Corporal Punishment in Schools; Due Process; Cruel and Unusual Punishment; Ingraham v. Wright

Corporal punishment as a means of disciplining school children has been used in this country since colonial days. There have been various constitutional attacks on the practice of inflicting corporal punishment, with varying results, and the issue was finally brought before the Supreme Court in Ingraham v. Wright. The Court decided on April 19, 1977 that the Cruel and Unusual Punishment Clause of the eighth amendment does not apply to disciplinary corporal punishment in public schools and that the Due Process Clause of the fourteenth amendment does not require notice and hearing prior to imposition of corporal punishment, as that practice is authorized and limited by the common law

Accumulation of Mg to Diffusive Gradients in Thin Films (DGT) devices: Kinetic and thermodynamic effects of the ionic strength

Availability of magnesium is a matter of concern due to its role in many environmental and biological processes. Diffusive Gradients in Thin Films (DGT) devices can measure Mg availability in situ. This work shows that Mg accumulation in water largely increases when ionic strength (I) decreases. This phenomenon can be explained from (i) the increase of both the association equilibrium (K) and rate (ka,R) constants for the reaction between Mg cations and resin sites, and (ii) the growing contribution of the partitioning of Mg cations at the resin–gel interface, as I decreases. Two theoretical models that take into account electrical interactions among Mg cations, background electrolyte, and resin sites can successfully be used to determine ka,R and K at each I. Both models yield similar ka,R values, which fulfill an expression for the kinetic salt effect. For freshwater (with a typical salinity of 10 mM and circumneutral pH), the binding of Mg is so fast and strong that the simplest perfect-sink DGT expression can be helpful to predict (overestimation lower than 5%) the accumulation in solutions with Mg concentrations up to 1 mM whenever the deployment time is below 9 h. Perfect sink conditions can still be applied for longer times, in systems with either a lower I or a lower Mg concentration.Financial support from FEDER and the Spanish Ministry of Education and Science (Projects CTM2012-39183 and CTM2013-48967) is gratefully acknowledged

Salmonella prevalence serotypes and patterns of antimicrobial resistance in cohorts of nursery and finishing pigs

Salmonella are now being monitored by the Food Safety Inspection Service of the USDA for purposes of process control in slaughter plants, and as a sentinel organism for emerging antimicrobial resistance (I). Public concerns about the emergence of foodborne bacteria with multi-resistant phenotypes, and about the use of antimicrobials in food animals, are increasing. Despite considerable research, the epidemiology of asymptomatic Salmonella in pigs is poorly understood (2). The purpose of this paper is to examine the association between nursery prevalence of Salmonella and finisher prevalence, and to describe patterns of antimicrobial use and antimicrobial resistant Salmonella in modern swine rearing facilities

Prion protein attenuates excitotoxicity by inhibiting NMDA receptors

It is well established that misfolded forms of cellular prion protein (PrP [PrPC]) are crucial in the genesis and progression of transmissible spongiform encephalitis, whereas the function of native PrPC remains incompletely understood. To determine the physiological role of PrPC, we examine the neurophysiological properties of hippocampal neurons isolated from PrP-null mice. We show that PrP-null mouse neurons exhibit enhanced and drastically prolonged N-methyl-d-aspartate (NMDA)–evoked currents as a result of a functional upregulation of NMDA receptors (NMDARs) containing NR2D subunits. These effects are phenocopied by RNA interference and are rescued upon the overexpression of exogenous PrPC. The enhanced NMDAR activity results in an increase in neuronal excitability as well as enhanced glutamate excitotoxicity both in vitro and in vivo. Thus, native PrPC mediates an important neuroprotective role by virtue of its ability to inhibit NR2D subunits

Role of angiotensin II type 1A receptor phosphorylation, phospholipase D, and extracellular calcium in isoform-specific protein kinase C membrane translocation responses

The angiotensin II type 1A receptor (AT(1A)R) plays an important role in cardiovascular function and as such represents a primary target for therapeutic intervention. The AT(1A)R is coupled via G(q) to the activation of phospholipase C, the hydrolysis of phosphoinositides, release of calcium from intracellular stores, and the activation of protein kinase C (PKC). We show here that PKC beta I and PKC beta II exhibit different membrane translocation patterns in response to AT(1A)R agonist activation. Whereas PKC beta II translocation to the membrane is transient, PKC beta I displays additional translocation responses: persistent membrane localization and oscillations between the membrane and cytosol following agonist removal. The initial translocation of PKC beta I requires the release of calcium from intracellular stores and the activation of phospholipase C, but persistent membrane localization is dependent upon extracellular calcium influx. The mutation of any of the three PKC phosphorylation consensus sites (Ser-331, Ser-338, and Ser-348) localized within the AT(1A)R C-tail significantly increases the probability that persistent increases in diacylglycerol levels and PKC beta I translocation responses will be observed. The persistent increase in AT(1A)R-mediated diacylglycerol formation is mediated by the activation of phospholipase D. Although the persistent PKC beta I membrane translocation response is absolutely dependent upon the PKC activity-dependent recruitment of an extracellular calcium current, it does not require the activation of phospholipase D. Taken together, we show that the patterning of AT(1A)R second messenger response patterns is regulated by heterologous desensitization and PKC isoform substrate specificity

BarA-UvrY Two-Component System Regulates Virulence of Uropathogenic E. coli CFT073

Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI) in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory cytokines (TNF-α and IL-6) and chemokine (IL-8). The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract

Acid-evoked Ca2+ signalling in rat sensory neurones: effects of anoxia and aglycaemia

Ischaemia excites sensory neurones (generating pain) and promotes calcitonin gene-related peptide release from nerve endings. Acidosis is thought to play a key role in mediating excitation via the activation of proton-sensitive cation channels. In this study, we investigated the effects of acidosis upon Ca2+ signalling in sensory neurones from rat dorsal root ganglia. Both hypercapnic (pHo 6.8) and metabolic–hypercapnic (pHo 6.2) acidosis caused a biphasic increase in cytosolic calcium concentration ([Ca2+]i). This comprised a brief Ca2+ transient (half-time approximately 30 s) caused by Ca2+ influx followed by a sustained rise in [Ca2+]i due to Ca2+ release from caffeine and cyclopiazonic acid-sensitive internal stores. Acid-evoked Ca2+ influx was unaffected by voltage-gated Ca2+-channel inhibition with nickel and acid sensing ion channel (ASIC) inhibition with amiloride but was blocked by inhibition of transient receptor potential vanilloid receptors (TRPV1) with (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide (AMG 9810; 1 μM) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropryazine-1(2H)-carbox-amide (BCTC; 1 μM). Combining acidosis with anoxia and aglycaemia increased the amplitude of both phases of Ca2+ elevation and prolonged the Ca2+ transient. The Ca2+ transient evoked by combined acidosis, aglycaemia and anoxia was also substantially blocked by AMG 9810 and BCTC and, to a lesser extent, by amiloride. In summary, the principle mechanisms mediating increase in [Ca2+]i in response to acidosis are a brief Ca2+ influx through TRPV1 followed by sustained Ca2+ release from internal stores. These effects are potentiated by anoxia and aglycaemia, conditions also prevalent in ischaemia. The effects of anoxia and aglycaemia are suggested to be largely due to the inhibition of Ca2+-clearance mechanisms and possible increase in the role of ASICs

Analysis of GPCR/ion channel interactions

Voltage-gated calcium channels are key regulators of calcium homeostasis in excitable cells. A number of cellular signaling pathways serve to fine tune calcium channel activity, including the activation of G protein-coupled receptors. Besides regulating channel activity via second messengers, GPCRs can also physically associate with calcium channels to directly regulate their functions, as well as their trafficking to and from the plasma membrane. Here we provide some methods that can be used to examine channel-receptor interactions and co-trafficking. While we focus on voltage-gated calcium channels, the techniques described herein are broadly applicable to other types of channels

The truth in complexes: why unraveling ion channel multi-protein signaling nexuses is critical for understanding the function of the nervous system

In the search for simple explanations of the natural world, its complicated textures are often filed down to a smoothened surface of our liking. The impetus for this Research Topic was borne out of a need to re-ignite interest in the complex – in this case in the context of ion channels in the nervous system. Ion channels are the large proteins that form regulated pores in the membranes of cells and, in the brain, are essential for the transfer, processing and storage of information. These pores full of twists and turns themselves are not just barren bridges into cells. More and more we are beginning to understand that ion channels are like bustling medieval bridges (packed with apartments and shops) rather than the more sleek modern variety – they are dynamic hubs connected with many structures facilitating associated activities. Our understanding of these networks continues to expand as our investigative tools advance. Together these articles highlight how the complexity of ion channel signaling nexuses is critical to the proper functioning of the nervous system