Activity

The sinoatrial node is perhaps one of the most important tissues in the entire body it is the natural pacemaker of the heart, making it responsible for initiating each-and-every normal heartbeat. As such, its activity is heavily controlled, allowing heart rate to rapidly adapt to changes in physiological demand. Control of sinoatrial node activity, however, is complex, occurring through the autonomic nervous system and various circulating and locally released factors. In this review we discuss the coupled-clock pacemaker system and how its manipulation by neurohumoral signaling alters heart rate, considering the multitude of canonical and non-canonical agents that are known to modulate sinoatrial node activity. For each, we discuss the principal receptors involved and known intracellular signaling and protein targets, highlighting gaps in our knowledge and understanding from experimental models and human studies that represent areas for future research. Copyright © 2020 MacDonald, Rose and Quinn.Background In the poorly understood relationship between orthostatic hypotension and falls, next to blood pressure (BP), baroreflex sensitivity (BRS) and cerebral autoregulation (CAR) may be key measures. The posture- and movement dependency of orthostatic hypotension requires continuous and unobtrusive monitoring. This may be possible using simultaneous photoplethysmography (PPG), electrocardiography (ECG), and near-infrared spectroscopy (NIRS) signal recordings, from which pulse wave velocity (PWV; potentially useful for BP estimation), BRS and CAR can be derived. The PPG, NIRS and PWV signal correlation with BP and BRS/CAR reliability and validity need to be addressed. Methods In 34 healthy adults (mean age 25 years, inter quartile range 22-45; 10 female), wrist and finger PPG, ECG, bifrontal NIRS (oxygenated and deoxygenated hemoglobin) and continuous BP were recorded during sit to stand and supine to stand movements. Sixteen participants performed slow and rapid supine to stand movements; eighteen other 0.49 (BRS) and 0.42-0.75 (CAR); validity was highest during rapid supine to stand movements, 0.54 and 0.79 respectively. Conclusion PPG-ECG-NIRS recordings showed high correlation with BP and enabled computation of reliable and valid BRS and CAR estimates, suggesting their potential for continuous unobtrusive monitoring of orthostatic hypotension key measures. Copyright © 2020 Mol, Maier, van Wezel and Meskers.Objective The degree of stenosis of a carotid plaque is a well-established risk factor for ischemic stroke. Nevertheless, the risk of ipsilateral stroke in asymptomatic carotid stenosis remains low and new imaging markers are needed to better target which patients would benefit most from endarterectomy or intensive medical therapy. Ultrafast ultrasound imaging offers parameters helping at characterizing the carotid plaque by shear wave elastography and Ultrafast Doppler (UFD). We aimed at using these techniques to characterize 3 different ultrasound biomarkers plaque stiffness heterogeneity, wall shear stress (WSS) and intraplaque micro-flows and to correlate these biomarkers with findings on computed tomography angiography (CTA) and the pathological examination. Methods We present the case of a multimodal evaluation of a carotid plaque using ultrasound. Elastography has been coupled to the WSS assessment and the detection of intraplaque micro-flows by UFD. The data have been compared to CTA and to the pathology examination of the tissue after carotid endarterectomy. Results Elastography allowed at identifying stiff areas corresponding to calcifications, as well as a soft area corresponding to an intraplaque hemorrhage. The flow evaluation with UFD showed an increase of the WSS along the plaque and identified the presence of a plaque rupture, confirmed by the pathologist. Conclusion Ultrafast ultrasound imaging is an innovative, easily accessible technique that provides imaging modalities on top of the conventional B-mode. Ultrafast ultrasound biomarkers such as plaque stiffness heterogeneity, WSS and intraplaque micro-flows could help to define the vulnerability of the carotid plaque in order to stratify patients that could benefit most from endarterectomy or intensive medical therapy. Copyright © 2020 Goudot, Khider, Pedreira, Poree, Julia, Alsac, Amemiya, Bruneval, Messas, Pernot and Mirault.Oncolytic viruses are of growing interest to cancer researchers and clinicians, due to their selectivity for tumor cells over healthy cells and their immunostimulatory properties. The immune response to an oncolytic virus plays a critical role in treatment efficacy. However, uncertainty remains regarding the circumstances under which the immune system either assists in eliminating tumor cells or inhibits treatment via rapid viral clearance, leading to the cessation of the immune response. In this work, we develop an ordinary differential equation model of treatment for a lethal brain tumor, glioblastoma, using an oncolytic Herpes Simplex Virus. We use a mechanistic approach to model the interactions between distinct populations of immune cells, incorporating both innate and adaptive immune responses to oncolytic viral therapy (OVT), and including a mechanism of adaptive immune suppression via the PD-1/PD-L1 checkpoint pathway. We focus on the tradeoff between viral clearance by innate immune cells and the innow that the innate and adaptive immune interactions significantly influence treatment response and that combining OVT with an immune checkpoint inhibitor expands the range of immune conditions that allow for tumor size reduction or clearance. Copyright © 2020 Storey, Lawler and Jackson.Dipeptidyl peptidase IV (DPP-IV) is a unique serine protease that exists in a membrane bound state and in a soluble state in most tissues in the body. DPP-IV has multiple targets including cytokines, neuropeptides, and incretin hormones, and plays an important role in health and disease. Recent work suggests that skeletal muscle releases DPP-IV as a myokine and participates in control of muscle blood flow. However, few of the functions of DPP-IV as a myokine have been investigated to date and there is a poor understanding about what causes DPP-IV to be released from muscle. Copyright © 2020 Kluess.The metabolic response to endotoxemia closely mimics those seen in sepsis. Here, we show that the urinary excretion of the metabolite 2-hydroxyglutarate (2HG) is dramatically suppressed following lipopolysaccharide (LPS) administration in vivo, and in human septic patients. We further show that enhanced activation of the enzymes responsible for 2-HG degradation, D- and L-2-HGDH, underlie this effect. To determine the role of supplementation with 2HG, we carried out co-administration of LPS and 2HG. This co-administration in mice modulates a number of aspects of physiological responses to LPS, and in particular, protects against LPS-induced hypothermia. Our results identify a novel role for 2HG in endotoxemia pathophysiology, and suggest that this metabolite may be a critical diagnostic and therapeutic target for sepsis. Copyright © 2020 Fitzpatrick, Lambden, Macias, Puthucheary, Pietsch, Mendil, McPhail and Johnson.In the current study, we used breath-by-breath respirometry to evaluate respiratory physiology under voluntary control in a male beluga calf [Delphinapterus leucas, body mass range (M b) 151-175 kg], an adult female (estimated M b = 500-550 kg) and a juvenile male (M b = 279 kg) false killer whale (Pseudorca crassidens) housed in managed care. Our results suggest that the measured breathing frequency (f R) is lower, while tidal volume (V T) is significantly greater as compared with allometric predictions from terrestrial mammals. Including previously published data from adult bottlenose dolphin (Tursiops truncatus) beluga, harbor porpoise (Phocoena phocoena), killer whale (Orcinus orca), pilot whale (Globicephala scammoni), and gray whale (Eschrichtius robustus) show that the allometric mass-exponents for V T and f R are similar to that for terrestrial mammals (V T 1.00, f R -0.20). In addition, our results suggest an allometric relationship for respiratory flow ( V . ), with a mass-exponent between 0.63 and 0.70, and where the expiratory V . was an average 30% higher as compared with inspiratory V . . These data provide enhanced understanding of the respiratory physiology of cetaceans and are useful to provide proxies of lung function to better understand lung health or physiological limitations. Copyright © 2020 Fahlman, Borque-Espinosa, Facchin, Ferrero Fernandez, Muñoz Caballero, Haulena and Rocho-Levine.Acute kidney injury (AKI) is a frequent complication of sepsis and contributes to increased mortality. Discovery of reliable biomarkers could enable identification of individuals with high AKI risk as well as early AKI detection and AKI progression monitoring. However, the current methods are insensitive and non-specific. This study aimed to identify new biomarkers through label-free mass spectrometry (MS) analysis of a sepsis model induced by cecal ligation and puncture (CLP). Urine samples were collected from septic rats at 0, 3, 6, 12, 24, and 48 h. Protein isolated from urine was subjected to MS. Immunoregulatory biological processes, including immunoglobin production and wounding and defense responses, were upregulated at early time points. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 77 significantly changed pathways. We further examined the consistently differentially expressed proteins to seek biomarkers that can be used for early diagnosis. FK506 price Notably, the expression of PARK7 and CDH16 were changed in a continuous manner and related to the level of Scr in urine from patients. Therefore, PARK7 and CDH16 were confirmed to be novel biomarkers after validation in sepsis human patients. In summary, our study analyzed the proteomics of AKI at multiple time points, elucidated the related biological processes, and identified novel biomarkers for early diagnosis of sepsis-induced AKI, and our findings provide a theoretical basis for further research on the molecular mechanisms. Copyright © 2020 Li, Long, Chen, Zhang, Qin, Zhong, Liu and Peng.Whitefly Bemisia tabaci is a global invasive pest that causes substantial losses to agricultural crops worldwide either by direct feeding or vectoring numerous plant viruses. Management with insecticides remains a big challenge due to its rapid resistance development potential as well as the impact of these chemicals on non-target organisms. Thus, in search of alternate and novel pest management strategies RNA interference (RNAi) has come up as potential future tool in this direction. The present study targets nine potential genes (Aquaporin (AQP), Calcitonin (CAL), CyclophilinB (CYCP), Knottin-1 (k-1), Heat shock proteins (Hsp20, Hsp40 and Hsp70), SWItch/Sucrose Non-fermentable (SNF7) and inhibitor of apoptosis (IAP) of whitefly that have been implicated to play a role in various vital physiological functions and virus transmission. The RNAi mediated knockdown efficiency of these genes has been improved through the conjugation of respective target gene dsRNA with CQD (carbon quantum dots) nanoparticles or simultaneous knockdown of dsRNA specific gut nucleases.