Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental regulation of edited CYb and COIII mitochondrial mRNAs is achieved by distinct mechanisms in Trypanosoma brucei

Abstract Trypanosoma brucei is a parasitic protozoan that undergoes a complex life cycle involving insect and mammalian hosts that present dramatically different nutritional environments. Mitochondrial metabolism and gene expression are highly regulated to accommodate these environmental changes, including regulation of mRNAs that require extensive uridine insertion/deletion (U-indel) editing for their maturation. Here, we use high throughput sequencing and a method for promoting life cycle changes in vitro to assess the mechanisms and timing of developmentally regulated edited mRNA expression. We show that edited CYb mRNA is downregulated in mammalian bloodstream forms (BSF) at the level of editing initiation and/or edited mRNA stability. In contrast, edited COIII mRNAs are depleted in BSF by inhibition of editing progression. We identify cell line-specific differences in the mechanisms abrogating COIII mRNA editing, including the possible utilization of terminator gRNAs that preclude the 3′ to 5′ progression of editing. By examining the developmental timing of altered mitochondrial mRNA levels, we also reveal transcript-specific developmental checkpoints in epimastigote (EMF), metacyclic (MCF), and BSF. These studies represent the first analysis of the mechanisms governing edited mRNA levels during T. brucei development and the first to interrogate U-indel editing in EMF and MCF life cycle stages.
Security and privacy in app ecosystems

Smartphones are highly-capable mobile computing devices that have dramatically changed how people do business, interact with online services, and receive entertainment. Smartphone functionality is enhanced by an ecosystem of apps seemingly covering the entire gamut of functionality. While smartphone apps have undoubtedly provided immeasurable benefit to users, they also contribute their fair share of drawbacks, such as increases in security risks and the erosion of user privacy. In this thesis, I focus on the Android smartphone operating system, and pave the way for improving the security and privacy of its app ecosystem. Chapter 3 starts by doing a comprehensive study on how Android apps have evolved over a three-year period, both in terms of their dangerous permission usage and the vulnerabilities they contain. It uncovers a trend whereby apps are using increasing numbers of dangerous permissions over time and at the same time becoming increasingly vulnerable to attack by adversaries. By analysing the Google Play Store, Android's official app marketplace, Chapter 4 shows that many general-purpose apps can be replaced with functionallysimilar alternatives to the benefit of the user. This confirms that users still wield power to improve their own security and privacy. Chapter 5 combines this insight with real-world data from approximately 30,000 smartphones to understand the actual risk that the average user faces as a result of their use of apps, and takes an important first step in measuring the improvements that can be made. Users, however, are not always aware of the risks they face and thus Chapter 6 demonstrates the feasibility of a classification system that can transparently and unobtrusively identify and alert users to the presence of apps of concern on their devices. This classification system identifies apps from features in the network traffic they generate, without itself analysing the payload of their traffic, thus maintaining a high threshold of privacy. While the work presented in this thesis has uncovered undesirable trends in app evolution, and shows that a large fraction of users are exposed to non-trivial risk from the apps they use, in many cases there is suficient diversity in the offerings of general-purpose apps in the Google Play Store to empower users to mitigate the risks coming from the apps they use. This work takes us a step further in keeping users safe as they navigate and enjoy app ecosystems.
Assessing and Visualizing Agricultural Management Practices: A Multivariable Hands-On Approach for Education and Extension

Abstract Agroecosystems are inherently complex, and practices aimed at managing one component of the system can have unintended consequences for other components of the system. Management decisions, therefore, can be improved by assessing and understanding the multivariate nature of agricultural systems and the multifunctional character of particular agricultural management practices. The act of simultaneously assessing and evaluating multiple characteristics or functions in agriculture also can be a valuable education and extension activity, because it draws on active and experiential methods of learning and because the process effectively reveals important functions and tradeoffs associated with agroecosystems and their management. Here we introduce a tool (the spider plot) and present a case-study exercise in which we used this tool to evaluate the multiple characteristics and functions of different cover crops within a field day workshop format. We also provide examples of how this approach could be used to assess other management practices or properties of agroecosystems and communicate multivariate concepts within a weed science classroom or extension environment.
Modulating disease-relevant tau oligomeric strains by small molecules

The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant brain-derived tau oligomers (BDTOs). Herein, using well-characterized BDTOs, isolated from brain tissues of different tauopathies, including Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies, we found that curcumin derivatives modulate the aggregation state of BDTOs by reshaping them and rescue neurons from BDTO-associated toxicity. Interestingly, compound CL3 showed an effect on the aggregation pattern of BDTOs from different tauopathies, resulting in the formation of less neurotoxic larger tau aggregates with decreased hydrophobicity and seeding propensity. Our results lay the groundwork for potential investigations of the efficacy and beneficial effects of CL3 and other promising compounds for the treatment of tauopathies. Furthermore, CL3 may aid in the development of tau imaging agent for the detection of tau oligomeric strains and differential diagnosis of the tauopathies, thus enabling earlier interventions.
Estimation of piperacillin clearance with different glomerular filtration rate formulas in critically ill children

Glomerular filtration rate (GFR) is difficult to assess in critically ill children using gold standard method and alternatives are needed. This study aimed to determine the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children, using a published piperacillin pharmacokinetics (PK) population model.
Effect of Plant Derived-phenolic Extracts on Antioxidant Enzyme Activity and Mucosal Damage Caused by Indomethacin in Rats

In this study, the antiulcerogenic effect of the hdroacoholic extracts obtained from of Acacia nilotica leaves and Retama raetam seeds were investigated using indimethacin-induced ulcer model in rats. Antiulcerogenic activities of hydroacoholic extract of A. nilotica (30 mg/kg body wt.) and hydroalcoholic extract of R. raetam (25 mg /kg) were determined by comparing the negative treated only with indomethacin and positive ranitidine control group. Although the dose of the hydroacoholic extract of A. nilotica and R. raetam showed significant antiulcerogenic activity as compared to negative control, the highest activity was observed with mixed (30 mg/kg) of A. nilotica and (25 mg /kg) of R. raetam (81%). The activities of enzymes superoxide dismutase (SOD), catalase (CAT) and gluthioneS-transferase (GST) were determined in the stomach tissues of rats and compared with those of negative and positive control groups. The enzymes activities in indomethacin-adminstrated were reduced significantly SOD, CAT, GST and increased by the plants extracts and ranitidine (p < 0.05). Phytochemical investigation of A. nilotica leaves resulted in the isolation of catechin, catechin 7-O- gallate, catechin 3’-O- gallate, catechin 4’-O-gallate, catechin 7, 3’-di -O-gallate, catechin 7, -4’-di-O-gallate. Genistein 8-C-glucoside, orobol 8-C-glucoside, apigenin 8-C-glucoside, orobol, genistein and apigenin have been isolated from the aqueous alcoholic extract of R. raetam seeds. The presence of these phenolic compounds may probably explain the antiulcerogenic and antioxidant effect of the plant extracts.
Effects of probiotics and antibiotics on diversity and structure of intestinal microflora in broiler chickens

Probitics and antibiotics are all used as growth promoters in domestic animal breeding and poultry raising. In the present study, the effects of probiotics and antibiotics on structure and diversity of the intestinal microflora of broiler 817 was investigated. Ammonia and sulfured hydrogen in fecal were detected. Then the intestinal microflora was analyzed by the pour plate method and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. The results showed that the probiotics used significantly reduced the fecal emission of ammonia and sulfured hydrogen in broilers, and increased the number of lactic acid bacteria whereas antibiotics reduced it. Diversity analysis of cecal microflora by PCR-DGGE DNA fingerprinting revealed that the richness and variety of microflora in probiotics were obviously better than that in antibiotics group and control group.
A Phase I Study of Dinaciclib in Combination With MK‐2206 in Patients With Advanced Pancreatic Cancer

The combination of drugs targeting Ral and PI3K/AKT signaling has antitumor efficacy in preclinical models of pancreatic cancer. We combined dinaciclib (small molecule cyclin dependent kinase inhibitor with MK‐2206 (Akt inhibitor) in patients with previously treated/metastatic pancreatic cancer. Patients were treated with dinaciclib (6–12 mg/m2 i.v.) and MK‐2206 (60–135 mg p.o.) weekly. Tumor biopsies were performed to measure pAKT, pERK, and Ki67 at baseline and after one completed cycle (dose level 2 and beyond). Thirty‐nine patients participated in the study. The maximum tolerated doses were dinaciclib 9 mg/m2 and MK‐2206 135 mg. Treatment‐related grade 3 and 4 toxicities included neutropenia, lymphopenia, anemia, hyperglycemia, hyponatremia, and leukopenia. No objectives responses were observed. Four patients (10%) had stable disease as their best response. At the recommended dose, median survival was 2.2 months. Survival rates at 6 and 12 months were 11% and 5%, respectively. There was a nonsignificant reduction in pAKT composite scores between pretreatment and post‐treatment biopsies (mean 0.76 vs. 0.63; P = 0.635). The combination of dinaciclib and MK‐2206 was a safe regimen in patients with metastatic pancreatic cancer, although without clinical benefit, possibly due to not attaining biologically effective doses. Given the strong preclinical evidence of Ral and AKT inhibition, further studies with better tolerated agents should be considered.
Latent Murine γ-Herpesvirus Infection Is Established in Activated B Cells, Dendritic Cells, and Macrophages1

Intranasal infection of mice with the murine γ-herpesvirus MHV-68 results in an acute lytic infection in the lung, followed by the establishment of lifelong latency. Development of an infectious mononucleosis-like syndrome correlates with the establishment of latency and is characterized by splenomegaly and the appearance of activated CD8+ T cells in the peripheral blood. Interestingly, a large population of activated CD8+ T cells in the peripheral blood expresses the Vβ4+ element in their TCR. In this report we show that MHV-68 latency in the spleen after intranasal infection is harbored in three APC types: B cells, macrophages, and dendritic cells. Surprisingly, since latency has not previously been described in dendritic cells, these cells harbored the highest frequency of latent virus. Among B cells, latency was preferentially associated with activated B cells expressing the phenotype of germinal center B cells, thus formally linking the previously reported association of latency gene expression and germinal centers to germinal center B cells. Germinal center formation, however, was not required for the establishment of latency. Significantly, although three cell types were latently infected, the ability to stimulate Vβ4+CD8+ T cell hybridomas was limited to latently infected, activated B cells.
Roux-en-Y gastric bypass surgery changes fungal and bacterial microbiota in morbidly obese patients—A pilot study

The Roux-en-Y gastric bypass (RYGB) remains the most effective treatment for morbidly obese patients to lower body weight and improve glycemic control. There is recent evidence that the mycobiome (fungal microbiome) can aggravate disease severity in a number of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and hepatitis; moreover, a dysbiotic fungal microbiota has been reported in the obese. We characterized fungal and bacterial microbial composition in fecal samples of 16 morbidly obese patients before and three months after RYGB surgery and compared with nine healthy controls. We found that RYGB surgery induced a clear alteration in structure and composition of the gut fungal and bacterial microbiota. Beta diversity analysis revealed significant differences in bacterial microbiota between obese patients before surgery and healthy controls (P < 0.005) and a significant, unidirectional shift in RYGB patients after surgery (P < 0.001 vs. before surgery). In contrast, there was no significant difference in fungal microbiota between groups but individually specific changes after RYGB surgery. Interestingly, RYGB surgery induced a significant reduction in fungal alpha diversity namely Chao1, Sobs, and Shannon diversity index (P<0.05, respectively) which contrasts the trend for uniform changes in bacteria towards increased richness and diversity post-surgery. We did not observe any inter-kingdom relations in RYGB patients but in the healthy control cohort and there were several correlations between fungi and bacteria and clinical parameters (P<0.05, respectively) that warrant further research. Our study identifies changes in intestinal fungal communities in RYGB patients that are distinct to changes in the bacterial microbiota.
Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury

The gastrointestinal peptide, secretin (Sct) is an important homeostatic regulator of pancreatic and liver secretory function. With regard to the liver, discoveries have been made, in the last decades, indicating a key role for the secretin/secretin receptor axis during normal or cholestatic conditions. Since large cholangiocytes are the only cells to express secretin receptor in the liver, research on secretin also expanded our knowledge on biliary epithelia. In this review we examined in detail the role of the secretin/secretin receptor axis, not only on biliary secretion, but also on cholangiocyte proliferation and senescence, as well as in prompting fibrotic processes involving biliary epithelia. Relevant data on human chronic cholestatic liver diseases, such as primary biliary cholangitis or primary sclerosing cholangitis, and obtained in animal models mimicking the diseases or in correlative studies on human are also reported. The aim of this review is to provide an update on the progress regarding the interactions between secretin and the biliary epithelia in normal and pathological conditions, underlining the aspects that suggests modulation of secretin pathway as a possible therapeutic approach for chronic cholestatic human liver disease.
High-density lipoproteins are a potential therapeutic target for age-related macular degeneration

Strong evidence suggests that dysregulated lipid metabolism involving dysfunction of the retinal pigmented epithelium (RPE) underlies the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly. A hallmark of AMD is the overproduction of lipid- and protein-rich extracellular deposits that accumulate in the extracellular matrix (Bruch's membrane (BrM)) adjacent to the RPE. We analyzed apolipoprotein A-1 (ApoA-1)-containing lipoproteins isolated from BrM of elderly human donor eyes and found a unique proteome, distinct from high-density lipoprotein (HDL) isolated from donor plasma of the same individuals. The most striking difference is higher concentrations of ApoB and ApoE, which bind to glycosaminoglycans. We hypothesize that this interaction promotes lipoprotein deposition onto BrM glycosaminoglycans, initiating downstream effects that contribute to RPE dysfunction/death. We tested this hypothesis using two potential therapeutic strategies to alter the lipoprotein/protein profile of these extracellular deposits. First, we used short heparan sulfate oligosaccharides to remove lipoproteins already deposited in both the extracellular matrix of RPE cells and aged donor BrM tissue. Second, an ApoA-1 mimetic, 5A peptide, was demonstrated to modulate the composition and concentration of apolipoproteins secreted from primary porcine RPE cells. Significantly, in a mouse model of AMD, this 5A peptide altered the proteomic profile of circulating HDL and ameliorated some of the potentially harmful changes to the protein composition resulting from the high-fat, high-cholesterol diet in this model. Together, these results suggest that targeting HDL interactions with BrM represents a new strategy to slow AMD progression in humans.
Impaired Succinate Response to a Mixed Meal in Obesity and Type 2 Diabetes Is Normalized After Metabolic Surgery

OBJECTIVE To explore the meal response of circulating succinate in patients with obesity and type 2 diabetes undergoing bariatric surgery and to examine the role of gastrointestinal glucose sensing in succinate dynamics in healthy subjects. RESEARCH DESIGN AND METHODS Cohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4 ± 1.9 kg/m2) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3 ± 1.4 kg/m2) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4 ± 0.5 kg/m2). Cohorts I and II completed a 2-h mixed-meal tolerance test (MTT) before the intervention and at 1 year of follow-up, and cohort II also completed a 3-h lipid test (LT). Cohort III underwent a 3-h oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) study. RESULTS In cohort I, succinate response to MTT at follow-up was greater than before the intervention (P < 0.0001). This response was confirmed in cohort II with a greater increase after 1 year of surgery (P = 0.009). By contrast, LT did not elicit a succinate response. Changes in succinate response were associated with changes in the area under the curve of glucose (r = 0.417, P < 0.0001) and insulin (r = 0.204, P = 0.002). In cohort III, glycemia, per se, stimulated a plasma succinate response (P = 0.0004), but its response was greater in the OGTT (P = 0.02; OGTT versus IIGI). CONCLUSIONS The meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.
Quality of concept maps is affected by map building strategies

Concept‐maps are widely used to assess students' conceptual understanding in different subject areas. Conventionally, it is mostly built maps which are assessed. In this study, we explore if “concept‐mapping” could be used as a case for constructive alignment of both the process and the outcome of learning. Specifically, we have studied how a simple measure of looking at the order in which concept map elements‐concepts (cards, C), links (arrows, A), and linking phrases (phrases, P)‐ are placed on the working space reveals information about the quality of the final generated map. We report findings from analysis of the concept‐mapping process in two separate groups of university students (N = 38 (18 + 20)) who were asked, individually, to build concept maps related to two separate concepts in biology and chemistry respectively. We found that, across both groups, students consistently followed the same order of element placement that they began with and found significant differences in the quality of eventual maps resulting from students' map building strategies. Our results suggest that the quality of students' concept maps depends considerably on the strategy used to build it, and point to the supplementary role that the physical working space of the concept‐mapping exercise offers to students' own working memory as a possible explanation for these quality differences.
Cryptic diversity within three South American whip spider species (Arachnida, Amblypygi)

Cryptic diversity (CD), the presence of highly divergent phylogenetic lineages within closed morphological species, has been documented for many taxa. Great arachnid orders such as Araneae or Scorpiones are well studied and many cases of CD have been described therein; to date, however, related research on smaller arachnid orders, such as whip spiders (Amblypygi), remains lacking. In the current study, we investigated CD based on cytochrome oxidase 1 (COI) in three nominal species of the genus Heterophrynus (H. alces, H. batesii, and H. longicornis), represented by 65 specimens. The sequences were compared using three different methods. All three species showed geographically structured CD. Thus, given its existence in this genus, it is important that CD and its spatial distribution be considered in future studies and possible conservation projects.
Nocardia seriolae sp. nov. Causing Nocardiosis of Cultured Fish

Five strains of bacteria causing nocardiosis in cultured fishes (yellowtails [Seriola quinqueradiata] and Japanese flounder [Paralichthys olivaceus]) were studied to establish their taxonomic status. Well-developed fragmenting vegetative mycelium was observed. The chemotype was type IVA containing meso-diaminopimelic acid, arabinose, and galactose. The predominant isoprenoid quinone was MK-8(H4), and mycolic acids were present. These morphological and chemical properties are characteristic of the genus Nocardia. The physiological and biochemical characteristics were most similar to those of Nocardia asteroides; however, these organisms were different in their decomposition of urea, growth temperature, utilization of nitrogen sources, survival at 50°C for 8 h, mycolic and fatty acid profiles, and deoxyribonucleic acid-deoxyribonucleic acid hybridization characteristics. Therefore, we propose a new species for these strains, Nocardia seriolae. The type strain is strain JCM 3360.