Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of SPT reduces Aβ and tau hyperphosphorylation in a mouse model, a safe therapeutic strategy for Alzheimer’s disease

The contribution of the autosomal dominant mutations to the etiology of familial Alzheimer’s disease (AD) is well characterized. However, the molecular mechanisms contributing to sporadic AD are less understood. Increased ceramide levels have been evident in AD patients. We previously reported that increased ceramide levels, regulated by increased serine palmitoyltransferase (SPT), directly mediate amyloid β (Aβ) levels. Therefore, we inhibited SPT in an AD mouse model (TgCRND8) through subcutaneous administration of L-cylcoserine (LCS). The cortical Aβ42 and hyperphosphorylated tau levels were down regulated with the inhibition of SPT/ceramide. Positive correlations were observed between cortical SPT, ceramide and Aβ42 levels. With no evident toxic effects observed, inhibition of SPT could be a safe therapeutic strategy to ameliorate the AD pathology. We previously observed that miR-137, -181c, -9 and 29a/b post-transcriptionally regulate SPT levels, and the corresponding miRNA levels in the blood sera are potential diagnostic biomarkers for AD. Here, we observe a negative correlation between cortical Aβ42 and sera Aβ42, and a positive correlation between cortical miRNA levels and sera miRNA levels suggesting their potential as non-invasive diagnostic biomarkers.
DERMATOPHILUS DERMATITIS ( STREPTOTRICHOSIS ) IN ONTARIO . II . LABORATORY FINDINGS *

Kramer, T. T. (1966). Serology of bovine vibriosis-Diss. Abstr. 26, 5380 (Coll. Vet. Med., Fort Collins, Colorado). The antigenic components of a strain of Vibrio fetus var. venerealis used to vaccinate cattle against a vibriosis were studied by the c.f. , passive haemagglutination and immunodiffusion tests. The strain reacted strongly with serotype-specific rabbit antisera against V. fetus bovine type I and bovine subtype 1, with the greater specificity for subtype 1 antisera. C.f. and passive haemagglutination tests were used to detect serum and cervicovaginal mucus antibodies in heifers showing various degrees of resistance to vibriosis. The serum titres of c.f. antibody were not significantly different in six groups of heifers vaccinated with five different vaccines and a live culture. Serum antibody levels were higher in heifers resistant to vibriosis after vaccination than in those remaining susceptible after vaccination. Serum antibodies appeared to be correlated with the elimination of vibrios from the vagina and cervix. Cervicovaginal mucus antibodies were not present after vaccination. The appearance of such antibodies after challenge was irregular and could not be associated with a particular state of resistance. Reprinted from "The Veterinary Bulletin", Vol. 37, No. 2, February, 1967.
promotor in endometrial cells

To understand the mechanisms responsible for endometrium-specific expression of the uteroglobin gene, we have compared transcription from the uteroglobin promoter in a human endometrial cell line (Ishikawa) and in HeLa cells. In transient transfection experiments and in nuclear extracts, sequences from 395 to +14 of the uteroglobin gene are able to promote transcription of a reporter gene more efficiently in Ishikawa cells than in HeLa cells relative to the RSV or the SV40 early promoter. Analysis of progressive 5'-deletion mutants identifies three promoter regions, 258/ 220, -205/-177, and 96/-35, that are important for preferential transcription in endometrial cells. DNase I footprinting experiments with nuclear extracts from Ishikawa and HeLa cells reveal a series of defined protections overlapping these regions. The relative intensity of individual protections differs between the two cell lines. Oligonucleotide competition experiments suggest that similar factor(s) bind(s) to the two relevant upstream regions of the promoter that share no homology to known regulatory elements. A protection over the TATA-box is detected only with extracts from Ishikawa cells. Band shift experiments show that an Ishikawaspecific factor binds to sequences overlapping the TATA-box region that are partially conserved in other endometrium-expressed genes. We propose that novel transcription factors mediate endometrium-specific expression of the uteroglobin gene in conjunction with a tissue-specific factor that binds to the TATA-box region.
Skeletal Muscle Fibers

Cut twitch muscle fibers mounted in a triple Vaseline-gap chamber were used to study the effects of ryanodine on intramembranous charge movement, and in particular on the repriming of charge 1. Charge 1 repriming was measured either under steady-state conditions or by using a pulse protocol designed to study the time course of repriming. This protocol consisted of repolarizing the fibers to -100 mV from a holding potential of 0 mV, and then measuring the reprimed charge moving in the potential range between -40 and +20 mV. Ryanodine at a high concentration (100 ,tM) did not affect the maximum amount of movable charge 1 and charge 2, or their voltage dependence. This indicates that the alkaloid does not interact with the voltage sensor molecules. However, ryanodine did reduce the amount of reprimed charge 1 by -60% suggesting the possibility of a retrograde interaction between ryanodine receptors and voltage sensors.
Summarize the damage caused by different types of laser beams

Laser damage is becoming more and more important part to consider in design of laser systems among these decade years, for high-power lasers are widely used in industry production, medicine, signal detection, and any other departments. There are two research directions of laser damage: one is the damage caused by ultra-short pulse, the other is that caused by ultraviolet beams. These two types of laser are usually combined to irradiate materials. Laser Induced Periodic Surface Structures (LIPPS) are special phenomena which can change many physical characters of materials, for example, surface absorptivity. LIPPS are usually caused by ultra-short pulse, as a step of laser processing. This paper will reveal the damage caused by ultra-short and ultraviolet beams, especially when they lead to LIPPS.
Structural and biochemical analysis of intramembrane prenyltransferases in the UbiA superfamiIy

The UbiA superfamily is a group of intramembrane prenyltransferases that generate lipophilic compounds essential in biological membranes. These compounds, which include various quinones, hemes, chlorophylls, and vitamin E, participate in electron transport and function as antioxidants, as well as acting as structural lipids of microbial cell walls and membranes. Prenyltransferases producing these compounds are involved in important physiological processes and human diseases. These UbiA superfamily members differ significantly in their enzymatic activities and substrate selectivities. This chapter describes examples of methods that can be used to group these intramembrane enzymes, analyze their activity, and screen and crystallize homolog proteins for structure determination. Recent structures of two archaeal homologs are compared with structures of soluble prenyltransferases to show distinct mechanisms used by the UbiA superfamily to control enzymatic activity in membranes. 2. Introduction to the UbiA Superfamily The intramembrane prenyltransferases of UbiA superfamily generate the basic skeleton of a variety of lipiophilic compounds. These prenyltransferases catalyze the fusion of an isoprenyl or phytyl chain to another molecule, often an aromatic compound from the aqueous phase of cells. Addition of the aliphatic tail confers lipid solubility on these compounds, which are recruited to cell membranes and become active in various biological pathways. These lipophilic compounds play essential roles in all living organisms (Nowicka and Kruk, 2010). Ubiquinones and menaquinones function as electron carriers in the cellular respiration chain that generates ATP, and as antioxidants that protect membranes against lipid peroxidation. Prenylated hemes are cofactors of the terminal oxidases in the respiration chain that converts oxygen to water. In photosynthetic organisms, chlorophylls absorb energy from light, and plastoquinones transport electrons during photosynthesis. Vitamin E is a group of potent antioxidants that reduce cell damage in plants (Bonitz et al., 2011). Correspondence should be sent to: Weikai Li, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA, Tel: +1 314-362-8687, liw@biochem.wustl. edu. HHS Public Access Author manuscript Methods Enzymol. Author manuscript; available in PMC 2017 May 15. Published in final edited form as: Methods Enzymol. 2017 ; 584: 309–347. doi:10.1016/bs.mie. 2016.10. 032. A uhor M anscript
p75 Mediates Neurotrophin-Induced Apoptosis of Vascular Smooth Muscle Cells

Shiyang Wang,* Paula Bray, Timothy McCaffrey, Keith March, Barbara L. Hempstead, and Rosemary Kraemer* From the Departments of Pathology * and Medicine, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York; and the Krannert Institute of Cardiology ‡ and Richard L. Roudebush Veterans Administration Medical Center, Indiana University School of Medicine, Indianapolis, Indiana
A PESCA ARTESANAL NO ALTO E MÉDIO RIO ARAGUARI , AMAPÁ, BRASIL

O presente estudo teve como objetivo avaliar a atividade pesqueira no alto e médio rio Araguari, Estado do Amapá. Aplicou-se 20 questionários aos pescadores associados à Colônia Z-16, com a finalidade de identificar os apetrechos de pesca, principais espécies capturadas, locais de pesca da atividade pesqueira no período de cheia e seca. A captura por unidade de esforço (CPUE) foi estimada através de dados de 1695 mapas de pesca do ano de 2003 a 2010. As embarcações foram caracterizadas por batelão e canoa, os principais petrechos descritos pelos pescadores foram o trapo/trapão, tiradeira, a rede de emalhar, bóia, linha de mão, caniço, trapinho, zagaia e tarrafa. As principais espécies explotadas são o H. aimara T.trilobatus, A. inermis M. asterias – Myloplus sp, H. malabaricus, S. rhombeus, Cichla, Pimelodus maculatus, L. trifasciatus, C. inornata, Prosomyleus rhomboidalis, Triportheus brachipomus e C. inornata. Os ambientes de pesca foram caracterizados por remansos, varjão, baixão, poços, corredeiras e igarapés. Os maiores picos de CPUE foi no período da seca, no mês de outubro de 2005 com 105 kg/pescador-1dia. A atividade é caracterizada como pesca artesanal comercial de pequena escala praticada por pescadores interioranos, multiespecífica e multiapetrecho.
Thermodynamic and structural consequences of flexible loop deletion by circular permutation

A circularly permuted streptavidin (CP5 1/46) has been designed to remove the flexible polypeptide loop that undergoes an open to closed conformational change when biotin is bound. The original termini have been joined by a tetrapeptide linker, and four loop residues have been removed, resulting in the creation of new Nand C-termini. Isothermal titration calorimetric studies show that the association constant has been reduced approximately six orders of magnitude below that of wild-type streptavidin to lo7 M-'. The A H o of biotin association for CP51/46 is reduced by 11.1 kcal/mol. Crystal structures of CP51/46 and its biotin complex show no significant alterations in the binding site upon removal of the loop. A hydrogen bond between Ser45 and Ser52 found in the absence of biotin is broken in the closed conformation as the side-chain hydroxyl of Ser45 moves to hydrogen bond to a ureido nitrogen of biotin. This is true in both the wild-type and CP5 1/46 forms of the protein, and the hydrogen bonding interaction might thus help nucleate closure of the loop. The reduced entropic cost of binding biotin to CP51/46 is consistent with the removal of this loop and a reduction in entropic costs associated with loop closure and immobilization. The reduced enthalpic contribution to the free energy of binding is not readily explainable in terms of the molecular structure, as the binding contacts are nearly entirely conserved, and only small differences in solvent accessible surfaces are observed relative to wild-type streptavidin.
The Breast Cancer Susceptibility Gene Product (γ-Synuclein) Alters Cell Behavior through it Interaction with Phospholipase Cβ

The breast cancer susceptibility gene protein, also known as γ-synuclein, is highly expressed in human breast cancer in a stage-specific manner, with highest expression in late stage cancer. In model systems, γ-synuclein binds phospholipase Cβ2 which is regulated by Gαq to generate intracellular Ca2+ signals. PLCβ2, which is also absent in normal tissue but highly expressed in breast cancer, is additionally regulated by Rac to promote migration pathways. We have found that γ-synuclein binds to the same region of PLCβ2 as Gαq. Using cells that mimic stage 4 breast cancer (MDA MB 231), we show that down-regulation of γ-synuclein reduces the protein level of PLCβ but increases the transcript level over 40 fold. γ-Synuclein down-regulation also promotes the interaction between Gαq and PLCβ resulting in a stronger Ca2+ response to Gαq agonists. The ability of γ-synuclein to interfere with Gαq-PLCβ interactions allows more PLCβ to colocalize with Rac impacting Rac-mediated pathways that may give rise to cancerous phenotypes.
Genetic and biochemical characterization of Drosophila Snipper: A promiscuous member of the metazoan 39hExo/ERI-1 family of 39 to 59 exonucleases

The DnaQ-H family exonuclease Snipper (Snp) is a 33-kDa Drosophila melanogaster homolog of 39hExo and ERI-1, exoribonucleases implicated in the degradation of histone mRNA in mammals and in the negative regulation of RNA interference (RNAi) in Caenorhabditis elegans, respectively. In metazoans, Snp, Exod1, 39hExo, ERI-1, and the prpip nucleases define a new subclass of structure-specific 39-59 exonucleases that bind and degrade double-stranded RNA and/or DNA substrates with 39 overhangs of 2–5 nucleotides (nt) in the presence of Mg with no apparent sequence specificity. These nucleases are also capable of degrading linear substrates. Snp efficiently degrades structured RNA and DNA substrates as long as there exists a minimum 39 overhang of 2 nt to initiate degradation. We identified a Snp mutant and used it to test whether Snp plays a role in regulating histone mRNA degradation or RNAi in vivo. Snp mutant flies are viable, and display no obvious developmental abnormalities. The expression pattern and level of histone H3 mRNA in Snp mutant embryos and third instar imaginal eye discs was indistinguishable from wild type, suggesting that Snp does not play a significant role in the turnover of histone mRNA at the end of the S phase. The loss of Snp was also unable to enhance the silencing capability of two different RNAi transgenes targeting the white and yellow genes, suggesting that Snp does not negatively modulate RNAi. Therefore, Snp is a nonessential exonuclease that is not a functional ortholog of either 39hExo or ERI-1.
A Cascade-Correlation Model of Balance Scale Phenomena

The Cascade-Correlation connectionist architecture was used to model human cognitive development on balance scale problems. The simulations were characterized by gradual expansion of the training patterns, training bias in favor of equal distance problems, and test problems balanced for torque difference. Both orderly rule stages and torque difference effects were obtained. Analyses of the development of network structure revealed progressive sensitivity to distance information. It was noted that information salience effects, such as that for torque difference, are particularly difficult to capture in symbolic level models.
Does Readiness to Change Predict Reduced Crack Use in HIV Prevention?

This study examines crack cocaine (crack) use, readiness to change, and gender in a sample of 923 men and women randomized to standard HIV education (SI) or peer-delivered intervention (EI). Four levels of crack use characterized frequency of use in the past 30 days; readiness was assessed on three levels (Precontemplation, Contemplation, Preparation/Action). Differences between intervention groups on crack use and readiness by gender were examined from baseline to 3-month follow-up. Overall, participants reduced their crack use from baseline, with those in the EI showing greater improvement than those in the SI. A small proportion of participants improved readiness; those who improved were more likely to improve their crack use. No significant gender differences were found. These findings suggest that the readiness construct does not fully capture the dynamics of change among out-of-treatment crack users. Further research is needed to fully comprehend the dynamics of change among this group.
The aim of the book: studying refugees and welfare

Summer 2015. While the beaches of Greek islands received boat after boat of refugees, a large part of the space of the central station in Copenhagen was occupied by young Danish volunteers who distributed sandwiches, drinks, blankets, and second-hand clothes to crowds of people on the move, most fleeing wars in Syria and Afghanistan. Locals bought train and bus tickets so the travellers could continue their journey onwards to Sweden and beyond. Across the strait forming the Swedish–Danish border, the Sound (hereafter Öresund), in Malmö, Swedish volunteers were doing the same as their Danish counterparts. Only a few weeks later did Malmö municipality and the local branch of the Swedish Migration Agency send some of their employees to meet those who were on the move. The asylum seekers were slowly registered and accommodated by different authorities. After their encounters with police and border patrol agents, they met caseworkers from the Migration Agency, healthcare professionals for medical check-ups, employees and managers from refugee camps, schoolteachers for their children, and many more representatives of the welfare state. Those encounters were to shape and form their experiences from that point onwards. From the news reports, it became evident that the situation was more or less the same at train stations and border crossings all over Europe. Within a few weeks, however, a refugee crisis had been declared by media outlets and politicians in many countries of Europe. The crowd at the Scandinavian stations was replaced by police officers after the Swedish government implemented border controls. The Danes followed suit. From that point onwards, the trains between Copenhagen and Malmö were stopped twice on their 40-minute journey; first, at the train station next to Copenhagen international airport, and second, at the next train station across the Öresund in Sweden, Malmö Hyllie. Guards met all travellers, asking for passports and ID cards, severely delaying the trains. Fewer and fewer people in line waiting to have their papers checked were asylum seekers. The crowd soon consisted of local commuters and European travellers. Talk of the refugee Dalia Abdelhady, Nina Gren, and Martin Joormann
75kDa SirT1 Blocks TNFα-Mediated Apoptosis in Human Osteoarthritic Chondrocytes

Objective—SirT1 has been previously implicated in the regulation of human cartilage homeostasis and chondrocyte survival. Exposing human osteoarthritic chondrocytes to TNFα generates a stable and enzymatically inactive 75kDa form of SirT1 (75SirT1) via Cathepsin Bmediated cleavage. Because 75SirT1 is resistant to further degradation, we assumed it has a distinct role in osteoarthritis (OA) pathology, which we sought out to identify in this study. Methods—OA and normal human chondrocytes were analyzed for the presence of Cathepsin B and 75SirT1. Confocal imaging of SirT1 monitored its subcellular trafficking following TNFα stimulation. Co-immunofluorescent staining was carried out for Cathepsin B, mitochondrial Cox IV and Lysosome-associated membrane protein I (LAMP-I) together with SirT1. Human chondrocyte were tested for apoptosis via FACS analysis and immunoblotting for caspase 3 and 8. Human chondrocyte mitochondrial extracts were obtained and analyzed for 75SirT1/Cytochrome C association. Results—Confocal imaging and immunoblot analyses following TNFα challenge of human chondrocytes, demonstrated that 75SirT1 was exported to the cytoplasm and colocalized with the mitochondrial membrane. Consistently, immunoprecipitation and immunoblot analyses revealed that 75SirT1 is enriched in mitochondrial extracts and associates with Cytochrome C, following TNFα stimulation. Preventing nuclear export of 75SirT1 or reducing levels of FLSirT1 and 75SirT1 augmented chondrocyte apoptosis in the presence of TNFα Cathepsin B and 75SirT1 were elevated in OA vs. normal chondrocytes. Additional analyses shows that human chondrocytes exposed to OA-derived synovial fluid generate the 75SirT1 fragment. Conclusion—These data suggest that 75SirT1 promotes chondrocyte survival following exposure to proinflammatory cytokines.
Strategic Targets To induce Neovascularization By Resveratrol In Hypercholesterolemic Rat Myocardium: Role of Caveolin-1, eNOS, HO-1 and VEGF

Endothelial dysfunction and impaired angiogenesis is a hallmark of hypercholesterolemia (HC). This study was designed to examine the effects of resveratrol (R), an antioxidant with lipid lowering properties like statin, on neovascularization along with caveolar interaction with proangiogenic molecules in hypercholesterolemic (HC) rats. Animals were divided into: control (C), maintained on normal diet; rats maintained on 5% high cholesterol diet for 8 weeks (HC); & HC + R (20mg/kg) orally for 2 weeks (HCR). Myocardial infarction was induced by ligating the left anterior descending artery (LAD). Herein we examined a novel method of stimulating myocardial angiogenesis by pharmacological preconditioning with resveratrol at both capillary and arteriolar levels and the potential role of hemeoxygenase-1 (HO-1), e-NOS and Caveolin-1(Cav-1) in mediating such a response. We also investigated the functional relevance of such treatment by assessing whether the induced neovascularization can help preserve LV–contractile functional reserve in the setting of chronic hypercholesterolemic condition. Four weeks after sham surgery and LAD occlusion, rats underwent echocardiographic evaluation which revealed improvement in ejection fraction and fractional shortening in HCR compared to HC. Left ventricular tissue sections displayed increased capillary and arteriolar density in HCR compared to HC. Western blot analysis displayed downregulation of VEGF, HO-1 and increased association of Cav-1 along with eNOS in HC, preventing availability of eNOS to the system which was reversed with resveratrol treatment in HCR. This study was further validated in cardiac specific HO-1 overexpressed mice assuming molecular cross talk between the targets. Hence, our data identified potential regulators that primarily attenuate and blunt endothelial dysfunction by resveratrol therapy in hypercholesterolemic myocardium. *Address correspondence to: Nilanjana Maulik, Ph.D., FACN, FICA, Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1110, USA, Phone No: (860) 679-2857; Fax No: (860) 679-2825, Email: nmaulik@neuron.uchc. edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Free Radic Biol Med. Author manuscript; available in PMC 2009 October 1. Published in final edited form as: Free Radic Biol Med. 2008 October 1; 45(7): 1027–1034. doi:10.1016/j.freeradbiomed. 2008.07. 012. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript