Climate change and epidemics in Chinese history: A multi-scalar analysis.

This study seeks to provide further insight regarding the relationship of climate-epidemics in Chinese history through a multi-scalar analysis. Based on 5961 epidemic incidents in China during 1370-1909 CE we applied Ordinary Least Square regression and panel data regression to verify the climate-epidemic nexus over a range of spatial scales (country, macro region, and province). Results show that epidemic outbreaks were negatively correlated with the temperature in historical China at various geographic levels, while a stark reduction in the correlational strength was observed at lower geographic levels. Furthermore, cooling drove up epidemic outbreaks in northern and central China, where population pressure reached a clear threshold for amplifying the vulnerability of epidemic outbreaks to climate change. Our findings help to illustrate the modifiable areal unit and the uncertain geographic context problems in climate-epidemics research. Researchers need to consider the scale effect in the course of statistical analyses, which are currently predominantly conducted on a national/single scale; and also the importance of how the study area is delineated, an issue which is rarely discussed in the climate-epidemics literature. Future research may leverage our results and provide a cross-analysis with those derived from spatial analysis.

Modes of direct modulation by taurine of the glutamate NMDA receptor in rat cortex.

Taurine is an endogenous brain substance with robust neuromodulatory and possible neuroprotective properties. Though other mechanisms of action have been reported, its interaction with the NMDA (N-methyl-D-aspartic acid) receptor is undocumented. We investigated taurine's interaction with the NMDA receptor using electrophysiological and receptor binding approaches. The effects of taurine on field potential responses in layer-5 of prelimbic cortex in rat brain slices evoked by single-pulse electrical stimulation of ventral medial cortex were determined. Picrotoxin (80 µM) was present in all control and drug solutions to block the Cl(-) channels associated with the GABA-, taurine-, and strychnine sensitive glycine- receptors. A typical response consisted of an NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]-quinoxaline-7-sulfonamide)-sensitive negative wave (N1) followed by a positive wave (P1) and a broad negativity (N2), both sensitive to dl-AP5 (dl-2-amino-5-phosphonopentanoic acid) inhibition. Taurine exerted a 41.5 ± 8.3% (n = 9) voltage reduction within the late phase of N2. This taurine action was prevented by 100 µM AP5, but not by 10 µM nifedipine, supporting a direct modulation of NMDA receptor function by taurine, without requiring the involvement of the L-type Ca(2+) channel. Taurine did not alter specific [(3)H] MK-801 binding to rat cortical membranes in the presence of glycine or glutamate; but inhibited spermine-potentiated specific [(3)H] MK-801 binding to NMDA receptors by 15-20% in the presence of glycine. In addition, taurine reduced the apparent affinity of the NMDA receptor for glycine (in the presence of spermine) by 10-fold. These results show that taurine interacts directly with the NMDA receptor by multiple mechanisms.

Neuropsychopharmacological actions of taurine.

Taurine, an endogenous amino sulfonic acid, exhibits numerous neuropsychopharmacological activities. Previous studies in our laboratory have shown that it is an effective anti-cataleptic and neuro-protective agent. Current investigations show that acute or chronic administration of psychotropic drug cocaine may increase extracellular release of endogenous taurine which may protect against deleterious effects of the substances of abuse. Taurine administration was found to prevent cocaine-induced addiction by suppressing spontaneous locomotor activity and conditioned place preference. Taurine markedly delayed tail-flick response in rats which was significantly different from that in the group of animal receiving the same volume of saline, thereby indicating that taurine is a potentially valuable analgesic agent. Both taurine and endomorphin-1 were found to suppress the delayed broad negative evoked field potentials in anterior insular cortex (upper layer 5) by partially inhibiting NMDA receptor system. Thus, taurine is a unique psychopharmacological compound with potential for a variety of therapeutic uses including as a neuro-protective, anti-cataleptic, anti-addicting, and analgesic agent.

Direct interaction of taurine with the NMDA glutamate receptor subtype via multiple mechanisms.

Taurine has neuroprotective capabilities against glutamate-induced excitotoxicity through several identified mechanisms including opening of the Cl(-)channel associated with GABA(A)and glycine receptors, or a distinct Cl(-)channel. No existing work has however shown a direct interaction of taurine with the glutamate NMDA receptor. Here we demonstrate such direct interactions using electrophysiological and receptor binding techniques on rat medial prefrontal cortical (mPFC) slices and well-washed rat cortical membrane. Electrically evoked field potential responses were recorded in layer 4/5 of mPFC in the presence of picrotoxin to prevent opening of Cl(-)channels gated by GABA or taurine. Applied taurine markedly diminished evoked-response amplitude at the peak and latter phases of the response. These phases were predominantly sensitive to the NMDA antagonist, MK-801, but not the AMPA/kainate receptor antagonist CNQX. Furthermore, this taurine effect was blocked by APV pretreatment. Taurine (0.1 mM) decreased spermine-induced enhancement of specific ((3)H) MK-801 binding to rat cortical membrane in the presence of glycine, though it was ineffective in the absence of spermine. Our preliminary work shows that taurine diminished the apparent affinity of NMDA receptor to glycine in the presence of spermine. These results indicate that taurine may directly interact with the NMDA receptor through multiple mechanisms.

Prenatal cocaine reduces AMPA receptor synaptic expression through hyperphosphorylation of the synaptic anchoring protein GRIP.

Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective AMPA receptors (AMPARs). We hypothesized that prenatal cocaine exposure attenuates AMPAR signaling by interfering with AMPAR synaptic targeting. AMPAR function is governed by receptor cycling on and off the synaptic membrane through its interaction with glutamate receptor-interacting protein (GRIP), a PDZ domain protein that is regulated by reversible phosphorylation. Our results show that prenatal cocaine exposure markedly reduces AMPAR synaptic targeting and attenuates AMPAR-mediated synaptic long-term depression in the frontal cortex of 21-d-old rats. This cocaine effect is the result of reduced GRIP-AMPAR interaction caused by persistent phosphorylation of GRIP by protein kinase C (PKC) and Src tyrosine kinase. These data support the restoration of AMPAR activation via suppressing excessive PKC-mediated GRIP phosphorylation as a novel therapeutic approach to treat the neurobehavioral consequences of prenatal cocaine.