Little cherry virus-2: Sequence and genomic organization of an unusual member of the <Emphasis Type="Italic">Closteroviridae</Emphasis>

Summary. The complete genomic sequence of variant USA6b of Little cherry virus-2 (LChV-2), has been determined and is 15045 nucleotides in length, coding for 11 open reading frames (ORFs). The sequence shares 77.2% identity with a previously published, ca. 6kb partial replicase sequence of LChV-2 (variant USA6a). Both LChV-2/USA6a and LChV-2/USA6b were obtained from the same tree infected with little cherry disease, and would suggest a mixed infection. LChV-2/USA6b is more closely related to the partially determined genomic sequence of a Canadian isolate of LChV-2, strain LC5 (92.9% identity). LChV-2/USA6b has an unusual genomic organization compared to other members of the Closteroviridae. The LChV-2/USA6b genome is potentially ambi-sense, with a negative sense ORF0 at the 5 terminus, from which an 18.1kDa protein of unknown function can be expressed in vitro. The N-terminal region of the LChV-2/USA6 ORF1a translation product does not code for a papain-like protease motif. ORF1 codes for a novel motif, of unknown function, also present in isolates of the Grapevine leafroll associated virus-3, (genus Ampelovirus) as well as viruses of the family Flexiviridae. ORF3 lacks an AUG start codon, but could potentially be expressed via read-through of the ORF2 stop codon. At the 3 end, there is a re-organization of encoded genes compared with other members of the Closteroviridae including separation of the coat protein and coat protein duplicate genes by 4 other genes as found for LChV-2/LC5.     

EAE in beta-2 microglobulin-deficient mice: axonal damage is not dependent on MHC-I restricted immune responses

There is accumulating evidence that CD8-positive (CD8+) T-cells and MHC-I expression may also play a role in neurodegeneration associated with multiple sclerosis (MS). We investigated the role of MHC-I and CD8+ T-cells by studying experimental autoimmune encephalomyelitis (EAE) in beta-2 microglobulin knockout mice induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 or whole rat myelin basic protein (rMBP). For both encephalitogens and even after reconstitution of the immune system with MHC-I-positive bone marrow and transfer of mature CD8+ T-cells (iMHC-I+ CD8+ beta2m-/- mice), the disease course in beta2m-/- mice was significantly more severe with a 10-fold increased mortality in the beta2m-/- mice as compared to wild-type C57BL/6 mice. EAE in beta2m-/- mice caused more severe demyelination after immunization with MOG than with rMBP and axonal damage was more marked with rMBP as well as MOG even in iMHC-I+ CD8+ beta2m-/- mice. Immunocytochemical analysis of spinal cord tissue revealed a significant increase in macrophage and microglia infiltration in beta2m-/- and iMHC-I+ CD8+ beta2m-/- mice. The different pattern of T-cell infiltration was underscored by a 2.5-fold increase in CD4-positive (CD4+) T-cells in beta2m-/- mice after induction of MOG 35-55 EAE. We conclude that lack of functional MHC-I molecules and CD8+ T-cells aggravates autoimmune tissue destruction in the CNS. Enhanced axonal damage speaks for pathways of tissue damage independent of CD8+ T-cells and neuronal MHC-I expression.     

Successful treatment of pure red cell aplasia associated with systemic lupus erythematosus with oral danazol and steroid

We describe a middle-aged Chinese systemic lupus erythematosus (SLE) patient developing steroid refractory and transfusion dependent red cell aplasia. Oral danazol 200 mg twice per day was started together with low-dose prednisolone therapy. There was no further recurrence of anemia 1 month after this combined therapy.     

Cognitive status and development in the oldest old: a longitudinal analysis from the Heidelberg Centenarian Study

In the present study, we investigated cognitive status, cognitive development and the effect of mortality on cognitive changes in very old age. Analyzing data from the population-based Heidelberg Centenarian Study, results revealed that centenarians differed quite strongly in their cognitive capacities. While about half of the population showed moderate to severe cognitive impairment, one quarter was found to be cognitively intact. Moreover, analyzing cognitive change over a period of 1.5 years, centenarians' cognitive performance was revealed to be rather stable. Finally, only a small effect of mortality on cognitive status and changes was detected, supporting a recent hypothesis that the terminal decline or drop in cognitive functioning decreases in very old age.     

Life-long intellectual activities mediate the predictive effect of early education on cognitive impairment in centenarians: a retrospective study

The purpose of this study was to examine the hypothesis of whether early education and/or maintaining intellectual activities over the life-course have the power to protect against cognitive impairment even in extremely old adults. Ninety centenarians from the population-based Heidelberg Centenarian Study were assessed with a modified version of the Mini Mental State Exam (MMSE). Data about education, occupational status, and life-long intellectual activities in four selected domains were obtained. Results demonstrated that 52% of the sample showed mild-to-severe cognitive impairment. Analyzing the influence of early education, occupational status, and intellectual activities on cognitive status we applied several (logistic) regression analyses. Results revealed independent, significant and strong influence of both formal school education and intellectual activities on the cognitive status in very late life, even after controlling for occupational status. However, about one fourth of the effect of early education on cognitive status was exerted indirectly via the assessed intellectual activities. In summary, the present study provides first evidence for the conclusion that even with regard to cognitive performance in very old age, both early education and life-long intellectual activities seem to be of importance.