Biological Training for Poultry Flock Advisors: Training the Trainer

Continuing training of poultry flock advisors is an important effort of many Extension specialists and agents in areas having significant poultry industries. The programs discussed in this article describe unique efforts to deliver training on a company-by-company basis. Collaborative efforts by industry, allied industry, and Extension personnel produced programs that were well received by the broiler industry nationally

Facilitating Transformations in a Human Genome Project Database

Human Genome Project databases present a confluence of interesting database challenges: rapid schema and data evolution, complex data entry and constraint management, and the need to integrate multiple data sources and software systems which range over a wide variety of models and formats. While these challenges are not necessarily unique to biological databases, their combination, intensity and complexity are unusual and make automated solutions imperative. We illustrate these problems in the context of the Human Genome Database for Chromosome 22 (Chr22DB), and describe a new approach to a solution for these problems, by means of a deductive language for expressing database transformations and constraints

Biochemical detection of Aβ isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer’s disease

AbstractPrior to the identification of the various abnormal proteins deposited as fibrillar aggregates in the Alzheimer’s disease (AD) brain, there was tremendous controversy over the importance of the various lesions with respect to primacy in the pathology of AD. Nevertheless, based on analogy to systemic amyloidosis, many investigators believed that the amyloid deposits in AD played a causal role and that characterization of these deposits would hold the key to understanding this complex disease. Indeed, in retrospect, it was the initial biochemical purifications of the ∼4 kDa amyloid β-peptide (Aβ) from amyloid deposits in the mid 1980s that launched a new era of AD research (Glenner and Wong, Biochem. Biophys. Res. Commun. 122 (1984) 1121–1135; Wong et al., Proc. Natl. Acad Sci. USA 82 (1985) 8729–8732; and Masters et al., Proc. Natl. Acad Sci. USA 82 (1985) 4245–4249). Subsequent studies of the biology of Aβ together with genetic studies of AD have all supported the hypothesis that altered Aβ metabolism leading to aggregation plays a causal role in AD. Although there remains controversy as to whether Aβ deposited as classic amyloid or a smaller, aggregated, form causes AD, the relevance of studying the amyloid deposits has certainly been proven. Despite the significant advances in our understanding of the role of Aβ in AD pathogenesis, many important aspects of Aβ biology remain a mystery. This review will highlight those aspects of Aβ biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study

Bifurcations of two coupled classical spin oscillators

Two classical, damped and driven spin oscillators with an isotropic exchange interaction are considered. They represent a nontrivial physical system whose equations of motion are shown to allow for an analytic treatment of local codimension 1 and 2 bifurcations. In addition, numerical results are presented which exhibit a Feigenbaum route to chaos.Comment: 16 pages, .dvi and postscrip

Defining Sickle Cell Disease Mortality Using a Population-Based Surveillance System, 2004 through 2008

Population-based surveillance data from California and Georgia for years 2004 through 2008 were linked to state death record files to determine the all-cause death rate among 12,143 patients identified with sickle cell disease (SCD)

Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

<p>Abstract</p> <p>Background</p> <p>Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates.</p> <p>Results</p> <p>Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis.</p> <p>Conclusions</p> <p>Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.</p

Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression

The microtubule-associated protein tau (MAPT) is a pathological component of several neurodegenerative diseases and clinical dementias. Here, we have investigated the effects of a series of commercially available FDA-approved compounds and natural products on total tau protein levels using a cell-based approach that allows for the rapid and efficient measurement of changes in protein expression. RESULTS: The compounds that reduced tau largely fell within 3 functional categories with the largest percentage being microtubule regulators. Several of these candidates were validated in both a human neuroglioma and a human neuroblastoma cell line. While these drugs lead to a rapid reduction in tau protein levels, a selective decrease in MAPT mRNA expression was also observed. CONCLUSION: These findings suggest that the identified compounds that reduce tau levels may act either through direct effects on the MAPT promoter itself or by altering a feedback transcriptional mechanism regulating MAPT transcription. This is particularly interesting in light of recent evidence suggesting that MAPT 5' UTR mutations in late-onset PD and PSP cases alter the expression of tau mRNA. In fact, one of the compounds we identified, rotenone, has been used extensively to model PD in rodents. These observations may provide key insights into the mechanism of tau turnover within the neuron while also providing the first evidence that selectively reducing tau protein levels may be possible using compounds that are FDA-approved for other uses

Spinal fluid IgG antibodies from patients with demyelinating diseases bind multiple sclerosis-associated bacteria

ABSTRACT: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. CSF responses from patients with demyelinating diseases (DD, N = 14) were compared to those with other neurological diseases (OND, N = 8) and controls (N = 13). Commercial positive and negative control CSF specimens were run with each assay. ELISA index values were derived for each specimen against each of the 10 bacterial lysates. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial species, suggesting intrathecal antibody production. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. KEY MESSAGES: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis. CSF reactivity was significantly higher in the demyelination group compared to the controls against the bacteria Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Several of the demyelination subjects had elevated antibody indexes against at least one of the 10 antigens, suggesting at least limited intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00109-021-02085-z