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Although North American and European serotypes of porcine reproductive and respiratory syndrome virus (PRRSV) are recognized, only the genome of the European Lelystad strain (LV) has been sequenced completely. Here, the genome of the pathogenic North American PRRSV isolate 16244B has been sequenced and compared with LV. The genomic organization of 16244B was the same as LV but with only 63n4 % nucleotide identity. The 189 nucleotide 5h non-coding region (NCR) of 16244B was distinct from the LV NCR, with good conservation (83 %) only over a 43 base region immediately upstream of open reading frame (ORF) 1a. Major differences were found in the region encoding the non-structural part of the ORF1a polyprotein, which shared only 47 % amino acid identity over 2503 residues of the six non-structural proteins (Nsps) encoded. Nsp2, thought to have a species-specific function, showed the greatest divergence, sharing only 32 % amino acid identity with LV and containing 120 additional amino acids in the central region. Nsps encoded by the 5h-proximal and central regions of ORF1b had from 66 to 75 % amino acid identity ; however, the carboxy-terminal protein CP4 was distinct (42 % identity). The ORF1a-1b frameshift region of 16244B had 98 % nucleotide identity with LV. Consistent with previous reports for North American isolates, the six structural proteins encoded were 58 to 79 % identical to LV proteins. The 3h NCR (150 nucleotides) was 76 % identical between isolates. These genomic differences confirm the presence of distinct North American and European PRRSV genotypes.

Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote ADlike pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2-3-fold increase in insoluble amyloid-␤ protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-␤ precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of A␤, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.Added sugars, mainly sucrose and high fructose corn syrup, are major components of a modern human diet. Compelling evidence indicates that excess consumption of sweet foods, particularly sugar-sweetened beverages, plays an important role in the epidemic of obesity around the world (1). In the United States, the percentage of children who are overweight has doubled, and the percentage of teenagers who are overweight has tripled (2, 3). Overweight children are at an increased risk to become obese adults (4). Even moderate obesity can contribute to chronic metabolic abnormalities leading to type 2 diabetes mellitus (5) characterized by glucose intolerance and hyperinsulinemia.Alzheimer disease (AD) 2 is a progressive neurodegenerative disease characterized clinically by progressive cognitive impairment. Pathological hallmarks of the AD brain include intracellular neurofibrillary tangles and deposits of aggregated amyloid-␤ protein (A␤) in neuritic plaques and cerebral vessels. The pathogenic mechanisms that lead to the development of AD, however, are not fully understood. One of the main hypotheses is that ␤-amyloidosis (production and deposition of A␤) plays a crucial role in the pathogenesis of AD (6). A␤ (39 -43 amino acids) is derived from a large transmembrane glycoprotein, amyloid-␤ precursor protein (APP), via proteolytic processing by secretases (6). This hypothesis is supported by discoveries of...

To date there is no effective therapy for Alzheimer disease (AD). High levels of circulating high density lipoprotein (HDL) and its main protein, apolipoprotein A-I (apoA-I), reduce the risk of cardiovascular disease. Clinical studies show that plasma HDL cholesterol and apoA-I levels are low in patients with AD. To investigate if increasing plasma apoA-I/HDL levels ameliorates AD-like memory deficits and amyloid-␤ (A␤) deposition, we generated a line of triple transgenic (Tg) mice overexpressing mutant forms of amyloid-␤ precursor protein (APP) and presenilin 1 (PS1) as well as human apoA-I (AI). Here we show that APP/PS1/AI triple Tg mice have a 2-fold increase of plasma HDL cholesterol levels. When tested in the Morris water maze for spatial orientation abilities, whereas APP/PS1 mice develop age-related learning and memory deficits, APP/PS1/AI mice continue to perform normally during aging. Interestingly, no significant differences were found in the total level and deposition of A␤ in the brains of APP/PS1 and APP/PS1/AI mice, but cerebral amyloid angiopathy was reduced in APP/PS1/AI mice. Also, consistent with the anti-inflammatory properties of apoA-I/HDL, glial activation was reduced in the brain of APP/ PS1/AI mice. In addition, A␤-induced production of proinflammatory chemokines/cytokines was decreased in mouse organotypic hippocampal slice cultures expressing human apoA-I. Therefore, we conclude that overexpression of human apoA-I in the circulation prevents learning and memory deficits in APP/ PS1 mice, partly by attenuating neuroinflammation and cerebral amyloid angiopathy. These findings suggest that elevating plasma apoA-I/HDL levels may be an effective approach to preserve cognitive function in patients with AD.

Using a combination of in situ hybridization and Northern (RNA) blot analysis, we investigated herpes simplex virus type 1 (HSV-1) transcriptional activity in an ocular rabbit model of HSV-1 latency. Radioactively labeled cloned fragments, representing virtually the entire HSV-1 genome, were individually hybridized to RNA in sections of trigeminal ganglia taken from rabbits during the latent phase of infection with HSV-1 (McKrae). Our results suggest that two discrete latency-related RNAs (LR-RNAs) may be present. The LR-RNAs were localized mainly in the nuclei of neurons. The more abundant LR-RNA was detected in approximately 3% of all neurons examined and was designated major LR-RNA. The other LR-RNA, designated minor LR-RNA, was detected in approximately 0.3% of neurons from latently infected rabbits. The genes for the LR-RNAs mapped in the vicinity of the immediate-early gene ICPO (also designated IE110). The gene for the major LR-RNA partially overlapped the left (3') end of the ICPO gene. In situ hybridization with single-stranded RNA probes showed that this LR-RNA was of complementary sense to that of ICPO mRNA. Northern blot analysis gave an approximate size for this LR-RNA of 1.8 to 2.2 kilobases. The minor LR-RNA mapped to or near the right (5') end of the ICPO gene. The detection of LR-RNAs suggests the possibility that these RNAs or their products may play significant roles in the initiation and/or maintenance of HSV-1 latency.