ROLE OF PANCREATIC AMYLIN IN ALZHEIMER’S AND BRAIN MICROVASCULAR PATHOLOGIES

Alzheimer disease (AD) and cerebral vascular disease (CVD) are common causes of impaired cognition and behavior in humans. Epidemiological studies have shown that AD and CVD development and progression associated with metabolic risk factors including type 2 diabetes (T2D). However, the underlying molecular mechanisms remain elusive, which hampers the development of treatment and prevention strategies. Research results from our laboratory and others have shown that amylin, a hormone secreted by the pancreas and involved in glucose homeostasis, induces small-vessel-type pathologies and modulates amyloid composition in both familial (genetically predisposed) and sporadic forms of AD. The results indicate amylin as a potential molecular modifier of the course of Alzheimer’s and brain microvascular pathologies. The present work provides a basis for understanding the role of pancreatic amylin in brain injury and neurologic deficits associated with aging and metabolic dysfunction. First, we used brain tissues from humans with T2D and AD, and a rat model expressing human amylin in the pancreas (the HIP rat), to test the impact of amylin dysregulation on the brain. We found that high blood levels of amylin promoted vascular accumulation of amylin leading to endothelial cell dysfunction and microvascular injury. Amylin-mediated injury of the cerebrovasculature leads to brain white matter disease and neurological dysfunction in HIP rats. Next, we sought to understand the role of amylin in the development of AD pathology and progression of the disease. Using brain tissues from humans with sporadic and familial forms of AD, AD model rats expressing human amylin (ADHIP rats) and AD model rats expressing non-amyloidogenic rat amylin, we found that high blood levels of amylin modulates AD pathology via amylin-Aβ cross-seeding in the grey matter and also contributes to non-AD molecular pathways such as injuries to small blood vessels supplying the white matter. By staining and imaging of brain amylin and Aβ, we showed that amylin accumulated in the brain parenchyma and small blood vessels, and formed mixed plaques with Aβ. Elevated plasma amylin with aging in ADHIP rats was associated with brain microvascular damage and neurological dysfunction. Based on these studies, we inferred that amyloid-forming amylin secreted by the pancreas modulates brain amyloid composition in both sporadic and familial forms of AD, and that pancreatic expression of human amylin in AD model rats accelerates behavioral deficits. Further, we tested effects of lowering peripheral amylin and the suppression of amylin secretion in AD model rats. We found that the amylin-related pathological processes are reduced by pharmacological lowering amylin deposition in brain capillaries and amylin-Aβ cross-seeding. Genetic suppression of amylin in AD model rats reduces amylin-Aβ cross-seeding and neurologic deficits. Our data show evidence for a role of pancreatic amylin in AD and cerebral microvascular pathology and suggest that drugs reducing amylin accumulation in brain capillaries or preventing amylin from interacting with Aβ-associated pathology could provide benefit in patients with AD. Therefore, targeting amylin dyshomeostasis may be an effective strategy to prevent or slow the advancement of Alzheimer and cerebrovascular disease

Diabetes-Related Amylin Dyshomeostasis: A Contributing Factor to Cerebrovascular Pathology and Dementia

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer\u27s disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical characteristics of animal models that could help to better understand molecular mechanisms underlying the increased risk of CVD and AD in patients with prediabetes or T2D

Justice Detained: The Effects of Deportation on Immigrant Families

In November 2002, driven by a growing awareness within the Asian and Pacific Islander immigrant communities that more and more people were getting deported, youth activists at AYPAL, based in Oakland, initiated a campaign to find out what was going on and what they could do about it. AYPAL found that the problem of deportation was much worse than the isolated incidents we had heard about, and it is only growing more severe. In 1996, Congress enacted the Illegal Immigration Reform and Immigrant Responsibility Act (IIRIRA), which made it a lot easier to deport immigrants, including many legal permanent residents who had lived in the United States for many years. They were considered deportable if they had committed any crime involving prison or probation time that added up to one year or more. (See "Overview of IIRIRA" section.)AYPAL's research findings:Hundreds of thousands of people are being deported every year to countries all around the world, and there was a huge increase in deportations from 1996 to 1998, coinciding with IIRIRA being implemented in April 1997.The overwhelming majority of "criminal removals" are for non-violent crimes.Deportations hurt families by potentially leaving hundreds of thousands of children who are left behind in poverty.Despite claims that immigrants are contributing to high crime rates, they are actually less likely than native-born citizens to commit crimes.Immigrants released from jail are less likely than the native born to be repeat offenders.Immigrants are being deported to countries that the US State Department deems too dangerous to travel to.Another reason besides IIRIRA for the huge increase in deportations is that many more people in general (both immigrants and native born) are being sent to prison and for longer sentences because of policy changes like "three strikes" and mandatory minimum sentencing

Effect of a point impurity on the vortex bound states in an s-wave superconductor: A self-consistent analysis

On the basis of self-consistent numerical solution of the Bogoliubov-de Gennes equations on a finite-size lattice, we study the variation of the vortex bound state when an impurity potential is added to the core of an isolated vortex line in an s-wave superconductor. The local density of states is investigated at both the core and its neighbor site. By analyzing the impurity-induced increase of the pair potential near the vortex core, we elucidate the mechanism of the vortex pinning in detail.published_or_final_versio

Electronic structure of the vortex lattice of d-, d+is-, and dx2-y2+idxy-wave superconductors

On the basis of the self-consistent Bogoliubov-de Gennes equations and a tight-binding lattice model, we investigate the quasiparticle spectrum of vortex-lattice state in pure d-, mixed d+is, and dx2-y2+idxy-wave superconductors. For a d-wave case, the local density of states (LDOS) at the vortex core shows a multipeak structure, and the positions of peaks as well as the width of splitting between peaks are sensitively dependent on both the magnetic-field strength and the orientation of the vortex lattice. For the mixed d+is- and dx2-y2+idxy-wave pairing states, we observe a double-peak structure of the local density of states at vortex center, where the two peaks are asymmetrically situated around the Fermi energy. By taking into account the matrix-element effect, the local density of states appears to be qualitatively consistent with the scanning-tunneling-microscopy experimental data.published_or_final_versio

Experimental and theoretical analyses of three-dimensional surface crack propagation

2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Genetic and phylogenetic analysis of ten Gobiidae species in China based on amplified fragment length polymorphism (AFLP) analysis

To study the genetic and phylogenetic relationship of gobioid fishes in China, the representatives of 10 gobioid fishes from 2 subfamilies in China were examined by amplified fragment length polymorphism (AFLP) analysis. We established 220 AFLP bands for 45 individuals from the 10 species, and the percentage of polymorphic bands was 100%. The percentage of polymorphic loci within species ranged from 3.61 to 58.56%. Chaeturichthys stigmatias showed the greatest percentage of polymorphic loci (58.56%), the highest Nei’s genetic diversity (0.2421 ± 0.2190) and Shannon’s information index (0.3506 ± 0.3092), while Pterogobius zacalles showed the lowest percentage polymorphic loci (3.61%), the lowest Nei’s genetic diversity (0.0150 ± 0.0778) and lowest Shannon’s information index (0.0219 ± 0.1136). The topology of UPGMA tree showed that the individuals from the same species clustered together and the 10 species formed two major clades. One clade consisted Cryptocentrus filifer, P. zacalles, Tridentiger trigonocephalus, Chaeturichthys hexanema, C. stigmatias, Acanthogobius flavimanus and Synechogobius ommaturus, and the other clade consisted Odontamblyopus rubicundus, Trypauchen vagina and Ctenotrypauchen microcephalus. The results agreed with the traditional taxonomy of the morphological characters. AFLP fingerprints were successfully used to study the phylogenetic relationship of the gobioid fishes and it identified species origins of morphologically similar taxa.Key words: Phylogenetic, amplified fragment length polymorphism (AFLP), gobiidae, Amblyopinae, gobiinae

Prediction of the functional class of metal-binding proteins from sequence derived physicochemical properties by support vector machine approach

Metal-binding proteins play important roles in structural stability, signaling, regulation, transport, immune response, metabolism control, and metal homeostasis. Because of their functional and sequence diversity, it is desirable to explore additional methods for predicting metal-binding proteins irrespective of sequence similarity. This work explores support vector machines (SVM) as such a method. SVM prediction systems were developed by using 53,333 metal-binding and 147,347 non-metal-binding proteins, and evaluated by an independent set of 31,448 metal-binding and 79,051 non-metal-binding proteins. The computed prediction accuracy is 86.3%, 81.6%, 83.5%, 94.0%, 81.2%, 85.4%, 77.6%, 90.4%, 90.9%, 74.9% and 78.1% for calcium-binding, cobalt-binding, copper-binding, iron-binding, magnesium-binding, manganese-binding, nickel-binding, potassium-binding, sodium-binding, zinc-binding, and all metal-binding proteins respectively. The accuracy for the non-member proteins of each class is 88.2%, 99.9%, 98.1%, 91.4%, 87.9%, 94.5%, 99.2%, 99.9%, 99.9%, 98.0%, and 88.0% respectively. Comparable accuracies were obtained by using a different SVM kernel function. Our method predicts 67% of the 87 metal-binding proteins non-homologous to any protein in the Swissprot database and 85.3% of the 333 proteins of known metal-binding domains as metal-binding. These suggest the usefulness of SVM for facilitating the prediction of metal-binding proteins. Our software can be accessed at the SVMProt server

The role of urban agriculture for a resilient city

Humans are simultaneously facing challenges as climate change, epidemics and scarcity of food and water. It is estimated that by 2021 over 690 million of people will face hunger; by 2050 the global population will increase up to 10 billion with 68% of the population living in urban areas. By providing 30% of self-sufficient food in 2030, urban agriculture will be a practical concept to face these challenges. The work studies the role of agricultural land as a critical part for a resilient city. Parameters related to food production are also explored. As study case, this work aims to investigate the current food security of the Ho Chi Minh city (HCMC), offering productive green solutions at different scales from land-use planning, urban design to green roofs. For a production of 6.7 kg/day of vegetables a day, the costs of are approximately $10,000 for nearly 5.6 square meters of land; this points out A-Go-Gro technology as an effective measure for vertical farming. For example, 0.18 ha of green space can produce 2 tons of vegetables per day in the Lake View settlement (district 2 in HCMC). Moreover, due to green roofs, stormwater volumes directed into the sewer system are decreased by 65% and the penetration of electromagnetic radiation is reduced by 99.4%.Loài người đang đồng thời đối mặt với những thách thức như biến đổi khí hậu, dịch bệnh, khan hiếm thực phẩm và nước. Ước tính đến năm 2021 có hơn 690 triệu người đói và đến năm 2050 dân số toàn cầu tăng lên gần 10 tỷ người, với 68% sống ở khu vực thành thị. Được sử dụng để tự cung tự cấp 30% lương thực vào năm 2030, nông nghiệp đô thị là một khái niệm hiệu quả cho những thách thức. Bài báo là nghiên cứu đất nông nghiệp như một phần quan trọng cho một thành phố có khả năng phục hồi. Các thông số liên quan đến sản xuất lương thực được nghiên cứu. Bài báo cũng tìm hiểu an ninh lương thực của thành phố Hồ Chí Minh hiện nay. Hơn nữa, bài báo đưa ra các giải pháp phủ xanh hiệu quả trên các quy mô khác từ quy hoạch sử dụng đất, thiết kế đô thị đến mái nhà xanh tại các hộ gia đình. Với chi phí 10.000 USD và gần 5,6 mét vuông đất trồng 6,7 kg rau mỗi ngày, công nghệ A-Go-Gro là một biện pháp hữu hiệu cho canh tác theo chiều dọc. Như vậy 0,18 ha không gian xanh có thể sản xuất 2 tấn rau mỗi ngày tại khu dân cư Lake View ở quận 2. Hơn nữa, bằng cách làm mái nhà xanh, nước mưa giảm đến 65% vào hệ thống cống và sự xâm nhập bức xạ điện từ giảm 99,4%

Facile Synthesis of High Quality Graphene Nanoribbons

Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres