Diminished trk A receptor signaling reveals cholinergic‐attentional vulnerability of aging

The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain ( BF ) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno‐associated viral vector‐based RNA interference ( AAV ‐ RNA i) strategy to suppress the expression of tropomyosin‐related kinase A (trk A ) receptors by cholinergic neurons in the nucleus basalis of M eynert/substantia innominata ( nMB / SI ) of adult and aged rats. Suppression of trk A receptor expression impaired attentional performance selectively in aged rats. Performance correlated with trk A levels in the nMB / SI . trk A knockdown neither affected nMB / SI cholinergic cell counts nor the decrease in cholinergic cell size observed in aged rats. However, trk A suppression augmented an age‐related decrease in the density of cortical cholinergic processes and attenuated the capacity of cholinergic neurons to release acetylcholine ( AC h). The capacity of cortical synapses to release AC h in vivo was also lower in aged/trk A ‐ AAV ‐infused rats than in aged or young controls, and it correlated with their attentional performance. Furthermore, age‐related increases in cortical pro NGF and p75 receptor levels interacted with the vector‐induced loss of trk A receptors to shift NGF signaling toward p75‐mediated suppression of the cholinergic phenotype, thereby attenuating cholinergic function and impairing attentional performance. These effects model the abnormal trophic regulation of cholinergic neurons and cognitive impairments in patients with early A lzheimer's disease. This rat model is useful for identifying the mechanisms rendering aging cholinergic neurons vulnerable as well as for studying the neuropathological mechanisms that are triggered by disrupted trophic signaling. The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain ( BF ) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno‐associated viral vector‐based RNA interference ( AAV ‐ RNA i) strategy to suppress the expression of trk A receptors by cholinergic neurons in the nucleus basalis of M eynert/substantia innominata (n MB / SI ) of adult and aged rats. This study provides novel evidence that reduced trkA receptors is not sufficient to trigger cholinergic dysfunction. Rather, aging interacts with disrupted trkA signaling to escalate the vulnerability of BF cholinergic neurons and the manifestation of age‐related attentional impairments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96365/1/ejn12090-sup-0001-SupportingInformation.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96365/2/ejn12090.pd

Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55962/1/21079_ftp.pd

Effects of paraprobiotic as replacements for antibiotic on performance, immunity, gut health and carcass characteristics in broiler chickens

Abstract This study sought to determine the effects of dietary paraprobiotic (PPB) on broiler chicken performance, immunity, gut health, and carcass traits. A total of 240 day-old CARIBRO Vishal commercial broiler chicks of identical body weight randomly divided into six treatment groups, each with five replicates and eight chicks in each replicate. Six dietary treatments were preapared: T1 = (control diet), T2 = T1 + 0.02% (w/v) chlortetracycline (CTC), T3 = T1 + 0.2% (w/v) PPB, T4 = T1 + 0.4% (w/v) PPB, T5 = T1 + 0.6% (w/v) PPB and T6 = T1 + 0.8% (w/v) PPB, respectively. Body weight gain (BWG) significantly (P ≤ 0.05) increased in the T5 (0.6% PPB) and T6 (0.8% PPB) group. At the same time the feed intake significantly (P ≤ 0.05) decreased and the feed conversion ratio (FCR) significantly (P ≤ 0.05) improved in T5 and T6 group. There was a significant (P ≤ 0.05) increase in cell-mediated immunity and haem-agglutination titre (HA titre) in the 0.6% and 0.8% PPB supplemented groups compare to the control group (T1). The percentage of carcass traits and organ weights did not significantly differ between the PPB-supplemented and control groups, but the percentage of live weight in cut up parts showed a significant improvement (P ≤ 0.05) in the PPB-supplemented group. At 42 days, villus height, width, and crypt depth all significantly (P ≤ 0.05) increased in the groups supplemented with 0.6 and 0.8% para-probiotics (T5 and T6). The results show that para-probiotics can be added to broiler diets at a rate of 0.6% (w/v) to enhance performance, immunity, gut health, and breast yield. The para-probiotic may therefore be a useful substitution for antibiotic growth promoters in the diet of chickens

Isolation and Characterization of Endophytes Bacterial Strains of Momordica charantia L. and Their Possible Approach in Stress Management

In the present study, eight endophytic bacterial strains, namely Bacillus licheniformis R1, Bacillus sp. R2, Agrobacterium tumefaciens R6, uncultured bacterium R11, Bacillus subtilis RS3, Bacillus subtilis RS6, uncultured bacterium RS8 and Lysinibacillus fusiformis RS9, were isolated from the root of Momordica charantia L. All the strains, except R6 exhibited positive for IAA production, siderophore production, and phosphate solubilization during plant growth-promoting traits analysis. Strains invariably utilized glucose and sucrose as a carbon source during substrate utilization, while yeast extract, ammonium sulphate, ammonium chloride, glycine, glutamine, and isoleucine as nitrogen sources. In addition, Spectinomycin was found as the most effective during antibiotic sensitivity TEST, followed by Chloramphenicol, Erythromycin, Rifampicin and Kanamycin, while Polymixin B was found least effective, while strains R1, R6, and RS8 were sensitive to all the antibiotics. Strains R1 and RS6 were able to withstand tolerance up to 10% of NaCl. The strains showing resistance against broad-spectrum antibiotics, especially chloramphenicol, can be used in hospital waste management. In addition, strains with a tolerance of 10 % of NaCl can improve plant growth in the saline affected area

Differences in Risk of Sudden Cardiac Death Between Blacks and Whites

BackgroundPrior studies have consistently demonstrated that blacks have an approximate 2-fold higher incidence of sudden cardiac death (SCD) than whites; however, these analyses have lacked individual-level sociodemographic, medical comorbidity, and behavioral health data.ObjectivesThe purpose of this study was to evaluate whether racial differences in SCD incidence are attributable to differences in the prevalence of risk factors or rather to underlying susceptibility to fatal arrhythmias.MethodsThe Reasons for Geographic and Racial Differences in Stroke study is a prospective, population-based cohort of adults from across the United States. Associations between race and SCD defined per National Heart, Lung, and Blood Institute criteria were assessed.ResultsAmong 22,507 participants (9,416 blacks and 13,091 whites) without a history of clinical cardiovascular disease, there were 174 SCD events (67 whites and 107 blacks) over a median follow-up of 6.1 years (interquartile range: 4.6 to 7.3 years). The age-adjusted SCD incidence rate (per 1,000 person-years) was higher in blacks (1.8; 95% confidence interval [CI]: 1.4 to 2.2) compared with whites (0.7; 95% CI: 0.6 to 0.9), with an unadjusted hazard ratio of 2.35; 95% CI: 1.74 to 3.20. The association of black race with SCD risk remained significant after adjustment for sociodemographics, comorbidities, behavioral measures of health, intervening cardiovascular events, and competing risks of non-SCD mortality (hazard ratio: 1.97; 95% CI: 1.39 to 2.77).ConclusionsIn a large biracial population of adults without a history of cardiovascular disease, SCD rates were significantly higher in blacks as compared with whites. These racial differences were not fully explained by demographics, adverse socioeconomic measures, cardiovascular risk factors, and behavioral measures of health