bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein–Ligand Interactions: Thermodynamic Basis and Mechanistic Consequences
Authors: Fisher Harvey F 
Published: March 2015

Abstract

It is difficult to imagine any biological process that is not initiated by the binding of some chemical entity (or ‘ligand’) to a protein. Thus, enzymatic catalysis, signal transduction, ion channel activity, immune responses and the various events involved in genetic expression are all obvious examples of events which, at the molecular level, must begin with the binding of some ligand to a specific binding site on a protein molecule. Furthermore, as each one of these processes proceeds along its reaction pathway, modulation of the affinities of such ligands, positive and negative interactions caused by the binding of other ligands and the release of these ligands either in their original or in altered form constitute obligatory steps in the driving forces and controlling restraints that adapt them to their specific tasks. We extend the basic conceptions set forth in this article to a on more detailed level focused the fundamental nature of ligand–ligand interactions of a protein–ligand complex and the energetic mechanistic consequences to which they lead.

Key Concepts

Every biological reaction is initiated by a protein–ligand binding step.

Such reactions never involve the binding of only a single ligand or a single step.

The binding of two ligands to the same protein always involves a mutual interaction.

The product of a ligand‐binding reaction is a new entity in itself; its structure and its properties may differ substantially from the simple sum of those of its initial components.

The concept of G Weber's ‘thermodynamic square’ permits the evaluation of a variety of interaction parameters.

Patterns of interaction parameters provide a basis for exploring ligand‐binding energy transduction.

Measurement of ligand‐binding heat by techniques using higher levels of mathematical integration provides more detailed dissection into parameters such as enthalpy, entropy, heat capacity and their corresponding interaction terms.

The ‘fluctuating protein’ concept suggests that protein reactions proceed as multiple traces on multi‐dimensional free‐energy landscapes.

Consequences of the thermodynamic complexity of ligand binding suggest new views of such processes as enzymatic catalysis, signalling events and evolutionary aspects.
Centrifugation Techniques
Authors: Rickwood David , Graham John 
Published: March 2015

Abstract

Centrifugation is the use of the centrifugal forces generated in a spinning rotor to separate biological particles, such as cells, viruses, sub‐cellular organelles, macromolecules (principally proteins and nucleic acids) and macromolecular complexes (such as ribonucleoproteins and lipoproteins). The three main methods of separation are differential pelleting, rate‐zonal centrifugation and isopycnic centrifugation. The first two methods separate particles primarily on the basis of size while isopycnic centrifugation separates particles on the basis of their density. The choice of centrifugation method depends on the nature of the particles and often more than one separation technique is required. For example, membrane fractionation often involves first making an enriched fraction from a cell homogenate by differential pelleting followed by isopycnic centrifugation to obtain purified fractions.

Key Concepts

Modern centrifuges and their rotors can generate centrifugal forces up to a million times that of the Earth's gravity that can separate very small particles.

Depending on the centrifugation force used, particles from cells to those as small as macromolecules can be separated.

Particles can be separated on the basis of their size using differential pelleting or rate‐zonal centrifugation. Alternatively, particles can be separated on the basis of their density using isopycnic centrifugation.

Once cells are broken open by homogenisation, they can be fractionated into a range of defined membrane fractions so that it is possible to analyse the functions of the different components of cells.

Many centrifugation purification procedures involve sequential centrifugation steps, often a size separation followed by purification using isopycnic gradient centrifugation.
Neural Orchestration of Food Intake and Energy Expenditure
Authors: Soleiman Matthew T 
Published: March 2015

Abstract

Eating is one of the most hard‐wired and ubiquitous behaviours. Yet, we have only begun to map the neural circuits underlying its control. By sensing peripheral metabolic states via hormonal signals such as leptin, insulin, ghrelin and cholecystokinin, circuits composed of specific cell types either drive or suppress food intake. Homeostatic inhibitory neurons of the hypothalamic arcuate nucleus co‐expressing agouti gene‐related protein and neuropeptide Y coordinate hunger through divergent projections, while additional circuitry seems dedicated to hedonic feeding and the motivation to eat. In contrast, the vagus nerve delivers visceral information to broadly projecting neurons of the nucleus tractus solitarius to acutely suppress appetite. One of their downstream targets includes excitatory calcitonin gene‐related peptide‐expressing neurons of the parabrachial nucleus that project to the central amygdala. Distinct circuitry seems to regulate energy expenditure and body weight independent of feeding. Hence, the nervous system differentially stimulates and suppresses eating via a number of separate, neuroanatomically distributed and molecularly distinct circuits.

Key Concepts

Peripheral metabolic signals influence neurons either by circulating through the blood and passing from vasculature into the central nervous system or by acting on interoceptive sensory neurons of the vagus nerve.

Each peripheral metabolic signal has the potential to have widespread and coordinated effects on different neural populations.

Separable neural circuitry is dedicated to appetite stimulation versus appetite suppression.

Considering either the neural circuitry of appetite stimulation or suppression, there are a number of circuit‐level mechanisms that likely interact and act in parallel.

Some neural circuits appear to affect energy expenditure independent of feeding.
Plant Behavioural Ecology
Authors: Trewavas Anthony J 
Published: March 2015

Abstract

Visible plant behaviour, exemplified by adaptive phenotypic plasticity, results from the challenge of exploiting patchy resource distribution and competition as well as herbivory and disease. Key concepts to understand plant behaviour and behavioural ecology require systems understanding and the consequences of self‐organisation and distributed control. This article extends these concepts into niche formation and its exploitation by intelligent foraging. Seed dormancy is employed to optimise the future niche for the seedling. Adaptive phenotypic plasticity, local signalling producing local responses, arises from distributed control. The ability of leaves to control their internal temperature is a prime example. Competition for plant resources is fundamental to selection and extends its system structure. Game theory describes the necessary individual interactions. The shade avoidance and root proliferation syndromes are reactive schedules designed to outwit other competing plants. The phenotypic changes necessary for these schedules are controlled by the cambium that demarcates resource distribution. Territory is also competed for and requires forms of self‐recognition, all experimentally observed. Finally, competition for mates, the ultimate determinant of fitness, occurs but in ways different to those in animals.

Key Concepts

Biology is a system of systems.

Self-organisation is key to behaviour.

Self-organisation requires distributed control.

The niche extends the plant system.

Intelligent foraging required for fitness.

Distributed control in tissues.

Competition extends the system.

Game theory and fitness.

Competition over territory requires self‐recognition.

Competition for plant mates.
Screening for Anti‐cancer Drugs inDrosophila
Authors: Richardson Helena E , Willoughby Lee , Humbert Patrick O 
Published: March 2015

AbstractThe vinegar fly,Drosophila melanogaster,has been a cornerstone of genetic analysis and cell and developmental biology research for over 100 years. Within the last decade,Drosophilais making its mark in translational research in its utilisation in modelling human diseases and in screens for small molecule inhibitors. In particular, its use in modelling cancer development and in identifying anti‐cancer therapeutics is beginning to make an important contribution to the current drug discovery pipeline, which to date has been only poorly successful in delivering drugs, identifiedin vitro,into the clinic for anti‐cancer therapy. The primary advantages of theDrosophilasystem for use in anti‐cancer drug screening are the conservation of cancer genes/pathways between flies and mammals, its suitability for rapid phenotypic screening of chemicals for anti‐cancer effectsin vivoin a high‐throughput and cost‐effective manner and its use in identifying drugs that can specifically target tumoursin vivo.Key ConceptsThe current drug screening pipeline has been only poorly efficient in progressing anti‐cancer drugs to the clinic because of differences betweenin vitroandin vivosystemsDrosophila melanogasteris an excellent model organism for cost‐effective high‐throughputin vivoscreening for anti‐cancer compounds relevant to human cancerDrosophilalarvae or adults can be readily screened in a high‐throughput manner for the effect of orally administered compounds on a particular phenotype using phenotypic or fluorescent read‐outsDrosophilamodels of cancer used for chemical screens include those generated by expression of cancer‐causing genes, whole animal synthetic lethality with radiation and specific cancer phenotypesBiological and technical limitations ofDrosophilamight restrict the discovery of compounds and their translation into the clinicScreening of orally administered drugs in flies has already proven to be successful in identifying new compounds or FDA‐approved compounds for use in cancer therapy
Molecular Genetics of Aortic Aneurysms and Aortic Dissections
Authors: Regalado Ellen S , Milewicz Dianna M 
Published: March 2015

Abstract

A genetic predisposition to aortic aneurysms and dissections can occur as part of a genetic syndrome, such as Marfan and Loeys‐Dietz syndrome, or as an isolated manifestation without other systemic features, referred to as familial thoracic aortic aneurysms and dissections. These genetic disorders are inherited as autosomal dominant conditions with reduced penetrance and variable expressivity in terms of aortic disease presentation, age of onset and extent of cardiovascular and other systemic involvement. Mutations in the
FBN1
,
TGFBR1
,
TGFBR2
,
SMAD3
,
SMAD4
,
TGFB2
,
ACTA2
,
MYH11
,
MYLK
and
PRKG1
have been identified in patients with syndromic and non‐syndromic TAAD, emphasising the important roles of the transcription growth factor beta signalling pathway and smooth muscle contraction in aortic disease development.

Key Concepts

Thoracic aortic aneurysms and dissections or TAAD can occur as part of a genetic syndrome, such as Marfan syndrome, Loeys‐Dietz syndrome or as an isolated manifestation without syndromic features.

Approximately 20% of patients with TAAD who do not have Marfan syndrome or related disorder have a similarly affected relative, referred to as familial thoracic aortic aneurysm and dissection or FTAAD.

Marfan syndrome, Loeys‐Dietz syndrome and FTAAD are primarily inherited in an autosomal dominant pattern with reduced penetrance and variable expressivity.

FTAAD is a genetically and clinically heterogeneous group of disorders caused by mutations in several genes, including
FBN1
,
TGFBR1
,
TGFBR2
,
SMAD3
,
SMAD4
,
TGFB2
,
ACTA2
,
MYH11
,
MYLK
and
PRKG1
.
Sergei Chetverikov (1880–1959)
Authors: Levit Georgy S 
Published: March 2015

AbstractChetverikov was a Russian (Soviet) geneticist and lepidopterologist, who significantly contributed to the growth of Darwinian evolutionary theory. He saw his primary task as overcoming a gap between Mendelism and Darwinian selectionism. In 1926, Chetverikov published his revolutionary paper ‘On Certain Features of the Evolutionary Process from the Viewpoint of Modem Genetics’, which laid the foundation for population genetics, along with the works by Ronald Fisher, Sewall Wright, and John Haldane. Chetverikov made significant efforts to develop a research programme synthesising biometric, naturalist and genetic approaches within a Darwinian framework. He played a special role in the history of Russian and Soviet biology, because he stood at the very cradle of the Russian (Soviet) school of evolutionary genetics.Key ConceptChetverikov (1880–1959), a Russian geneticist who made important conceptual contributions to population genetics and evolutionary theory.
Progressive Supranuclear Palsy
Authors: Josephs Keith A 
Published: March 2015

Abstract

Progressive supranuclear palsy (PSP) is a neurodegenerative disease that was first described approximately 50 years ago in 1964. When first described, PSP was thought to have a unique clinical presentation characterised by loss of balance leading to early falls, slowness of movements, stiffness of muscles and loss of the ability to voluntarily move the eyes up and down. Subsequently, it has been recognised that patients who have died and have shown microscopic changes in the brain consistent with PSP had other clinical presentations not involving balance, falls or eye movement problems. The term PSP is, therefore, now best reserved for pathological diagnosis. There have been numerous advances in our understanding of PSP, including the fact that patients with PSP can have many different clinical presentations. In this review, we will focus on the pathological, clinical, neuroimaging and genetic characteristics of PSP.

Key Concepts

Progressive supranuclear palsy (PSP) is a pathological diagnosis.

The cause of PSP is unknown but is thought to be related to abnormal hyperphosphorylated 4R tau.

PSP can present as one of many different clinical syndromes.

Impaired balance with early falls and vertical eye movement problems are highly predictive of PSP pathology.

Atrophy of the premotor cortex, midbrain and superior cerebellar peduncle are the main MRI findings in PSP.

There is some evidence that PSP could have genetic underpinnings.
Associations between workplace factors and carpal tunnel syndrome: A multi‐site cross sectional study
Authors: Fan Z. Joyce , Harris‐Adamson Carisa , Gerr Fred , Eisen Ellen A. , Hegmann Kurt T. , Bao Stephen , Silverstein Barbara , Evanoff Bradley , Dale Ann Marie , Thiese Matthew S. , Garg Arun , Kapellusch Jay , Burt Susan , Merlino Linda , Rempel David 
Published: March 2015

BackgroundFew large epidemiologic studies have used rigorous case criteria, individual‐level exposure measurements, and appropriate control for confounders to examine associations between workplace psychosocial and biomechanical factors and carpal tunnel syndrome (CTS).MethodsPooling data from five independent research studies, we assessed associations between prevalent CTS and personal, work psychosocial, and biomechanical factors while adjusting for confounders using multivariable logistic regression.ResultsPrevalent CTS was associated with personal factors of older age, obesity, female sex, medical conditions, previous distal upper extremity disorders, workplace measures of peak forceful hand activity, a composite measure of force and repetition (ACGIH Threshold Limit Value for Hand Activity Level), and hand vibration.ConclusionsIn this cross‐sectional analysis of production and service workers, CTS prevalence was associated with workplace and biomechanical factors. The findings were similar to those from a prospective analysis of the same cohort with differences that may be due to recall bias and other factors. Am. J. Ind. Med. 58:509–518, 2015. © 2015 Wiley Periodicals, Inc.
Enzymatically Active Ultrathin Pepsin Membranes
Authors: Raaijmakers Michiel J. T. , Schmidt Thomas , Barth Monika , Tutus Murat , Benes Nieck E. , Wessling Matthias 
Published: March 2015

AbstractEnzymatically active proteins enable efficient and specific cleavage reactions of peptide bonds. Covalent coupling of the enzymes permits immobilization, which in turn reduces autolysis‐induced deactivation. Ultrathin pepsin membranes were prepared by facile interfacial polycondensation of pepsin and trimesoyl chloride. The pepsin membrane allows for simultaneous enzymatic conversion and selective removal of digestion products. The large water fluxes through the membrane expedite the transport of large molecules through the pepsin layers. The presented method enables the large‐scale production of ultrathin, cross‐linked, enzymatically active membranes.
Sekundärionen‐Massenspektrometrie von genetisch kodierten Zielproteinen
Authors: Vreja Ingrid C. , Kabatas Selda , Saka Sinem K. , Kröhnert Katharina , Höschen Carmen , Opazo Felipe , Diederichsen Ulf , Rizzoli Silvio O. 
Published: March 2015

AbstractSekundärionen‐Massenspektrometrie (SIMS) wird üblicherweise für die Analyse der Isotopenzusammensetzung verschiedener Materialen eingesetzt. In der Biologie findet sie immer häufiger Anwendung, vor allem um den Stoffwechsel in Zellen zu untersuchen. Einzelne Zielproteine sind mit SIMS jedoch schwer zu identifizieren, wodurch diese Methode in ihren Anwendungsmöglichkeiten bezüglich Studien bestimmter Kompartimente oder Proteinkomplexe eingeschränkt wird. Wir stellen hier eine Methode vor, mit der spezifische Proteine durch eine Klick‐Reaktion mit Isotopen‐ und Fluoreszenzmarkierungen versehen werden (specific protein isotopic and fluorescence labeling, SPILL). Wir haben mit dieser Methode verschiedene Proteine mit 19F markiert und mit NanoSIMS und Fluoreszenzmikroskopie abgebildet. Anhand des 19F‐Signals (mit minimalem Hintergrund) konnten Zielproteine präzise lokalisiert werden, wodurch korrelative Studien der Proteinverteilung und des Zellstoffwechsels oder der Zellzusammensetzung ermöglicht wurden. SPILL kann in allen biologischen Proben angewendet werden, in denen Klick‐Reaktionen durchführbar sind, welche die meisten Zellkultursysteme und kleine Modellorganismen umfassen.
Heterogen katalysierte direkte C‐H‐Thiolierung von Heteroarenen
Authors: Vásquez‐Céspedes Suhelen , Ferry Angélique , Candish Lisa , Glorius Frank 
Published: March 2015

AbstractDie erste generelle Methode zur direkten Thiolierung elektronenreicher Heteroarene wird vorgestellt. Sie nutzt den kommerziell erhältlichen Heterogenkatalysator Pd/Al2O3 und CuCl2. Die Methode eröffnet einen einfachen Zugang zu solchen wertvollen Verbindungen. Mechanistische Experimente deuten auf ein heterogenkatalytisches System hin, in dem beide Metalle eine komplementäre Rolle bei der Bildung der thiolierten Produkte spielen.
Fabrication of b‐Oriented MFI Zeolite Films under Neutral Conditions without the Use of Hydrogen Fluoride
Authors: Peng Yong , Lu Xiaofei , Wang Zhengbao , Yan Yushan 
Published: March 2015

AbstractThe fabrication of MFI zeolite films with particular b‐axis orientation is especially fascinating. Unlike the conventional alkaline or hydrofluoric acid (HF) assisted neutral synthesis route, here we develop a novel neutral synthesis solution system of TPABr/fumed silica/H2O without the use of HF and successfully synthesize highly b‐oriented MFI zeolite films on glass‐plate substrates by secondary growth. The localized weak alkaline environment created by the dissolved Na2O species from the substrate is identified as the key factor for the depolymerization of fumed silica and subsequently the in‐plane growth of zeolite seed layers. Continuous b‐oriented MFI films can also be synthesized on other substrates in the presence of a glass plate or a trace amount of NaOH, which making our neutral synthesis route promising for the direct synthesis of MFI zeolite films and membranes on various substrates.
Glycopeptide Mimetics Recapitulate High‐Mannose‐Type Oligosaccharide Binding and Function
Authors: Lusvarghi Sabrina , Ghirlando Rodolfo , Wong Chi‐Huey , Bewley Carole A. 
Published: March 2015

AbstractHigh‐mannose‐type glycans (HMTGs) decorating viral spike proteins are targets for virus neutralization. For carbohydrate‐binding proteins, multivalency is important for high avidity binding and potent inhibition. To define the chemical determinants controlling multivalent interactions we designed glycopeptide HMTG mimetics with systematically varied mannose valency and spacing. Using the potent antiviral lectin griffithsin (GRFT) as a model, we identified by NMR spectroscopy, SPR, analytical ultracentrifugation, and microcalorimetry glycopeptides that fully recapitulate the specificity and kinetics of binding to Man9GlcNAc2Asn and a synthetic nonamannoside. We find that mannose spacing and valency dictate whether glycopeptides engage GRFT in a face‐to‐face or an intermolecular binding mode. Surprisingly, although face‐to‐face interactions are of higher affinity, intermolecular interactions are longer lived. These findings yield key insights into mechanisms involved in glycan‐mediated viral inhibition.
Makromolekulare Oberflächen: Photomusterung mit funktionellen stabilen Nitriloxiden
Authors: Altintas Ozcan , Glassner Mathias , Rodriguez‐Emmenegger Cesar , Welle Alexander , Trouillet Vanessa , Barner‐Kowollik Christopher 
Published: March 2015

AbstractDas effiziente Abfangen photogenerierter Thioaldehyde durch funktionelle stabile Nitriloxide in einer 1,3‐dipolaren Cycloaddition ist eine neue und vielseitige photochemische Strategie zur Funktionalisierung von Polymeren und zur Oberflächenmodifikation unter milden und äquimolaren Bedingungen. Die modulare Ligation in Lösung wird im Detail durch ESI‐MS verfolgt. XPS wird zur Analyse der funktionalisierten Oberflächen verwendet, während ToF‐SIMS die durch Anwendung einer Schattenmaske erreichte räumliche Kontrolle der Oberflächenfunktionalisierung belegt. Polymerbürsten wurden in einem räumlich begrenzten Bereich durch SI‐ATRP von der Oberfläche aus wachsen gelassen, was mithilfe von ToF‐SIMS, XPS sowie Ellipsometrie belegt wird.
A Single‐Chain Magnet Tape Based on Hexacyanomanganate(III)
Authors: Zhang Yuan‐Zhu , Zhao Han‐Hua , Funck Edward , Dunbar Kim R. 
Published: March 2015

AbstractThe tape‐like chain {[(tptz)MnII(H2O)MnIII(CN)6]2MnII(H2O)2}n⋅4n MeOH⋅2n H2O based on the anisotropic building block hexacyanomanganate(III) exhibits long‐range magnetic ordering below 5.1 K as well as single‐chain magnetic behavior at lower temperatures with an effective energy barrier of 40.5(7) K.
Secondary‐Ion Mass Spectrometry of Genetically Encoded Targets
Authors: Vreja Ingrid C. , Kabatas Selda , Saka Sinem K. , Kröhnert Katharina , Höschen Carmen , Opazo Felipe , Diederichsen Ulf , Rizzoli Silvio O. 
Published: March 2015

AbstractSecondary ion mass spectrometry (SIMS) is generally used in imaging the isotopic composition of various materials. It is becoming increasingly popular in biology, especially for investigations of cellular metabolism. However, individual proteins are difficult to identify in SIMS, which limits the ability of this technology to study individual compartments or protein complexes. We present a method for specific protein isotopic and fluorescence labeling (SPILL), based on a novel click reaction with isotopic probes. Using this method, we added 19F‐enriched labels to different proteins, and visualized them by NanoSIMS and fluorescence microscopy. The 19F signal allowed the precise visualization of the protein of interest, with minimal background, and enabled correlative studies of protein distribution and cellular metabolism or composition. SPILL can be applied to biological systems suitable for click chemistry, which include most cell‐culture systems, as well as small model organisms.