Miracle-dz/UniFAR-FTUs huggingface dataset:
Enzyme- and transporter-based drug-drug Interactions : progress and future challenges

Enzyme systems have evolved in humans to maintain cellular homeostasis and to facilitate the disposition of xenobiotics. These enzymes possess complementary, and sometimes overlapping, functions, a feature which can set the stage for drug–drug interactions. In this chapter, we provide an overview of the phase I and phase II families of detoxification enzymes, their potential for induction and inhibition, and the role of genetic variants in the occurrence of drug–drug interactions. 1.
Effect of the biological controls Trifesol and Nemacid on root-knot nematodes in sheltered vegetable production.

Root-knot nematode (Meloidogyne spp.) has become one of the main phytosanitary problems in sheltered vegetable production in Cuba. Several tactics have been used to its management with positive results. The biological controls Trifesol and Nemacid were evaluated as alternatives of methyl bromide to control the root-knot nematode (M. incognita race 2) in a sheltered crop system. The study was carried out in a protected crop house at the INIFAT with a high level of infestation of this nematode. The effect of Nemacid and Trifesol was compared with Dazomet (chemical nematicide) and an untreated control in plots of 2,40 m2. Cucumber (Cucumis sativus L.), hybrid HA 456, was used as indicator plant. Trifesol reduced the nematode population from grade 3,03 and infestation indexes of 50,04% to 1,2 and of 28,0%, respectively, and Nemacid from grade 3,10 and indexes of 51,5% to 1,3 and 32,5%, respectively, which were significantly (p<0,05%) better values than those of the untreated control. With both products, a significant increase of cucumber growth was observed one month after planting when compared with the control. In all cases, the best results were obtained with Dazomet. However, Trifesol and Nemacid were shown to be good alternatives to methyl bromide for being used in an integrated management programme in protected vegetable production. (
Topogenèse des transporteurs d'acides aminés chez le champignon filamenteux Aspergillus nidulans

Deux types de voies qui regulent specifiquement et pleiotropiquement l'expression des genes des transporteurs d'acides amines ont ete decouvertes chez Aspergillus nudulans. La premiere voie comprend les produits des genes aauZ et aauY. AauZ code pour une " casein kinase" de type I (CKI) et aauY+ agit comme suppresseur multicopie de la mutation aauZ102 qui affecte drastiquement l'utilisation de la plupart des acides amines comme sources d'azote du a l'incapacite de la souche a les incorporer. AauY coderait pour une proteine similaire, dans son extremite N-terminale, a Gti1p et Pac2p de Schizosaccharomyces pombe. Ces extremites presentent une region hydrophobe conservee (helice-α putative) et deux autres sequences conservees, une cible putative des CKI et une cible putative d'une kinase de type Pka1p. AauZ et AauY sont necessaires pour l'expression des genes des transporteurs d'acides amines a un niveau post-transcriptionnel car aauZ1O2 n'affecte pas l'accumulation de l'ARN messager d'agtA (identifie au cours de cette these) codant pour le transporteur principal des acides amines acides. Elles agiraient au sein de la meme voie ou dans des voies paralleles regulant le meme processus cellulaire. La deuxieme voie depend des produits des genes affectes chez les mutants aau21 et aau22. Chez aau21 l'expression du gene de l'arginosuccinate synthetase est fortement diminuee et chez aau22 celle du gene de la threonyl ARNt synthetase. Les mutations correspondantes affectent la croissance de la souche en presence de nombreux acides amines comme seules sources d'azote du au defaut de leur incorporation. Les "pools " intracellulaires des ARNt charges d'arginine chez aau21 et de threonine chez aau22 sont modifies ce qui pourrait entrainer une reponse de carence en acides amines. L'etude de l'expression d'agtA a montre que les deux mutations affectent l'expression des genes des transporteurs d'acides amines a un niveau post-transcriptionnel.
Konsekvenser av sjuksköterskors skiftarbete i relation till patientsäkerhet

For att akutsjukhus skall kunna erbjuda vard 24 timmar om dygnet ar det nodvandigt att sjukskoterskor arbetar i skift. Skiftarbete kan dock paverka dygnsrytmen och somnen och leda till fatigue, hog .
Fever: Its Biology, Evolution, and Function

One day, you will discover a new adventure and knowledge by spending more money. But when? Do you think that you need to obtain those all requirements when having much money? Why don't you try to get something simple at first? That's something that will lead you to know more about the world, adventure, some places, history, entertainment, and more? It is your own time to continue reading habit. One of the books you can enjoy now is fever its biology evolution and function here.
Functional ingredients from algae for foods and nutraceuticals.

Algae as a source of biologically active ingredients for the formulation of functional foods and nutraceuticals. Part 1 Structure and occurrence of the major algal components: Chemical structures of algal polysaccharides Algal lipids, fatty acids and sterols Algal proteins, peptides and amino acids Phlorotannins Pigments and minor compounds in algae. Part 2 Biological properties of algae and algal components: Antioxidant properties of algal components and fractions Antimicrobial activity of compounds isolated from algae Anticancer agents derived from marine Anti-inflammatory properties of algae Algae and cardiovascular health Gastric and hepatic protective effects of algal components Anti-obesity and anti-diabetic activities of algae. Part 3 Extraction of bioactive components from algae: Conventional and alternative technologies for the extraction of algal polysaccharides Enzymatic extraction of bioactives from algae Subcritical water extraction of bioactive components from algae Supercritical CO2 extraction of bioactive components from algae Ultrasonic- and microwave-assisted extraction and modification of algal components. Part 4 Applications of algae and algal components in foods, functional foods and nutraceuticals: Design of healthier foods and beverages containing whole algae Development of nutraceuticals containing marine algae oils Prebiotic properties of algae and algae-supplemented products Algal hydrocolloids for the production and delivery of probiotic bacteria Cosmeceuticals from algae.
Centers for Disease Control and Prevention Public Health Response to Humanitarian Emergencies, 2007–2016

Humanitarian emergencies, including complex emergencies associated with fragile states or areas of conflict, affect millions of persons worldwide. Such emergencies threaten global health security and have complicated but predictable effects on public health. The Centers for Disease Control and Prevention (CDC) Emergency Response and Recovery Branch (ERRB) (Division of Global Health Protection, Center for Global Health) contributes to public health emergency responses by providing epidemiologic support for humanitarian health interventions. To capture the extent of this emergency response work for the past decade, we conducted a retrospective review of ERRB’s responses during 2007–2016. Responses were conducted across the world and in collaboration with national and international partners. Lessons from this work include the need to develop epidemiologic tools for use in resource-limited contexts, build local capacity for response and health systems recovery, and adapt responses to changing public health threats in fragile states. Through ERRB’s multisector expertise and ability to respond quickly, CDC guides humanitarian response to protect emergency-affected populations.
Characterization of Protein-Protein Interaction Within a Polyamine Responsive Signaling System in Vibrio Cholerae

The Gram-negative bacterium Vibrio cholerae is a natural inhabitant of aquatic environments and the causative agent of the severe diarrheal disease cholera. This bacterium is able to form biofilms on both abiotic and biotic surfaces. Biofilm formation is vital to the survival of V. cholerae both within aquatic reservoirs and during transmission to the human host. The bacterial second messenger cyclic-di-GMP is an important signaling system that is known to regulate biofilm formation in response to environmental signals. Previous research investigating a putative c-di-GMP-signaling pathway involving the periplasmic protein NspS and the GGDEF-EAL protein MbaA, revealed that the polyamines spermidine and norspermidine likely act as specific extracellular environmental signals to modulate NspS-MbaA interaction and affect biofilm formation. These proteins have opposite effects on biofilm formation in vitro and are encoded by adjacent genes with overlapping reading frames as part of an operon structure. The objective of this study has been to provide evidence of direct protein-protein interaction between NspS and MbaA, and to further elucidate the molecular details of the putative norspermidine/spermidine-MbaA/NspS signaling system in V. cholerae. Our results further characterize the role periplasmic polyamine-binding proteins play in cyclic-di-GMP-mediated signal transduction within the first polyamine-responsive signaling system identified in bacteria.
Arbeit und Karriere

Karrieren werden oft in Verbindung mit erfolgreichen gesellschaftlichen Posi-tionierungen gebracht. Um dahin zu gelangen, ist Arbeit notwendig. Darüber, welche Arbeit und welche Form der Karriere „erfolgversprechend“ sind, gibt es individuell unterschiedliche Vorstellungen. Allerdings sind weder Arbeit noch Karrieren konstante Konstrukte und somit auch schwer planbar. Welche vielfältigen Verflechtungen zwischen Arbeit und Karriere existieren und welche Mythen damit verbunden sind, wird in diesem Beitrag kritisch diskutiert.
Environmental Aspects of Salmonella

Salmonella remains a major cause of economic loss in domestic livestock and human food poisoning worldwide. In the last 10 years there have been major advances in understanding the salmonella organism, meaning a compiled source of the new research is urgently needed. With fully updated chapters and new coverage of genome structure, virulence, vaccine development, molecular methods for epidemiology and exotics, this second edition is an invaluable resource for researchers of animal and human health.
The continuing challenges of testing species distribution models

1Species distribution models could bring manifold benefits across ecology, but require careful testing to prove their reliability and guide users. Shortcomings in testing are often evident, failing to reflect recent methodological developments and changes in the way models are applied. We considered some of the fundamental issues.2Generalizability is a basic requirement for predictive models, describing their capacity to produce accurate predictions with new data, i.e. in real applications beyond model training. Tests of generalizability should be as rigorous as possible: ideally using a large number of independent test sites (≥ 200–300) that represent anticipated applications. Bootstrapping identifies the role of overfitting of the training data in limiting a model's generalizability.3Predictions from most distribution models are continuous variables. Their accuracy may be described by discrimination and calibration components. Discriminatory ability describes how well a model separates occupied from unoccupied sites. It is independent of species prevalence and is readily comparable between models. Rank correlation coefficients, such as the concordance index, are effective measures.4Calibration describes the numerical accuracy of predictions (e.g. whether 40% of sites with predicted probabilities of 0·40 are occupied) but is frequently overlooked in model testing. Poor calibration could mislead any conservation efforts utilizing models to estimate the ‘value’ of different sites for a given species. Effective assessments can be made using smoothed calibration plots.5The effects of species prevalence on nominal presence–absence predictions are well known. The currently preferred accuracy measure, Cohen's κ, has weaknesses. We argue that mutual information measures, based in information theory, may be more appropriate.6Synthesis and applications. Model evaluation must be informative and should ideally: (i) define generalizability in detail; (ii) separate the discrimination and calibration components of accuracy and test both; (iii) adopt assessment techniques that permit more valid intermodel comparisons; (iv) avoid nominal presence–absence evaluation where possible and consider information-theoretic measures; and (v) utilize the full range of techniques to help diagnose the causes of prediction problems. Few modellers in applied ecology and conservation biology satisfy these needs, making it difficult for others to evaluate models and identify potential misuses. The problems are real, and if uncorrected will damage conservation efforts through the inaccurate assessment of distribution and habitat preferences of important organisms.
Vitamin C: A potential regulator of inflammatory response

xvi CHAPTER 1. BACKGROUND . 1 1.1 Ascorbic Acid . 1 1.1.1 History and Discovery . 1 1.1.2 Overview . 1 1.1.3 Pharmacokinetics (Absorption/Distribution/Metabolism/Elimination) . 3 1.2 Ascorbic acid and clinical disease states . 8 1.3 Ascorbic acid as a modulator of inflammation (Hands-on experience) . 10 1.4 Safety . 19 1.5 Setting the stage . 21 CHAPTER 2: VITAMIN C: A NOVEL REGULATOR OF NEUTROPHIL EXTRACELLULAR TRAP FORMATION . 22 2.
The ‘go for’ construction in Sicilian

In this paper, I offer a semantic and syntactic analysis of the Sicilian periphrasis ‘jiri pi (go for) + infinitive’ (GFC, ‘go for construction’), which is used to emphasize the surprising or unexpected result of an uncompleted action. This construction conveys that the action denoted by the complement verb is interrupted and followed by a sudden and unexpected event. The informative meaning of GFC can thus be described as ‘conative’, in that the subject attempts to perform an action that is partially or fully unaccomplished. On the other hand, the effect of surprise and unexpectedness associated with this construction – but spelled out by the event expressed by the following clause – must be characterized as a conventional implicature that adds up to the propositional content of the sentence. In contrast to the lexical occurrences of the verb go followed by a final clause, GFC semantically and syntactically behaves as a single periphrastic unit, as confirmed by a variety of transparency effects such as clitic climbing and by other diagnostics used to test the degree of grammaticalization of the motion verb and of the construction as a whole.
Genetic and gene expression analysis of nasopharyngeal carcinoma (NPC)

We examined both the chromosomal copy number changes and differential RNA expression profiles in Nasopharyngeal carcinoma (NPC). Gene expression profiles identified a large number of differentially regulated genes involved in diverse functional processes, while genetic analysis detected extensive genomic abnormalities including large and small, discrete regions of copy number change and loci that exhibit uniparental disomy (UPD). The relationship between chromosomal copy number and level of gene expression were analysed. This revealed that the direct copy number/expression link applies in about 60% of the instances of copy number loss/down-expression and less than 35% of instances of copy number gain/up-expression that were examined. Signalling pathway analysis revealed that numerous components involved in the TGF-β, Wnt/β-catenin and Hedgehog pathways were universally upregulated in NPC tumours, and gene expression pattern of the C666-1 cell line approximated to other NPC tumours, indicating that it is a good tumour model. A preliminary in vitro investigation of signalling pathways revealed that the C666-1 cell line is intact in the activin and Hh signalling pathways but not in the TGF-β pathway. However, the C666-1 cells appear to resist activin-mediated cell growth inhibition
A unification of niche and neutral theories quantifies the impact of competition on extinction

Efforts to reconcile Hubbell's neutral theory with classical niche theory have been limited by the lack of a nested analytical framework in which departures from the neutral hypothesis might be quantified in fits to empirical data. Here, we present the first extension of Hubbell's theory to allow for asymmetries in competitive, density-dependent interactions such that niche dynamics stabilize or destabilize coexistence over intermediate time scales, while speciation and extinction regulate an unstable coexistence over evolutionary time scales. As a result, we obtain the first mechanistic metacommunity model to quantify the impact of competition on extinction. Intraspecific exceeding interspecific competition delays extinction beyond neutral expectations, while the opposing scenario generates a stochastic Allee effect that speeds extinction below a critical threshold in population abundance. Surprisingly, this unification of niche and neutral theory provides an economical resolution to the problem of short species lifetimes in Hubbell's original model.
Regulatory Cells and Multiple Myeloma

Large evidence is available in hematological malignancies and solid tumors for elevated level of various regulatory and suppressor cells which impede anti-tumor responses. Therefore, targeting the regulatory cells could be a useful strategy to enhance the anti-tumor immunity. Approaches of depletion or inhibition of regulatory cells showed countable benefits in pre-clinical and clinical studies of some cancers including renal cell carcinoma, metastatic melanoma and colorectal carcinoma. Targeting regulatory T cells in a non-specific approach might cause detrimental autoimmune toxicities which is the key issue. Further studies are necessary to identify tumor associated regulatory cells which will enhance the depletion of specific regulatory cells but not the global population of regulatory cells.
フェンバレレートおよびその〔2S,αS〕‐体のラットおよびマウスにおける比較代謝

フェンバレレート [(RS)-α-cyano-3-phenoxybenzyl-(RS)-2-(4-chlorophenyl) isovalerate] およびその[2S,αS]-体の酸側, アルコール側もしくはCN基の14C標識体をそれぞれ4. 2～30mg/kgの割合でラット, マウスに1回経口投与すると, 両動物種で酸側およびアルコール側由来の14Cは速やかにかつほぼ完全に尿, 糞に排泄され, 14C組織残留量はきわめて低かった. 一方, CN基標識体では前2標識体に比べて14C排泄率はやや低く, 14C組織残留量も高かった. またマウスはラットに比べて14C排泄率が高く組織残留量も低かった. しかし, いずれの標識体を用いても14C排泄率や14C組織残留量に性および異性体間での顕著な差は認められなかった. 500ppmのフェンバレレートをラット, マウスに2週間給餌したのち, 14CN-フェンバレレートを1回経口投与すると, 給餌しない場合に比べて, 14Cはより速やかに排泄され, 組織残留量もいっそう低かった. フェンバレレートおよびその [2S,αS]-体はラットとマウスでエステル結合の開裂, 酸側の2および3位での酸化, アルコール側の2′および4′位での水酸化を経て代謝され, 生成したフェノールおよびカルボン酸はグルクロン酸, 硫酸, アミノ酸などと抱合体を形成した. 代謝物の構造および量には性, 異性体および投与量による顕著な差は認められなかったが動物種間には次のような明瞭な差が認められた. すなわち, 1) 3-phenoxybenzoic acid のタウリン抱合体はマウスに認められラットには検出されなかった. 2) アルコール側の4′位の水酸化体はマウスよりもラットでより多く得られた. 3) 3-(4′-hydroxyphenoxy) benzoic acid の硫酸抱合体はマウスよりラットで多く生成した. 3) SCN-はラットよりマウスで多く認められた.
Cellular signaling and apoptosis research

Preface Trends in Apoptosis Research in Hematology Development of Sepsis Therapeutics and Molecular Diagnostics Apoptosis During Pregnancy Cytochemical and Apoptotic Markers of Tissue Remodeling Understanding the Molecular Pathways for Renal Tubular Epithelial Cell Apoptosis Multisite Phosphorylation of the cAMP Response Element-Binding Protein (CREB) by a Diversity of Protein Kinases TNF Signaling Cascades Cell Death and Survival Profilin: From Allergen to Tumor Suppressor Yeast Therapy for the Treatment of Cancer and its Enhancement by MGN-3/Biobran, an Arabinoxylan Rice Bran Nuclear Calcium Signalling: The Nuclear Envelope Store and the Regulation of Transcription Index.
Dynamics of leaf mass, leaf area and element retranslocation efficiency during leaf senescence in Phyllostachys pubescens

Dynamics of leaf mass (LM), leaf area (LA) and element retranslocation efficiency during leaf senescence was investigated in Phyllostachys pubescens Mazel ex H. de Lehaie in Yongchun, Fujian, China. Comparison of differences in element retranslocation efficiencies (RE) based on per gram leaf dry weight, per leaf and per LA during leaf senescence was carried out. With leaf senescence, the mean decreases of LM, LA and specific leaf mass (SLM) were 19.55%, 15.16% and 5.07%, respectively. The seasonal changes in decrease percentage of LM and LA were similar, indicating that certain mass to area ratios occurred in P. pubescens leaves. On different bases, RE of N and K was positive, while RE of Ca was negative, suggesting that with leaf senescence, N and K were translocated out of senescing leaves to other parts of plant, while Ca accumulated in senescing leaves. For the mean RE of N, P, K, Ca and Mg on different bases, the rank order was RE2 (mg element/leaf)>RE3 (mg element/cm leaf)>RE1 (mg element/g), therefore, RE on the basis of leaf weight or LA would be underestimated.
Truthlikeness for Quantitative Deterministic Laws

Truthlikeness is a property of a theory or a proposition that represents its closeness to the truth. According to Niiniluoto, truthlikeness for quantitative deterministic laws can be defined by the Minkowski metric. I present some counterexamples to the definition and argue that it fails because it considers truthlikeness for quantitative deterministic laws to be just a function of accuracy, but an accurate law can be wrong about the actual ‘structure’ or ‘behaviour’ of the system it intends to describe. I develop a modification of Niiniluoto’s proposal that defines truthlikeness for quantitative deterministic laws according to two parameters: accuracy and nomicity. The presented proposal solves the counterexamples and defines a new way of understanding scientific progress.
Role of tyrosyl-DNA-phosphodiesterase I in mitochondrial DNA repair

i Acknowledgements ii Table of contents iii List of figures vi List of tables viii Abbreviations x Chapter 1 1 1.1 General aspects of mitochondria 1 1.1.1 Mitochondrial evolution 2 1.1.2 Mitochondrial structure 3 1.1.3 Oxidative phosphorylation 4 1.1.4 Mitochondrial DNA 8 1.1. 5 Mitochondrial involvement in disease and ageing 11 1.2 Mitochondrial DNA damage and repair 14 1.2.1 Forms of mitochondrial DNA damage 14 1.2.2 Mitochondrial DNA repair pathways and potential for further identification 16 1.3 Tyrosyl-DNA-phosphodiesterase 1 19 1.3. 1 Function of enzyme in nucleus 20 1.3. 2 Spinocerebellar ataxia with axonal neuropathy 1 21 1.3. 3 Relationship with topoisomerase 1 22 1.3. 4 Mitochondrial topoisomerase 1 24 1.4 Overall aims of study 26 Chapter 2. General materials and methods 2.1 Materials 28 2.1.1 Chemicals and reagents 28 2.1.2 Bacterial strains 28 2.1.3 Mammalian cell lines 28 2.1.4 Mouse strains 29 2.1. 5 Vectors 30 2.1. 6 DNA oligonucleotides 30 2.1. 7 siRNA duplexes 31 2.2 General methods 32 2.2.1 Bacterial culture 32 i) Transformation of chemically competent cells 32 ii) Plasmid DNA isolation from bacteria 33 2.2.2 Tissue culture 33 i) Cell storage 33 ii) Cell maintenance 33 iii) Freezing cells for long term storage 34 iv) Thawing cells from long term storage 34 v) Cell counting 35 vi) Mycoplasma testing and treatment 35 vii) Transformation of Flp-In T-Rex HEK293 cells 35 viii) Poly-L-ornithine treating flasks 36 2.2. 3 Protein manipulation 36 i) Isolation of cytoplasmic protein from human cell lines 36 ii) Isolation of mitochondria from human cell lines 37 iii) Isolation of mitochondria from mouse brain 38 iv iv) Mitochondrial purification 39 v) Mitochondrial localisation assay 39 vi) Protein quantification through Bradford assay 40 vii) SDS-PAGE 41 viii) Western blotting 43 2.2. 4 DNA manipulation 45 i) DNA amplification by polymerase chain reaction 45 ii) Real-time polymerase chain reaction (qRT-PCR) to assess mtDNA copy number 46 iii) Restriction digests of DNA 47 iv) DNA ligation 48 v) Gel electrophoresis of DNA 48 vi) Phenol/chloroform extraction of DNA constructs from agarose 48 vii) Phenol/chloroform extraction of DNA from mammalian cells in culture 49 viii) DNA quantification 50 ix) DNA sequencing 50 Chapter 3. Is TDP1 present and active in the mitochondrion? 51 3.