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DNA restriction fragments ranging from 79 to 789 base pairs in length have been characterized by transient electric birefringence (TEB) measurements at various temperatures between 4 and 43 degrees C. The DNA fragments do not contain runs of four or more adenine residues in a row and migrate with normal electrophoretic mobilities in polyacrylamide gels, indicating that they are not intrinsically curved or bent. The low ionic strength buffers used for the measurements contained 1 mM Tris Cl, pH 8.0, EDTA, and variable concentrations of Na(+) or Mg(2+) ions. The rotational relaxation times were obtained by fitting the TEB field-free decay signals with a nonlinear least-squared fitting program; the decay of the birefringence was monoexponential for fragments < or = 241 base pair (bp) in length and multiexponential for larger fragments. The terminal relaxation times, characteristic of the end-over-end rotation of the DNA molecules, were then used to determine the persistence length (p) and hydrodynamic radius (r) of DNA as a function of temperature and ionic strength, using several different hydrodynamic models. The specific values obtained for p and r are model dependent. The wormlike chain model of P. J. Hagerman and B. H. Zimm (Biopolymers 1981, Vol. 20, pp. 1481-1502) combined with the revised Broersma equation (J. Newman et al., Journal of Mol Biol 1997, Vol. 116, pp. 593-606) appears to be the most suitable for describing the flexibility of DNA in low ionic strength solutions. The values of p and r obtained from the global least squares fitting of this equation are independent of DNA length, and the deviations of the individual values from the average are reasonably small. The consensus r value calculated for DNA in various low ionic strength solutions containing 1 mM Tris buffer is 14.7 +/- 0.4 A at 20 degrees C. The consensus p values decrease from 814 approximately 564 A in solutions containing 1 mM Tris buffer plus 0.2-1 mM NaCl and decrease still further to 440 A in solutions containing 0.2 mM Mg(2+) ions. The persistence length exhibits a shallow maximum at 20 degrees C and decreases slowly upon either increasing or decreasing the temperature, regardless of the model used to fit the data. By contrast, the consensus values of the hydrodynamic radius are independent of temperature. The calculated persistence lengths and hydrodynamic radii are compared with other data in the literature.

The electrophoretic mobilities and diffusion coefficients of single- and double-stranded DNA molecules up to 50,000 bases or base pairs in size have been analyzed, using mobilities and diffusion coefficients either measured by capillary electrophoresis or taken from the literature. The Einstein equation suggests that the electrophoretic mobilities (mu) and diffusion coefficients (D) should be related by the expression mu/D = Q/k(B)T, where Q is the charge of the polyion (Q = ze(o), where z is the number of charged residues and e(o) is the fundamental electronic charge), k(B) is Boltzmann's constant, and T is the absolute temperature. If this equation were true, the ratio mu/zD should be a constant equal to e(o)/k(B)T (39.6 V(-1)) at 20 degrees C. However, the ratio mu/zD decreases with an increase in molecular weight for both single- and double-stranded DNAs. The mobilities and diffusion coefficients are better described by the modified Einstein equation mu/N(m)D = e(o)/k(B)T, where N is the number of repeat units (bases or base pairs) in the DNA and m is a constant equal to the power law dependence of the diffusion coefficients on molecular weight. The average value of the ratio mu/N(m)D is 40 +/- 4 V(-1) for 36 single- and double-stranded DNA molecules of different sizes, close to the theoretically expected value. The generality of the modified Einstein equation is demonstrated by analyzing literature values for sodium polystyrenesulfonate (PSS). The average value of the ratio mu/N(m)D is 35 +/- 6 V(-1) for 14 PSS samples containing up to 855 monomers.

SUMMARY Arterial baroreceptors provide a neural sensory input that reflexly regulates the autonomic drive of the circulation. Our goal was to test the hypothesis that a member of the acid sensing ion channel (ASIC) subfamily of the DEG/ENaC superfamily is an important determinant of the arterial baroreceptor reflex. We found that aortic baroreceptor neurons in the nodose ganglia and their terminals express ASIC2. Conscious ASIC2 null mice developed hypertension, had exaggerated sympathetic and depressed parasympathetic control of the circulation, and a decreased gain of the baroreflex, all indicative of an impaired baroreceptor reflex. Multiple measures of baroreceptor activity each suggests that mechanosensitivity is diminished in ASIC2- null mice. The results define ASIC2 as an important determinant of autonomic circulatory control and of baroreceptor sensitivity. The genetic disruption of ASIC2 recapitulates the pathological dysautonomia seen in heart failure and hypertension and defines a molecular defect that may be relevant to its development.

Rationale increased sympathetic nerve activity has been linked to the pathogenesis of hypertension in humans and animal models. Enhanced peripheral chemoreceptor sensitivity which increases sympathetic nerve activity has been observed in established hypertension but has not been identified as a possible mechanism for initiating an increase in SNA prior to the onset of hypertension. Objective we tested this hypothesis by measuring the pH sensitivity of isolated carotid body glomus cells from young spontaneously hypertensive rats (SHR) prior to the onset of hypertension and their control normotensive Wistar Kyoto (WKY) rats. Methods and Results we found a significant increase in the depolarizing effect of low pH in SHR versus WKY glomus cells which was caused by overexpression of two acid-sensing non-voltage gated channels. One is the amiloride-sensitive acid-sensing sodium channel (ASIC3) which is activated by low pH and the other is the two-pore domain acid sensing K+ channel (TASK1) which is inhibited by low pH and blocked by quinidine. Moreover we found that the increase in sympathetic nerve activity in response to stimulation of chemoreceptors with sodium cyanide was markedly enhanced in the still normotensive young SHR compared to control WKY rats. Conclusions our results establish a novel molecular basis for increased chemotransduction that contributes to excessive sympathetic activity prior to the onset of hypertension.

Sexting is the sharing of sexually explicit images, videos, and/or messages via electronic devices. Prevalence estimates of sexting have varied substantially, potentially due to broad age ranges being examined. The current study sought to synthesize relevant findings examining the prevalence of consensual and non-consensual sexting in a specific developmental period, emerging adulthood (≥ 18-< 29), to try to explain discrepancies in the literature. Searches were conducted in electronic databases for articles published up to April 2018. Relevant data from 50 studies with 18,122 emerging adults were extracted. The prevalence of sexting behaviors were: sending 38.3% (k = 41; CI 32.0-44.6), receiving 41.5% (k = 19; CI 31.9-51.2), and reciprocal sexting 47.7% (k = 16;). Thus, sexting is a common behavior among emerging adults. The prevalence of non-consensual forwarding of sexts was also frequent in emerging adults at 15.0% (k = 7; CI 6.9-23.2). Educational awareness initiatives on digital citizenship and psychological consequences of the non-consensual forwarding of sexts should be targeted to youth and emerging adults with the hopes of mitigating this potentially damaging and illegal behavior.

Rationale Acid-Sensing Ion Channels (ASICs) are Na+ channels that are activated by acidic pH. Their expression in cardiac afferents and remarkable sensitivity to small pH changes has made them leading candidates to sense cardiac ischemia. Objective Four genes encode six different ASIC subunits, however it is not yet clear which of the ASIC subunits contribute to the composition of ASICs in cardiac afferents. Methods and Results Here we labeled cardiac afferents using a retrograde tracer dye in mice, which allowed for patch-clamp studies of murine cardiac afferents. We found that a higher percentage of cardiac sensory neurons from the dorsal root ganglia (DRG) respond to acidic pH and generated larger currents compared to those from the nodose ganglia (NG). The ASIC-like current properties of the cardiac DRG neurons from wild-type mice most closely matched the properties of ASIC2a/3 heteromeric channels. This was supported by studies in ASIC null mice: acid-evoked currents from ASIC3 −/− cardiac afferents matched the properties of ASIC2a channels, and currents from ASIC2 −/− cardiac afferents matched the properties of ASIC3 channels. Conclusions We conclude that ASIC2a and -3 are the major ASIC subunits in cardiac DRG neurons, and provide potential molecular targets to attenuate chest pain and deleterious reflexes associated with cardiac disease.

Abstract-Calcitonin gene-related peptide (CGRP) is a powerful vasodilator that interacts with the autonomic nervous system. A subunit of the CGRP receptor complex, receptor activity-modifying protein 1 (RAMP1), is required for trafficking of the receptor to the cell surface and high-affinity binding to CGRP. We hypothesized that upregulation of RAMP1 would favorably enhance autonomic regulation and attenuate hypertension. Blood pressure, heart rate, and locomotor activity were measured by radiotelemetry in transgenic mice with ubiquitous expression of human RAMP1 (hRAMP1) and littermate controls. Compared with control mice, hRAMP1 mice exhibited similar mean arterial pressure, a lower mean heart rate, increased heart rate variability, reduced blood pressure variability, and increased baroreflex sensitivity (2.83Ϯ0.20 versus 1.49Ϯ0.10 ms/mm Hg in controls; PϽ0.05). In control mice, infusion of angiotensin II (Ang-II) increased mean arterial pressure from 118Ϯ2 mm Hg to 153Ϯ4 and 174Ϯ6 mm Hg after 7 and 14 days of infusion, respectively (PϽ0.05). In contrast, Ang-II hypertension was markedly attenuated in hRAMP1 mice with corresponding values of mean arterial pressure of 111Ϯ2, 119Ϯ2, and 132Ϯ3 mm Hg. Ang-II induced decreases in baroreflex sensitivity and heart rate variability, and increases in blood pressure variability observed in control mice were also abrogated or reversed in hRAMP1 mice (PϽ0.05). Moreover, during the Ang-II infusion, the pressor response to the CGRP receptor antagonist CGRP 8-37 was significantly greater (PϽ0.05) in hRAMP1 mice (ϩ30Ϯ2 mm Hg) than in control mice (ϩ19Ϯ2 mm Hg), confirming a significantly greater antihypertensive action of endogenous CGRP in hRAMP1 mice. We conclude that RAMP1 overexpression attenuates Ang-II-induced hypertension and induces a protective change in cardiovascular autonomic regulation. (Hypertension. 2010;55:627-635.)Key Words: calcitonin gene-related peptide Ⅲ parasympathetic nerve activity Ⅲ heart rate variability Ⅲ baroreflex sensitivity Ⅲ blood pressure Ⅲ transgenic mice C alcitonin gene-related peptide (CGRP) is expressed predominantly in the nervous system and contributes to a variety of physiological and pathological processes, including neurogenic inflammation, inhibition of cell proliferation and oxidative stress, and cardiovascular regulation. 1,2 CGRP is one of the most powerful vasodilators known, and sensory nerves containing CGRP provide extensive innervation of blood vessels. 1,2 Furthermore, CGRP and/or CGRP receptor expression are increased in several models of hypertension, including that induced by infusion of the vasoconstrictor peptide angiotensin II (Ang-II). [3][4][5][6] Although pharmacological blockade of CGRP receptors does not influence mean arterial pressure (MAP) of normotensive subjects, receptor blockade increases the severity of hypertension in several experimental models. 6 -8 These findings suggest that endogenous CGRP operates through a negative-feedback mechanism to oppose the development of hypertension.Although it is reason...