Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the function of CLU in Alzheimer's Disease in in vitro and in vivo models

Alzheimer’s disease (AD) is a neurodegenerative disease that is responsible for 50-80% of dementia cases and is characterised by lack of visuospatial perception, impairment of language and memory. One of the main physiological attributions towards this disease is the accumulation of large insoluble deposits of amyloid beta, a toxic peptide, which results in the generation of amyloid plaques found in between neurons in the brain. Currently no therapeutic treatments are available. Clusterin (CLU) is an apolipoprotein that when defective is the second highest genetic risk factor for AD. It has been strongly debated whether CLU counteracts or promotes AD pathology. With the roles of CLU including but not limited to acting as a chaperone for cholesterol transport and aiding autophagy functionality in cancer models, this thesis investigates these two specific functionalities by overexpressing CLU in an in vitro SH-SY5Y and in an in vivo AD model of Drosophila melanogaster (fruit fly). Conclusions from this study reveal that within D. melanogaster, CLU reduced Aβ42 levels and increased cholesterol effect through the blood brain barrier. Additionally, in human cells, CLU ameliorated the defective flux in autophagy. This thesis sheds light into how CLU plays a protective role within an Alzheimer’s disease mammalian system.
Mitochondrial structure and distribution in Saccharomyces cerevisiae

Mitochondria play diverse roles in the physiology and metabolism of eukaryotic cells. Like most membrane bounded organelles, they cannot be synthesized de novo but grow and split into distinct organelles and must be inherited to daughter cells upon cell division. The structure of the highly dynamic mitochondrial network is adjusted to fit cellular needs by orchestrating mitochondrial movement, fusion, and fission. All three processes are important for the maintenance of functional mitochondria. The core components of the transport, fusion, and division machineries have been identified in baker’s yeast. However, the mechanisms controlling mitochondrial dynamics remain poorly understood. The synoptic aim of this work was to characterize the molecular function of three genes that are involved in maintaining structural integrity of mitochondria: NUM1, MDM33, and UPS1. Yeast cells lacking NUM1 or MDM33 show defects in mitochondrial fission, whereas UPS1 has been reported to be involved in mitochondrial fusion and the biosynthesis of the mitochondrial signature lipid cardiolipin. This work assigns a specific process to each of the three genes and provides evidence how these processes influence mitochondrial behavior. In summary, this study elucidates how various processes influence the fusion and fission of a double membrane bounded organelle. First, Num1 was identified as key component of a tethering complex that anchors mitochondria at the mother cell cortex. The tethering complex serves to counteract bud-directed mitochondrial movement and assures that a part of the mitochondria remains in the mother cell upon cell division. It acts antagonistically to a known mitochondrial anchor containing Mmr1 at the tip of the daughter cell. Thus, Num1 in the mother and Mmr1 in the bud form two separate cortical tethers to ensure proper distribution of mitochondria by generating opposing forces at spatially distinct and exclusive locations. Strikingly, the tethering of mitochondria at the mother cell cortex was identified as a prerequisite for efficient mitochondrial division. Second, it was shown that Mdm33 orchestrates mitochondrial fission and phospholipid biosynthesis. Genetic analysis revealed a tight association of MDM33 and genes affecting mitochondrial phospholipid metabolism. Consistently, Mdm33 overexpression alters mitochondrial lipid composition and directly influences mitochondrial phospholipid biosynthesis. Mutants lacking Mdm33 show reduced mitochondrial fission activity, indicating that Mdm33 promotes mitochondrial division but is no essential component of the fission machinery. Furthermore, Mdm33 was found to act upstream of mitochondrial fission and fusion and to be required to keep mitochondria in a fission competent shape. The results suggest an intriguing connection between mitochondrial fission and phospholipid homeostasis. Third, it was investigated by electron microscopy whether cells lacking Ups1 or other cardiolipin biosynthesis factors show aberrant mitochondrial ultrastructure. Intriguingly, reduction…
Defining Arabidopsis NPR1 orthologues in crops for translational plant immunity

Abstract Arabidopsis has been the model dicot plant system to study a variety of processes including immunity. One type of immunity, termed systemic acquired resistance (SAR), is deployed upon detection of avirulent pathogens by a plant. SAR deployment is dependent on the small molecule salicylic acid (SA) and confers immunity against a broad range of biotrophic pathogens. In this process, SA is perceived by NPR1, a key transcriptional co-activator. Recruitment of SA by NPR1 leads to changes in the conformation of NPR1, which frees a C-terminal transactivation domain from the auto-inhibitory effect of the N-terminal BTB/POZ domain. During this unfolding process, NPR1 is itself recruited by TGA2 and together they form an enhanceosome capable of activating downstream genes, including the SAR marker gene PR1. NPR1 is conserved in sequence and function in both dicot and monocot species. As such, it is portable from one plant species to another. In Arabidopsis, NPR1 is part of a multigene family containing six members, labelled NPR1 to NPR6, which show no redundancy with respect to NPR1 function in immunity. Arabidopsis NPR1 and NPR2 share 63% amino acid sequence identity and yet NPR2 is not a functional NPR1 with respect to immune functions. When looking across plant species, the per cent amino acid identity between Arabidopsis NPR1 and potential NPR1 orthologues tends to be below the 63% shared between NPR1 and NPR2. In this paper, we will show that relying on sequence identity alone to identify NPR1 orthologues can be misleading.
The Composition and Function of Surface-Active Lipids in the Goldfish Swim Bladder

Goldfish (Carassius auratus: Cyprinidae) have a two-chambered swim bladder. The anterior chamber is thick walled, undergoes small volume changes, does not empty itself of gas, and assists in hearing. The posterior chamber is thin walled, undergoes extensive volume change that often results in bladder collapse, and controls animal buoyancy. Both chambers possess relatively thick inner lipid linings that differ in composition. The anterior-chamber lipids are rich in cholesterol and phospholipids, particularly in disaturated phospholipids. Posterior-chamber lipids are exceptionally rich in cholesterol but not in saturated phospholipid. Lipids from both chambers lower surface tension below that of water but are not more surface active than a cell membrane preparation. This study demonstrates a new technique for determining the role of the lipids in bladder inflation and compliance. The pressure required to initiate the inflation of a collapsed bladder (termed "opening pressure") increased after lipids were removed from the posterior chamber but not after they were removed from the anterior chamber. Posterior-chamber lipids act as an antiglue for collapsed bladders by preventing the folded inner surfaces from adhering. Anterior-chamber lipids did not act as an antiglue, and their function remains unknown.
Deficiency mapping and correlation of the genetic and physical maps in the unc-22(IV) region of Caenorhabditis elegans

In this thesis, the physical arrangement of genes in the unc-22(ZV) region of the nematode Caenorhabditis elegans was studied using the methods of deficiency mapping and germline transformation rescue. In Part 1, I describe the isolation and characterization of 22 deficiencies affecting the unc-22 gene. These deficiencies were recovered following treatment with formaldehyde or 254-nm ultraviolet light. The extents of these deficiencies were determined by either standard complementation tests, or, in the case of two of the deficiencies, by a polymerase chain reaction based method. This analysis has resulted in the unambiguous placement of eight genes on the genetic map, and shown that of eight genes which have thus far been molecularly identified in the let-56 unc-22 interval, at least five and as many as seven are not required for viability under laboratory conditions. Analysis of the breakpoints of the 22 new deficiencies, and of 15 previously identified unc-22 deficiencies, indicate that the unc-22 let-52 interval is a hot spot for unc-22 deficiency breakpoints. In Part 2, I describe the systematic correlation of the genetic and physical maps immediately to the right of the unc-22 gene. This was accomplished by the technique of germline transformation using cosmid clones from the physical map. Three genetic loci, let-52,let-661 and let-93, were positioned on the physical map using this procedure. Analysis of these data indicates an average of one essential gene per every two cosrnids in the region immediately to the right of the unc-22 gene, and suggests that the clustering of deficiency breakpoints between unc-22 and let-52 is not due to a large physical distance separating the two loci.
Sanitizer Efficacy Against Attached Bacteria in a Milk Biofilm.

Pseudomonas fluorescens , Yersinia enterocolitica , and Listeria monocytogenes were shown to readily attach to both rubber and Teflon® surfaces. Sanitizer efficacy testing done in the laboratory with nonadherent bacteria could lead to false assumptions as to the sanitizer's true effectiveness under processing conditions where cells may be attached. The objectives in this study were: (a) evaluate the efficacy of in-use concentrations of sanitizers on bacteria attached to gasket materials, (b) compare bacterial attachment to rubber and Teflon® gaskets, (c) examine different methods of enumeration, and (d) compare sanitizer efficacy on attached and suspended bacteria. The goal reduction for all of the sanitizers tested was ≥3 log cycles or 99.9%. Results indicated that iodophor, hypochlorite, acid anionic, peroxyacetic acid, fatty acid, and quaternary ammonium sanitizers failed to provide an adequate reduction in the numbers of attached bacteria at levels of 104 to 105/mm2 in most cases. The test organisms attached in slightly higher numbers to the rubber surface versus Teflon®. Plate counts, impedance microbiology, and the direct epifluorescent filter technique were tested as methods of enumeration. Impedance microbiology was the best method of enumeration, since it allowed the estimation of both reversibly and irreversibly attached bacteria. The efficacy of sanitizers versus a bacterial suspensions resulted in a ≥ 5 log-cycle reduction. The same concentrations were relatively ineffective against the attached bacteria. The goal reduction was reached on the Teflon® surface with the iodophor, hypochlorite, and fatty acid sanitizers with a log-cycle reduction in the number of Yersinia enterocolitica of 3.09, 3.19, and 3.31, respectively. Pseudomonas fluorescens was reduced by 3.16 on both the rubber and Teflon® surfaces when exposed to the hypochlorite sanitizer.
Extraction and analysis of ancient DNA from human remains of Masjede Kabood burial site

Extraction and analysis of DNA from ancient remains has numerous applications in archeology and molecular evolution. However, it has become obvious that ancient DNA (aDNA) can be easily contaminated with modern DNA, so it is crucial to detect contamination and to distinguish contaminant from authentic results. In the present study, we report the successful extraction and amplification of aDNA from 3000-3500 yearold human remains excavated from Masjede kabood (Tabriz, North-West of Iran) burial site. To test the authenticity of the extracted aDNA, we have developed a nested PCR/restriction enzyme digestion method for molecular sex determination of the skeletal remains, which their gender was known based on their morphology and belongings (Crown, Sword, Bracelet etc.). A simple and effective modified ethanol precipitation-based protocol was used for DNA extraction from 35 human skeletal remains. A segment of Homologous Amelogenin Gene (AMG), which has different alleles on X and Y-chromosomes, was amplified and analyzed. The obtained data were compared with anthropometric reports as a control for the rate of precision in aDNA analysis. The results showed that reliable aDNA can be extracted and amplified from archeological remains. The presented sex determination procedure could also be used as a reliable control for testing the authenticity of aDNA results.
The BioPAX community standard for pathway

Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery.
Design, synthesis and anti-diabetic activity of some novel xanthone derivatives targeting ?-glucosidase

Twenty eight xanthone derivatives were designed and docked into the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM) by considering Miglitol as standard drug. Most of the molecules showed excellent docking scores and docking interaction as compared to the binding cavity of the standard molecule. The five best scoring ligands were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were screened for the in vivo antidiabetic activity in streptozotocin (STZ) induced diabetic animal model in Wistar rats. Compound P4 showed the most prominent inhibition among others. The synthesized compounds reported significant (p< 0.01) effect of lowering glucose levels in the blood compared to miglitol as a standard ? -glucosidase inhibitor. Video Clips of Methodology: Synthesis of hydroxyxanthones: 7 min 2 sec Full Screen Alternate Induction of diabetes: 1 min 39 sec Full Screen Alternate
A Python Script for Aligning the STIS Echelle Blaze Function

Accurate flux calibration for the STIS echelle modes is heavily dependent on the proper alignment of the blaze function for each spectral order. However, due to changes in the instrument alignment over time and between exposures, the blaze function can shift in wavelength. This may result in flux calibration inconsistencies of up to 10%. We present the stisblazefix Python module as a tool for STIS users to correct their echelle spectra. The stisblazefix module assumes that the error in the blaze alignment is a linear function of spectral order, and finds the set of shifts that minimizes the flux inconsistencies in the overlap between spectral orders. We discuss the uses and limitations of this tool, and show that its use can provide significant improvements to the default pipeline flux calibration for many observations.
Paraphaeosphaeria schoenoplecti sp. nov. from senescent culms of Schoenoplectus litoralis in Hong Kong

Paraphaeosphaeria schoenoplecti sp. novo is described and illustrated, based on collections of senescent Schoenoplectus litoralis from Hong Kong. Ascospores are 3-celled, with the central cell markedly shorter than the two end cells. The ascospores are comparatively longer than those of all other species in the genus with 3-celled ascospores and these are surrounded by a wide spreading mucilaginous sheath. Paraphaeosphaeria schoenoplecti is compared with P. concentrica, P. michotii, and P. microspora, which also consistently possess 3-celled ascospores.
Temperature variability and thermal performance in ectotherms: acclimation, behaviour, and experimental considerations

Background: Among the predictions of the effect of future climate change, the impact of thermal conditions at local levels on the performance of individuals and their acclimation capacities is key to understanding animals’ responses to global warming. Woodlice (the terrestrial isopod Porcellio laevis) exhibit a readily observed behaviour that may reflect their acclimation capacities. When they find themselves on their back, they sometimes roll over (i.e. right themselves). Whether they do, and how fast they do it, are measures of their behaviour and performance that vary with ambient temperature. Goal: Measure experimentally the effect of acclimation to environmental thermal variability on the rollover behaviour of Porcellio laevis. Methods: Maintain woodlice in 24 C laboratory environments. Each individual lived in one of three thermal treatments: constant temperature regime (δ = 0); a regime with alternating temperatures of 27 C during daytime and 21 C at night (δ = 3); and a regime with alternating temperatures of 32 C during daytime and 16 C at night (δ = 8). After 3 months, measure the rollover behaviour (percentage that rolled over) and rollover speed of the woodlice at 5, 15, 25, 32, and 38 C. Rollover speed is the inverse of the time it took an individual to right itself. Results: At 5 and 38 C, most woodlice seemed to be in thermal coma and had very slow rollover speed. At 15, 25, and 32 C, rollover speed was in the range 0.12–0.18 rollovers per second. At 15, 25, and 32 C, 52% of individuals righted themselves in ∼4 s. At these temperatures, most individuals either rolled quickly or remained inactive for the entire 10-min test period. When we examined rollover speed in the cooler (night) and warmer (daytime) periods, individuals subjected to the three regimes of temperature variation differed: woodlice acclimated to δ = 8 roll over very fast when temperature (T ) is low and very slowly when T is high; woodlice acclimated to δ = 3 roll over fairly fast when T is low and somewhat slowly when T is high; and woodlice acclimated to δ = 0 roll over quite quickly when T is low and quite Correspondence: F. Bozinovic, Departamento de Ecología, Pontificia Universidad Católica de Chile, Santiago 6513677, Chile. e-mail: fbozinovic@bio.puc. cl Consult the copyright statement on the inside front cover for non-commercial copying policies. Evolutionary Ecology Research, 2016, 17: 111–124 © 2016 Francisco Bozinovic slowly when T is high. However, the higher and lower speeds at different regimes neutralized each other so that average rollover speed over the course of a whole day did not depend on the size of the daily fluctuation. Conclusions: The impact of temperature variability must be taken into consideration. Behavioural responses that are seemingly costly in the very short term may be beneficial in the
Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening.

Abstract A new model was developed to study endothelial regeneration and the effects of endothelial denudation in large arteries. Complete endothelial loss was produced in a sharply defined, unbranched segment of the rat common carotid artery by brief drying with a gentle stream of air along the lumen of the vessel. Platelets became attached to the denuded surface, but no polymorphonuclear or mononuclear leukocytic adherence or infiltration was observed. Regeneration occurred by the ingrowth, from each end of the denuded segment, of sheets of rapidly dividing endothelial cells. Endothelial replacement was complete by 7 to 10 days after drying. It was also noted that, by 14 days after drying, a striking myointimal thickening developed in the central region of the denuded segment. This central region was the last area to be covered with new endothelium; while still denuded, the region showed edema and signs of cellular proliferation in the innermost medial layer. The myointimal thickening consisted of smooth muscle-like cells in a fibroelastic stroma in the deeper zones, and a layer of rounded, relatively undifferentiated cells in the superficial zones. Progressive regression and condensation of the thickening was observed between 14 days and 3 months. In this model, the clear demarcation and completeness of endothelial denudation in the arterial segment allow study of the over-all process of endothelial replacement, avoiding the confusion imposed by islands of residual endothelium or contributions from branch vessels. The results suggest that the new endothelium in this situation is derived from each end of the segment. In addition, because the method of inducing denudation does not cause significant damage to the underlying media (as shown by the absence of inflammatory cell attachment or infiltration), the model offers a unique opportunity to study the relationship between endothelial loss and changes in the vessel wall. The correlation between the duration of endothelial denudation and the extent of myointimal thickening suggests that sustained insudation of certain, as yet undefined, factors from the lumen may provoke cellular proliferation in the arterial wall. Further investigation of this model should provide information relevant to the pathogenesis of the fibromuscular thickenings of human atherosclerosis.
EVALUATION OF INVITRO ANTIOXIDANT POTENTIAL OF THE TOTAL CRUDE ALKALOID EXTRACT OF GLYCOSMIS PENTAPHYLLA (RETZ.) CORREA LEAVES

Objective: The present investigation was undertaken to appraise the antioxidant properties and the total crude alkaloid extract of Glycosmis pentaphylla leaves. Methods: Radical attenuating abilities of total crude alkaloid extract were ascertained by six in vitro assays such as 2, 2-diphenyl 1-picryl hydrazyl (DPPH · ) radical scavenging assay, ferric reducing antioxidant power assay (FRAP), 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) radical scavenging assay, nitric oxide (NO) scavenging assay, hydroxyl radical (OH · ) scavenging assay, and reducing power capacity assessment. Results: The total crude alkaloid extract showed a considerable antioxidant potentiality in comparison with the standards as evidenced by the IC 50 values obtained in the DPPH · (966.93 µg/ml), FRAP (510.81 µg/ml), ABTS•+(400.47 µg/ml), OH · (1805.28 µg/ml), NO (1426.50 µg/ml). In the reducing power assay, the total crude alkaloid extract showed a concentration dependent reducing power potential. Conclusion: These results suggest the potential of Glycosmis pentaphylla as a curative against free-radical-associated oxidative damage diseases. Keywords: Glycosmis pentaphylla, Antioxidant assay, Total crude alkaloid, IC 50
The Growth and Food Ration of Piscivorous Brown Trout (Salmo trutta)

1. In this study we examined how temperature, a major determinant of energy budgets and thus the biological success of ectothermal animals, affects growth and feeding rate of a teleost fish species. 2. Feeding experiments with piscivorous brown trout from the Norwegian River Laerdalselva were performed in the laboratory at water temperatures from 8 to 18°C, to estimate the optimal temperature for growth fed at maximum rations. 3. Optimal temperature for growth was found to be approximately 16°C, which is 2-4 °C higher than reported previously. 4. In contrast to earlier studies, the optimal temperature for growth was similar to the temperature at which maximum feeding rates occurred. 5. Growth increased more rapidly with increasing temperature for small and young fish than for large and old fish