bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Products as Cytotoxic Agents
Authors: Cutler Stephen J. , Cutler Horace G. 
Published: September 2010

AbstractIn the first decade of the twenty‐first century, the occurrence of cancers has increased not only in First World countries but also in those countries considered to have a lower standard of living, according to a world cancer report issued in 2008 for the IARC Nonserial Publication by Boyle and Levin. So widespread is cancer, in its various forms, that most adults have either had family members or had friends who have been afflicted by the disease. Projected figures for cancers indicate, in the aforementioned publication, that 12 million cancer cases were diagnosed in 2008 alone and that the number of cancer victims has doubled since 1978. Coupled to the psychological impact that a diagnosis has on an individual is the cost of treatment that must also be considered. Again, according to the National Cancer Institute (December 2008) these costs are estimated to be US$147 billion by 2020. An article, published inUSA Today, claims that new cancer cases in 2008 were projected to be 40,480. And the cost for elderly Medicare patients will be US$21.1 billion for 5 years of treatment for the period 2004–2009. Sadly, one in eight patients with advanced stages of cancer will turn down the offer of recommended care because of costs. While cases may have been misdiagnosed in the twentieth century, the sophisticated techniques available today give a clearer graph of the incidence of the disease. With advanced diagnostics, there has been a concomitant advance in anticancer chemotherapy.
PARP
Inhibitors As Anticancer Agents
Authors: Costantino Gabriele , Pellicciari Roberto 
Published: September 2010

Abstract
Poly(ADP‐ribosyl)ation is posttranslation covalent modification, which is operated by a family of enzymes whose founding member, named PARP‐1, has been involved in a variety of physiological as well as pathological processes. In particular, PARP‐1 is activated by DNA‐strand breaks, and is a key component of the DNA repairing machinery thus acting as a caretaker of genomic stability. Over the last decade, many evidence have accumulated suggesting that PARP inhibitors may find utility as cotherapy with DNA damaging agents in many preclinical models of cancer, and also as monotherapy in some important DNA repair defective tumors. These findings are now translating into clinically useful agents that are undergoing clinical trials. In this chapter, we review the diversity of the PARP family, the significance of poly(ADP‐ribosyl)ation in DNA repairing and the mechanism of PARP inhibitors in cancer therapy. Finally, an overview of the most promising PARP inhibitors under clinical evaluation is given.
TheFDAApprovedHIV‐1 Protease Inhibitors for Treatment ofHIV/AIDS
Authors: Ghosh Arun K. , Anderson David D. , Mitsuya Hiroaki 
Published: September 2010

AbstractOver the past two decades, HIV protease inhibitors have helped revolutionize the treatment of HIV/AIDS transforming this deadly ailment into a more manageable chronic infection. Due to intensive research in the area, a variety of protease inhibitors are now commercially available each of which possesses distinct characteristics and a unique tale of discovery. This manuscript reviews the design and development of the 10 currently available protease inhibitors saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, and darunavir. Special attention is given to the research efforts leading to their discovery and the successes and limitations of these drugs in the clinics. A brief review of the biology associated with the HIV‐1 protease target is provided in addition to a discussion of novel drug candidates currently under investigation.
β‐Lactam Antibiotics
Authors: Testero Sebastian A. , Fisher Jed F. , Mobashery Shahriar 
Published: September 2010

AbstractThe β‐lactam classes of antibacterials are preeminent in the treatment of bacterial infection due to their unparalleled clinical efficacy and clinical safety. Following the discovery of the penicillins, successive β‐lactam drug discovery has added the cephalosporin, penem cephamycin, clavulanate, monobactam, nocardicin, and carbapenem subclasses. The driving force behind much of this era of discovery is the staggering ability of pathogenic bacteria to adapt previous generations of the β‐lactam by the acquisition and expression of resistance mechanisms. Although many factors contribute to β‐lactam resistance, alterations to the molecular targets of the β‐lactams (the penicillin binding proteins) and the use of enzymes (the β‐lactamases) capable of the hydrolytic deactivation of the β‐lactams are paramount. This review traces the historical development of β‐lactam drug discovery, with emphasis on the most recent progress in the medicinal chemistry, biochemistry, and microbiology of the β‐lactams leading to the discovery of new generation β‐lactam antibacterials effective against the Gram‐negative and ‐positive bacterial pathogens of current medical concern.
Therapeutic Agents for the Treatment of Migraine
Authors: Dubowchik Gene M. , Macor John E. 
Published: September 2010

AbstractMigraine is a debilitating condition, often with nearly unbearable throbbing pain, nausea, and greatly reduced thresholds to sensory stimulation. Despite the availability of specific acute medications (such as triptans), for over 15 years, migraine remains an undertreated condition. Although representing a revolution in headache therapy at the time, triptans have a number of shortcomings including cardiovascular side effects resulting from their inherent vasoconstrictive properties, and a significant proportion of refractory patients. CGRP antagonists appear to represent the next revolution in migraine therapy, with clinical safety issues shown to be comparable to placebo and 2 h response rates identical to the triptans. Preventative migraine therapy has been dominated by older drugs developed for other indications such as hypertension, epilepsy, and depression. These agents often have significant side effects. Drugs that act on other relevant mechanisms such as ion channels and nitric oxide generation have been developed and tested in the clinic. These have yet to emerge as rivals to the triptans. However, the pathophysiology of migraine is complex and combination therapies that target multiple mechanisms, including one or more of these, may turn out to be more efficacious than monotherapy. An important aspect of migraine therapy that has been addressed with only partial success is speed of onset. Intranasal and pulmonary delivery offer the potential for more rapid systemic exposure and perhaps faster onset of efficacy. Migraine patients are in particular need of improved nonoral drug delivery systems that can provide rapid relief of headache pain along with associated symptoms.
PET
and
SPECT
in Drug Development
Authors: Welch Andy , Pimlott Sally 
Published: September 2010

Abstract
Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are noninvasive molecular imaging techniques that can be used to provide functional information in the living human body. They use radiolabeled compounds that bind to specific sites on a biological target, known as radiotracers, enabling us to visualize and characterize specific aspects of a biological process. This chapter describes these techniques and how they can be utilized in the drug development process.
Cotton
Authors: Wakelyn Phillip J. , Condon Brian , Thibodeaux Devron P. 
Published: September 2010

AbstractCotton is both a fiber and a food crop that is grown in about 130 countries in the world. About 60 countries cultivate at least 5000 ha and use about 2.5% of the world's total arable land area. In 2009/2010 in the world, about 103 million 217.7‐kg (480‐lb) bales [∼22.4 million metric tons (24.7 million tons)] of cotton fiber and 32.4 million metric tons (35.8 million tons) of cottonseed were produced. Cotton is the most important natural fiber (about 35% of the textile fiber consumed in the world in 2008) used to produce apparel, home furnishings, and industrial products. Cottonseed is one of the world's important oilseeds, used for vegetable oil, animal feed, and linters. About 95% of the world's cotton production is derived from varieties of upland cotton (Gossypium hirsutum) and about 5% is extra long staple cotton (“ELS”;G. barbadense). In 2010 biotech varieties make up more than 60% of the cotton grown in the world. Commercial cottons are white. There has been some interest in organic cotton (∼0.6% of world production) and naturally colored cottons (shades of brown and green are the main colors; only a trace is produced). The demand for more “sustainable” / “ecofriendly” cotton and cotton textiles continues to increase. The origin, biosynthesis, biology, development, production, harvesting, ginning, classification, physical properties, textile processing, morphology, physical structure, chemistry, reactivity, economic aspects, utilization, and health and safety are reviewed.
Graft Copolymers
Authors: Hadjichristidis N. , Pitsikalis M. , Iatrou H. , Driva P. , Chatzichristidi M. , Sakellariou G. , Lohse D. 
Published: September 2010

AbstractThis article deals with the synthesis by different strategies, molecular characterization, solution, and bulk properties as well as potential and industrial applications of graft copolymers.
Thermal Properties
Authors: Thompson Edward V. 
Published: September 2010

AbstractThermal properties of polymeric materials are always important and often critical in both processing stages and product uses. Most polymeric substances are processed and fabricated at elevated temperatures, often as a melt, necessitating the transfer of substantial quantities of heat first to the material to reach the desired temperatures and then to return to the formed or cured product to a solidified state at room temperature. This process can be slow and expensive. Heaters and heat‐exchange equipments must be carefully designed to ensure efficient and effective heat transfer. Accurate thermal property data are needed during the formation or curing processes and for the modeling steps such as extrusion or molding. The term thermal properties include a wide range of properties and phenomena. This article gives detailed data on four polymer properties: thermal conductivity, thermal diffusivity, specific heat capacity, and linear thermal expansivity. These properties are sometimes referred to as thermophysical properties.
Calcium Channels
Authors: Bean Bruce P , McDonough Stefan I 
Published: September 2010

Abstract

Calcium channels are plasma membrane proteins containing calcium‐selective pores that are opened by depolarisation of the membrane voltage. They produce depolarisation‐induced calcium entry in neurons, muscle and other excitable cells, as well as some nonexcitable cells. Functions mediated by calcium channels include contraction of muscle, release of neurotransmitters and hormones by neurons and neuroendocrine cells, and control of gene transcription. Calcium channels are multi‐subunit proteins encoded by many separate genes, and the resulting proteins often govern distinct functional roles within a given cell type. They are targets for modulation by many intracellular signalling pathways including G proteins and phosphorylation. Calcium channels play pivotal roles in many human diseases, particularly of the cardiac and nervous systems, including pain, seizure, hypertension and migraine. Pharmacological blockers for some types of calcium channels are known, including clinically used drugs for hypertension and pain. In some cases such calcium channel blockers are highly selective for specific types of calcium channels, but there is great potential for developing more selective and more potent drugs targeting calcium channels.

Key Concepts:

Voltage‐gated calcium channels are proteins that selectively conduct calcium ions from the outside to the inside of the cell in response to a change in transmembrane voltage from more to less negative.

At the cellular level, calcium channels are a major link between electrical signalling and intracellular biochemical signalling. Calcium channel function is modulated strongly by a variety of intracellular enzymes and signalling pathways.

Many genes encode calcium channels. Different subtypes often carry out distinct physiological functions, via distinct cellular locations and biophysical properties.

Calcium channels govern physiological functions including neurotransmitter and hormone release, muscle contraction and the regulation of gene expression.

Calcium channel dysfunction contributes to diseases including cardiac arrhythmia, hypertension, chronic pain, epilepsy and migraine. They are under investigation for their role in diseases including autism, schizophrenia and bipolar spectrum disorder.
Neuroendocrine Parvocellular Neurons
Authors: Watts Alan G 
Published: September 2010

Abstract

Two sets of neuroendocrine neurons in the hypothalamus form a critical interface between the nervous and the endocrine systems. Neuroendocrine magnocellular neurons that release oxytocin and vasopressin from the neural lobe of the pituitary gland into the general vasculature constitute one of these sets; neuroendocrine parvocellular neurons comprise the other. These neurons release chemical signals into the hypophysial portal vasculature that then control the release of hormones from the anterior pituitary gland. These neurons form part of the neural network that generates pulsatile hormone release. However, more complex patterns of neuroendocrine release are enabled by more widely sourced neural afferents. In some cases, they are direct targets of feedback control by the hormones whose release neuroendocrine parvocellular neurons ultimately control.

Key Concepts:

Neuroendocrine parvicellular neurons release chemical signals (releasing factors) directly into the hypophysial portal vasculature.

Most of the body's hormones are released in pulsatile manner.

Feedback control of neuroendocrine activity is a key regulatory feature for neuroendocrine parvicellular neurons.

The brain contains complex neural networks that can influence the activity patterns of neuroendocrine parvicellular neurons.
Serotonin Receptors
Authors: Hoyer Daniel 
Published: September 2010

AbstractSerotonin (5‐hydroxytryptamine, 5‐HT) receptors are found both in the central and peripheral nervous system as well as in a number of nonneuronal tissues in the gut, gastrointestinal, pulmonary, cardiovascular systems and blood cells. There are at least 15 different receptors organised in six families of theG protein‐coupled receptor(GPCR) type and one family of the Cys‐loop ligand‐gated channel type. Although the number of 5‐HT neurons in the brain is rather limited to the raphe system, projections occur across the brain and most receptors subtypes are largely distributed throughout the central nervous system (CNS). However, 95% of the 5‐HT is produced peripherally, especially in the gut, and most 5‐HT receptors are also present peripherally. It is to be expected that drugs targeting peripheral 5‐HT receptors will represent a wave of 5‐HT‐related therapies. 5‐HT has been implicated in the aetiology of a number of diseases such as migraine, hypertension, depression, anxiety, schizophrenia, irritable bowel syndrome, eating disorders and vomiting. Many of the current treatments for such disorders interact with the 5‐HT system.Key Concepts:Serotonin (5‐hydroxytryptamine, 5‐HT) is one of the oldest neurotransmitters. 5‐HT acts through a multitude of receptors in the brain and the periphery. Serotonin receptors are targeted by many drugs on the market or in clinical development for various central and peripheral pathologies such as depression, anxiety, schizophrenia, migraine, functional bowel disorders, chemotherapy‐induced emesis, eating disorders and others.
Locomotion
Authors: Grey MJ 
Published: September 2010

AbstractLocomotion is an animal's ability to move itself from place to place. Locomotion requires the movements of the body or specialised parts of the body to generate propulsive forces on land, water or air. Muscles produce these forces in multicellular organisms. Muscle specialisation, mechanics and skeletal form combine to establish the speed, efficiency and endurance of locomotion. Most locomotor movements involve the rhythmic, co‐ordinated contractions of numerous muscles with the basic motor pattern provided by networks of neurons called central pattern generators (CPGs). In vertebrates, the integration of sensory information into CPGs occurs primarily within the spinal cord. However, the supraspinal integration of sensory information is more important in humans. Effective locomotion also requires the correct orientation of the body with respect to the environment, and this is particularly important in humans.Key Concepts:The type of motor unit used in locomotion is dependent on the speed of locomotion.Specific muscle forces produced during locomotion are almost independent of body size.Energy is stored and released by tendons.Central pattern generators produce the rhythmic alternation flexion/extension bursts of muscle activity associated with locomotion.Afferent feedback reinforces the locomotor muscle activity and controls the phase transition from stance to swing.Locomotion is initiated by command neurons located in the brain stem and lateral hypothalamus.Information from the somatosensory, vestibular and visual systems is used to provide stability for bipedal human walking.Many of the concepts about the control of locomotion derived from animal studies apply to humans; however, human walking requires greater supraspinal control than that for other animals.
Bursa of Fabricius
Authors: Mustonen Laura , Alinikula Jukka , Lassila Olli , Nera Kalle‐Pekka 
Published: September 2010

Abstract

The bursa of Fabricius plays a central role in the development of the antibody‐producing B‐lymphocyte lineage in birds. It consists of more than 10 000 follicles surrounded by connective tissue. These follicles provide an appropriate microenvironment for generating a primary repertoire of antibodies. Immunoglobulin gene diversification is achieved by gene conversion and is antigen independent. Follicular B cells undergo very rapid cell division while expressing several genes also expressed in proliferating germinal centre B cells, such as
AID
,
UNG
,
Pax5
and
Bcl6
. Bursal B cell line DT40 provides a unique model system for gene‐targeting studies clarifying the B‐cell development, function and Ig diversification.

Key Concepts:

Bursa of Fabricius is the primary site for B‐cell development and antibody repertoire formation in birds.

Antibody diversification in the bursa of Fabricius is antigen independent and occurs mostly by Ig gene conversion.

Bursal derived DT40 B cell line provides a reverse genetic model to study molecular function of B cells.
Immunodeficiency, Primary: Affecting the Adaptive Immune System
Authors: Vihinen Mauno 
Published: September 2010

Abstract

Primary immunodeficiency (PID) is an intrinsic defect of the immune system. Patients with PID have increased susceptibility to recurrent and persistent infections, and they may also have autoimmune and cancer‐related symptoms. PIDs are mainly rare hereditary disorders of the immune system which often have serious consequences. Infections are the hallmarks of PIDs. Clinical descriptions have already been made for more than 200 PIDs, for which approximately 170 genetic aetiologies have been described. There are several different mechanisms behind PIDs. Some PIDs affect T‐ or B‐cell functions and when both cell types are affected lead to severe combined immunodeficiencies (SCIDs). Other PIDs affect major histocompatibility complex, antibody production, lymphocyte apoptosis, phagocytosis, complement cascade or the innate immune system.

Key Concepts:

Adaptive immunity is a specific and long‐lasting response of lymphocytes to antigens.

Combined immunodeficiency affects both B‐ and T cells.

Lymphocytes are white blood cells including B‐ and T cells.

Signal transduction is a process by which a cell converts one kind of signal or stimulus into another. In a signalling cascade an extracellular signal interacts with a cell surface receptor, which leads to a change in the level of a second messenger and ultimately a change in the cells functioning.
Tiering in the Sea – Reefs and Burrows (Late Palaeozoic)
Authors: Wood Rachel A 
Published: September 2010

AbstractTiering is often considered as a proxy for the ecological complexity of ancient communities. Ancient reefs in the Late Palaeozoic were dominated by microbial communities that formed complex substrate topographies, together with a variety of calcified algae and suspension‐feeding metazoans that populated open and cryptic surfaces. Tiering in epifaunal communities increased significantly in the Ordovician to form complex tiered communities that persisted throughout the Palaeozoic. By contrast, infaunal tiering developed slowly, with occupation of deeper depths being achieved only by the Lower Carboniferous.Post‐Permian mass extinction epibenthic and infaunal biotas were of very low diversity, and composed of small‐sized, low‐tiered suspension‐feeding opportunists. Epifaunal communities increased in complexity and tiering after ∼1 million years as crinoids and bryozoans returned. Complexity and depth of burrowing communities only returned to pre‐crisis levels by the Middle Triassic.Key Concepts:Tiering is considered as a proxy for the ecological complexity of ancient communities.Late Palaeozoic reefs and mud mounds bore complex substrate topographies produced in part by microbial carbonate production: these supported diverse and well‐tiered open and cryptic communities that persisted to the end of the Permian.Infaunal tiering developed slowly from the Ordovician, with occupation of deeper depths being achieved only by the Lower Carboniferous.Post‐Permian mass extinction epibenthic and infaunal biotas consisted of very low diversity, small‐sized and low‐tiered communities.Epifaunal communities increased in complexity and tiering as crinoids and bryozoans returned. Infaunal communities saw the return of suspension feeders and finally crustaceans, but the size and depth of burrowing communities only returned to pre‐crisis levels by the Middle Triassic.