of pericytes in the diabetic retina.