bluuebunny/crossref_metadata_2025 huggingface dataset:
Pacific offshore record of plinian arc volcanism in Central America: 1. Along‐arc correlations
Authors: Kutterolf S. , Freundt A. , Peréz W. , Mörz T. , Schacht U. , Wehrmann H. , Schmincke H.‐U.
Published: February 2008

We collected 56 marine gravity cores from the Pacific seafloor offshore Central America which contain a total of 213 volcanic ash beds. Ash‐layer correlations between cores and with their parental tephras on land use stratigraphic, lithologic, and compositional criteria. In particular, we make use of our newly built database of bulk‐rock, mineral, and glass major and trace element compositions of plinian and similarly widespread tephras erupted since the Pleistocene along the Central American Volcanic Arc. We thus identify the distal ashes of 11 Nicaraguan, 8 El Salvadorian, 6 Guatemalan, and 1 Costa Rican eruptions. Relatively uniform pelagic sedimentation rates allow us to determine ages of 10 previously undated tephras by their relative position between ash layers of known age. Linking the marine and terrestrial records yields a tephrostratigraphic framework for the Central American volcanic arc from Costa Rica to Guatemala. This is a useful tool and prerequisite to understand the evolution of volcanism at a whole‐arc scale.
Dynamic modeling of the 2004 Mw6.0 Parkfield, California, earthquake
Authors: Ma Shuo , Custódio Susana , Archuleta Ralph J. , Liu Pengcheng
Published: February 2008

We present two spontaneous rupture models of the 2004 Mw6.0 Parkfield earthquake constrained by near‐source ground motions. We start with a stress drop distribution calculated from a kinematic slip distribution. Using a linear slip‐weakening friction law, we utilize trial and error to obtain both the stress conditions and frictional parameters on the fault that produce synthetics consistent with records. The material contrast across the San Andreas Fault is incorporated using different one‐dimensional velocity structures on each side of the fault. An approximately constantSparameter of 0.3 and a uniform slip‐weakening distance of 0.15 m are used in the dynamic models. In our preferred dynamic model, consistent with the ground motion and GPS, the slip is bounded by seismicity streaks at 5 and 10 km depths, confirming a locked zone at depth. The stress drop is approximately 10 MPa in the hypocentral region and about 2 MPa elsewhere. The material contrast across the fault causes significant normal stress variations (∼1 MPa), leading to a larger strength drop to the southeast than to the northwest. The main rupture front propagates at nearly a constant subshear rupture velocity ∼3 km/s in both directions. The total radiated energy determined from the preferred dynamic model is 1.1 × 1013J, seismic moment is 1.0 × 1018Nm, and fracture energy is 3.0 × 1013J. The limited number of aftershocks in the slipped area suggests the important role of stress on the distribution of seismicity in the locked zone.
Stress tolerance in plants via habitat-adapted symbiosis
Authors: Rodriguez Rusty J , Henson Joan , Van Volkenburgh Elizabeth , Hoy Marshal , Wright Leesa , Beckwith Fleur , Kim Yong-Ok , Redman Regina S
Published: February 2008

We demonstrate that native grass species from coastal and geothermal habitats require symbiotic fungal endophytes for salt and heat tolerance, respectively. Symbiotically conferred stress tolerance is a habitat-specific phenomenon with geothermal endophytes conferring heat but not salt tolerance, and coastal endophytes conferring salt but not heat tolerance. The same fungal species isolated from plants in habitats devoid of salt or heat stress did not confer these stress tolerances. Moreover, fungal endophytes from agricultural crops conferred disease resistance and not salt or heat tolerance. We define habitat-specific, symbiotically-conferred stress tolerance as habitat-adapted symbiosis and hypothesize that it is responsible for the establishment of plants in high-stress habitats. The agricultural, coastal and geothermal plant endophytes also colonized tomato (a model eudicot) and conferred disease, salt and heat tolerance, respectively. In addition, the coastal plant endophyte colonized rice (a model monocot) and conferred salt tolerance. These endophytes have a broad host range encompassing both monocots and eudicots. Interestingly, the endophytes also conferred drought tolerance to plants regardless of the habitat of origin. Abiotic stress tolerance correlated either with a decrease in water consumption or reactive oxygen sensitivity/generation but not to increased osmolyte production. The ability of fungal endophytes to confer stress tolerance to plants may provide a novel strategy for mitigating the impacts of global climate change on agricultural and native plant communities.
Microbial burden and diversity of commercial airline cabin air during short and long durations of travel
Authors: Osman Shariff , La Duc Myron T , Dekas Anne , Newcombe David , Venkateswaran Kasthuri
Published: February 2008

Total microbial burden and diversity associated with commercial airliner cabin air was assessed by molecular methods in 125 air samples from the business-class sections of 16 domestic and international flights. Viable microbial burden within these cabin air parcels constituted only 1–10% of the total microbial population and ranged from below detection limits to 1.2 × 104 cells m–3 as determined with a validated ATP-based technology. Cultivable bacterial diversity was almost entirely limited to Gram-positive bacteria such as Staphylococcus and Bacillus. In contrast, cloning and sequencing 16S rRNA gene directly from the samples without cultivation indicated a significantly broader diversity, as sequences representing more than 100 species, and encompassing 12 classes of bacteria, were retrieved in varying abundance. Sequences of proteobacterial and Gram-positive lineage were retrieved most frequently (58% and 31% of all clone sequences, respectively), with Gram-positive and α-proteobacterial sequences dominating international flight samples and β- and γ-proteobacterial sequences comprising the largest portion of those retrieved from domestic flights. Significant differences in bacterial load and diversity were noted between samples obtained on domestic and international flights. The disparities observed in microbial abundance and diversity further underscore the immense value of state-of-the art molecular assays in augmenting traditional culture-based techniques.
Myosins II and V in chromaffin cells: myosin V is a chromaffin vesicle molecular motor involved in secretion
Authors: Rosé Sergio D. , Lejen Tatiana , Casaletti Luciana , Larson Roy E. , Pene Teodora Dumitrescu , Trifaró José‐María
Published: February 2008

The presence of myosin II and V in chromaffin cells and their subcellular distribution is described. Myosin II and V distribution in sucrose density gradients showed only a strong correlation between the distribution of myosin V and secretory vesicle markers. Confocal microscopy images demonstrated colocalization of myosin V with dopamine β‐hydroxylase, a chromaffin vesicle marker, whereas myosin II was present mainly in the cell cortex. Cell depolarization induced, in a Ca2+ and time‐dependent manner, the dissociation of myosin V from chromaffin vesicles suggesting that this association was not permanent but determined by secretory cycle requirements. Myosin II was also found in the crude granule fraction, however, its distribution was not affected by cell depolarization. Myosin V head antibodies were able to inhibit secretion whereas myosin II antibodies had no inhibitory effect. The pattern of inhibition indicated that these treatments interfered with the transport of vesicles from the reserve to the release‐ready compartment, suggesting the involvement of myosin V and not myosin II in this transport process. The results described here suggest that myosin V is a molecular motor involved in chromaffin vesicle secretion. However, these results do not discard an indirect role for myosin II in secretion through its interaction with F‐actin networks.
1‐Methyl‐4‐phenylpyridinium accumulates in cerebellar granule neurons via organic cation transporter 3
Authors: Shang Tiesong , Uihlein Alexander V. , Van Asten Jennifer , Kalyanaraman Balaraman , Hillard Cecilia J.
Published: February 2008

1‐Methyl‐4‐phenylpyridinium (MPP+), the toxic metabolite of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, induces apoptosis in cerebellar granule neurons (CGNs). We have tested the hypothesis that organic cation transporter (OCT) 3 mediates the accumulation and, hence, the toxicity of MPP+in CGNs. CGNs in primary culture express OCT3 but do not express mRNA for OCT1, OCT2 or the dopamine transporter. Cerebellar astrocytes are negative for OCT3 protein by immunocytochemistry. [3H]MPP+accumulation by CGNs exhibits first‐order kinetics, and aKtvalue of 5.3 ± 1.2 µmand aTmaxof 0.32 ± 0.02 pmol per min per 106cells. [3H]MPP+accumulation is inhibited by corticosterone, β‐estradiol and decynium 22 withKivalues of 0.25 µm, 0.17 µmand 4.0 nmrespectively. [3H]MPP+accumulation is also inhibited by desipramine, dopamine, serotonin and norepinephrine, but is not affected by carnitine (10 mm), mazindol (9 µm) or GBR 12909 (1 µm). MPP+‐induced caspase‐3‐like activation and cell death are prevented by pretreatment with 5 µmβ‐estradiol. In contrast, the neurotoxic effects of rotenone are unaffected by β‐estradiol. Interestingly, GBR 12909 protects CGNs from both MPP+and rotenone toxicity. In summary, CGNs accumulate MPP+in manner that is consistent with uptake via OCT3 and the presence of this protein in CGNs explains their sensitivity to MPP+toxicity.
Further evidence that the CCK2receptor is coupled to two transduction pathways using site‐directed mutagenesis
Authors: Pommier Blandine , Marie‐Claire Cynthia , Da Nascimento Sophie , Wang Hung‐Li , Roques Bernard P. , Noble Florence
Published: February 2008

A heterogeneity of CCK2receptors has been reported which could correspond to different states of coupling to G proteins and/or association with different second messenger systems. To investigate these hypotheses, the wild‐type CCK2receptor and three mutants F347A, D100N and K333M/K334T/R335L, expected to modify the coupling of the G protein with the third intracellular loop of the receptor, were transfected into Cos‐7 cells and their binding and signalling properties were evaluated using the natural ligand CCK8. Activation of wild‐type as well as F347A, D100N or K333M/K334T/R335L CCK2receptors by this ligand led to a similar arachidonic acid release which was blocked by pertussis toxin and the phospholipase A2inhibitor, mepacrine. Nevertheless, in contrast to the wild‐type CCK2receptor, addition of CCK8to cells transfected with the F347A or K333M/K334T/R335L mutants did not result in the production of inositol phosphates while the maximum increase in this second messenger formation was reduced by 30% with the D100N mutant. Taken together, these results suggest that the CCK2receptor is coupled to two G proteins and that Phe347 and the cluster of basic residues K333/K334/R335 probably play a key role in Gqprotein stimulation leading to inositol phosphate production but not in activation of the G protein coupled to phospholipase A2. These data bring additional support at the molecular level to the existence of different affinity states of CCK2receptors suggested from the results of binding assays and behavioural studies.
Noradrenergic depletion increases inflammatory responses in brain: effects on IκB and HSP70 expression
Authors: Heneka Michael T. , Gavrilyuk Vitaliy , Landreth Gary E. , O'Banion M. Kerry , Weinberg Guy , Feinstein Douglas L.
Published: February 2008

The inflammatory responses in many cell types are reduced by noradrenaline (NA) binding to β‐adrenergic receptors. We previously demonstrated that cortical inflammatory responses to aggregated amyloid beta (Aβ) are increased if NA levels were first depleted by lesioning locus ceruleus (LC) noradrenergic neurons, which replicates the loss of LC occurring in Alzheimer's disease. To examine the molecular basis for increased responses, we used the selective neurotoxin DSP4 to lesion the LC, and then examined levels of putative anti‐inflammatory molecules. Inflammatory responses were achieved by injection of aggregated Aβ1–42 peptide and IL‐1β into frontal cortex, which induced neuronal inducible nitric oxide synthase (iNOS) and microglial IL‐1β expression. DSP4‐treatment reduced basal levels of nuclear factor kappa B (NF‐κB) inhibitory IκB proteins, and of heat shock protein (HSP)70. Inflammatory responses were prevented by co‐injection (ibuprofen or ciglitzaone) or oral administration (pioglitazone) of peroxisome proliferator‐activated receptor gamma (PPARγ) agonists. Treatment with PPARγ agonists restored IκBα, IκBβ, and HSP70 levels to values equal or above those observed in control animals, and reduced activation of cortical NF‐κB. These results suggest that noradrenergic depletion reduces levels of anti‐inflammatory molecules which normally limit cortical responses to Aβ, and that PPARγ agonists can reverse that effect. These findings suggest one mechanism by which PPARγ agonists could provide benefit in neurological diseases having an inflammatory component.
Photic regulation of heme oxygenase activity in the golden hamster retina: involvement of dopamine
Authors: Sacca Geraldine B. , Sáenz Daniel A. , Jaliffa Carolina O. , Minces Luciana , Sarmiento María I. Keller , Rosenstein Ruth E.
Published: February 2008

The photic regulation of heme oxygenase (HO) activity was examined in the golden hamster retina. This enzymatic activity was significantly higher at midday than at midnight. When the hamsters were placed under constant darkness for 48 h and killed at subjective day or at subjective night, the differences in HO activity disappeared. Western blot analysis showed no differences in HO levels among these time points. Dopamine significantly increased this activity in retinas excised at noon or at midnight, with a higher sensitivity at night. The effect of dopamine was reversed by SCH 23390 but not by spiperone and clozapine and it was not reproduced by quinpirole.In vitro, the increase in HO activity found in retinas incubated under light for 1 h was significantly reduced by SCH 23390. Two cAMP analogs increased HO activity and their effect, as well as the effect of dopamine was blocked by H‐89, a protein kinase A (PKA) inhibitor. Tin protoporphyrin IX, an HO inhibitor, significantly decreased cGMP accumulation with maximal effects during the day. Low concentrations of bilirubin decreased retinal thiobarbituric acid substances levels (an index of lipid peroxidation) in basal conditions and after exposing retinal cells to H2O2. These results suggest that hamster retinal HO activity is regulated by the photic stimulus, probably through a dopamine/cAMP/PKA dependent pathway.
SKF83959 selectively regulates phosphatidylinositol‐linked D1 dopamine receptors in rat brain
Authors: Jin Li‐Qing , Goswami Satindra , Cai Guoping , Zhen Xuechu , Friedman Eitan
Published: February 2008

Previously a distinct D1‐like dopamine receptor (DAR) that selectively couples to phospholipase C/phosphatidylinositol (PLC/PI) was proposed. However, lack of a selective agonist has limited efforts aimed at characterizing this receptor. We characterized the in vitro and in vivo effects of SKF83959 in regulating PI metabolism. SKF83959 stimulates (EC50, 8 µm) phosphatidylinositol 4,5‐biphosphate hydrolysis in membranes of frontal cortex (FC) but not in membranes from PC12 cells expressing classical D1A DARs. Stimulation of FC PI metabolism was attenuated by the D1 antagonist, SCH23390, indicating that SKF83959 activates a D1‐like DAR. The PI‐linked DAR is located in hippocampus, cerebellum, striatum and FC. Most significantly, administration of SKF83959 induced accumulations of IP3 in striatum and hippocampus. In contrast to other D1 DAR agonists, SKF83959 did not increase cAMP production in brain or in D1A DAR‐expressing PC12 cell membranes. However, SKF83959 inhibited cAMP elevation elicited by the D1A DAR agonist, SKF81297, indicating that the compound is an antagonist of the classical D1A DAR. Lastly, we demonstrated that SKF83959 enhances [35S]guanosine 5′‐O‐(3‐thiotriphosphate) binding to membrane Gαq and Gαi proteins, suggesting that PI stimulation is mediated by activation of these guanine nucleotide‐binding regulatory proteins. Results indicate that SKF83959 is a selective agonist for the PI‐linked D1‐like DAR, providing a unique tool for investigating the functions of this brain D1 DAR subtype.
X-ray magnetic circular dichroism in d and f ferromagnetic materials: recent theoretical progress. Part I (Review Article)
Authors: Antonov V. N. , Shpak A. P. , Yaresko A. N.
Published: February 2008

The present state of theoretical understanding of the x-ray magnetic circular dichroism (XMCD) of 3d compounds is reviewed. Energy band theory based upon the local spin-density approximation (LSDA) describes the XMCD spectra of transition metal compounds reasonably well. Examples which we examine in detail are XPt3 compounds (with X=V, Cr, Mn, Fe, Co, and Ni) in the AuCu3 structure, the Heusler compounds Co2MnGe and Co2NbSn, and the compounds with noncollinear magnetic structure IrMnAl and Mn3ZnC. Recently achieved improvements for describing the electronic and magnetic structures of 3d compounds are discussed.
Tunneling conductance of phase-coherent double-layer systems in a parallel magnetic field
Authors: Bezuglyj A. I.
Published: February 2008

A high and narrow peak of the interlayer differential tunneling conductance was found recently in experiments on double-layer electron systems in the quantum Hall effect regime at a total filling of the Landau levels νT=1. This peak is a consequence of phase coherence that is established in the system owing to the Bose condensation of electron-hole pairs with components belonging to different layers. The influence of a parallel magnetic field on the tunneling conductance of double-layer systems of small size is considered. It is shown that at finite temperatures the magnetic-field dependence of the height of the peak of the tunneling conductance has a form that resembles a Fraunhofer diffraction pattern.
Magnetization reversal in single domain Permalloy wires probed by magnetotransport
Authors: Chung T. Y. , Hsu S. Y.
Published: February 2008

We have measured the in-plane magnetoresistance (MR) of a series of submicron single domain Permalloy wires to study two important magnetization reversal modes, coherent rotation and curling. With the consideration of both micromagnetic configurations, the MR curve can be decomposed in a reversibly bell-shaped curve and an irreversibly V-shaped discontinuity in low field, respectively. The discontinuity jump occurs at a switching field characterizing the curling mode. The angular dependence of the switching field is well described by the theoretical prediction of Aharoni model under the consideration of the whole volume curling. Moreover, we found that the low angle switching field decreases with increasing wire width (decreasing the aspect ratio) as 1/width, consistent with the curling model for a long slender ellipsoid.
Ferroelectric properties of nanometer-scale barium titanate films from first principles
Authors: Tang Y.-H. , Tsai M.-H.
Published: February 2008

Ferroelectric properties of nanometer-scale barium titanate films with one, two, and three TiO6 octahedral layers stacking along the [001] direction have been studied by the first-principles calculation method. The freestanding barium titanate films are found to be ferroelectric with spontaneously formed electric dipoles parallel to the films by the existence of double-well potentials. The depth of the potential well of the free standing film is found to decrease with the increase of the thickness. However, when the substrate effect is considered, the depth of the potential well becomes deeper for thicker films, which suggests an enhancement of the ferroelectric property for thicker films.
Atomic scale study of the degradation mechanism of boron contaminated hafnium oxide
Authors: Sun Qing-Qing , Dong Lin , Shi Yu , Liu Han , Ding Shi-Jin , Zhang David Wei
Published: February 2008

Boron penetration is a big problem existing in the integration of modern fully silicided metal gate with high k dielectrics. We performed first-principles calculation to study the boron penetration induced degradation of hafnium based gate dielectrics. According to our calculation, The positive charged nature of B defects at normal working condition of p-type metal oxide semiconductor field effect transistor and its large diffusion coefficient in HfO2 result in the negative Vth (VFB) shifting or the canceling out of interface dipole for work function modulation. Moreover, remote Coulomb scattering, band offset reduction, and gap states induced by boron degrade the channel mobility and gate leakage, respectively.
Interface modification and bonding of lithium tantalate crystals
Authors: Torchinsky I. , Rosenman G.
Published: February 2008

Intermolecular interactions defined by surface free energy of solids are a critical factor affecting adhesion and bonding of the materials. An experimental technique for surface free energy and related properties (wettability and adhesion) modification has been developed and applied to lithium tantalate ferroelectric crystals. The method is based on combination of ultraviolet illumination and low-energy electron irradiation. These two techniques provide controllable wettability tailoring in a wide range of contact angles of 6°–87°. Fabrication of various wetting configurations of contacted and bonded lithium tantalate (LT) pair plates, such as hydrophilic/hydrophilic, hydrophilic/hydrophobic, and hydrophobic/hydrophobic, allows us to demonstrate direct bonding for modified hydrophilic polar LT faces.
Atomic force microscopy reveals parallel mechanical unfolding pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism
Authors: Peng Qing , Li Hongbin
Published: February 2008

Kinetic partitioning is predicted to be a general mechanism for proteins to fold into their well defined native three-dimensional structure from unfolded states following multiple folding pathways. However, experimental evidence supporting this mechanism is still limited. By using single-molecule atomic force microscopy, here we report experimental evidence supporting the kinetic partitioning mechanism for mechanical unfolding of T4 lysozyme, a small protein composed of two subdomains. We observed that on stretching from its N and C termini, T4 lysozyme unfolds by multiple distinct unfolding pathways: the majority of T4 lysozymes unfold in an all-or-none fashion by overcoming a dominant unfolding kinetic barrier; and a small fraction of T4 lysozymes unfold in three-state fashion involving unfolding intermediate states. The three-state unfolding pathways do not follow well defined routes, instead they display variability and diversity in individual unfolding pathways. The unfolding intermediate states are local energy minima along the mechanical unfolding pathways and are likely to result from the residual structures present in the two subdomains after crossing the main unfolding barrier. These results provide direct evidence for the kinetic partitioning of the mechanical unfolding pathways of T4 lysozyme, and the complex unfolding behaviors reflect the stochastic nature of kinetic barrier rupture in mechanical unfolding processes. Our results demonstrate that single-molecule atomic force microscopy is an ideal tool to investigate the folding/unfolding dynamics of complex multimodule proteins that are otherwise difficult to study using traditional methods.
Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure
Authors: Chen Jian-Fu , Murchison Elizabeth P. , Tang Ruhang , Callis Thomas E. , Tatsuguchi Mariko , Deng Zhongliang , Rojas Mauricio , Hammond Scott M. , Schneider Michael D. , Selzman Craig H. , Meissner Gerhard , Patterson Cam , Hannon Gregory J. , Wang Da-Zhi
Published: February 2008

Cardiovascular disease is the leading cause of human morbidity and mortality. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy associated with heart failure. Here, we report that cardiac-specific knockout of Dicer, a gene encoding a RNase III endonuclease essential for microRNA (miRNA) processing, leads to rapidly progressive DCM, heart failure, and postnatal lethality. Dicer mutant mice show misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicate significantly reduced heart rates and decreased fractional shortening of Dicer mutant hearts. Consistent with the role of Dicer in animal hearts, Dicer expression was decreased in end-stage human DCM and failing hearts and, most importantly, a significant increase of Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions.
PTC124 is an orally bioavailable compound that promotes suppression of the human
CFTR
-G542X nonsense allele in a CF mouse model
Authors: Du Ming , Liu Xiaoli , Welch Ellen M. , Hirawat Samit , Peltz Stuart W. , Bedwell David M.
Published: February 2008

Nonsense mutations inactivate gene function and are the underlying cause of a large percentage of the individual cases of many genetic disorders. PTC124 is an orally bioavailable compound that promotes readthrough of premature translation termination codons, suggesting that it may have the potential to treat genetic diseases caused by nonsense mutations. Using a mouse model for cystic fibrosis (CF), we show that s.c. injection or oral administration of PTC124 to
Cftr
−/− mice expressing a human
CFTR
-G542X transgene suppressed the G542X nonsense mutation and restored a significant amount of human (h)CFTR protein and function. Translational readthrough of the premature stop codon was demonstrated in this mouse model in two ways. First, immunofluorescence staining showed that PTC124 treatment resulted in the appearance of hCFTR protein at the apical surface of intestinal glands in
Cftr
−/−
hCFTR
-G542X mice. In addition, functional assays demonstrated that PTC124 treatment restored 24–29% of the average cAMP-stimulated transepithelial chloride currents observed in wild-type mice. These results indicate that PTC124 can effectively suppress the
hCFTR
-G542X nonsense mutation
in vivo
. In light of its oral bioavailability, safety toxicology profile in animal studies, and efficacy with other nonsense alleles, PTC124 has the potential to be an important therapeutic agent for the treatment of inherited diseases caused by nonsense mutations.
Evidence for a role of the 5-HT1Breceptor and its adaptor protein, p11, inl-DOPA treatment of an animal model of Parkinsonism
Authors: Zhang Xiaoqun , Andren Per E. , Greengard Paul , Svenningsson Per
Published: February 2008

Parkinson's disease (PD) is characterized by a progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Restoration of dopamine transmission byl-DOPA relieves symptoms of PD but causes prominent side effects. There is a strong serotonin innervation of the striatum by serotonergic neurons that remains relatively preserved in PD. The study of this innervation has been largely neglected. Here, we demonstrate that chronicl-DOPA administration to 6-OHDA-lesioned rodents increases, via D1receptors, the levels of the 5-HT1Breceptor and its adaptor protein, p11, in dopamine-denervated striatonigral neurons. Using unilaterally 6-OHDA-lesioned p11 WT and KO mice, it was found that administration of a selective 5-HT1Breceptor agonist, CP94253, inhibitedl-DOPA-induced rotational behavior and abnormal involuntary movements in a p11-dependent manner. These data reveal anl-DOPA-induced negative-feedback mechanism, whereby the serotonin system may influence the symptomatology of Parkinsonism.
The microbial mimic poly IC induces durable and protective CD4+T cell immunity together with a dendritic cell targeted vaccine
Authors: Trumpfheller Christine , Caskey Marina , Nchinda Godwin , Longhi Maria Paula , Mizenina Olga , Huang Yaoxing , Schlesinger Sarah J. , Colonna Marco , Steinman Ralph M.
Published: February 2008

CD4+Th1 type immunity is implicated in resistance to global infectious diseases. To improve the efficacy of T cell immunity induced by human immunodeficiency virus (HIV) vaccines, we are developing a protein-based approach that directly harnesses the function of dendritic cells (DCs) in intact lymphoid tissues. Vaccine proteins are selectively delivered to DCs by antibodies to DEC-205/CD205, a receptor for antigen presentation. We find that polyriboinosinic:polyribocytidylic acid (poly IC) independently serves as an adjuvant to allow a DC-targeted protein to induce protective CD4+T cell responses at a mucosal surface, the airway. After two doses of DEC-targeted, HIV gag p24 along with poly IC, responder CD4+T cells have qualitative features that have been correlated with protective function. The T cells simultaneously make IFN-γ, tumor necrosis factor (TNF)-α, and IL-2, and in high amounts for prolonged periods. The T cells also proliferate and continue to secrete IFN-γ in response to HIV gag p24. The adjuvant role of poly IC requires Toll-like receptor (TLR) 3 and melanoma differentiation-associated gene-5 (MDA5) receptors, but its analog poly IC12U requires only TLR3. We suggest that poly IC be tested as an adjuvant with DC-targeted vaccines to induce numerous multifunctional CD4+Th1 cells with proliferative capacity.
The First Day of Class Affects Student Motivation: An Experimental Study
Authors: Wilson Janie H. , Wilson Shauna B.
Published: February 2008

Teaching experts assert that the first day of class impacts students, with potential negative effects lasting the entire term. However, no empirical research supports this supposition. We randomly assigned students to view a video of their professor either providing a positive or negative first-day experience. Students with the positive experience reported better attitudes and more positive expectations at the end of the first day. Although several differences dissipated by the end of the first week, students with the positive first-day experience reported higher motivation for the majority of the course, and their grades were significantly higher by the end of the term.
STRADα Regulates LKB1 Localization by Blocking Access to Importin-α, and by Association with Crm1 and Exportin-7
Authors: Dorfman Julia , Macara Ian G.
Published: February 2008

LKB1, a serine/threonine kinase, regulates cell polarity, metabolism, and cell growth. The activity and cellular distribution of LKB1 are determined by cofactors, STRADα and MO25. STRADα induces relocalization of LKB1 from the nucleus to the cytoplasm and stimulates its catalytic activity. MO25 stabilizes the STRADα/LKB1 interaction. We investigated the mechanism of nucleocytoplasmic transport of LKB1 in response to its cofactors. Although LKB1 is imported into the nucleus by importin-α/β, STRADα and MO25 passively diffuse between the nucleus and the cytoplasm. STRADα induces nucleocytoplasmic shuttling of LKB1. STRADα facilitates nuclear export of LKB1 by serving as an adaptor between LKB1 and exportins CRM1 and exportin7. STRADα inhibits import of LKB1 by competing with importin-α for binding to LKB1. MO25 stabilizes the LKB1–STRADα complex but it does not facilitate its nucleocytoplasmic shuttling. Strikingly, the STRADβ, isoform which differs from STRADα in the N- and C-terminal domains that are responsible for interaction with export receptors, does not efficiently relocalize LKB1 from the nucleus to the cytoplasm. These results identify a multifactored mechanism to control LKB1 localization, and they suggest that the STRADβ-LKB1 complex might possess unique functions in the nucleus.
UNC-98 and UNC-96 Interact with Paramyosin to Promote Its Incorporation into Thick Filaments ofCaenorhabditis elegans
Authors: Miller Rachel K. , Qadota Hiroshi , Mercer Kristina B. , Gernert Kim M. , Benian Guy M.
Published: February 2008

Mutations in unc-96 or -98 cause reduced motility and a characteristic defect in muscle structure: by polarized light microscopy birefringent needles are found at the ends of muscle cells. Anti-paramyosin stains the needles in unc-96 and -98 mutant muscle. However there is no difference in the overall level of paramyosin in wild-type, unc-96, and -98 animals. Anti-UNC-98 and anti-paramyosin colocalize in the paramyosin accumulations of missense alleles of unc-15 (encodes paramyosin). Anti-UNC-96 and anti-UNC-98 have diffuse localization within muscles of unc-15 null mutants. By immunoblot, in the absence of paramyosin, UNC-98 is diminished, whereas in paramyosin missense mutants, UNC-98 is increased. unc-98 and -15 or unc-96 and -15 interact genetically either as double heterozygotes or as double homozygotes. By yeast two-hybrid assay and ELISAs using purified proteins, UNC-98 interacts with paramyosin residues 31-693, whereas UNC-96 interacts with a separate region of paramyosin, residues 699-798. The importance of surface charge of this 99 residue region for UNC-96 binding was shown. Paramyosin lacking the C-terminal UNC-96 binding region fails to localize throughout A-bands. We propose a model in which UNC-98 and -96 may act as chaperones to promote the incorporation of paramyosin into thick filaments.
Analysis of sequence variability in the macronuclear DNA of Paramecium tetraurelia: A somatic view of the germline
Authors: Duret Laurent , Cohen Jean , Jubin Claire , Dessen Philippe , Goût Jean-François , Mousset Sylvain , Aury Jean-Marc , Jaillon Olivier , Noël Benjamin , Arnaiz Olivier , Bétermier Mireille , Wincker Patrick , Meyer Eric , Sperling Linda
Published: February 2008

Ciliates are the only unicellular eukaryotes known to separate germinal and somatic functions. Diploid but silent micronuclei transmit the genetic information to the next sexual generation. Polyploid macronuclei express the genetic information from a streamlined version of the genome but are replaced at each sexual generation. The macronuclear genome of Paramecium tetraurelia was recently sequenced by a shotgun approach, providing access to the gene repertoire. The 72-Mb assembly represents a consensus sequence for the somatic DNA, which is produced after sexual events by reproducible rearrangements of the zygotic genome involving elimination of repeated sequences, precise excision of unique-copy internal eliminated sequences (IES), and amplification of the cellular genes to high copy number. We report use of the shotgun sequencing data (>106 reads representing 13× coverage of a completely homozygous clone) to evaluate variability in the somatic DNA produced by these developmental genome rearrangements. Although DNA amplification appears uniform, both of the DNA elimination processes produce sequence heterogeneity. The variability that arises from IES excision allowed identification of hundreds of putative new IESs, compared to 42 that were previously known, and revealed cases of erroneous excision of segments of coding sequences. We demonstrate that IESs in coding regions are under selective pressure to introduce premature termination of translation in case of excision failure.
Mouse consomic strains: Exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies
Authors: Gregorová Sona , Divina Petr , Storchova Radka , Trachtulec Zdenek , Fotopulosova Vladana , Svenson Karen L. , Donahue Leah Rae , Paigen Beverly , Forejt Jiri
Published: February 2008

Consomic (chromosome substitution) strains (CSs) represent the most recent addition to the mouse genetic resources aimed to geneticaly analyze complex trait loci (QTLs). In this study, we report the development of a set of 28 mouse intersubspecific CSs. In each CS, we replaced a single chromosome of the C57BL/6J (B6) inbred strain (mostly Mus m. domesticus) with its homolog from the PWD/Ph inbred strain of the Mus m. musculus subspecies. These two progenitor subspecies diverged less than 1 million years ago and accumulated a large number of genetic differences that constitute a rich resource of genetic variation for QTL analyses. Altogether, the 18 consomic, nine subconsomic, and one conplastic strain covered all 19 autosomes, X and Y sex chromosomes, and mitochondrial DNA. Most CSs had significantly lower reproductive fitness compared with the progenitor strains. CSs homosomic for chromosomes 10 and 11, and the C57BL/6J-Chr X males, failed to reproduce and were substituted by less affected subconsomics carrying either a proximal, central, or distal part of the respective chromosome. A genome-wide scan of 965 DNA markers revealed 99.87% purity of the B6 genetic background. Thirty-three nonsynonymous substitutions were uncovered in the protein-coding regions of the mitochondrial DNA of the B6.PWD-mt conplastic strain. A pilot-phenotyping experiment project revealed a high number of variations among B6.PWD consomics.
MISSBRAUCH VON BENZODIAZEPINDERIVATEN BEI ALKOHOLKRANKEN*
Authors: KRYSPIN‐EXNER K.
Published: February 2008

—Seit der Einführung der Benzodiazepine in die psychiatrische Therapie wurden diese Substanzen im weiten Bereich zur Therapie von Alkoholkranken verwendet. Um festzustellen welche Suchtgefährdung diese Substanzen beinhalten. wurden 491 ambulant behandelte Alkoholiker in der Alkoholabstinenz in dieser Hinsicht einer genauen Untersuchung unterzogen. 111 dieser Patienten waren auf Chlordiazepoxyd und 302 auf Diazepam eingestellt. Über die dabei beobachteten Fälle von Sucht und Mißbrauch wird berichtet. wobei ein Fall von Chlordiaz‐epoxydmißbrauch und ein Fall von Diazepamsucht mit einem schweren Entziehungssyndrom ausführlich beschrieben werden. Es wird auf den zum Unterschied von der Barbituratsucht und Alkoholsucht unterschiedlichen Mechanismus des Tranquilizer‐Mißbrauches hingewiesen. Die selbstaggressiven Tendenzen, die dazu führen sind geringer ausgeprägt. Den Tranquilizern fehlt die primär euphorisierende Wirkung. Die klinischen Bilder der Suchtfälle erreichen nicht den Schweregrad der Barbituratsucht. Die Rückbildung der Ausfallserscheinungen geht wesentlich rascher vor sich und ist in allen Fällen vollständig. Es besteht daher keine Kontraindikation zur Verwendung der Benzodiazepine bei den an sich suchtgefährdeten Alkoholkranken, doch ist eine regelmäßige ärztliche Kontrolle, der unter Benzodiazepinmedikation stehenden Patienten erforderlich. Polytoxikomane sollten nicht mit Tranquilizern behandelt werden.
The Use of Methadone for Narcotic Blockade
Authors: DOLE VINCENT P. , NYSWANDER MARIE E.
Published: February 2008

Résumé— Methadone, une drogue narcotique, peut être utilisée comme un agent antinarcotique s'il est administré aux patients dans une dose constante, orale, journalière. La drogue bloquée, les intoxiqués à l'héroine ne peuvent plus l'utiliser pour obtenir l'euphorie. Ils sont dans un état normal fonctionnel et sont capables de devenir des membres responsables de leur communauté. En traitant 750 cas d'intoxiqués á l'héroine, tenaces, dans les quatres dernières années, on a eu 90% de succès.

Zusammenfassung— Methadon, eine narkotische Medizin, kann als antinarkotisches Mittel verwendent werden, wenn es Patienten in gleichbleibenden, oralen, täglichen Dosen verabreicht wird. Derartig blockierte Heroinsüchtige können dieses Rauschgift nicht mehr zur Erzielung von Euphorie benützen. Sie befinden sich in einem normalen, funktionellen Zustand und sind in der Lage, verantwortungsvolle Mitglieder ihrer Gemeinschaft zu werden. Mit dieser Behandlung wurde ein 90% Erfolg bei 750 eingefleischten Heroinsüchtigen während der vergangenen vier Jahre erzielt.
Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome
Authors: Hama Asahito , Yagasaki Hiroshi , Takahashi Yoshiyuki , Nishio Nobuhiro , Muramatsu Hideki , Yoshida Nao , Tanaka Makito , Hidaka Hirokazu , Watanabe Nobuhiro , Yoshimi Ayami , Matsumoto Kimikazu , Kudo Kazuko , Kato Koji , Horibe Keizo , Kojima Seiji
Published: February 2008

To characterize childhood acute megakaryoblastic leukaemia (AMKL), we reviewed 45 children with AMKL diagnosed between 1986 and 2005 at Nagoya University Hospital and Japanese Red Cross Nagoya First Hospital. Twenty‐four patients (53%) had AMKL associated with Down syndrome (DS‐AMKL) and 21 (47%) had non‐DS‐AMKL. The median age of the DS‐AMKL patients was 21 months (range, 8–38 months) and that of non‐DS‐AMKL patients was 15 months (range, 2–185 months). The morphology of blast cells was categorized into three groups according to the stage of megakaryocyte maturation. The blast cells were more immature in DS‐AMKL than in non‐DS‐AMKL in terms of morphology and immunophenotyping. Cytogenetic abnormalities of leukaemic cells were classified into seven categories: normal karyotype including constitutional trisomy 21 in DS‐AMKL; numerical abnormalities only; t(1;22)(p13;q13); 3q21q26 abnormalities; t(16;21)(p11;q22); −5/del(5q) and/or −7/del(7q); and other structural changes. The outcome of children with either DS‐AMKL or non‐DS‐AMKL is excellent. The 10‐year overall survival estimate was 79% [95% confidence interval (CI): 54–90] for DS‐AMKL and 76% (95% CI: 58–91) for non‐DS‐AMKL (P = 0·81) with a median follow‐up of 78 months (range, 20–243 months). Our study shows the diverse heterogeneity of childhood AMKL and the need for subclassification according to cytogenetic and morphological features.
Maternal Antenatal Anxiety and Amniotic Fluid Cortisol and Testosterone: Possible Implications for Foetal Programming
Authors: Sarkar P. , Bergman K. , O’Connor T. G. , Glover V.
Published: February 2008

Both animal and human studies have shown that maternal stress or anxiety during pregnancy is associated with increased risk of disturbance in offspring neurodevelopment and behaviour. In animal models, increased foetal exposure to glucocorticoids has been found to be one mechanism for such foetal programming. Little is understood of the mediating mechanisms in humans, and one aim of our research programme is to investigate this further. This review presents a synopsis of some of our recent results. We aimed to test the hypothesis that maternal anxiety was associated with raised maternal cortisol, and that this in turn was related to increased foetal exposure to cortisol. We studied this by recruiting women at amniocentesis, obtained their Spielberger State Anxiety scores, and assessed maternal plasma cortisol and amniotic fluid cortisol. We also examined maternal plasma and amniotic fluid testosterone levels. Awaiting amniocentesis was in general anxiogenic, but with a wide range of anxiety scores. Maternal anxiety was significantly associated with plasma cortisol before 17 weeks, albeit of modest magnitude (r = 0.0.23), and not after 17 weeks of gestation. This is probably due to the known attenuation of the maternal hypothalamic‐pituitary‐adrenal axis with increasing gestation. We found a strong correlation between maternal plasma and amniotic fluid cortisol levels, which increased with gestation and became robust after 18 weeks. This correlation increased with maternal anxiety, suggesting a possible effect of maternal mood on placental function. There was a positive correlation between cortisol and testosterone in amniotic fluid, in both male and female foetuses independent of maternal anxiety, plasma testosterone, gestational age, and time of collection. Foetal stress may be associated with increased foetal exposure to testosterone. However, maternal anxiety did not predict amniotic fluid cortisol or testosterone level. Thus, the role of these hormones in mediating the effect of maternal mood on foetal development in humans remains to be demonstrated.
The influence of clients' perceptions of the helping relationship in the development of an empathy scale
Authors: REYNOLDS B.
Published: February 2008

The paper includes a discussion about the origins of items on a measure of cognitive–behavioural empathy. This scale was originally produced by the author as a teaching tool for an empathy education programme (for RNs) and subsequently developed into a quantitative measure of empathy. The instrument is being used as part of a triangulated approach for data collection on research into the effectiveness of an educational programme about registered nurses' empathy.

Antecedents of the initial item pool for the scale stem from theoretical views about empathy, the professional experience of others, and the researcher's experience with clients. While this scale has undergone some investigation for reliability and validity, this work will only be summarized briefly. The major focus for the paper is clients' reports of interpersonal conditions which they perceive as being helpful, or unhelpful, in respect of building therapeutic nurse–client relationships.
Stories about living in a hospital ward as narrated by schizophrenic patients
Authors: PEJLERT A. , ASPLUND K. , NORBERG A.
Published: February 2008

Stories about living in a hospital ward as narrated by schizophrenic patients

Ten schizophrenic patients were interviewed about their own experiences of life in a hospital ward, of their care provider and of the care received. The interview texts were analysed using a phenomenological hermeneutic method. Fatigue, thinking about problems/inner activities, relations and longings for the pre‐illness days were themes that occurred in the stories. Seven of the ten interviewees stated that they suffered from fatigue. They were preoccupied with an inner dialogue, trying to solve problems on their own. The patients were alone in their stories. The problems that the patients expressed with regard to relationships arose because they both longed for and feared contact with others, and they felt that they were not ‘themselves’ when they were with others. For developing care, the importance of learning more about the patients' experiences, especially regarding fatigue, is emphasized.
Schizophrenic patients' image of their carers and the carers' image of their patients: an interview study
Authors: HELLZENRN O. , NORBERGRN A. , SANDMANRN P.O.
Published: February 2008

Schizophrenic patients' image of their carers and the carers' image of their patients: an interview study

In order to gain a deeper understanding of how long‐term adult schizophrenic patients perceive themselves, their carers and the care they receive in relation to how the carers perceive their patients, themselves and the care they provide, a narrative interview study, analysed using a method inspired by Ricoeur's philosophy, was performed. The main findings of this study were that both patients and carers who saw the patients as a subject stressed the confirming relation between the parties as an essential element of the care. The carers who saw the patient as an object did not share this opinion. They had a more restricted point of view, seeing their goal only as providing a variety of care activities and keeping the schizophrenic patients at the hospital. This study also points out that confirmation is provided in the meeting between patient and carers.
The phenomenon of clinical supervision in psychiatric health care
Authors: SEVERINSSON E. I.
Published: February 2008

The main objective of this study is to describe how nurses experience clinical supervision in psychiatric care. The study design is explorative and descriptive. A clinical supervision process with a theoretical approach to caring includes a learning process, the application of a caring process, and a relationship process. An important aspect of this theoretical approach is the spiritual dimension of caring and its manifestation in the supervision process as well as in the development of the nurse's identity. The results indicate the following phenomena: guilt and a feeling of guilt, reconciliation, forgiveness and loneliness.