Subnormal vitamin B12 concentrations and anaemia in older people: a systematic review

<p>Abstract</p> <p>Background</p> <p>Pernicious anaemia is undeniably associated with vitamin B12 deficiency, but the association between subnormal vitamin B12 concentrations and anaemia in older people is unclear. The aim of this systematic review was to evaluate the association between subnormal vitamin B12 concentrations and anaemia in older people.</p> <p>Methods</p> <p>Clinical queries for aetiology and treatment in bibliographic databases (PubMed [01/1949-10/2009]; EMBASE [01/1980-10/2009]) were used. Reference lists were checked for additional relevant studies. Observational studies (≥50 participants) and randomized placebo-controlled intervention trials (RCTs) were considered.</p> <p>Results</p> <p>25 studies met the inclusion criteria. Twenty-one observational cross-sectional studies (total number of participants n = 16185) showed inconsistent results. In one longitudinal observational study, low vitamin B12 concentrations were not associated with an increased risk of anaemia (total n = 423). The 3 RCTs (total n = 210) were well-designed and showed no effect of vitamin B12 supplementation on haemoglobin concentrations during follow-up in subjects with subnormal vitamin B12 concentrations at the start of the study. Due to large clinical and methodological heterogeneity, statistical pooling of data was not performed.</p> <p>Conclusions</p> <p>Evidence of a positive association between a subnormal serum vitamin B12 concentration and anaemia in older people is limited and inconclusive. Further well-designed studies are needed to determine whether subnormal vitamin B12 is a risk factor for anaemia in older people.</p

Presenilin 2 Is the Predominant γ-Secretase in Microglia and Modulates Cytokine Release

Presenilin 1 (PS1) and Presenilin 2 (PS2) are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP) to release amyloid beta (Aβ) peptide. PS deficiency in mice results in neuroinflammation and neurodegeneration in the absence of accumulated Aβ. We hypothesize that PS influences neuroinflammation through its γ-secretase action in CNS innate immune cells. We exposed primary murine microglia to a pharmacological γ-secretase inhibitor which resulted in exaggerated release of TNFα and IL-6 in response to lipopolysaccharide. To determine if this response was mediated by PS1, PS2 or both we used shRNA to knockdown each PS in a murine microglia cell line. Knockdown of PS1 did not lead to decreased γ-secretase activity while PS2 knockdown caused markedly decreased γ-secretase activity. Augmented proinflammatory cytokine release was observed after knockdown of PS2 but not PS1. Proinflammatory stimuli increased microglial PS2 gene transcription and protein in vitro. This is the first demonstration that PS2 regulates CNS innate immunity. Taken together, our findings suggest that PS2 is the predominant γ-secretase in microglia and modulates release of proinflammatory cytokines. We propose PS2 may participate in a negative feedback loop regulating inflammatory behavior in microglia

Anatomical Response and Infection of Soybean during Latent and Pathogenic Infection by Type A and B of Phialophora gregata

Growth and anatomical responses of plants during latent and pathogenic infection by fungal pathogens are not well understood. The interactions between soybean (Glycine max) and two types of the pathogen Phialophora gregata were investigated to determine how plants respond during latent and pathogenic infection. Stems of soybean cultivars with different or no genes for resistance to infection by P. gregata were inoculated with wildtype or GFP and RFP-labeled strains of types A or B of P. gregata. Plants were sectioned during latent and pathogenic infection, examined with transmitted light or fluorescent microscopy, and quantitative differences in vessels and qualitative differences in infection were assessed using captured images. During latent infection, the number of vessels was similar in resistant and susceptible plants infected with type A or B compared to the control, and fungal infection was rarely observed in vessels. During pathogenic infection, the resistant cultivars had 20 to 25% more vessels than the uninfected plants, and fungal hyphae were readily observed in the vessels. Furthermore, during the pathogenic phase in a resistant cultivar, P. gregata type A-GFP was limited to outside of the primary xylem, while P. gregata type B-RFP was observed in the primary xylem. The opposite occurred with the susceptible cultivar, where PgA-GFP was observed in the primary xylem and PgB-RFP was limited to the interfascicular region. In summary, soybean cultivars with resistance to BSR produced more vessels and can restrict or exclude P. gregata from the vascular system compared to susceptible cultivars. Structural resistance mechanisms potentially compensate for loss of vessel function and disrupted water movement