Juxtaglomerular neurons represent one of the largest cellular populations in the mammalian olfactory bulb yet their role for signal processing remains unclear. We used two-photon imaging and electrophysiological recordings to clarify the properties of these cells and their functional organization in the juxtaglomerular space. Juxtaglomerular neurons coded for many perceptual characteristics of the olfactory stimulus such as (1) identity of the odorant, (2) odorant concentration, (3) odorant onset, and (4) offset. The odor-responsive neurons clustered within a narrow area surrounding the glomerulus with the same odorant specificity, with ~80% of responding cells located ≤20 μm from the glomerular border. This stereotypic spatial pattern of activated cells persisted at different odorant concentrations and was found for neurons both activated and inhibited by the odorant. Our data identify a principal glomerulus with a narrow shell of juxtaglomerular neurons as a basic odor coding unit in the glomerular layer and underline the important role of intraglomerular circuitry.
Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.
Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.
Iron, potassium, zinc, and other minerals might impact the development of premenstrual syndrome (PMS) through multiple mechanisms, but few studies have evaluated these relations. We conducted a case-control study nested within the prospective Nurses' Health Study II (1991-2001). Participants were free from PMS at baseline. After 10 years, 1,057 women were confirmed as PMS cases and 1,968 as controls. Mineral intake was assessed using food frequency questionnaires completed in 1991, 1995, and 1999. After adjustment for calcium intake and other factors, women in the highest quintile of nonheme iron intake had a relative risk of PMS of 0.64 (95% confidence interval (CI): 0.44, 0.92; P for trend = 0.04) compared with women in the lowest quintile. Women in the highest quintile of potassium intake had a relative risk of 1.46 (95% CI: 0.99, 2.15; P for trend = 0.04) compared with women in the lowest quintile. High intake of zinc from supplements was marginally associated with PMS (for intake of ≥25 mg/day vs. none, relative risk = 0.69, 95% CI: 0.46, 1.02; P for trend = 0.05). Intakes of sodium, magnesium, and manganese were unrelated to PMS risk. These findings suggest that dietary minerals may be useful in preventing PMS. Additional studies are needed to confirm these relations.
Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii and Himantura toshi, and the bony fish Platycephalus fucus, Girella tricuspidata, Mugil cephalus, and Dentex tumifrons. All venoms (10-100 μg/kg, i.v.), except G. tricuspidata and P. fuscus, induced a biphasic response on mean arterial pressure (MAP) in the anesthetised rat. P. fucus venom exhibited a hypotensive response, while venom from G. tricuspidata displayed a single depressor response. All venoms induced cardiovascular collapse at 200 μg/kg, i.v. The in vitro neurotoxic effects of venom were examined using the chick biventer cervicis nerve-muscle (CBCNM) preparation. N. kuhlii, H. toshi, and P. fucus venoms caused concentration-dependent inhibition of indirect twitches in the CBCNM preparation. These three venoms also inhibited responses to exogenous acetylcholine (ACh) and carbachol (CCh), but not potassium chloride (KCl), indicating a post-synaptic mode of action. Venom from G. tricuspidata, M. cephalus, and D. tumifrons had no significant effect on indirect twitches or agonist responses in the CBCNM. Our results demonstrate that envenoming by these species of fish may result in moderate cardiovascular and/or neurotoxic effects. Future studies aimed at identifying the molecules responsible for these effects could uncover potentially novel lead compounds for future pharmaceuticals, in addition to generating new knowledge about the evolutionary relationships between venomous animals.
Cardiovascular benefits associated with higher dietary K+ versus lower dietary Na+: Evidence from population and mechanistic studies
- American journal of physiology. Endocrinology and metabolism
- Published 12 months ago
The WHO ranks hypertension the leading global risk factor for disease, specifically, cardiovascular disease. Blood pressure is higher in westernized populations consuming sodium-rich processed foods compared to isolated societies consuming potassium-rich natural foods. Evidence suggests that lowering dietary Na(+) is particularly beneficial in hypertensives who consume a high Na(+) diet. Nonetheless, numerous population studies demonstrate a relationship between higher dietary K(+), estimated from urinary excretion or dietary recall, and lower blood pressure regardless of sodium intake. Interventional studies with potassium supplementation suggest it provides a direct benefit; K(+) may also be a marker for other beneficial components of a “natural” diet. Recent studies in rodent models indicate mechanisms for the potassium benefit: the distal tubule Na(+)- Cl(-) cotransporter (NCC) controls Na(+) delivery downstream to the collecting duct where Na(+) reabsorbed by epithelial Na(+) channels (ENaC) drives K(+) secretion and excretion through K(+) channels in the same region. High dietary K(+) provokes a decrease in the NCC activity to drive more K(+) secretion (and Na(+) excretion, analogous to the actions of a thiazide diuretic) whether Na(+) intake is high or low; low dietary K(+) provokes an increase in NCC activity and Na(+) retention, also independent of dietary Na(+) Taken together, the findings suggest that public health efforts directed towards increasing consumption of natural potassium rich foods would reduce blood pressure and, thus, cardiovascular and kidney disease.
Hypertension is a common and major risk factor for the leading U.S. killer, cardiovascular disease.(1)-(5) Reducing excess dietary sodium can lower blood pressure, with a greater response among persons with hypertension.(6)-(9) Nine of 10 Americans consume excess dietary sodium, defined as more than 2300 mg per day.(10),(11) Many leading medical and public health organizations recommend reducing dietary sodium to a maximum of 2300 mg per day on the basis of evidence indicating a public health benefit.(11)-(17) Yet this benefit has been questioned, mainly on the basis of studies suggesting that low sodium intake is also associated . . .
The degradation of some organophosphorus pesticides (OPPs) in the presence of metal ions was studied by (31)P-NMR spectroscopy. Both (31)P-NMR and gas chromatography/mass spectroscopy results were used in order to determine the nature of metabolites formed after degradation. The degraded organophosphorus pesticide were investigated for chlorpyrifos and phoxim in the presence of several metal ions including Hg(2+), Cu(2+), Cd(2+), Ni(2+), Pb(2+), and Ag(+). (31)P-NMR results indicated Ag(+) and Hg(2+) ion promoted degradation of OPPs and other metal ions formed complex with OPPs and cannot degrade OPPs. We found that the degradation of chlorpyrifos and phoxim with Ag(+) or Hg(2+) led to the formation of O,O-diethyl-O-methyl phosphorothionate, (C(2)H(5)O)(2)(CH(3)O)PS, at metal ion/pesticide mole ratios ≤1.0 and completely decomposed at a higher mole ratio of 10. Finally, the method was successfully applied to the degradation study of a number of technical and formulated pesticides in the presence of Ag(+) ion at a metal ion/pesticide mole ratio of 10.
Excess sodium intake correlates positively with high blood pressure. Blood pressure varies by region, but whether sodium content of foods sold varies across regions is unknown. We combined nutrition and sales data from 2009 to assess the regional variation of sodium in packaged food products sold in 3 of the 9 US census divisions. Although sodium density and concentration differed little by region, fewer than half of selected food products met Food and Drug Administration sodium-per-serving conditions for labeling as “healthy.” Regional differences in hypertension were not reflected in differences in the sodium content of packaged foods from grocery stores.