bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular p
H
Measurement
Authors: Malhotra Darpan , Casey Joseph R 
Published: February 2015

Abstract

p
H
is a profound regulator of cellular function. It is, therefore, often important to assess intracellular p
H
. Given the small size of individual cells and their sensitivity to perturbation, measurement of intracellular p
H
requires sensitive, indirect measurement approaches. These include equilibration of weak acids/bases, nuclear magnetic resonance spectroscopy, p
H
microelectrodes, fluorescent p
H
indicator dyes and p
H
‐sensitive fluorescent proteins. Presently, the use of fluorescence techniques predominates, as these permit sensitive detection and the possibility to discretely measure p
H
in different cellular compartments. The selection of intracellular p
H
measurement technique is guided by consideration of their strengths and weaknesses, in addition to technical considerations. Cells resist changes of p
H
through p
H
buffering molecules, including proteins and bicarbonate, which together are called the cell's buffer capacity.

Key Concepts

Cellular processes are highly sensitive to pH, so cells have redundant mechanisms to control their pH.

Buffer capacity is the ability of cells to control pH by absorbing or releasing H
+
from chemical pH buffering molecules.

Cell membranes contain embedded transport proteins able to move H
+
, or pH‐buffering HCO
3
−
in order to tightly control cytosolic and organellar pH.

pH of the cytosol and other intracellular compartments can be measured.

Certain molecules will absorb light and release a photon of light at a longer wavelength, a process known as fluorescence.

Fluorescent dyes and proteins are the most common means to report on intracellular pH.
Bütschli,O
Authors: Fokin Sergei I 
Published: February 2015

AbstractOtto Bütschli (1848–1920) – professor of zoology and palaeontology at Heidelberg University, made fundamental contributions to cytology and the investigation of unicellular organisms, first of all ciliates. Bütschli was the first to recognise and to demonstrate that conjugation of ciliates was not a reproductive process but a sexual reorganisation of the cell similar to cross‐fertilisation. His protozoan studies culminated in a three‐volume monograph (Bütschli, 1880–1882, 1883–1887, 1887–1889), which also contained many of his own original works. This 2000‐page critical review of contemporary knowledge actually established protozoology as an autonomous discipline. Moreover, in 1875, Bütschli was the first to identify and determine the sequence of the stages of nuclear division (mitosis) in several types of animal cells. He provided excellent descriptions of dividing cells.
Weller, Thomas Huckle
Authors: Mawdsley Stephen E 
Published: February 2015

AbstractDr. Thomas H. Weller, MD, was an American virologist and paediatrician who was jointly awarded the 1954 Nobel Prize in Physiology or Medicine with Dr. John F. Enders and Dr. Frederick C. Robbins for discovering a method to culture poliovirus in various tissues. The method transformed the field of virology and led to the discovery of many vaccines.
History of Classical Anatomy
Authors: Cosans Christopher E 
Published: February 2015

Abstract

Anatomy was developed in ancient Greece by physicians and natural philosophers who used dissection and vivisection to investigate the nature of the body. The earliest medical texts are written by Hippocratic authors that make reference to the location of parts within the body but do not describe them on a level of detail that indicates dissection. Writing in the fourth century
bce
, Plato advanced a detailed account of how the bodies' various parts might be interconnected and organised in his
Timaeus
. After him, Aristotle began the first systematic dissections and offered an extensive study of how the parts of animals are interconnected within the body and vary between different life forms. In Alexandria Egypt, Herophilus and Erasistratus applied anatomical methods to medicine with the dissection of human bodies. Anatomical practice continued to be refined throughout antiquity until it reached its pinnacle with Galen's monkey dissections and vivisection experiments (
c
. 129–
c
. 216
ce
).

Key Concepts

Analogismos
is a mode of reasoning used by rationalists in which conclusions about theoretical entities were made from observable appearances.

Anatome
is a transliteration of Greek term
anatome
that means a cutting up and refers to both dissection and vivisection.

Epilogismos
is a type of reasoning advocated by empiricists in response to the rationalists in which the physician reasons from one experience to another without considering theoretical entities.

Nous
is a term used by Plato to refer to a principle of intelligence that he saw as underlying the order within the body, as well as within the universe as a whole.

Pneuma
is a subtle substance believed to be taken into the lungs with breathing and passed on into the arteries. Often translated into English as breath or spirit. Galen believed that the vital pneuma delivered to the brain by the arteries was concocted into psychic pneuma important for the function of the nervous system.

Sinews are strands within the body that were associated with locomotion by early physicians and natural philosophers. In the third century
bc,
distinctions were made among sinews between nerves, tendons and ligaments.

Soul is an aspect of the living being that distinguishes it from inanimate objects and dead bodies. In ancient biology, the soul was regarded as a natural entity that could be studied.

Vessels are long tubes within the body that were distinguished as arteries and veins during the early third century
bc
.
The History of Anaesthetics
Authors: Wilkinson David J 
Published: February 2015

Abstract

The history of the development of anaesthesia can be traced back for many centuries and is closely linked with the development of surgery. Most current descriptions of this history tend to focus on the affluent Western World from the mid‐nineteenth century onwards. Although rich in stories about many aspects of anaesthesia development, this provides a very narrow viewpoint and ignores the contributions made by early civilisations that are difficult to quantify due to inadequate translations of original documents and persistent repetition of inaccurate myths. The history of anaesthesia varies from country to country and should always be considered in relation to who has written the document. It is a process that is still continuing and there is much still to be learnt and recorded from the past and present.

Key Concepts

Anaesthesia history varies according to the culture from which it is written.

Anaesthesia history varies from country to country as historians tend to emphasise their own cultural contributions to the exclusion of others.

Much in anaesthesia history can be traced back for centuries as an understanding of human physiology slowly evolved.

It is likely that there are many written documents, particularly in Arabic and Indian languages, that could augment current understanding of anaesthesia history significantly.

Many anaesthesia historians continue to repeat previously published stories without any attempt to verify their accuracy.

The development of modern anaesthesia has allowed the anaesthetist increasing control over a patient's physiology that has in turn permitted surgery to expand and develop.

The history of anaesthesia in the less affluent world may well be limited to a few decades and bear no relationship to that seen in the affluent world.
Informed Consent: Ethical and Legal Issues
Authors: Holm Søren 
Published: February 2015

Abstract

Informed consent from research participants is a necessary legal and ethical requirement for research involving human subjects. Valid informed consent relies on giving full information and on the capacity of research participants to consent.
The article describes the historical development of the concept of informed consent in biomedical research and explores its current embedding in international legal documents. It discusses the specific problems of informed consent in fast‐moving research areas and possible solutions in ‘broad’ or ‘dynamic’ consent. The specific issues raised in relation to consent from minors and other incompetent persons are discussed, as are the secondary research use of routine clinical data and the research use of old tissue samples and other historical materials and data obtained without consent.

Key Concepts

Informed consent is a central concept in modern research ethics and law.

Valid consent can only be obtained if the prospective research participant is fully informed, is competent to consent and not subject to coercion or undue pressure. In fast‐moving research fields where future research use is difficult to predict, ‘broad’ or ‘dynamic’ consent may be used in certain circumstances.

For persons who are incompetent to consent, researchers must often rely on proxy consent (e.g. parents consenting for small children).

A proxy must make a decision to consent based solely on considerations of the best interest of the incompetent person.
Intelligence, Heredity and Genes: A Historical Perspective
Authors: Goodey CF 
Published: February 2015

Abstract

The idea of an intelligence specific to humans has not always existed but grew from pre‐modern ideas of cultural and religious status, becoming fully established at the end of the seventeenth century as part of the application of logic to natural history categories. John Locke, seeing empirical learning as the route towards human reason, also helped establish modern notions of intellectual disability and deficiency. The late nineteenth century began to see these as hereditary traits, capable of moulding by eugenics. Its attachment of ‘intelligence’ to an existing statistical abstraction (the Gaussian curve) enabled this metaphysical concept to be correlated with the physical phenomenon of genetic material, as both were now apparently measurable. The ‘nature/nurture’ and ‘normal/abnormal’ frameworks dominating today's cognitive genetics are not trans‐historical but outcomes of this eugenic mind‐set.

Key Concepts

The idea that there is a peculiarly human intelligence defining and circumscribing the species dates only from the early modern period.

Intelligence denotes primarily a status group, which has evolved from earlier categories of status that were social and religious in character.

Definitions of intelligence, including current ones, are historically contingent.

Definitions of intelligence in the last resort have no common denominator.

Theories of heredity and genetic explanations of cause are the product of social anxieties around status.

Theories aligning intelligence with heredity can only be understood in relation to theories of intellectual disability that are equally historically contingent.
Macrophage Foam Cells
Authors: Valledor Annabel F , Lloberas Jorge , Celada Antonio 
Published: February 2015

Abstract

Foam cells are lipid‐loaded macrophages that are generated from the massive uptake of modified low‐density lipoproteins and the intracytoplasmatic accumulation of cholesteryl esters. Foam cells are present in all stages of atherosclerosis and participate in inflammatory responses and tissue remodelling within the arterial intima. Foam cells can also be generated as a consequence of infection by persistent pathogens, such as
Mycobacterium
,
Chlamydia
and
Toxoplasma
. These pathogens meet nutritional advantages by residing within cells that accumulate lipids. When the immune system is unable to eliminate substances perceived as foreign, it produces a granuloma, composed mostly of macrophages, attempting to wall off the non‐self material. This article reviews the processes that lead to the regulation of foam cell formation in atherosclerosis and infection.

Key Concepts

Foam cells are lipid‐loaded macrophages.

Foam cells are generated upon massive uptake of modified low‐density lipoproteins and the intracellular accumulation of cholesteryl esters.

Foam cells form during development of atherosclerosis and as a result of different infections.

Foam cells participate in inflammatory responses and tissue remodelling.

Endothelial transmigration of monocytes is the first step in the development of atherosclerosis.

Once monocytes reach the arterial wall intima, they undergo phenotypic transformation into macrophages, internalise large amounts of modified LDLs and become foam cells.

Heterodimers of liver X receptors (LXR) and retinoid X receptors (RXR) directly upregulate the expression of several genes involved in lipid and lipoprotein homeostasis.

When the immune system is unable to eliminate substances perceived as foreign, it produces a granuloma, composed mostly of macrophages, that attempts to wall off the non‐self material.
Membrane Insertion of Tail‐anchored Proteins
Authors: Borgese Nica 
Published: February 2015

AbstractTail‐anchored proteins are a special class of transmembrane proteins, consisting of a cytosolic domain anchored to the phospholipid bilayer by a single hydrophobic segment adjacent to their most C‐terminus. Because of their particular topology, the C‐terminal anchor must be inserted into membranes post‐translationally by mechanisms that differ from the well‐known targeting/translocation co‐translational pathway. Recently, several advances have created a new understanding of the tail‐anchored protein insertion machinery. Because of the essential cellular roles carried out by tail‐anchored proteins, including vesicle fusion, regulation of apoptosis and formation of interorganellar contact sites, uncovering the machinery responsible for their biogenesis should further our ability to understand a wide variety of diseases such as forms of cancer caused by activation of the tail‐anchored protein oncogene BCL2.Key ConceptsTail‐anchored proteins have C‐terminal hydrophobic domains.Tail‐anchored proteins are inserted post‐translationally into the membrane.The GET complex inserts tail‐anchored proteins into the endoplasmic reticulum membrane in yeast.The TRC complex chaperones tail‐anchored proteins into endoplasmic reticulum membranes in mammals.The mitochondrial outer membrane appears to be the preferred destination of tail‐anchored proteins that fail to engage the GET/TRC complex.Functions of the GET/TRC pathway additional to tail‐anchored protein targeting are presently under intense investigation.
Bioscience Policies
Authors: Dickenson Donna L 
Published: February 2015

AbstractThe rapid pace of change in the biosciences makes setting biotechnology policies and regulating the life sciences difficult for governments, but no less necessary. Although government policies around the globe are sometimes classed as ‘pro‐science’ or ‘anti‐science’, that is a misleading oversimplification. Nurturing the ‘bioeconomy’ is a key goal for most national governments, leading in the United Kingdom to a comparatively loose regulatory policy, for example, in relation to mitochondrial transfer and germline genetic modification. But in genetic patenting, a recentUScourt decision has reversed the trend towards privatisation of the human genome, which many scientists perceived as impeding their research. Opposition to permissive regulatory policies thus often comes not only from civic or religious groups but also from within bioscience itself. In the area of vaccination against infectious disease, governments face an additional challenge from pandemics at the same time that financial austerity has prompted cutbacks in public health funding.Key ConceptsIt is an oversimplification to divide government policies into ‘pro‐science’ or ‘anti‐science’ categories.Governments are under pressure to promote the ‘bioeconomy’ but must not ignore ethical dilemmas or permit new developments uncritically.Scientists and the general public have formed surprising alliances in favour of greater transparency in intellectual property and against permissive patent laws that may actually impede rather than benefit science.In addition to government, civic bodies and individual researchers, we need to examine the role of the private biosciences sector in lobbying for particular policies.Religious groups are not the only source of opposition to some new scientific developments, and the so‐called ‘war’ between science and religion diverts our attention from other more important issues such as the commodification of bioscience.Government bioscience policy on vaccination needs to address social issues of public safety and equality, not just individual autonomy to choose or reject immunisation.
On Human Brain Networks in Health and Disease
Authors: Braun Urs , Muldoon Sarah F , Bassett Danielle S 
Published: February 2015

Abstract

The brain is a complex system whose function relies on a diverse set of connections or interactions between brain regions. Using the mathematical framework of complex networks, these interaction patterns can be parsimoniously represented as brain graphs: each brain area is represented as a network node and each connection is represented as a network edge. These methods have been used to demonstrate that human brain networks display properties such as a small‐world architecture that may directly facilitate cognitive processes. Moreover, mounting evidence suggests that these properties are altered in disease states, potentially providing important biomarkers for psychiatric and neurological disorders and informing our understanding of the mechanisms of altered cognitive function. Here, the basic concepts in network science are reviewed, and the properties of healthy and diseased brain networks discussed. Relationships between network diagnostics and alterations in behavioural or cognitive variables associated with Alzheimer's disease, schizophrenia and epilepsy are highlighted.

Key Concepts

The brain is a complex system that can be represented by a graph.

In a graph, nodes represent brain regions and edges represent the links or connections between those areas, forming a complex network.

Brain networks display properties such as a small‐world architecture or a hierarchical modular organisation that may directly facilitate cognitive processes.

These properties are altered in disease states, potentially providing important biomarkers for psychiatric and neurological disorders.
Cilia on the Brain: Primary Cilia and Their Roles in Brain Function
Authors: Guadiana Sarah M , Grove Elizabeth A 
Published: February 2015

AbstractThe primary cilium was first discovered over 100 years ago but only relatively recently has it been widely regarded as an integral cellular organelle for brain development, maturation and function. Defects in primary cilia contribute to a set of human disorders, ciliopathies, which are multi‐systemic in pathology and often include abnormalCNSarchitecture and intellectual deficits. The intricate structure of the cilium and the molecules that localise to the axoneme all contribute to elegantly orchestrated signalling pathways that influence the whole cell. From their role in neural tube development, neuronal migration and differentiation, to their putative role in adult cognition, primary cilia are critical for diverse aspects of brain function. Yet our current understanding is still very limited: much remains to be discovered about primary cilia biology and ciliary function in the mammalian brain.Key ConceptsPrimary cilia are unusual cell organelles that look similar to antennae protruding from the cell.Almost all brain cell types have primary cilia, which transduce signals from the milieu.Ciliopathies in humans result from primary cilia defects and often include cognitive impairments and cortical malformations.Primary cilia contribute to brain development and function.
Children's Requests for Clarification in Investigative Interviews About Suspected Sexual Abuse
Authors: Malloy Lindsay C. , Katz Carmit , Lamb Michael E. , Mugno Allison P. 
Published: February 2015

SummaryIn investigative interviews, it is vital that children request clarification when necessary so that crucial legal decisions can take into account the most accurate and detailed information. In the present study, 91 investigative interview transcripts about suspected child sexual abuse were coded to answer these research questions: (i) How often and how do children request clarification in investigative interviews? (ii) What factors (age, alleged abuse frequency, interviewer prompt type) are associated with children's requests? and (iii) How do interviewers respond to clarification requests, and are these interventions associated with relevant responses from children? Children rarely requested clarification, although, as expected, older children made more requests. Most requests were explicit (e.g., What do you mean?) and in response to invitation prompts. Question ‘rephrasing’ was the most common interviewer intervention regardless of child age. Results have implications for interviewing children in various contexts and for advancing our understanding of children's cognitive and communicative development. Copyright © 2015 John Wiley & Sons, Ltd.
Total Syntheses and Biological Evaluation of Miuraenamides
Authors: Karmann Lisa , Schultz Katharina , Herrmann Jennifer , Müller Rolf , Kazmaier Uli 
Published: February 2015

AbstractThe miuraenamides, relatively simple representatives of a class of cyclodepsipeptides with high antitumor activity, can be easily and flexibly obtained by the concept of peptide modification. A reaction sequence consisting of an aldol reaction, oxidation, and methylation of the glycine subunit of the cyclodepsipeptides allows the incorporation of the unusual α,β‐unsaturated dehydroamino acid in one of the last steps of the synthesis.
A Separation‐Integrated Cascade Reaction to Overcome Thermodynamic Limitations in Rare‐Sugar Synthesis
Authors: Wagner Nina , Bosshart Andreas , Failmezger Jurek , Bechtold Matthias , Panke Sven 
Published: February 2015

AbstractEnzyme cascades combining epimerization and isomerization steps offer an attractive route for the generic production of rare sugars starting from accessible bulk sugars but suffer from the unfavorable position of the thermodynamic equilibrium, thus reducing the yield and requiring complex work‐up procedures to separate pure product from the reaction mixture. Presented herein is the integration of a multienzyme cascade reaction with continuous chromatography, realized as simulated moving bed chromatography, to overcome the intrinsic yield limitation. Efficient production of D‐psicose from sucrose in a three‐step cascade reaction using invertase, D‐xylose isomerase, and D‐tagatose epimerase, via the intermediates D‐glucose and D‐fructose, is described. This set‐up allowed the production of pure psicose (99.9 %) with very high yields (89 %) and high enzyme efficiency (300 g of D‐psicose per g of enzyme).
Rhodium(II) Metallopeptide Catalyst Design Enables Fine Control in Selective Functionalization of Natural SH3 Domains
Authors: Vohidov Farrukh , Coughlin Jane M. , Ball Zachary T. 
Published: February 2015

AbstractChemically modified proteins are increasingly important for use in fundamental biophysical studies, chemical biology, therapeutic protein development, and biomaterials. However, chemical methods typically produce heterogeneous labeling and cannot approach the exquisite selectivity of enzymatic reactions. While bioengineered methods are sometimes an option, selective reactions of natural proteins remain an unsolved problem. Here we show that rhodium(II) metallopeptides combine molecular recognition with promiscuous catalytic activity to allow covalent decoration of natural SH3 domains, depending on choice of catalyst but independent of the specific residue present. A metallopeptide catalyst succeeds in modifying a single SH3‐containing kinase at endogenous concentrations in prostate cancer (PC‐3) cell lysate.