bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria: Structure and Role in Respiration
Authors: Fontanesi Flavia 
Published: May 2015

AbstractMitochondria are eukaryotic organelles of endosymbiotic origin, which conserve their own genome and gene expression machinery. They are highly dynamics organelles and form an elaborated network in the cell cytosol. Mitochondria fulfil various important roles in cellular metabolism. They are commonly known as ‘the powerhouse of the cell’ for their pivotal role in the conversion of nutrient‐derived energy in the form of ATP molecules, through the mitochondria‐housed pathways of citric acid cycle and oxidative phosphorylation. Besides, much broader is the role that these organelles play in cellular metabolism and survival. Mitochondria fulfil important roles in the biosynthesis of essential molecules, such as lipids, amino acids, haem and iron–sulphur cluster, and are a major cellular site of reactive oxygen species production. Moreover, mitochondrial dysfunction is the cause of devastating human encephalomyopathies and it has been linked with neurodegeneration, cancer and ageing.Key ConceptsMitochondria are semi‐autonomous organelles that are descendants of endosymbiotic bacteria.Mitochondria play a pivotal role in cellular energy production through the mitochondria‐housed pathways of citric acid cycle, fatty acid oxidation, respiration and oxidative phosphorylation (OXPHOS).Mitochondria have an important anabolic role in cellular metabolism, as they are fundamental for the synthesis of several amino acids, nucleobases and enzymatic cofactors such as haem and Fe‐S clusters.Mitochondria are membrane‐bound organelles. They have two distinct membranes: the outer and the inner membrane. The inner membrane is highly impermeable to ions and forms an extensive series of invaginations called cristae.In the cell, mitochondria form a continuous and highly dynamic network. In addition, they intimately interact with other cellular structures, such as the cytoskeleton and the endoplasmic reticulum.Mitochondria retain their own hereditary material, the mitochondrial DNA (mtDNA), and their own translation apparatus or mitoribosomes.mtDNA is present in ∼1000–10 000 copies per cell and encodes for a handful of proteins, all subunits of the OXPHOS system.The OXPHOS system is located in the mitochondrial cristae and is formed by the mitochondrial respiratory chain (MRC) and the ATP synthase or complex V. The MRC is formed by four multimeric complexes (complex I–IV) and two mobile electron carriers, coenzyme Q and cytochromec. In addition, MRC complexes interact to form organised supra‐structures called supercomplexes or respirasomes.The assembly of the OXPHOS complexes is a complicated and highly regulated process requiring a large number of ancillary factors.In humans, defects of the OXPHOS system are associated with devastating diseases, known as mitochondrial disorders, which are multisystemic, although mainly affecting highly energy‐demanding tissues such as brain, heart and muscle.
Phospholipases
Authors: Vines Charlotte M , Bill Colin A 
Published: May 2015

AbstractPhospholipases play central roles in regulating signalling during numerous cellular events including proliferation, G protein‐coupled receptor signalling and neuronal activation by catalysing the lysis of phosphorylated lipids. In turn, second messengers are released, which control downstream events. Four distinct families of phospholipases have been described and are named A, B, C and D and range in size from 13 to 250 kDa. These enzyme family members are categorised based on the stereospecifically numbered sites within phospholipids where they promote cleavage. Within the phospholipase families, there are isoforms, which have differential distribution patterns and functions within specific cell types. These enzymes are widely expressed, can be regulated by different substrates or by [Ca2+] and can be found in the cytoplasm, membrane and in a soluble form outside of cells. Within the cytoplasm, different family members can be found within distinct organelles, including the mitochondria. In this article, we discuss these enzymes, their expression patterns and identified functions for each family member.Key ConceptsFour different families of phospholipases control levels of phospholipid substrates by cleaving different sites of phospholipids.Phospholipases are ubiquitously expressed in nature.Phospholipase families are either calcium‐dependent or calcium‐independent enzymes.Enzymes are often found in membranes, but some phospholipases are secreted.Phospholipases have important functions in membrane integrity, digestion and cell signalling.Phospholipases are important in health and certain disease states.
Nucleus and Nuclear Envelope: Methods for Preparation
Authors: Jafferali Mohammed H , Beckman Marie , Kihlmark Madeleine , Hallberg Einar 
Published: May 2015

Abstract

The nucleus of eukaryotic cells contains the genome surrounded by a nuclear envelope (NE) consisting of two lipid membranes with embedded nuclear pores and an underlying nuclear lamina. The uniformity in size and density makes it possible to isolate pure intact nuclei at high yields from tissue homogenates by centrifugation through a sucrose cushion. NEs can be prepared from isolated nuclei by enzymatic degradation of their nucleic acid content. The resulting NE preparations contain structurally well‐conserved inner and outer nuclear membranes with attached ribosomes, nuclear pore complexes and nuclear lamina. Reliable methods for preparation of nuclei and NEs play an important role in the successful identification of components and their interacting partners that are located in nuclei and in nuclear subcompartments.

Key Concepts

Pure intact nuclei can be isolated at high yields from tissue homogenates, and nuclear envelopes can be prepared from the isolated nuclei.

The preparation of pure nuclei is important for the identification of nuclear and subnuclear components and their interacting partners.

Animal behaviourists must participate in conservation planning to protect the future of biodiversity.

Lipid bilayers provide the fundamental architecture of biological membranes.
Cell Staining: Fluorescent Labelling of the Golgi Apparatus
Authors: Dejgaard Selma Y , Dejgaard Kurt , Presley John F 
Published: May 2015

Abstract

Immunofluorescence has been the primary method for labelling the Golgi apparatus for light microscopic observation in fixed cells. The Golgi apparatus was initially labelled in living cells using the fluorescent ceramide analogue
N
‐6[7‐nitro‐2,1,3‐benzoxadiazol‐4‐yl] aminocaproyl sphingosine or by microinjection of fluorescently conjugated antibodies to exposed Golgi epitopes. With the common availability of the green fluorescent protein (GFP) and advanced fluorescence microscopes including confocal microscopes, imaging of the Golgi apparatus in living cells is now a major experimental approach. Time‐lapse imaging of living cells has also been combined with photobleach techniques in order to study the dynamics of transient protein association with the Golgi apparatus. Similar live‐cell imaging approaches have been used to study the dynamics of the cargo transport through the exocytic pathway. Recent advances in microscopy have allowed bypassing the diffraction limit which has traditionally limited image resolution. These new methods may be applied to fluorescence imaging of the Golgi apparatus, although they are not easily applied to living cells at present.

Key Concepts

Immunofluorescence can be used to visualise proteins in the Golgi apparatus or its subdomains.

Live‐cell visualisation of the Golgi apparatus is possible with GFP‐tagged proteins.

Fluorescence images can be quantitated in a rigorous way.

Photobleaching and photoactivation techniques permit visualisation of protein dynamics and flux through the Golgi apparatus in living cells.

Super‐resolution imaging promises a new generation of imaging approaches to the Golgi apparatus.
Chromatofocusing
Authors: El‐Sayed Mayyada MH , Frey Douglas D 
Published: May 2015

Abstract

Chromatofocusing is a form of gradient elution chromatography performed using an ion‐exchange column packing and an internally generated pH gradient that travels through the column as a retained front. The interaction between the pH gradient and amphoteric substances such as proteins causes these substances to exit the chromatographic column at characteristic locations in the effluent as focused bands. The method was first introduced in the 1970s. Over the last several decades, the performance and the range of applications of the method have been significantly increased through the efforts of numerous investigators.

Key Concepts

Proteins can be focused into narrow bands similar to those produced in isoelectric focusing using an ion‐exchange chromatography column and a pH gradient that moves through the column packing more slowly than the interparticle fluid.

The focusing effects produced in chromatofocusing yield unique dynamic behaviour for the species being separated which, if properly optimised, can produce high‐resolution separations.

Numerical simulation methods and analytical local‐equilibrium theories can be used to optimise the compositions of the elution and presaturation buffers used in chromatofocusing.

Chromatofocusing can be applied not only to proteins, but also to related types of amphoteric species including small peptides and macromolecular complexes such as viruses.

Chromatofocusing can usefully employ mixed‐mode column packings where both electrostatic and hydrophobic interactions determine the adsorption affinity of the species being separated.
Peptidyl Prolylcis/transIsomerases
Authors: Schiene‐Fischer Cordelia 
Published: May 2015

AbstractPeptidyl prolylcis/transisomerases (PPIases) are ubiquitous enzymes that catalyse thecis/transisomerisation of peptide bonds preceding proline in peptides and proteins. PPIases can thus catalyse proline‐limited slow kinetic steps in the folding and rearrangement of proteins. Generally, by the regulation of the biological functions of their target proteins, PPIases are involved in the control of a wide variety of cellular processes, including transcription, cell proliferation, cell differentiation and apoptosis. They are implicated in many diseases such as cancer, inflammation, infection and neurodegeneration. PPIases comprise three families, the cyclophilins, the FK506‐binding proteins (FKBPs) and the parvulins, which are unrelated in their amino acid sequence and their three‐dimensional structure. Binding of cyclophilins and FKBP to their respective tight binding inhibitors, cyclosporin A and FK506, mediates the immunosuppressive action of these drugs by a gain‐of‐function mechanism.Key ConceptsPeptidyl prolylcis/transisomerases catalyse thecis/transisomerisation of peptide bonds preceding proline in peptides and proteins.The enzyme class of PPIases comprises three families, the cyclophilins, the FK506‐binding proteins (FKBPs) and the parvulins unrelated in their amino acid sequence and their three‐dimensional structure.The PPIase activity of members of the cyclophilin family is inhibited by the tight binding inhibitor cyclosporin A.The PPIase activity of members of the FKBP family is inhibited by FK506 and rapamycin.Members of the cyclophilin and FKBP families of PPIases are called immunophilins, because they mediate immunosuppression of the immunosuppressive drugs cyclosporin A, FK506 and rapamycin.Beside a role in protein folding, specific members of the three PPIase families perform specific tasks by the interaction with distinct substrate proteins in their native state, thereby regulating their functional properties.
Genotype Imputation
Authors: Krawczak Michael 
Published: May 2015

Abstract

A missing data problem arises in genetic epidemiological studies when genotypes of particular markers are unavailable for analysis for reasons of data quality, cost efficiency or technical design. In such instances, imputation methods can be used to extend the process of scientific inference making from the typed to the un‐typed markers. The information required to infer unobserved genotypes from observed genotypes is provided by the so‐called imputation base, an internal or external set of comprehensively typed individuals (often taken from HapMap or the 1000 Genomes Project) that is representative of the study population as a whole. The most popular genotype imputation methods, including IMPUTE, fastPHASE, MaCH and BEAGLE, employ a Markov chain model of the haplotype distribution in the population of interest. Although these frameworks have been shown to provide accurate and efficient tools of ‘
in silico
genotyping’ under certain conditions, their uncritical use nevertheless must be cautioned against.

Key Concepts

Relevant genotype data may be missing in genetic epidemiological studies for technical or efficiency reasons.

Scientific inference that takes missing genotype data properly into account can be made using data imputation methods.

Genotype imputation requires an imputation base, that is, a population‐representative set of individuals (such as the HapMap or the 1000 Genomes Project) who are genotyped for all markers of interest.

Established genotype imputation methods employ a Markov chain model of the haplotype distribution in the population under study.

Genotype imputation may achieve 90% accuracy for highly polymorphic markers but performs less well for rare variants.

While genotype imputation may provide valid statistical tests of genotype–phenotype association, their use for effect size estimation and significance assessment must proceed with caution.

Genotype imputation needs to follow the same rules of good scientific practice as laboratory‐based data generation.
Molecular Genetics of Limb‐Girdle Muscular Dystrophies
Authors: Filosto Massimiliano , Scarpelli Mauro , Padovani Alessandro 
Published: May 2015

AbstractThe limb‐girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles. Most of these diseases present with wide clinical heterogeneity and the limb‐girdle phenotype should be regarded as one of the possible phenotypic expressions of a specific protein defect.Therefore, a precise clinical evaluation is often difficult, and an appropriate diagnostic approach using clinical, pathological, biochemical and genetic resources is essential to achieve the correct diagnosis.The current classification of LGMDs is based on inheritance pattern. Dominant forms are classified as type 1 (LGMD1), whereas the recessive forms are classified as type 2 (LGMD2). A progressive alphabetical letter identifies the different involved genes and indicates the order of identification.This review reports a comprehensive update on the genetic bases and the main clinical aspects of these groups of diseases according to protein defect and transmission modality.Key ConceptsThe limb‐girdle muscular dystrophies (LGMDs) are a heterogeneous group of hereditary neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles.The current classification of LGMDs is based on inheritance pattern. Dominant forms are classified as type 1 (LGMD1), whereas the recessive forms are classified as type 2 (LGMD2). A progressive alphabetical letter identifies the different involved genes and indicates the order of identification.LGMDs are diseases having wide inter‐ and intra‐familial phenotypic heterogeneity and therefore the limb‐girdle phenotype is often the only one of the possible phenotypic expressions of a specific protein defect.Four recessive LGMDs are caused by mutations in the genes encoding the four members of the skeletal muscle sarcoglycan complex which is a part of the large macromolecular complex of proteins named the dystrophin‐associated protein complex (DAPC) which is thought to have structural functions in providing membrane stability, maintaining the integrity of sarcolemma and in ensuring transduction during muscle contraction.Eight genes have been found to be responsible for an LGMD‐dystroglycanopathy until now. Mutations in these genes reduce dystroglycan glycosylation and cause different phenotypes ranging from mild to dramatic conditions. Limb‐girdle muscular dystrophies should to be considered the mildest expression of the phenotypic spectrum of dystroglycanopathies.
Disconnection Syndromes
Authors: Mulroy Eoin , Gleeson Sarah , McCarthy Allan , Kavanagh Eoin , Lynch Tim 
Published: May 2015

Abstract

Evolutionary pressures on a finite amount of cortical space led the cerebral hemispheres to evolve into subspecialised regions subserving specific functions. Impaired communication between these highly specialised brain regions gives rise to a variety of clinical syndromes known as the disconnection syndromes. While some of the original concepts proposed by the initial protagonists of the disconnection theory in the mid‐nineteenth century have been disproved, other conditions are now recognised as having a disconnectionist aetiology (e.g. autism and dyslexia). With improved neuroimaging, especially functional brain imaging, it is conceivable that the number of disorders attributable to disconnection syndromes will continue to increase. Disconnection syndromes may be under‐recognised, owing to both lack of physician knowledge of and difficulties elucidating these disorders, because of their subtle presentations (e.g.
anterior callosal lesions
).

Key Concepts

Disconnection syndromes should be considered when dealing with aphasia, alexia and agnosia and impaired hand function.

Autism and dyslexia can be thought of as congenital disconnection syndromes.

Presentations of disconnection syndromes may be subtle and need to be specifically examined for in order to avoid missing the diagnosis.

Disconnection syndromes involve interruption of communication between highly specialised brain regions.
Hippo Growth Control Pathway and Organ Size
Authors: Waghmare Indrayani , Verghese Shilpi , Kango‐Singh Madhuri 
Published: May 2015

Abstract

In multicellular organisms, regulation of growth control occurs because of the concerted action of multiple growth‐regulatory and patterning pathways. Among these, the Hippo (Hpo) pathway gained notoriety for its unique ability to simultaneously regulate cell proliferation and apoptosis to achieve the correct organ size. Initially discovered in
Drosophila
, this pathway is evolutionarily conserved, and acts as a universal regulator of organ size in metazoa. A complete pathway that integrates signals from the cell membrane to the nucleus has emerged, and multiple modes of Hpo pathway regulation have been elucidated. When the Hpo pathway is active, it acts as a brake on growth – cell proliferation is suppressed and apoptosis is promoted, whereas when the Hpo pathway is inactive, growth occurs – cell proliferation is promoted and apoptosis is suppressed. While the initial discovery of the pathway established its role in regulation of organ size and development, the focus has shifted considerably towards understanding its role in other biological processes such as maintaining tissue homeostasis, stem cell and tissue differentiation, cancer and regeneration. The Hpo signalling pathway functions in organ size control, and understanding its physiological functions will provide insights on its tissue‐ and cell‐type‐specific functions, and its involvement in diseases such as cancer.

Key Concepts

Cell proliferation and cell death must be regulated for balanced growth.

The regulation of Hippo pathway activity is key to regulating cell number to achieve the correct organ size and growth during normal development.

Hippo pathway activation promotes apoptosis and suppresses cell proliferation, whereas Hippo pathway inactivation promotes cell proliferation and suppresses apoptosis.

The Hippo pathway is a network of tumour suppressor genes, and genes regulating cell‐ and planar‐polarity.

Signalling interactions in the Hippo pathway ultimately converge on the regulation of the oncogene Yorkie pathway activity.

The Hippo pathway is conserved across species.

Hippo pathway is dysregulated in human cancer (e.g. loss of tumour suppressor gene neurofibromin 2 (NF2) is causal to schwannomas, and the YAP/TAZ oncoproteins are overexpressed in many human cancers [lung, breast, prostate and liver]).

Hippo pathway regulates stem cell renewal, regeneration and differentiation in a tissue‐ and context‐specific manner.
Alternative Polities
Authors: McIntosh Roderick J. 
Published: May 2015

Abstract
The prehistoric landscape has exploded with examples, just recently recognized, of alternative polities—heterogeneous communities of interaction, of variable territorial and demographic extent, in which the constituent individuals participate in unifying networks of economic or political obligations or share commonalities of beliefs. Archaeologists are no longer constrained to look for the emergence of complex society in a framework of sequential, evolutionary stages the essential elements of which were defined ethnographically (neo‐evolutionism). We can now begin to appreciate the enormous variability in the courses taken, and in the circumstances leading to more and more people living together and interacting in ever more complex ways.
Biology and Culture
Authors: Hobson Robert Peter 
Published: May 2015

Abstract
How are we to think of the developmental relations between individual and social dimensions of human psychology? On the one hand, an individual's mental development depends on social engagement and socially constructed symbolic systems and institutions. On the other hand, the very existence of a social system depends on the biologically provided constitution of the individuals who make up its members. I shall consider these matters at the interface between the behavioral and social sciences through the perspective of developmental psychopathology, and, in particular, the study of autism.
Computer Technology and Children's Mental Health
Authors: Kendall Philip C. , Carper Matthew M. , Khanna Muniya S. , Sue Harris M. 
Published: May 2015

Abstract
Computer technology has sparked rapid change for children's mental health, altering how treatments can be delivered (e.g., stand‐alone, computer‐assisted). Research has found that computerized approaches produce comparable outcomes as treatments provided face‐to‐face. We define terms related to computer‐assisted treatment and, with a focus on anxiety in youth, we consider the outcomes of computer‐based and computer‐assisted interventions (programs for youth, programs for training therapists, and programs for parents). We conclude with consideration of advances in technology and benefits for service providers, consumers, and researchers, and a discussion of key issues.