julilili42/papers huggingface dataset:
High frequency of ENG and ALK1/ACVRL1 mutations in German HHT patients
2005-01-01

Morbus Osler or HHT (hereditary hemorrhagic telangiectasia) is a disorder of the fibrovascular tissue that is inherited in an autosomal dominant way with frequency rates between 1:2,500 and 1:40,000. The disease provokes malformations of the blood vessels sometimes resulting in life-threatening complications. Presently, two genes involved in the development of HHT have been identified: ACVRL1 and ENG. Both of them encode proteins that belong to the TGF-beta receptor complex family and play an essential role in the formation of the vascular system. Recently, several mutations in ACVRL1 and ENG have been described in other European populations. However, no data concerning mutation frequencies in the German population have been reported so far. Therefore, we screened our collective of German HHT patients (28 single cases and 11 familial cases) for mutations in both genes by direct sequencing. We detected 11 mutations already described elsewhere and 19 novel ones. Furthermore, evidence for the pathogenic role of four new missense mutations was collected by screening a healthy control collective using RFLP analysis. Interestingly, the majority of ACVRL1 mutations represented missense mutations, whereas mutations in ENG mostly resulted in a shortened protein. Our results demonstrate the importance of ACVRL1 and ENG mutations in German HHT patients displaying mutation frequencies over 80%.
Stress tolerance abilities and competitive responses in a watering and fertilization field experiment
2005-01-01

Abstract Question: Do water gradients produce patterns of responses to stress and competition similar to those induced by nutrient gradients? Location: French Alps. Methods: We established a split-plot design in a calcareous grassland, with watering and fertilization as main plot treatments and competition as subplot treatment. We followed individual and competitive responses of transplants of the three potential dominant grass species: Bromus erectus, Brachypodium rupestre and Arrhenatherum elatius, in all plots during two growing seasons. Changes in natural relative abundances of the three grass species were also monitored. Results: The growth and the relative abundance of A. elatius were primarily stimulated by nutrient addition and those of B. rupestre by water addition, whereas B. erectus decreased in abundance and had a very low flexibility with enhanced resource supply. Competition intensity increased for all species with both watering and fertilization and the ranking in competitive responses did not change with treatments: A. elatius &gt; B. rupestre &gt; B. erectus. Conclusions: Patterns of dominance were efficiently explained by stress tolerance abilities and competitive responses for dry and poor sites, and wet and rich sites for B. erectus and A. elatius respectively, whereas competitive responses were poor predictors of dominance for B. rupestre in wet and nutrient-poor sites. Further studies are needed to assess the potential role of other processes, such as increasing competitive effect on light with increasing age as well as interference, to explain the dominance of this conservative competitor type of species in wet and nutrient-poor sites. Abbreviations: C = Control plot; F = Fertilized plot; PAR = Photosynthetically active radiation; RNE = Relative Neighbour Effect index; W = Watered plot; WF = Watered and Fertilized plot. Nomenclature: Tutin et al. (1964–1980).
Lesions of the Dorsal Hippocampus Block Trace Fear Conditioned Potentiation of Startle.
2005-01-01

Several studies show that the hippocampus is critical for the memories mediating trace and contextual fear conditioning. This study investigates whether N-methyl-D-aspartate-induced lesions of the dorsal hippocampus made prior to training affect context fear conditioning and trace fear conditioning measured with the fear-potentiated startle. Pretraining excitotoxic lesions of the dorsal hippocampus blocked acquisition of trace fear conditioning to a tone stimulus but did not affect context fear conditioning. These data indicate that without a dorsal hippocampus rats are unable to acquire trace conditioning but can acquire contextual fear when fear is measured by potentiation of the startle response.
Expression of KIT (CD117) in Renal Cell Carcinoma and Renal Oncocytoma
2005-01-01

&lt;i&gt;Objective:&lt;/i&gt; Overexpression of KIT (CD117), a tyrosine kinase receptor, has been reported in a variety of tumors, some of which are susceptible to therapy with imatinib mesylate. Our aim was to analyze KIT expression immunohistochemically in renal cell carcinomas (RCCs) and in oncocytomas. &lt;i&gt;Methods:&lt;/i&gt; Routinely processed, paraffin-embedded specimens from 61 RCCs and 13 renal oncocytomas were investigated immunohistochemically. Cytoplasmic and membrane-bound KIT staining of tumor cells was determined semiquantitatively. A subset of cases was additionally analyzed for point mutations of &lt;i&gt;c-kit &lt;/i&gt;exon 17 by peptide nucleic acid-mediated nested polymerase chain reaction-clamping. &lt;i&gt;Results:&lt;/i&gt; All cases of oncocytomas and chromophobe RCCs showed membrane-bound KIT positivity, while about three-quarters of cases showed cytoplasmic reactivity. All other types of RCC were found KIT negative. Within the group of chromophobe RCCs, negative cytoplasmatic KIT reactivity was significantly correlated with advanced tumor stage (pT ≧ 2; p = 0.036). Analysis of &lt;i&gt;c-kit&lt;/i&gt; exon 17 revealed no ‘gain-of-function’ mutation like the codon 816 Asp→Val mutation (D816V). &lt;i&gt;Conclusions:&lt;/i&gt; KIT expression is a hallmark of oncocytoma and chromophobe RCC. Since all other types of RCC were found to be KIT negative, immunohistochemical KIT reactivity may be used as an additional diagnostic criterion to distinguish chromophobe RCC from other RCC types. KIT reactivity and the absence of &lt;i&gt;c-kit&lt;/i&gt; mutation D816V in chromophobe RCC justify speculations that imatinib mesylate therapy could be effective in patients with advanced disease.
Regulation of KCNQ4 Potassium Channel Prepulse Dependence and Current Amplitude by SGK1 in <i>Xenopus</i> oocytes
2005-01-01

The KCNQ gene family comprises voltage-gated potassium channels expressed in epithelial tissues (KCNQ1, KCNQ5), inner ear structures (KCNQ1, KCNQ4) and the brain (KCNQ2-5). KCNQ4 is expressed in inner and outer hair cells of the inner ear where it determines electrical excitability. Accordingly, loss of function mutations of the KCNQ4 gene cause hearing loss. Several K+ channels including the closely related KCNQ1/KCNE1 channel are regulated by the serum- and glucocorticoid-inducible kinase (SGK) family. The present study utilized the Xenopus oocyte system to explore effects of SGK isoforms on KCNQ4 mediated K(+)-currents: KCNQ4 channels activated in a voltage dependent manner with half maximal activation at -10 mV. The peak channel activity was significantly increased by prepulsing. Coexpression of wild type SGK1 but not coexpression of the inactive mutant (K127N)SGK1 significantly increased current amplitudes (by 67 %) and significantly increased the resting potential of KCNQ4 expressing oocytes. Here we describe for the first time a prepulse dependence of KCNQ4 channels with increased currents after hyperpolarizing prepulses. Coexpression of SGK1 significantly attenuated the effect of prepulsing on peak currents. Mutation of Ser to Asp or Ala in the putative phosphorylation consensus sequence in KCNQ4 significantly decreased the sensitivity to SGK1-coexpression. In conclusion, SGK1 regulates current amplitudes and kinetic properties of KCNQ4 channel activity, an effect sensitive to mutations in the SGK1 consensus sequence of the channel.
Trefoil Factor 2 (Tff2) Deficiency in Murine Digestive Tract Influences the Immune System
2005-01-01

On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach.
A new docodont mammal from the Late Jurassic of the Junggar Basin in Northwest China
2005-01-01

tonomous Region) produced teeth and mandibular fragments of a new docodont. The new taxon has a large “pseudo− talonid ” on the lower molars, and by retention of crest b−g exhibits closer affinities to Simpsonodon and Krusatodon from the Middle Jurassic of Europe than to the other known Asian docodonts Tashkumyrodon, Tegotherium, and Sibirotherium. It differs from the Haldanodon–Docodon−lineage by the “pseudotalonid ” and large cusps b and g. A PAUP analysis based on lower molar characters produced a single most parsimonious tree with two main clades. One clade comprises Docodon, Haldanodon, and Borealestes, and the other Dsungarodon, Simpsonodon, and Krusatodon plus the Asian tegotheriids. Analysis of the molar occlusal relationships using epoxy casts mounted on a micromanipulator revealed a four−phase chewing cycle with transverse component. The molars of the new docodont exhibit a well developed grinding function be− sides cutting and shearing, probably indicating an omnivorous or even herbivorous diet. A grinding and crushing function is also present in the molars of Simpsonodon, Krusatodon, and the Asian tegotheriids, whereas Borealestes, Haldanodon,
New Therapeutic Strategies for the Treatment of Type 2 Diabetes Mellitus Based on Incretins
2005-01-01

Orally ingested glucose leads to a greater insulin response compared to intravenously administered glucose leading to identical postprandial plasma glucose excursions, a phenomenon referred to as the "incretin effect". The incretin effect comprises up to 60% of the postprandial insulin secretion and is diminished in type 2 diabetes. One of the very important gastrointestinal hormones promoting this effect is glucagon-like peptide 1 (GLP-1). It only stimulates insulin secretion and normalizes blood glucose in humans under hyperglycemic conditions, therefore it does not cause hypoglycemia. Other important physiological actions of GLP-1 are the inhibition of glucagon secretion and gastric emptying. It further acts as a neurotransmitter in the hypothalamus stimulating satiety. In vitro and animal data demonstrated that GLP-1 increases beta-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. In humans, the improvement of beta-cell function can be indirectly observed from the increased insulin secretory capacity after GLP-1 infusions. GLP-1 represents an attractive therapeutic principle for type 2 diabetes. However, native GLP-1 is degraded rapidly upon exogenous administration and is therefore not feasible for routine therapy. The first long-acting GLP-1 analog ("incretin mimetic") Exenatide (Byetta) has just been approved for type 2 diabetes therapy. Other compounds are being investigated in clinical trials (e.g. liraglutide, CJC1131). Dipeptidyl-peptidase IV inhibitors (DPP-IV inhibitors; e.g. Vildagliptin, Sitagliptin) that inhibit the enzyme responsible for incretin degradation are also under study.
The dimethyldioxirane-mediated oxidation of phenylethyne
2005-01-01

The product pattern found for the dimethyldioxirane-mediated oxidation of phenylethyne strongly depends on the reaction conditions. Dimethyldioxirane generated in situ from caroate (HSO5−) and acetone in acetonitrile–water furnishes phenylacetic acid as the main product. With solutions of dimethyldioxirane in acetone, mandelic acid and phenylacetic acid are mainly formed. The relative abundances of the two acids depend on the residual water present in the dimethyldioxirane–acetone solution. Application of thoroughly dried solutions of the reagent effects increased formation of mandelic acid. When phenylethyne is oxidized by dimethyldioxirane transferred into tetrachloromethane, to minimize traces of water even further, oligomeric mandelic acid is obtained. The results are rationalized by the initial formation of phenyloxirene, which is known to equilibrate with phenylformylcarbene and benzoylcarbene. Subsequent Wolff rearrangement produces intermediate phenylketene, which can be trapped by water as phenylacetic acid or suffer from further oxidation to the α-lactone of mandelic acid. The α-lactone can either react with water to yield mandelic acid or, under anhydrous conditions, to yield oligomeric mandelic acid. In addition to mandelic acid and phenylacetic acid phenylglyoxylic acid, benzoic acid and benzaldehyde are observed as reaction products. The formation of phenylglyoxylic acid by transfer of two oxygen atoms to the unrearranged carbon skeleton of phenylethyne followed by oxygen insertion into the aldehydic C–H bond of the intermediately formed phenylglyoxal is discussed. In a second pathway this acid is formed by partial oxidation of mandelic acid. Benzaldehyde and benzoic acid are explained as products of the oxidative degradation of the α-lactone by dimethyldioxirane. Under in situ conditions benzoic acid is also formed by caroate initiated oxidative decarboxylation of phenylglyoxylic acid and/or intermediate phenylglyoxal.
The Posterior Contralateral Negativity as a Temporal Indicator of Visuo-Spatial Processing
2005-01-01

Abstract. The temporal segmentation of the processing stream between stimulus and response is a declared aim of many EEG-studies on cognitive processing. This goal, however, can only be reached when measures of high temporal sensitivity are available that are unequivocally assigned to a particular cognitive process. The present study evaluates the peak latency of the posterior contralateral negativity (PCN) as a temporal measure of visual spatial processing. In three experiments, we show systematic variability of the PCN latency with task demands. In visual search, PCN latency varied in the same direction as response times with the number of distractors. These effects, however, were smaller than the effects observed on response times, indicating that the process underlying the PCN might contribute to but did not determine response time effects. In contrast, in attentional cueing tasks and a stimulus localization task, where stimulus detection was the primarily addressed process, PCN latency varied to the same amount as manual response times. Thus, it is suggested that the latency of the PCN provides a reliable and valid temporal measure of target localization.
Non-invasive imaging of glycoprotein VI binding to injured arterial lesions
2005-01-01

Summary Glycoprotein VI (GPVI) is the major platelet collagen receptor and plays a critical role in the process of thrombosis at sites of atherosclerotic lesions. This study evaluates the feasibility of radiolabeled soluble GPVI to identify injured arterial lesions. Radiolabeling was carried out using the iodogen method and resulted in the radioiodinated GPVI in radiochemical yields between 97–100%. The biodistribution of [125I]GPVI was determined in normal mice and demonstrated a blood clearance halftime of approximately 5.5 hours. Vascular lesions were induced in the carotid artery in wild type and ApoE -/- mice. Immediately after injury radioiodinated GPVI was injected intravenously. Binding of [123I]GPVI to carotid lesions was assessed by szinti-graphic in vivo imaging. Carotid arteries were explanted for ex vivo autoradiography and histological characterization of the lesion. In vivo and ex vivo imaging revealed substantial accumulation of radioiodinated GPVI in the injured artery wall, with a ratio of lesion to control vessel of 3:1 and 7:1, respectively. Because GPVI is the critical collagen receptor that mediates platelet adhesion to vascular lesions, soluble radiolabeled GPVI may be an agent for non-invasive imaging of thrombogenic thus, vulnerable atherosclerotic plaques.
Bifunctional chimeric SuperCD suicide gene -YCD: YUPRT fusion is highly effective in a rat hepatoma model
2005-01-01

Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model, thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.
Delayed otogenic hydrocephalus after acute otitis media in pediatric patients: the changing presentation of a serious otologic complication
2005-01-01

We report on five cases with otogenic DST following AOM. All but one of them presented initially with diplopia caused by otogenic hydrocephalus. In four cases the otologic complaints had already disappeared by the time of MRI confirmation of the diagnosis. Only one child was referred with severe otologic symptoms. Management included systemic antibiotics, short-term heparin anticoagulation and surgical decompression. In our cases, even after intensive i.v. antibiotic treatment, only surgery led to a significant improvement in the clinical condition.
Primary intrasellar schwannoma: clinical, aetiopathological and surgical considerations
2005-01-01

Schwannomas originating within the sella turcica are extremely rare. We describe the clinical, radiological and intraoperative findings of a patient with an intrasellar and suprasellar schwannoma. Gross total tumour removal was performed by a trans-sphenoidal approach. Perivascular or ectopic Schwann cells, lateral nerve plexus within the cavernous sinus, as well as Schwann cells from small nerve twigs of the dura are some of the current histopathological hypotheses for the origin of these lesions.
Dissociation of Temporal Dynamics of Heart Rate and Blood Pressure Responses Elicited by Conditioned Fear but Not Acoustic Startle.
2005-01-01

Fear-inducing stimuli were hypothesized to elicit fast heart rate (HR) responses but slow mean arterial blood pressure (MAP) responses and thus were studied in auditory fear conditioning and acoustic startle at high temporal resolution in freely moving mice and rats. Fear-induced instantaneous acceleration of HR reaching maximum physiological values and subsequent recovery to baseline were observed. The MAP response consisted of an immediate, mild, and transient increase followed by a sluggish, profound elevation and slow recovery. HR and MAP responses served as reliable indicators of conditioned fear in mice with dissociated temporal dynamics. Unconditioned auditory stimuli, including acoustic startle stimuli, elicited only fast, mild, and transient MAP and HR elevations in mice and rats, reflecting arousal and attention under these experimental conditions.
Gas‐chromatographic separation of tri(hetero)halogenomethane enantiomers
2005-01-01

Abstract Five‐atomic tri(hetero)halogenomethanes represent the simplest class of non‐isotopic small chiral molecules suitable for the study of fundamental aspects of chirality. The analytical gas‐chromatographic separation of the enantiomers of bromochlorofluoromethane 1 and of chlorofluoroiodomethane 2 on the immobilized chiral stationary phase octakis(3‐ O ‐butanoyl‐2,6‐di‐ O ‐ n ‐pentyl)‐γ‐cyclodextrin 3, chemically linked to polydimethylsiloxane, is described. By temperature‐dependent thermodynamic measurements very low isoenantioselective temperatures T iso are found and for optimum enantiomeric separations cryogenic temperatures are required. The ee values of enantiomerically enriched tri(hetero)halogenomethanes 1 and 2 are determined and relative configurations are correlated with the chromatographic elution order of 1 and 2 on 3 . © 2005 Wiley‐Liss, Inc. Chirality 17:488–493, 2005.
Plasminogen and matrix metalloproteinase activation by enzymatically modified low density lipoproteins in monocytes and smooth muscle cells
2005-01-01

Summary Protease activity promotes the progression and rupture of atherosclerotic plaques. LDL has been described to become enzymatically modified within the vessel wall yielding an atherogenic moiety (E-LDL). We studied the effect of E-LDL on the activation of plasminogen and matrix metalloproteinases (MMPs) in mono-cytes and vascular smooth muscle cells (VSMCs) as well as on MMP activation during cellular interactions. Human monocytes, monocytic MonoMac6 cells and human VSMCs were incubated with human native LDL (n-LDL) or E-LDL for 24 hours. E-LDL in contrast to n-LDL induced substantial activation of the plasminogen activation system as well as of the MMP system in monocytic cells, as measured by enhanced cell surface expression of the urokinase receptor (uPAR), the extracellular matrix metalloproteinase Inducer (EMMPRIN) and the membrane type-1 MMPs (MT1-MMP, MMP-14), as well as by secretion of active uPA, and of MMP-9. Consistently, E-LDL-treated monocytes exhibited increased transmigration through “matrigel”, which was specifically abrogated by the MMP inhibitor galardin or the plasmin inhibitor aprotinin. In VSMCs, E-LDL induced MMP-1 and MMP-2 secretion. Moreover, monocyte incubation with supernatants of E-LDL-treated (but not n-LDL-treated)VSMCs strongly induced MMP-9 in monoytes, which was inhibited by blocking mAb anti-TNF-α. Together, enzymatical modification of LDL allows a direct activation of MMP expression in monocytes and VSMCs, and indirectly promotes the induction of paracrine, cytokine-mediated intercellular activation processes. Thereby, E-LDL may contribute to atheroprogression, inflammation and plaque rupture.
Effect of Magnesium on Red Blood Cell Deformability in Pregnancy
2005-01-01

Intravenous magnesium therapy over a 24-hour period increases RBC-deformability even in pregnancies with normal RBC-deformability. In vitro measurements show an increase of RBC-deformability in preeclampsia in response to magnesium, which could offer additional therapeutic benefit for the treatment of reduced blood flow seen in most cases of preeclampsia.
Requirement of PDZ Domains for the Stimulation of the Epithelial Ca<sup>2+</sup> Channel TRPV5 by the NHE Regulating Factor NHERF2 and the Serum and Glucocorticoid Inducible Kinase SGK1
2005-01-01

Renal calcium reabsorption involves the epithelial calcium channel ECaC1 (TRPV5) which is tightly regulated by 1,25(OH)2D3. As shown recently, TRPV5 is activated by the serum and glucocorticoid inducible kinase SGK1, a kinase transcriptionally upregulated by 1,25(OH)2D3. This stimulatory effect is due to enhanced TRPV5 abundance in the plasma membrane and requires the presence of the scaffold protein NHERF2 (sodium hydrogen exchanger regulating factor 2). The present study aims to define the molecular requirements for the interaction of TRPV5 with SGK1 and NHERF2. Pull-down experiments and overlay assays revealed that the TRPV5 C-tail interacts in a Ca2+-independent manner with NHERF2. Deletion of the second but not of the first PDZ domain in NHERF2 abrogates the stimulating effect of SGK1/NHERF2 on TRPV5 protein abundance in the plasma membrane as quantified by chemiluminescence and electrophysiology. Thus, the second PDZ domain in NHERF2 is required for stabilization at or TRPV5 targeting to the plasma membrane. The experiments demonstrate the significance of SGK1 and NHERF2 as TRPV5 modulators which are likely to participate in the regulation of calcium homeostasis by 1,25(OH)2D3.