julilili42/papers huggingface dataset:
Suicidal Erythrocyte Death Following Cellular K<sup>+</sup> Loss
2007-01-01

Hallmarks of apoptosis include cell shrinkage, which is at least partially due to cellular K(+) loss. The decline of cellular K(+) concentration has been suggested to participate in the triggering of apoptosis. Suicidal erythrocyte death or eryptosis is triggered by increased cytosolic Ca(2+) activity leading to activation of Ca(2+)-sensitive K(+) channels with subsequent cellular K(+) loss and cell shrinkage, and to Ca(2+)-sensitive scambling of the cell membrane with subsequent phosphatidylserine (PS) exposure at the cell surface. Phosphatidylserine exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. The present study explored whether cellular loss of K(+) and/or cell shrinkage actively participate in the triggering of cell membrane phospholipid scrambling. Cellular K(+) loss was achieved by treatment of human erythrocytes with the K(+) ionophore valinomycin (1 nM) at different extracellular K(+) concentrations (5-125 mM) and osmolarities (300-550 m Osm). Cell volume was estimated from forward scatter and PS exposure from annexin V binding in FACS analysis. Treatment with 1 nM valinomycin indeed decreased forward scatter and increased annexin V binding. The effect was significantly blunted in the presence of staurosporine (1 microM). Increase of extracellular K(+) concentration gradually blunted the decrease of forward scatter but inhibited annexin V binding only at extracellular K(+) concentrations >or=75 mM. An increase of extracellular osmolarity (+150 mM or 250 mM sucrose) reversed the protective effect of 75 mM KCl during valinomycin treatment. A correlation between forward scatter and annexin binding at different osmolarities and K(+) concentrations suggests that the cellular K(+) content determines the rate of suicidal erythrocyte death primarily through its influence on cell volume.
Amyloid Induced Suicidal Erythrocyte Death
2007-01-01

Amyloid peptides are known to induce apoptosis in a wide variety of cells. Erythrocytes may similarly undergo suicidal death or eryptosis, which is characterized by scrambling of the cell membrane with subsequent exposure of phosphatidylserine (PS) at the cell surface. Eryptosis is triggered by increase of cytosolic Ca(2+) activity and by activation of acid sphingomyelinase with subsequent formation of ceramide. Triggers of eryptosis include energy depletion and isosmotic cell shrinkage (replacement of extracellular Cl(-) by impermeable gluconate for 24 h). The present study explored whether amyloid peptide Abeta (1-42) could trigger eryptosis and to possibly identify underlying mechanisms. Erythrocytes from healthy volunteers were exposed to amyloid and PS-exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca(2+) activity (Fluo3 fluorescence) and ceramide formation (anti-ceramide antibody) were determined by FACS analysis. Exposure of erythrocytes to the amyloid peptide Abeta (1-42) (> or = 0.5 microM) for 24 h significantly triggered annexin V binding, an effect mimicked to a lesser extent by the amyloid peptide Abeta (1-40) (1 microM). Abeta (1-42) (> or = 1.0 microM) further significantly decreased forward scatter of erythrocytes. The effect of Abeta (1-42) (> or = 0.5 microM) on erythrocyte annexin V binding was paralleled by formation of ceramide but not by significant increase of cytosolic Ca(2+) activity. The presence of Abeta (1-42) further significantly enhanced the eryptosis following Cl(-) depletion but not of glucose depletion for 24 hours. The present observations disclose a novel action of Abeta (1-42), which may well contribute to the pathophysiological effects of amyloid peptides, such as vascular complications in Alzheimer's disease.
Induction of Suicidal Erythrocyte Death by Listeriolysin from <i>Listeria monocytogenes</i>
2007-01-01

Listeriolysin, the secreted cytolysin of the facultative intracellular bacterium Listeria monocytogenes, is its major virulence factor. Previously, non-lytic concentrations of listeriolysin were shown to induce Ca2+-permeable nonselective cation channels in human embryonic kidney cells. In erythrocytes, Ca2+ entry is followed by activation of K+ channels resulting in K+-exit as well as by membrane scrambling resulting in phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. Phosphatidylserine exposure is a key event of eryptosis, the suicidal death of erythrocytes. The present study utilized patch-clamp technique, Fluo3-fluorescence, and annexin V-binding in FACS analysis to determine the effect of listeriolysin on cell membrane conductance, cytosolic free Ca2+ concentration, and phosphatidylserine exposure, respectively. Within 30 minutes, exposure of human peripheral blood erythrocytes to low concentrations of listeriolysin (which were non-hemolytic for the majority of cells) induced a Ca2+-permeable cation conductance in the erythrocyte cell membrane, increased cytosolic Ca2+ concentration, and triggered annexin V-binding. Increase of extracellular K+ concentration blunted, but did not prevent, listeriolysin-induced annexin V-binding. In conclusion, listeriolysin triggers suicidal death of erythrocytes, an effect at least partially due to depletion of intracellular K+. Listeriolysin induced suicidal erythrocyte death could well contribute to the pathophysiology of L. monocytogenes infection.
Platelet interaction with progenitor cells: Potential implications for regenerative medicine
2007-01-01

Summary Circulating endothelial progenitor cells have been shown to instigate new vessel formation via angiogenesis and neovascularisation and to induce ongoing vascular and tissue repair by domiciliation to sites of vascular or tissue damage. However, the mechanisms that recruit circulating endothelial progenitor cells towards vascular lesions and regulate repair mechanisms of ischemic peripheral organs are poorly described. Domiciliation of endothelial progenitor cells in peripheral tissue is a multi-step cascade including initial adhesion to subendothelial matrix or endothelium, transmigration and invasion of the target tissue. Platelets are the first circulating blood cells that interact with the injured vessel wall. They contain a number of growth factors, chemokines, cytokines and adhesive proteins that are released or surface-expressed upon platelet activation including adhesion. Recent studies suggest that platelet interaction with endothelial progenitor cells influences chemotaxis, adhesion, activation and differentiation of progenitor cells. Release of the chemokine SDF-1 from platelets enhances neovascularization through mobilization of progenitor cells. Adherent platelets recruit bone marrow-derived progenitor cells to arterial thrombi in vitroand in vivoand induce their subsequent differentiation towards an endothelial phenotype. Moreover, platelet accumulation in a co-culture system with CD34+ progenitor cells results in the differentiation of the latter to macrophages in vitro. Although further studies are needed to elucidate the mechanisms that platelets determine the fate of endothelial progenitor cells into vascular lesions, platelet interaction with progenitor cells seems to play a decisive role in vascular and tissue regeneration.
Curcumin Induced Suicidal Erythrocyte Death
2007-01-01

The natural nutrient component Curcumin with anti-inflammatory and antitumor activity has previously been shown to stimulate apoptosis of several nucleated cell types. The present study has been performed to explore whether Curcumin could similarly induce suicidal death of erythrocytes or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing cells are phagocytosed and thus rapidly cleared from circulating blood. Erythrocyte membrane scrambling may be triggered by increase of cytosolic Ca(2+) activity or formation of ceramide. To test for eryptosis, erythrocyte phosphatidylserine exposure has been estimated from annexin V binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to Curcumin (= 1 microM) increased annexin V binding and decreased forward scatter, pointing to phosphatidylserine exposure at the cell surface and cell shrinkage. According to Fluo3 fluorescence Curcumin increased cytosolic Ca(2+) activity and according to immunofluorescence Curcumin increased ceramide formation. As shown previously, hypertonic shock (addition of 550mM sucrose), chloride removal and glucose depletion decreased the forward scatter and increased annexin V binding. The effects on annexin binding were enhanced in the presence of Curcumin. Exposure to Curcumin did, however, not significantly enhance the shrinking effect of hypertonic shock or Cl(-) removal and reversed the shrinking effect of glucose withdrawal. The present observations disclose a proeryptotic effect of Curcumin which may affect the life span of circulating erythrocytes.
Differential radioactive quantification of protein abundance ratios between benign and malignant prostate tissues: Cancer association of annexin A3
2007-01-01

Abstract A differential quantitative protein expression study, comparing matched prostate cancerous and benign tissues from 31 patients, revealed proteins newly associated with prostate cancer. Average effects for 17 proteins whose abundance was significantly different ( p &lt;0.01) across patients ranged from 1.5‐ to 6.1‐fold, and included a number of known cancer markers. The most differentially abundant proteins between cancer and benign samples were isopeptidase T, serum amyloid P (SAP), annexin A3 (ANXA3) and mitochondrial enoyl coenzyme‐A hydratase. SAP is restricted to stroma in healthy tissue, and the lower abundance in tumours may be explained by the reduced stromal content. ANXA3 is present in healthy epithelial cells, exhibits strong staining in precancerous prostatic intraepithelial neoplasia, and is relatively less abundant in individual tumour cells of increasing Gleason pattern (GP), despite exhibiting higher overall tissue abundance in tumours. ANXA3 staining was predominantly cytoplasmic, yet nuclear localization was also observed. Strongly staining single cells, possibly phagocytes, were interspersed in highly dedifferentiated GP5 tumour areas among tumour cells without measurable ANXA3. Local recurrent androgen ablation therapy‐resistant tumours exhibit heterogenous low levels of ANXA3 staining. Results are discussed focussing on the potential implications for tumour tissues.
Decomposing sources of response slowing in the PRP paradigm.
2007-01-01

The mechanism underlying the reaction time (RT2) slowing to the 2nd of 2 successively presented stimuli (S1 and S2) in the psychological refractory period paradigm was investigated. Stimulus onset synchrony (SOA) between S1 and S2, contrast of S2, and Task 2 set-level compatibility was manipulated. Specifically, the authors used a psychophysiological approach to examine RT2 slowing in trials in which the reaction time to S1 (RT1) was shorter than the SOA. For trials with RT1 < SOA, the clear decrease in RT2 with increasing SOA was underadditive with the S2 contrast effect, but additive with compatibility. Electrophysiological measures revealed an exclusively premotoric locus of RT2 slowing. These findings indicate that a central bottleneck stage is occupied for some period after response to S1 execution, consistent with an extended response selection bottleneck account.
PHENOTYPICALLY FLEXIBLE SEX ALLOCATION IN A SIMULTANEOUS HERMAPHRODITE
2007-01-01

Previous studies on sex allocation in simultaneous hermaphrodites have typically focused either on evolutionary or one-time, ontogenetic optimization of sex allocation, ignoring variation within an individual's lifetime. Here, we study whether hermaphrodites also possess facultative sex allocation, that is, a phenotypic flexibility, allowing them to distribute resources to either sex in an opportunistic way during their adult lifetime. We used the simultaneously hermaphroditic free-living flatworm Macrostomum lignano and raised individuals in pairs and groups of eight worms (further called octets) until sexual maturity was reached and sex allocation for the current conditions was expected to be set. Treatment groups were subsequently transferred to the alternative group size, that is, from pairs to octets or from octets to pairs, and compared to two control groups, which were transferred without changing group size. The results show that worms in treatment groups responded as expected by the local mate competition theory for simultaneous hermaphrodites: increasing group size resulted in a shift toward a more male-biased sex allocation and vice versa. These findings reveal that sex allocation in these animals is not fixed during ontogeny, but remains flexible after maturation. We argue that phenotypically flexible sex allocation in hermaphroditic animals may help us to understand the evolution and ecology of hermaphroditism.
Phase II, randomized, multicenter, comparative study of peginterferon–α–2a (40 kD) (Pegasys®)versusinterferon α-2a (Roferon®-A) in patients with treatment-naïve, chronic-phase chronic myelogenous leukemia
2007-01-01

The efficacy and safety of peginterferon-alpha-2a (40 kD) (PEG-IFNalpha-2a), 450 microg once weekly, versus IFNalpha-2a, 9 MIU once daily, for 12 months, was evaluated in a Phase II study in IFN-naïve patients with chronic-phase, Philadelphia-chromosome-positive CML. At the end of the treatment, complete hematological response was observed in 66.2% (47/71) and 45.2% (33/73) of the PEG-IFNalpha-2a group and IFNalpha-2a groups, respectively (p = 0.009), and major cytogenetic response occurred in 35.2% and 17.8%, respectively (p = 0.016). PEG-IFNalpha-2a was at least as effective as IFNalpha-2a overall, including progression-free survival at the end of treatment, and overall survival after 30 months of follow-up. Adverse events necessitated fewer withdrawals but more dose adjustments in the PEG-IFNalpha-2a group compared with the IFNalpha-2a group (11%versus 23%, and 84.5%versus 65.8%, respectively). In conclusion, PEG-IFNalpha-2a (40 kD), 450 microg once weekly, compared with IFNalpha-2a, 9 MIU once daily, resulted in higher rates of hematologic and cytogenetic response and greater overall survival.
The Border Sequence of the Balhimycin Biosynthesis Gene Cluster from <i>Amycolatopsis balhimycina</i> Contains <i>bbr</i>, Encoding a StrR-Like Pathway-Specific Regulator
2007-01-01

Balhimycin, produced by the actinomycete &lt;i&gt;Amycolatopsis balhimycina&lt;/i&gt; DSM5908, is a glycopeptide antibiotic highly similar to vancomycin, the antibiotic of ‘last resort’ used for the treatment of resistant Gram-positive pathogenic bacteria. Partial sequence of the balhimycin biosynthesis gene cluster was previously reported. In this work, cosmids which overlap the region of the characterized gene cluster were isolated and sequenced. At the ‘left’ end of the cluster, genes were identified which are involved in balhimycin biosynthesis, transport, resistance and regulation. The ‘right’ end border is defined by a putative 3-deoxy-&lt;i&gt;D&lt;/i&gt;-arabino-heptulosonate 7-phosphate synthase &lt;i&gt;(dahp)&lt;/i&gt; gene. The proximate gene is similar to a type I polyketide synthase gene of the rifamycin producer &lt;i&gt;Amycolatopsis mediterranei&lt;/i&gt; indicating that another biosynthesis gene cluster might be located directly next to the balhimycin gene cluster. The newly identified StrR-like pathway-specific regulator, Bbr, was characterized to be a DNA-binding protein and may have a role in balhimycin biosynthesis. Purified N-terminally His-tagged Bbr shows specific DNA-binding to five promoter regions within the gene cluster. By in silico analysis and by comparison of the DNA sequences binding Bbr, conserved inverted repeat sequences for the Bbr-binding site are proposed. The putative Bbr consensus sequence differs from that published for StrR.
Sitagliptin: Profile of a novel DPP-4 inhibitor for the treatmentof type 2 diabetes
2007-01-01

Novel therapeutic strategies for type 2 diabetes are needed, since the current treatment options neither address all pathophysiological mechanisms nor achieve the glycemic target goals. A general islet-cell dysfunction including insulin- and glucagon-secretion defects contributes to the pathophysiology of type 2 diabetes. Improving islet function by incretin hormone action is a novel therapeutic approach. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are important incretin hormones contributing to 50-70% of the stimulation of insulin secretion after a meal. Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of GLP-1 and GIP as well as that of other regulatory peptides. Sitagliptin, a DPP-4 inhibitor, is orally active and has been shown to be efficacious and safe in clinical studies. Sitagliptin has received approval in Mexico, the United States and other countries. Like other DPP-4 inhibitors, sitagliptin reduces hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. Sitagliptin is weight neutral. Indirect measures show a possible improvement of beta-cell function. Sitagliptin does not cause a higher rate of hypoglycemia in comparison to metformin or placebo. This article gives an overview of the mechanisms of action, pharmacology and clinical trial results of sitagliptin.
Influence of Nebivolol and Metoprolol on Inflammatory Mediators in Human Coronary Endothelial or Smooth Muscle Cells. Effects on Neointima Formation After Balloon Denudation in Carotid Arteries of Rats Treated with Nebivolol
2007-01-01

We found that nebivolol reduced the expression of proinflammatory genes in endothelial cells and vascular smooth muscle cells in vitro whereas metoprolol did not. In vivo, nebivolol inhibited neointima formation by reducing SMC proliferation and macrophage accumulation.
An innovative model for teaching complex clinical procedures: Integration of standardised patients into ward round training for final year students
2007-01-01

Ward round training with standardized patients is greatly appreciated by final year students and is viewed as an important part of their education, easing the transition from observing ward rounds to conducting them on their own.
Activation of the RAGE pathway: a general mechanism in the pathogenesis of polyneuropathies?
2007-01-01

These data suggest that activation of the RAGE pathway might contribute to the pathogenesis of CIDP, PNP owing to vitamin B12 deficiency, diabetes and vasculitis, whereas it does not seem to be involved in the pathogenesis of PNP owing to alcohol, MGUS, CMT I or II and idiopathic PNP.
The nature of vendobionts
2007-01-01

Abstract The notion that the majority of Ediacaran fossils do not represent stem groups to modern metazoan phyla is now increasingly accepted. Nevertheless, the further claim of the vendobiont hypothesis needs to be elaborated: that these large and seemingly complex organisms were not truly multicellular. Arguments for interpreting vendobionts as an extinct class of rhizopodan Protozoa are: (1) negative allometry of the quilts; (2) presence of a loosely englutinated, but sandy fill skeleton similar to the xenophyophorian stercomare; (3) a disparity of designs and lifestyles that would be incompatible with metazoan bauplans and feeding strategies; (4) unusual patterns of regeneration; (5) resting traces of some mobile, epibenthic species.
Conditioned behavioral responses to a context paired with the predator odor trimethylthiazoline.
2007-01-01

Contextual fear conditioning is the learning of a fear response in a specific context in response to repeated application of aversive stimuli (e.g., foot shocks) or danger-related stimuli (predator odors) within that context. Cat odor, a danger-related stimulus common in laboratory studies of fear in the past, has often been replaced recently with trimethylthiazoline (TMT), a component of fox feces. No contextual fear conditioning in response to TMT has been reported so far, whereas cat odor has often been shown to induce such fear conditioning in rats. Using TMT in both a 1-compartment and a 2-compartment setup, the authors found conditioned fear behavior (expressed as avoidance behavior) in the 2-compartment setup but not--as reported by others--in the 1-compartment setup. Detailed analysis revealed 2 different coping strategies in the 2-compartment setup: Half of the rats showed pronounced avoidance behavior, whereas the other half showed intense risk assessment behavior. These results indicate that expression of conditioned fear behavior in response to a TMT-paired context is dependent on the experimental setup used, as well as the strategy of the individual rat.
Towards the automatic extraction of definitions in Slavic
2007-01-01

This paper presents the results of the prelim-inary experiments in the automatic extrac-tion of definitions (for semi-automatic glos-sary construction) from usually unstructured or only weakly structured e-learning texts in Bulgarian, Czech and Polish. The ex-traction is performed by regular grammars over XML-encoded morphosyntactically-annotated documents. The results are less than satisfying and we claim that the rea-son for that is the intrinsic difficulty of the task, as measured by the low interannota-tor agreement, which calls for more sophis-ticated deeper linguistic processing, as well as for the use of machine learning classifica-tion techniques. 1
Talonavicular arthrodesis or triple arthrodesis: Peak pressure in the adjacent joints measured in 8 cadaver specimens
2007-01-01

Our findings from this cadaver study indicate a lower and more evenly distributed peak pressure load in the ankle joint after talonavicular arthrodesis than after triple arthrodesis; thus, mechanically, a selective arthrodesis appears to be more favorable. In contrast, triple arthrodesis leads to an increase in peak pressure in the ankle joint, which may in turn lead to joint degeneration.
Construction and validation of a rigorous surface hopping algorithm for conical crossings
2007-01-01

This article presents and evaluates a surface hopping algorithm for\\ntime-dependent two-level Schrödinger systems with conically\\nintersecting eigenvalues. The algorithm implements an asymptotic semigroup\\nfor approximating the solution’s Wigner function, which was rigorously\\ndefined and derived from the Schrödinger equation by two of the\\nauthors in previous work. It is applied to two-dimensional isotropic\\nsystems, which include linear Jahn-Teller Hamiltonians and Gaussian initial\\ndata. It reproduces energy level populations and expectation values with an\\naccuracy of two to three percent.