Mese: Settembre 2019

Cereal yellow dwarf virus (CYDV) RNA has a 5′-terminal genome-linked protein (VPg). We have expressed the VPg region of the CYDV genome in bacteria and used the purified protein (bVPg) to raise an antiserum which was able to detect free VPg in extracts of CYDV-infected oat plants. A template-dependent RNA-dependent RNA polymerase (RdRp) has been produced from a CYDV membrane-bound RNA polymerase by treatment with BAL 31 nuclease. The RdRp was template specific, being able to utilize templates from CYDV plus- and minus-strand RNAs but not those of three unrelated viruses, Red clover necrotic mosaic virus, Cucumber mosaic virus, and Tobacco mosaic virus.

RNA synthesis catalyzed by the RdRp required a 3′-terminal GU sequence and the presence of bVPg. Additionally, synthesis of minus-strand RNA on a plus-strand RNA template required the presence of a putative stem-loop structure near the 3′ terminus of CYDV RNA. The base-paired stem, a single-nucleotide (A) bulge in the stem, and the sequence of a tetraloop were all required for the template activity. Evidence was produced showing that minus-strand synthesis in vitro was initiated by priming by bVPg at the 3′ end of the template. The data are consistent with a model in which the RdRp binds to the stem-loop structure which positions the active site to recognize the 3′-terminal GU sequence for initiation of RNA synthesis by the addition of an A residue to VPg.

In vitro RNA-dependent RNA polymerase (RdRp) systems have been established for several plus-strand RNA plant viruses and, along with in vivo methods, have been useful in elucidating the mechanisms of the virus RNA replication. Generally the isolated RdRp complexes are comprised of the virus RdRp per se, other virus replication proteins, and host proteins. In many cases, these RdRps are template specific and are able to initiate RNA synthesis de novo at or near the 3′ end of the template 

As many as 4 out of every 10 people will get sciatica, or irritation of the sciatic nerve, at some point in their life. This nerve comes from either side of the lower spine and travels through the pelvis and buttocks. Then the nerve passes along the back of each upper leg before it divides at the knee into branches that go to the feet.

Anything that puts pressure on or irritates this nerve can cause pain that shoots down the back of one buttock or thigh. The sensation of pain can vary widely. Sciatica may feel like a mild ache; a sharp, burning sensation; or extreme discomfort. Sciatica can also cause feelings of numbness, weakness, and tingling.

Pain may be made worse by prolonged sitting, standing up, coughing, sneezing, twisting, lifting, or straining. Treatment for sciatic pain ranges from hot and cold packs and medications to exercises and complementary and alternative remedies.

Immunosenescence involves a series of ageing-induced alterations in the immune system and is characterized by two opposing hallmarks: defective immune responses and increased systemic inflammation. The immune system is modulated by intrinsic and extrinsic factors and undergoes profound changes in response to the ageing process. Immune responses are therefore highly age-dependent.

Emerging data show that immunosenescence underlies common mechanisms responsible for several age-related diseases and is a plastic state that can be modified and accelerated by non-heritable environmental factors and pharmacological intervention. In the kidney, resident macrophages and fibroblasts are continuously exposed to components of the external environment, and the effects of cellular reprogramming induced by local immune responses, which accumulate with age, might have a role in the increased susceptibility to kidney disease among elderly individuals.

Additionally, because chronic kidney disease, especially end-stage renal disease, is often accompanied by immunosenescence, which affects these patients independently of age, and many kidney diseases are strongly age-associated, treatment approaches that target immunosenescence might be particularly clinically relevant.