Pseudorabies Virus Infection Alters Neuronal Activity and Connectivity In Vitro

Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV-infected animals

El Niño-Southern Oscillation diversity and Southern Africa teleconnections during Austral Summer

A wide range of sea surface temperature (SST) expressions have been observed during the El Niño–Southern Oscillation events of 1950–2010, which have occurred simultaneously with different global atmospheric circulations. This study examines the atmospheric circulation and precipitation during December–March 1950–2010 over the African Continent south of 15 S, a region hereafter known as Southern Africa, associated with eight tropical Pacific SST expressions characteristic of El Niño and La Niña events. The self-organizing map method along with a statistical distinguishability test was used to isolate the SST expressions of El Niño and La Niña. The seasonal precipitation forcing over Southern Africa associated with the eight SST expressions was investigated in terms of the horizontal winds, moisture budget and vertical motion. El Niño events, with warm SST across the east and central Pacific Ocean and warmer than average SST over the Indian Ocean, are associated with precipitation reductions over Southern Africa. The regional precipitation reductions are forced primarily by large-scale mid-tropospheric subsidence associated with anticyclonic circulation in the upper troposphere. El Niño events with cooler than average SST over the Indian Ocean are associated with precipitation increases over Southern Africa associated with lower tropospheric cyclonic circulation and mid-tropospheric ascent. La Niña events, with cool SST anomalies over the central Pacific and warm SST over the west Pacific and Indian Ocean, are associated with precipitation increases over Southern Africa. The regional precipitation increases are forced primarily by lower tropospheric cyclonic circulation, resulting in mid-tropospheric ascent and an increased flux of moisture into the region

Changes in the Use of Do-not-resuscitate Orders After Implementation of the Patient Self-determination Act

OBJECTIVE: To determine changes in the use of do-not-resuscitate (DNR) orders and mortality rates following a DNR order after the Patient Self-determination Act (PSDA) was implemented in December 1991. DESIGN: Time-series. SETTING: Twenty-nine hospitals in Northeast Ohio. PATIENTS/PARTICIPANTS: Medicare patients (N = 91,539) hospitalized with myocardial infarction, heart failure, gastrointestinal hemorrhage, chronic obstructive pulmonary disease, pneumonia, or stroke. MEASUREMENTS AND MAIN RESULTS: The use of “early” (first 2 hospital days) and “late” DNR orders was determined from chart abstractions. Deaths within 30 days after a DNR order were identified from Medicare Provider Analysis and Review files. Risk-adjusted rates of early DNR orders increased by 34% to 66% between 1991 and 1992 for 4 of the 6 conditions and then remained flat or declined slightly between 1992 and 1997. Use of late DNR orders declined by 29% to 53% for 4 of the 6 conditions between 1991 and 1997. Risk-adjusted mortality during the 30 days after a DNR order was written did not change between 1991 and 1997 for 5 conditions, but risk-adjusted mortality increased by 21% and 25% for stroke patients with early DNR and late DNR orders, respectively. CONCLUSIONS: Overall use of DNR orders changed relatively little after passage of the PSDA, because the increase in the use of early DNR orders between 1991 and 1992 was counteracted by decreasing use of late DNR orders. Risk-adjusted mortality rates after a DNR order generally remained stable, suggesting that there were no dramatic changes in quality of care or aggressiveness of care for patients with DNR orders. However, the increasing mortality for stroke patients warrants further examination

Genetically timed, activity-sensor and rainbow transsynaptic viral tools.

We developed retrograde, transsynaptic pseudorabies viruses (PRVs) with genetically encoded activity sensors that optically report the activity of connected neurons among spatially intermingled neurons in the brain. Next we engineered PRVs to express two differentially colored fluorescent proteins in a time-shifted manner to define a time period early after infection to investigate neural activity. Finally we used multiple-colored PRVs to differentiate and dissect the complex architecture of brain regions

Ocean acidification alters fish populations indirectly through habitat modification

Ocean ecosystems are predicted to lose biodiversity and productivity from increasing ocean acidification1. Although laboratory experiments reveal negative effects of acidification on the behaviour and performance of species2, 3, more comprehensive predictions have been hampered by a lack of in situ studies that incorporate the complexity of interactions between species and their environment. We studied CO2 vents from both Northern and Southern hemispheres, using such natural laboratories4 to investigate the effect of ocean acidification on plant–animal associations embedded within all their natural complexity. Although we substantiate simple direct effects of reduced predator-avoidance behaviour by fishes, as observed in laboratory experiments, we here show that this negative effect is naturally dampened when fish reside in shelter-rich habitats. Importantly, elevated CO2 drove strong increases in the abundance of some fish species through major habitat shifts, associated increases in resources such as habitat and prey availability, and reduced predator abundances. The indirect effects of acidification via resource and predator alterations may have far-reaching consequences for population abundances, and its study provides a framework for a more comprehensive understanding of increasing CO2 emissions as a driver of ecological change