Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the Role of BET Bromodomain Proteins in AR Transcriptional Regulation: A Perpetuating Cycle of JQ1 Resistance in CRPC Therapy

Abstract : During the inevitable progression to castration resistant stage, prostate cancer cells acquire resistance to anti-androgens.Paradoxically, despite the prolonged AR antagonist treatment, expression of AR is not abated in CRPCs, signifying AR as the Achilles heel to achieve realistic therapeutic benefit in CRPC patients. Recently, it has been reported that prostate cancer cells positive for AR-signaling and CRPC xenograft tumors display exquisite sensitivity to JQ1, a BET bromodomain inhibitor. Mechanistically, JQ1 binds the N-terminal BET bromodomain of BRD4 to disrupt its interaction with AR and prevent expression of DHT dependent AR target genes. Ironically, while JQ1 ablated AR target gene transcription, it significantly increased AR transcription and this increase was concomitant with increasing concentrations of JQ1 treatment. This incongruous observation suggests that in androgen-responsive PC cells, AR-BRD4 interaction may regulate AR transcription by a negative feedback loop. One potential mechanism is the presence of an AR transcriptional repressor that is directly regulated by the BRD4-AR complex, which maintains AR homeostasis. The hypothesis is that in cells treated with JQ1, inhibition of BRD4-AR signaling would prevent transcription of the AR repressor, consequently inducing AR transcription. Thus, greater the JQ1 mediated inhibition, greater is the up regulation of AR. Additionally, since only a fraction of the AR binding sites are co-enriched for BRD4 binding in androgen stimulated PC cells, JQ1 mediated inhibition will at the most have a modest effect on long-term CRPC treatments. It is this BRD4-independent AR target gene expression that will continue to promote CRPCs progression and metastasis. This proposal will explore novel molecular mechanisms by which prostate cancer cells develop resistance to BET bromodomain inhibitors.
Survival of Shiga Toxin-producing Escherichia coli and Salmonella serotypes in the feces of five animal species.

ii Acknowledgments . iii Vita . iv List of Tables. vi List of Figures . vii Chapter 1 – Literature Review . 1 Chapter 2 Plasmid loss limits the use of GFP labeled Escherichia coli O157 in longterm survival studies . 34 Chapter 3 The Survival of Salmonella and Shigatoxin producing Escherichia coli serotypes in the feces of five different animal species. 56 References . 87
An evaluation of oocyte size in multiple regressions predicting gonad weight from body weight : a test using hawaiian ehu, Etelis carbunculus

The interrelations of body size, ovary weight, and size of oocytes (ovarian eggs) were evaluated for 4 0 specimens of the Hawaiian snapper, Etelis carbunculus. The potential contribution of oocyte size (volume) for predicting ovary weight from body weight was assessed in multiple regressions relating ovary and body weights, with or without several measures of egg volume. Egg volume was first characterized using the median diameter of 2 5 oocytes in the largest, most advanced size mode present in each fish specimen. Weighted mean egg volumes were next estimated for each fish based on the diameters of 300 oocytes of all sizes, measured in increments of 50. Finally, the numbers of oocytes measured were evaluated in terms of benefit (gain in precision) versus cost (processing time). In the basic model, ovary-free body weight (OFBW) explained 58% of the variation in gonad weight (GW) after each variable was transformed to logarithms. Addition of oocyte volume as a second independent variable contributed another 38 f 1% to the explained variance in GW. Egg volume based on the simple median diameter of the 25 largest oocytes was no less precise than egg volume characterized using the more time-consuming measurements of 50300 diameters of all-sized oocytes. It is likely that larger (especially hydrated) oocytes have a disproportionate influence on ovary weight. The implications of reproductive cycling and allometric ovary-body weight relations are discussed. We conclude that the potential benefit of using the simply estimated egg volume measure may be greater for other ehu samples,
Correlates of complete brood failure in blue tits: could extra‐pair mating provide unexplored benefits to females?

Behavioural ecologists have for decades investigated the adaptive value of extra‐pair copulation (EPC) for females of socially monogamous species. Despite extensive effort testing for genetic benefits, there now seems to be a consensus that the so‐called ‘good genes’ effects are at most weak. In parallel the search for direct benefits has mostly focused on the period surrounding egg laying, thus neglecting potential correlates of EPC that might be expressed at later stages in the breeding cycle. Here we used Bayesian methods to analyse data collected over four years in a population of blue tits Cyanistes caeruleus, where no support was previously found for ‘good genes’ effects. We found that broods with mixed paternity experienced less brood failure at the nestling stage than broods with single paternity, and that females having experienced complete brood failure in their previous breeding attempt had higher rates of mixed paternity than either yearling or previously successful females. To better understand these observations we also explored relationships between extra‐pair mating, male and female phenotype, and local breeding density. We found that in almost all cases the sires of extra‐pair offspring were close neighbours, and that within those close neighbourhoods extra‐pair sires were older than other males not siring extra‐pair offspring. Also, females did not display consistent EPC status across years. Taken together our results suggest that multiple mating might be a flexible female behaviour influenced by previous breeding experience, and motivate further experimental tests of causal links between extra‐pair copulation and predation.
A global spatially explicit database of changes in island palaeo-area and archipelago configuration during the late Quaternary

Motivation: Past sea level fluctuations have shaped island area and archipelago configuration. The availability of global high-resolution data on bathymetry and past sea levels allows reconstruction of island palaeo-geography. Studies on the role of palaeo-area often consider only the Last Glacial Maximum, which neglects the dynamics of island fusion and fission resulting from cyclic sea level fluctuations throughout the Quaternary. Currently, no global database is available to test the role of changing island geographies driven by Quaternary sea level change on evolutionary, ecological and archaeological patterns. However, data on island palaeo-environments is crucial for understanding insular biodiversity distributions and human settlement patterns. Here, we present the Palaeo-Islands and Archipelago Configuration (PIAC) database, containing sea level-driven palaeo-geography changes over the late Quaternary of 178 islands in 27 archipelagos, and discuss its relevance, limitations and uncertainties. The R functions developed to create the PIAC database are provided to allow calculations for other islands, time steps, sea-level curves and higher spatio-temporal resolutions. Main types of variables contained: Polygon shapefiles with archipelago configuration and tables with palaeo-area per island. Spatial location and grain: The database has a global representation, with 27 archipelagos being covered: Aldabra, Azores, Balearic Islands, California Channel Islands, Canary Islands, Cape Verde, Comoros, Cook Islands, Crozet Islands, Dutch Caribbean, Galapagos, Gulf of Guinea, Hawaii, Inner Seychelles, Juan Fernandez, Kuril Islands, Madeira, Marianas, Marquesas, Mascarenes, Phoenix Islands, Pitcairn Islands, Prince Edward Islands, Revillagigedo, Samoan Islands, Society Islands and Tristan da Cunha. All data are at 1 km2 spatial resolution. Time period and grain: The focus of this paper is on the last 35 kyr; data for the last 140 kyr are also provided. The grain is 1 kyr temporal resolution. Level of measurement: Data are per island, grouped per archipelago. Software format: The data were produced in the R programming language.
Electrophysiological analysis of the synaptic vesicle priming process

Chemical synaptic transmission is the most prominent communication channel employed by neural circuits. It is initiated by the action potential triggered fusion of transmitter-filled synaptic vesicles with the presynaptic plasma membrane. Proteins of the CAPS and Munc13 families are required to prime synaptic vesicles for fusion before these can release their contents into the synaptic cleft. In the present study, I dissected the functional interplay of both protein families during the priming process and furthermore tested the significance of two recently described presynaptic proteins in the modulation of the Munc13- and CAPS dependent priming reaction. The data presented here indicate that CAPSs and Munc13s differentially prime SVs at low versus high levels of presynaptic activity in a lipid-dependent manner. Specifically, CAPSs engage in a lipid-sensitive priming step at low intraterminal Ca2+ concentrations, while Munc13-lipid interactions predominate at high Ca2+ levels. This step, in turn, likely precedes the partial assembly of fusogenic SNARE complexes, which is catalyzed by the MUN domain of Munc13s. The two recently described presynaptic proteins, mSYD1A and Mover, did not modulate the priming reactions as assessed in the autaptic hippocampal culture system. In addition, I studied the relevance of the priming process in the etiology of bipolar disorder, which involved a detailed structure function analysis of disease associated CADPS1 mutations in cultured hippocampal neurons and the generation of a knock-in mouse carrying one such mutation. Two out of eight mutations led to altered forms of short-term synaptic plasticity in cultured neurons, which may indicate that perturbations of the priming process contribute to the etiology of bipolar disorder. Lastly, I established an experimental system for the future study of the significance of the priming process for short-term synaptic plasticity phenomena in the context of visual information processing in-vivo.
Obligate annual and successive facultative diapause establish a bet‐hedging strategy of Rhagoletis cerasi (Diptera: Tephritidae) in seasonally unpredictable environments

To cope with temporal and spatial heterogeneity of habitats, herbivorous insects in the temperate zone usually enter diapause that facilitates synchronization of their life cycle with specific stages of host plants, such as fruit ripening. In the present study, we address those factors regulating dormancy responses as part of a ‘longer strategy’ to persist and thrive in temperate environments, focusing on Rhagoletis cerasi, a univoltine, oligophagous species, which overwinters as pupae and emerges when host fruits are available for oviposition at local scale. To ensure population survival and reproduction at habitats with ecological heterogeneity, R. cerasi has evolved a sophisticated diapause strategy based on a combination of local adaptation and diversified bet‐hedging strategies. Diapause duration is determined both by (i) the adaptive response to local host fruit phenology patterns (annual diapause) and (ii) the plastic responses to unpredictable inter‐annual (temporal) climatic variability that drives a proportion of the populations to extend dormancy by entering a second, successive, facultative cycle of prolonged diapause as part of a bet‐hedging strategy. Besides the dormant periods, post‐diapause development (which varies among populations) exerts ‘fine tune’ adjustments that assure synchronization and may correct possible errors. Adults emerging from pupae with prolonged diapause are larger in body size compared with counterparts emerging during the first year of diapause. However, female fecundity rates are reduced, followed by an extended post‐oviposition period, whereas adult longevity remains unaffected. Overall, it appears that R. cerasi populations are adapted to ecological conditions of local habitats and respond plastically to unpredictable environmental (climatic) conditions.
Discrimination of canopy gaps and non-regenerating openings in old-growth temperate deciduous forests using airborne LiDAR data

The use of LiDAR in the study of gap regimes has seen significant progress in recent years. Researchers have assumed that canopy gaps detected in this manner are ecologically equivalent to gaps sampled in situ by more traditional methods. However, those latter methods usually include canopy gaps only and ignore non-regenerating openings that are produced by causes limiting tree establishment. We developed a predictive model capable of discriminating between canopy gaps and non-regenerating openings using LiDAR-derived data. Selected predictive variables were related to conditions that limit tree establishment such as zones of moisture accumulation and steep slopes or to the resulting vegetation physiognomy. The model was applied to three old-growth maple forests to predict the fractions of canopy openings belonging to these two types. On average, non-regenerating openings represented 19.5% of the total area detected as canopy openings and occupied 1.37% of the sites. Canopy gaps formed 80.5% of the total area in canopy openings and covered 5.71% of sites that were studied. The non-regenerating opening seemed more frequent on thin surficial deposits. The canopy gap fraction was similar among study sites but had lower values than usually reported for temperate deciduous forest.
Phytochemical Screening, HPTLC Fingerprint Analysis of Leaf Extract of Bridelia montana (Roxb) Willd

This research analyzed the major chemical constituents present in the ethanolic extract of the leaves of Bridelia montana (ROXB) WILLD. The leaves of Bridelia montana were collected, powdered, de-fatted with n-hexane and then extracted with 90%ethyl alcohol. Preliminary phytochemical screening of the ethanolic leaf extract of Bridelia montana showed the presence of chemical constituents like alkaloids, glycosides, phenolic compounds, tannins and resins. HPTLC fingerprint analysis of the extract was carried out using CAMAG HPTLC system equipped with Linomat 5 sample applicator, UV cabinet and WIN-CATS-4 software. The results from HPTLC fingerprint analysis of the ethanolic leaf extract of Bridelia montana revealed the presence of 6 polyvalent constituents.
Connection between the Southern Ocean Mode and the Weddell Polynya

During the mid-1970s, a large open and ice free area in the Southern Ocean appeared, better known as the Weddell Polynya. Very recently in 2017, the Weddell Polynya appeared after more than 50 years. It has been suggested that the formation of the Weddell Polynya is driven by oceanic processes. Positive subsurface temperature anomalies destabilise the stratification of the water column which lead to mixing and eventually influence the ice formation in the Southern Ocean. However, the mechanisms of the build-up of this anomalous heat and the multidecadal timescale of the appearance of the Weddell Polynya are still unknown. Here we present results of an analysis of model output from a long (∼250 years) control simulation with a high horizontal resolution (ocean: 0.1◦, atmosphere: 0.5◦) version of the global Community Earth System Model (CESM). In this simulation, the area, position and life cycle of the Weddell Polynya correspond well to that in observations. The variability in ocean heat content near the Weddell Polynya is mainly driven by multidecadal variability in the Southern Ocean due to the so-called Southern Ocean Mode (Le Bars et al. 2016; van Westen and Dijkstra, 2017). Ten years before the formation of the Weddell Polynya, the Southern Ocean Mode generates positive anomalies in ocean heat content. The variability in the Southern Ocean enters the Weddell Gyre and influences the subsurface ocean heat content. The results provide a new mechanism for the formation and evolution of the Weddell Polynya.
Mucopolissacaridose IVA : análise molecular e caracterização de haplótipos intragênicos no gene Galns

Background: Mucopolysaccharidosis IVA is an autosomal recessive lysosomal disease, caused by deficiency of N-acetilgalactosamina-6-sulfatase. It is a rare disease and the incidence ranges from 1: 76,000 to 1:640,000 live births. To date 319 mutations have been identified in this gene, demonstrating the wide variability of disease causing mutations. Objective: Analyze and characterize the genotype of patients with MPS IVA, through molecular analysis of GALNS. Methods: Molecular analysis of 45 patients with confirmed biochemical diagnosis for MPS IVA was performed. Mutation analysis was performed by PCR followed by Sanger sequencing. Haplotype analysis was performed using 6 intragenic polymorphisms by Real-Time PCR. Results: In this study we found 18 different mutations among 45 Brazilian patients and identified 5 common mutations (p.Ser341Arg, p.Arg386Cys, p.Gly301Cys, p.Arg94Leu e p.Gly116Ser). Four novel mutations were also identified through molecular analysis, including: p.Gly115Arg, p.Asn45Gly, p.Thr394Ala e c.759-2A>G. Patients are distributed in Northeast, Southeast and South regions of Brazil. Six different haplotypes were identified among patients. The p.Ser341Arg mutation showed the highest frequency, and most patients are located in the Northeast, additionally, all patients with this mutation show the same haplotype.Conclusion: These analyzes are important to identify carriers in families, for prenatal diagnosis, and in order to identify the mutation origin when certain recurrent mutation is associated with the same haplotype. In this study, we observed a high frequency of p.Ser341Arg mutation in Northeast, mainly in the state of Paraíba. This mutation was detected with higher frequency among patients, and showed only a haplotype. This mutation is unique for the Brazilian population and thus, we could suggest that a possible founder effect for this mutation could exist.
Body stores persist as fitness correlate in a long-distance migrant released from food constraints

Long-distance migratory birds rely on the acquisition of body stores to fuel their migration and reproduction. Breeding success depends on the amount of body stores acquired prior to migration, which is thought to increase with access to food at the fueling site. Here, we studied how food abundance during fueling affected time budgets and reproductive success. In a regime of plenty, we expected that 1) limitations on food harvesting would become lifted, allowing birds to frequently idle, and 2) birds would reach sufficient fuel loads, such that departure weight would no longer affect reproductive success. Our study system comprised brent geese (Branta b. bernicla) staging on high-quality agricultural pastures. Fueling conditions were assessed by a combination of high-resolution GPS tracking, acceleration-based behavioral classification, thermoregulation modeling, and measurements of food digestibility and excretion rates. Mark-resighting analysis was used to test for correlations between departure weight and offspring recruitment. Our results confirm that birds loafed extensively, actively postponed fueling in early spring, and took frequent digestion pauses, suggesting that traditional time constraints on harvest and fueling rates are absent on modern-day fertilized grasslands. Nonetheless, departure weight remained correlated with recruitment success. The persistence of this correlation after a prolonged stopover with access to abundant high-quality food, suggests that between-individual differences in departure condition are not so much enforced by food quality and availability during stopover, but reflect individual quality and longer-lived life-history traits, such as health status and digestive capacity, which may be developed before the fueling period.
Deoxinivalenol: métodos de análisis de residualidad en cereales. Toxicidad en animales de granjas

Cereals are the staple food of persons and animals worldwide, hense their production increases every year. Cuba currently imports large quantities of cereals from Europe and America, with an investment of up to 240 million dollars in 2012. Often, cereals may be contaminated with mycotoxins, including deoxynivalenol (DON). This can damage animal health, reduce food consumption and gain weight, and alter the immune system, among other adverse effects, forcing countries to implement policies to monitor waste and contaminants to ensure the safety of the foods produced, exported and imported. For this purpose, they apply maximum permissible limits (MPL), established by international organizations that vary depending on the type of cereal, destination and the regulatory entity itself. However, in recent years, there have been numerous reports of grain contamination by DON and its conjugates, with concentrations of 4374.4 and 2990 μgkg -1 in maize and 2352 μgg -1 in feed, in countries such as China, Switzerland and South Africa, respectively. In Cuba, concentrations over 1000 µgkg -1 have been detected in grains like wheat. For the quantification of this mycotoxin there are several analytical methods. Among the most used are the High Performance Liquid Chromatography (HPLC) and its coupling to Mass Spectrometry (HPLC/MS). This review is aimed at providing information on the methodologies applied in the analysis of DON in cereals and the toxicity caused by this mycotoxin in farm animals. It is expressed as a general conclusion that this trichothecene affects health, reflected in the decrease of productive indexes; and has several analytical methodologies that allow its determination and the regulations established by the MPL to protect animal health. Keywords: deoxynivalenol, residues, toxicity, analytical methods, cereals, farm animals.