Lichtheim 2: synthesizing aphasia and the neural basis of language in a neurocomputational model of the dual dorsal-ventral language pathways

Traditional neurological models of language were based on a single neural pathway (the dorsal pathway underpinned by the arcuate fasciculus). Contemporary neuroscience indicates that anterior temporal regions and the "ventral" language pathway also make a significant contribution, yet there is no computationally-implemented model of the dual pathway, nor any synthesis of normal and aphasic behavior. The "Lichtheim 2" model was implemented by developing a new variety of computational model which reproduces and explains normal and patient data but also incorporates neuroanatomical information into its architecture. By bridging the "mind-brain" gap in this way, the resultant "neurocomputational" model provides a unique opportunity to explore the relationship between lesion location and behavioral deficits, and to provide a platform for simulating functional neuroimaging data.     

The level of orally ingested vitamin C affected the expression of vitamin C transporters and vitamin C accumulation in the livers of ODS rats

We investigated the effects of vitamin C administration on vitamin C-specific transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter levels increased in the livers of the rats not administered vitamin C and decreased in the livers of those administered vitamin C at 100 mg/d, indicating that these transporter levels can be influenced by the amount of vitamin C administered.     

Inhibition of ubiquitin ligase F-box and WD repeat domain-containing 7α (Fbw7α) causes hepatosteatosis through Krüppel-like factor 5 (KLF5)/peroxisome proliferator-activated receptor γ2 (PPARγ2) pathway but not SREBP-1c protein in mice

F-box and WD repeat domain-containing 7α (Fbw7α) is the substrate recognition component of a ubiquitin ligase that controls the degradation of factors involved in cellular growth, including c-Myc, cyclin E, and c-Jun. In addition, Fbw7α degrades the nuclear form of sterol regulatory element-binding protein (SREBP)-1a, a global regulator of lipid synthesis, particularly during mitosis in cultured cells. This study investigated the in vivo role of Fbw7α in hepatic lipid metabolism. siRNA knockdown of Fbw7α in mice caused marked hepatosteatosis with the accumulation of triglycerides. However, inhibition of Fbw7α did not change the level of nuclear SREBP-1 protein or the expression of genes involved in fatty acid synthesis and oxidation. In vivo experiments on the gain and loss of Fbw7α function indicated that Fbw7α regulated the expression of peroxisome proliferator-activated receptor (PPAR) γ2 and its target genes involved in fatty acid uptake and triglyceride synthesis. These genes included fatty acid transporter Cd36, diacylglycerol acyltransferase 1 (Dgat1), and fat-specific protein 27 (Cidec). The regulation of PPARγ2 by Fbw7α was mediated, at least in part, by the direct degradation of the Krüppel-like factor 5 (KLF5) protein, upstream of PPARγ2 expression. Hepatic Fbw7α contributes to normal fatty acid and triglyceride metabolism, functions that represent novel aspects of this cell growth regulator.     

How do you RUN on?

RUN domain is present in several proteins related to the functions of Rap and Rab family GTPases. Accumulating evidence supports the hypothesis that RUN domain-containing proteins act as a component of vesicle traffic and might be responsible for an interaction with a filamentous network linked to actin cytoskeleton or microtubules. That is to say, on one hand, RUN domains associate with Rab or Rap family proteins, on the other hand, they also might interact with motor proteins such as kinesin or myosin via intervention molecules. In this review, we summarize the background and current status of RUN domain research with an emphasis on the interaction between RUN domain and motor proteins with respect to the vesicle traffic on filamentous network.     

Comparison of morphological and molecular traits for species identification and taxonomic grouping of oncaeid copepods

The pelagic marine copepod family Oncaeidae is highly diversified (over 100 species worldwide) and includes a great number of sibling species, which are difficult to identify morphologically, because of their very small size (0.18–1.2 mm total length as adults). Global investigations of oncaeid biodiversity are severely hampered by insufficient taxonomic knowledge, in particular for species which have first been described from the European Mediterranean Sea (type locality). Many of these species have been reported as key taxa of small-sized copepod communities in very distant oceanic regions. However, due to the taxonomic uncertainties it cannot be excluded that at least some of these allegedly cosmopolitan species in reality represent a complex of distinct, yet closely related, species. To improve the basis for the identification of Oncaeidae of Mediterranean origin, new diagnostic characters in combination with traditional methods were applied in the present study. Copepods were sampled with fine nets of 0.1 mm mesh size down to a maximum depth of 1,000 m on a west-east-transect in the Mediterranean Sea. Oncaeid species and form variants were predefined morphologically and the genetic identity of the morphospecies was analysed by about 650 and 500 bp region of the mitochondrial COI and 12S srRNA gene sequence, respectively (barcoding). A total of 67 individuals from 24 oncaeid species and forms were successfully analysed, including 12 species and one form of Mediterranean origin. For Oncaeidae, the 12S amplification turned out to be more successful (23 species) than the COI amplification (13 species and 1 form). Together, the morphological and molecular results are discussed with respect to three topics: (1) confirmation of a genetic distinction of three Triconia species, which have been interpreted as sibling species by morphological characters, (2) genetic distance of species within the ovalis-complex of oncaeids and (3) the taxonomic status of two form variants of Oncaea mediterranea (Claus).     

Caloric restriction mimetic 2-deoxyglucose antagonizes doxorubicin-induced cardiomyocyte death by multiple mechanisms

Caloric restriction (CR) is a dietary intervention known to enhance cardiovascular health. The glucose analog 2-deoxy-D-glucose (2-DG) mimics CR effects in several animal models. However, whether 2-DG is beneficial to the heart remains obscure. Here, we tested the ability of 2-DG to reduce cardiomyocyte death triggered by doxorubicin (DOX, 1 μm), an antitumor drug that can cause heart failure. Treatment of neonatal rat cardiomyocytes with 0.5 mm 2-DG dramatically suppressed DOX cytotoxicity as indicated by a decreased number of cells that stained positive for propidium iodide and reduced apoptotic markers. 2-DG decreased intracellular ATP levels by 17.9%, but it prevented DOX-induced severe depletion of ATP, which may contribute to 2-DG-mediated cytoprotection. Also, 2-DG increased the activity of AMP-activated protein kinase (AMPK). Blocking AMPK signaling with compound C or small interfering RNA-mediated knockdown of the catalytic subunit markedly attenuated the protective effects of 2-DG. Conversely, AMPK activation by pharmacological or genetic approach reduced DOX cardiotoxicity but did not produce additive effects when used together with 2-DG. In addition, 2-DG induced autophagy, a cellular degradation pathway whose activation could be either protective or detrimental depending on the context. Paradoxically, despite its ability to activate autophagy, 2-DG prevented DOX-induced detrimental autophagy. Together, these results suggest that the CR mimetic 2-DG can antagonize DOX-induced cardiomyocyte death, which is mediated through multiple mechanisms, including the preservation of ATP content, the activation of AMPK, and the inhibition of autophagy.     

Cyst morphology of a chain-forming unarmored dinoflagellate Gyrodinium impudicum Fraga et Bravo

Cysts of a chain‐forming dinoflagellate Gyrodinium impudicum Fraga et Bravo (Gymnodiniales) were found in surface sediments of Harima‐Nada and Nakaumi, western Japan. The detailed morphology of living and empty cysts is described. The living cysts are roundish to ellipsoidal in polar view, and hemispherical in lateral view. Among three empty cysts obtained, two different archeopyles were observed; either a long slit with an operculum, or a hole with irregular zigzag outline. The living cysts of Gyro. impudicum are morphologically similar to those of the genus Chattonella antiqua (Hada) Ono and Chattonella marina (Subrahmanyan) Y. Hara et Chihara (Raphidophyceae), except cyst color and contents. The living cysts of Gyro. impudicum were rarely encountered, and their density was always less than 1 cell in 1 cm^?3 in the present samples.