LymeNet Europe

When your countries life blood is spilling, when do you think is a good time to say NO MORE? 8000, 10,000, 100,000? How many soldiers and innocent babies have to die before the people say no more?

Primary Blast-induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury.
http://www.ncbi.nlm.nih.gov/pubmed/25058115
J Neurotrauma. 2014 Jul 24. [Epub ahead of print]

Pham N1, Sawyer T, Wang Y, Rastgar Jazii F, Vair C, Taghibiglou C.
Author information
Abstract

Traumatic brain injury (TBI) is deemed the 'signature injury' of recent military conflicts in Afghanistan and Iraq, due largely to increased blast exposure. Injuries to the brain can often be misdiagnosed, leading to further complications in the future.

Therefore, the use of protein biomarkers for the screening and diagnosis of TBI is urgently needed.

In the present study, we have investigated the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker for the diagnosis of primary blast-induced TBI (bTBI).

We hypothesize that the primary blast wave can disrupt the brain and dislodge extracellular localized PrPC,

leading to a rise in concentration within the systemic circulation.

Adult male Sprague-Dawley rats were exposed to single pulse shockwave overpressures of varying intensities [15-30 Pounds/Sq. Inch (PSI) or 103.4-206.8 kPa] using an Advanced Blast Simulator. Blood plasma was collected 24 hours after insult, and PrPC concentration was determined with a modified commercial enzyme-linked immunosorbent assay (ELISA) specific for PrPC.

We provide the first report that mean PrPC concentration in primary blast exposed rats (3.97 ng/mL ± 0.13 S.E.)

is significantly increased compared to control (2.46 ng/mL ± 0.14 S.E.;2-tailed test p<0.0001).

Furthermore, we report a mild positive rank correlation between PrPC concentration and increasing blast intensity (PSI) ,

reflecting a plateaued response at higher pressure which magnitudes, which may allow for improved injury outcome assessment in the future have implications for all military service members exposed to blast events.

In conclusion, it appears that plasma levels of PrPC may be a novel biomarker for the detection of primary bTBI. Key words: A. Blast exposure; B. Blood Plasma; C. Brain injury; D. ELISA; D. Cellular prion protein.

Corroboration:
http://www.ncbi.nlm.nih.gov/pubmed/25044276

http://www.ncbi.nlm.nih.gov/pubmed/25043188

http://www.ncbi.nlm.nih.gov/pubmed/25039275

The Cellular Prion Protein Negatively Regulates Phagocytosis and Cytokine Expression in Murine Bone Marrow-Derived Macrophages.
http://www.ncbi.nlm.nih.gov/pubmed/25058617
PLoS One. 2014 Jul 24;9(7):e102785. doi: 10.1371/journal.pone.0102785. eCollection 2014.

SNIP- E. coli infection induced an increase in the PRNP mRNA level.
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Remarkably, knockout of PrPC suppressed the proliferation of internalized bacteria

and increased the expression of cytokines such as interleukin-1β.
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It was originally intended to be, behaviorally, an analog of E. coli Lipid A.

Real scientists understand that structure is function, and thus, via their FUNCTION - handled by TLR2 - we can speak of these antigens mechanistically, or, "What is the DISEASE(S) it creates?"
http://www.actionlyme.org/Pam3Cys_Version15.htm
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Remember they can't crystallize a Lipid......

Int J Biol Macromol. 2014 Mar;64:168-73. doi: 10.1016/j.ijbiomac.2013.11.035. Epub 2013 Dec 7.
Crystal structure of PfbA, a surface adhesin of Streptococcus pneumoniae, provides hints into its interaction with fibronectin.
Beulin DS1, Yamaguchi M2, Kawabata S3, Ponnuraj K4.
Author information
Abstract

PfbA is a surface adhesin and invasin of Streptococcus pneumoniae that binds to human fibronectin and plasminogen of the host extracellular matrix. It is a virulence factor for its pathogenesis.

The crystal structure of recombinant PfbA150-607 from S. pneumoniae strain R6, was determined using multiwavelength anomalous dispersion (MAD) method and refined to 1.90Å resolution. The structure of rPfbA150-607 revealed that residues Thr150 to Lys570 form a rigid parallel beta helix, followed by a short disordered region (571-607) that consists of beta hairpins.

The structural organization of the beta helix resembles that of polysaccharide-modifying enzymes.

The structural and sequence features essential for fibronectin-binding observed in the well characterized fibronectin-binding proteins such as FnBPA of Staphylococcus aureus, SfbI of Streptococcus pyogenes and

BBK32 of Borrelia burgdorferi has been found in rPfbA150-607.

Based on this, it is predicted that the disordered region following the beta helix could be the fibronectin-binding region in PfbA.

PfbA150-607 contains relatively high number of surface exposed lysines and these residues are probably involved

in binding plasmin(ogen) as observed in other plasminogen-binding proteins.
http://www.ncbi.nlm.nih.gov/pubmed/24321492

Emerg Infect Dis. 2014 Aug;20(8):1391-4. doi: 10.3201/eid2008.131761.

Human Infections with Borrelia miyamotoi, Japan.

http://www.ncbi.nlm.nih.gov/pubmed/25061761
Sato K, Takano A, Konnai S, Nakao M, Ito T, Koyama K, Kaneko M, Ohnishi M, Kawabata H.
Abstract

We confirmed infection of 2 patients with Borrelia miyamotoi in Japan by retrospective surveillance of Lyme disease patients and detection of B. miyamotoi DNA in serum samples.

One patient also showed seroconversion for antibody against recombinant glycerophosphodiester phosphodiesterase of B. miyamotoi.

Indigenous relapsing fever should be considered a health concern in Japan.
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25 December
MERRY CHRISTMAS- JAPAN TRYING TO SAVE YOU...
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Insect Cell-Derived Cofactors Become Fully Functional after Proteinase K and Heat Treatment for High-Fidelity Amplification of

Glycosylphosphatidylinositol-Anchored Recombinant Scrapie and BSE Prion Proteins.

http://www.ncbi.nlm.nih.gov/pubmed/24367521
PLoS One. 2013 Dec 18;8(12):e82538. doi: 10.1371/journal.pone.0082538.
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I believe we should give honorable researchers the privilege of renaming AIDS/LYME/MADCOW to whatever name they see fit!

J Alzheimers Dis. 2014 Jul 30. [Epub ahead of print]
Helicobacter pylori Filtrate Induces Alzheimer-Like Tau Hyperphosphorylation by Activating Glycogen Synthase Kinase-3β
Xiu-Lian W1, Ji Z2, Yang Y3, Yan X3, Zhi-Hua Z4, Mei Q3, Xiong Y3, Xu-Ying S3, Qing-Zhang T3, Rong L3, Jian-Zhi W3.
Author information
Abstract

Abnormal hyperphosphorylation of microtubule-associated protein tau

is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD).

Helicobacter pylori (H. pylori) infection has been reported to be related with a high risk of AD, but the direct laboratory evidence is lacking.

Here we explored the effect of H. pylori infection on tau phosphorylation.

The results showed that

+++H. pylori filtrate induced significant tau hyperphosphorylation at several AD-related tau phosphorylation sites+++,

such as Thr205, Thr231, and Ser404, both in mouse neuroblastoma N2a cells and rat brains with activation of glycogen synthase kinase-3β (GSK-3β).

+++Application of GSK-3 inhibitors efficiently attenuated the H. pylori-induced tau hyperphosphorylation.+++

Our data provide evidence supporting the role of H. pylori infection in AD-like tau pathology,

suggesting that H. pylori eradication may be beneficial in the prevention of tauopathy.
http://www.ncbi.nlm.nih.gov/pubmed/25079798

Whoops, we have another winner!

A Micellar On-Pathway Intermediate Step Explains the Kinetics of Prion Amyloid Formation.
http://www.ncbi.nlm.nih.gov/pubmed/25101755
http://www.ploscompbiol.org/article/inf ... bi.1003735


Biophys J. Jul 6, 2011; 101(1): 245–254.
doi: 10.1016/j.bpj.2011.05.033
PMCID: PMC3127186
Label-Free Critical Micelle Concentration Determination of Bacterial Quorum Sensing Molecules
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127186/

+++IMMUNE SUPPRESSION+++
http://www.ncbi.nlm.nih.gov/pubmed/25103253
Sci Rep. 2014 Aug 8;4:6006. doi: 10.1038/srep06006.

Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3.

Homma T1, Ishibashi D1, Nakagaki T2, Fuse T2, Sano K2, Satoh K2, Atarashi R3, Nishida N2.
Author information
Abstract

As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types.

We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions.

Here, we found that stable infection of prion suppressed IRF-3 gene-expression.

The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription.

We further investigated promoter activity of 5'- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity.

Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region.

In addition, overexpression of Oct-1 increased the promoter activity of IRF-3.

Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups.

Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.
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Notice they did not delineate between so called normal or abnormal prions. There is no normal. And yes we all have Prion.

White blood cell-based detection of asymptomatic scrapie infection by ex vivo assays.
http://www.ncbi.nlm.nih.gov/pubmed/25122456

Neuropathology. 2014 Aug 14. doi: 10.1111/neup.12143. [Epub ahead of print]
Astrocytic inclusions in progressive supranuclear palsy and corticobasal degeneration.
Yoshida M.
Tufted astrocytes (TAs) in progressive supranuclear palsy (PSP) and astrocytic plaques (APs) in corticobasal degeneration (CBD) have been regarded as the pathological hallmarks of major sporadic 4-repeat tauopathies.

To better define the astrocytic inclusions in PSP and CBD and to outline the pathological features of each disease, we reviewed 95 PSP cases and 30 CBD cases that were confirmed at autopsy.

TAs exhibit a radial arrangement of thin, long, branching accumulated tau protein from the cytoplasm to the proximal processes of astrocytes. APs show a corona-like arrangement of tau aggregates

in the distal portions of astrocytic processes and are composed of fuzzy, short processes.

Immunoelectron microscopic examination using quantum dot nanocrystals revealed filamentous tau accumulation of APs

located in the immediate vicinity of the synaptic structures,

which suggested synaptic dysfunction by APs. The pathological subtypes of PSP and CBD have been proposed to ensure that the clinical phenotypes are in accordance with the pathological distribution and degenerative changes.

The pathological features of PSP are divided into 3 representative subtypes: typical PSP type, pallido-nigro-luysian type (PNL type), and CBD-like type. CBD is divided into three pathological subtypes: typical CBD type, basal ganglia- predominant type, and PSP-like type. TAs are found exclusively in PSP, while APs are exclusive to CBD,

regardless of the pathological subtypes, although some morphological variations exist, especially with regard to TAs.

The overlap of the pathological distribution of PSP and CBD makes their clinical diagnosis complicated, although the presence of TAs and APs differentiate these two diseases.

"""The characteristics of tau accumulation in both neurons and glia suggest a different underlying mechanism """

with regard to the sites of tau aggregation and fibril formation between PSP and CBD:

proximal-dominant aggregation of TAs and formation of filamentous NFTs in PSP in contrast to the distal-dominant aggregation of APs and formation of less filamentous pretangles in CBD