bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metals in Cells:
X
‐Ray Fluorescence Microscopy
Authors: Penner‐Hahn James E. 
Published: December 2013

Abstract
X‐ray fluorescence is one of the few tools that can be used to determine the concentration and localization of metals and nonmetals in cells. Depending on the element and the experimental conditions, X‐ray fluorescence typically provides modest concentration sensitivity, in the micromolar range (i.e., high parts per billion sensitivity), and superb mass detection limits, as low as attomoles. Spatial resolution ranges from micrometers to tens of nanometers. In addition to basic quantification, X‐ray fluorescence also offers the possibility of defining the chemical speciation of an element based on changes in its X‐ray absorption near‐edge structure. This article reviews the physical principles of X‐ray fluorescence microscopy and summarizes its applications to biological samples, including a discussion of its strengths and weaknesses in comparison to other analytical methods.
Metal Homeostasis: Cyanobacterial Models That Address Cross‐Talk
Authors: Patterson Carl J. , Pernil Rafael , Foster Andrew W. , Robinson Nigel J. 
Published: December 2013

AbstractCyanobacteria, the ancestors of chloroplasts, have additional demands for metals in proteins to support oxygenic photosynthesis. These bacteria are thought to have generated an aerobic planet, altering metal speciation and changing the subsequent recruitment of metals in cells. Today, metal availability influences cyanobacterial ecology, which is in turn a determinant of oceanic productivity and of the fixation of atmospheric carbon dioxide. Their capacity to assimilate inorganic elements into organic molecules, deriving energy merely from sunlight, has created interest in the exploitation of cyanobacteria as green‐factories. With such a large proportion of enzymes requiring metals, efforts in synthetic biology may require a deep understanding of how cells help proteins to acquire the correct metals if we are to rewire inorganic circuitry to optimize metalation of introduced pathways. Here, we estimate that 27% of metalloenzyme sites in the Metal‐MACiE database lie at the end of specialized delivery and/or assembly pathways. We review insights into the cell biology of metals that have emerged from studies of model cyanobacteria and especially studies ofSynechocystisPCC 6803 that address how metals selectively partition to their metalloprotein partners.
Metal Homeostasis: Regulation of Manganese and Iron in the Rhizobia and Related α‐Proteobacteria
Authors: O'Brian Mark R. 
Published: December 2013

AbstractIron is required for many cellular processes, but can be toxic at high concentrations. Thus, iron homeostasis is strictly regulated so that iron acquisition, storage, and consumption are geared to iron availability, and that intracellular levels of free iron do not reach toxic levels. Recently, the roles of manganese and its control in cells have been investigated, and it is becoming clear that some aspects of the metabolism of iron and manganese are interrelated. Manganese is best understood in its role in oxidative stress responses, and the pro‐oxidative effects of intracellular iron functionally link these two metals. Iron and manganese appear to have complementary or compensatory functions as well. In bacteria, it may not be universally true that manganese is an essential nutrient under nonstressed conditions, underscoring a gap in our knowledge of the role of this metal in prokaryotes. Studies ofBradyrhizobium japonicumand other rhizobia reveal that control of iron‐responsive gene expression is fundamentally different in these bacteria when compared with model organisms such asEscherichia coliandBacillus subtilis. Moreover, the Fur regulatory protein that dominates iron‐responsive gene expression in those model systems has been co‐opted to respond to manganese in the rhizobia. Finally, it appears that mechanisms of iron‐ and manganese‐responsive gene expression in the rhizobia are paradigmatic for the α‐proteobacteria. This is remarkable because the α‐proteobacteria are metabolically and ecologically diverse, making it difficult to correlate their unique metalloregulation with specific adaptations.
Copper Transport in Fungi
Authors: Labbé Simon , Beaudoin Jude , Ioannoni Raphaël 
Published: December 2013

Abstract

A clear understanding of copper metabolism is critical because copper is absolutely essential but also toxic. Significant new knowledge in this field was achieved through research using yeast models, including
Saccharomyces cerevisiae
and
Schizosaccharomyces pombe
. Both yeasts are highly needed model organisms for identifying the molecular mechanisms whereby cells appropriately acquire copper and regulate gene expression in response to changes in copper levels. This article summarizes our current understanding of a number of components involved in copper uptake, trafficking, compartmentalization, and copper sensing to establish and maintain normal copper homeostasis.
Zinc Transporters and Trafficking in Yeast
Authors: Wu Yi‐Hsuan , Eide David J. 
Published: December 2013

AbstractZinc is an essential nutrient that plays important roles in cells as a structural or catalytic cofactor in hundreds of different proteins. The functions of many zinc transporter genes, including genes with orthologs that play similar roles in mammals, were first characterized in the yeastSaccharomyces cerevisiae. The study of zinc metabolism using this yeast as a model organism has had profound impact on the field of zinc biology. It has advanced the zinc field by aiding the identification of new transporter genes and improving our understanding of regulatory mechanisms underlying various cellular stresses and responses in higher eukaryotes as well as other organisms. This report provides a comprehensive review of yeast zinc homeostasis, emphasizing our current knowledge of the regulation of zinc transport mechanisms and cellular distributions of zinc.
Cadmium Transport in Eukaryotes
Authors: Smith Nathan , Wei Wenzhong , Lee Jaekwon 
Published: December 2013

AbstractCadmium (Cd) is a highly toxic metal implicated in various public health concerns. Identification and characterization of Cd targets, which manifests its toxic effects and molecular factors involved in Cd transport and detoxification, has been an important scientific problem for many years.CdIIenters biological systems via the transport pathways of divalent nutritional metals, such asZnII,FeII,MnII, andCaII, through chemical mimicry with these metals. High affinity for thiol (SH) groups is known to be a major mechanism underlying Cd toxicity, which is consistent of theCdIIdetoxification by thiol‐containing cellular molecules such as glutathione (GSH), metallothionein (MT), and phytochelatin (PC). Along with expressional control of these Cd chelators, compartmentalization and efflux are also evolutionally conserved for Cd tolerance. Further insights into Cd transport and detoxification would ultimately control Cd's detrimental effects, minimize human exposure to this toxic metal via the food chain, and develop methods for Cd remediation from the environment. This chapter provides a brief overview of mechanisms underlying Cd toxicity, its metabolic pathways, and adaptive responses to Cd stress in eukaryotes, with a focus on yeastSaccharomyces cerevisiae, plants, and mammals.
Metal Homeostasis and Oxidative Stress in
Bacillus subtilis
Authors: Ma Zhen , Helmann John D. 
Published: December 2013

Abstract

Bacteria have evolved mechanisms to maintain proper concentration of different metal ions, a process known as
metal ion homeostasis
. Metal‐dependent transcription regulators, or metalloregulatory proteins, play major roles in coordinating the expression of metal ion homeostasis genes.
Bacillus subtilis
has been a model Gram‐positive bacterium for studies of metal ion homeostasis for decades. In this article, we review how
B. subtilis
senses and responds to metal ion deficiency, sufficiency, and excess. Generally, metal deficiency leads to the expression of high‐affinity metal uptake systems and mobilization of stored metal ions, and may additionally activate elemental sparing responses to minimize metal ion requirements. Excess metal leads to the expression of sequestration or efflux mechanisms. In
B. subtilis
, these responses are coordinated at the transcription level by metalloregulatory proteins that sense metal ion status. We discuss in detail how each metal ion is sensed by the cognate regulator and how each regulatory circuit achieves a metal‐specific response. Importantly, recent studies suggest an intimate linkage between oxidative stress responses and metal ion homeostasis. In
B. subtilis
, the peroxide stress regulator (PerR) appears to be a key component linking these two stress responses, as suggested both by the metal‐dependent nature of PerR repression and functions of genes regulated by PerR.
Selenoproteins—Regulation
Authors: Seale Lucia A. , Berry Marla J. 
Published: December 2013

AbstractSelenium is an essential trace element that is required for life, owing to its presence in selenoproteins as the unique amino acid selenocysteine. Selenoproteins are thought to be responsible for most or all of the biological functions of selenium. Incorporation of selenocysteine into proteins requires several specific factors, and it is a tightly regulated process. In addition to the requirement for selenium in selenoprotein biosynthesis, dietary intake of selenium regulates expression or activity of some of the elements of the selenocysteine incorporation machinery. Several transcription factors are implicated in regulating transcription of selenoprotein mRNAs, including members of the NFκB, Nrf2, HIF1, and Sp family. Translation of selenoprotein mRNAs is subject to a hierarchical prioritization that is tissue‐specific and dependent on mechanisms of nonsense‐mediated decay, proper assembling of selenocysteine incorporation factors, as well as selenium concentration. In this article, recent advances in our understanding of the regulation of selenoproteins are discussed.
Iron: Molecular Basis of Hemochromatosis
Authors: Schmidt Paul J. 
Published: December 2013

AbstractIron can be deleterious in excess because of its ability to generate reactive oxygen species. Consequently, the appropriate maintenance of organismal iron balance is crucial. Disturbances in iron metabolism are the root cause of many prevalent human diseases. Hereditary hemochromatosis is a genetic disorder resulting in a chronic increase of iron uptake from the diet leading to disease. Although first mentioned in the medical literature by Trousseau in 1865, until recently, the genetic and the pathophysiological bases of this disorder were poorly understood. The vast majority of cases are caused by mutations inHFE, the classic hemochromatosis gene. More recently, genetic studies have implicated hemochromatosis disease‐causing mutations in hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2), and ferroportin (SLC40A1). Research involving these five genetically distinct causes of hemochromatosis has increased our knowledge of the underlying pathogenic mechanisms of the disease and has led to a better general understanding of iron metabolism. Current thought places hepcidin, a soluble 25‐amino‐acid peptide, as the master regulator of iron homeostasis. Hepcidin acts as a ligand for the iron transporter ferroportin, negatively regulating iron release from red blood cell‐recycling macrophages or dietary iron uptake in the duodenum. Perturbance of the hepcidin–ferroportin regulatory apparatus in hemochromatosis leads to dysregulated dietary iron uptake eventuating in disease. Recent work has augmented our understanding of how iron regulates hepcidin expression. Hemojuvelin, a bone morphogenetic protein (BMP) coreceptor, plays a central role in the regulation of hepcidin expression through aSMAD‐mediated signaling pathway. BothHFEandTFR2are thought to play essential roles in the sensing of total body iron needs, but the mechanism by which these molecules affectHJV/BMP/SMAD‐mediated hepcidin control is not completely elucidated. Recent insights into the molecular basis of hereditary hemochromatosis and iron metabolism will be reviewed in this article.
Selenoenzymes and Selenium Trafficking: An Emerging Target for Therapeutics
Authors: Self William , Rosario Sarah 
Published: December 2013

AbstractSelenoproteins exist within all three domains of life. It is estimated that one‐third of prokaryotes utilize selenium for specific biological purposes, whereas the majority of microorganisms do not use or need selenium. Selenoproteins are unique proteins in which selenocysteine is inserted into the polypeptide chain by highly specialized translational machinery. Alternatively, some selenoproteins in which selenium is incorporated as a labile cofactor have been characterized, and this class of selenoproteins also contains either molybdenum or tungsten. Although several selenoproteins have been well characterized for several decades, the biological functions of these proteins are still being defined. The role of selenoproteins, particularly in human pathogens, has received little attention, yet there is evidence that targeting such proteins could play a major role in drug development. In addition, emerging evidence suggests that many well‐known cancer drugs target a specific class of selenoproteins in mammals, lending credence to the notion that selenoproteins may indeed already be substantial drug targets in the clinic.
Iron: Mitochondrial Iron Metabolism and the Synthesis of Iron–Sulfur Clusters
Authors: Dancis Andrew , Lindahl Paul A. 
Published: December 2013

Abstract

Mitochondria play a major role in cellular iron metabolism. These organelles contain respiratory complexes that are rich in hemes and iron–sulfur clusters (ISCs), including [Fe
4
S
4
], [Fe
3
S
4
], and [Fe
2
S
2
] clusters. Moreover, these organelles are able to synthesize ISCs on their own, even in isolation from the cell, in a process mediated by the ISC machinery housed therein. In order for iron to be used by the mitochondrial ISC machinery for new cluster synthesis, it must first transit from the environment into the cellular cytoplasm and from the cytoplasm into the mitochondria. In mitochondria, a regulated transit iron pool, recognized by a characteristic biophysical signature, is used for generating new Fe–S clusters. Iron levels in mitochondria are generally maintained by homeostatic controls, although in some settings iron accumulates in the form of ferric phosphate nanoparticles that remain invisible to the homeostatic control mechanism. This review summarizes recent genetic and biophysical results associated with mitochondrial iron metabolism and ISC assembly, primarily in yeast mitochondria.
Iron–Sulfur Cluster Biogenesis in Archaea and Bacteria
Authors: Chahal Harsimranjit K. , Boyd Jeff M. , Outten F. Wayne 
Published: December 2013

AbstractIron–sulfur (Fe–S) clusters are key cofactors required for the activity of essential metalloproteins. Biogenesis of Fe–S clusters is carried out by multiple proteins that work together to mobilize iron and sulfide, assemble nascent clusters, and traffic them to target metalloproteins. While the Isc, Nif, and Suf pathways are the most well‐studied Fe–S cluster biogenesis systems, it is clear that a variety of accessory proteins and metabolites cooperate with these systems for cluster assembly. Here, we review the current status of Fe–S cluster biogenesis research in Bacteria and Archaea.
[
FeFe
]‐Hydrogenase Cofactor Assembly
Authors: Shepard Eric M. , Byer Amanda S. , Boyd Eric S. , Swanson Kevin D. , Peters John W. , Broderick Joan B. 
Published: December 2013

Abstract

This article highlights recent advances in our understanding of the biosynthetic pathway for active site H‐cluster assembly in [
FeFe
]‐hydrogenases. The H‐cluster is composed of a [
4Fe–4S
] cubane bridged via one cysteine thiolate to a
2Fe
subcluster; the
2Fe
subcluster is further coordinated by carbon monoxide, cyanide, and bridging dithiolate ligands. Biosynthesis of the H‐cluster occurs through stepwise modification of simple
Fe–S
cluster precursors; these chemical modifications are carried out by three gene products denoted
HydE
,
HydF
, and
HydG
. Maturation of the [
FeFe
]‐hydrogenase requires the presence of a preformed [
4Fe–4S
] cluster, indicating that
HydE
,
HydF
, and
HydG
are directed toward the biosynthesis of the
2Fe
subcluster.
HydE
and
HydG
are both radical
S
‐adenosylmethionine (
SAM
) enzymes and utilize a

CX
3
CX
2
C

motif to bind site‐differentiated [
4Fe–4S
]
2+/+
clusters that promote the reductive cleavage of
SAM
into methionine and a 5′‐deoxyadenosyl radical responsible for hydrogen atom abstraction from substrate. In an extraordinary biochemical reaction,
HydG
uses this chemistry to catalyze the radical degradation of tyrosine into
p
‐cresol and a glycine‐like intermediate; an accessory, C‐terminal [
4Fe–4S
] cluster then degrades the latter intermediate into cyanide and carbon monoxide.
HydE
is presumed to be responsible for bridging dithiolate ligand biosynthesis from an unknown substrate.
HydF
contains an N‐terminal
GTPase
domain and a C‐terminal
Fe–S
‐cluster‐binding domain and binds both [
2Fe–2S
] and [
4Fe–4S
] clusters; evidence suggests that the former cluster is modified by
HydE
and
HydG
to form a
2Fe
H‐cluster precursor on
HydF
. The role of
GTP
hydrolysis in H‐cluster maturation remains largely unexplained; however, it may be related to gating the protein–protein interactions between
HydF
and
HydE
and
HydG
. The reactions catalyzed by
HydE
and
HydG
can be thought of as specific ligand modification events designed to fine‐tune H‐cluster reactivity; not only do the chemical transformations themselves have direct links to reactions important on early Earth, but radical
SAM
enzymes with their canonical

CX
3
CX
2
C

motif are likely very ancient. The modern diversity that is observed in chemical reactions catalyzed by the radical
SAM
superfamily can be explained evolutionarily through the recruitment of distinct protein domains that impart specific substrate activation capabilities. Recruitment of these domains is discussed in the context of
HydE
and
HydG
and important links are made to the nitrogenase system where intriguing parallels between [
FeFe
]‐hydA H‐cluster biosynthesis and nitrogenase
FeMo
‐cofactor assembly clearly exist.
[
NiFe
]‐Hydrogenase Cofactor Assembly
Authors: Soboh Basem , Sawers R. Gary 
Published: December 2013

Abstract

Heterodimeric [
NiFe
]‐hydrogenases catalyze the activation of dihydrogen. The large subunit of all [
NiFe
]‐hydrogenases studied to date harbors a bimetallic catalytic center comprising a nickel ion and an iron ion. Both ions are connected via four highly conserved cysteinyl thiolates. All four thiolates coordinate the nickel, while two of the thiolates also coordinate the Fe ion. The iron is decorated with one carbonyl and two cyanyl moieties. Biosynthesis of this complex bimetallic center and its insertion into the large subunit requires the concerted action of six highly conserved Hyp (hydrogenase pleiotropic) proteins. Further accessory proteins also contribute to cofactor synthesis. Both diatomic ligands are generated within enzyme complexes and therefore are not released to bulk solvent. The carbamoyltransferase
HypF
catalyzes the
ATP
(adenosine triphosphate)‐dependent transfer of the carbamoyl moiety of carbamoylphosphate to the C‐terminal cysteinyl of
HypE
. In a further
ATP
‐dependent reaction, the
HypF–HypE
heterotetrameric complex then dehydrates the thiocarboxamide to thiocyanate. The cyano groups are transferred to an iron ion bound by the
HypC
and
HypD
protein complex. The source of the
CO
ligand has not been definitively identified, but current evidence suggests carbon dioxide might be the precursor and the
HypCD
complex appears to generate
CO
. The
HypD
protein is the only one of the Hyp proteins capable of performing redox chemistry and its low‐potential [4Fe–
4S
] cluster presumably delivers the electrons for the reduction of

CO
2

to
CO
as well as for the transfer of the cyano ligands to the Fe ion. As the
HypC
chaperone also interacts specifically with the precursor form of the large subunit, it likely delivers the Fe(
CN
)

2
CO

center via thiol‐transfer to the aposubunit. The nickel ion is inserted by the combined actions of the
HypA
,
HypB
(a
GTPase
), and the prolyl
cis–trans
isomerase
SlyD
but only after insertion of the iron center. Little is known about the biochemical mechanisms underlying Ni ion insertion. Specificity of metal insertion is governed by a hydrogenase‐specific endoprotease that completes the insertion process by release of a C‐terminal peptide resulting in a conformational shift in the protein, which closes the active site. All of the components of the active site cofactor are derived from inorganic sources abundant on primitive earth, perhaps suggesting that strong selective pressure has maintained this highly effective ancient bioinorganic catalyst of dihydrogen activation throughout evolution.
Non‐minimum phase switched systems: HOSM‐based fault detection and fault identification via Volterra integral equation
Authors: Ríos H. , Efimov D. , Davila J. , Raïssi T. , Fridman L. , Zolghadri A. 
Published: December 2013

SUMMARYIn this paper, the problem of continuous and discrete state estimation for a class of linear switched systems with additive faults is studied. The class of systems under study can contain non‐minimum phase zeroes in some of their ‘operating modes’. The conditions for exact reconstruction of the discrete state are given using structural properties of the switched system. The state space is decomposed into the strongly observable part, the non‐strongly observable part, and the unobservable part, to analyze the effect of the unknown inputs. State observers based on high‐order sliding mode to exactly estimate the strongly observable part and Luenberger‐like observers to estimate the remaining parts are proposed. For the case when the exact estimation of the state cannot be achieved, the ultimate bounds on the estimation errors are provided. The proposed strategy includes a high‐order sliding‐mode‐based fault detection and a fault identification scheme via the solution of a Volterra integral equation. The feasibility of the proposed method is illustrated by simulations. Copyright © 2013 John Wiley & Sons, Ltd.
Robust actuator fault compensation accounting for uncertainty in the fault estimation
Authors: Seron María M. , De Doná José A. 
Published: December 2013

SUMMARYWe propose a fault tolerant control scheme that compensates for actuator faults by adjusting the controller gain based on an estimate of the fault magnitude. The scheme consists of a plant in closed loop with an observer‐based feedback tracking controller, which is adapted to the fault situation diagnosed by a fault detection and isolation algorithm. We give conditions for correct fault detection and isolation and for robust closed‐loop stability accounting for possible errors in the fault estimation. Copyright © 2013 John Wiley & Sons, Ltd.