bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via Scaffolding Protein p62/SQSTM1
Authors: Lee Hye-Mi , Shin Dong-Min , Yuk Jae-Min , Shi Ge , Choi Dae-Kyoung , Lee Sang-Hee , Huang Song Mei , Kim Jin-Man , Kim Chang Deok , Lee Jeung-Hoon , Jo Eun-Kyeong 
Published: December 2010

Abstract
The scaffolding adaptor protein p62/SQSTM1 (p62) has been shown to be an autophagy receptor that acts as a link between the ubiquitination and autophagy machineries. However, the roles of autophagy and p62 in human keratinocytes are not well understood. In this study, we show that keratinocyte autophagy negatively regulates p62 expression, which is essential for the prevention of excessive inflammation and the induction of cathelicidin in human keratinocytes. Stimulation of TLR2/6 or TLR4 in primary human keratinocytes robustly activated autophagy pathways and up-regulated p62 expression through induction of NADPH oxidases 2 and 4 and the generation of reactive oxygen species. MyD88 and TNFR-associated factor 6, key signaling molecules that mediate TLR activation, played an essential role in the induction of autophagy and p62 expression. Additionally, blockade of autophagy significantly increased the generation of inflammatory cytokines and expression of p62 in primary human keratinocytes. Notably, silencing hp62 through RNA interference resulted in a significant decrease in NF-κB activation, inflammatory cytokine production, cathelicidin expression, and cell proliferation (as well as cyclin D1 expression) in keratinocytes. Epidermal expression of p62 was further found to be significantly higher in psoriatic skin than in skin affected by atopic dermatitis or from healthy controls. Collectively, our data provide new insights into the roles of autophagy and p62 in controlling cutaneous inflammation.
Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial
Authors: Laidlaw Maggie , Cockerline Carla A. , Sepkovic Daniel W. 
Published: December 2010

Introduction Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers. Methods Forty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed. Results In pre-menopausal women, treatment supplementation resulted in a significant increase ( P < 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend ( P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups. Conclusions Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated. Trial Registration ClinicalTrials.gov registration #NCT01089049.
Dissimilatory Adenosine‐5′‐Phosphosulfate Reductase
Authors: Schiffer Alexander , Fritz Günter , Büchert Thomas , Herrmanns Karolin , Steuber Julia , Ermler Ulrich , Kroneck Peter MH 
Published: December 2010

AbstractThe iron‐sulfur flavoenzyme adenosine‐5′‐phosphosulfate reductase (APSR) catalyzes the reductive cleavage of APS (adenosine‐5′‐phosphosulfate) to sulfite plus AMP and the reverse reaction, both important reactions within the biogeochemical sulfur cycle. The structure of the dissimilatory enzyme from the hyperthermophilic sulfate reducerArchaeoglobus fulgidusat 1.6 Å resolution reveals APSR as heterotetrameric α2ß2complex; however, the αß heterodimer is the functionally active unit. The FAD(flavin adenine dinucleotide) binding α‐subunit of APSR is structurally similar to the corresponding subunit of fumarate reductases, suggesting a common ancestor that resembles archaeal APSR. A clear separation is observed between the electron transfer process that extends over 25 Å from the protein surface via two [4Fe‐4S] clusters to thesi‐side of FAD and the chemical process of APS reduction at there‐side of FAD. The structures of APSR complex with the substrates APS, sulfite, and AMP trapped the enzyme in four different states and allowed, together with information from spectroscopic studies, to develop a detailed picture of the catalytic cycle. The nucleophilic attack of the N5 atom of FADH−onto the sulfur of APS, both negatively charged, proceeds in a compressed enzyme‐substrate complex relaxed in the formed FAD‐APS and FAD‐sulfite adducts.
Medicinal Inorganic Chemistry: An Introduction
Authors: Thompson Katherine H. 
Published: December 2010

AbstractMetal ions in clinical use today include bismuth compounds, which have been in use for over a hundred years, lithium carbonate, which has been in use for over 50 years, and cisplatin, which was introduced almost 40 years ago. “Metals in medicine” also covers a wealth of newer diagnostic and therapeutic compounds, such as gadolinium‐based contrast agents for magnetic resonance imaging (MRI), samarium‐based compounds for relief of bone pain in intractable cancer, and lanthanum carbonate for the treatment of hyperphosphatemia. In the process, mystical/magical use of metals in medicine has given way to rational design and testing of new metallopharmaceutical compounds. Advances in our understanding of bioinorganic chemistry and increasingly sensitive analytical instrumentation enable an accelerated pace of development in medicinal inorganic chemistry.
Chromatography, Preparative
Authors: Cox Geoffrey 
Published: December 2010

AbstractThe article gives a brief history of the origins and growth of preparative chromatography. The basic theoretical considerations that underlie all preparative chromatographic separations are discussed, mainly describing the influence of the adsorption isotherms on the outcome of the preparative experiment. The various categories of preparative separations are described with some reference to the technologies employed to enable them. Preparative supercritical fluid, chromatography is an important and growing area in preparative separations and is used extensively for the isolation of pure species in pharmaceutical discovery and development. At the other end of the preparative scale, simulated moving bed, a continuous chromatographic production process is discussed. The specific question of bioseparations is treated with particular reference to the reversed phase purification of peptides and proteins.An important section is devoted to the practicalities of preparative separations. This considers the metrics used to quantify the separations, the appropriate particle size and sample introduction techniques. It concludes with a discussion of the various techniques used to enhance product purity and production rate, dealing with recycle, shave recycle, steady‐state recycling, step gradients, backflush, “flip‐flop,” and displacement chromatography.
Speciation and the Fossil Record
Authors: Liow Lee Hsiang 
Published: December 2010

Abstract

The process of the initiation, formation and establishment of descendent species from existing ancestral species is called speciation. Several aspects of this process can be studied using the fossil record, including how and why rates of speciation have changed through geologic history and how the morphology of lineages change over time as descendents gain phylogenetic independence from their ancestors. The fossil record also provides ancient
deoxyribonucleic acid
(DNA) which allows genetic analyses of extinct populations and species that give insight into genetic differentiation, among other processes. Organisms are neither all equally likely to be preserved in the fossil record, nor do they have similar rates of achieving reproductive isolation and morphological differentiation from their ancestors. We know more about the fossil record of speciation in groups such as marine bivalves, gastropods, plankton and bryozoans, which have comparatively better fossil records, than groups such as mammals or plants.

Key Concepts:

Speciation is the process of the evolution and establishment of new species from existing species: parts of this process can only be studied using the fossil record while others are better studied using extant organisms.

Rates of speciation and the temporal sequences of morphological change associated with speciation are two aspects of speciation that are tractable using the fossil record.

The Evolutionary Species Concept (ESC), which states that species are temporal populations that maintain their evolutionary cohesiveness and uniqueness from other such populations, is the most natural and commonly used species concept when dealing with species in the fossil record.

To be suitable for being subjects of the study of speciation using the fossil record, organisms have to be well fossilised in sufficiently large quantities for time intervals during which speciation processes took place, and beyond.

Morphology is one of the most conveniently and accurately measured traits in fossilised organisms.

Studies on living organisms with fossilised representatives tell us that morphological differences can be a good proxy for genetic differences and potential reproductive isolation.

Speciation can occur very rapidly (a few generations) or slowly over extremely long periods of time (millions of years).

The temporal resolution of the fossil record has to be suited to the particular speciation process one is interested in observing, in order for sound inferences to be made.
Lyell, Charles
Authors: Oldroyd David 
Published: December 2010

Abstract
Charles Lyell (1797–1875) a British geologist, well known for his ‘uniformitarian’ geology, his arguments on geological time and the Earth's age, his influence on Darwin and the application of Darwinian theory to humans. His theory involved the piecemeal extinction and emergence of species, the latter by some unknown process. The gradual changeover of forms allowed a ‘statistical’ subdivision of the Tertiary according to the percentages of extant species. Lyell envisaged the slow rise and fall of land in different parts of the globe (which idea was supported by observations of the so‐called ‘Temple of Serapis’ near Naples). Such movements led to climate changes, according to the proportion of high land located at high latitudes at different times. Thereby, Lyell tried to accommodate the evidence for the ‘Ice Age’.
Insect Cell Culture
Authors: van Oers Monique M , Lynn Dwight E 
Published: December 2010

Abstract

Insect cell cultures are widely used in studies on insect cell physiology, developmental biology and microbial pathology. In particular, insect cell culture is an indispensable tool for the study of insect viruses. The first continuously growing insect cell cultures were established from lepidopteran insects around 1960. Since then, more than 600 insect cell lines have been described from over 100 insect species, the majority from lepidopteran (moths) and dipteran (flies and mosquitoes) insects. Among these, the

Drosophila

S2, the

Spodoptera frugiperda

Sf9 and

Trichoplusia ni

High Five cell lines are used most widely. The latter two are susceptible to the baculovirus

Autographa californica

multiple capsid nucleopolyhedrovirus and are used for the expression of foreign genes, for example, for the production of subunit vaccines, to make proteins for functional analyses or crystallography and to produce gene delivery vectors for mammalian cells.

Key Concepts:

Insect cell cultures are a crucial tool in studying the pathology of insect viruses and human viruses vectored by insects.

Insect cells can be grown serum free, at high density and in suspension cultures, allowing the application of bioreactors.

Insect cell cultures are indispensable for the baculovirus expression system.

Insect cells are important for the production of subunit vaccines.

Insect cells are increasingly important to produce human vaccines and gene delivery vectors.
Titration and p
H
Measurement
Authors: Jennings Patricia A , Mullen Christine A , Roy Melinda 
Published: December 2010

Abstract

Titration is the quantitative addition of a solution of known concentration to a solution of unknown concentration until the reaction between them is complete to determine the concentration of the second solution. An acid–base titration is the quantitative determination of the concentration of an acid or a base. Titration of an acid with a base requires that the pH, or relative concentrations of the two reactants, be monitored. pH can be assessed by litmus paper or by indicators, for example, phenolphthalein, but these methods lack precision. Typically, pH measurement in the laboratory is done by measuring the cell potential of that sample in reference to a standard hydrogen electrode. A plot of the pH of an acidic (or basic) solution as a function of the amount of added base (or acid) is a titration curve. From this, the endpoint or equivalent points can be determined.

Key Concepts:

Acid–base titrations determine the concentration of an acidic (or basic) solution (the analyte) by the delivery of a measured volume of base (or acid) of known concentration (the titrant).

The progress of an acid–base titration is often monitored by a titration curve.
Ethics of Research: Scientific Misconduct
Authors: Blom Erica C , De Vries Raymond 
Published: December 2010

AbstractScientific misconduct presents a challenge, not just to the reputation of the misbehaving scientist, but also to research institutions, the integrity of the scientific record and to the enterprise of science itself. In this article we discuss the varied definitions of scientific misconduct and explore the social sources of the concern with the misbehaviour of researchers as well as competing explanations of the causes of that misbehaviour. We review efforts to prevent scientific misconduct and look at how the (mis)conduct of researchers will be influenced by the trend towards interdisciplinary collaboration and the globalisation of research.Key Concepts:Common misbehaviours in research threaten the integrity of science in addition to the more egregious, yet less frequent, acts of falsification, fabrication and plagiarism.Scientific misconduct results from the behaviour of ‘bad apples’ and the organisation of science.Responses to scientific misconduct must address individual and organisational sources of misbehaviour.The rise of interdisciplinary science and the globalisation of science present new challenges to integrity in research conduct.
DNACloning
Authors: Quail Michael Andrew 
Published: December 2010

AbstractDeoxyribonucleic acid(DNA) cloning is the art of creating recombinant DNA molecules that can be introduced into living cells, replicated and stably inherited, such that multiple ‘clonal’ copies of that DNA are produced. Here, DNA of interest is spliced into a DNA vector that has the ability to replicate in host cells and be inherited into future generations of those cells.This article describes the theory behind cloning; the preparation of vector and insert DNA for cloning; the techniques that can be used to create recombinant DNA molecules (including traditional ligation of blunt and sticky ends, TA cloning, topo cloning, ligation‐independent cloning, recombineering and gateway cloning); introduction of recombinant DNA molecules into host cells; the major classes of vectors available and the variety and utility of the various features and that can be present in those vectors.Key Concepts:DNA can be joined, or ligated, together to form a recombinant DNA molecule.When cloning DNA, that DNA is ligated to a vector molecule allowing it to be subsequently immortalised.Recombinant vector:DNA constructs can be introduced into living cells, so‐called host cells, through the process of transformation.Once introduced into host cells, the DNA and vector construct is immortalised and can be replicated and stored.Different vectors allow for introduction and maintenance in different host cells.A range of vectors are available, or can be constructed, that contain a variety of elements that confer upon that clone its usefulness. Such elements may include one or more of the following: sequences that control replication and inheritance within the host cell and sequences that allow selection of the recombinant molecule, for example, antibiotic resistance genes, reporter genes and promoter sequences that drive expression of a gene that has been cloned.
Said, Edward
Authors: Keller Richard C 
Published: December 2010

Abstract

Edward Said (1935–2003) was an American literary critic, university professor and political activist. Said's 1978 book
Orientalism
made a major contribution to the understanding of how the human sciences have reflexively shaped and been shaped by the politics of empire. Much of his work detailed the ways in which European perceptions of the colonial world, and of the Islamic world in particular, relied on spurious claims of academic science which were themselves influenced by imperial ambitions. For Said, politically predetermined biases profoundly shaped European perspectives on race, ethnicity and religion in the colonial world.

Key Concepts:

Academic inquiry is easily influenced by political ideology and vice versa.

The pursuit of knowledge has historically shaped global politics; for example, the scientific study of race and culture had powerful consequences for European colonialism in the nineteenth and twentieth centuries.

That knowledge is socially and politically constructed does nothing to weaken its force; indeed, that fact immeasurably strengthens its power.
Tay–Sachs Disease
Authors: Tropak Michael , Mahuran Don J 
Published: December 2010

AbstractGM2 gangliosidosis is a family of three diseases that include Tay–Sachs disease (described over a century ago), Sandhoff disease and the AB‐variant form, reflecting the need of three gene products to hydrolyse GM2 ganglioside. The recent elucidation of the crystal structures these three proteins have provided a better understanding of the molecular basis of GM2 gangliosidosis. The discovery that most deleterious missense mutations affect the folding or the assembly of the heterodimeric enzyme, and that delays in these processes invoke premature degradation by the endoplasmic reticulum‐quality control system, have suggested a novel therapeutic approach, enzyme enhancement therapy, for some forms of this and other genetic diseases. Progress is also being made on developing a more generally applicable approach, based on gene therapy, for Tay–Sachs and Sandhoff disease. If successful, this will also serve as a model for developing similar therapies for other diseases with neurological involvement.Key Concepts:The history of research into Tay–Sachs disease demonstrates the power of the classical scientific approach to problem solving involving building, over many decades, on the contributions from scientists with diverse interests and expertise.The study or rare diseases often lead to unexpected discoveries of broader‐based metabolic pathways and disease mechanisms.The study of rare diseases can also lead to the development of novel therapeutic approaches that can be adapted to more common diseases.
Pancreatic Cancer: Molecular Genetics and Clinical Applications
Authors: Sakorafas George H , Pappa Irene , Smyrniotis Vasileios 
Published: December 2010

Abstract

Pancreatic cancer (PC) is a relatively common type of cancer with a dismal prognosis. Recent advances in molecular biology allowed the identification of many of the genes involved in pancreatic carcinogenesis; currently, it is accepted that PC is fundamentally a genetic disease caused by inherited and acquired (somatic) mutations in cancer‐associated genes (oncogenes, tumour‐suppressor genes, genome‐maintenance genes). Other genetic/molecular pathways (such as telomere shortening, upregulation and overexpression of growth factors or their receptors (such as EGFR, TGFβ), tumour angiogenesis and alterations of developmental signalling pathways (such as the Hedgehog signalling pathway)) are also involved in pancreatic carcinogenesis. Pancreatic carcinogenesis is a multistep phenomenon, characterised by the progressive accumulation of multiple genetic alterations, which occur in an ordered sequence rather than a random fashion. Advances in our understanding of molecular biology of PC will improve clinical management of patients with PC by providing better diagnostic, prognostic and therapeutic tools.

Key Concepts:

Pancreatic cancer has been associated with inherited and acquired (somatic) mutations in cancer‐related genes.

Genes involved in pancreatic carcinogenesis include oncogenes, tumour‐suppressor genes and genome‐maintenance genes.

Other genetic/molecular pathways are also involved in pancreatic carcinogenesis, such as telomere shortening, developmental signalling pathways (such as the Hedgehog signalling pathway), and upregulation and overexpression of growth factors or their receptors (such as EGFR, TGFβ, VEGF‐A, VEGFR1, VEGFR2).

Pancreatic carcinogenesis is a multistep phenomenon, characterised by the progressive accumulation of multiple genetic/molecular alterations, occurring in an ordered sequence rather than a random fashion.

Potential clinical implications include the recognition of groups of individuals with high risk for PC development (in these groups an as yet undefined programme of intensive surveillance may diagnose pancreatic lesions at a pre‐invasive stage) and the development of new and effective diagnostic, prognostic and therapeutic tools.