SUMMARYCell proliferation can be dependent on the non-essential amino acid serine, and dietary restriction of serine inhibits tumor growth, but the underlying mechanisms remain incompletely understood. Using a metabolomics approach, we found that serine deprivation most predominantly impacts cellular acylcarnitine levels, a signature of altered mitochondrial function. Fuel utilization from fatty acid, glucose, and glutamine is affected by serine deprivation, as are mitochondrial morphological dynamics leading to increased fragmentation. Interestingly, these changes can occur independently of nucleotide and redox metabolism, two known major functions of serine. A lipidomics analysis revealed an overall decrease in ceramide levels. Importantly, supplementation of the lipid component of bovine serum or C16:0-ceramide could partially restore defects in cell proliferation and mitochondrial fragmentation induced by serine deprivation. Together, these data define a role for serine in supporting mitochondrial function and cell proliferation through ceramide metabolism.

SUMMARY Herpes simplex virus-1 (HSV-1) establishes infections in humans and mice but some non-human primates exhibit resistance via unknown mechanisms. Innate immune recognition pathways are highly conserved but are pivotal in determining susceptibility to DNA virus infections. We report that variation of a single amino acid residue in the innate immune sensor cGAS determines species-specific inactivation by HSV-1. The HSV-1 UL37 tegument protein deamidates human and mouse cGAS. Deamidation impairs the ability of cGAS to catalyze cGAMP synthesis, which activates innate immunity. HSV-1 with deamidase-deficient UL37 promotes robust antiviral responses and is attenuated in mice, in a cGAS- and STING-dependent manner. Mutational analyses identified a single asparagine in human and mouse cGAS that is not conserved in many non-human primates. This residue underpins UL37-mediated cGAS deamidation and species permissiveness of HSV-1. Thus, HSV-1 mediates cGAS deamidation for immune evasion and exploits species sequence variation to disarm host defenses.

Recent studies continue to examine teledermatology for a wide variety of disorders (Table 1); teledermoscopy has been mostly studied for assessing melanocytic and keratinocytic lesions [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Accuracy and Interobserver ConcordanceMost studies show comparable diagnostic accuracy between teledermatology and face-to-face (FTF) care [55,64,66,71,72], although 3 earlier studies reviewed by Lee and English [71] found teledermatology either significantly superior [9] or inferior [73,74]. More specifically, Finnane et al [75] reviewed accuracy of diagnosis for skin cancer; most studies showed that FTF consultations were more accurate than teledermatology (67%-85% vs 51%-85%); however, some studies found teledermatology was more accurate.

BackgroundNon-invasive ventilation is sometimes unable to provide the respiratory needs of very premature infants in the delivery room. While airway obstruction is thought to be the main problem, the site of obstruction is unknown. We investigated whether closure of the larynx and epiglottis is a major site of airway obstruction.MethodsWe used phase contrast X-ray imaging to visualise laryngeal function in spontaneously breathing premature rabbits immediately after birth and at approximately 1 hour after birth. Non-invasive respiratory support was applied via a facemask and images were analysed to determine the percentage of the time the glottis and the epiglottis were open.HypothesisImmediately after birth, the larynx is predominantly closed, only opening briefly during a breath, making non-invasive intermittent positive pressure ventilation (iPPV) ineffective, whereas after lung aeration, the larynx is predominantly open allowing non-invasive iPPV to ventilate the lung.ResultsThe larynx and epiglottis were predominantly closed (open 25.5%±1.1% and 17.1%±1.6% of the time, respectively) in pups with unaerated lungs and unstable breathing patterns immediately after birth. In contrast, the larynx and the epiglottis were mostly open (90.5%±1.9% and 72.3%±2.3% of the time, respectively) in pups with aerated lungs and stable breathing patterns irrespective of time after birth.ConclusionLaryngeal closure impedes non-invasive iPPV at birth and may reduce the effectiveness of non-invasive respiratory support in premature infants immediately after birth.

Abstract-Ghrelin is a growth hormone-releasing peptide secreted by the stomach with potent effects on appetite.Experimental and clinical studies indicate that ghrelin also influences cardiovascular regulation and metabolic function and mediates behavioral responses to stress. We investigated the effects of ghrelin on blood pressure (BP), sympathetic nervous system activity, and mental stress responses in lean (nϭ13) and overweight or obese (nϭ13) individuals. Subjects received an intravenous infusion of human ghrelin (5 pmol/kg per minute for 1 hour) and saline in a randomized fashion. Ghrelin decreased systolic (Ϫ6 and Ϫ11 mm Hg) and diastolic BP (Ϫ8 mm Hg for both), increased muscle sympathetic nervous system activity (18Ϯ2 to 28Ϯ3 bursts per min, PϽ0.05 and from 21Ϯ2 to 32Ϯ3 bursts per min, PϽ0.001) in lean and overweight or obese subjects, respectively, without a significant change in heart rate, calf blood flow, or vascular resistance. Ghrelin induced a rise in plasma glucose concentration in lean individuals (PϽ0.05) and increased cortisol levels in both groups (PϽ0.05). Stress induced a significant change in mean BP (ϩ22 and ϩ27 mm Hg), heart rate (ϩ36 and ϩ29 bpm), and muscle sympathetic nervous system activity (ϩ6.1Ϯ1.6 and ϩ6.8Ϯ2.7 bursts per min) during saline infusion in lean and overweight or obese subjects, respectively. During ghrelin infusion, the changes in BP and muscle sympathetic nerve activity in response to stress were significantly reduced in both groups (PϽ0.05). In conclusion, ghrelin exerts unique effects in that it reduces BP and increases muscle sympathetic nervous system activity and blunts cardiovascular responses to mental stress. These responses may represent a combination of peripheral (baroreflex-mediated) and central effects of ghrelin. (Hypertension. 2011;58:43-50.)