Conjoint Control of Hippocampal Place Cell Firing by Two Visual Stimuli: II. a Vector-Field Theory That Predicts Modifications of the Representation of the Environment

Changing the angular separation between two visual stimuli attached to the wall of a recording cylinder causes the firing fields of place cells to move relative to each other, as though the representation of the floor undergoes a topological distortion. The displacement of the firing field center of each cell is a vector whose length is equal to the linear displacement and whose angle indicates the direction that the field center moves in the environment. Based on the observation that neighboring fields move in similar ways, whereas widely separated fields tend to move relative to each other, we develop an empirical vector-field model that accounts for the stated effects of changing the card separation. We then go on to show that the same vector-field equation predicts additional aspects of the experimental results. In one example, we demonstrate that place cell firing fields undergo distortions of shape after the card separation is changed, as though different parts of the same field are affected by the stimulus constellation in the same fashion as fields at different locations. We conclude that the vector-field formalism reflects the organization of the place-cell representation of the environment for the current case, and through suitable modification may be very useful for describing motions of firing patterns induced by a wide variety of stimulus manipulations

Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells

When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function

Revisiting Protocols for the NMR Analysis of Bacterial Metabolomes

Over the past decade, metabolomics has emerged as an important technique for systems biology. Measuring all the metabolites in a biological system provides an invaluable source of information to explore various cellular processes, and to investigate the impact of environmental factors and genetic modifications. Nuclear magnetic resonance (NMR) spectroscopy is an important method routinely employed in metabolomics. NMR provides comprehensive structural and quantitative information useful for metabolomics fingerprinting, chemometric analysis, metabolite identification and metabolic pathway construction. A successful metabolomics study relies on proper experimental protocols for the collection, handling, processing and analysis of metabolomics data. Critically, these protocols should eliminate or avoid biologicallyirrelevant changes to the metabolome. We provide a comprehensive description of our NMR-based metabolomics procedures optimized for the analysis of bacterial metabolomes. The technical details described within this manuscript should provide a useful guide to reliably apply our NMR-based metabolomics methodology to systems biology studies

Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation

Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was higher in mice fed a high NaCl (1.57% Na+) diet for 7 weeks or fed a K+free diet for 2 weeks. BP was highest on a K+-free/high NaCl diet. Commensurate with increased abundance and phosphorylation of the thiazide sensitive sodium-chloride-cotransporter (NCC) on the K+-free/high NaCl diet, BP returned to normal with thiazides. Three weeks of a high K+ diet (5% K+) increased BP (predominantly during the night) independently of dietary Na+ or anion intake. Conversely, 4 days of KCl feeding reduced BP. Both feeding periods resulted in lower NCC levels but in increased levels of cleaved (active) α and γ subunits of the epithelial Na+ channel ENaC. The elevated BP after chronic K+ feeding was reduced by amiloride but not thiazide. Our results suggest that dietary K+ has an optimal threshold where it may be most effective for cardiovascular health

The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population

Context:Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. Objective:To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Design:Prospective population-based cohort study (Rotterdam Study). Setting:General population. Participants:2178 participants (65% female, age 64 +/- 8 years) Intervention(s):None. Main Outcome:Measure(s) Serum sodium levels. Results:Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 -0.19 mmol/L [95% confidence interval (CI) -0.31 to -0.06], PGEM -0.29 mmol/L (95% CI -0.41 to -0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 -0.73 vs -0.12 mmol/L and PGEM -0.6 vs -0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Conclusion:Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically

Dynamic edge effects in small mammal communities across a conservation-agricultural interface in Swaziland

Across the planet, high-intensity farming has transformed native vegetation into monocultures, decreasing biodiversity on a landscape scale. Yet landscape-scale changes to biodiversity and community structure often emerge from processes operating at local scales. One common process that can explain changes in biodiversity and community structure is the creation of abrupt habitat edges, which, in turn, generate edge effects. Such effects, while incredibly common, can be highly variable across space and time; however, we currently lack a general analytical framework that can adequately capture such spatio-temporal variability. We extend previous approaches for estimating edge effects to a non-linear mixed modeling framework that captures such spatio-temporal heterogeneity and apply it to understand how agricultural land-uses alter wildlife communities. We trapped small mammals along a conservation-agriculture land-use interface extending 375 m into sugarcane plantations and conservation land-uses at three sites during dry and wet seasons in Swaziland, Africa. Sugarcane plantations had significant reductions in species richness and heterogeneity, and showed an increase in community similarity, suggesting a more homogenized small mammal community. Furthermore, our modeling framework identified strong variation in edge effects on communities across sites and seasons. Using small mammals as an indicator, intensive agricultural practices appear to create high-density communities of generalist species while isolating interior species in less than 225 m. These results illustrate how agricultural land-use can reduce diversity across the landscape and that effects can be masked or magnified, depending on local conditions. Taken together, our results emphasize the need to create or retain natural habitat features in agricultural mosaics.Texas A&M Agrilife Researchhttp://www.plosone.orgam2013Zoology and EntomologyMammal Research Institut

Superhumps in Cataclysmic Binaries. XXIII. V442 Ophiuchi and RX J1643.7+3402

We report the results of long observing campaigns on two novalike variables: V442 Ophiuchi and RX J1643.7+3402. These stars have high-excitation spectra, complex line profiles signifying mass loss at particular orbital phases, and similar orbital periods (respectively 0.12433 and 0.12056 d). They are well-credentialed members of the SW Sex class of cataclysmic variables. Their light curves are also quite complex. V442 Oph shows periodic signals with periods of 0.12090(8) and 4.37(15) days, and RX J1643.7+3402 shows similar signals at 0.11696(8) d and 4.05(12) d. We interpret these short and long periods respectively as a "negative superhump" and the wobble period of the accretion disk. The superhump could then possibly arise from the heating of the secondary (and structures fixed in the orbital frame) by inner-disk radiation, which reaches the secondary relatively unimpeded since the disk is not coplanar. At higher frequencies, both stars show another type of variability: quasi-periodic oscillations (QPOs) with a period near 1000 seconds. Underlying these strong signals of low stability may be weak signals of higher stability. Similar QPOs, and negative superhumps, are quite common features in SW Sex stars. Both can in principle be explained by ascribing strong magnetism to the white dwarf member of the binary; and we suggest that SW Sex stars are borderline AM Herculis binaries, usually drowned by a high accretion rate. This would provide an ancestor channel for AM Hers, whose origin is still mysterious.Comment: PDF, 41 pages, 4 tables, 16 figures; accepted, in press, to appear December 2002, PASP; more info at http://cba.phys.columbia.edu

Gender Differences in Demographic and Clinical Correlates among Veterans with Musculoskeletal Disorders

Background Studies suggest that women may be at greater risk for developing chronic pain and pain-related disability. Methods Because musculoskeletal disorders (MSD) are the most frequently endorsed painful conditions among veterans, we sought to characterize gender differences in sociodemographic and clinical correlates among veterans upon entry into Veterans Health Administration's Musculoskeletal Disorders Cohort (n = 4,128,008). Results Women were more likely to be younger, Black, unmarried, and veterans of recent conflicts. In analyses adjusted for gender differences in sociodemographics, women were more likely to have diagnoses of fibromyalgia, temporomandibular disorders, and neck pain. Almost one in five women (19.4%) had more than one MSD diagnosis, compared with 15.7% of men; this higher risk of MSD multimorbidity remained in adjusted analyses. Adjusting for sociodemographics, women with MSD were more likely to have migraine headache and depressive, anxiety, and bipolar disorders. Women had lower odds of cardiovascular diseases, substance use disorders, and several MSDs, including back pain conditions. Men were more likely to report “no pain” on the pain intensity Numeric Rating Scale, whereas more women (41%) than men (34%) reported moderate to severe pain (Numeric Rating Scale 4+). Conclusions Because women veterans are more likely to have conditions such as fibromyalgia and mental health conditions, along with greater pain intensity in the setting of MSD, women-specific pain services may be needed