In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs 1 and rodents ...2–4. Hypothetically, ultrasonic stimulation of the brain possesses several advantages 5: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution.
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•Focused online ultrasound stimulation modulates behavior in nonhuman primates•Ultrasonic-stim might confer higher spatial resolution to other noninvasive methods
Oxidation reactions that involve several oxygen and nitrogen reactive species together with nucleobase radical cations give rise among various classes of lesions to modified bases. About 70 of ...oxidized nucleosides that include diastereomeric forms have been characterized in mechanistic studies involving isolated DNA and related model compounds. However, only eight modified bases have been accurately measured within cellular DNA upon exposure to either γ or UVA radiations. Emphasis is placed in this survey on recent developments of HPLC associated with tandem mass spectrometry (MS/MS) operating in the mild electrospray ionization mode. Interestingly, the HPLC-MS/MS assay in the multiple reaction monitoring mode appears to be the more sensitive and accurate method currently available for singling out several oxidized nucleosides including 8-oxo-7,8-dihydro-2′-deoxyguanosine, 8-oxo-7,8-dihydro-2′-deoxyadenosine, 5-formyl-2′-deoxyuridine, 5-(hydroxymethyl-2′-deoxyuridine, 5-hydroxy-2′-deoxyuridine, and the four diastereomers of 5,6-dihydroxy-5,6-dihydrothymidine within isolated and cellular DNA. However, one limitation of the assay that also applied to all chromatographic methods is the slight side-oxidation of normal bases during DNA extraction and subsequent work-up. This explains why the combined use of DNA repair glycosylases with either the comet assay or the alkaline elution technique is a better alternative to monitor the formation of low levels of oxidized bases within cellular DNA.
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is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis.
has a high level of antibiotic resistance and is a ...common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant
(CA-MRSA), combined with the important severity of
infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant
continues to be a major health concern, necessitating the development of novel therapeutic strategies.
uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize
toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.
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