Effects of low-chloride solutions on action potentials of sheep cadiac purkinje fibers

The rapid repolarization during phase 1 of the action potential of sheep cardiac purkinje fibers has been attributed to a time- and voltage-dependent chloride current. In part, this conclusion was based on experiments that showed a substantial slowing of phase 1 when larger, presumably impermeant, anions were substituted for chloride in tyrode’s solution. We have re- examined the electrical effects of low-chloride solutions. We recorded action potentials of sheep cardiac purkinje fibers in normal tyrode’s solution and in low-chloride solutions made by substituting sodium propionate, acetylglycinate, methylsulfate, or methanesulfonate for the NaCl of Tyrode’s solution. Total calcium was adjusted to keep calcium ion activity of test solutions equal to that of control solutions. Propionate gave qualitatively variable results in preliminary experiments; it was not tested further. Low-chloride solutions made with the other anions gave much more consistent results: phase 1 and the notch that often occurs between phases 1 and 2 were usually unaffected, and the action potential duration usually increased. The only apparent change in the resting potential was a transient 3-6 mV depolarization when low-chloride solution was first admitted to the chamber, and a symmetrical transient hyperpolarization when chloride was returned to normal. If a time- and voltage-dependent chloride current exists in sheep cardiac purkinje fibers, our results suggest that it plays little role in generating phase 1 of the action potential.     

Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts

Background  

Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction.     

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.     

Facilitation by previous activity in a pacinian corpuscle

A period of supernormal excitability is left by a propagated impulse in a Pacinian corpuscle. The increase in excitability is found 6 to 10 msec. after an impulse occurs in the corpuscle. Supernormality is produced by either mechanically elicited dromic impulses, or by electrically excited antidromic impulses. Generator potentials do not cause supernormality. Local potentials discharged spontaneously by the corpuscle, and which fall on the supernormal trail left by an antidromic impulse, become enhanced in amplitude, an eventually are turned into propagated dromic potentials. The supernormal period is interpreted as caused by a negative after-potential left at the first intracorpuscular node of Ranvier which outlasts both the recovery time of the firing level and that of the generator potential during the corpuscle's relative refractory period.     

The sites for mechano-electric conversion in a Pacinian corpuscle

The sensory nerve ending in the Pacinian corpuscle is surrounded by a non-nervous capsular structure which occupies about 99.9 per cent of the corpuscle's entire mass. After extirpation of practically all of the non-nervous structure, the sense organ's remains continue to function as a mechano-receptor, namely to produce generator and all-or-nothing potentials in response to mechanical stimuli. Compression of the first intracorpuscular node of Ranvier abolishes the production of "all-or-nothing" potentials in the corpuscle. Graded generator potentials constitute then the only response to mechanical stimulation. This reveals that the first node is the site of origin of the all-or-nothing potential and that the non-myelinated ending is incapable of producing all-or-nothing responses in response to mechanical stimulation. Compression of the entire length of non-myelinated ending suppresses the production of generator potentials. Partial compression of the ending abolishes mechano-responsiveness only of the compressed part. The intact remains of the ending continue to give generator potentials upon mechanical stimulation. This suggests that the generator potential arises at functionally independent membrane parts distributed all over the non-myelinated nerve ending. 24 to 36 hours after denervation of the corpuscle by transection of its sensory axon, no sign of electric activity is detected. Failure of mechano-reception at the nerve ending precedes that of conduction at the degenerating myelinated axon.     

Genetic affinities of inbred mouse strains of uncertain origin

Phylogenetic analyses of genetic data arising from 144 gene loci are used to describe the interrelationships among 24 widely used inbred strains of mice. An unordered-parsimony analysis gives a cladogram that is virtually identical to the known genealogy of the mouse strains. A loss-parsimony analysis is used to evaluate the hypothesis that the observed patterns of genetic divergence among these 24 strains can be explained by the segregation of residual heterozygosity arising from a small population of highly heterozygous mice. The loss-parsimony cladogram is very similar to both the unordered-parsimony cladogram and the known genealogy of the mice. The phylogenetic analyses of these 144 loci are integrated with data on the type and origin of the Y chromosome. Inclusion of the Y-chromosome data provides additional insights into the genetic composition of several of the original stocks used to produce the current inbred strains of mice. Ten strains of uncertain origin are contained in these analyses, including AKR, BUB, CE, I, NZB, P, RF, SJL, ST, and SWR. SJL is hypothesized to have been derived from the same Swiss albino stock previously used to produce SWR. The BUB strain appears to have had a complex origin and shows closest genetic similarity to SWR and ST. AKR and RF are shown to be closely related, while the I strain shows greatest genetic similarity to DBA/2 for the 144 loci. However, I and DBA possess different types of Y chromosome. The NZB strain shows genetic similarity to several stocks of both U.S. and European origins. The power of the genetic data used in these analyses reiterates that inbred strains of mice can be a valuable paradigm for studies in evolutionary biology.      

Generator processes of repetitive activity in a pacinian corpuscle

Response patterns resulting from repetitive mechanical stimulation of the corpuscle depend on (1) the time course of recovery of the generator potential, on (2) the recovery of critical firing height, and on (3) the stimulus strength/generator potential function. By either augmenting stimulus frequency at constant strength, or by reducing strength at constant frequency, a sequence of propagated potentials is turned into a pattern of alternating regenerative and generator responses. In such a pattern an extra impulse can be set up whenever an extra stimulus produces a generator potential of enough amplitude to reach the firing height of the corresponding period. The new requirements of firing height introduced by the refractory trail of the extra impulse determine resetting of periodicity and appearance of a "compensatory pause." The decay time of the single generator potential is independent of stimulus duration. This is interpreted as a factor determining receptor adaptation. Upon repetitive stimulation at intervals above ½ decay time of the single generator potential, a compound generator potential is built up which shows no spontaneous decline. However, in spite of being considerably greater than the firing height for single impulses, the constant level of depolarization of the compound generator potential is unable to produce propagated potentials. A hypothesis is brought forward which considers the generator potential to arise from membrane units with fluctuating excitability scattered over the non-myelinated nerve ending.     

The role of disjunction and postglacial population expansion on phylogeographical history and genetic diversity of the circumboreal plant Chamaedaphne calyculata

In the last decade a number of studies has illustrated quite different phylogeographical patterns amongst plants with a northern present‐day geographical distribution, spanning the entire circumboreal region and/or circumarctic region and southern mountains. These works, employing several marker systems, have brought to light the complex evolutionary histories of this group. Here I focus on one circumboreal plant species, Chamaedaphne calyculata (leatherleaf), to unravel its phylogeographical history and patterns of genetic diversity across its geographical range. A survey of 29 populations with combined analyses of chloroplast DNA (cpDNA), internal transcribed spacer (ITS) and AFLP markers revealed structuring into two groups: Eurasian/north‐western North American, and north‐eastern North American. The present geographical distribution of C. calyculata has resulted from colonization from two putative refugial areas: east Beringia and south‐eastern North America. The variation of chloroplast DNA (cpDNA) and ITS sequences strongly indicated that the evolutionary histories of the Eurasian/north‐western North American and the north‐eastern North American populations were independent of each other because of a geographical disjunction in the distribution area and ice‐sheet history between north‐eastern and north‐western North America. Mismatch analysis using ITS confirmed that the present‐day population structure is the result of rapid expansion, probably since the last glacial maximum. The AFLP data revealed low genetic diversity of C. calyculata (P = 19.5%, H = 0.085) over the whole geographical range, and there was no evidence of loss of genetic diversity within populations in the continuous range, either at the margins or in formerly glaciated and nonglaciated regions. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105 , 761–775.