Prospects and Pitfalls of Desalination Development: Insights From Three States

Like Coleridge’s sailor in the Rime of the Ancient Mariner, burgeoning coastal communities in the United States have long lamented the fact that while situated by vast expanses of ocean water, they could not slake their growing thirst with it. Increasing populations, steady demand, and declining. Freshwater sources have amplified the problem across the U.S., particularly in the country’s three most populous states: California, Texas, and Florida. This paper examines efforts in three states to bring desalination plants online to transform saline water into a secure water supply

The 2018 U.S. Trust® Study of High Net Worth Philanthropy

The results of the 2018 U.S. Trust Study of High Net Worth Philanthropy demonstrate, in many ways, a continuation of the broad trends seen in previous years’ Studies. Taken as a whole, giving by high net worth households appears to be stronger than ever. The familiarity of these ongoing trends is reassuring, but it may also be deceptive. Trends are, by definition, dynamic, and the trends in this year’s Study reveal a powerful undercurrent of social, economic, political and demographic forces that will compel nonprofit organizations to adopt strategies and business practices that are more inclusive and transparent

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Sensitization of lamina I spinoparabrachial neurons parallels heat hyperalgesia in the chronic constriction injury model of neuropathic pain

It has been proposed that spinal lamina I neurons with ascending axons that project to the midbrain play a crucial role in hyperalgesia. To test this hypothesis the quantitative properties of lamina I spinoparabrachial neurons in the chronic constriction injury (CCI) model of neuropathic pain were compared to those of unoperated and sham-operated controls. Behavioural testing showed that animals with a CCI exhibited heat hyperalgesia within 4 days of the injury, and this hyperalgesia persisted throughout the 14-day post-operative testing period. In the CCI, nociceptive lamina I spinoparabrachial neurons had heat thresholds that were significantly lower than controls (43.0 ± 2.8°C vs. 46.7 ± 2.6°C; P < 10−4, ANOVA). Nociceptive lamina I spinoparabrachial neurons were also significantly more responsive to graded heat stimuli in the CCI, compared to controls (P < 0.02, 2-factor repeated-measures ANOVA), and increased after-discharges were also observed. Furthermore, the heat-evoked stimulus–response functions of lamina I spinoparabrachial neurons in CCI animals co-varied significantly (P < 0.03, ANCOVA) with the amplitude of heat hyperalgesia determined behaviourally. Taken together these results are consistent with the hypothesis that lamina I spinoparabrachial neurons have an important mechanistic role in the pathophysiology of neuropathic pain

Leptin Activates Anorexigenic POMC Neurons through a Neural Network in the Arcuate Nucleus

The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus7 are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (g-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamu

Baclofen inhibits guinea pig magnocellular neurones via activation of an inwardly rectifying K+ conductance

The GABAB receptors GABAB-R1 and GABAB-R2 have been cloned in several mammalian species, and the functional receptor has been shown to exist as a heterodimeric complex. We have cloned guinea pig GABAB-R1 and GABAB-R2 receptor sequences and, using in situ hybridization and immunocytochemistry for vasopressin (AVP), we found that GABAB-R1 and -R2 receptors are expressed in vasopressin neurones of the supraoptic (SON) and paraventricular nuclei (PVN). Therefore, we used both sharp electrode and whole-cell patch recording techniques to examine the effects of the selective GABAB agonist baclofen on SON and PVN magnocellular neurones and to determine the coupling of the GABAB receptor to effector pathways. Recordings were made in coronal hypothalamic slices from both female (ovariectomized) and male guinea pigs. In the presence of tetrodotoxin (TTX), baclofen hyperpolarized (ΔVmax = 5.6 mV, EC50 = 2.3 μM) SON magnocellular neurones (n = 27) under current clamp, or induced an outward current that reversed at EK (ΔImax = 24.2 pA) in PVN magnocellular neurones (n = 33) under voltage clamp. Seventeen of the 24 biocytin-labelled SON magnocellular neurones were identified as AVP neurones, and ten of the 33 biocytin-labelled PVN neurones were identified as AVP or neurophysin-containing neurones, although all of the cells were clustered in the vasopressin-rich core. In the absence of TTX, baclofen activated an outward K+ current that hyperpolarized SON and PVN neurones and significantly reduced their firing rate. The outward current showed inward rectification and was blocked by the K+ channel blocker barium and the GABAB receptor antagonist CGP 35348. Therefore, GABAB receptors are coupled to inwardly rectifying K+ channels in SON and PVN magnocellular neurones and may play a prominent role in modulating phasic bursting activity in guinea pig vasopressin neurones