SUMMARY
Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is non-additive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging.
SUMMARY
The blood, cerebrospinal fluid (CSF), and extracellular fluid of the parenchyma form the fluid compartments of the brain with three interfaces between, namely the blood–brain interface (BBB), the CSF–brain interface, and the blood–CSF interface. When either water‐soluble iodinated contrast media (CM) or water‐soluble paramagnetic CM are injected intravenously, they are rapidly brought into contact with both the BBB and the blood–CSF interface. It is the behaviour of the water‐soluble CM at these two interfaces that determines the normal and abnormal enhancement patterns demonstrated by either CT or MRI. Unlike lipophilic solutes, current iodinated and MRI contrast media all have high affinities for plasma water, low affinities for plasma proteins and, in particular, extremely low partition coefficients. Therefore they do not penetrate the normal BBB. On the other hand, radiopharmaceuticals used in positron emission tomography (PET) and single photon emission computed tomography (SPECT) to demonstrate regional cerebral blood flow are highly lipophilic and readily cross the intact BBB completely during the first pass through the cerebral vasculature. It is the inability of the current iodinated and MRI contrast media to cross the normal intact BBB that is the basis of their use in CT and MRI studies of the brain.
SUMMARY
Activation of Sir2-orthologs is proposed to increase lifespan downstream of dietary restriction (DR). Here we describe an examination of the effect of 32 different lifespan-extending mutations and four methods of dietary restriction on replicative lifespan (RLS) in the short-lived sir2Δ yeast strain. In every case, deletion of SIR2 prevented RLS extension; however, RLS extension was restored when both SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not directly required for RLS extension. These findings indicate that suppression of the sir2Δ lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Δ cells senesce rapidly by a mechanism distinct from that of wild-type cells. They also demonstrate that failure to observe life span extension in a short-lived background, such as cells or animals lacking sirtuins, should be interpreted with caution.
A review of 2000 consecutive magnetic resonance imaging (MRI) brain studies identified 18 (0.9%) patients with lesions that satisfied MRI criteria for cavernous haemangiomas. The clinical, computed tomography (CT) and MRI findings in 23 patients with probable cavernous haemangiomas were compared. Thirty-three lesions were identified with multiple lesions in five (22%) patients. In 19 (82%) patients the neurological presentation corresponded to a cavernous haemangioma. The presenting symptoms were: seizures in 11 patients (48%); progressive neurological symptoms and signs in four (17%); and acute symptoms and signs due to haemorrhage in four (17%). T2 weighted images suggested the diagnosis in all cases, with 24 (73%) lesions showing the typical appearance of an area of mixed signal intensity with a rim of low signal intensity. In the absence of acute haemorrhage, CT demonstrated well circumscribed, round or oval hyperdense lesions without significant mass effect and with normal surrounding brain tissue in the majority of cases. Although not diagnostic, these CT features are strongly suggestive of cavernous haemangiomas.
BackgroundIn preterm infants, the time from initiation to full oral feeding can take weeks, which represents a very worrisome problem in neonatal medicine. Although current knowledge suggests that oral feeding should be introduced early, this is often delayed due to the need for prolonged nasal continuous positive airway pressure (nCPAP). Indeed, most caregivers fear that nCPAP could disrupt sucking-swallowing-breathing coordination and induce tracheal aspiration. The goal of the present study was to assess the impact of nCPAP delivered by the Infant Flow System on the physiology of sucking-swallowing-breathing coordination during bottle-feeding in preterm lambs over 24 h.MethodsSeventeen lambs (8 control, 9 nCPAP of 6 cmHO) born 14 days prematurely were instrumented to record sucking, swallowing, respiration, ECG, and oxygenation. They were fed via a nasogastric tube for the first 5 days of life until introduction of bottle-feeding every 4 h for 24 h.ResultsnCPAP increased the feeding efficiency while maintaining higher oxygenation without any deleterious cardiorespiratory events. However, coughs were observed in lambs under nCPAP immediately following bottle-feeding and may be related to the high milk flow in preterm lambs.ConclusionFurther studies documenting tracheal aspirations are needed, especially in preterm lambs under nCPAP for moderate respiratory difficulties, to further inform future clinical studies.
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