Miracle-dz/UniFAR-FTUs huggingface dataset:
Circuit Analysis of Synaptic Dysfunctions in the CA3 Area of BACE1 Knockout Mice

Title of Document: CIRCUIT ANALYSIS OF SYNAPTIC DYSFUNCTIONS IN THE CA3 AREA OF BACE1 KNOCKOUT MICE Hui Wang, Ph.D, 2012 Directed By: Professor Elizabeth Quinlan Department of Biology / NACS University of Maryland Beta-amyloid precursor protein cleavaging enzyme 1 (BACE1), a major neuronal βsecretase critical for the formation of β-amyloid (Aβ) peptide, is thought to be one of the key therapeutic targets that can prevent the progression of Alzheimer’s disease (AD). Although complete ablation of BACE1 gene prevents Aβ formation, I found that at the mossy fiber projections in CA3 area of hippocampus, where BACE1 is highly expressed in normal brain, BACE1 knockout (KO) mice display reduced presynaptic function, as measured by an increase in paired-pulse facilitation ratio, and abolished mossy fiber LTP, which is very likely due to presynaptic Ca signaling abnormality. In order to determine the function of BACE1 in an intact CA3 circuit, whole-cell recordings were performed from pyramidal cells and inhibitory interneurons in the CA3 area that receive mossy fiber inputs. My analyses revealed a decrease in presynaptic release at mossy fiber synapses onto CA3 pyramidal cells of BACE1 KO mice as determined by a significantly reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and enhanced paired-pulse facilitation ratio. In contrast, BACE1 KO mice do not exhibit significant dysfunction at mossy fiber input on CA3 inhibitory interneurons. However, presynaptic function at inhibitory input on CA3 pyramidal neurons is impaired in BACE1 KOs, as seen from a reduction in paired-pulse depression of inhibitory postsynaptic responses and a significant decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Finally, to restore the deficits caused by BACE1 inhibition, I demonstrated that brief application of nicotine can improve presynaptic release and recover mossy fiber LTP in BACE1 KOs by activating α7-nAChRs, which recruits Ca induced Ca release to rescue the abnormal presynaptic Ca signaling. In summary, my studies suggest that BACE1 may play a critical role in regulating presynaptic function, especially activity-dependent strengthening of presynaptic release. The presynaptic dysfunction seen in BACE1 KOs is likely specified by the postsynaptic target, the CA3 pyramidal neurons, independent of the type of inputs. And nicotine or α7-nAChR agonists may be a potential pharmacological means to circumvent the synaptic dysfunctions caused by BACE1 inhibition. CIRCUIT ANALYSIS OF SYNAPTIC DYSFUNCTIONS IN THE CA3 AREA OF BACE1 KNOCKOUT MICE
NF-κB/Rel Participation in the Lymphokine-Dependent Proliferation of T Lymphoid Cells1

Proliferative responses of lymphoid cells to IL-2 and IL-4 depend on activation of the cells, but the mechanism(s) by which activation enhances cellular competence to respond to cytokines is not fully understood. The NF-κB/Rel family represents one signal transduction pathway induced during such activation. We show in this study that inhibition of NF-κB through the expression of an IκBα (inhibitory protein that dissociates from NF-κB) mutant refractory to signal-induced degradation (IκBα(ΔN)) interfered with the acquisition of competence to proliferate in response to IL-4 as well as IL-2. Thymocytes and T cells from IκBα(ΔN) transgenic mice expressed normal levels of IL-2R subunits. However, transgenic cells exhibited a dramatic defect in Stat5A activation treatment with IL-2, and a similar defect was observed for IL-4-induced Stat5. In contrast, T lymphoid cells with inhibition of NF-κB showed normal insulin receptor substrate-2 phosphorylation and only a modest decrease in Stat6 activation and insulin receptor substrate-1 phosphorylation after IL-4 stimulation. These results indicate that the NF-κB/Rel/IκBα system can regulate cytokine receptor capacitation through effects on the induction of downstream signaling by the Stat transcription factor family.
Carcinogenesis by Ultraviolet Light

Feel lonely? What about reading books? Book is one of the greatest friends to accompany while in your lonely time. When you have no friends and activities somewhere and sometimes, reading book can be a great choice. This is not only for spending the time, it will increase the knowledge. Of course the b=benefits to take will relate to what kind of book that you are reading. And now, we will concern you to try reading carcinogenesis by ultraviolet light as one of the reading material to finish quickly.
IDH1/2 (isocitrate dehydrogenase 1/2) Mutations in Gliomas : genotype-Phenotype Correlation, Prognostic impact, and Response to Irradiation

Since Parsons et al. (2008) found the frequent mutations of IDH1 (12%) in GBMs, various reports have studied the prevalence and characteristic of IDH1 and IDH2 mutations.The mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in nearly 40% of gliomas. The frequency of IDH1 mutations are inversely connected with grade II (~80%), III (~50%), and IV (~ 10%) gliomas. Importantly, the status of IDH1 mutations is associated with a better outcome and demonstrated a diagnostic value. We analyzed also these mutations in distribution, association with tumor-derived other genetic alterations and the diagnostic and prognostic value in a cohort of 1332 glioma patients.A synonymous single nucleotide polymorphism [SNP rs 11554137; C (cytosine) substituted by T (thymin)] has been studied in gliomas patients. The SNP rs 11554137 (in codon 105) are located in the same exon with the IDH1 R132 mutations (in codon 132). And gliomas patients with SNP rs 11554137: C>T had a poorer outcome than patients without SNP rs 11554137. This was observed a similarly adverse effect in survival in patients with AML. Mutations in codon 132 can cause a decrease of IDH1/2 activity and also gain a new enzyme function for the NADPH dependent reduction of alpha-ketoglutarate to 2-hydroxyglutarate. High 2HG and low NADPH levels might sensitize tumors to oxidative stress, potentiating response to radiotherapy, and may account for the prolonged survival of patients harboring the mutations. So we studied further the alterations of function in IDH1R132H mutant cells in vitro. Based on the decrease of defence and the increase of impairing factors in tumor cells, we found that the tumors harbouring IDH1 mutations may have an elevated radiosensitivity. In the present study, we described the impact of IDH1 mutations in gliomas and search for new perspectives for the treatment strategy.
The branched broomrape eradication program in Australia.

The Branched Broomrape Eradication Program is of substantial scale, with an annual budget of around $4m and a 20 year horizon. It is in its eighth year and will receive national and state funding for another three. The motivation for the program and its organisational background and structure are showcased as an example of a program that is making satisfactory progress.
Preclinical modelling of immune checkpoint blockade (P2012)

Harnessing the power of the immune system to identify and eliminate cancer is a promising area of development in cancer therapy. Increasing T-cell activation, in particular, is now a clinically validated approach to the treatment of cancer. Cytotoxic T lymphocyte antigen 4 (CTLA-4, CD152) and PD-L1 (B7-H1, CD274) are part of a complex system of receptors and ligands that are involved in limiting T-cell activation through the delivery of inhibitory signals. MedImmune is currently developing tremelimumab (anti-CTLA4) and MEDI4736 (anti-PD-L1), for the treatment of advanced or metastatic solid tumours. Both of these antibodies antagonise T-cell inhibition signals with the aim of enhancing anti-tumor T cell activity. We have established and characterised a panel of syngeneic mouse tumor models and employed these to explore the activity of anti-mouse CTLA-4 and PD-L1 antibodies using pharmacodynamic (PD) and tumor growth inhibition (TGI) endpoints. Published studies characterising the immunogenic nature of some existing cancer therapeutics provide reason to believe that a combination strategy, utilising checkpoint blockade together with current standard of care, or novel therapeutics, could result in increased activity. We have gone on to explore the value of such combinations in preclinical mouse models.
Biokatalytische Wege zur Darstellung funktioneller Sesquiterpene

Enzymes belonging to the class of terpene synthases catalyze the formation of flavor and fragrance compounds, also known as terpenes. Longchained isoprenoid diphosphates with varying numbers of carbon atoms, are transformed to these complex natural compounds by cyclizationand rearrangement-reactions. Three plant sesquiterpene synthases (an isoform of (-)-patchoulol synthase, an α-humulene synthase and a (+)-zizaene synthase) were successfully expressed in a soluble and active form in E. coli. To provide sufficient amounts of the enzyme substrate, farnesyl diphosphosphate, two established organic synthesis methods for the compound were evaluated. The most feasible protocol was optimized and scaled-up to a bigger lab-scale, which yielded substrate amounts in the gram-range. By use of the fusion proteins thioredoxin and an ubiquitin-derivative (SUMO), soluble yields of the synthases were significantly improved. Active enzymes were purified via peptide tags and functionally characterized extensively. Important protein parameters e. g. the isoelectric point, as well as kinetic data of the reaction, were determined. The products of each enzyme were evaluated via GC-MS and GC-FID analytical methods. Feeding the substrate to the respective purified enzymes, resulted in the formation of patchouli essential oil, α-humulene, or (+)-zizaene. All these terpenoids are valuable and complex fragrance compounds. In this context, an unknown isoform (cDNA variant) of the (-)-patchoulol synthase, with a slightly varying product spectrum, was successfully identified. By coexpression of central pathway enzymes, the terpene α-humulene was produced in vivo by a modified E. coli strains. This concept was adapted for production of the complex fragrance precursor (+)-zizaene. With this strategy, (+)-zizaene yields of over 300 mg L−1 were achieved in shake flask scale fermentations, using only glucose as a carbon source. Besides the identification and characterization of two previously undescribed sesquiterpene synthases, this work also illustrates several aspects of sustainable production of fragrance compounds by use of metabolic engineering.
KARAKTERISTIK PSEUDOMONAS VIRIDIFLAVA: PENYEBAB PENYAKIT BUSUK LUNAK DAN EVALUASI VIRULENSINYA PADA KLON ANGGREK PHALAENOPSIS

The objectives of this research were to determine the typical symptoms and isolates chararteristics of Pseudomonas viridiflava as the causal agent of soft rot bacterial disease and to find out orchid Phalaenopsis clones resistant to the disease. The scope of this study included exploration and isolation of the pathogens, pathogenicity, biochemical and LOPAT tests, also screening the Phalaenopsis F1 clones resistant to the pathogen. The results showed that isolates Vd-6, Ph-7 and Ph-18 obtained from Vanda (in Bandung Nursery) and Phalaenopsis orchids respectively, in glass house of Indonesian Ornamental Crops Research Institute, were identified as P. viridiflava and highly virulent on tested orchid plants. Typical symptoms were soft rots characterized by moist and watery decay of the whole leaves, which were initiated as small water-soaked lesions and enlarged rapidly to the entire leaves. Based on biochemical and LOPAT tests, the causal organisms were fluorescent green colonies in King’s B medium, not producing levan compound and arginine hydrolase reaction. Pectinolytic activities on potato and tobacco hypersensibility were also positive. According to evaluation test, 10 F1 accecions Phalaenopsis clones (VL 231, VL 232, VL 233, and VL 240; M22.213 and M22.223; 599.201, 599.205, 599.215 and 599.243) were resistant to that pathogen.
A Simple Rule for Pricing with Limited Knowledge of Demand

How should a firm price a new product for which little is known about demand? We propose a simple and practical pricing rule for new products where demand information is limited. The rule is simple: Set price as though the demand curve were linear. Our pricing rule can be used if three conditions hold: the firm can estimate the maximum price it can charge and still expect to sell some units, the firm need not plan in advance the quantity it will sell, and marginal cost is known and constant. We show that if the true demand curve is one of many commonly used demand functions, or even a more complex (randomly generated) function, the firm can expect its profit to be close to what it would earn if it knew the true demand curve. We derive analytical performance bounds for a variety of demand functions, calculate expected profit performance for randomly generated demand curves, and evaluate the welfare implications of our pricing rule. We show that with limited demand information (maximum price and marginal cost), our simple pricing rule can be used for new products while often achieving a near-optimal performance. We also discuss the limitations of our method by identifying cases where our pricing rule does not perform well. This paper was accepted by Joshua Gans, business strategy.
Biomarkers of cell stress and cell death detected by proton high resolution magic angle spinning (¹H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in a rat glioma cell line.

Early detection of biomarkers of tumour treatment response improves clinical management, in vivo. Magnetic resonance spectroscopy (MRS) has demonstrated potential for identifying early biomarkers of effective treatment. However, more detailed in vitro studies are required to improve our understanding and facilitate its use. The aim of this study is to determine \(^1\)H high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) biomarkers of cytostasis and cell death in a rat glioma BT4C cell line. Cytostasis and cell death were induced in BT4C cells using cisplatin and substrate free medium, respectively. Cell viability was examined by various techniques. The lipid and metabolite alterations in whole cells were investigated by \(^1\)H HR-MAS NMR. Significant alterations in lipids and metabolites were detected in response to cytostasis or necrosis. NMR lipid accumulation was associated with an increase in cytoplasmic lipid droplets seen prior to morphological and molecular markers of cell death. Significant differences were detected in individual choline containing metabolites (CCMs), emphasising the importance of identifying CCMs separately. Alterations were also detected in lactate, alanine, glycine, glutamate, and succinate levels, suggesting changes in the energy metabolism pathways which may provide novel biomarkers in vivo. \(^1\)H HR-MAS NMR reveals alterations in lipids and metabolites during cytostasis and cell death which may provide early markers of treatment efficacy.
CLIL, English teachers and the three dimensions of content

I’m a CLIL militant, and I confess that militants can be a tiresome breed spreading their educational gospel and chivvying those around them to see the light. CLIL an acronym conceived in the deep forests of Finland in 1994 and delivered to the world by an ever-expanding but largely voluntary band of teacher enthusiasts has suffered ever since for this very reason, as if its converts and sirens were so convinced of its efficacy that they really had no need to prove their point. As a consequence, the world of language teaching has often sailed by regardless, without even strapping itself to the mast. Nevertheless, beware of the CLIL sirens. They’re always around. There are tales of language teachers swimming for the shores of CLIL, to never return. Whatever happened to the poor things once they reached the shore and disappeared into the strange world of content and language, seduced by false claims of pedagogic wonders and wizardry?
Multivariate analysis based on the physicochemical characteristics of samples of honey produced by Apis mellifera L. (Hymenoptera: Apidae) from the northern coast of Bahia state, Brazil

This research was carried out to determine how honey samples are grouped based on physicochemical characteristics. A total of 36 honey samples, collected from January of 1999 to June of 2000, in the northern coast of Bahia State, were evaluated. with regard to humidity, color, protein, pH, acidity, formol index, electrical conductivity, ash, diastase number, hydroxymethylfurfural (HMF), total sugar, reducing sugars, sucrose, and types of pollen. The results indicate that HMF, reducing sugar and total sugars are the characteristics that most influenced the grouping. Two plant genera, Eucalyptus and Mimosa, were observed as predominant bee plants in the region.
Ecophysiological responses of Baltic and Atlantic Fucus vesiculosus to environmental factors

Cadmium (Cd) uptake capacities and Cd tolerance of the marine alga Fucus vesiculosus from the Irish Sea (salinity 35 psu) and from the Bothnian Sea (northern Baltic, 5 psu) were quantified. These data were complemented by measurements of changes in maximal photosynthetic rate (Pmax), dark respiration rate and variable fluorescence vs. maximal fluorescence (Fv:Fm). At concentrations between 0.01 and 1 mmol Cd l−1, F. vesiculosus from the Bothnian Sea adsorbed significantly more (about 98%) Cd compared with F. vesiculosus from the Irish Sea. The photosynthetic measurements showed that the Bothnian Sea F. vesiculosus were more sensitive to Cd exposure than the Irish Sea algae. The algae from the Irish Sea showed negative photosynthetic effects only at 1 mmol Cd l−1, which was expressed as a decreased Pmax (−12.3%) and Fv:Fm (−4.6%). On the contrary, the algae from the Bothnian Sea were negatively affected already at Cd concentrations as low at 0.1 mmol Cd l−1. They exhibited increased dark respiration (+11.1%) and decreased Fv:Fm (−13.9%). The results show that F. vesiculosus from the Bothnian Sea may be an efficient sorption substrate for Cd removal from Cd contaminated seawater and this algae type may also have applications for wastewater treatment.
Protective Effect of Vitis amurensis Stems and Leaves Extract on Hydrogen Peroxide-induced Oxidative Neuronal Cell Damage in Cultured Neurons

Vitis amurensis (VA; Vitaceae) has long been used in oriental herbal medicine. It has been reported that roots and seeds of VA have anti-inflammatory and antioxidant effects. In the present study, the protective effect of ethanol extract from stems and leaves of VA on hydrogen peroxide () (100 )-induced neuronal cell damage was examined in primary cultured rat cortical neurons. VA (10-100 /ml) concentration-dependently inhibited -induced apoptotic neuronal cell death measured by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. VA inhibited -induced elevation of intracellular concentration () and generation of reactive oxygen species (ROS), which were measured by fluorescent dyes. Pretreatment of VA also prevented glutamate release into medium induced by 100 , which was measured by HPLC. These results suggest that VA showed a neuroprotective effect on -induced neuronal cell death by interfering with -induced elevation of , glutamate release, and ROS generation. This has a significant meaning of finding a new pharmacological activity of stems and leaves of VA in the CNS.
The sugar code : fundamentals of glycosciences

CHEMICAL BASIS The Biochemical Basis and Coding Capacity of the Sugar Code (Rudiger, Gabius) Three-dimensional Aspects of the Sugar Code (Kozar, Andre, Ulicny, Gabius) The Chemist's Way to Synthesize Glycosides (Oscarson) The Chemist's Way to Prepare Multivalency (Chabre, Roy) Analytical Aspects: The Analysis of Protein-Bound Glycans (Nakagawa) NATURAL GLYCOSYLATION - GLYCOPROTEINS N-Glycosylation (Zuber, Roth) O-Glycosylation: Structural Diversity and Functions (Patsos, Corfield) Glycosylation of Model and "Lower" Organisms (Wilson, Paschinger, Rendic) Glycosylphosphatidylinositol Anchors: Structure, Biosynthesis and Functions (Shams-Eldin, Debierre-Grockiego, Schwarz) NATURAL GLYCOSYLATION - GLYCOLIPIDS, PROTEOGLYCANS, CHITIN Glycolipids (Kopitz) Proteoglycans (Buddecke) Chitin (Merzendorfer) PROTEIN-CARBOHYDRATE INTERACTIONS Protein-Carbohydrate Interactions: Basic Concepts and Methods for Analysis (Solis, Romero, Menendez, Jimenez-Barbero) How to Determine Specificity: From Lectin Profiling to Glycan Mapping and Arrays (Tateno, Kuno, Hirabayashi) The History of Lectinology (Rudiger, Gabius) Ca2+: Mastermind and Active Player for Lectin Activity (Including a Gallery of Lectin Folds) (Gabius) Bacterial and Viral Lectins (Holgersson, Gustafsson, Gaunitz) Plant Lectins (Rudiger, Gabius) Animal and Human Lectins (Gabius) Routes in Lectin Evolution: Case Study on the C-Type Lectin-Like Domains (Gready, Zelensky) Carbohydrate-Carbohydrate Interactions (Bucior, Burger, Fernandez-Busquets) BIOMEDICAL ASPECTS AND CASE STUDIES Diseases of Glycosylation (Hennet) Animal Models to Delineate Glycan Functionality (Honke, Taniguchi) Glycobiology of Fertilization and Early Embryonic Development (Habermann, Sinowatz) Glycans as Functional Markers in Malignancy? (Andre, Kopitz, Kaltner, Villalobo, Gabius) Small is Beautiful: Mini-Lectins in Host Defense (Lehrer) Inflammation and Glycosciences (Schwartz-Albiez) Sugars as Pharmaceuticals (Osborn, Turkson) Platelet Glycoproteins as Lectins in Hematology (Hoffmeister, Falet) Neurobiology meets Glycosciences (Ledeen, Wu) COMPANION WEB-SITE: www.wiley-vch.de/home/thesugarcode
Mathematical models for vector-borne disease: effects of periodic environmental variations.

Firstly, I proposed a very simple SIS/SIR model for a general vector-borne disease transmission considering constant population sizes over the season, where contact between the host and the vector responsible of the transmission is assumed to occur only during the summer of each year. I discussed two different types of threshold for pathogen persistence that I explicitly computed: a "short-term threshold" and a "long-term threshold". Later, I took into account the seasonality of the populations involved in the transmission. For a single season, the model consists of system of non linear differential equations considering the various stages of the infection transmission between the vector and the host population. Assuming the overwintering in the mosquito populations, I simulated the model for several years. Finally, I studied the spatial spread of a vector-borne disease throught an impusive reaction-diffusion model and I showed some simulations.