bluuebunny/crossref_metadata_2025 huggingface dataset:
Ready Player Two
Authors: Chess Shira
Published: September 2018

Since the mid-2000s, an increasing number of video games have been designed for women audiences. The market is tenuous, and has grown in spurts, but has resulted in a reality where roughly half of all video game players are now women. What once was considered a masculine domain is currently embedded in a stylistic and economic shift. With this in mind, Ready Player Two: Women, Video Games, and Designed Identity is an analysis of video games designed and advertised for women audiences, with the goal of better understanding what is really “at play” in these games. Games in this category range in style: from Diner Dash to Mystery Case Files and from Kim Kardashian: Hollywood to the Nintendo Wii, even distinctly different games have commonalities. Using the premise of “Designed Identity” or “a hybrid outcome of industry conventions, textual constructs, and audience placements in the design and structure of video games” the book introduces the premise of Player Two. Player Two is not a real player, but a ghost of a player, imagined by the video game industry. While feminine, Player Two also comes packaged with other identity markers: she is white, middle class, heterosexual, cis-gendered, and abled. Breaking down how Player Two is constructed in the games created for her, Ready Player Two considers both the positive and negative aspects of this fictionalized, yet transformational character in the video game industry.
Patient and Caregiver Understanding of Prognosis After Hip Fracture
Authors: Eikelboom Rachel , Gagliardi Anna R. , Gandhi Rajiv , Soong Christine , Cram Peter
Published: September 2018

BackgroundHip fracture (HF) is common and requires communication between patient, family, surgeons, and hospitalists. Patient and family understanding of the seriousness of HF is unclear.MethodsWe interviewed older patients (age > 65 years) hospitalized with HF at two Canadian academic hospitals, or their surrogate decision-makers (SDMs). We used qualitative methods to explore understanding of HF treatment options and prognosis. Participants estimated probability of mortality and living independently 30 days after surgery. Results were compared with estimates from the National Surgery Quality Improvement Program (NSQIP) surgical risk calculator.Results9 patients and 3 SDMs were interviewed. Mean age of 12 patients was 82.5 years (75% female). Participants were uncertain about recovery timeline and degree of functional recovery, as well as content and duration of rehabilitation. Participants’ mean estimated 30-day mortality of 6.7% did not differ significantly from estimated mortality predicted by NSQIP (7.5%; p = .88). Participants’ mean estimated probability of living independently 30 days after surgery was 90.8% (range 65–100%).ConclusionsOlder patients and SDMs lack understanding about prognosis and functional recovery even after providing informed consent for HF surgery. Clinical teams should improve communication of prognosis and recovery information to patients and surrogates.
Graveside and Other Asymmetrical Promises
Authors: Albrecht Ingrid V. ,   Department of Philosophy, Florida State University
Published: September 2018

People who make graveside promises consider themselves bound by them, which raises the question of whether a promise can morally obligate a promisor directly to a promisee who cannot acknowledge the promise. I show that it can by using the theoretical framework provided by “transaction accounts” of promising. Paradigmatically, these accounts maintain that the creation of a promissory obligation requires that the promisee consent to the promise. I extend these accounts to capture promises made by proxy and self-promises, and conclude that we can make promises to absent promisees when we bear responsibility for their moral and personal development.
Follicular Lymphoma Diagnostic Caveats and Updates
Authors: Choi Sarah M. , Betz Bryan L. , Perry Anamarija M.
Published: September 2018

Context.—

Follicular lymphoma is a common small B-cell lymphoma, likely to be encountered by any practicing pathologist, regardless of specialty. Although the features of typical follicular lymphoma are well known and in most instances easily identifiable, there are lesser-appreciated morphologic appearances that can raise alternative diagnostic possibilities. The limited tissue available in core needle biopsies can make it additionally challenging to thoroughly evaluate those features in the context of architecture. Furthermore, ancillary testing including immunohistochemistry and molecular/genetic analysis do not always show classic findings and may pose additional challenges to interpretation.

Objectives.—

To review the morphologic features of follicular lymphoma with a discussion of morphologic variants and mimics; to discuss pitfalls of ancillary testing and provide the practicing pathologist with an appropriate context for interpretation of immunohistochemical and molecular/genetic studies when follicular lymphoma is part of the differential diagnosis; and to propose diagnostic strategies when there is limited tissue for evaluation.

Data Sources.—

We used examples of follicular lymphoma from our institution as well as a review of the literature, with a focus on the diagnostic aspects that are broadly relevant to a general pathology practice.

Conclusions.—

Follicular lymphoma can occasionally present with atypical morphologic, immunohistochemical, or molecular/genetic features. In particular, those findings can be difficult to interpret in the setting of a limited tissue sample. Awareness of those possibilities will help guide the pathologist to a more accurate and precise diagnosis.
Phylogeography ofSwertia perennisin Europe based on cpDNA markers
Authors: Urbaniak Jacek , Kwiatkowski Paweł , Pawlikowski Paweł
Published: September 2018

Background

Swertia perennis(Gentianaceae) is a perennial diploid and clonal plant species that is discontinuously distributed in peat bogs in the mountains of Europe, Asia and North America as well as in the lowlands of Europe. The current geographical dispersion ofS. perennisis probably the result of quaternary climatic changes that have played an important role in determining the distribution ofSwertiaand other plant and animal species.

Methods

In this study we used molecular techniques and combined data from chloroplast DNA markers (trnLF region andtrnH-psbA spacer) to elucidate the phylogeography ofS. perennisin Europe. Plants were collected from 28 populations in different locations in the lowlands and mountainous areas of Europe (e.g., the Carpathians, Sudetes, Bohemian Forest and Alps). cDNA was analysed to detect the genetic relationship between specimens from different locations.

Results

A total of 20 haplotypeswere identifiedacross the dataset. Theywere characterised by a high level of genetic variability but showed a lack of phylogeographical structure. This pattern may be the result of repeated recolonization and expansion from several areas. Such genetic differentiation may also be attributed to the relatively long-term isolation ofS. perennisin Pleistocene refugia in Europe, which resulted in independent separation of different cpDNA phylogenetic lineages and variation in the nucleotide composition of cpDNA.

Discussion

The lack of strong phylogeographical structure makes it impossible to indicate the centre of haplotype diversity; however, refugia located in the Carpathians, Sudetes or Alps are the most probable sites whereS. perennisexisted in Europe. This lack of structure may also indicate a high level of gene flow in times when the landscape and fen systems were not fragmented in numerous geographically-isolated populations. This makes it difficult to speculate about the relationships between Asiatic and European plant populations and the origin and distribution of this species in Europe. Today, it seems to be restricted due to the occurrence of plants which clearly reflects the genetic variability from the ancient period.
Nonspecific stress response to temperature increase in Gammarus lacustris Sars with respect to oxygen-limited thermal tolerance concept
Authors: Vereshchagina Kseniya , Kondrateva Elizaveta , Axenov-Gribanov Denis , Shatilina Zhanna , Khomich Andrey , Bedulina Daria , Zadereev Egor , Timofeyev Maxim
Published: September 2018

The previously undescribed dynamics of the heat shock protein HSP70 and subsequent lipid peroxidation products have been assessed alongside lactate dehydrogenase activity for Gammarus lacustris Sars, an amphipod species from the saltwater Lake Shira (Republic of Khakassia). Individuals were exposed to a gradual temperature increase of 1 °C/hour (total exposure duration of 26 hours) starting from the mean annual temperature of their habitat (7 °C) up to 33 °C. A complex of biochemical reactions occurred when saltwater G. lactustris was exposed to the gradual changes in temperature. This was characterized by a decrease in lactate dehydrogenase activity and the launching of lipid peroxidation. The HSP70 level did not change significantly during the entire experiment. In agreement with the concept of oxygen-limited thermal tolerance, an accumulation of the most toxic lipid peroxides (triene conjugates and Schiff bases) in phospholipids occurred at the same time and temperature as the accumulation of lactate. The main criterion overriding the temperature threshold was, therefore, the transition to anaerobiosis, confirmed by the elevated lactate levels as observed in our previous associated study, and by the development of cellular stress, which was expressed by an accumulation of lipid peroxidation products. An earlier hypothesis, based on freshwater individuals of the same species, has been confirmed whereby the increased thermotolerance of G. lacustris from the saltwater lake was caused by differences in energy metabolism and energy supply of nonspecific cellular stress-response mechanisms. With the development of global climate change, these reactions could be advantageous for saltwater G. lacustris. The studied biochemical reactions can be used as biomarkers for the stress status of aquatic organisms when their habitat temperature changes.
60S dynamic state of bacterial ribosome is fixed by yeast mitochondrial initiation factor 3
Authors: Levitskii Sergey , Derbikova Ksenia , Baleva Maria V. , Kuzmenko Anton , Golovin Andrey V. , Chicherin Ivan , Krasheninnikov Igor A. , Kamenski Piotr
Published: September 2018

The processes of association and dissociation of ribosomal subunits are of great importance for the protein biosynthesis. The mechanistic details of these processes, however, are not well known. In bacteria, upon translation termination, the ribosome dissociates into subunits which is necessary for its further involvement into new initiation step. The dissociated state of the ribosome is maintained by initiation factor 3 (IF3) which binds to free small subunits and prevents their premature association with large subunits. In this work, we have exchanged IF3 inEscherichia colicells by its ortholog fromSaccharomyces cerevisiaemitochondria (Aim23p) and showed that yeast protein cannot functionally substitute the bacterial one and is even slightly toxic for bacterial cells. Our in vitro experiments have demonstrated that Aim23p does not splitE. coliribosomes into subunits. Instead, it fixes a state of ribosomes characterized by sedimentation coefficient about 60S which is not a stable structure but rather reflects a shift of dynamic equilibrium between associated and dissociated states of the ribosome. Mitochondria-specific terminal extensions of Aim23p are necessary for “60S state” formation, and molecular modeling results point out that these extensions might stabilize the position of the protein on the bacterial ribosome.
Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer
Authors: Liu Stephanie S. , Chan Karen K. L. , Chu Daniel K. H. , Wei Tina N. , Lau Lesley S. K. , Ngu Siew F. , Chu Mandy M. Y. , Tse Ka Yu , Ip Philip P. C. , Ng Enders K. O. , Cheung Annie N. Y. , Ngan Hextan Y. S.
Published: September 2018

Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre‐malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR‐20a, miR‐92a, miR‐141, miR‐183*, miR‐210 and miR‐944) were found to be significantly up‐regulated in cervical cancer and pre‐malignant lesions compared to normal cervical samples, indicating that they are oncogenic miRNAs. Receiver operating characteristic curve analysis showed that these six miRNAs can be used to distinguish patients with cervical pre‐malignant lesions or cancer from normal individuals and they also had a good predictive performance, particularly in cervical lesions. Combined use of these six miRNAs further enhanced the diagnostic accuracy over any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959, a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%, 96.6% and 87.6% for low‐grade lesions, high‐grade lesions and cancer, respectively. This six oncogenic miRNA signature may be suitable for use as diagnostic marker for cervical pre‐malignant lesions and cancer in the near future.
Acidophiles
Authors: Oren Aharon
Published: September 2018

Microorganisms growing in highly acidic environments (pH values below three) are found in all three domains of life: Archaea, Bacteria and Eucarya. Such organisms thrive in acidic sulfur springs and in association with mining activities where microbial oxidation of pyrite and other reduced sulfur compounds lead to the formation of sulfuric acid. Acidophilic bacteria and archaea are also involved in the industrial leaching of copper and other metals from ores. Some acidophiles grow at high temperatures. Physiologically, the acidophiles are very diverse; there are aerobic and facultative anaerobic chemolithotrophs and different types of heterotrophic bacteria and archaea, photoautotrophic eukaryotes, predatory protozoa and others. Acidophilic microorganisms maintain their intracellular pH close to neutrality, and their cytoplasmic membrane may support proton gradients up to five orders of magnitude; their membrane potential is often reversed in comparison with neutrophiles and alkaliphiles, with an intracellular positive charge.

Key Concepts

Microbial life is possible in strongly acidic environments and even at pH values below zero.

The low pH of highly acidic environments in volcanic areas and environments associated with metal ore mining is generally caused by the activities of acidophilic microorganisms that oxidise reduced sulfur compounds to sulfuric acid.

Acidophilic microorganisms are found in all three domains of life: Archaea, Bacteria and Eucarya.

Unicellular eukaryotic green algae such as
Dunaliella acidophila
and
Chlamydomonas acidophila
perform photosynthesis at pH values down to 0–1 and the red alga
Cyanidium caldarium
grows as a photoautotroph in acidic hot springs up to 57 °C and at pH<2–4.

Some thermoacidophilic Archaea thrive at low pH up to very high temperatures.
Sulfolobus
and
Acidanus
spp. grow up to 96 °C at pH 1–5;
Picrophilus oshimae
tolerates pH<0 and grows up to 65 °C.

Acidophilic microorganisms keep their intracellular pH at values close to neutrality and maintain a proton gradient over their cytoplasmic membranes of up to five orders of magnitude.

In contrast to neutrophilic and alkaliphilic microorganisms that maintain an outside‐positive membrane potential, the membrane potential over the cytoplasmic membrane can be reversed, positive‐inside, in acidophilic microorganisms.

Extracellular enzymes of acidophilic microorganisms are optimally active at low pH.

Acid mine drainage is caused by the chemolithotrophic oxidation of pyrite and other reduced sulfur compounds in the ores by acidophilic archaea such as
Acidithiobacillus
,
Leptospirillum
and
Ferroplasma
.

The activities of the same types of organisms that cause acid mine drainage are exploited industrially for the bioleaching of copper and other metals from ores.
Promoter Fusions to Study Gene Expression
Authors: Ma Jun
Published: September 2018

One important tool in molecular biology takes advantage of promoter fusions where the expression of one gene is controlled by the promoter or regulatory elements of another gene. Promoter fusions engineered
in vitro
can help to determine how gene expression is regulated in cells and whole organisms. Promoter fusions generated
in vivo
, for example by promoter trapping, can help to identify new genes and generate useful genetic resources for dissecting important biological processes. A binary effector–reporter system can be used to direct the production of a protein of interest in specific cells of an organism for functional studies. It can also be used to direct the production of interference ribonucleic acid molecules that can inhibit the activity of their target genes in specific cells of an organism. The GAL4–UAS version of this binary system is a valuable genetic tool for investigations of mechanisms that control development.

Key Concepts

The first step towards expressing a gene is transcription.

Gene transcription is controlled by regulatory DNA sequences (elements) that contain binding sites for regulatory proteins.

The regulatory DNA element of one gene can exert its effect on the expression of another gene in a chimaeric (fusion) construct.

Engineered fusion constructs can be introduced to cells or whole organisms.

Reporter genes are used in fusion constructs because their encoded proteins can be monitored or assayed easily.

Reporter fusion constructs can be used to analyse the functions of the regulatory DNA elements.

An effector–reporter system can be used to study the relationship between a regulatory DNA element and the regulatory proteins that bind to it.

Promoter trapping and enhancer trapping are useful techniques to generate genome‐scale resources for genetic studies.

A binary effector–reporter system (a version of which is commonly known as the GAL4–UAS system) is a powerful genetic tool.
Retroviruses in Human Gene Therapy
Authors: Pedersen Finn S , Mikkelsen Jacob G
Published: September 2018

A retrovirus‐based gene transfer system consists of two components: the transfer vector, which harbours a foreign gene linked to elements needed for retroviral replication, and the packaging constructs, which supply the necessary retroviral proteins for transfer of the vector from a producer cell through a single round of viral replication. A hallmark of retroviral replication is the stable maintenance of the transferred gene(s) during cell division. The first type of transfer vectors used in gene therapy trials were derived from mouse retroviruses and referred to as retroviral vectors. Lentiviral vectors are derived from human immunodeficiency virus type 1 and exhibit distinct features that provide advantages in some settings. Retroviral and lentiviral vectors are being used in clinical trials for several diseases, including monogenic diseases and cancer. The clinical protocols include primarily
ex vivo
gene transfer followed by introduction of the genetically modified cells into the body.

Key Concepts

The retroviral replication machinery leads to stable maintenance of a transferred gene.

The stable integration of retroviral vectors into a chromosome of the target cell may have adverse effects on neighbouring genes.

Retroviral gene transfer does not require the expression of retroviral genes in the target cell.

The term retroviral vector is used for a vector based on murine leukaemia virus.

The term lentiviral vector is used for a vector based on human immunodeficiency virus type 1.

Retroviral and lentiviral vectors differ in their integration patterns with respect to genes and gene regulatory regions.

To treat inherited monogenic disease affecting e.g. skin or blood, stem cells can be corrected
ex vivo
by using retroviral and lentiviral vectors.

Retroviral and lentiviral vectors are used in clinical protocols to generate modified T‐lymphocytes that target cancer cells.

New designs of lentiviral vectors are being developed as a toolbox for therapy by the CRISPR/Cas9 genome editing technology.
Facioscapulohumeral Muscular Dystrophy: Genetics
Authors: Magdinier Frédérique , Upadhyaya Meena
Published: September 2018

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited muscular dystrophy that presents clinically with progressive weakness of the facial, scapular and humeral muscles, with later involvement of the trunk and lower extremities. FSHD is a unique disease with complex genetic and epigenetic aetiology and the underlying biological mechanisms are still not fully deciphered. FSHD1 is more frequent (95%) and is associated with the contraction of the D4Z4 macrosatellite repeat array located on a permissive 4qA chromosome combined with decreased methylation of cytosines at the 4q35‐linked D4Z4 units. D4Z4 contraction allows epigenetic derepression of the D4Z4 array allowing the expression of the toxic
DUX4
transcription factor encoded within the terminal D4Z4 repeat in skeletal muscles. FSHD2 associated with approximately 2–3% of the FSHD patients results from haploinsufficiency of the
SMCHD1
gene in individuals carrying a permissive 4qA allele and marked hypomethylation of 4q and 10q D4Z4, which leads to the derepression of
DUX4
hence
DUX4
appears to be a key player in both types of FSHD. Currently, there is no reliable treatment for this condition, therefore for the successful development of new treatments, an integration of clinical and pathogenetic information is vital.

Key Concepts

FSHD is the third most common inherited muscular dystrophy characterised by a typical phenotype and involvement of specific groups of muscles.

FSHD is characterised by a highly variable penetrance and clinical severity.

In most cases, FSHD involves shortening of a repetitive macrosatellite array.

The D4Z4 macrosatellite linked to FSHD encodes the DUX4 transcription factor.

A small proportion of FSHD patients carry mutation in the
SMCHD1
gene.

Epigenetic changes in FSHD are closely associated with molecular features.

FSHD is a unique disease with complex genetic and epigenetic aetiology and the underlying biological mechanisms are still not fully deciphered.

There is no reliable treatment for the disease.
Centrosomes in Asymmetric Cell Division and Neocortical Development
Authors: Mora‐Bermúdez Felipe , Huttner Wieland B
Published: September 2018

Centrosomes play crucial roles in the homeostasis and cell cycle progression of many different cell types, and neural stem and progenitor cells (NSPCs) are not the exception. In fact, NSPCs could be among the cell types where the functions and characteristics of centrosomes are most diverse and unique. From spindle orientation to subcellular organization to primary cilium formation and beyond, centrosome functions are intimately linked to the highly polarized and dynamic architecture of NSPCs in the cerebral neocortex. This leads us to argue that centrosomes are among the organelles that most influence the cytoarchitecture of NSPCs, which translates into a decisive influence in their proliferation, differentiation and tissue and organ formation properties.

Key Concepts

Centrosomes are crucial for the cell and tissue biology of neural stem and progenitor cells (NSPCs).

Centrosomes control symmetric vs. asymmetric cell division in NSPCs.

Many genes implicated in neurodevelopmental disorders, such as primary microcephaly, encode centrosome proteins.

Centrosomes also fulfil essential nonmitotic functions, such as primary cilium formation.

NSPC proliferation and differentiation are influenced in diverse ways by centrosomes.
G
oldstein,
K
urt
Authors: Ferrario Chiara Elettra
Published: September 2018

Kurt Goldstein (1878–1965) was a philosophically minded neurologist, psychiatrist and psychotherapist. Known in neurology for the first clinical description of the Alien Hand Syndrome, and in psychology for having inspired the American Humanistic movement, Goldstein's broader reflection on the nature of biological knowledge had fallen into relative neglect.

In recent years, his organicist theory of biological knowledge, outlined in his classic
The Organism
(1934), has attracted increasing attention in philosophical circles. Organicist theories of biology represent an important milestone in the history of ideas, having anticipated themes that are now relevant to contemporary philosophy of biology.

The relative lack of recognition of Goldstein's work may be imputed to a combination of biographical factors (most notably the personal and intellectual setback following his forced exile from Nazi Germany, due to his Jewish origins) and of unwavering eclecticism, which may have hampered absorption and conveyance within the boundaries of particular disciplines.

Key Concepts

Kurt Goldstein is an important figure in the history of neurology and more broadly neuroscience, whose legacy might have gone relatively unnoticed due to his eclecticism and biographical vicissitudes.

His 1934 magnum opus, the monumental
The Organism
, encapsulates the empirical findings and clinical observations of a lifetime and organises them under the innovative theoretical framework of organicism.

The organicist stance applied to neuroscience leads to a contextual, dynamic and distributed view of the nervous system that has been vindicated by later research.

Goldstein's ideas on neuropathology, psychotherapy and individually tailored healthcare have influenced psychological movements such as humanist psychology and are still appreciated for their originality and intrinsic ethical value.

Goldstein's organicism, intended as a theoretical framework of interpretation for biology, has recently attracted the attention of philosophers of biology.

Under the philosophical respect, Goldstein's organicism presents some stark peculiarities, especially if compared with coeval positions from the same theoretical family. One especially evident feature is the virtual absence of evolutionary dimension to it.
Foetal Diagnosis
Authors: Miny Peter , Filges Isabel , Tercanli Sevgi , Holzgreve Wolfgang
Published: September 2018

New genetic testing approaches as well as a constant progress in the imaging technologies of the foetus have changed the practice of prenatal diagnosis during the past decade fundamentally. The greatly improved noninvasive risk assessment for common foetal aneuploidies by recent cell‐free DNA (cfDNA) testing technologies on maternal plasma (NIPT or NIPS) has been much acclaimed by pregnant women and their doctors as well and resulted in a significant decline of invasive testing requiring chorionic villus sampling or amniocentesis. Exclusion of foetal aneuploidy is still by far the most frequent indication for prenatal testing, and the growing number of options must be addressed in routine care for all pregnancies. Pregnancies at high risk for foetal aneuploidy or other copy number variations profit from high‐resolution karyotyping using chromosomal microarrays. Noninvasive prenatal diagnosis (NIPD) is established for the foetal sex or blood group markers and progressing for numerous monogenic conditions.

Key Concepts

Noninvasive testing of cell‐free DNA in the maternal plasma is an established screening tool for trisomy 21 and other common trisomies and has caused a significant decrease of invasive testing.

Cell‐free DNA testing for common aneuploidies with current technologies will likely not become diagnostic owing to its origin from trophoblast cells.

Targeted cell‐free DNA testing is a diagnostic option for a growing number of monogenic conditions.

Genomic testing approaches such as symptom‐ or disease‐based gene panels or whole‐exome sequencing spread slowly into invasive as well as noninvasive prenatal testing.

Genetic testing on amniotic fluid cells or placental villi is most comprehensive and accurate and remains the gold standard of foetal diagnosis.
Dynamic Chromatin Architecture of the Epidermal Differentiation Complex (
EDC
)
Authors: Mathyer Mary Elizabeth , de Guzman Strong Cristina
Published: September 2018

Transcription is a tightly regulated process that enables genomic loci to be expressed in a tissue‐specific manner. The molecular mechanisms of transcriptional regulation are complex and multimodal, from enzymatic epigenetic modifications associated with either repressed or active chromatin at specific loci to physical enhancer–promoter contacts conducive to gene expression, and the nonrandom positioning of the chromatin within the nucleus. The skin epidermis provides an accessible model to investigate tissue‐specific expression and differentiation. Central to keratinocyte differentiation is the transcriptional activation of many genes encoded by the Epidermal Differentiation Complex (EDC). The past decade has witnessed pivotal discoveries for deoxyribonucleic acid (DNA) methylation and histone methylation and acetylation in the regulation of the EDC and epidermal differentiation. Moreover, chromatin conformation capture studies have revealed the importance of dynamic chromatin remodelling at the EDC upon epidermal differentiation. The studies, modelled on the EDC and described herein, have revolutionised our understanding of tissue‐specific expression.

Key Concepts

Tissue‐specific transcription is tightly regulated and complex.

Epidermal differentiation and the regulation of the EDC locus provide an accessible model towards understanding the molecular mechanisms of tissue‐specific transcriptional regulation.

Distinct epigenetic patterns of DNA methylation and histone modifications contribute to locus‐specific expression at a genome‐wide level.

Histone methyltransferases JMJD3, EZH2 and SETD8 and histone deacetylase HDAC1/2 modify the chromatin of the EDC to permit proper epidermal development.

The EDC preferentially migrates towards the interior of the nucleus for active transcription.

Enhancers are regulatory elements whose proximal interactions with gene promoters drive tissue‐specific expression.

Epidermal enhancer–promoter interactions are dynamic between proliferative and differentiated keratinocytes with a second class of interactions stable between developmental states.

The capturing of cell type‐specific chromatin states identifies topologically associated domains (TADs) comprised of enriched physical chromatin contacts that include enhancer–promoter interactions.

The EDC is spatially organised into four TADs.
DNA
Replication: Yeast
Authors: Smith Shanna J , Li Caroline M , Raoof Mustafa , Lingeman Robert G , Hickey Robert J , Malkas Linda H
Published: September 2018

DNA replication is a complex biological process essential to maintaining the fidelity of genetic information passed to subsequent generations, while allowing for the mutations necessary for natural selection. The cellular machinery required for DNA replication must be precisely controlled throughout the cycle. A variety of DNA polymerases have proofreading and repairing capabilities to avoid catastrophic errors, thus maintaining genomic stability. Much of the mechanism involved in this process is evolutionarily conserved. Because yeast is a relatively simple and inexpensive organism to work with, much of our understanding of DNA replication in eukaryotes originates from experiments with yeast. The most thoroughly characterized model yeast systems are
Saccharomyces cerevisiae
(budding yeast) and
Saccharomyces pombe
(fission yeast).

Key Concepts

Yeast is a good model organism for simplifying and characterising cellular processes, such as DNA replication.

The two most commonly used yeast models are
S. cerevisiae
and
S. pombe
.

DNA replication is a complex biological process essential to genomic replication.

DNA replication is a process that involves timely organisation of proteins and is regulated during the cell cycle by cyclin‐dependent protein kinases.

Termination of DNA replication in yeast is generally not sequence specific, except in special circumstances in the cellular process.
Tracing Pathogen Transmission by Mosquitoes under a Global Change Perspective: On the Role of the Identification of Mosquito Bloodmeals
Authors: la Puente Josué Martínez‐de , Ferraguti Martina , Ruiz Santiago , Montalvo Tomás , Casimiro Soriguer Ramón , Figuerola Jordi
Published: September 2018

Mosquitoes play a central role in the transmission of vector‐borne pathogens causing important diseases in humans, livestock and wildlife. The identification of mosquito blood feeding preferences represents an essential step in epidemiological studies to identify the potential reservoirs and the contact rates between infective and susceptible hosts. Different methods have been used to trace mosquito bloodmeal origins in ecology and public health studies providing valuable results. These studies are specially relevant under a global change scenario, where habitat alteration and changes in the distribution of the ecological community of mosquitoes could affect the dynamics of transmission of mosquito‐borne pathogens.

Key Concepts

Mosquitoes play a central role in the transmission of many vector‐borne pathogens.

Environmental conditions determine the mosquito community structure in the area, potentially affecting the dynamics of transmission of vector‐borne pathogens.

Female mosquitoes feed on blood to obtain resources for egg development.

The bloodmeals of mosquitoes provide a valuable source of genetic material allowing the identification of vertebrate species origin even to the level of individuals host and the pathogens interacting with them.

Integrating information on the feeding patterns of mosquitoes into epidemiological models contributes to identifying the risk of transmission of vector‐borne pathogens to human and other animals.
GPCR Signal Transduction: Evolution by Gene Duplication
Authors: McMullen Timothy P , Brown Robin Isadora , Ausrafuggaman Nahid , Sahu Alisha , Güler Ali D , Deppmann Christopher D
Published: September 2018

Signal transduction cascades initiated by G‐protein‐coupled receptors (GPCRs) integrate a number of components including seven‐pass transmembrane receptors (7TM), heterotrimeric G‐proteins, downstream protein kinases and responsive transcription factors. This signalling pathway has evolved to facilitate a number of cellular responses related to metabolism, cell proliferation, neurotransmission, DNA repair and many other critical processes. Gene duplication and subfunctionalisation events have contributed to the emergence of several core components of the GPCR signalling pathway over the course of eukaryotic evolutionary history. Four key components of this pathway include GPCRs, receptor‐associated heterotrimeric G‐proteins, downstream kinase targets, such as protein kinase A (PKA) and transcription factors such as cAMP response element binding protein (CREB).

Key Concepts

G‐protein‐coupled receptors (GPCRs) are seven‐pass transmembrane proteins, which have diversified into five main families over evolutionary time.

Heterotrimeric G‐proteins transduce nuanced responses via different combinations of α, β and γ‐subunits, which have evolved from numerous well‐defined duplication events.

Protein kinase A (PKA) is a downstream hub whose catalytic and regulatory subunits have diversified in eukaryotic lineages.

The cAMP response element‐binding protein (CREB) function is highly conserved in eukaryotes while the auxiliary components of its pathway have changed.
Oxidation of Alcohols and Amines
Authors: Uyanik Muhammet , Ishihara Kazuaki
Published: September 2018

Oxidation of alcohols and amines is one of the central reactions in synthetic organic chemistry. Traditionally, highly toxic heavy metal oxidants have been used for these fundamental reactions. Transition metal‐catalyzed oxidation reactions have been extensively investigated, particularly since gaseous oxygen could be used as a stoichiometric oxidant. Nevertheless, more environmentally benign catalytic and chemoselective oxidation methods such as organocatalysis are needed, especially in pharmaceutical industry. Over the past three decades, hypervalent iodine compounds have been the focus of a great attention due to their mild and chemoselective oxidizing properties and their environmentally benign character. This chapter focuses on the design of hypervalent iodine compound reagents or catalysts for the oxidation of alcohols and amine derivatives.
The Evolving Marsick and Watkins (1990) Theory of Informal and Incidental Learning
Authors: Watkins Karen E. , Marsick Victoria J. , Wofford M. Grant , Ellinger Andrea D.
Published: September 2018

Examples of informal and incidental learning, including an extended discussion of informal learning in flight instruction, are used to illustrate the model of informal and incidental learning in practice, as well as the nonlinear nature of this learning.
Connections, Questions, Controversies, and the Potential Paths Forward
Authors: Nicolaides Aliki , Scully‐Russ Ellen
Published: September 2018

In this final chapter, we identify and elaborate the connections throughout the volume. We explore the philosophical underpinnings of the original model and analyze how the different lenses in these chapters lead the authors to new understandings of informal and incidental learning that trouble some of the features of the original model. We examine how these different lenses impact informal and incidental theory, practice, and research.
Development of a dedicated phantom for multi‐target single‐isocentre stereotactic radiosurgery end to end testing
Authors: Poder Joel , Brown Ryan , Porter Harry , Gupta Rashmi , Ralston Anna
Published: September 2018

Purpose

The aim of this project was to design and manufacture a cost‐effective end‐to‐end (E2E) phantom for quantifying the geometric and dosimetric accuracy of a linear accelerator based, multi‐target single‐isocenter (MTSI) frameless stereotactic radiosurgery (SRS) technique.

Method

A perspex Multi‐Plug device from a Sun Nuclear ArcCheck phantom (Sun Nuclear, Melbourne, FL) was enhanced to make it more applicable for MTSI SRS E2E testing. The following steps in the SRS chain were then analysed using the phantom: magnetic resonance imaging (MRI) distortion, planning computed tomography (CT) scan and MRI image registration accuracy, phantom setup accuracy using CBCT, dosimetric accuracy using ion chamber, planar film dose measurements and coincidence of linear accelerator mega‐voltage (MV), and kilo‐voltage (kV) isocenters using Winston‐Lutz testing (WLT).

Results

The dedicated E2E phantom was able to successfully quantify the geometric and dosimetric accuracy of the MTSI SRS technique. MRI distortions were less than 0.5 mm, or half a voxel size. The average MRI‐CT registration accuracy was 0.15 mm (±0.31 mm), 0.20 mm (±0.16 mm), and 0.39 mm (±0.11 mm) in the superior/inferior, left/right and, anterior/posterior directions, respectively. The phantom setup accuracy using CBCT was better than 0.2 mm and 0.1°. Point dose measurements were within 5% of the treatment planning system predicted dose. The comparison of planar film doses to the planning system dose distributions, performed using gamma analysis, resulted in pass rates greater than 97% for 3%/1 mm gamma criteria. Finally, off‐axis WLT showed MV/kV coincidence to be within 1 mm for off‐axis distances up to 60 mm.

Conclusion

A novel, versatile and cost‐effective phantom for comprehensive E2E testing of MTSI SRS treatments was developed, incorporating multiple detector types and fiducial markers. The phantom is capable of quantifying the accuracy of each step in the MTSI SRS planning and treatment process.
Use of Wearable Activity Trackers to Improve Physical Activity Behavior in Patients With Rheumatic and Musculoskeletal Diseases: A Systematic Review and Meta‐Analysis
Authors: Davergne Thomas , Pallot Adrien , Dechartres Agnès , Fautrel Bruno , Gossec Laure
Published: September 2018

Objective

Wearable activity trackers (WATs) could be a promising strategy to improve physical activity in patients with rheumatic and musculoskeletal diseases (RMDs). The aim was to assess the adherence to and effectiveness of WATs to increase physical activity levels in patients with RMDs.

Methods

A systematic review was performed to identify all cohorts and controlled trials evaluating WATs in patients with RMDs, published between 2000 and 2018, by searching Medline, Embase, PsycINFO, and Cochrane. Data collected pertained to adherence, effectiveness on physical activity, or effectiveness on symptoms (pain, function, quality of life, or fatigue). Meta‐analyses were performed with a random effects model.

Results

Of 2,806 references, 17 studies were included, with a total of 1,588 patients: 8 studies (47%) in osteoarthritis, 5 (29%) in low‐back pain, and 3 (18%) in inflammatory arthritis. Adherence assessed in 4 studies was high (weighted mean ± SD time worn was 92.7% ± 4.6%). A significant increase in physical activity was noted (mean difference 1,520 steps [95% confidence interval (95% CI) 580, 2,460], I² = 77%; or 16 minutes [95% CI 2, 29] of moderate‐to‐vigorous physical activity, I² = 0%). A significant increase in pain was found for long interventions (>8 weeks) (standardized mean difference 0.25 [95% CI 0.07, 0.43], I² = 0%).

Conclusion

WATs in patients with RMDs had a high short‐term adherence, with a significant increase in the number of steps and time spent in moderate‐to‐vigorous physical activity, although pain should be monitored. WATs may be an effective option to increase physical activity in this at‐risk population.
Fungal Component Coating Enhances Titanium Implant‐Bone Integration
Authors: Shi Yuchen , Wang Lintao , Niu Yiming , Yu Na , Xing Panfei , Dong Lei , Wang Chunming
Published: September 2018

Bioactive coating on bone and dental implants is widely used to increase their integration with the host tissue, with millions of implantations performed globally each year. Numerous coating strategies focus on creating a cell‐adhesive surface by employing bone matrix components, but insufficient integration and its associated complications remain a substantial clinical challenge. Designing an implant coating to more comprehensively promote healing while appropriately modulating host immune response is still an unfulfilled promise. This study reports the development of a polysaccharide coating that can improve osseointegration by targeting and regulating inflammatory activity at the implant surface. Zymosan—a fungal component—is screened and covalently grafted onto titanium (Ti) substrates. The zymosan coating specifically stimulates macrophages through toll‐like receptors into a proregenerative phenotype, which produces abundant osteogenic/angiogenic cytokines to enhance osteogenic activities locally. Further assessment in a rat femur condyle defect indicates that zymosan coated at a medium dose (0.1 µg mm−2) remarkably increases the integration of Ti column with bone tissue, causing no abnormality to the host. This is the first demonstration that modulating inflammation with an immunoactive coating material can promote bone‐implant integration, which may inspire new strategies for the design of bone and dental implants.
Incorporating 4D into Bioprinting: Real‐Time Magnetically Directed Collagen Fiber Alignment for Generating Complex Multilayered Tissues
Authors: Betsch Marcel , Cristian Catalin , Lin Ying‐Ying , Blaeser Andreas , Schöneberg Jan , Vogt Michael , Buhl Eva Miriam , Fischer Horst , Duarte Campos Daniela Filipa
Published: September 2018

In vitro multilayered tissues with mimetic architectures resembling native tissues are valuable tools for application in medical research. In this study, an advanced bioprinting strategy is presented for aligning collagen fibers contained in functional bioinks. Streptavidin‐coated iron nanoparticles are embedded in printable bioinks with varying concentrations of low gelling temperature agarose and type I collagen. By applying a straightforward magnetic‐based mechanism in hydrogels during bioprinting, it is possible to align collagen fibers in less concentrated hydrogel blends with a maximum agarose concentration of 0.5 w/v%. Conversely, more elevated concentrations of agarose in printable blends show random collagen fiber distribution. Interestingly, hydrogel blends with unidirectionally aligned collagen fibers show significantly higher compression moduli compared to hydrogel blends including random fibers. Considering its application in the field of cartilage tissue engineering, bioprinted constructs with alternating layers of aligned and random fibers are fabricated. After 21 days of culture, cell‐loaded constructs with alternating layers of aligned and random fibers express markedly more collagen II in comparison to solely randomly oriented fiber constructs. These encouraging results translate the importance of the structure and architecture of bioinks used in bioprinting in light of their use for tissue engineering and personalized medical applications.
Toward Mass Production of CVD Graphene Films
Authors: Deng Bing , Liu Zhongfan , Peng Hailin
Published: September 2018

Chemical vapor deposition (CVD) is considered to be an efficient method for fabricating large‐area and high‐quality graphene films due to its excellent controllability and scalability. Great efforts have been made to control the growth of graphene to achieve large domain sizes, uniform layers, fast growth, and low synthesis temperatures. Some attempts have been made by both the scientific community and startup companies to mass produce graphene films; however, there is a large difference in the quality of graphene synthesized on a laboratory scale and an industrial scale. Here, recent progress toward the mass production of CVD graphene films is summarized, including the manufacturing process, equipment, and critical process parameters. Moreover, the large‐scale homogeneity of graphene films and fast characterization methods are also discussed, which are crucial for quality control in mass production.
Interfacial Defect Vibrations Enhance Thermal Transport in Amorphous Multilayers with Ultrahigh Thermal Boundary Conductance
Authors: Giri Ashutosh , King Sean W. , Lanford William A. , Mei Antonio B. , Merrill Devin , Li Liyi , Oviedo Ron , Richards John , Olson David H. , Braun Jeffrey L. , Gaskins John T. , Deangelis Freddy , Henry Asegun , Hopkins Patrick E.
Published: September 2018

The role of interfacial nonidealities and disorder on thermal transport across interfaces is traditionally assumed to add resistance to heat transfer, decreasing the thermal boundary conductance (TBC). However, recent computational studies have suggested that interfacial defects can enhance this thermal boundary conductance through the emergence of unique vibrational modes intrinsic to the material interface and defect atoms, a finding that contradicts traditional theory and conventional understanding. By manipulating the local heat flux of atomic vibrations that comprise these interfacial modes, in principle, the TBC can be increased. In this work, experimental evidence is provided that interfacial defects can enhance the TBC across interfaces through the emergence of unique high‐frequency vibrational modes that arise from atomic mass defects at the interface with relatively small masses. Ultrahigh TBC is demonstrated at amorphous SiOC:H/SiC:H interfaces, approaching 1 GW m−2 K−1 and are further increased through the introduction of nitrogen defects. The fact that disordered interfaces can exhibit such high conductances, which can be further increased with additional defects, offers a unique direction to manipulate heat transfer across materials with high densities of interfaces by controlling and enhancing interfacial thermal transport.