Anti-tau conformational scFv MC1 antibody efficiently reduces pathological tau species in adult JNPL3 mice.

Tau, the main component of the neurofibrillary tangles (NFTs), is an attractive target for immunotherapy in Alzheimer\u27s disease (AD) and other tauopathies. MC1/Alz50 are currently the only antibodies targeting a disease-specific conformational modification of tau. Passive immunization experiments using intra-peritoneal injections have previously shown that MC1 is effective at reducing tau pathology in the forebrain of tau transgenic JNPL3 mice. In order to reach a long-term and sustained brain delivery, and avoid multiple injection protocols, we tested the efficacy of the single-chain variable fragment of MC1 (scFv-MC1) to reduce tau pathology in the same animal model, with focus on brain regional differences. ScFv-MC1 was cloned into an AAV delivery system and was directly injected into the hippocampus of adult JNPL3 mice. Specific promoters were employed to selectively target neurons or astrocytes for scFv-MC1 expression. ScFv-MC1 was able to decrease soluble, oligomeric and insoluble tau species, in our model. The effect was evident in the cortex, hippocampus and hindbrain. The astrocytic machinery appeared more efficient than the neuronal, with significant reduction of pathology in areas distant from the site of injection. To our knowledge, this is the first evidence that an anti-tau conformational scFv antibody, delivered directly into the mouse adult brain, is able to reduce pathological tau, providing further insight into the nature of immunotherapy strategies

Information diffusion in the U.S. real estate investment trust market

This study examines the information diffusion process in the U.S. Real Estate Investment Trust (REIT) market with a focus on the impacts of changing market environments, information supply, and information demand on the lead-lag effect. The results suggest that a significant lead-lag relationship exists between the lagged returns of big REITs and the current returns of small REITs. This relationship has slightly decreased along with policy and environment changes that occurred in the U.S. REIT market during the study period from 1986 to 2012, while still remaining significant in the most recent REIT market. The process of information diffusion is becoming unstable in recent years and the reverse lead-lag effect from small REITs to big REITs is observed especially when REIT market liquidity and return volatility are high. The lead-lag effect among REITs is driven largely by slow adjustment to negative information, which is magnified by a lack of information supply, especially as demand for such information increases. Finally, information flow from REITs with more media coverage to those with less media coverage becomes even more sluggish than the information flow from big REITs to small REITs

Creutzfeldt-Jakob disease presenting as psychiatric disorder: case presentation and systematic review

Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy caused by misfolded human prion proteins (PrP)s. Due to variability in presentation, the diagnosis may be missed in lieu of various psychiatric disorders. Our study reports on a prototypical case and psychiatric mimic for CJD, and the workup used to establish the correct diagnosis. A 54-year-old male with a past medical history of traumatic brain injury and major depressive disorder presented with chest pain. During the hospital stay, he was found to be increasingly aggressive, and behaved out of character. Further review of clinical history revealed that the patient was diagnosed with cognitive impairment and depression one year prior. The patient was agitated, poorly redirectable, and had unstable gait on neurological examination. Magnetic resonance imaging (MRI) of the brain demonstrated restricted diffusion (DWI) along the parietooccipital and temporal regions (L > R) and in the subcortical structures, including the basal ganglia and thalami, with accompanying subtle fluid attenuation inversion recovery (FLAIR) hyperintense signal abnormality in these regions, deemed as artifactual at the time. Repeat MRI brain two months later demonstrated progression of the DWI signal with ADC correlate and FLAIR findings. Cerebrospinal fluid 14-3-3 and RT-QuIC samples were positive. Upon passing a few months later, brain autopsy and Western Blot confirmed the CJD diagnosis. Literature review was conducted on PubMed to identify CJD cases initially diagnosed as psychiatric disorder. Search terms included “CJD” or “Creutzfeldt-Jakob disease” with three common psychiatric diagnoses, “Depression,” “Psychosis,” and “Mania.” Positive EEG, MRI, PET, and CSF (including protein 14-3-3 and tau) findings for CJD were found in 66.7, 81.1, 50, and 72.7% of cases, respectively. Overall, CJD can present as a psychiatric mimic. In suspicious cases, EEG, imaging, and CSF studies should be promptly utilized to arrive at the correct diagnosis. Repeated MRI imaging is often required to help in the diagnostic process. Brain biopsy should be considered in selected cases

Using Light to Improve Commercial Value

The plasticity of plant morphology has evolved to maximize reproductive fitness in response to prevailing environmental conditions. Leaf architecture elaborates to maximize light harvesting, while the transition to flowering can either be accelerated or delayed to improve an individual's fitness. One of the most important environmental signals is light, with plants using light for both photosynthesis and as an environmental signal. Plants perceive different wavelengths of light using distinct photoreceptors. Recent advances in LED technology now enable light quality to be manipulated at a commercial scale, and as such opportunities now exist to take advantage of plants' developmental plasticity to enhance crop yield and quality through precise manipulation of a crops' lighting regime. This review will discuss how plants perceive and respond to light, and consider how these specific signaling pathways can be manipulated to improve crop yield and quality

Anatomic and radiologic relationships of neck structures to cervical spine: Implications for anterior surgical approaches

The position of the pharyngolaryngeal framework is very important in choosing the best surgical approach for cervical spine disease. The aim of the present paper is to investigate the position of the hyoid bone and cricoid cartilage in relation to the cervical spine. Moreover, the surgical implications for anterior transcervical approaches to the upper spine and the prevertebral space are discussed. To minimise complication rates and increase surgical effectiveness, the location and extent of the cervical spine disease should be evaluated in the context of the patient’s specific anatomy. A retrospective analysis of 100 cervical spine MRIs was conducted. Patients with diseases that could alter anatomic relationships of cervical structures were excluded. The mid-sagittal view of the hyoid and the inferior margin of the cricoid cartilage were projected perpendicularly to the anterior surface of the cervical vertebrae. The distance between these two landmarks was measured on the same view. The distribution of hyoid projections ranged between C2-C3 and C4-C5 intervertebral space, while the cricoid cartilage ranged between C4-C5 and C7-T1 intervertebral spaces. The mean distance between these two landmarks was 49.1 ± 7.7 mm, with statistically significant differences between males and females. The position of the cricoid cartilage significantly influenced the length of the pharyngolaryngeal framework, while the position of hyoid did not. A wide range of variability in the position of the hyoid bone and the cricoid cartilage in relation to cervical levels exists. This implies that an a priori association of a cervical level to neck structures at risk might be inaccurate. The use of these easily identifiable landmarks on pre-operative imaging may help to guide the choice among different anterior surgical approaches to cervical spine and reduce the risk of surgical complications

Futures trading, spot price volatility and market efficiency: evidence from European real estate securities futures

In 2007 futures contracts were introduced based upon the listed real estate market in Europe. Following their launch they have received increasing attention from property investors, however, few studies have considered the impact their introduction has had. This study considers two key elements. Firstly, a traditional Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model, the approach of Bessembinder & Seguin (1992) and the Gray’s (1996) Markov-switching-GARCH model are used to examine the impact of futures trading on the European real estate securities market. The results show that futures trading did not destabilize the underlying listed market. Importantly, the results also reveal that the introduction of a futures market has improved the speed and quality of information flowing to the spot market. Secondly, we assess the hedging effectiveness of the contracts using two alternative strategies (naïve and Ordinary Least Squares models). The empirical results also show that the contracts are effective hedging instruments, leading to a reduction in risk of 64 %

Transgenic Expression of the Amyloid-β Precursor Protein-Intracellular Domain Does Not Induce Alzheimer's Disease–Like Traits In Vivo

BACKGROUND: Regulated intramembranous proteolysis of the amyloid-beta precursor protein by the gamma-secretase yields amyloid-beta, which is the major component of the amyloid plaques found in Alzheimer's disease (AD), and the APP intracellular domain (AID). In vitro studies have involved AID in apoptosis and gene transcription. In vivo studies, which utilize transgenic mice expressing AID in the forebrain, only support a role for AID in apoptosis but not gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have further characterized several lines of AID transgenic mice by crossing them with human Tau-bearing mice, to determine whether over-expression of AID in the forebrain provokes AD-like pathologic features in this background. We have found no evidence that AID overexpression induces AD-like characteristics, such as activation of GSK-3beta, hyperphosphorylation of Tau and formation of neurofibrillary pathology. CONCLUSIONS/SIGNIFICANCE: Overall, these data suggest that AID transgenic mice do not represent a model that reproduces the overt biochemical and anatomo-pathologic lesions observed in AD patients. They can still be a valuable tool to understand the role of AID in enhancing the cell sensitivity to apoptotic stimuli, whose pathways still need to be characterized