Dissecting gene expression at the blood-brain barrier

The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published datasets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier datasets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published datasets, combined with forthcoming genomic and proteomic blood-brain barrier datasets, will continue to fuel the molecular genetic revolution of blood-brain barrier biology

Classification of pig farms regarding environmental risk and internal use of pig manure

224pThis paper presents the practices of Vietnamese farmers in handling animal excreta, i.e., pig manure, and highlights the difference of farms in terms of their operation relative to waste management and utilization. The environmental risks associated with these practices, and the attempt to quantify the difference of pork production systems, are also explored. Finally, a typology constructed based on the difference of practices and the quantification of risks is also given

Assessment of the Effectiveness of Ich Tam Khang as a Supportive Therapy for Chronic Heart Failure

Background: Heart failure is a chronic disease needing lifelong management. Despite the advances that have been made in the treatment of the disease, both the longevity and quality of life for those with chronic heart failure remain impaired. A more effective therapeutic approach with less negative side effects is still needed. In this study, we evaluate Ich Tam Khang (ITK), the poly-ingredient herbal and nutritional preparation with multiple physiological actions, as a supportive therapy for patients with chronic heart failure.Aims of Study: To evaluate the effectiveness and safety of Ich Tam Khang as an adjunctive treatment of chronic heart failure.Methods: A total of 60 patients with chronic congestive heart failure were enrolled in this open label, cross-sectional and prospective study. All patients were treated with a conventional regimen (digoxin, diuretics, angiotensin-converting-enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers) for at least 4 weeks before being divided into two equal groups. In the treated patients with ITK, patients received conventional therapy plus 4 tablets ITK per day added in two divided doses. In the control patients, all patients kept the same conventional regimen without ITK. All patients were followed up for 3 months for clinical and para-clinical outcomes.Result: The symptoms of heart failure (dyspnea, palpitation, peripheral edema, neck vein distention, heptojugular reflex) decreased. Heart rate and blood pressure stabilized during treatment in the treated patients with ITK. Additionally, total cholesterol and HDL-cholesterol normalized in the patients treated with ITK. Most of echocardiography parameters in the ITK treated patients were superior to the control patients. ITK is safe and it has no side effects.Conclusion: ITK as a combination of herbal and nutritional preparation is effective in reducing heart failure symptoms, improving patient's quality of life for the patients with decompensated heart failure and reducing total cholesterol and LDL-C

Promoting skills-based education in the 21st century: A dataset of Vietnamese secondary students

As the world has become more digitally interconnected than ever before in the 21stcentury, the next generation is required to possess various sets of new skills to succeed in their works and lives. The purpose of the article is to present a dataset of socio-demographic, in-school, out-of-school factors as well as the eight domains of 21st-century skills of Vietnamese secondary school students. A total of 1183 observations from 30 secondary schools in both rural and urban areas of Vietnam are introduced in this dataset. The linear regression analysis was also utilized as an analysis example for this dataset. The insights generated from the dataset are hoped to contribute to skills-based education and policy planning in Vietnam

Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis

The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD). The influence of apoE on amyloid β (Aβ) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with Aβ and facilitates Aβ fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-Aβ antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1ΔE9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60–80% and significantly reduced insoluble Aβ40 and Aβ42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around Aβ plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in Aβ binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases

In vitro and in vivo evaluation of a single chain antibody fragment generated in planta with potent rabies neutralisation activity.

Rabies causes more than 60,000 human deaths annually in areas where the virus is endemic. Importantly, rabies is one of the few pathogens for which there is no treatment following the onset of clinical disease with the outcome of infection being death in almost 100% of cases. Whilst vaccination, and the combination of vaccine and rabies immunoglobulin treatment for post-exposure administration are available, no tools have been identified that can reduce or prevent rabies virus replication once clinical disease has initiated. The search for effective antiviral molecules to treat those that have already developed clinical disease associated with rabies virus infection is considered one of the most important goals in rabies research. The current study assesses a single chain antibody molecule (ScFv) based on a monoclonal antibody that potently neutralises rabies in vitro as a potential therapeutic candidate. The recombinant ScFv was generated in Nicotiana benthamiana by transient expression, and was chemically conjugated (ScFv/RVG) to a 29 amino acid peptide, specific for nicotinic acetylcholine receptor (nAchR) binding in the CNS. This conjugated molecule was able to bind nAchR in vitro and enter neuronal cells more efficiently than ScFv. The ability of the ScFv/RVG to neutralise virus in vivo was assessed using a staggered administration where the molecule was inoculated either four hours before, two days after or four days after infection. The ScFv/RVG conjugate was evaluated in direct comparison with HRIG and a potential antiviral molecule, Favipiravir (also known as T-705) to indicate whether there was greater bioavailability of the ScFv in the brains of treated mice. The study indicated that the approach taken with the ScFv/RVG conjugate may have utility in the design and implementation of novel tools targetting rabies virus infection in the brain

Association of plasma and cortical beta-amyloid is modulated by APOE ε4 status.

Background: APOE ε4’s role as a modulator of the relationship between soluble plasma beta-amyloid (Aβ) and fibrillar brain Aβ measured by Pittsburgh Compound-B positron emission tomography ([11C]PiB PET) has not been assessed. Methods: Ninety-six Alzheimer’s Disease Neuroimaging Initiative participants with [11C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at time of scan were included. Regional and voxel-wise analyses of [11C]PiB data were used to determine the influence of APOE ε4 on association of plasma Aβ1-40, Aβ1-42, and Aβ1-40/Aβ1-42 with [11C]PiB uptake. Results: In APOE ε4− but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [11C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [11C]PiB binding compared to using APOE and plasma Aβ1-40/Aβ1-42 as separate terms. Conclusions: The results suggest that plasma Aβ is a potential Alzheimer’s disease biomarker and highlight the importance of genetic variation in interpretation of plasma Aβ levels