Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

Alzheimer disease is the most common cause of dementia among the elderly, accounting for ∼60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing β-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease—that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble β-amyloid oligomers in disease pathogenesis, as well as of the relationship between β-amyloid and Tau pathologies

Pemilihan Level Kinerja Struktur Pada Bangunan Sistem Rangka Pemikul Momen Yang Direncanakan Secara Direct Displacement-based Design Studi Kasus : Bangunan Beraturan Dengan Bentang Tidak Seragam

Sesuai dengan konsep Performance Based Design, Direct Displacement-Based Design (DDBD) memberikan opsi bagi perencana untuk memilih level kinerja struktur yang dikehendaki. Penelitian ini mengeksplorasi ketiga opsi desain yang dapat dipilih dalam DDBD, yaitu Level 1-No Damage, Level 2-Repairable Damage, dan Level 3-No Collapse pada tiga level gempa yang berbeda sesuai DDBD Model Code. Bangunan perkantoran dari struktur beton bertulang dengan bentang tidak seragam diambil sebagai studi kasus. Struktur direncanakan sebagai sistem rangka pemikul momen pada daerah beresiko gempa rendah dan tinggi di Indonesia. Dari ketiga level desain yang dilakukan, ternyata desain Level 2 dipandang sebagai opsi terbaik ditinjau dari kriteria efisiensi dan level kerusakan yang masih dapat ditoleransi. Hasil desain tersebut diuji kinerjanya menggunakan analisis dinamis riwayat waktu nonlinier. Untuk parameter drift, bangunan menunjukkan kinerja yang memuaskan untuk semua level gempa. Namun pada level gempa kecil dan sedang, terjadi pelelehan kolom pada lokasi yang tidak semestinya sehingga beam side sway mechanism tidak terjadi dengan sempurna. Meskipun demikian, upaya capacity design mampu menjamin terjadinya kondisi strong column weak beam

Variability of M giant stars based on Kepler photometry: general characteristics

M giants are among the longest period pulsating stars which is why their studies were traditionally restricted to analyses of low-precision visual observations, and, more recently, accurate ground-based data. Here we present an overview of M giant variability on a wide range of time-scales (hours to years), based on the analysis of 13 quarters of Kepler long-cadence observations (one point per every 29.4 min), with a total time-span of over 1000 d. About two-thirds of the sample stars have been selected from the All Sky Automated Survey (ASAS)-North survey of the Kepler field, with the rest supplemented from a randomly chosen M giant control sample. We first describe the correction of the light curves from different quarters, which was found to be essential. We use Fourier analysis to calculate multiple frequencies for all stars in the sample. Over 50 stars show a relatively strong signal with a period equal to the Kepler-year and a characteristic phase dependence across the whole field of view. We interpret this as a so far unidentified systematic effect in the Kepler data. We discuss the presence of regular patterns in the distribution of multiple periodicities and amplitudes. In the period-amplitude plane we find that it is possible to distinguish between solar-like oscillations and larger amplitude pulsations which are characteristic for Mira/semiregular stars. This may indicate the region of the transition between two types of oscillations as we move upward along the giant branch

Kontribusi Ibu Rumah Tangga Sebagai Pemulung Sampah Dalam Meningkatkan Ekonomi Keluarga ( Di Tpa Kelurahan Sumompo Kecamatan Tuminting)

Metode penelitian yang di gunakan dalam penelitian ini adalah metode penelitian kualitatif. Dengan memanfaatkan informan sebagai sumber data penelitian. Lokasi penelitian ini adalah tempat pembuangan akhir Kelurahan Sumompo Kecamatan Tuminting Kota Manado. Hasil Penelitian adalah: (1) Latar belakang kehidupan sosial pemulung di kelurahan sumompo lingkungan III adalah yang paling banyak menjadi pemulung adalah kaum perempuan atau para ibu-ibu rumah tangga yang kodisi ekonominya dalam keluarganya lemah sehingga membuat mereka menjadi seorang pemulung. Pekerjaan sebagai pemulung bukan menjadi pilihan utama bagi mereka, dan hampir setiap hari waktu mereka hanya dihabiskan ditempat pembuangan sampah. (2)Faktor yang menyebabkan mereka ibu rumah tangga berprofesi sebagai pemulung di TPA dikelurahan sumompo yaitu karena faktor ekonomi yang pada umunya karena pekerjaan suami mereka yang tidak tetap dan pendapatan suami tidak dapat mencukupi kebutuhan dalam keluarga karena sebagian besar dari mereka suaminya hanya bekerja sebaga buruh sampah, sehingga tingkat ekonomi mereka lemah dan menyebakan mereka bekerja sehingga mereka mampu untuk memenuhi kebutuhan dan kehidupan mereka dan salah satu pekerjaan yang dapat mereka lakukan adalah menjadi pemulung, hal ini juga didukung oleh adanya TPA yang dekat dengan tempat tinggal mereka. Faktor keterbatasan sumber daya manusia (SDM) yang sangat diperlukan karena salah satu yang dihadapi oleh masyrakat pemulung adalah SDM yang rendah karena tingkat pendidikan mereka pada umumnya hanya sampai sekolah dasar sehingga para ibu-ibu rumah tangga terpaksa menjadi seorang pemulung agar dapat memberi kontribusi didalam keluarga mereka dengan bekerja menjadi pemulung sampah agar dapat membantu meningkatkan ekonomi dalam keluarga mereka

Enriquecimento ambiental como estratégia para promover a neurogênese na doença de Alzheimer: possível participação da fosfolipase A2

BACKGROUND: With the discovery that constitutive neurogenesis persists in the adult brain, has emerged the hypothesis in the literature that Alzheimer disease (AD) could be overcome, or at least ameliorated, since the generation of new neurons might help to compensate for the loss of neurons in the disease. OBJECTIVES: In this work the literature on endogenous neurogenesis in the brain of subjects with AD and animal models of AD, the effects of cognitive activity on neurogenesis, and the relationship between the enzyme phospholipase A2 (PLA2) and neurogenesis was reviewed. METHODS: MedLine database was searched using the keywords Alzheimer disease, cognitive activity, phospholipase A2, neurogenesis, and neuritogenesis. RESULTS: The literature review evidenced increased neuroproliferation in AD brain, however, the new neurons fail to differentiate into mature neurons. A non-pharmacological strategy, enriched environment, increases neurogenesis (including neuronal maturation) in experimental animals. Relationship between PLA2 and neurogenesis has been demonstrated in in vitro and in vivo experimental models. DISCUSSION: The data indicate that environmental enrichment (with cognitive and physical stimulations) might be a suitable strategy to promote endogenous neurogenesis in AD, and suggest the participation of PLA2 in the neurogenesis promoted by cognitive stimulation.CONTEXTO: Com a descoberta de que a neurogênese constitutiva persiste no cérebro adulto, surgiu a hipótese na literatura de que a doença de Alzheimer (DA) poderia ser superada, ou pelo menos melhorada, visto que a geração de novos neurônios poderia ajudar a compensar a perda de neurônios na doença. OBJETIVOS: Neste trabalho, foi revisada a literatura sobre a neurogênese endógena no cérebro de sujeitos com DA e modelos animais de DA, os efeitos de atividade cognitiva sobre a neurogênese, e a relação entre a enzima fosfolipase A2 (PLA2) e a neurogênese. MÉTODOS: A base de dados MedLine foi pesquisada utilizando as palavras-chave doença de Alzheimer, atividade cognitiva, fosfolipase A2, neurogênese e neuritogênese. RESULTADOS: A revisão da literatura evidenciou neuroproliferação aumentada no cérebro com DA, no entanto, os novos neurônios falham em se diferenciar em neurônios maduros. Uma estratégia não farmacológica, ambiente enriquecido, aumenta a neurogênese (incluindo amadurecimento neuronal) em animais experimentais. Relação entre PLA2 e neurogênese tem sido demonstrada em modelos experimentais in vitro e in vivo. CONCLUSÃO: Os dados indicam que o enriquecimento ambiental (com estimulações cognitiva e física) poderia ser uma estratégia apropriada para promover a neurogênese endógena na DA e sugerem a participação da PLA2 na neurogênese promovida por estimulação cognitiva

Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission

Additional file 3: Figure S1. Contains the bootstrap re-sample statistics for comparing genetic relatedness

A Vacuum-driven Origami “Magic-ball” Soft Gripper

Soft robotics has yielded numerous examples of soft grippers that utilize compliance to achieve impressive grasping performances with great simplicity, adaptability, and robustness. Designing soft grippers with substantial grasping strength while remaining compliant and gentle is one of the most important challenges in this field. In this paper, we present a light-weight, vacuum-driven soft robotic gripper made of an origami “magic-ball” and a flexible thin membrane. We also describe the design and fabrication method to rapidly manufacture the gripper with different combinations of lowcost materials for diverse applications. Grasping experiments demonstrate that our gripper can lift a large variety of objects, including delicate foods, heavy bottles, and other miscellaneous items. The grasp force on 3D-printed objects is also characterized through mechanical load tests. The results reveal that our soft gripper can produce significant grasp force on various shapes using negative pneumatic pressure (vacuum). This new gripper holds the potential for many practical applications that require safe, strong, and simple graspingUnited States. Defense Advanced Research Projects Agency (award number FA8650-15-C-7548)National Science Foundation (U.S.) (award number 1830901)Wyss Institute for Biologically Inspired EngineeringJD.co

Uji Antagonis Cendawan Patogen Ikutan Benih Pometia pinnata, Pterocarpus indicus, Aquilaria filaria dengan Bakteri Proteus penneri dan Enterobacter hormaechei

The use of microbial antagonists is one alternative to reduce the rate of a population of pathogenic fungi. This study aims to determine the ability of an antagonist of the bacteria Proteus penneri and Enterobacter hormaechei isolated from spores Endomikoriza types Glomus sp. with fungal pathogens. The research object is a pathogenic fungus that comes from the seed Pometia pinnata, Pterocarpus indicus and Aquilaria filaria. Test antagonists using Varese et al (1996) by observing the inhibition of bacterial to fungal pathogens tested. The results showed that the percent inhibition of bacteria against fungi P. penneri follow Pometia pinnata seed of 56.11%, Pterocarpus indicus 28.70% and 30.56% Aquilaria filaria. Testing bacteria E. hormaechei generating percent inhibition of fungus P. pinnata seed followup of 18.56%, P. indicus  46.85% and  A. filaria 32.41%. Inhibition of pathogenic bacteria in the fungus P. penneri ultimate origin of P. pinnata seed and the lowest in P. indicus. Whereas inhibition of pathogenic bacteria E. hormaechei highest on fungal origin P. indicus and lowest seed in P.pinnata

A Heuristic Approach for the Design of UAV-Based Disaster Relief in Optical Metro Networks

We propose a novel algorithm to dimension the backup elements in an optical metro network, by considering the adoption of Unmanned Aerial Vehicles (UAVs) and wireless interfaces to realize backup wireless links. Our key idea is to efficiently find the set of node pairs that have to be connected by means of multi-hop UAV-based wireless links, which are selected based on the simulation of multiple disaster events. Results, obtained over a set of meaningful scenarios, demonstrate that our solution can greatly reduce the total installation costs compared to a naive approach, which is instead solely tailored to the restoration of the disrupted links in a given disaster scenario

Plasmodium Impairs Antibacterial Innate Immunity to Systemic Infections in Part Through Hemozoin-Bound Bioactive Molecules

One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through heme-oxygenase I (HO-I)-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during both acute parasitemia and up to 2 months after clearance of Py infected red blood cells that was independent of HO-I and IL-10. Py-infected mice were also susceptible to Streptococcus pneumoniae (Sp) bacteremia, a common malaria-bacteria co-infection, with higher blood and spleen bacterial burdens and decreased survival compared to naïve mice. Mechanistically, impaired immunity to Sp was independent of HO-I, but was dependent on Py-induced IL-10. Splenic phagocytes from Py infected mice exhibit an impaired ability to restrict growth of intracellular Lm, and neutrophils from Py-infected mice produce less reactive oxygen species (ROS) in response to Lm or Sp. Analysis also identified a defect in a serum component in Py-infected mice that contributes to reduced production of ROS in response to Sp. Finally, treating naïve mice with Plasmodium-derived hemozoin containing naturally bound bioactive molecules, excluding DNA, impaired clearance of Lm. Collectively, we have demonstrated that Plasmodium infection impairs host immunity to diverse bacteria, including S. pneumoniae, through multiple effects on innate immunity, and that a parasite-specific factor (Hz+bound bioactive molecules) directly contributes to Plasmodium-induced suppression of antibacterial innate immunity