Alternative Splicing and Polyadenylation Contribute to the Generation of hERG1 C-terminal Isoforms

The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel. Several hERG1 isoforms with different N- and C-terminal ends have been identified. The hERG1a, hERG1b, and hERG1-3.1 isoforms contain the full-length C terminus, whereas the hERG1USOisoforms, hERG1aUSO and hERG1bUSO, lack most of the C-terminal domain and contain a unique C-terminal end. The mechanisms underlying the generation of hERG1USOisoforms are not understood. We show that hERG1 isoforms with different C-terminal ends are generated by alternative splicing and polyadenylation of hERG1 pre-mRNA. We identified an intrinsically weak, noncanonical poly(A) signal, AGUAAA, within intron 9 of hERG1 that modulates the expression of hERG1a and hERG1aUSO. Replacing AGUAAA with the strong, canonical poly(A) signal AAUAAA resulted in the predominant production of hERG1aUSO and a marked decrease in hERG1 current. In contrast, eliminating the intron 9 poly(A) signal or increasing the strength of 5′ splice site led to the predominant production of hERG1a and a significant increase in hERG1 current. We found significant variation in the relative abundance of hERG1 C-terminal isoforms in different human tissues. Taken together, these findings suggest that post-transcriptional regulation of hERG1 pre-mRNA may represent a novel mechanism to modulate the expression and function of hERG1 channels

Corn supplements and substitutes for fattening lambs

This test was planned to determine the advisability of adding a protein supplement to a basal ration of shelled com, corn silage, alfalfa hay and block salt for fattening range lambs; to compare the relative value of linseed oil meal, velvet bean feed meal and peanut meal as protein supplements added to the same basal ration; and to note the practicability of replacing the shelled corn in the basal ration with corn gluten feed, a corn by-product. Linseed oil meal is a well established and popular supplement to corn widely used for lamb feeding. Velvet bean feed meal and peanut meal are comparatively new supplements, neither being fed to any great extent to live stock in the corn belt. However, both velvet beans and peanuts have been used in the southern states with fairly good results

Corn Oil Cake Meal for Growing and Fattening Pigs

Corn oil cake meal is really a residue of the germs of corn grain which remains after most of the oil is extracted therefrom. The particular corn oil cake meal which we used in our test is a by-product from the manufacture of glucose. These four main products are made from the corn grain: Glucose, corn oil, gluten feed, and corn oil cake meal. It is with the latter that we are to deal

Peaks of Otter Salamander (Plethodon hubrichti) Condition: Optimal Elevations for This Montane Species of Salamander

Undergraduate Basi

Limiting the grain ration for fattening cattle

During the past few years, the Iowa cattle feeder has been confronted with the big problem of determining how much corn grain to feed fattening cattle with corn silage allowed in conjunction with linseed oil meal as the supplement and a leguminous hay, such as alfalfa, as the dry roughage. Should the cattle be full-fed or limited-fed ? How limited should the grain ration be? If full-fed, how should the grain be given the cattle, by hand-fed or self-fed methods? Can all of the silage be replaced, economically, with alfalfa from the roughage standpoint? Should the same methods be employed for feeding from 150 to 160 days as for 120 days

Corn substitutes for fattening lambs—Parts I and II

Shelled corn is a superior basal grain for fattening lambs in dry lot, in the cornbelt and under the conditions of the experiments reported in this bulletin. This fact stands out clearly in the results of the two years’ work at the Iowa Agricultural Experiment Station in the winters of 1918-19 and 1919-20. Shelled corn proved to be more efficient than either oats or barley when fed alone, this being the case when all factors, such as feed required per hundred pounds gain, feed costs, cost of shipping and margin of profit or loss per lamb, are considered

Geographic Variation in Informed Consent Law: Two Standards for Disclosure of Treatment Risks

We analyzed 714 jury verdicts in informed consent cases tried in 25 states in 1985–2002 to determine whether the applicable standard of care (“patient” vs. “professional” standard) affected the outcome. Verdicts for plaintiffs were significantly more frequent in states with a patient standard than in states with a professional standard (27 percent vs. 17 percent, P = 0.02). This difference in outcomes did not hold for other types of medical malpractice litigation (36 percent vs. 37 percent, P = 0.8). The multivariate odds of a plaintiff’s verdict were more than twice as high in states with a patient standard than in states with a professional standard (odds ratio = 2.15, 95% confidence interval = 1.32–3.50). The law’s expectations of clinicians with respect to risk disclosure appear to vary geographically

Propagation of woody plants, Station Bulletin, no.465

The Bulletin is a publication of the New Hampshire Agricultural Experiment Station, College of Life Sciences and Agriculture, University of New Hampshire, Durham, New Hampshire

Persistent isolated hypocortisolism following brief treatment with trilostane

A 12-year-old male neutered Miniature Poodle with confirmed pituitary-dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism ('atypical hypoadrenocorticism'), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life-threatening situation

Evidence for a compact jet dominating the broadband spectrum of the black hole accretor XTE J1550-564

[abridged] The black hole X-ray binary XTE J1550-564 was monitored extensively at X-ray, optical and infrared wavelengths throughout its outburst in 2000. We show that it is possible to separate the optical/near-infrared (OIR) jet emission from the OIR disc emission. Focussing on the jet component, we find that as the source fades in the X-ray hard state, the OIR jet emission has a spectral index consistent with optically thin synchrotron emission (alpha ~ -0.6 to -0.7, where F_nu \propto nu^alpha). This jet emission is tightly and linearly correlated with the X-ray flux; L_OIR,jet \propto L_X^(0.98 +- 0.08) suggesting a common origin. This is supported by the OIR, X-ray and OIR to X-ray spectral indices being consistent with a single power law (alpha = -0.73). Ostensibly the compact, synchrotron jet could therefore account for ~ 100 % of the X-ray flux at low luminosities in the hard state. At the same time, (i) an excess is seen over the power law decay of the X-ray flux at the point in which the jet would start to dominate, (ii) the X-ray spectrum slightly softens, which seems to be due to a high energy cut-off or break shifting to a lower energy, and (iii) the X-ray rms variability increases. This may be the strongest evidence to date of synchrotron emission from the compact, steady jet dominating the X-ray flux of an X-ray binary. For XTE J1550-564, this is likely to occur within the luminosity range ~ (2 e-4 - 2 e-3) L_Edd on the hard state decline of this outburst. However, on the hard state rise of the outburst and initially on the hard state decline, the synchrotron jet can only provide a small fraction (~ a few per cent) of the X-ray flux. Both thermal Comptonization and the synchrotron jet can therefore produce the hard X-ray power law in accreting black holes.Comment: MNRAS accepted, 12 pages, 9 figure