This relatively high level of splicing errors explains why most splice variants are rapidly degraded by nonsense-mediated decay.The presence of sloppy binding sites within genes causes splicing errors and it may seem strange that these sites havent been eliminated by natural selection. The argument for their persistence is similar to the argument for junk DNA. Although mutations which create or disrupt binding sites may be slightly deleterious, the large number of possible such mutations makes it inevitable that some will reach fixation in a population. This is particularly relevant in species, such as humans, with relatively small long-term effective population sizes. It is plausible, then, that the human genome carries a substantial load of suboptimal sequences which cause the generation of aberrant transcript isoforms. In this study, we present direct evidence that this is indeed the case. While the catalytic reaction may be accurate enough for effective processing most of the time, the overall error rate may be partly limited by the fidelity of transcription because transcription errors will introduce mutations that create cryptic splice sites. In addition, the transcription error rate of 10−5 - 10−6 is high enough that one in every 25,000 transcribed exons will have an incorporation error in one of the splice sites leading to a skipped intron or a skipped exon.
Infective endocarditis is an infection of the inner surface of the heart, usually the valves. Signs and symptoms may include fever, small areas of bleeding into the skin, heart murmur, feeling tired, and low red blood cell count. Complications may include backward blood flow in the heart, heart failure – the heart struggling to pump a sufficient amount of blood to meet the bodys needs, abnormal electrical conduction in the heart, stroke, and kidney failure.The cause is typically a bacterial infection and less commonly a fungal infection. Risk factors include valvular heart disease, including rheumatic disease, congenital heart disease, artificial valves, hemodialysis, intravenous drug use, and electronic pacemakers. The bacteria most commonly involved are streptococci or staphylococci. Diagnosis is suspected based on symptoms and supported by blood cultures or ultrasound of the heart. There is also a noninfective form of endocarditis.The usefulness of antibiotics following dental procedures for prevention is unclear. Some recommend them for people at high risk. Treatment is generally with intravenous antibiotics. The choice of antibiotics is based on the results of blood cultures. Occasionally heart surgery is required.The number of people affected is about 5 per 100,000 per year. Rates, however, vary between regions of the world. Infective endocarditis occurs in males more often than in females. The risk of death among those infected is about 25%. Without treatment, it is almost universally fatal. Classification
Infective endocarditis is divided into the three categories of acute, subacute, and chronic based on the duration of symptoms.