Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical role of cholesterol transfer protein in atherosclerosis development

Cholesterol ester transfer protein (CETP) is a plasma protein that facilitates the transport of cholesterol esters and triglicerides between the lipoproteins. CETP collects triglycerides from very-low-density lipoproteins (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesterol esters from high-density lipoproteins (HDL). Mutations wich lead to the cholesterol ester transfer protein function reduction have been involved in atherosclerosis development. This mutations also increase the prevalence of coronary heart disease in patients with hypertriglyceridemia. There is a wide variety of HDL-C increase therapies that have been tested during the last ten years. Among them is the modification of cholesterol ester transfer protein function. A novel pharmacologic strategy was proposed where drugs are designed to modify the lipid substrate preference of cholesterol ester transfer protein instead of simply blocking its activity. This approach provides an opportunity to improve the lipid transfer properties of cholesterol ester transfer protein and to harness its capacity to alter lipid metabolism to achieve specific beneficial outcomes. lipoproteins
Shared genetic contribution to type 1 and type 2 diabetes risk

The role of shared genetic risk in the etiology of type 1 diabetes (T1D) and type 2 diabetes (T2D) and the mechanisms of these effects is unknown. In this study, we generated T1D association data of 15k samples imputed into the HRC reference panel which we compared to T2D association data of 159k samples imputed into 1000 Genomes. The effects of genetic variants on T1D and T2D risk at known loci and genome-wide were positively correlated, which we replicated using data from the UK Biobank and clinically-defined diabetes in the WTCCC. Increased risk of T1D and T2D was correlated with higher fasting insulin and fasting glucose level and decreased birth weight, among T1D- and T2D-specifc correlations, and T1D and T2D associated variants were enriched in regulatory elements for pancreatic, insulin resistance (adipose, CD19+ B cell), and developmental (CD184+ endoderm) cell types. We fine-mapped causal variants at known T1D and T2D loci and found evidence for co-localization at five signals, four of which had same direction of effect, including CENPW and GLIS3. Shared risk variants at GLIS3 and other signals were associated with measures of islet function, while CENPW was associated with early growth, and we identified shared risk variants at GLIS3 in islet accessible chromatin with allelic effects on islet regulatory activity. Our findings support shared genetic risk involving variants affecting islet function as well as insulin resistance, growth and development in the etiology of T1D and T2D.
Growth performance of broiler starter chickens fed varying levels of fibre and energy in multi-fibre source-based diets

There is dearth of information on the crude fibre (CF) tolerance limit of broiler chickens for optimum performance in relation to dietary metabolisable energy (ME) level in the tropics. Hence, this study examined the CF-dietary energy relationship in multi-fibre source-based broiler starter diets at fixed calorie: protein ratio of 123:1. Two hundred and sixteen day-old unsexed Obamarshal broiler chicks were allotted to nine treatments at 24 birds each with three replicates per dietary treatment and fed for 28 days with diets containing ME levels of 2600, 2800 and 3000 ME (kcal/kg) and CF levels of 4, 8 and 12% per energy level to determine their optimal inclusion levels. Live weight, average daily gain (ADG), feed intake, feed conversion ratio (FCR), protein intake, protein efficiency ratio (PER), calorie intake, fibre intake, water intake, water intake: feed intake, water intake: weight gain, faecal output and mortality rate were evaluated and analysed statistically using 3x3 factorial arrangement and significant means separated by Duncan's Multiple Range Test at P 0.05) in broiler starters fed diets containing 8% CF at 2800 and 3000 ME (kcal/kg) respectively. However, these parameters were lower (P<0.05) in broiler starters fed diets containing 2600 ME (kcal/kg) at the three CF levels. Feed cost per kg weight gain was least in broiler starters fed 8%CF diet at 2800KcalME/kg and relatively better than at 8%CF-3000Kcal ME /kg diet. Conclusively, optimum growth and minimal feed cost were obtained with broiler starters raised on diet containing 8% CF at 2800ME(kcal/kg). Keywords : Broiler starter, crude fibre, metabolisable energy, growth
Cytoplasmic and nuclear maturation of oocytes in mammals – living in the shadow of cells developmental capability

Abstract The pig is a polyestrous animal in which the ovarian cycle lasts about 21 days and results in ovulation of 10-25 oocytes. Ovum reaches 120-150 μm in diameter, with the surrounding corona radiata providing communication with the environment. The zona pellucida is composed of glycoproteins: ZP1, ZP2, ZP3. In the course of oogenesis, RNA and protein accumulation for embryonic development occurs. Maternal mRNA is the template for protein production. Nuclear, cytoplasmic and genomic maturity condition the ability of the ovum to undergo fertilization. There are several differences in protein expression profiles observed between in vitro and in vivo conditions. Oogenesis is the process of differentiating female primary sex cells into gametes. During development gonocytes migrate from the yolk sac into the primary gonads with TGF-1, fibronectin, and laminin regulating this process. Cell cycle is blocked in dictyotene. Primary oocyte maturation is resumed before each ovulation and lasts until the next block in metaphase II. At the moment of penetration of the sperm into the ovum, the metaphase block is broken. The oocytes, surrounded by a single layer of granular cells, form the ovarian follicle. The exchange of signals between the oocyte and the cumulus cells done by gap-junctions, as well as various endo and paracrine signals. The contact between the corona radiata cells provides substances necessary for growth, through the same gap junctions. Studies on follicular cells can be used to amplify the knowledge of gene expression in these cells, in order to open way for potential clinical applications.
Search strategies for conservation detection dogs

Monitoring rare or cryptic species can be challenging, especially with limited time and resources. Dogs are often used for this purpose, but methods are highly variable. There is a need to optimise search methods for dog teams so that time and resources are used as efficiently as possible. Some degree of standardisation is also desirable so that search results are comparable between different times and places. The discipline of search theory has developed effective methods to maximise the probability of detecting a search object and/or maximise the efficiency of a search. However, these advances have not been explicitly applied to the use of dogs to search for plants and animals in the wild. Here, we provide a brief introduction to search theory, then discuss how ideas from search theory might be used to standardise and optimise the use of conservation detection dogs. We describe approaches that have been used, discuss their strengths and weaknesses, and suggest priorities for further research. Standardised methods based on search theory could increase the effectiveness of conservation detection dogs, and make search results more comparable across different locations and times.
Effects of combined crude alkaloid‐rich extracts from alligator pepper (Aframomum melegueta) and bastered melegueta (Aframomum danielli) on the enzymes crucial to erectile dysfunction—in vitro

The effects of combined crude alkaloid‐rich extracts of alligator pepper (AP) and bastered melegueta (BM) on the enzymes [acetylcholinesterase (AChE), angiotensin‐1‐converting enzyme (ACE), phosphodiesterase‐5 (PDE‐5), and arginase] crucial to erectile dysfunction were investigated—in vitro. Mixtures of the alkaloid‐rich extracts (100% AP, 75% AP + 25% BM, 50% AP + 50% BM, 25% AP + 75% BM, and 100% BM) prepared and their effects on AChE, ACE, PDE‐5, and arginase activities were determined. The highest inhibitory effect on AChE and ACE activities was observed in 100% AP while 100% BM had similar effect against PDE‐5 and arginase activities. All the extracts had strong antioxidant properties. Gas chromatography (GC) characterization of extracts revealed the presence of theophylline, sparteine, among others. Biological effects of the combined extracts from AP and BM could be part of the possible mechanism of actions in ED management as reported in folkloric medicine. PRACTICAL APPLICATIONS: Spices have been widely used in Nigeria for food seasoning with numerous health benefits. However, the benefits of spices are under‐utilized in the management/treatment of erectile dysfunction. The results of this study suggest that the combination of alligator pepper and bastered melegueta seeds could be applied as functional foods and nutraceuticals for erectogenic purposes.
Vascular remodelling in malignant hypertension

1 Chapter One Introduction 1.1 Malignant hypertension 3 1.1.1 Risk factors and outcome predictors 7 1.1.2 Diagnosis and treatment 9 1.2 Rodent models of hypertension 11 1.2.1 Non-transgenic models resulting in hypertension 14 1.2.1.1 One clip two kidney model 14 1.2.1.2 Angiotensin II infusion 16 1.2.1.3 Inhibition of nitric oxide 17 1.2.1.4 The deoxycorticosterone acetate salt sensitive rat 19 1.2.2 Transgenic models of malignant hypertension 20 over expressing prorenin 1.2.2.1 TGR(mRen2)27 20 1.2.2. 2 Constitutive tissue specific renin expressing 26 transgenics 1.2.2.3 The double "human" transgenic rat 27 1.2.2.4 Brain specific angiotensinogen depletion 29
The role of intracellular organelles in Ca2+-homeostasis in secretory cells of the lacrimal gland

It is known that different Ca2+-transport systems make distinct contribution to the formation of Ca2+-signal in various secretory cells. In recent years there has been a significant increase in interest in study of the lacrimal glands functioning. However, the results of study of the Ca2+-signalling in lacrimal gland have not yet been summarized in the literature. This review is devoted to analysis of functioning of Ca2+-transport system of secretory cells in the rat exorbital lacrimal gland. IP3Rs in exorbital lacrimal gland cells were effectively inhibited by 2-APB (10 μM) and activated by IP3 (2 μM), as well as by cholinomimetics, carbacholine (10 μM) and purine receptor agonists, ATP (1 mM). Signaling pathways activated by P2Y-receptors in the lacrimal gland secretory cells were partially mediated by IP3R activation. RyRs of lacrimal gland secretory cells were activated by Ca2+ and low concentrations of ryanodine (0,05–1 μM). Simultaneous activation of RyRs and IP3Rs in these cells caused Ca2+ release from the same store. Ca2+ mobilization from the intracellular stores induced by carbacholine (10 μM) or thapsigargin (1 μM) caused store-operated Ca2+ entry in secretory cells of the studied glands, which was partially inhibited by 2-APB. SERCA of exorbital lacrimal gland cells was efficiently inhibited by eosin Y (5–10 μM) and by thapsigrgin (1 μM). In contrast to permeabilized cells, the Ca2+ content in intact cells did not change under the influence of eosin Y (5–20 μM), indicating the inhibition of PMCA. Ca2+-ATPase activity of permeabilized cells of studied glands depended on the incubation time, the substrate amount and Ca2+ concentration in the incubation medium. Mitochondrial Ca2+-uniporter of lacrimal gland secretory cells was inhibited by ruthenium red (10 μM). Effects of ryanodine and ruthenium red on the Ca2+ content in cells were statistically significantly non-additive. Furthermore, ryanodine at concentrations of 1–3 μM caused a dose-dependent decrease in the respiration rate of the studied cells and this effect persisted after cells preincubation with ruthenium red or thapsigargin. This suggests that in addition to the endoplasmic reticulum RyRs activation, ryanodine inhibited the Ca2+ transport to the mitochondrial matrix, which was insensitive to the ruthenium red.
Genetic variation and population structure of Apis cerana in northern, central and southern mainland China, based on COXI gene sequences

The eastern honey bee (Apis cerana), a Chinese native bee species, plays an important role in local ecosystems and agriculture, as it pollinates flowering plants. In this study, we assessed the genetic variation and population structure of A. cerana using the mitochondrial sequences of cytochrome c oxidase subunit I (COXI). We collected samples from 11 provinces of China and also included previously-collected data from two provinces of southern China. A total of 1,518 sequences with a length of 760 bp in 51 A. cerana populations were analyzed. We found 111 haplotypes within these sequences, of which 78 haplotypes were newly-defined in this study. The star-like median-joining network revealed that the haplotypes found in this study were monophyletic. A large difference in genetic diversity was found, including a gradual decrease from southern to northern populations. The southern populations harbored most of the genetic diversity and should therefore be protected. We also found a significant genetic structure among the studied populations, and defined five populations as key conservation populations. These results could be valuable in making management and conservation strategies, and for a better understanding of the evolutionary history of A. cerana populations in China.
An investigation of the relationships between common stressors, brood-signaling, hygienic behavior, and selective breeding in the Honey Bee (Apis mellifera)

Despite the importance of the honey bee (Apis mellifera) to scientific advancement, food security and natural ecosystems, managed honey bee colonies are dying at alarming rates in much of the Northern Hemisphere. Recent declines are largely attributed to anthropogenic stressors and to the spread of natural parasites and diseases, most notably the ectoparasitic mite Varroa (Varroa destructor), which is considered by many to be the most important threat to apiculture today. Varroa resistance programs have been successful and rely primarily on selection for hygienic behavior. However adequate mite resistance through hygienic behavior has not yet been fully achieved, and the signal responsible for triggering the hygienic removal of Varroa-infested brood has remained elusive. Employing behavioral, chemical and molecular analyses, the following dissertation investigates the relationships between honey bee stressors, chemical brood signals, and hygienic behavior for bees originating from three distinct breeding programs. Cross-fostering experiments and chemical analyses suggest that hygienic behavior is influenced by a specific chemical originating from honey bee brood, and that the stressor that triggers this chemical signal is different for brood originating from distinct breeding programs. Additional behavioral and chemical analyses provide evidence of increased iron content and higher rates of hygienic removal of brood from cells overlapping steel wires commonly used by beekeepers to add stability to wax-foundation frames. Improved understanding of the relationships between honey bee stressors, brood signals, and hygienic behavior described in this dissertation has the potential to make a positive impact on the health of honey bees. The broad-scale applicability of results presented here stems primarily from the practicality of the solutions these results imply. Through the development of sustainable strategies to combat the Varroa mite, and by discouraging the use of steel wire stabilizers in wax-foundation frames, this work has the potential to improve honey bee health, and thus positively influence the honey bee’s enormous contribution to the economy and the environment.
Selective Alteration of Snyder-Theilen feline sarcoma virus transforming gene (v-fes) integration in chemically-treated human fibroblasts /

2. When an image on the film is obliterated with a round black mark, it is an indication of either blurred copy because o f movement during exposure, duplicate copy, or copyrighted materials that should not have been filmed. For blurred pages, a good image of the page can be found in the adjacent frame. If copyrighted materials were deleted, a target note will appear listing the pages in the adjacent frame.
Sensory transduction in the gastrointestinal tract : regulation of 5-hydroxytryptamine (5-HT) release from human bon cells /

5-hydroxytryptamine (5-HT) is an important paracrine mediator in the gut that excites intrinsic and extrinsic neurons in reflex regulation of intestinal motility and secretion. The highest concentration of 5-HT in the mammalian body is found in enterochromaffin cells, which are endocrine cells dispersed throughout the small and large intestinal epithelium. Enterochromaffin cells have been suggested as sensory cells in the intestine displaying mechanoand chemosensitivity. The aim of this study was to define the regulatory mechanisms of 5-HT release from human carcinoid BON cells, a model for enterochromaffin cells. Mechanical stimulation by rotational shaking activates Gaq and mobilizes intracellular calcium and stimulates 5-HT release, assayed by enzyme immunoassay. Electron microscopy revealed that BON cells have cholesterol rich membrane domains indicative of caveolae whose structural integrity is necessary fpr mesbanically evoked activation of Gaq and subsequent 5-HT release. Caveolin-1, a structural protein of caveolae, acts as a suppressor of the activated state of Gaq. Complex adenosinergic regulatory mechanisms modulate 5-HT
Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer’s Disease

The severe semantic memory impairments in semantic dementia have been attributed to a pronounced anterior temporal lobe atrophy and a functional disruption of this brain region. In contrast, medial and posterior temporal lobe damage is predominantly found in patients with Alzheimer’s disease, and has been associated with episodic memory disturbance. Despite these seemingly distinct neuropathological signatures that correspond well with the syndrome-typical symptomatology, the hippocampal deterioration common in Alzheimer’s disease and semantic dementia appears paradoxical. In attempting to gain more insight into the mutual and divergent functional alterations seen in Alzheimer’s disease and semantic dementia, we assessed the differences in intrinsic functional connectivity between temporal lobe regions in patients with Alzheimer’s disease (n = 16), semantic dementia (n = 23), and healthy controls (n =17). In contrast to the majority of studies that conducted comparable analyses, we were particularly interested in connectivity alterations between functional rather than anatomical regions, and therefore used a functional parcellation of the temporal cortex. The Alzheimer’s disease group showed only a single connection with reduced functional connectivity as compared to the controls. This connection was located between the right orbitofrontal cortex and the right anterior temporal lobe. In contrast, functional connectivity was decreased in the semantic dementia group in six connections, mainly involving the hippocampus, lingual gyrus, temporal pole, and orbitofrontal cortex. We identified a common pathway with semantic dementia, since the functional connectivity between the right anterior temporal lobe and the right orbitofrontal cortex was reduced in both types of dementia. This might be related to semantic impairments observed in both dementia types, and abnormal social behavior at more progressed disease stages. However, to substantiate such claims, longitudinal studies that more strongly relate clinical and behavioral outcomes to functional connectivity are needed. Abbreviations: AD = Alzheimer’s disease; FC = functional connectivity; HC = healthy controls; ROI = region of interest; SD = semantic dementia
Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In Vivo

Diacylglycerol (DAG) has been proposed to mediate lipid-induced hepatic insulin resistance. Accumulated hepatic DAG activates PKCe which phosphorylates insulin receptor kinase (IRK) at T1160 to inhibit IRK activation and cause insulin resistance. However, the importance of DAG in lipid-induced hepatic insulin resistance remains controversial. To test the physiological effect of acute DAG accumulation on hepatic insulin sensitivity, we used antisense oligonucleotide (ASO) to specifically inhibit hepatic diglyceride acyltransferase 2 (DGAT2) which catalyzes the conversion of DAG to triglyceride. Previously, chronic DGAT2 inhibition was shown to paradoxically decrease hepatic DAG content due to decreased SREBP-1c-mediated lipogenesis and improve hepatic insulin sensitivity. However, we hypothesized that acute DGAT2 inhibition might provide a narrow window to transiently increase hepatic DAG content and allow us to identify the association between DAG, PKCe activation/translocation and hepatic insulin resistance. As hypothesized, an acute (2-day) DGAT2 inhibition increased hepatic DAG content and PKCe activation (cytosol to membrane translocation). DGAT2 ASO-treated rats on regular chow diet displayed impaired insulin-mediated suppression of hepatic glucose production. This defect of hepatic insulin action was at the level of IRK as indicated by impaired insulin-stimulated IRK Y1158/1162 phosphorylation. Furthermore, measured by a novel LC-MS/MS method, hepatic sn-1,2 DAG, which is the DAG stereoisomer capable of activating PKCe, was increased in the subcellular membrane compartment with DGAT2 ASO treatment. Conclusion: These data support the importance of membrane sn-1,2 DAG in mediating lipid-induced hepatic insulin resistance through “increased membrane sn-1,2 DAG content -> PKCe activation/translocation -> increased IRK T1160 phosphorylation -> decreased IRK Y1158/1162 phosphorylation -> decreased IRK activity” in vivo. Disclosure K. Lyu: None. D. Zhang: None. Y. Nozaki: None. Y. Zhang: None. S. Bhanot: Employee; Self; Ionis Pharmaceuticals, Inc. G. Cline: None. V. Samuel: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. Research Support; Self; Gilead Sciences, Inc.