Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella

Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment

Anesthesia during and Immediately after Spaceflight

The increasing presence of humans in space and long-duration manned missions to the Moon or Mars pose novel challenges to the delivery of medical care. Even now, cumulative person-days in space exceed 80 years and preparations for a return to the Moon are actively underway. Medical care after an emergent de-orbit or an accident during a non-nominal landing must not only address the specific disease or injuries but also the challenges posed by physiologic adaptations to microgravity. In the highly autonomous situation of a long-term space mission the situation is even more complex, because personnel, equipment, specific training, and clinical experience are by definition limited. To summarize our current knowledge specifically for anesthetic care during and immediately after spaceflight, we will review physiologic adaptations to microgravity with particular emphasis on the resulting anesthetic risks, discuss veterinary experiences with anesthesia in weightlessness or in animals adapted to microgravity, describe current research that pertains to anesthesia and spaceflight and point out unresolved questions for future investigation

Roles of aldosterone and oxytocin in abnormalities caused by sevoflurane anesthesia in neonatal rats

ABSTRACT Background: The authors sought to determine whether subjects with pathophysiological conditions that are characterized by increased concentrations of aldosterone have increased susceptibility to the side effects of neonatal anesthesia with sevoflurane. Methods: Postnatal day 4 -20 (P4 -P20) rats were exposed to sevoflurane, 6% and 2.1%, for 3 min and 60 -360 min, respectively. Exogenous aldosterone was administered to imitate pathophysiological conditions with increased concentrations of aldosterone. Results: Six hours of anesthesia with sevoflurane on P4 -P5 rats resulted in a more than 30-fold increase in serum concentrations of aldosterone (7.02 Ϯ 1.61 ng/dl vs. 263.75 Ϯ 22.31 ng/dl, mean Ϯ SE, n ϭ 5-6) and reduced prepulse inhibition of the acoustic startle response (F (2,37) ϭ 5.66, P Ͻ 0.001). Administration of exogenous aldosterone during anesthesia with sevoflurane enhanced seizure-like electroencephalogram patterns in neonatal rats (48.25 Ϯ 15.91 s vs. 222.00 Ϯ 53.87 s, mean Ϯ SE, n ϭ 4) but did not affect electroencephalographic activity in older rats. Exogenous aldosterone increased activation of caspase-3 (F (3,28) ϭ 11.02, P Ͻ 0.001) and disruption of prepulse inhibition of startle (F (3,46) ϭ 6.36; P ϭ 0.001) caused by sevoflurane. Intracerebral administration of oxytocin receptor agonists resulted in depressed seizure-like electroencephalogram patterns (F (2,17) ϭ 6.37, P ϭ 0.009), reduced activation of caspase-3 (t (11) ϭ 2.83, P ϭ 0.016), and disruption of prepulse inhibition of startle (t (7) ϭ Ϫ2.9; P ϭ 0.023) caused by sevoflurane

Proof of principle: Preoperative cognitive reserve and brain integrity predicts intra-individual variability in processed EEG (Bispectral Index Monitor) during general anesthesia.

BackgroundPreoperative cognitive reserve and brain integrity may explain commonly observed intraoperative fluctuations seen on a standard anesthesia depth monitor used ubiquitously in operating rooms throughout the nation. Neurophysiological variability indicates compromised regulation and organization of neural networks. Based on theories of neuronal integrity changes that accompany aging, we assessed the relative contribution of: 1) premorbid cognitive reserve, 2) current brain integrity (gray and white matter markers of neurodegenerative disease), and 3) current cognition (specifically domains of processing speed/working memory, episodic memory, and motor function) on intraoperative neurophysiological variability as measured from a common intraoperative tool, the Bispectral Index Monitor (BIS).MethodsThis sub-study included participants from a parent study of non-demented older adults electing unilateral Total Knee Arthroplasty (TKA) with the same surgeon and anesthesia protocol, who also completed a preoperative neuropsychological assessment and preoperative 3T brain magnetic resonance imaging scan. Left frontal two-channel derived EEG via the BIS was acquired preoperatively (un-medicated and awake) and continuously intraoperatively with time from tourniquet up to tourniquet down. Data analyses used correlation and regression modeling.ResultsFifty-four participants met inclusion criteria for the sub-study. The mean (SD) age was 69.5 (7.4) years, 54% were male, 89% were white, and the mean (SD) American Society of Anesthesiologists score was 2.76 (0.47). We confirmed that brain integrity positively and significantly associated with each of the cognitive domains of interest. EEG intra-individual variability (squared deviation from the mean BIS value between tourniquet up and down) was significantly correlated with cognitive reserve (r = -.40, p = .003), brain integrity (r = -.37, p = .007), and a domain of processing speed/working memory (termed cognitive efficiency; r = -.31, p = .021). Hierarchical regression models that sequentially included age, propofol bolus dose, cognitive reserve, brain integrity, and cognitive efficiency found that intraoperative propofol bolus dose (p = .001), premorbid cognitive reserve (p = .008), and current brain integrity (p = .004) explained a significant portion of intraoperative intra-individual variability from the BIS monitor.ConclusionsOlder adults with higher premorbid reserve and less brain disease were more stable intraoperatively on a depth of anesthesia monitor. Researchers need to replicate findings within larger cohorts and other surgery types