Lithium distribution across the membrane of motoneurons in the isolated frog spinal cord

Lithium sensitive microelectrodes were used to investigate the transmembrane distribution of lithium ions (Li+) in motoneurons of the isolated frog spinal cord. After addition of 5 mmol·l–1 LiCl to the bathing solution the extracellular diffusion of Li+ was measured. At a depth of 500 m, about 60 min elapsed before the extracellular Li+ concentration approached that of the bathing solution. Intracellular measurements revealed that Li+ started to enter the cells soon after reaching the motoneuron pool and after up to 120 min superfusion, an intra — to extracellular concentration ratio of about 0.7 was obtained. The resting membrane potential and height of antidromically evoked action potentials were not altered by 5 mmol·l–1 Li+

Characterisation of Connexin Expression and Electrophysiological Properties in Stable Clones of the HL-1 Myocyte Cell Line

The HL-1 atrial line contains cells blocked at various developmental stages. To obtain homogeneous sub-clones and correlate changes in gene expression with functional alterations, individual clones were obtained and characterised for parameters involved in conduction and excitation-contraction coupling. Northern blots for mRNAs coding for connexins 40, 43 and 45 and calcium handling proteins (sodium/calcium exchanger, L- and T-type calcium channels, ryanodine receptor 2 and sarco-endoplasmic reticulum calcium ATPase 2) were performed. Connexin expression was further characterised by western blots and immunofluorescence. Inward currents were characterised by voltage clamp and conduction velocities measured using microelectrode arrays. The HL-1 clones had similar sodium and calcium inward currents with the exception of clone 2 which had a significantly smaller calcium current density. All the clones displayed homogenous propagation of electrical activity across the monolayer correlating with the levels of connexin expression. Conduction velocities were also more sensitive to inhibition of junctional coupling by carbenoxolone (∼80%) compared to inhibition of the sodium current by lidocaine (∼20%). Electrical coupling by gap junctions was the major determinant of conduction velocities in HL-1 cell lines. In summary we have isolated homogenous and stable HL-1 clones that display characteristics distinct from the heterogeneous properties of the original cell line

Adult Attention Deficit Hyperactivity Disorder and Violence in the Population of England: Does Comorbidity Matter?

It is unclear whether the association between Attention Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms or co-existing psychopathology. We investigated associations of ADHD and its symptom domains of hyperactivity and inattention, among individuals reporting violence in the UK population. Methods We report data from the Adult Psychiatric Morbidity Survey (2007), a representative sample of the household population of England. A randomly selected sample of 7,369 completed the Adult Self-Report Scale for ADHD and the self-reported violence module, including repetition, injury, minor violence, victims and location of incidents. All models were weighted to account for non-response and carefully adjusted for demography and clinical predictors of violence: antisocial personality, substance misuse and anxiety disorders. Results ADHD was moderately associated with violence after adjustments (OR 1.75, p = .01). Hyperactivity, but not inattention was associated with several indicators of violence in the domestic context (OR 1.16, p = .03). Mild and moderate ADHD symptoms were significantly associated with violence repetition, but not severe ADHD where the association was explained by co-existing disorders. Stratified analyses further indicated that most violence reports are associated with co-occurring psychopathology. Conclusions The direct effect of ADHD on violence is only moderate at the population level, driven by hyperactivity, and involving intimate partners and close persons. Because violence associated with severe ADHD is explained by co-existing psychopathology, interventions should primarily target co-existing disorders

Gang membership and sexual violence: associations with childhood maltreatment and psychiatric morbidity.

BACKGROUND: Gang members engage in many high-risk sexual activities that may be associated with psychiatric morbidity. Victim-focused research finds high prevalence of sexual violence towards women affiliated with gangs. AIMS: To investigate associations between childhood maltreatment and psychiatric morbidity on coercive and high-risk sexual behaviour among gang members. METHOD: Cross-sectional survey of 4665 men 18-34 years in Great Britain using random location sampling. The survey oversampled men from areas with high levels of violence and gang membership. Participants completed questionnaires covering violent and sexual behaviours, experiences of childhood disadvantage and trauma, and psychiatric diagnoses using standardised instruments. RESULTS: Antisocial men and gang members had high levels of sexual violence and multiple risk behaviours for sexually transmitted infections, childhood maltreatment and mental disorders, including addictions. Physical, sexual and emotional trauma were strongly associated with adult sexual behaviour and more prevalent among gang members. Other violent behaviour, psychiatric morbidity and addictions accounted for high-risk and compulsive sexual behaviours among gang members but not antisocial men. Gang members showed precursors before age 15 years of adult preference for coercive rather than consenting sexual behaviour. CONCLUSIONS: Gang members show inordinately high levels of childhood trauma and disadvantage, sexual and non-sexual violence, and psychiatric disorders, which are interrelated. The public health problem of sexual victimisation of affiliated women is explained by these findings. Healthcare professionals may have difficulties promoting desistance from adverse health-related behaviours among gang members whose multiple high-risk and violent sexual behaviours are associated with psychiatric morbidity, particularly addictions

EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Determination of the number of J/ψ events with J/ψ → inclusive decays

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The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Two-photon widths of the χ c0,2 states and helicity analysis for χ c2→γγ

Based on a data sample of 106×106 ψ ′ events collected with the BESIII detector, the decays ψ ′→γχ c0,2, χ c0,2→γγ are studied to determine the two-photon widths of the χ c0,2 states. The two-photon decay branching fractions are determined to be B(χ c0→γγ)=(2. 24±0.19±0.12±0.08)×10 -4 and B(χ c2→γγ)=(3.21±0.18±0. 17±0.13)×10 -4. From these, the two-photon widths are determined to be Γ γγ(χ c0)=(2. 33±0.20±0.13±0.17)keV, Γ γγ(χ c2)=(0.63±0.04±0. 04±0.04)keV, and R=Γ γγ(χ c2)/ Γ γγ(χ c0)=0.271±0. 029±0.013±0.027, where the uncertainties are statistical, systematic, and those from the PDG B(ψ ′→γχ c0,2) and Γ(χ c0,2) errors, respectively. The ratio of the two-photon widths for helicity λ=0 and helicity λ=2 components in the decay χ c2→γγ is measured for the first time to be f 0/2=Γγγλ= 0(χ c2)/Γγγλ=2(χ c2)=0. 00±0.02±0.02. © 2012 American Physical Society.published_or_final_versio